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Kurtzberg, Joanne

Overview:

Dr. Kurtzberg conducts both clinical and laboratory-based translational research efforts, all involving various aspects of normal and malignant hematopoiesis. In the laboratory, her early work focused on studies determining the mechanisms that regulate the choice between the various pathways of differentiation available to the pluripotent hematopoietic stem cell. Her laboratory established a CD7+ cell line, DU.528, capable of multilineage differentiation as well as self-renewal, and subsequently described the aggressive leukemic syndrome of CD7+ALL and demonstrated that a normal counterpart of the CD7+, TN malignant cell can be isolated from postnatal human thymus, bone marrow, umbilical cord blood and G-CSF mobilized peripheral blood progenitor cells. The leukemic CD7+ cell has been established in model systems nude and SCID mice where direct IL2-cytotoxicity has been demonstrated. The mechanism of IL2-induced cytotoxicity is currently a major focus of work in the laboratory. One focus of Dr. Kurtzberg's translational research is the use of novel deoxynucleosides to purge normal and malignant T-cells from human bone marrow. She has also played an important role in the development of PEG-L Asparaginase and Nelarabine, two novel antileukemia drugs that are now used routinely in the clinic. Dr. Kurtzberg is active in the Children's Oncology Group and coordinated the ALinC 16 high risk study for children with newly diagnosed B-lineage acute lymphoblastic leukemia (ALL) as well as relapsed studies for children with T- and B-lineage ALL. Under Dr. Kurtzberg's leadership, Duke has established an internationally known children's transplant program which currently treats children with cancer, blood disorders, immune deficiencies, hemoglobinopathies and inherited metabolic diseases. Over the past 2 years, the cord blood transplant program at Duke has initiated studies of autologous cord blood in children with neonatal brain injury and cerebral palsy. Dr. Kurtzberg’s laboratory is also pursuing preclinical studies isolating oligodendrocytes from cord blood with the goal of using these cells for cell therapy to treat acquired agenetic brain injuries in the next few years. Over the past 2 decades, Dr. Kurtzberg pioneered and is investigating the use of banked umbilical cord blood as an alternative stem cell source for unrelated marrow transplantation. She was awarded with a banking and transplant center contract from NHLBI for 1996-2005, to establish the Carolinas Cord Blood Bank (CCBB)at Duke and was the PI on the cord blood transplantation study (COBLT) in children with hematological malignancies and inborn errors of metabolism. In 2006, the CCBB was awarded a contract from HRSA to become a member bank of the National Cord Blood Inventory (NCBI) of the CW Bill Young Cell Transplantation Program after legislation was passed in 2005 to establish this network. Dr. Kurtzberg is also the Duke PI for the NIH-sponsored, Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) and the PI on a national trial comparing single and double cord blood transplantation in children with hematological malignancies. In 2008-2009, Dr. Kurtzberg’s lab pioneered studies to predict cord blood potency through novel assays on segments attached to cryopreserved cord blood units. The program is also performing translational research testing cord blood expansion, cellular targeted therapies and tissue repair and regeneration.

Positions:

Jerome S. Harris Professor of Pediatrics

Pediatrics, Blood and Marrow Transplantation
School of Medicine

Professor of Pediatrics

Pediatrics, Blood and Marrow Transplantation
School of Medicine

Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1976

M.D. — New York University

News:

Grants:

HRSA National Cord Blood Inventory, Fifth Cohort

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Health Resources and Service Administration
Role
Principal Investigator
Start Date
September 26, 2015
End Date
June 08, 2026

HRSA National Cord Blood Inventory

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Health Resources and Service Administration
Role
Principal Investigator
Start Date
November 02, 2006
End Date
August 23, 2019

Marcus Foundation Award (2016 Amendment)

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
The Marcus Foundation
Role
Principal Investigator
Start Date
July 01, 2016
End Date
June 30, 2019

Fate Therapeutics Inherited Metabolic Disorders

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Fate Therapeutics
Role
Principal Investigator
Start Date
May 01, 2015
End Date
April 30, 2019

Mesoblast GVHD001

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Mesoblast International Sarl
Role
Principal Investigator
Start Date
January 01, 2015
End Date
December 31, 2018

Mesoblast GVHD 002

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Mesoblast International Sarl
Role
Principal Investigator
Start Date
October 19, 2015
End Date
October 18, 2018

Optimized Procedures and SOP's for Thymus Tissue Processing

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Orphavant Sciences GmbH
Role
Principal Investigator
Start Date
January 01, 2017
End Date
June 30, 2018

Tissue Collection and Processing for Thymus Transplantation

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Orphavant Sciences GmbH
Role
Principal Investigator
Start Date
January 01, 2017
End Date
June 30, 2018

Potency and Release Assays for Thymus Tissue Processing

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Orphavant Sciences GmbH
Role
Principal Investigator
Start Date
January 01, 2017
End Date
June 30, 2018

Hypoxic Ischemic Encephalopathy-Phase II-Robertson Foundation

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Robertson Foundation
Role
Principal Investigator
Start Date
July 01, 2015
End Date
June 30, 2018

High Fidelity Diffusion MRI for Children with Cerebral Palsy in Stem Cell Therapy

Administered By
Duke-UNC Center for Brain Imaging and Analysis
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
February 15, 2012
End Date
January 31, 2018

NMDP New or Expanded Collection Hospital Development for Public Cord Blood Collection

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
National Marrow Donor Program
Role
Principal Investigator
Start Date
September 30, 2016
End Date
September 29, 2017

Marcus Foundation Award

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
The Marcus Foundation
Role
Principal Investigator
Start Date
May 01, 2014
End Date
June 30, 2017

Comparing Red Int Allo HCT to Hypomethylating Therapy High Risk Myelodysplastic Syndrome

Administered By
Pediatrics, Blood and Marrow Transplantation
AwardedBy
National Marrow Donor Program
Role
Principal Investigator
Start Date
April 29, 2014
End Date
June 30, 2017

RIC for Children and Adults with Hemophagocytic Syndromes or Selected Primary Immune Deficiencies

Administered By
Pediatrics, Blood and Marrow Transplantation
AwardedBy
National Marrow Donor Program
Role
Principal Investigator
Start Date
February 11, 2014
End Date
June 30, 2017

Blood and Marrow Transplant Clinical Trials Network

Administered By
Pediatrics, Blood and Marrow Transplantation
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 2001
End Date
June 30, 2017

Kit Collection Project Agreement

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
National Marrow Donor Program
Role
Principal Investigator
Start Date
June 01, 2015
End Date
May 31, 2017

Notch Mediated Expansion of Cord Blood Progenitors for Stem Cell Transplant

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Fred Hutchinson Cancer Research Center
Role
Principal Investigator
Start Date
May 16, 2012
End Date
April 30, 2017

Duke-UNC Clinical Hematology and Transfusion Research Career Development Program

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 28, 2006
End Date
April 30, 2017

(TEACH) Atemtuzumab, Costimulation Blockade and Sirolimus: A Tolerogenic Canvas for Donor Antigen Delivery via Mesenchymal

Administered By
Surgery, Abdominal Transplant Surgery
AwardedBy
Benaroya Research Institute at Virginia Mason
Role
Investigator
Start Date
October 01, 2014
End Date
January 31, 2017

Autologous Umbilical Cord Blood Infusion for Children with Autism Spectrum Disorder, ASD

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Perkin-Elmer
Role
Principal Investigator
Start Date
January 01, 2014
End Date
December 31, 2016

Correlating TCR Diversity to Immune Reconstitution after CBT

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Fred Hutchinson Cancer Research Center
Role
Principal Investigator
Start Date
September 10, 2013
End Date
October 31, 2016

NMDP New or Expanded Collection Hospital Development for Public Cord Blood Collection

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
National Marrow Donor Program
Role
Principal Investigator
Start Date
September 30, 2015
End Date
September 29, 2016

Research Training In Neuro-Oncology

Administered By
Neurosurgery, Neuro-Oncology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 1998
End Date
August 31, 2016

Cord Blood Biomarkers for Engraftment

Administered By
Pediatrics, Blood and Marrow Transplantation
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 2011
End Date
June 30, 2016

UNC-Duke Collaborative Clinical Pharmacology Postdoctoral Training Program

Administered By
Duke Clinical Research Institute
AwardedBy
University of North Carolina - Chapel Hill
Role
Mentor
Start Date
July 01, 2011
End Date
June 30, 2016

NMDP Amend 1 to Duke University CB Collection Agrmt 206432

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
National Marrow Donor Program
Role
Principal Investigator
Start Date
September 30, 2014
End Date
September 29, 2015

HRSA National Cord Blood Inventory, Fifth Cohort

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Health Resources and Service Administration
Role
Principal Investigator
Start Date
September 26, 2014
End Date
September 25, 2015

Multidisciplinary Neonatal Training Grant

Administered By
Pediatrics, Neonatology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
April 01, 2010
End Date
June 30, 2015

NMDP ISBT 128 Implementation Project Agreement 205793

Administered By
Pediatrics, Blood and Marrow Transplantation
AwardedBy
National Marrow Donor Program
Role
Principal Investigator
Start Date
July 22, 2013
End Date
September 30, 2014

Maintenance of NHLBI Cord Blood Units

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
National Heart, Lung, and Blood Institute
Role
Principal Investigator
Start Date
October 01, 2004
End Date
September 30, 2014

New or Expanded Collection Hospital Development for Public Cord Blood Collection

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
National Marrow Donor Program
Role
Principal Investigator
Start Date
September 30, 2013
End Date
September 29, 2014

HRSA National Cord Blood Inventory, Fifth Cohort

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Health Resources and Service Administration
Role
Principal Investigator
Start Date
September 26, 2013
End Date
September 25, 2014

Nutrition, Deregulation of Imprinted Genes

Administered By
Obstetrics and Gynecology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
April 01, 2009
End Date
March 31, 2014

HRSA National Cord Blood Inventory, Fifth Cohort

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
Health Resources and Service Administration
Role
Principal Investigator
Start Date
September 09, 2010
End Date
September 08, 2012

CTSA UL

Administered By
Duke Clinical & Translational Science Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 30, 2006
End Date
September 01, 2012

Research Training In Neuro-Oncology

Administered By
Neurosurgery, Neuro-Oncology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 15, 2005
End Date
August 31, 2010

Non-Myeloablative Cord Blood Transplantation

Administered By
Medicine, Cellular Therapy
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
April 01, 1999
End Date
December 31, 2008

In-utero Exposure and Infant Loss of IGF2 Imprinting

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 20, 2006
End Date
August 31, 2008

Parental Caregiving of Children PostStem Cell Transplant

Administered By
School of Nursing
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
August 01, 2004
End Date
July 31, 2008

Transplant Centers For Clinical Research On

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 1996
End Date
April 30, 2005

Collection And Storage Centers For Clinical Research...

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 01, 1997
End Date
February 28, 2005

Pediatric Oncology Group (POG)

Administered By
Pediatrics, Blood and Marrow Transplantation
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
January 01, 1983
End Date
December 31, 2002

Pediatric Oncology Group

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
January 01, 1998
End Date
December 31, 1999

Pediatric Oncology Group Studies

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1997
End Date
December 31, 1999

Pediatric Oncology Group Studies

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1996
End Date
December 31, 1999

Viral Control And Immune Reconstitution In Hiv Infection

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1996
End Date
August 31, 1999

Viral Control & Immune Reconstitution In Hiv Infection

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 30, 1995
End Date
August 31, 1999

Cancer Center Core Support Grant

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1976
End Date
December 31, 1998

Comprehensive Cancer Center Core Support Grant

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1976
End Date
December 31, 1998

Autologous Bone Marrow Transplantation In Breast And Ovari

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
June 01, 1990
End Date
March 31, 1997

Autologous Bone Marrow Transplantation-Breast And Ovarian

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
June 01, 1990
End Date
March 31, 1997

Pediatric Oncology Group Studies

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1995
End Date
December 31, 1995

Pediatric Oncology Group Studies

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
January 01, 1994
End Date
December 31, 1995

Effect Of Swainsonine On Human Bone Marrow Stem Cells Trea

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
October 01, 1993
End Date
September 30, 1994

Effect Of Swainsonine On Human Bone Marrow Stem Cells Trea

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 22, 1993
End Date
September 30, 1993
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Publications:

Brincidofovir for Asymptomatic Adenovirus Viremia in Pediatric and Adult Allogeneic Hematopoietic Cell Transplant Recipients: A Randomized Placebo-Controlled Phase II Trial.

Adenovirus infection in immunocompromised patients contributes to significant morbidity and mortality, especially after allogeneic hematopoietic cell transplantation (HCT). Brincidofovir (BCV, CMX001) is an orally bioavailable lipid conjugate of cidofovir that has in vitro activity against adenoviruses and other double-stranded DNA viruses. This randomized placebo-controlled phase II trial evaluated pre-emptive treatment with BCV for the prevention of adenovirus disease in pediatric and adult allogeneic HCT recipients with asymptomatic adenovirus viremia. Allogeneic HCT recipients with adenovirus viremia were randomized 1:1:1 to receive oral BCV 100 mg (2 mg/kg if <50 kg) twice weekly (BIW), BCV 200 mg (4 mg/kg if <50 kg) once weekly (QW), or placebo for 6 to 12 weeks, followed by 4 weeks of post-treatment follow-up. For randomization, subjects were stratified by screening absolute lymphocyte count (<300 cells/mm3 versus ≥300 cells/mm3). Assignment to BCV or placebo was double blinded; dose frequency was unblinded. The primary endpoint was the proportion of subjects experiencing treatment failure, defined as either progression to probable or definitive adenovirus disease or confirmed increasing adenovirus viremia (≥1 log10 copies/mL) during randomized therapy. Between June 2011 and December 2012, 48 subjects were randomized to the BCV BIW (n = 14), BCV QW (n = 16), or placebo (n = 18) groups. The proportion of subjects with treatment failure in the BCV BIW group was 21% (odds ratio, .53; 95% confidence interval [CI], .11 to 2.71; P = .45), 38% (odds ratio, 1.23; 95% CI, .30 to 5.05, P = .779) in the BCV QW group, and 33% in the placebo group. All-cause mortality was lower in the BCV BIW (14%) and BCV QW groups (31%) relative to the placebo group (39%), but these differences were not statistically significant. After 1 week of therapy, 8 of 12 subjects (67%) randomized to BCV BIW had undetectable adenovirus viremia (<100 copies/mL), compared with 4 of 14 subjects (29%) randomized to BCV QW and 5 of 15 subjects (33%) randomized to placebo. In a post hoc analysis of subjects with viremia ≥1000 copies/mL at baseline, 6 of 7 BCV BIW subjects (86%) achieved undetectable viremia compared with 2 of 8 placebo subjects (25%; P = .04). Early treatment discontinuation because of adverse events was more common in subjects treated with BCV than with placebo. Diarrhea was the most common event in all groups (57% BCV BIW, 38% BCV QW, 28% placebo), but it led to treatment discontinuation in only 1 subject receiving BCV QW. Events diagnosed as acute graft-versus-host disease, primarily of the gastrointestinal tract, were more frequent in the BCV BIW group (50%) than in the BCV QW (25%) and placebo (17%) groups. There was no evidence of myelotoxicity or nephrotoxicity in BCV-treated subjects. The results of this trial confirm the antiviral activity of BCV against adenoviruses. Further investigation is ongoing to define the optimal treatment strategy for HCT recipients with serious adenovirus infection and disease.

Authors
Grimley, MS; Chemaly, RF; Englund, JA; Kurtzberg, J; Chittick, G; Brundage, TM; Bae, A; Morrison, ME; Prasad, VK
MLA Citation
Grimley, MS, Chemaly, RF, Englund, JA, Kurtzberg, J, Chittick, G, Brundage, TM, Bae, A, Morrison, ME, and Prasad, VK. "Brincidofovir for Asymptomatic Adenovirus Viremia in Pediatric and Adult Allogeneic Hematopoietic Cell Transplant Recipients: A Randomized Placebo-Controlled Phase II Trial." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 23.3 (March 2017): 512-521.
PMID
28063938
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
23
Issue
3
Publish Date
2017
Start Page
512
End Page
521
DOI
10.1016/j.bbmt.2016.12.621

Gallbladder abnormalities in children with metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is a lysosomal storage disease that leads to neurological deterioration and visceral involvement, including sulphatide deposition in the gallbladder wall. Using our institution's extensive experience in treating MLD, we examined the incidence of gallbladder abnormalities in the largest cohort of children with MLD to date.We conducted a retrospective review of all children with MLD, adrenoleukodystrophy (ALD), or Krabbe disease who underwent hematopoietic stem cell transplantation (HSCT) at our institution between 1994 and 2015. Baseline characteristics and unadjusted outcomes were compared using the Kruskal-Wallis test for continuous variables and Pearson χ2 test for categorical variables, with significance defined as P < 0.05.In total, 87 children met study criteria: 29 children with MLD and 58 children with ALD or Krabbe disease. Children with MLD were more likely to demonstrate gallbladder abnormalities on imaging, both before HSCT (41.4% versus 5.2%, P < 0.001) and after HSCT (75.9% versus 41.4%, P = 0.002). Consequently, a larger proportion of children with MLD underwent surgical or interventional management of biliary disease (10.3% versus 3.4%, P = 0.03).Children with MLD have a significantly greater incidence of gallbladder abnormalities than children with other lysosomal storage diseases. Biliary disease should be considered in children with MLD who develop abdominal pain, and cholecystectomy should be considered for persistent, symptomatic gallbladder abnormalities.

Authors
Kim, J; Sun, Z; Ezekian, B; Schooler, GR; Prasad, VK; Kurtzberg, J; Rice, HE; Tracy, ET
MLA Citation
Kim, J, Sun, Z, Ezekian, B, Schooler, GR, Prasad, VK, Kurtzberg, J, Rice, HE, and Tracy, ET. "Gallbladder abnormalities in children with metachromatic leukodystrophy." The Journal of surgical research 208 (February 2017): 187-191.
PMID
27993207
Source
epmc
Published In
Journal of Surgical Research
Volume
208
Publish Date
2017
Start Page
187
End Page
191
DOI
10.1016/j.jss.2016.08.081

A case of eczema coxsackium with erythema multiforme-like histopathology in a 14-year-old boy with chronic graft-versus-host disease.

Authors
Miller, PK; Zain-Ul-Abideen, M; Paul, J; Perry, AE; Linos, K; Carter, JB; Kurtzberg, J; Mann, JA
MLA Citation
Miller, PK, Zain-Ul-Abideen, M, Paul, J, Perry, AE, Linos, K, Carter, JB, Kurtzberg, J, and Mann, JA. "A case of eczema coxsackium with erythema multiforme-like histopathology in a 14-year-old boy with chronic graft-versus-host disease." JAAD case reports 3.1 (January 2017): 49-52.
PMID
28203622
Source
epmc
Published In
JAAD Case Reports
Volume
3
Issue
1
Publish Date
2017
Start Page
49
End Page
52
DOI
10.1016/j.jdcr.2016.11.007

Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation.

Despite advances in supportive therapy to prevent complications of sickle cell disease (SCD), access to care is not universal. Hematopoietic cell transplantation is, to date, the only curative therapy for SCD, but its application is limited by availability of a suitable HLA-matched donor and lack of awareness of the benefits of transplant. Included in this study are 1000 recipients of HLA-identical sibling transplants performed between 1986 and 2013 and reported to the European Blood and Marrow Transplant, Eurocord and the Center for International Blood and Marrow Transplant Research. The primary endpoint was event-free survival, defined as being alive without graft failure; risk factors were studied using Cox regression model. The median age at transplantation was 9 years and the median follow-up, longer than 5 years. Most patients received a myeloablative conditioning regimen (n=873; 87%) and the remainder, reduced-intensity conditioning regimens (n=125; 13%). Bone marrow was the predominant stem cell source (n=839; 84%), while peripheral blood and cord blood progenitors were used in 73 (7%) and 88 patients (9%), respectively. The 5-year event-free and overall survival was 91.4% (95% CI 89.6%-93.3%) and 92.9% (95% CI 91.1%-94.6%), respectively. Event-free survival was lower with increasing age at transplantation (hazard ratio [HR] 1.09; p<0.001) and higher for transplantations performed after 2006 (HR 0.95, p=0.013). Twenty-three patients experienced graft failure; 70 patients (7%) died, the most common cause of death being infection. The excellent outcome of a cohort transplanted over 3 decades confirms the role of HLA-identical sibling transplantation for children and adults with SCD.

Authors
Gluckman, E; Cappelli, B; Bernaudin, F; Labopin, M; Volt, F; Carreras, J; Simões, BP; Ferster, A; Dupont, S; de la Fuente, J; Dalle, J-H; Zecca, M; Walters, MC; Krishnamurti, L; Bhatia, M; Leung, K; Yanik, G; Kurtzberg, J; Dhedin, N; Kuentz, M; Michel, G; Apperley, J; Lutz, P; Neven, B; Bertrand, Y; Vannier, JP; Ayas, M; Cavazzana, M; Matthes-Martin, S; Rocha, V; Elayoubi, H; Kenzey, C; Bader, P; Locatelli, F; Ruggeri, A; Eapen, M
MLA Citation
Gluckman, E, Cappelli, B, Bernaudin, F, Labopin, M, Volt, F, Carreras, J, Simões, BP, Ferster, A, Dupont, S, de la Fuente, J, Dalle, J-H, Zecca, M, Walters, MC, Krishnamurti, L, Bhatia, M, Leung, K, Yanik, G, Kurtzberg, J, Dhedin, N, Kuentz, M, Michel, G, Apperley, J, Lutz, P, Neven, B, Bertrand, Y, Vannier, JP, Ayas, M, Cavazzana, M, Matthes-Martin, S, Rocha, V, Elayoubi, H, Kenzey, C, Bader, P, Locatelli, F, Ruggeri, A, and Eapen, M. "Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation." Blood (December 13, 2016).
PMID
27965196
Source
epmc
Published In
Blood
Publish Date
2016

Clinical outcomes of children with abnormal newborn screening results for Krabbe disease in New York State.

Early infantile Krabbe disease is rapidly fatal, but hematopoietic stem cell transplantation (HSCT) may improve outcomes if performed soon after birth. New York State began screening all newborns for Krabbe disease in 2006.Infants with abnormal newborn screen results for Krabbe disease were referred to specialty-care centers. Newborns found to be at high risk for Krabbe disease underwent a neurodiagnostic battery to determine the need for emergent HSCT.Almost 2 million infants were screened. Five infants were diagnosed with early infantile Krabbe disease. Three died, two from HSCT-related complications and one from untreated disease. Two children who received HSCT have moderate to severe developmental delays. Forty-six currently asymptomatic children are considered to be at moderate or high risk for development of later-onset Krabbe disease.These results show significant HSCT-associated morbidity and mortality in early infantile Krabbe disease and raise questions about its efficacy when performed in newborns diagnosed through newborn screening. The unanticipated identification of "at risk" children introduces unique ethical and medicolegal issues. New York's experience raises questions about the risks, benefits, and practicality of screening newborns for Krabbe disease. It is imperative that objective assessments be made on an ongoing basis as additional states begin screening for this disorder.Genet Med 18 12, 1235-1243.

Authors
Wasserstein, MP; Andriola, M; Arnold, G; Aron, A; Duffner, P; Erbe, RW; Escolar, ML; Estrella, L; Galvin-Parton, P; Iglesias, A; Kay, DM; Kronn, DF; Kurtzberg, J; Kwon, JM; Langan, TJ; Levy, PA; Naidich, TP; Orsini, JJ; Pellegrino, JE; Provenzale, JM; Wenger, DA; Caggana, M
MLA Citation
Wasserstein, MP, Andriola, M, Arnold, G, Aron, A, Duffner, P, Erbe, RW, Escolar, ML, Estrella, L, Galvin-Parton, P, Iglesias, A, Kay, DM, Kronn, DF, Kurtzberg, J, Kwon, JM, Langan, TJ, Levy, PA, Naidich, TP, Orsini, JJ, Pellegrino, JE, Provenzale, JM, Wenger, DA, and Caggana, M. "Clinical outcomes of children with abnormal newborn screening results for Krabbe disease in New York State." Genetics in medicine : official journal of the American College of Medical Genetics 18.12 (December 2016): 1235-1243.
PMID
27171547
Source
epmc
Published In
Genetics in Medicine
Volume
18
Issue
12
Publish Date
2016
Start Page
1235
End Page
1243
DOI
10.1038/gim.2016.35

Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis.

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for most children with osteopetrosis (OP). Timing of HSCT is critical; therefore, umbilical cord blood transplantation (UCBT) is an attractive option. We analyzed outcomes after UCBT in 51 OP children. Median age at UCBT was 6 months. Seventy-seven percent of the cord blood grafts had 0 or 1 HLA disparity with the recipient. Conditioning regimen was myeloablative (mostly busulfan-based in 84% and treosulfan-based in 10%). Antithymocyte globulin was given to 90% of patients. Median number of total nucleated and CD34(+) cells infused was 14 × 10(7)/kg and 3.4 × 10(5)/kg, respectively. Median follow-up for survivors was 74 months. Cumulative incidence (CI) of neutrophil recovery was 67% with a median time to recovery of 23 days; 33% of patients had graft failure, 81% of engrafted patients had full donor engraftment, and 19% had mixed donor chimerism. Day 100 CI of acute graft-versus-host disease (grades II to IV) was 31% and 6-year CI of chronic graft-versus-host disease was 21%. Mechanical ventilation was required in 28%, and veno-occlusive disease was diagnosed in 16% of cases. Six-year overall survival rate was 46%. Comparative studies with other alternative donors should be performed to evaluate whether UCBT remains a valid alternative for children with OP without an HLA-matched donor.

Authors
Chiesa, R; Ruggeri, A; Paviglianiti, A; Zecca, M; Gónzalez-Vicent, M; Bordon, V; Stein, J; Lawson, S; Dupont, S; Lanino, E; Abecasis, M; Al-Seraihy, A; Kenzey, C; Bierings, M; Locatelli, F; Gluckman, E; Schulz, A; Gennery, A; Page, K; Kurtzberg, J; Rocha, V
MLA Citation
Chiesa, R, Ruggeri, A, Paviglianiti, A, Zecca, M, Gónzalez-Vicent, M, Bordon, V, Stein, J, Lawson, S, Dupont, S, Lanino, E, Abecasis, M, Al-Seraihy, A, Kenzey, C, Bierings, M, Locatelli, F, Gluckman, E, Schulz, A, Gennery, A, Page, K, Kurtzberg, J, and Rocha, V. "Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 22.11 (November 2016): 1997-2002.
Website
http://hdl.handle.net/10161/12493
PMID
27470286
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
11
Publish Date
2016
Start Page
1997
End Page
2002
DOI
10.1016/j.bbmt.2016.07.015

The Blood and Marrow Transplant Clinical Trials Network: An Effective Infrastructure for Addressing Important Issues in Hematopoietic Cell Transplantation

MLA Citation
"The Blood and Marrow Transplant Clinical Trials Network: An Effective Infrastructure for Addressing Important Issues in Hematopoietic Cell Transplantation." Biology of Blood and Marrow Transplantation 22.10 (October 2016): 1747-1757.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
10
Publish Date
2016
Start Page
1747
End Page
1757
DOI
10.1016/j.bbmt.2016.07.003

How transplant centers deal with the dextran shortage: recommendations for comparing alternatives.

In the United States, dextran 40 in 0.9% NaCl is the preferred reagent for the thawing and preparation of cord blood units for hematopoietic stem cell transplantation. The recurring nationwide shortage of this reagent could have implications that extend to the avoidance of cord blood for transplantation.To address the shortage, the National Marrow Donor Program and its Cord Blood Advisory Group sought to identify available alternative reagents or manufacturers. A sample of transplant centers (TCs) were surveyed to determine their process to compare these alternatives. The TCs were then asked to share their comparability protocols for review.The 12 TCs that responded to the survey studied various types of alternative reagents and manufacturers of the standard dextran 40 in 0.9% NaCl. Four TCs submitted their protocols from which a model comparability protocol was created for centers who need assistance.Whether comparing dextran 40 in 0.9% NaCl to that of a different manufacturer or a different reagent, the results of the comparability studies submitted by the TCs indicated equivalency. During a shortage, the model comparability study protocol can be used as a reference to establish an alternative to dextran 40 in 0.9% NaCl.

Authors
Brady, C; Armitage, S; Freed, B; Duffy, M; Gass, A; Spellman, S; Kurtzberg, J; Regan, D
MLA Citation
Brady, C, Armitage, S, Freed, B, Duffy, M, Gass, A, Spellman, S, Kurtzberg, J, and Regan, D. "How transplant centers deal with the dextran shortage: recommendations for comparing alternatives." Transfusion (September 5, 2016).
PMID
27596242
Source
epmc
Published In
Transfusion
Publish Date
2016
DOI
10.1111/trf.13783

Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning.

Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.9 years) post-CBT. Patients were conditioned with high-dose chemotherapy using Bu-containing regimens. No patient received total body irradiation. The median age at transplant was 1 year (range, .1 to 2). Diagnoses included inherited metabolic diseases (59.8%), leukemia (17.6%), congenital immune deficiency (20.2%), bone marrow failure/myelodysplastic syndrome (3.9%), and hemoglobinopathy (2%). Among patients surviving 5 years, the overall survival rate at 10 years post-CBT was 93% (95% CI, 84.9 to 96.8). Virtually all patients (98%) experienced at least 1 significant late effect. Most (83.3%) experienced 2 or more late effects, and more than half of the patients (64.7%) experienced 3 or more late effects. The most commonly observed late effects included dental problems (92.2%), short stature (55.9%), cognitive deficits (53.6%), pulmonary dysfunction (18.6%), and abnormal pubertal development (27.9%). This is the first report of late effects of Bu-based conditioning in a cohort of very young patients at the time of transplant. These results will inform clinical care guidelines for long-term follow-up and add to the growing information regarding outcomes of hematopoietic stem cell transplantation.

Authors
Allewelt, H; El-Khorazaty, J; Mendizabal, A; Taskindoust, M; Martin, PL; Prasad, V; Page, K; Sanders, J; Kurtzberg, J
MLA Citation
Allewelt, H, El-Khorazaty, J, Mendizabal, A, Taskindoust, M, Martin, PL, Prasad, V, Page, K, Sanders, J, and Kurtzberg, J. "Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 22.9 (September 2016): 1627-1635.
PMID
27264632
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
9
Publish Date
2016
Start Page
1627
End Page
1635
DOI
10.1016/j.bbmt.2016.05.024

Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning

Authors
Allewelt, H; El-Khorazaty, J; Mendizabal, A; Taskindoust, M; Martin, PL; Prasad, V; Page, K; Sanders, J; Kurtzberg, J
MLA Citation
Allewelt, H, El-Khorazaty, J, Mendizabal, A, Taskindoust, M, Martin, PL, Prasad, V, Page, K, Sanders, J, and Kurtzberg, J. "Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 22.9 (September 2016): 1627-1635.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
9
Publish Date
2016
Start Page
1627
End Page
1635
DOI
10.1016/j.bbmt.2016.05.024

A cord blood monocyte-derived cell therapy product accelerates brain remyelination.

Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14+ monocytes. We compared the ability of freshly isolated CB CD14+ monocytes and DUOC-01 cells to accelerate remyelination of the brains of NOD/SCID/IL2Rγnull mice following cuprizone feeding-mediated demyelination. The corpus callosum of mice intracranially injected with DUOC-01 showed enhanced myelination, a higher proportion of fully myelinated axons, decreased gliosis and cellular infiltration, and more proliferating oligodendrocyte lineage cells than those of mice receiving excipient. Uncultured CB CD14+ monocytes also accelerated remyelination, but to a significantly lesser extent than DUOC-01 cells. Microarray analysis, quantitative PCR studies, Western blotting, and flow cytometry demonstrated that expression of factors that promote remyelination including PDGF-AA, stem cell factor, IGF1, MMP9, MMP12, and triggering receptor expressed on myeloid cells 2 were upregulated in DUOC-01 compared to CB CD14+ monocytes. Collectively, our results show that DUOC-01 accelerates brain remyelination by multiple mechanisms and could be beneficial in treating demyelinating conditions.

Authors
Saha, A; Buntz, S; Scotland, P; Xu, L; Noeldner, P; Patel, S; Wollish, A; Gunaratne, A; Gentry, T; Troy, J; Matsushima, GK; Kurtzberg, J; Balber, AE
MLA Citation
Saha, A, Buntz, S, Scotland, P, Xu, L, Noeldner, P, Patel, S, Wollish, A, Gunaratne, A, Gentry, T, Troy, J, Matsushima, GK, Kurtzberg, J, and Balber, AE. "A cord blood monocyte-derived cell therapy product accelerates brain remyelination." JCI insight 1.13 (August 18, 2016): e86667-.
PMID
27699230
Source
epmc
Published In
JCI insight
Volume
1
Issue
13
Publish Date
2016
Start Page
e86667

Voriconazole pharmacokinetics following HSCT: results from the BMT CTN 0101 trial.

Voriconazole is a first-line agent for the prevention and treatment of a number of invasive fungal diseases. Relatively little is known about the relationship between drug exposure and the prevention of invasive fungal infections.A pharmacokinetic-pharmacodynamic substudy was performed as part of the BMT CTN 0101 trial, which was a randomized clinical trial comparing voriconazole with fluconazole for the prevention of invasive fungal infections in HSCT recipients. A previously described population pharmacokinetic model was used to calculate the maximum a posteriori Bayesian estimates for 187 patients. Drug exposure in each patient was quantified in terms of the average AUC and average trough concentrations. The relationship between drug exposure and the probability of breakthrough infection was investigated using logistic regression. AUC and trough concentrations in patients with and without breakthrough infection were compared.Pharmacokinetic data from each patient were readily described using the maximum a posteriori Bayesian estimates. There were only five patients that had a breakthrough infection while receiving voriconazole in the first 100 days post-HSCT. For these patients, there was no statistically significant relationship between the average AUC or average trough concentration and the probability of breakthrough infection [OR (95% CI) 1.026 (0.956-1.102) and 1.108 (0.475-2.581), respectively]. P value for these estimates was 0.474 and 0.813, respectively.Given the very small number of proven/probable infections, it was difficult to identify any differences in drug exposure in HSCT recipients with and without breakthrough fungal infections.

Authors
Hope, WW; Walsh, TJ; Goodwin, J; Peloquin, CA; Howard, A; Kurtzberg, J; Mendizabal, A; Confer, DL; Bulitta, J; Baden, LR; Neely, MN; Wingard, JR
MLA Citation
Hope, WW, Walsh, TJ, Goodwin, J, Peloquin, CA, Howard, A, Kurtzberg, J, Mendizabal, A, Confer, DL, Bulitta, J, Baden, LR, Neely, MN, and Wingard, JR. "Voriconazole pharmacokinetics following HSCT: results from the BMT CTN 0101 trial." The Journal of antimicrobial chemotherapy 71.8 (August 2016): 2234-2240.
PMID
27121401
Source
epmc
Published In
Journal of Antimicrobial Chemotherapy
Volume
71
Issue
8
Publish Date
2016
Start Page
2234
End Page
2240
DOI
10.1093/jac/dkw127

Chagas Disease Screening in Maternal Donors of Publicly Banked Umbilical Cord Blood, United States.

To assess patterns of Chagas disease, we reviewed results of screening umbilical cord blood from a US public cord blood bank during 2007-2014. Nineteen maternal donors tested positive for Trypanosoma cruzi parasites (0.04%). Because perinatal transmission of Chagas disease is associated with substantial illness, targeted prenatal programs should screen for this disease.

Authors
Edwards, JM; Gilner, JB; Hernandez, J; Kurtzberg, J; Heine, RP
MLA Citation
Edwards, JM, Gilner, JB, Hernandez, J, Kurtzberg, J, and Heine, RP. "Chagas Disease Screening in Maternal Donors of Publicly Banked Umbilical Cord Blood, United States." Emerging infectious diseases 22.8 (August 2016): 1468-1470.
PMID
27433974
Source
epmc
Published In
Emerging infectious diseases
Volume
22
Issue
8
Publish Date
2016
Start Page
1468
End Page
1470
DOI
10.3201/eid2208.151622

LONG-TERM FUNCTIONAL OUTCOMES FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR INFANTILE KRABBE DISEASE

Authors
Allewelt, HB; Page, K; Taskindoust, M; Troy, JD; Wood, S; Parikh, S; Prasad, V; Kurtzberg, J
MLA Citation
Allewelt, HB, Page, K, Taskindoust, M, Troy, JD, Wood, S, Parikh, S, Prasad, V, and Kurtzberg, J. "LONG-TERM FUNCTIONAL OUTCOMES FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR INFANTILE KRABBE DISEASE." PEDIATRIC BLOOD & CANCER 63 (June 2016): S97-S97.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
63
Publish Date
2016
Start Page
S97
End Page
S97

Long-Term Functional Outcomes Following Hematopoietic Stem Cell Transplantation for Early Infantile Krabbe Disease

Authors
Allewelt, H; Taskindoust, M; Troy, J; Page, K; Wood, S; Parikh, S; Prasad, V; Kurtzberg, J
MLA Citation
Allewelt, H, Taskindoust, M, Troy, J, Page, K, Wood, S, Parikh, S, Prasad, V, and Kurtzberg, J. "Long-Term Functional Outcomes Following Hematopoietic Stem Cell Transplantation for Early Infantile Krabbe Disease." June 2016.
Source
wos-lite
Published In
Transfusion
Volume
56
Issue
6
Publish Date
2016
Start Page
7A
End Page
8A

Development and validation of a rapid, aldehyde dehydrogenase bright-based cord blood potency assay.

Banked, unrelated umbilical cord blood provides access to hematopoietic stem cell transplantation for patients lacking matched bone marrow donors, yet 10% to 15% of patients experience graft failure or delayed engraftment. This may be due, at least in part, to inadequate potency of the selected cord blood unit (CBU). CBU potency is typically assessed before cryopreservation, neglecting changes in potency occurring during freezing and thawing. Colony-forming units (CFUs) have been previously shown to predict CBU potency, defined as the ability to engraft in patients by day 42 posttransplant. However, the CFU assay is difficult to standardize and requires 2 weeks to perform. Consequently, we developed a rapid multiparameter flow cytometric CBU potency assay that enumerates cells expressing high levels of the enzyme aldehyde dehydrogenase (ALDH bright [ALDH(br)]), along with viable CD45(+) or CD34(+) cell content. These measurements are made on a segment that was attached to a cryopreserved CBU. We validated the assay with prespecified criteria testing accuracy, specificity, repeatability, intermediate precision, and linearity. We then prospectively examined the correlations among ALDH(br), CD34(+), and CFU content of 3908 segments over a 5-year period. ALDH(br) (r = 0.78; 95% confidence interval [CI], 0.76-0.79), but not CD34(+) (r = 0.25; 95% CI, 0.22-0.28), was strongly correlated with CFU content as well as ALDH(br) content of the CBU. These results suggest that the ALDH(br) segment assay (based on unit characteristics measured before release) is a reliable assessment of potency that allows rapid selection and release of CBUs from the cord blood bank to the transplant center for transplantation.

Authors
Shoulars, K; Noldner, P; Troy, JD; Cheatham, L; Parrish, A; Page, K; Gentry, T; Balber, AE; Kurtzberg, J
MLA Citation
Shoulars, K, Noldner, P, Troy, JD, Cheatham, L, Parrish, A, Page, K, Gentry, T, Balber, AE, and Kurtzberg, J. "Development and validation of a rapid, aldehyde dehydrogenase bright-based cord blood potency assay." Blood 127.19 (May 2016): 2346-2354.
Website
http://hdl.handle.net/10161/12492
PMID
26968535
Source
epmc
Published In
Blood
Volume
127
Issue
19
Publish Date
2016
Start Page
2346
End Page
2354
DOI
10.1182/blood-2015-08-666990

Development of AAVidua Vector for the Treatment of Cornea Associated Vision Loss in Bone Marrow Treated-Hurler Patients

Authors
Vance, M; Llanga, L; Kurtzberg, J; Samulski, RJ; Hirsch, M
MLA Citation
Vance, M, Llanga, L, Kurtzberg, J, Samulski, RJ, and Hirsch, M. "Development of AAVidua Vector for the Treatment of Cornea Associated Vision Loss in Bone Marrow Treated-Hurler Patients." May 2016.
Source
wos-lite
Published In
Molecular Therapy
Volume
24
Publish Date
2016
Start Page
S40
End Page
S41

Newborn screening for Krabbe disease in New York State: the first eight years' experience.

Krabbe disease (KD) results from galactocerebrosidase (GALC) deficiency. Infantile KD symptoms include irritability, progressive stiffness, developmental delay, and death. The only potential treatment is hematopoietic stem cell transplantation. New York State (NYS) implemented newborn screening for KD in 2006.Dried blood spots from newborns were assayed for GALC enzyme activity using mass spectrometry, followed by molecular analysis for those with low activity (≤12% of the daily mean). Infants with low enzyme activity and one or more mutations were referred for follow-up diagnostic testing and neurological examination.Of >1.9 million screened, 620 infants were subjected to molecular analysis and 348 were referred for diagnostic testing. Five had enzyme activities and mutations consistent with infantile KD and manifested clinical/neurodiagnostic abnormalities. Four underwent transplantation, two are surviving with moderate to severe handicaps, and two died from transplant-related complications. The significance of many sequence variants identified is unknown. Forty-six asymptomatic infants were found to be at moderate to high risk for disease.The positive predictive value of KD screening in NYS is 1.4% (5/346) considering confirmed infantile cases. The incidence of infantile KD in NYS is approximately 1 in 394,000, but it may be higher for later-onset forms.

Authors
Orsini, JJ; Kay, DM; Saavedra-Matiz, CA; Wenger, DA; Duffner, PK; Erbe, RW; Biski, C; Martin, M; Krein, LM; Nichols, M; Kurtzberg, J; Escolar, ML; Adams, DJ; Arnold, GL; Iglesias, A; Galvin-Parton, P; Kronn, DF; Kwon, JM; Levy, PA; Pellegrino, JE; Shur, N; Wasserstein, MP; Caggana, M
MLA Citation
Orsini, JJ, Kay, DM, Saavedra-Matiz, CA, Wenger, DA, Duffner, PK, Erbe, RW, Biski, C, Martin, M, Krein, LM, Nichols, M, Kurtzberg, J, Escolar, ML, Adams, DJ, Arnold, GL, Iglesias, A, Galvin-Parton, P, Kronn, DF, Kwon, JM, Levy, PA, Pellegrino, JE, Shur, N, Wasserstein, MP, and Caggana, M. "Newborn screening for Krabbe disease in New York State: the first eight years' experience." Genetics in medicine : official journal of the American College of Medical Genetics 18.3 (March 2016): 239-248.
PMID
26795590
Source
epmc
Published In
Genetics in Medicine
Volume
18
Issue
3
Publish Date
2016
Start Page
239
End Page
248
DOI
10.1038/gim.2015.211

To Match or Not to Match in Cord Blood Transplantation: A Modern Look at a Recurring Question.

Authors
Kurtzberg, J
MLA Citation
Kurtzberg, J. "To Match or Not to Match in Cord Blood Transplantation: A Modern Look at a Recurring Question." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 22.3 (March 2016): 398-399.
PMID
26797399
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
398
End Page
399
DOI
10.1016/j.bbmt.2016.01.020

Long-Term Functional Outcomes following Hematopoietic Stem Cell Transplantation for Krabbe Disease

Authors
Allewelt, HB; Page, K; Taskindoust, M; Troy, JD; Wood, S; Parikh, S; Prasad, VK; Kurtzberg, J
MLA Citation
Allewelt, HB, Page, K, Taskindoust, M, Troy, JD, Wood, S, Parikh, S, Prasad, VK, and Kurtzberg, J. "Long-Term Functional Outcomes following Hematopoietic Stem Cell Transplantation for Krabbe Disease." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S102
End Page
S103

Targeting Cord Blood Units with Higher Total Nucleated Cell Count for Inclusion in a Public Cord Blood Bank: Impact on Inventory Diversity and Self-Sustainability

Authors
Page, K; Hernandez, J; Troy, JD; Vidal, AV; Kurtzberg, J
MLA Citation
Page, K, Hernandez, J, Troy, JD, Vidal, AV, and Kurtzberg, J. "Targeting Cord Blood Units with Higher Total Nucleated Cell Count for Inclusion in a Public Cord Blood Bank: Impact on Inventory Diversity and Self-Sustainability." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S81
End Page
S81

Adequately Dosed Autologous Cord Blood Infusion Is Associated with Motor Improvement in Children with Cerebral Palsy

Authors
Sun, J; Mikati, M; Troy, JD; Gustafson, K; Simmons, R; Goldstein, R; Petry, J; McLaughlin, C; Waters-Pick, B; Case, L; Worley, G; Kurtzberg, J
MLA Citation
Sun, J, Mikati, M, Troy, JD, Gustafson, K, Simmons, R, Goldstein, R, Petry, J, McLaughlin, C, Waters-Pick, B, Case, L, Worley, G, and Kurtzberg, J. "Adequately Dosed Autologous Cord Blood Infusion Is Associated with Motor Improvement in Children with Cerebral Palsy." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S61
End Page
S62

Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis

Authors
Patel, S; Allewelt, HB; Martin, PL; Page, K; Driscoll, TA; Prasad, VK; Kurtzberg, J; Parikh, S
MLA Citation
Patel, S, Allewelt, HB, Martin, PL, Page, K, Driscoll, TA, Prasad, VK, Kurtzberg, J, and Parikh, S. "Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S257
End Page
S257

Umbilical Cord Blood Transplantation for Cartilage Hair Hypoplasia: A Single Center Experience Demonstrates Excellent Outcomes Using Myeloablative Preparative Regimens

Authors
Allewelt, HB; Patel, S; Prasad, VK; Kurtzberg, J; Driscoll, TA; Martin, PL; Page, K; Parikh, S
MLA Citation
Allewelt, HB, Patel, S, Prasad, VK, Kurtzberg, J, Driscoll, TA, Martin, PL, Page, K, and Parikh, S. "Umbilical Cord Blood Transplantation for Cartilage Hair Hypoplasia: A Single Center Experience Demonstrates Excellent Outcomes Using Myeloablative Preparative Regimens." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S235
End Page
S235

Interim Analysis of an Observational Study Assessing T Cell Receptor Diversity As an Early Predictor of NRM in Cord Blood Transplant Recipients

Authors
Salit, RB; Emerson, R; Karanes, C; Gutman, JA; Nikiforow, S; Duncan, C; Kurtzberg, J; Robins, H; Rieder, M; Delaney, C
MLA Citation
Salit, RB, Emerson, R, Karanes, C, Gutman, JA, Nikiforow, S, Duncan, C, Kurtzberg, J, Robins, H, Rieder, M, and Delaney, C. "Interim Analysis of an Observational Study Assessing T Cell Receptor Diversity As an Early Predictor of NRM in Cord Blood Transplant Recipients." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S44
End Page
S44

Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke

Authors
Kurtzberg, J; Durham, R; Laskowitz, D; Balber, AE; Bennett, E
MLA Citation
Kurtzberg, J, Durham, R, Laskowitz, D, Balber, AE, and Bennett, E. "Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S141
End Page
S142

Use of Umbilical Cord Blood to Treat Non-Fatal Submersion Events

Authors
McLaughlin, C; Fitzgerald, RA; Waters-Pick, B; Allison, J; Sun, J; Kurtzberg, J
MLA Citation
McLaughlin, C, Fitzgerald, RA, Waters-Pick, B, Allison, J, Sun, J, and Kurtzberg, J. "Use of Umbilical Cord Blood to Treat Non-Fatal Submersion Events." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S142
End Page
S143

Optimization of the Aldehyde Dehydrogenase-Based Cord Blood Potency Assay Using Red Blood Cell Depletion

Authors
Shoulars, K; Gentry, T; Lam, B; Wognum, B; Szilvassy, S; Kurtzberg, J
MLA Citation
Shoulars, K, Gentry, T, Lam, B, Wognum, B, Szilvassy, S, and Kurtzberg, J. "Optimization of the Aldehyde Dehydrogenase-Based Cord Blood Potency Assay Using Red Blood Cell Depletion." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S424
End Page
S425

Ex-Vivo Expansion of Previously Cryopreserved, Thawed and Re-Cryopreserved Cord Blood Mononuclear Cells (CBMC) Utilizing K562-mbIL21-41BBL; Potential for Adoptive Cellular Immunotherapy Post Umbilical Cord Blood Transplantation (UCBT)

Authors
Flower, A; Chu, Y; Ayello, J; Kurtzberg, J; Lee, D; Cairo, MS
MLA Citation
Flower, A, Chu, Y, Ayello, J, Kurtzberg, J, Lee, D, and Cairo, MS. "Ex-Vivo Expansion of Previously Cryopreserved, Thawed and Re-Cryopreserved Cord Blood Mononuclear Cells (CBMC) Utilizing K562-mbIL21-41BBL; Potential for Adoptive Cellular Immunotherapy Post Umbilical Cord Blood Transplantation (UCBT)." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S153
End Page
S153

Effect of Human Mesenchymal Stem Cells (Remestemcel-L) on Clinical Response and Survival Confirmed in a Large Cohort of Pediatric Patients with Severe High-Risk Steroid Refractory Acute Graft Versus Host Disease

Authors
Kurtzberg, J; Prockop, SE; Prasad, VK; Chaudhury, S; Teira, P; Nemecek, ER; Horn, B; Burke, E; Hayes, J; Skerrett, D
MLA Citation
Kurtzberg, J, Prockop, SE, Prasad, VK, Chaudhury, S, Teira, P, Nemecek, ER, Horn, B, Burke, E, Hayes, J, and Skerrett, D. "Effect of Human Mesenchymal Stem Cells (Remestemcel-L) on Clinical Response and Survival Confirmed in a Large Cohort of Pediatric Patients with Severe High-Risk Steroid Refractory Acute Graft Versus Host Disease." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S59
End Page
S59

Use of privately banked autologous umbilical cord blood to treat brain injuries in paediatric patients

Authors
Smith, A; Sun, J; Allison, J; Mimbrero-Ramirez, M; Hussain, K; Kurtzberg, J
MLA Citation
Smith, A, Sun, J, Allison, J, Mimbrero-Ramirez, M, Hussain, K, and Kurtzberg, J. "Use of privately banked autologous umbilical cord blood to treat brain injuries in paediatric patients." March 2016.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
51
Publish Date
2016
Start Page
S568
End Page
S568

AAV Gene Therapy for MPS1-associated Corneal Blindness.

Although cord blood transplantation has significantly extended the lifespan of mucopolysaccharidosis type 1 (MPS1) patients, over 95% manifest cornea clouding with about 50% progressing to blindness. As corneal transplants are met with high rejection rates in MPS1 children, there remains no treatment to prevent blindness or restore vision in MPS1 children. Since MPS1 is caused by mutations in idua, which encodes alpha-L-iduronidase, a gene addition strategy to prevent, and potentially reverse, MPS1-associated corneal blindness was investigated. Initially, a codon optimized idua cDNA expression cassette (opt-IDUA) was validated for IDUA production and function following adeno-associated virus (AAV) vector transduction of MPS1 patient fibroblasts. Then, an AAV serotype evaluation in human cornea explants identified an AAV8 and 9 chimeric capsid (8G9) as most efficient for transduction. AAV8G9-opt-IDUA administered to human corneas via intrastromal injection demonstrated widespread transduction, which included cells that naturally produce IDUA, and resulted in a >10-fold supraphysiological increase in IDUA activity. No significant apoptosis related to AAV vectors or IDUA was observed under any conditions in both human corneas and MPS1 patient fibroblasts. The collective preclinical data demonstrate safe and efficient IDUA delivery to human corneas, which may prevent and potentially reverse MPS1-associated cornea blindness.

Authors
Vance, M; Llanga, T; Bennett, W; Woodard, K; Murlidharan, G; Chungfat, N; Asokan, A; Gilger, B; Kurtzberg, J; Samulski, RJ; Hirsch, ML
MLA Citation
Vance, M, Llanga, T, Bennett, W, Woodard, K, Murlidharan, G, Chungfat, N, Asokan, A, Gilger, B, Kurtzberg, J, Samulski, RJ, and Hirsch, ML. "AAV Gene Therapy for MPS1-associated Corneal Blindness." Scientific reports 6 (February 22, 2016): 22131-.
PMID
26899286
Source
epmc
Published In
Scientific Reports
Volume
6
Publish Date
2016
Start Page
22131
DOI
10.1038/srep22131

Current perspectives on the use of ancillary materials for the manufacture of cellular therapies.

Continued growth in the cell therapy industry and commercialization of cell therapies that successfully advance through clinical trials has led to increased awareness around the need for specialized and complex materials utilized in their manufacture. Ancillary materials (AMs) are components or reagents used during the manufacture of cell therapy products but are not intended to be part of the final products. Commonly, there are limitations in the availability of clinical-grade reagents used as AMs. Furthermore, AMs may affect the efficacy of the cell product and subsequent safety of the cell therapy for the patient. As such, AMs must be carefully selected and appropriately qualified during the cell therapy development process. However, the ongoing evolution of cell therapy research, limited number of clinical trials and registered cell therapy products results in the current absence of specific regulations governing the composition, compliance, and qualification of AMs often leads to confusion by suppliers and users in this field. Here we provide an overview and interpretation of the existing global framework surrounding AM use and investigate some common misunderstandings within the industry, with the aim of facilitating the appropriate selection and qualification of AMs. The key message we wish to emphasize is that in order to most effectively mitigate risk around cell therapy development and patient safety, users must work with their suppliers and regulators to qualify each AM to assess source, purity, identity, safety, and suitability in a given application.

Authors
Solomon, J; Csontos, L; Clarke, D; Bonyhadi, M; Zylberberg, C; McNiece, I; Kurtzberg, J; Bell, R; Deans, R
MLA Citation
Solomon, J, Csontos, L, Clarke, D, Bonyhadi, M, Zylberberg, C, McNiece, I, Kurtzberg, J, Bell, R, and Deans, R. "Current perspectives on the use of ancillary materials for the manufacture of cellular therapies." Cytotherapy 18.1 (January 2016): 1-12.
PMID
26596503
Source
epmc
Published In
Cytotherapy (Informa)
Volume
18
Issue
1
Publish Date
2016
Start Page
1
End Page
12
DOI
10.1016/j.jcyt.2015.09.010

Preterm umbilical cord blood is enriched for progenitor cells

Authors
Sun, J; Gilner, J; Troy, J; Waters-Pick, B; Page, K; Murtha, A; Kurtzberg, J
MLA Citation
Sun, J, Gilner, J, Troy, J, Waters-Pick, B, Page, K, Murtha, A, and Kurtzberg, J. "Preterm umbilical cord blood is enriched for progenitor cells." January 2016.
Source
wos-lite
Published In
American Journal of Obstetrics & Gynecology
Volume
214
Issue
1
Publish Date
2016
Start Page
S286
End Page
S287

Accelerating stem cell trials for Alzheimer's disease.

At present, no effective cure or prophylaxis exists for Alzheimer's disease. Symptomatic treatments are modestly effective and offer only temporary benefit. Advances in induced pluripotent stem cell (iPSC) technology have the potential to enable development of so-called disease-in-a-dish personalised models to study disease mechanisms and reveal new therapeutic approaches, and large panels of iPSCs enable rapid screening of potential drug candidates. Different cell types can also be produced for therapeutic use. In 2015, the US Food and Drug Administration granted investigational new drug approval for the first phase 2A clinical trial of ischaemia-tolerant mesenchymal stem cells to treat Alzheimer's disease in the USA. Similar trials are either underway or being planned in Europe and Asia. Although safety and ethical concerns remain, we call for the acceleration of human stem cell-based translational research into the causes and potential treatments of Alzheimer's disease.

Authors
Hunsberger, JG; Rao, M; Kurtzberg, J; Bulte, JWM; Atala, A; LaFerla, FM; Greely, HT; Sawa, A; Gandy, S; Schneider, LS; Doraiswamy, PM
MLA Citation
Hunsberger, JG, Rao, M, Kurtzberg, J, Bulte, JWM, Atala, A, LaFerla, FM, Greely, HT, Sawa, A, Gandy, S, Schneider, LS, and Doraiswamy, PM. "Accelerating stem cell trials for Alzheimer's disease." The Lancet. Neurology (December 15, 2015).
PMID
26704439
Source
epmc
Published In
The Lancet Neurology
Publish Date
2015
DOI
10.1016/s1474-4422(15)00332-4

Autologous Cord Blood Infusion for the Treatment of Brain Injury in Children with Cerebral Palsy

Authors
Sun, J; Mikati, M; Troy, J; Gustafson, K; Simmons, R; Goldstein, R; Petry, J; McLaughlin, C; Waters-Pick, B; Case, L; Worley, G; Kurtzberg, J
MLA Citation
Sun, J, Mikati, M, Troy, J, Gustafson, K, Simmons, R, Goldstein, R, Petry, J, McLaughlin, C, Waters-Pick, B, Case, L, Worley, G, and Kurtzberg, J. "Autologous Cord Blood Infusion for the Treatment of Brain Injury in Children with Cerebral Palsy." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

Cord Blood Unit Cryopreservation: Positioning Segments for Potency Assessment

Authors
Shoulars, K; Gentry, T; Noldner, P; Page, KM; Kurtzberg, J
MLA Citation
Shoulars, K, Gentry, T, Noldner, P, Page, KM, and Kurtzberg, J. "Cord Blood Unit Cryopreservation: Positioning Segments for Potency Assessment." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

Impact of GvHD and Other Patient-, Disease-, Donor and Transplantation-Related Factors on 5 Year Relapse after Unrelated Cord Blood Transplantation for Children with Acute Lymphoblastic Leukemia in Remission

Authors
Page, KM; Labopin, M; Ruggeri, A; Michel, G; Diaz de Heredia, C; O'Brien, T; Picardi, A; Ayas, M; Bittencourt, H; Vora, AJ; Volt, F; Gluckman, E; Bader, P; Kurtzberg, J; Rocha, V
MLA Citation
Page, KM, Labopin, M, Ruggeri, A, Michel, G, Diaz de Heredia, C, O'Brien, T, Picardi, A, Ayas, M, Bittencourt, H, Vora, AJ, Volt, F, Gluckman, E, Bader, P, Kurtzberg, J, and Rocha, V. "Impact of GvHD and Other Patient-, Disease-, Donor and Transplantation-Related Factors on 5 Year Relapse after Unrelated Cord Blood Transplantation for Children with Acute Lymphoblastic Leukemia in Remission." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

AAV Gene Therapy for MPS1 Corneal Clouding and Joint Stiffness

Authors
Vance, MA; Hirsch, M; Samulski, RJ; Kurtzberg, J; Goodrich, L; Telmo, L
MLA Citation
Vance, MA, Hirsch, M, Samulski, RJ, Kurtzberg, J, Goodrich, L, and Telmo, L. "AAV Gene Therapy for MPS1 Corneal Clouding and Joint Stiffness." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

Repeated autologous umbilical cord blood infusions are feasible and had no acute safety issues in young babies with congenital hydrocephalus.

Babies with congenital hydrocephalus often experience developmental disabilities due to brain injury associated with prolonged increased pressure on the developing brain parenchyma. Umbilical cord blood (CB) infusion has favorable effects in animal models of brain hypoxia and stroke and is being investigated in clinical trials of brain injury in both children and adults. We sought to establish the safety and feasibility of repeated intravenous infusions of autologous CB in young babies with congenital hydrocephalus.Infants with severe congenital hydrocephalus and an available qualified autologous CB unit traveled to Duke for evaluation and CB infusion. When possible, the CB unit was utilized for multiple infusions. Patient and CB data were obtained at the time of infusion and analyzed retrospectively.From October 2006 to August 2014, 76 patients with congenital hydrocephalus received 143 autologous CB infusions. Most babies received repeated doses, for a total of two (n = 45), three (n = 18), or four (n = 4) infusions. There were no infusion-related adverse events. As expected, all babies experienced developmental delays.Cryopreserved CB products may be effectively manipulated to provide multiple CB doses. Repeated intravenous infusion of autologous CB is safe and feasible in young babies with congenital hydrocephalus.

Authors
Sun, JM; Grant, GA; McLaughlin, C; Allison, J; Fitzgerald, A; Waters-Pick, B; Kurtzberg, J
MLA Citation
Sun, JM, Grant, GA, McLaughlin, C, Allison, J, Fitzgerald, A, Waters-Pick, B, and Kurtzberg, J. "Repeated autologous umbilical cord blood infusions are feasible and had no acute safety issues in young babies with congenital hydrocephalus." Pediatric research 78.6 (December 2015): 712-716.
PMID
26331765
Source
epmc
Published In
Pediatric Research
Volume
78
Issue
6
Publish Date
2015
Start Page
712
End Page
716
DOI
10.1038/pr.2015.161

Hydroxyethyl starch as a substitute for dextran 40 for thawing peripheral blood progenitor cell products.

Removing DMSO post-thaw results in: reduced infusion reactions, improved recovery and stability of viable CD34+ cells. Validated methods use 5%-8.3% Dextran 40 with 2.5%-4.2% HSA for this purpose. Recent shortages of clinical grade Dextran require identification of suitable alternatives.PBPC were used to compare a standard 2X wash medium of 5 parts 10% Dextran 40 in saline (DEX) with 1 part 25% HSA (8.3% DEX/ 4.2% HSA) with Hydroxyethyl Starch (HES)-based solutions. Cells in replicate bags were diluted with an equal volume of wash solution, equilibrated 5 minutes, the bag filled with wash medium, pelleted and the supernatant expressed. Bags were restored to the frozen volume in wash medium and tested by single platform flow cytometry and CFU. Total viability, viable TNC, MNC, and CD34+ cell recovery, and CD34+ cell viability were compared immediately post-thaw and after 90 minutes.5.2% HES/4.2% HSA did not differ from our standard in CD34 recovery or viability. Due to concerns that high concentrations of HES could affect renal function we tested 0.6% HES/2.5% HSA resulting in significantly poorer CD34 recovery and viability. Results improved using 2.4% HES/4.2% HSA and when 0.6% HES/4.2%HSA was used no significant differences were seen. CFU assays confirmed no differences between the standard dextran arm and HES at 2.4% or 0.6% so long as HSA was at 4.2%.We conclude that HES from 0.6% to 5.2% with 4.2% HSA is a suitable substitute for Dextran 40 as a reconstitution/washing medium for PBPC products.

Authors
Zhu, F; Heditke, S; Kurtzberg, J; Waters-Pick, B; Hari, P; Margolis, DA; Keever-Taylor, CA
MLA Citation
Zhu, F, Heditke, S, Kurtzberg, J, Waters-Pick, B, Hari, P, Margolis, DA, and Keever-Taylor, CA. "Hydroxyethyl starch as a substitute for dextran 40 for thawing peripheral blood progenitor cell products." Cytotherapy 17.12 (December 2015): 1813-1819.
PMID
26454752
Source
epmc
Published In
Cytotherapy (Informa)
Volume
17
Issue
12
Publish Date
2015
Start Page
1813
End Page
1819
DOI
10.1016/j.jcyt.2015.08.007

Chagas disease screening in umbilical cord blood: an opportunity for prevention

Authors
Edwards, J; Gilner, J; Kurtzberg, J; Heine, R
MLA Citation
Edwards, J, Gilner, J, Kurtzberg, J, and Heine, R. "Chagas disease screening in umbilical cord blood: an opportunity for prevention." December 2015.
Source
wos-lite
Published In
American Journal of Obstetrics & Gynecology
Volume
213
Issue
6
Publish Date
2015
Start Page
906
End Page
907

Durable engraftment and correction of hematological abnormalities in children with congenital amegakaryocytic thrombocytopenia following myeloablative umbilical cord blood transplantation.

The use of HSCT is the only potentially curative treatment for CAMT, but access is limited by the availability of suitable donors. We report five consecutive patients with CAMT who received MAC and partially HLA-mismatched, UCBT (unrelated, n = 4). Median times to neutrophil (>500/μL) and platelet (≥20 000 and ≥50 000/μL) engraftment were 19, 57, and 70 days, respectively. Acute GvHD, grade II, developed in one patient, who subsequently developed limited chronic GvHD. At median follow-up of 14 yr, all patients are alive with sustained donor cell engraftment. To our knowledge, this is the largest single-center series of UCBT for patients with this disease and suggests that UCBT is a successful curative option for patients with CAMT.

Authors
Mahadeo, KM; Tewari, P; Parikh, SH; Driscoll, TA; Page, K; Martin, PL; Kurtzberg, J; Prasad, VK
MLA Citation
Mahadeo, KM, Tewari, P, Parikh, SH, Driscoll, TA, Page, K, Martin, PL, Kurtzberg, J, and Prasad, VK. "Durable engraftment and correction of hematological abnormalities in children with congenital amegakaryocytic thrombocytopenia following myeloablative umbilical cord blood transplantation." Pediatric transplantation 19.7 (November 2015): 753-757.
PMID
26369627
Source
epmc
Published In
Pediatric Transplantation
Volume
19
Issue
7
Publish Date
2015
Start Page
753
End Page
757
DOI
10.1111/petr.12577

Umbilical cord blood donation: public or private?

Umbilical cord blood (UCB) is a graft source for patients with malignant or genetic diseases who can be cured by allogeneic hematopoietic cell transplantation (HCT), but who do not have an appropriately HLA-matched family or volunteer unrelated adult donor. Starting in the 1990s, unrelated UCB banks were established, accepting donations from term deliveries and storing UCB units for public use. An estimated 730 000 UCB units have been donated and stored to date and ~35 000 UCB transplants have been performed worldwide. Over the past 20 years, private and family banks have grown rapidly, storing ~4 million UCB units for a particular patient or family, usually charging an up-front and yearly storage fee; therefore, these banks are able to be financially sustainable without releasing UCB units. Private banks are not obligated to fulfill the same regulatory requirements of the public banks. The public banks have released ~30 times more UCB units for therapy. Some countries have transitioned to an integrated banking model, a hybrid of public and family banking. Today, pregnant women, their families, obstetrical providers and pediatricians are faced with multiple choices about the disposition of their newborn's cord blood. In this commentary, we review the progress of UCB banking technology; we also analyze the current data on pediatric and adult unrelated UCB, including the recent expansion of interest in transplantation for hemoglobinopathies, and discuss emerging studies on the use of autologous UCB for neurologic diseases and regenerative medicine. We will review worldwide approaches to UCB banking, ethical considerations, criteria for public and family banking, integrated banking ideas and future strategies for UCB banking.

Authors
Ballen, KK; Verter, F; Kurtzberg, J
MLA Citation
Ballen, KK, Verter, F, and Kurtzberg, J. "Umbilical cord blood donation: public or private?." Bone marrow transplantation 50.10 (October 2015): 1271-1278.
PMID
26030051
Source
epmc
Published In
Bone Marrow Transplantation
Volume
50
Issue
10
Publish Date
2015
Start Page
1271
End Page
1278
DOI
10.1038/bmt.2015.124

Reprint of: Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases.

Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period.DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by direct biochemical analysis; alloreactivity of DUOC-01 and of peripheral blood (PB) mononuclear cells (MNC) to DUOC-01 by mixed lymphocyte culture methods; and cytokine secretion by Bioplex assays.DUOC-01 cultures contained highly active, attached, motile, slowly proliferating cells that expressed common (cluster of differentiation [CD]11b, CD14 and Iba1), M1 type (CD16, inducible nitric oxide synthase), and M2-type (CD163, CD206) macrophage or microglia markers. Activities of 11 disease-relevant lysosomal enzymes in DUOC-01 products were similar to those of normal PB cells. All DUOC-01 products secreted interleukin (IL)-6 and IL-10. Accumulation of transforming growth factor-β, IL-1β, interferon-γ and TNF-α in supernatants was variable. IL-12, IL-2, IL-4, IL-5 and IL-13 were not detected at significant concentrations. Galactocerebrosidase, transforming growth factor-β and IL-10 transcripts were specifically enriched in DUOC-01 relative to CB cells. PB MNCs proliferated and released cytokines in response to DUOC-01. DUOC-01 did not proliferate in response to mismatched MNC.DUOC-01 has potential as an adjunctive cell therapy to myeloablative CB transplant for treatment of inherited metabolic diseases.

Authors
Kurtzberg, J; Buntz, S; Gentry, T; Noeldner, P; Ozamiz, A; Rusche, B; Storms, RW; Wollish, A; Wenger, DA; Balber, AE
MLA Citation
Kurtzberg, J, Buntz, S, Gentry, T, Noeldner, P, Ozamiz, A, Rusche, B, Storms, RW, Wollish, A, Wenger, DA, and Balber, AE. "Reprint of: Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases." Cytotherapy 17.9 (September 2015): 1314-1326.
PMID
26276011
Source
epmc
Published In
Cytotherapy (Informa)
Volume
17
Issue
9
Publish Date
2015
Start Page
1314
End Page
1326
DOI
10.1016/j.jcyt.2015.07.014

Rapid and Efficient Generation of Transgene-Free iPSC from a Small Volume of Cryopreserved Blood.

Human peripheral blood and umbilical cord blood represent attractive sources of cells for reprogramming to induced pluripotent stem cells (iPSCs). However, to date, most of the blood-derived iPSCs were generated using either integrating methods or starting from T-lymphocytes that have genomic rearrangements thus bearing uncertain consequences when using iPSC-derived lineages for disease modeling and cell therapies. Recently, both peripheral blood and cord blood cells have been reprogrammed into transgene-free iPSC using the Sendai viral vector. Here we demonstrate that peripheral blood can be utilized for medium-throughput iPSC production without the need to maintain cell culture prior to reprogramming induction. Cell reprogramming can also be accomplished with as little as 3000 previously cryopreserved cord blood cells under feeder-free and chemically defined Xeno-free conditions that are compliant with standard Good Manufacturing Practice (GMP) regulations. The first iPSC colonies appear 2-3 weeks faster in comparison to previous reports. Notably, these peripheral blood- and cord blood-derived iPSCs are free of detectable immunoglobulin heavy chain (IGH) and T cell receptor (TCR) gene rearrangements, suggesting they did not originate from B- or T- lymphoid cells. The iPSCs are pluripotent as evaluated by the scorecard assay and in vitro multi lineage functional cell differentiation. Our data show that small volumes of cryopreserved peripheral blood or cord blood cells can be reprogrammed efficiently at a convenient, cost effective and scalable way. In summary, our method expands the reprogramming potential of limited or archived samples either stored at blood banks or obtained from pediatric populations that cannot easily provide large quantities of peripheral blood or a skin biopsy.

Authors
Zhou, H; Martinez, H; Sun, B; Li, A; Zimmer, M; Katsanis, N; Davis, EE; Kurtzberg, J; Lipnick, S; Noggle, S; Rao, M; Chang, S
MLA Citation
Zhou, H, Martinez, H, Sun, B, Li, A, Zimmer, M, Katsanis, N, Davis, EE, Kurtzberg, J, Lipnick, S, Noggle, S, Rao, M, and Chang, S. "Rapid and Efficient Generation of Transgene-Free iPSC from a Small Volume of Cryopreserved Blood." Stem cell reviews 11.4 (August 2015): 652-665.
PMID
25951995
Source
epmc
Published In
Stem Cell Reviews and Reports
Volume
11
Issue
4
Publish Date
2015
Start Page
652
End Page
665
DOI
10.1007/s12015-015-9586-8

Identification of cis-suppression of human disease mutations by comparative genomics.

Patterns of amino acid conservation have served as a tool for understanding protein evolution. The same principles have also found broad application in human genomics, driven by the need to interpret the pathogenic potential of variants in patients. Here we performed a systematic comparative genomics analysis of human disease-causing missense variants. We found that an appreciable fraction of disease-causing alleles are fixed in the genomes of other species, suggesting a role for genomic context. We developed a model of genetic interactions that predicts most of these to be simple pairwise compensations. Functional testing of this model on two known human disease genes revealed discrete cis amino acid residues that, although benign on their own, could rescue the human mutations in vivo. This approach was also applied to ab initio gene discovery to support the identification of a de novo disease driver in BTG2 that is subject to protective cis-modification in more than 50 species. Finally, on the basis of our data and models, we developed a computational tool to predict candidate residues subject to compensation. Taken together, our data highlight the importance of cis-genomic context as a contributor to protein evolution; they provide an insight into the complexity of allele effect on phenotype; and they are likely to assist methods for predicting allele pathogenicity.

Authors
Jordan, DM; Frangakis, SG; Golzio, C; Cassa, CA; Kurtzberg, J; Davis, EE; Sunyaev, SR; Katsanis, N
MLA Citation
Jordan, DM, Frangakis, SG, Golzio, C, Cassa, CA, Kurtzberg, J, Davis, EE, Sunyaev, SR, and Katsanis, N. "Identification of cis-suppression of human disease mutations by comparative genomics." Nature 524.7564 (August 2015): 225-229.
PMID
26123021
Source
epmc
Published In
Nature
Volume
524
Issue
7564
Publish Date
2015
Start Page
225
End Page
229
DOI
10.1038/nature14497

Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases.

Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period.DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by direct biochemical analysis; alloreactivity of DUOC-01 and of peripheral blood (PB) mononuclear cells (MNC) to DUOC-01 by mixed lymphocyte culture methods; and cytokine secretion by Bioplex assays.DUOC-01 cultures contained highly active, attached, motile, slowly proliferating cells that expressed common (cluster of differentiation [CD]11b, CD14 and Iba1), M1 type (CD16, inducible nitric oxide synthase), and M2-type (CD163, CD206) macrophage or microglia markers. Activities of 11 disease-relevant lysosomal enzymes in DUOC-01 products were similar to those of normal PB cells. All DUOC-01 products secreted interleukin (IL)-6 and IL-10. Accumulation of transforming growth factor-β, IL-1β, interferon-γ and TNF-α in supernatants was variable. IL-12, IL-2, IL-4, IL-5 and IL-13 were not detected at significant concentrations. Galactocerebrosidase, transforming growth factor-β and IL-10 transcripts were specifically enriched in DUOC-01 relative to CB cells. PB MNCs proliferated and released cytokines in response to DUOC-01. DUOC-01 did not proliferate in response to mismatched MNC.DUOC-01 has potential as an adjunctive cell therapy to myeloablative CB transplant for treatment of inherited metabolic diseases.

Authors
Kurtzberg, J; Buntz, S; Gentry, T; Noeldner, P; Ozamiz, A; Rusche, B; Storms, RW; Wollish, A; Wenger, DA; Balber, AE
MLA Citation
Kurtzberg, J, Buntz, S, Gentry, T, Noeldner, P, Ozamiz, A, Rusche, B, Storms, RW, Wollish, A, Wenger, DA, and Balber, AE. "Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases." Cytotherapy 17.6 (June 2015): 803-815.
PMID
25770677
Source
epmc
Published In
Cytotherapy (Informa)
Volume
17
Issue
6
Publish Date
2015
Start Page
803
End Page
815
DOI
10.1016/j.jcyt.2015.02.006

Cord blood for brain injury.

Recovery from neurological injuries is typically incomplete and often results in significant and permanent disabilities. Currently, most available therapies are limited to supportive or palliative measures, aimed at managing the symptoms of the condition. Because restorative therapies targeting the underlying cause of most neurological diseases do not exist, cell therapies targeting anti-inflammatory, neuroprotective and regenerative potential hold great promise. Cord blood (CB) cells can induce repair through mechanisms that involve trophic or cell-based paracrine effects or cellular integration and differentiation. Both may be operative in emerging CB therapies for neurologic conditions, and there are numerous potential applications of CB-based regenerative therapies in neurological diseases, including genetic diseases of childhood, ischemic events such as stroke and neurodegenerative diseases of adulthood. CB appears to hold promise as an effective therapy for patients with brain injuries. In this Review, we describe the state of science and clinical applications of CB therapy for brain injury.

Authors
Sun, JM; Kurtzberg, J
MLA Citation
Sun, JM, and Kurtzberg, J. "Cord blood for brain injury." Cytotherapy 17.6 (June 2015): 775-785.
PMID
25800775
Source
epmc
Published In
Cytotherapy (Informa)
Volume
17
Issue
6
Publish Date
2015
Start Page
775
End Page
785
DOI
10.1016/j.jcyt.2015.03.004

Cord blood is the optimal graft source for the treatment of pediatric patients with lysosomal storage diseases: clinical outcomes and future directions.

Initially used as an alternative hematopoietic stem cell source for patients without a human leukocyte antigen-matched bone marrow or peripheral blood stem cell donor, unrelated cord blood (UCB) is now the preferred donor source when hematopoietic stem cell transplantation (HSCT) is used to treat patients with lysosomal storage disorders (LSD). Without transplantation, these patients have serious progressive multi-system deterioration and premature death. UCB transplantation favorably alters the natural history of these diseases and prolongs survival. It primarily works through cellular enzyme replacement by healthy engrafted donor cells providing a continuous endogenous supply of enzyme throughout the body and, thorough engraftment of donor-derived microgial cells, in the central nervous system. HSCT in LSD, the majority performed in patients with mucopolysaccharidoses and leukodystrophies, is associated with remarkably high rates of engraftment and survival. Importantly, recipients of UCB, as compared with other donor sources, more often achieve full-donor chimerism and normalization of enzyme levels, which has been associated with superior long-term clinical prognosis. Additionally, UCB units are readily available, reducing time to transplantation and thereby providing access to transplant at young ages, another highly important predictor for long-term neuro-developmental function. For these reasons, UCB grafts are nowadays considered to be the optimal graft source for HSCT in patients with LSD.

Authors
Aldenhoven, M; Kurtzberg, J
MLA Citation
Aldenhoven, M, and Kurtzberg, J. "Cord blood is the optimal graft source for the treatment of pediatric patients with lysosomal storage diseases: clinical outcomes and future directions." Cytotherapy 17.6 (June 2015): 765-774.
PMID
25840940
Source
epmc
Published In
Cytotherapy (Informa)
Volume
17
Issue
6
Publish Date
2015
Start Page
765
End Page
774
DOI
10.1016/j.jcyt.2015.03.609

THE USE OF HYDROXYETHYL STARCH (HES) AS A SUBSTITUTE FOR DEXTRAN 40 IN THE THAW AND WASHING OF HPC, APHERESIS PRODUCTS

Authors
Zhu, F; Heidtke, SM; Kurtzberg, J; Hari, P; Margolis, DA; Keever-Taylor, C
MLA Citation
Zhu, F, Heidtke, SM, Kurtzberg, J, Hari, P, Margolis, DA, and Keever-Taylor, C. "THE USE OF HYDROXYETHYL STARCH (HES) AS A SUBSTITUTE FOR DEXTRAN 40 IN THE THAW AND WASHING OF HPC, APHERESIS PRODUCTS." CYTOTHERAPY 17.6 (June 2015): S60-S60.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
17
Issue
6
Publish Date
2015
Start Page
S60
End Page
S60

CORD BLOOD DERIVED CELL THERAPY PRODUCT, DUOC-01, ACCELERATES REMYELINATION IN A MURINE MODEL OF CUPRIZONE INDUCED DEMYELINATION

Authors
Saha, A; Buntz, S; Patel, S; Bentz, M; Snyder, D; Ozamiz, A; Rusche, B; Gentry, T; Glenn, M; Kurtzberg, J; Balber, A
MLA Citation
Saha, A, Buntz, S, Patel, S, Bentz, M, Snyder, D, Ozamiz, A, Rusche, B, Gentry, T, Glenn, M, Kurtzberg, J, and Balber, A. "CORD BLOOD DERIVED CELL THERAPY PRODUCT, DUOC-01, ACCELERATES REMYELINATION IN A MURINE MODEL OF CUPRIZONE INDUCED DEMYELINATION." CYTOTHERAPY 17.6 (June 2015): S55-S55.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
17
Issue
6
Publish Date
2015
Start Page
S55
End Page
S55

HUMAN CORD BLOOD DERIVED CD14 CELL THERAPY PROVIDES NEUROPROTECTION IN AQUIRED BRAIN INJURY

Authors
Patel, S; Saha, A; Buntz, S; Bentz, M; Scotland, P; Storms, R; Ramamurthy, P; Kurtzberg, J; Balber, A
MLA Citation
Patel, S, Saha, A, Buntz, S, Bentz, M, Scotland, P, Storms, R, Ramamurthy, P, Kurtzberg, J, and Balber, A. "HUMAN CORD BLOOD DERIVED CD14 CELL THERAPY PROVIDES NEUROPROTECTION IN AQUIRED BRAIN INJURY." CYTOTHERAPY 17.6 (June 2015): S57-S57.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
17
Issue
6
Publish Date
2015
Start Page
S57
End Page
S57

ALDEHYDE DEHYDROGENASE, BUT NOT VIABILITY OF CD34 CELLS, PREDICTS POTENCY AND ENGRAFTMENT AFTER CORD BLOOD TRANSPLANTATION

Authors
Shoulars, K; Troy, JD; Gentry, T; Noldner, P; Page, K; Balber, A; Kurtzberg, J
MLA Citation
Shoulars, K, Troy, JD, Gentry, T, Noldner, P, Page, K, Balber, A, and Kurtzberg, J. "ALDEHYDE DEHYDROGENASE, BUT NOT VIABILITY OF CD34 CELLS, PREDICTS POTENCY AND ENGRAFTMENT AFTER CORD BLOOD TRANSPLANTATION." CYTOTHERAPY 17.6 (June 2015): S14-S14.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
17
Issue
6
Publish Date
2015
Start Page
S14
End Page
S14

NEURAL ENGRAFTMENT OF A CORD BLOOD-DERIVED CELL PRODUCT FOLLOWING INTRATHECAL TRANSPLANTATION

Authors
Storms, R; Lew, J; Liu, C; Gentry, T; Ozamiz, A; Rusche, B; Balber, A; Kurtzberg, J
MLA Citation
Storms, R, Lew, J, Liu, C, Gentry, T, Ozamiz, A, Rusche, B, Balber, A, and Kurtzberg, J. "NEURAL ENGRAFTMENT OF A CORD BLOOD-DERIVED CELL PRODUCT FOLLOWING INTRATHECAL TRANSPLANTATION." CYTOTHERAPY 17.6 (June 2015): S56-S56.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
17
Issue
6
Publish Date
2015
Start Page
S56
End Page
S56

Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation

© 2015 American Society for Blood and Marrow Transplantation.Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P=001) or plasma and red cell reduced (odds ratio, .54; P=05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P=04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery.

Authors
Ballen, KK; Logan, BR; Laughlin, MJ; He, W; Ambruso, DR; Armitage, SE; Beddard, RL; Bhatla, D; Hwang, WYK; Kiss, JE; Koegler, G; Kurtzberg, J; Nagler, A; Oh, D; Petz, LD; Price, TH; Quinones, RR; Ratanatharathorn, V; Rizzo, JD; Sazama, K; Scaradavou, A; Schuster, MW; Sender, LS; Shpall, EJ; Spellman, SR; Sutton, M; Weitekamp, LA; Wingard, JR; Eapen, M
MLA Citation
Ballen, KK, Logan, BR, Laughlin, MJ, He, W, Ambruso, DR, Armitage, SE, Beddard, RL, Bhatla, D, Hwang, WYK, Kiss, JE, Koegler, G, Kurtzberg, J, Nagler, A, Oh, D, Petz, LD, Price, TH, Quinones, RR, Ratanatharathorn, V, Rizzo, JD, Sazama, K, Scaradavou, A, Schuster, MW, Sender, LS, Shpall, EJ, Spellman, SR, Sutton, M, Weitekamp, LA, Wingard, JR, and Eapen, M. "Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation." Biology of Blood and Marrow Transplantation 21.4 (April 1, 2015): 688-695.
Source
scopus
Published In
Biology of Blood and Marrow Transplantation
Volume
21
Issue
4
Publish Date
2015
Start Page
688
End Page
695
DOI
10.1016/j.bbmt.2014.12.017

Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation.

Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery.

Authors
Ballen, KK; Logan, BR; Laughlin, MJ; He, W; Ambruso, DR; Armitage, SE; Beddard, RL; Bhatla, D; Hwang, WYK; Kiss, JE; Koegler, G; Kurtzberg, J; Nagler, A; Oh, D; Petz, LD; Price, TH; Quinones, RR; Ratanatharathorn, V; Rizzo, JD; Sazama, K; Scaradavou, A; Schuster, MW; Sender, LS; Shpall, EJ; Spellman, SR; Sutton, M; Weitekamp, LA; Wingard, JR; Eapen, M
MLA Citation
Ballen, KK, Logan, BR, Laughlin, MJ, He, W, Ambruso, DR, Armitage, SE, Beddard, RL, Bhatla, D, Hwang, WYK, Kiss, JE, Koegler, G, Kurtzberg, J, Nagler, A, Oh, D, Petz, LD, Price, TH, Quinones, RR, Ratanatharathorn, V, Rizzo, JD, Sazama, K, Scaradavou, A, Schuster, MW, Sender, LS, Shpall, EJ, Spellman, SR, Sutton, M, Weitekamp, LA, Wingard, JR, and Eapen, M. "Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 21.4 (April 2015): 688-695.
PMID
25543094
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
21
Issue
4
Publish Date
2015
Start Page
688
End Page
695
DOI
10.1016/j.bbmt.2014.12.017

Newborns of obese parents have altered DNA methylation patterns at imprinted genes.

BACKGROUND: Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity. OBJECTIVE: We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT). METHODS: We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ⩾30 kg m(-2), was ascertained through standardized questionnaires. RESULTS: After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (β=-2.57; s.e.=0.95; P=0.008), PEG3 (β=-1.71; s.e.=0.61; P=0.005) and NNAT (β=-3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: β-coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR. CONCLUSION: We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood.

Authors
Soubry, A; Murphy, SK; Wang, F; Huang, Z; Vidal, AC; Fuemmeler, BF; Kurtzberg, J; Murtha, A; Jirtle, RL; Schildkraut, JM; Hoyo, C
MLA Citation
Soubry, A, Murphy, SK, Wang, F, Huang, Z, Vidal, AC, Fuemmeler, BF, Kurtzberg, J, Murtha, A, Jirtle, RL, Schildkraut, JM, and Hoyo, C. "Newborns of obese parents have altered DNA methylation patterns at imprinted genes." Int J Obes (Lond) 39.4 (April 2015): 650-657.
PMID
24158121
Source
pubmed
Published In
International Journal of Obesity
Volume
39
Issue
4
Publish Date
2015
Start Page
650
End Page
657
DOI
10.1038/ijo.2013.193

Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study.

Mucopolysaccharidosis type I-Hurler syndrome (MPS-IH) is a lysosomal storage disease characterized by multisystem morbidity and death in early childhood. Although hematopoietic cell transplantation (HCT) has been performed in these patients for more than 30 years, large studies on the long-term outcome of patients with MPS-IH after HCT are lacking. The goal of this international study was to identify predictors of the long-term outcome of patients with MPS-IH after successful HCT. Two hundred seventeen patients with MPS-IH successfully engrafted with a median follow-up age of 9.2 years were included in this retrospective analysis. Primary endpoints were neurodevelopmental outcomes and growth. Secondary endpoints included neurologic, orthopedic, cardiac, respiratory, ophthalmologic, audiologic, and endocrinologic outcomes. Considerable residual disease burden was observed in the majority of the transplanted patients with MPS-IH, with high variability between patients. Preservation of cognitive function at HCT and a younger age at transplantation were major predictors for superior cognitive development posttransplant. A normal α-l-iduronidase enzyme level obtained post-HCT was another highly significant predictor for superior long-term outcome in most organ systems. The long-term prognosis of patients with MPS-IH receiving HCT can be improved by reducing the age at HCT through earlier diagnosis, as well as using exclusively noncarrier donors and achieving complete donor chimerism.

Authors
Aldenhoven, M; Wynn, RF; Orchard, PJ; O'Meara, A; Veys, P; Fischer, A; Valayannopoulos, V; Neven, B; Rovelli, A; Prasad, VK; Tolar, J; Allewelt, H; Jones, SA; Parini, R; Renard, M; Bordon, V; Wulffraat, NM; de Koning, TJ; Shapiro, EG; Kurtzberg, J; Boelens, JJ
MLA Citation
Aldenhoven, M, Wynn, RF, Orchard, PJ, O'Meara, A, Veys, P, Fischer, A, Valayannopoulos, V, Neven, B, Rovelli, A, Prasad, VK, Tolar, J, Allewelt, H, Jones, SA, Parini, R, Renard, M, Bordon, V, Wulffraat, NM, de Koning, TJ, Shapiro, EG, Kurtzberg, J, and Boelens, JJ. "Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study." Blood 125.13 (March 2015): 2164-2172.
PMID
25624320
Source
epmc
Published In
Blood
Volume
125
Issue
13
Publish Date
2015
Start Page
2164
End Page
2172
DOI
10.1182/blood-2014-11-608075

Early HSCT corrects the skeleton in MPS.

In this issue of Blood, Pievani et al have identified a potential solution to the remaining barrier to the success of hematopoietic stem cell transplantation (HSCT) in children with severe phenotype Hurler syndrome (mucopolysaccharidosis type I [MPS I]).

Authors
Kurtzberg, J
MLA Citation
Kurtzberg, J. "Early HSCT corrects the skeleton in MPS." Blood 125.10 (March 2015): 1518-1519.
PMID
25745184
Source
epmc
Published In
Blood
Volume
125
Issue
10
Publish Date
2015
Start Page
1518
End Page
1519
DOI
10.1182/blood-2014-11-606681

Impact of Clinical Phenotype of Wiskott-Aldrich Syndrome on Outcomes after Unrelated Cord Blood Transplantation: a Risk Factor Analysis

Authors
Shekhovtsova, Z; Bonfim, C; Ruggeri, A; Nichele, S; Page, K; AlSeraihy, A; Barriga, FC; de Toledo Codina, JS; Veys, P; Boelens, JJ; Mellgren, K; Bittencourt, H; O'Brien, T; Shaw, PJ; Chybicka, A; Volt, F; Giannotti, F; Gluckman, E; Kurtzberg, J; Gennery, A; Rocha, V
MLA Citation
Shekhovtsova, Z, Bonfim, C, Ruggeri, A, Nichele, S, Page, K, AlSeraihy, A, Barriga, FC, de Toledo Codina, JS, Veys, P, Boelens, JJ, Mellgren, K, Bittencourt, H, O'Brien, T, Shaw, PJ, Chybicka, A, Volt, F, Giannotti, F, Gluckman, E, Kurtzberg, J, Gennery, A, and Rocha, V. "Impact of Clinical Phenotype of Wiskott-Aldrich Syndrome on Outcomes after Unrelated Cord Blood Transplantation: a Risk Factor Analysis." March 2015.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
50
Publish Date
2015
Start Page
S469
End Page
S469

Efficacy and Safety of Hematopoietic Stem Cell Therapy in Adrenoleukodystrophy: a Multi-Institutional Study

Authors
Paker, A; Dalle, J-H; Balser, J; Paedre, S; Gerard, M; Escolar, M; Aubourg, P; Fischer, A; Kurtzberg, J; Baruchel, A; Raymond, G; Orchard, P
MLA Citation
Paker, A, Dalle, J-H, Balser, J, Paedre, S, Gerard, M, Escolar, M, Aubourg, P, Fischer, A, Kurtzberg, J, Baruchel, A, Raymond, G, and Orchard, P. "Efficacy and Safety of Hematopoietic Stem Cell Therapy in Adrenoleukodystrophy: a Multi-Institutional Study." March 2015.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
50
Publish Date
2015
Start Page
S44
End Page
S44

Outcomes Of Allogeneic Cord Blood Transplantation For Leukodystrophies; A Joint Study of Eurocord, Duke University Medical Center Cord blood committee of Cellular Therapy and Immunobiology and Inborn Errors WP-EBMT

Authors
Boelens, JJ; Hol, J; Ruggeri, A; Page, K; Gluckman, E; Gennery, A; Rocha, V; Kurtzberg, J; University, D
MLA Citation
Boelens, JJ, Hol, J, Ruggeri, A, Page, K, Gluckman, E, Gennery, A, Rocha, V, Kurtzberg, J, and University, D. "Outcomes Of Allogeneic Cord Blood Transplantation For Leukodystrophies; A Joint Study of Eurocord, Duke University Medical Center Cord blood committee of Cellular Therapy and Immunobiology and Inborn Errors WP-EBMT." March 2015.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
50
Publish Date
2015
Start Page
S106
End Page
S106

Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma.

The outcome of children, adolescents and young adults (CAYA) with poor-risk recurrent/refractory lymphoma is dismal (⩽30%). To overcome this poor prognosis, we designed an approach to maximize an allogeneic graft vs lymphoma effect in the setting of low disease burden. We conducted a multi-center prospective study of myeloablative conditioning (MAC) and autologous stem cell transplantation (AutoSCT), followed by a reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (AlloHCT) in CAYA, with poor-risk refractory or recurrent lymphoma. Conditioning for MAC AutoSCT consisted of carmustine/etoposide/cyclophosphamide, RIC consisted of busulfan/fludarabine. Thirty patients, 16 Hodgkin lymphoma (HL) and 14 non-Hodgkin lymphoma (NHL), with a median age of 16 years and median follow-up of 5years, were enrolled. Twenty-three patients completed both MAC AutoSCT and RIC AlloHCT. Allogeneic donor sources included unrelated cord blood (n=9), unrelated donor (n=8) and matched siblings (n=6). The incidence of transplant-related mortality following RIC AlloHCT was only 12%. In patients with HL and NHL, 10 year EFS was 59.8% and 70% (P=0.613), respectively. In summary, this approach is safe, and long-term EFS with this approach is encouraging considering the poor-risk patient characteristics and the use of unrelated donors for RIC AlloHCT in the majority of cases.

Authors
Satwani, P; Jin, Z; Martin, PL; Bhatia, M; Garvin, JH; George, D; Chaudhury, S; Talano, J; Morris, E; Harrison, L; Sosna, J; Peterson, M; Militano, O; Foley, S; Kurtzberg, J; Cairo, MS
MLA Citation
Satwani, P, Jin, Z, Martin, PL, Bhatia, M, Garvin, JH, George, D, Chaudhury, S, Talano, J, Morris, E, Harrison, L, Sosna, J, Peterson, M, Militano, O, Foley, S, Kurtzberg, J, and Cairo, MS. "Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma." February 2015.
PMID
24938649
Source
epmc
Published In
Leukemia
Volume
29
Issue
2
Publish Date
2015
Start Page
448
End Page
455
DOI
10.1038/leu.2014.194

Outcomes of Second Unrelated Donor Cord Blood Transplants (UCBT) Performed in Children with Graft Failure of Autologous Recovery Following the First UCBT

Authors
McFarren, A; Smith, PB; Page, K; Allewelt, HB; Parikh, S; Driscoll, TA; Martin, PL; Kurtzberg, J; Prasad, VK
MLA Citation
McFarren, A, Smith, PB, Page, K, Allewelt, HB, Parikh, S, Driscoll, TA, Martin, PL, Kurtzberg, J, and Prasad, VK. "Outcomes of Second Unrelated Donor Cord Blood Transplants (UCBT) Performed in Children with Graft Failure of Autologous Recovery Following the First UCBT." February 2015.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
21
Issue
2
Publish Date
2015
Start Page
S37
End Page
S38

Hyperthyroidism As a Complication Following Myloablative Therapy and Stem Cell Transplantation for Childhood Diseases

Authors
Ciocci, G; Stafford, L; Driscoll, TA; Martin, PL; Kurtzberg, J
MLA Citation
Ciocci, G, Stafford, L, Driscoll, TA, Martin, PL, and Kurtzberg, J. "Hyperthyroidism As a Complication Following Myloablative Therapy and Stem Cell Transplantation for Childhood Diseases." February 2015.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
21
Issue
2
Publish Date
2015
Start Page
S214
End Page
S215

Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma

Authors
Satwani, P; Jin, Z; Martin, PL; Bhatia, M; Garvin, JH; George, D; Chaudhury, S; Talano, J; Morris, E; Harrison, L; Sosna, J; Peterson, M; Militano, O; Foley, S; Kurtzberg, J; Cairo, MS
MLA Citation
Satwani, P, Jin, Z, Martin, PL, Bhatia, M, Garvin, JH, George, D, Chaudhury, S, Talano, J, Morris, E, Harrison, L, Sosna, J, Peterson, M, Militano, O, Foley, S, Kurtzberg, J, and Cairo, MS. "Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma." LEUKEMIA 29.2 (February 2015): 448-455.
Source
wos-lite
Published In
Leukemia
Volume
29
Issue
2
Publish Date
2015
Start Page
448
End Page
455
DOI
10.1038/leu.2014.194

Treatment with Human Mesenchymal Stem Cells (Remestemcel-L) Is Effective in Pediatric Patients with Refractory Acute Graft Versus Host Disease

Authors
Kurtzberg, J; Prockop, SE; Prasad, VK; Chaudhury, S; Teira, P; Nemecek, E; Horn, B; Burke, E; Hayes, J; Skerrett, D
MLA Citation
Kurtzberg, J, Prockop, SE, Prasad, VK, Chaudhury, S, Teira, P, Nemecek, E, Horn, B, Burke, E, Hayes, J, and Skerrett, D. "Treatment with Human Mesenchymal Stem Cells (Remestemcel-L) Is Effective in Pediatric Patients with Refractory Acute Graft Versus Host Disease." February 2015.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
21
Issue
2
Publish Date
2015
Start Page
S338
End Page
S339

Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy.

Cerebral Palsy (CP) refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005). Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years) in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI) is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI) and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17), who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM) connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study.

Authors
Englander, ZA; Sun, J; Laura Case, ; Mikati, MA; Kurtzberg, J; Song, AW
MLA Citation
Englander, ZA, Sun, J, Laura Case, , Mikati, MA, Kurtzberg, J, and Song, AW. "Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy." NeuroImage. Clinical 7 (January 9, 2015): 315-324.
PMID
25610796
Source
epmc
Published In
NeuroImage: Clinical
Volume
7
Publish Date
2015
Start Page
315
End Page
324
DOI
10.1016/j.nicl.2015.01.002

Newborns of obese parents have altered DNA methylation patterns at imprinted genes

Background:Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity.Objective:We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT).Methods:We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ≥30 kg m -2, was ascertained through standardized questionnaires.Results:After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (β=-2.57; s.e.=0.95; P=0.008), PEG3 (β=-1.71; s.e.=0.61; P=0.005) and NNAT (β=-3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: β-coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR.Conclusion:We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood.

Authors
Soubry, A; Murphy, SK; Wang, F; Huang, Z; Vidal, AC; Fuemmeler, BF; Kurtzberg, J; Murtha, A; Jirtle, RL; Schildkraut, JM; Hoyo, C
MLA Citation
Soubry, A, Murphy, SK, Wang, F, Huang, Z, Vidal, AC, Fuemmeler, BF, Kurtzberg, J, Murtha, A, Jirtle, RL, Schildkraut, JM, and Hoyo, C. "Newborns of obese parents have altered DNA methylation patterns at imprinted genes." International Journal of Obesity 39.4 (January 1, 2015): 650-657.
Source
scopus
Published In
International Journal of Obesity
Volume
39
Issue
4
Publish Date
2015
Start Page
650
End Page
657
DOI
10.1038/ijo.2013.193

Cord blood for brain injury

© 2015 International Society for Cellular Therapy.Recovery from neurological injuries is typically incomplete and often results in significant and permanent disabilities. Currently, most available therapies are limited to supportive or palliative measures, aimed at managing the symptoms of the condition. Because restorative therapies targeting the underlying cause of most neurological diseases do not exist, cell therapies targeting anti-inflammatory, neuroprotective and regenerative potential hold great promise. Cord blood (CB) cells can induce repair through mechanisms that involve trophic or cell-based paracrine effects or cellular integration and differentiation. Both may be operative in emerging CB therapies for neurologic conditions, and there are numerous potential applications of CB-based regenerative therapies in neurological diseases, including genetic diseases of childhood, ischemic events such as stroke and neurodegenerative diseases of adulthood. CB appears to hold promise as an effective therapy for patients with brain injuries. In this Review, we describe the state of science and clinical applications of CB therapy for brain injury.

Authors
Sun, JM; Kurtzberg, J
MLA Citation
Sun, JM, and Kurtzberg, J. "Cord blood for brain injury." Cytotherapy 17.6 (January 1, 2015): 775-785. (Review)
Source
scopus
Published In
Cytotherapy (Informa)
Volume
17
Issue
6
Publish Date
2015
Start Page
775
End Page
785
DOI
10.1016/j.jcyt.2015.03.004

Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases

© 2015 International Society for Cellular Therapy.Background aims: Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period. Methods: DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by direct biochemical analysis; alloreactivity of DUOC-01 and of peripheral blood (PB) mononuclear cells (MNC) to DUOC-01 by mixed lymphocyte culture methods; and cytokine secretion by Bioplex assays. Results: DUOC-01 cultures contained highly active, attached, motile, slowly proliferating cells that expressed common (cluster of differentiation [CD]11b, CD14 and Iba1), M1 type (CD16, inducible nitric oxide synthase), and M2-type (CD163, CD206) macrophage or microglia markers. Activities of 11 disease-relevant lysosomal enzymes in DUOC-01 products were similar to those of normal PB cells. All DUOC-01 products secreted interleukin (IL)-6 and IL-10. Accumulation of transforming growth factor-β, IL-1β, interferon-γ and TNF-α in supernatants was variable. IL-12, IL-2, IL-4, IL-5 and IL-13 were not detected at significant concentrations. Galactocerebrosidase, transforming growth factor-β and IL-10 transcripts were specifically enriched in DUOC-01 relative to CB cells. PB MNCs proliferated and released cytokines in response to DUOC-01. DUOC-01 did not proliferate in response to mismatched MNC. Conclusions: DUOC-01 has potential as an adjunctive cell therapy to myeloablative CB transplant for treatment of inherited metabolic diseases.

Authors
Kurtzberg, J; Buntz, S; Gentry, T; Noeldner, P; Ozamiz, A; Rusche, B; Storms, RW; Wollish, A; Wenger, DA; Balber, AE
MLA Citation
Kurtzberg, J, Buntz, S, Gentry, T, Noeldner, P, Ozamiz, A, Rusche, B, Storms, RW, Wollish, A, Wenger, DA, and Balber, AE. "Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases." Cytotherapy 17.6 (January 1, 2015): 803-815.
Source
scopus
Published In
Cytotherapy (Informa)
Volume
17
Issue
6
Publish Date
2015
Start Page
803
End Page
815
DOI
10.1016/j.jcyt.2015.02.006

Cord Blood Transplantation in Hematological and Metabolic Diseases

© 2016 Elsevier Inc. All rights reserved.Umbilical cord blood (CB), as a source of hematopoietic stem and progenitor cells for hematopoietic reconstitution, has been used for over two decades in allogeneic transplantation to treat patients with hematological malignancies, bone marrow failure, immunodeficiency syndromes, hemoglobinopathies, and certain inherited metabolic disorders. CB banks have been established worldwide, and regulatory pathways for licensure of publicly banked units are in place in the USA and other countries around the world. CB is immunologically tolerant thereby expanding access to transplantation for patients unable to find a fully matched donor and, because of rapid availability, is also a unique option for treatment of children with otherwise lethal inherited metabolic diseases affecting the brain. CB is likely to be an important source of cells for use in the emerging fields of cellular therapies and regenerative medicine.

Authors
Sun, JM; Kurtzberg, J
MLA Citation
Sun, JM, and Kurtzberg, J. "Cord Blood Transplantation in Hematological and Metabolic Diseases." Translating Regenerative Medicine to the Clinic. January 1, 2015. 285-295.
Source
scopus
Publish Date
2015
Start Page
285
End Page
295
DOI
10.1016/B978-0-12-800548-4.00019-X

One-unit versus two-unit cord-blood transplantation.

Authors
Wagner, JE; Eapen, M; Kurtzberg, J
MLA Citation
Wagner, JE, Eapen, M, and Kurtzberg, J. "One-unit versus two-unit cord-blood transplantation." The New England journal of medicine 372.3 (January 2015): 288-.
PMID
25587953
Source
epmc
Published In
The New England journal of medicine
Volume
372
Issue
3
Publish Date
2015
Start Page
288
DOI
10.1056/nejmc1414419

Progress toward curing HIV infection with hematopoietic cell transplantation.

HIV-1 infection afflicts more than 35 million people worldwide, according to 2014 estimates from the World Health Organization. For those individuals who have access to antiretroviral therapy, these drugs can effectively suppress, but not cure, HIV-1 infection. Indeed, the only documented case for an HIV/AIDS cure was a patient with HIV-1 and acute myeloid leukemia who received allogeneic hematopoietic cell transplantation (HCT) from a graft that carried the HIV-resistant CCR5-∆32/∆32 mutation. Other attempts to establish a cure for HIV/AIDS using HCT in patients with HIV-1 and malignancy have yielded mixed results, as encouraging evidence for virus eradication in a few cases has been offset by poor clinical outcomes due to the underlying cancer or other complications. Such clinical strategies have relied on HIV-resistant hematopoietic stem and progenitor cells that harbor the natural CCR5-∆32/∆32 mutation or that have been genetically modified for HIV-resistance. Nevertheless, HCT with HIV-resistant cord blood remains a promising option, particularly with inventories of CCR5-∆32/∆32 units or with genetically modified, human leukocyte antigen-matched cord blood.

Authors
Petz, LD; Burnett, JC; Li, H; Li, S; Tonai, R; Bakalinskaya, M; Shpall, EJ; Armitage, S; Kurtzberg, J; Regan, DM; Clark, P; Querol, S; Gutman, JA; Spellman, SR; Gragert, L; Rossi, JJ
MLA Citation
Petz, LD, Burnett, JC, Li, H, Li, S, Tonai, R, Bakalinskaya, M, Shpall, EJ, Armitage, S, Kurtzberg, J, Regan, DM, Clark, P, Querol, S, Gutman, JA, Spellman, SR, Gragert, L, and Rossi, JJ. "Progress toward curing HIV infection with hematopoietic cell transplantation." Stem cells and cloning : advances and applications 8 (January 2015): 109-116. (Review)
PMID
26251620
Source
epmc
Published In
Stem Cells and Cloning: advances and applications
Volume
8
Publish Date
2015
Start Page
109
End Page
116
DOI
10.2147/sccaa.s56050

Human Umbilical Cord Blood Cells Ameliorate Motor Deficits in Rabbits in a Cerebral Palsy Model.

Cerebral palsy (CP) has a significant impact on both patients and society, but therapy is limited. Human umbilical cord blood cells (HUCBC), containing various stem and progenitor cells, have been used to treat various brain genetic conditions. In small animal experiments, HUCBC have improved outcomes after hypoxic-ischemic (HI) injury. Clinical trials using HUCBC are underway, testing feasibility, safety and efficacy for neonatal injury as well as CP. We tested HUCBC therapy in a validated rabbit model of CP after acute changes secondary to HI injury had subsided. Following uterine ischemia at 70% gestation, we infused HUCBC into newborn rabbit kits with either mild or severe neurobehavioral changes. Infusion of high-dose HUCBC (5 × 10(6) cells) dramatically altered the natural history of the injury, alleviating the abnormal phenotype including posture, righting reflex, locomotion, tone, and dystonia. Half the high dose showed lesser but still significant improvement. The swimming test, however, showed that joint function did not restore to naïve control function in either group. Tracing HUCBC with either MRI biomarkers or PCR for human DNA found little penetration of HUCBC in the newborn brain in the immediate newborn period, suggesting that the beneficial effects were not due to cellular integration or direct proliferative effects but rather to paracrine signaling. This is the first study to show that HUCBC improve motor performance in a dose-dependent manner, perhaps by improving compensatory repair processes.

Authors
Drobyshevsky, A; Cotten, CM; Shi, Z; Luo, K; Jiang, R; Derrick, M; Tracy, ET; Gentry, T; Goldberg, RN; Kurtzberg, J; Tan, S
MLA Citation
Drobyshevsky, A, Cotten, CM, Shi, Z, Luo, K, Jiang, R, Derrick, M, Tracy, ET, Gentry, T, Goldberg, RN, Kurtzberg, J, and Tan, S. "Human Umbilical Cord Blood Cells Ameliorate Motor Deficits in Rabbits in a Cerebral Palsy Model." Developmental neuroscience 37.4-5 (January 2015): 349-362.
PMID
25791742
Source
epmc
Published In
Developmental neuroscience
Volume
37
Issue
4-5
Publish Date
2015
Start Page
349
End Page
362
DOI
10.1159/000374107

Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks.

Cord blood is an important source of stem cells. However, nearly 90% of public cord blood banks have declared that they are struggling to maintain their financial sustainability and avoid bankruptcy. The objective of this study is to evaluate how characteristics of cord blood units influence their utilization, then use this information to model the economic viability and therapeutic value of different banking strategies.Retrospective analysis of cord blood data registered between January 1st, 2009 and December 31st, 2011 in Bone Marrow Donor Worldwide. Data were collected from four public banks in France, Germany and the USA. Samples were eligible for inclusion in the analysis if data on cord blood and maternal HLA typing and biological characteristics after processing were available (total nucleated and CD34+ cell counts). 9,396 banked cord blood units were analyzed, of which 5,815 were Caucasian in origin. A multivariate logistic regression model assessed the influence of three parameters on the CBU utilization rate: ethnic background, total nucleated and CD34+ cell counts. From this model, we elaborated a Utilization Score reflecting the probability of transplantation for each cord blood unit. We stratified three Utilization Score thresholds representing four different banking strategies, from the least selective (scenario A) to the most selective (scenario D). We measured the cost-effectiveness ratio for each strategy by comparing performance in terms of number of transplanted cord blood units and level of financial deficit.When comparing inputs and outputs over three years, Scenario A represented the most extreme case as it delivered the highest therapeutic value for patients (284 CBUs transplanted) along with the highest financial deficit (USD 5.89 million). We found that scenario C resulted in 219 CBUs transplanted with a limited deficit (USD 0.98 million) that charities and public health could realistically finance over the long term. We also found that using a pre-freezing level of 18 x 10(8) TNC would be the most cost-effective strategy for a public bank.Our study shows that a swift transition from strategy A to C can play a vital role in preventing public cord blood banks worldwide from collapsing.

Authors
Magalon, J; Maiers, M; Kurtzberg, J; Navarrete, C; Rubinstein, P; Brown, C; Schramm, C; Larghero, J; Katsahian, S; Chabannon, C; Picard, C; Platz, A; Schmidt, A; Katz, G
MLA Citation
Magalon, J, Maiers, M, Kurtzberg, J, Navarrete, C, Rubinstein, P, Brown, C, Schramm, C, Larghero, J, Katsahian, S, Chabannon, C, Picard, C, Platz, A, Schmidt, A, and Katz, G. "Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks." PloS one 10.12 (January 2015): e0143440-.
PMID
26624279
Source
epmc
Published In
PloS one
Volume
10
Issue
12
Publish Date
2015
Start Page
e0143440
DOI
10.1371/journal.pone.0143440

The authors reply

Authors
Wagner, JE; Eapen, M; Kurtzberg, J
MLA Citation
Wagner, JE, Eapen, M, and Kurtzberg, J. "The authors reply." New England Journal of Medicine 372.3 (2015): 288--.
Source
scival
Published In
The New England journal of medicine
Volume
372
Issue
3
Publish Date
2015
Start Page
288-
DOI
10.1056/NEJMc1414419

Rapid and efficient generation of transgene-free iPSC from a small volume of cryopreserved blood

© The Author(s) 2015.Human peripheral blood and umbilical cord blood represent attractive sources of cells for reprogramming to induced pluripotent stem cells (iPSCs). However, to date, most of the blood-derived iPSCs were generated using either integrating methods or starting from T-lymphocytes that have genomic rearrangements thus bearing uncertain consequences when using iPSC-derived lineages for disease modeling and cell therapies. Recently, both peripheral blood and cord blood cells have been reprogrammed into transgene-free iPSC using the Sendai viral vector. Here we demonstrate that peripheral blood can be utilized formedium-throughput iPSC production without the need to maintain cell culture prior to reprogramming induction. Cell reprogramming can also be accomplished with as little as 3000 previously cryopreserved cord blood cells under feeder-free and chemically defined Xeno-free conditions that are compliant with standard Good Manufacturing Practice (GMP) regulations. The first iPSC colonies appear 2–3 weeks faster in comparison to previous reports. Notably, these peripheral blood- and cord bloodderived iPSCs are free of detectable immunoglobulin heavy chain (IGH) and T cell receptor (TCR) gene rearrangements, suggesting they did not originate from B- or T- lymphoid cells. The iPSCs are pluripotent as evaluated by the scorecard assay and in vitro multi lineage functional cell differentiation. Our data show that small volumes of cryopreserved peripheral blood or cord blood cells can be reprogrammed efficiently at a convenient, cost effective and scalable way. In summary, our method expands the reprogramming potential of limited or archived samples either stored at blood banks or obtained from pediatric populations that cannot easily provide large quantities of peripheral blood or a skin biopsy.

Authors
Zhou, H; Martinez, H; Sun, B; Li, A; Zimmer, M; Katsanis, N; Davis, EE; Kurtzberg, J; Lipnick, S; Noggle, S; Rao, M; Chang, S
MLA Citation
Zhou, H, Martinez, H, Sun, B, Li, A, Zimmer, M, Katsanis, N, Davis, EE, Kurtzberg, J, Lipnick, S, Noggle, S, Rao, M, and Chang, S. "Rapid and efficient generation of transgene-free iPSC from a small volume of cryopreserved blood." Stem Cell Reviews and Reports 11.4 (2015): 652-665.
Source
scival
Published In
Stem Cell Reviews and Reports
Volume
11
Issue
4
Publish Date
2015
Start Page
652
End Page
665
DOI
10.1007/s12015-015-9586-8

Umbilical cord blood donation: Public or private?

© 2015 Macmillan Publishers Limited.Umbilical cord blood (UCB) is a graft source for patients with malignant or genetic diseases who can be cured by allogeneic hematopoietic cell transplantation (HCT), but who do not have an appropriately HLA-matched family or volunteer unrelated adult donor. Starting in the 1990s, unrelated UCB banks were established, accepting donations from term deliveries and storing UCB units for public use. An estimated 730 000 UCB units have been donated and stored to date and ∼35 000 UCB transplants have been performed worldwide. Over the past 20 years, private and family banks have grown rapidly, storing ∼4 million UCB units for a particular patient or family, usually charging an up-front and yearly storage fee; therefore, these banks are able to be financially sustainable without releasing UCB units. Private banks are not obligated to fulfill the same regulatory requirements of the public banks. The public banks have released ∼30 times more UCB units for therapy. Some countries have transitioned to an integrated banking model, a hybrid of public and family banking. Today, pregnant women, their families, obstetrical providers and pediatricians are faced with multiple choices about the disposition of their newborn's cord blood. In this commentary, we review the progress of UCB banking technology; we also analyze the current data on pediatric and adult unrelated UCB, including the recent expansion of interest in transplantation for hemoglobinopathies, and discuss emerging studies on the use of autologous UCB for neurologic diseases and regenerative medicine. We will review worldwide approaches to UCB banking, ethical considerations, criteria for public and family banking, integrated banking ideas and future strategies for UCB banking.

Authors
Ballen, KK; Verter, F; Kurtzberg, J
MLA Citation
Ballen, KK, Verter, F, and Kurtzberg, J. "Umbilical cord blood donation: Public or private?." Bone Marrow Transplantation 50.10 (2015): 1271-1278.
Source
scival
Published In
Bone Marrow Transplantation
Volume
50
Issue
10
Publish Date
2015
Start Page
1271
End Page
1278
DOI
10.1038/bmt.2015.124

Emerging uses of cord blood in regenerative medicine-neurological applications

© 2015 Elsevier Inc. All rights reserved.Regenerative medicine is dedicated to the study of repairing, replacing, or regenerating damaged human cells, tissues, or organs to restore or establish normal function, and it is predicted to develop into numerous applications to treat a wide variety of conditions. Umbilical cord blood (CB) is a relatively safe, easily collected, readily available, and noncontroversial source of stem and progenitor cells for use in standard hematopoietic stem cell transplantation. It has also recently emerged as a promising source of stem and progenitor cells for use in novel cell therapies. In this chapter, we will explore some of the potential applications of CB in regenerative medicine.

Authors
Sun, JM; Kurtzberg, J
MLA Citation
Sun, JM, and Kurtzberg, J. "Emerging uses of cord blood in regenerative medicine-neurological applications." Cord Blood Stem Cells Medicine. December 10, 2014. 167-177.
Source
scopus
Publish Date
2014
Start Page
167
End Page
177
DOI
10.1016/B978-0-12-407785-0.00013-X

Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation.

A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients.

Authors
Kim, S-Y; Le Rademacher, J; Antin, JH; Anderlini, P; Ayas, M; Battiwalla, M; Carreras, J; Kurtzberg, J; Nakamura, R; Eapen, M; Deeg, HJ
MLA Citation
Kim, S-Y, Le Rademacher, J, Antin, JH, Anderlini, P, Ayas, M, Battiwalla, M, Carreras, J, Kurtzberg, J, Nakamura, R, Eapen, M, and Deeg, HJ. "Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation." Haematologica 99.12 (December 2014): 1868-1875.
PMID
25107891
Source
epmc
Published In
Haematologica
Volume
99
Issue
12
Publish Date
2014
Start Page
1868
End Page
1875
DOI
10.3324/haematol.2014.108977

Multi-site evaluation of the BD Stem Cell Enumeration Kit for CD34(+) cell enumeration on the BD FACSCanto II and BD FACSCalibur flow cytometers.

BACKGROUND AIMS: Evaluation of the BD Stem Cell Enumeration Kit was conducted at four clinical sites with flow cytometry CD34(+) enumeration to assess agreement between two investigational methods: (i) the BD FACSCanto II and BD FACSCalibur systems and (ii) the predicate method (Beckman Coulter StemKit and StemTrol, Immunotech SAS, Beckman Coulter, Marseille Cedex 9, France). METHODS: Leftover and delinked specimens (n = 1032) from clinical flow cytometry testing were analyzed on the BD FACSCanto II (n = 918) and BD FACSCalibur (n = 905) in normal and mobilized blood, frozen and thawed bone marrow and leucopheresis and cord blood anticoagulated with citrate phosphate dextrose, anticoagulant citrate dextrose-solution A, heparin and ethylenediaminetetraacetate, alone or in combination. Fresh leucopheresis analysis addressed site equivalency for sample preparation, testing and analysis. RESULTS: The mean relative bias showed agreement within predefined parameters for the BD FACSCanto II (-2.81 to 4.31 ±7.1) and BD FACSCalibur (-2.69 to 5.2 ±7.9). Results are reported as absolute and relative differences compared with the predicate for viable CD34(+), percentage of CD34(+) in CD45(+) and viable CD45(+) populations (or gates). Bias analyses of the distribution of the predicate low, mid and high bin values were done using BD FACSCanto II optimal gating and BD FACSCalibur manual gating for viable CD34(+), percentage of CD34(+) in CD45(+) and viable CD45(+). Bias results from both investigational methods show agreement. Deming regression analyses showed a linear relationship with R(2) > 0.92 for both investigational methods. DISCUSSION: In conclusion, the results from both investigational methods demonstrated agreement and equivalence with the predicate method for enumeration of absolute viable CD34(+), percentage of viable CD34(+) in CD45(+) and absolute viable CD45(+) populations.

Authors
Preti, RA; Chan, WS; Kurtzberg, J; Dornsife, RE; Wallace, PK; Furlage, R; Lin, A; Omana-Zapata, I; Bonig, H; Tonn, T
MLA Citation
Preti, RA, Chan, WS, Kurtzberg, J, Dornsife, RE, Wallace, PK, Furlage, R, Lin, A, Omana-Zapata, I, Bonig, H, and Tonn, T. "Multi-site evaluation of the BD Stem Cell Enumeration Kit for CD34(+) cell enumeration on the BD FACSCanto II and BD FACSCalibur flow cytometers." Cytotherapy 16.11 (November 2014): 1558-1574.
PMID
24927716
Source
epmc
Published In
Cytotherapy (Informa)
Volume
16
Issue
11
Publish Date
2014
Start Page
1558
End Page
1574
DOI
10.1016/j.jcyt.2014.03.006

Outcomes after hematopoietic stem cell transplantation for children with I-cell disease.

Mucolipidosis type II (MLII), or I-cell disease, is a rare but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplantation (HSCT) has been used to successfully treat some lysosomal storage diseases, only 2 cases have been reported on the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, overall survival was low, with only 6 patients (27%) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development and often required complex medical support, such as gastrostomy tubes for nutrition and tracheostomy with mechanical ventilation. Although HSCT has demonstrated efficacy in treating some lysosomal storage disorders, the neurologic outcome and survival for patents with MLII were poor. Therefore, new medical and cellular therapies should be sought for these patients.

Authors
Lund, TC; Cathey, SS; Miller, WP; Eapen, M; Andreansky, M; Dvorak, CC; Davis, JH; Dalal, JD; Devine, SM; Eames, GM; Ferguson, WS; Giller, RH; He, W; Kurtzberg, J; Krance, R; Katsanis, E; Lewis, VA; Sahdev, I; Orchard, PJ
MLA Citation
Lund, TC, Cathey, SS, Miller, WP, Eapen, M, Andreansky, M, Dvorak, CC, Davis, JH, Dalal, JD, Devine, SM, Eames, GM, Ferguson, WS, Giller, RH, He, W, Kurtzberg, J, Krance, R, Katsanis, E, Lewis, VA, Sahdev, I, and Orchard, PJ. "Outcomes after hematopoietic stem cell transplantation for children with I-cell disease." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20.11 (November 2014): 1847-1851.
PMID
25016194
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
11
Publish Date
2014
Start Page
1847
End Page
1851
DOI
10.1016/j.bbmt.2014.06.019

Standardization of health care provider competencies for intrathecal access procedures.

This quality improvement (QI) project addresses a method for experienced health care providers to maintain skill-based competence for intrathecal access procedures.A prospective QI design using intrathecal access simulation to assess, educate, and evaluate skill competency. Simulation was used as a strategy to promote patient safety and standardize practice patterns. Pretest and posttest methodology using paired t tests were performed to assess anxiety, confidence, and knowledge.Fourteen pediatric providers participated in this QI project. There was a statistically significant improvement in confidence measuring intracranial pressure (ICP; t = -2.92, P = .013), performance-related overall anxiety (t = -2.132, P = .05) and administering intrathecal chemotherapy (t = -2.144, P = .053). Fifty percent of participants missed a medication error demonstrating confirmation bias.This simulation strategy resulted in improved confidence in measuring ICP, performance-related overall anxiety, and confidence in administering chemotherapy. Confirmation bias occurred during simulation testing for a medication error. We propose this method for maintaining clinical competencies in health care providers and introducing new skills to existing practices.

Authors
McLaughlin, CA; Hockenberry, MJ; Kurtzberg, J; Hueckel, R; Martin, PL; Docherty, SL
MLA Citation
McLaughlin, CA, Hockenberry, MJ, Kurtzberg, J, Hueckel, R, Martin, PL, and Docherty, SL. "Standardization of health care provider competencies for intrathecal access procedures." Journal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses 31.6 (November 2014): 304-316.
PMID
25057001
Source
epmc
Published In
Journal of Pediatric Oncology Nursing (Elsevier)
Volume
31
Issue
6
Publish Date
2014
Start Page
304
End Page
316
DOI
10.1177/1043454214543019

Umbilical cord blood transplantation to treat Pelizaeus-Merzbacher Disease in 2 young boys.

Pelizaeus-Merzbacher Disease (PMD) is a rare X-linked recessive leukodystrophy caused by mutations in the proteolipid protein 1 gene on the Xq22 chromosome. PMD is a dysmyelinating disorder characterized by variable clinical presentation and course. Symptoms range from mild motor deficits to progressive spasticity and neurologic decline resulting in death at an early age. There is no definitive curative treatment. This report presents the clinical course of 2 young boys with PMD who are the first known patients to receive umbilical cord blood transplantation as a therapeutic intervention to stabilize disease progression. Pretransplantation evaluation revealed that both patients had significant motor deficits as well as delayed cognitive function as compared with age-matched peers. Brain imaging revealed varying degrees of hypomyelination. Both patients received myeloablative chemotherapy followed by an unrelated donor umbilical cord blood infusion, which they tolerated well with no major transplantation-related complications. At 7-years and 1-year posttransplantation, respectively, both boys are making slow neurocognitive improvements and show no evidence of functional decline. Imaging results show stable or improving myelination. Although the results of unrelated donor umbilical cord blood transplantation in these 2 boys with PMD are encouraging, longer-term follow-up will be necessary to assess the effect of this treatment on the variable natural disease course.

Authors
Wishnew, J; Page, K; Wood, S; Galvin, L; Provenzale, J; Escolar, M; Gustafson, K; Kurtzberg, J
MLA Citation
Wishnew, J, Page, K, Wood, S, Galvin, L, Provenzale, J, Escolar, M, Gustafson, K, and Kurtzberg, J. "Umbilical cord blood transplantation to treat Pelizaeus-Merzbacher Disease in 2 young boys." Pediatrics 134.5 (November 2014): e1451-e1457.
PMID
25287453
Source
epmc
Published In
Pediatrics
Volume
134
Issue
5
Publish Date
2014
Start Page
e1451
End Page
e1457
DOI
10.1542/peds.2013-3604

Abstract B22: Altered methylation profiles of imprinted genes in response to prenatal exposure to cigarette smoke in the Newborn Epigenetic STudy (NEST) cohort

Authors
Nye, MD; Hoyo, C; Wang, F; Murtha, AP; Schildkraut, JM; Kurtzberg, J; Jirtle, RL; Huang, Z; Murphy, SK
MLA Citation
Nye, MD, Hoyo, C, Wang, F, Murtha, AP, Schildkraut, JM, Kurtzberg, J, Jirtle, RL, Huang, Z, and Murphy, SK. "Abstract B22: Altered methylation profiles of imprinted genes in response to prenatal exposure to cigarette smoke in the Newborn Epigenetic STudy (NEST) cohort." Cancer Epidemiology Biomarkers & Prevention 23.11 Supplement (November 2014): B22-B22.
Source
crossref
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
23
Issue
11 Supplement
Publish Date
2014
Start Page
B22
End Page
B22
DOI
10.1158/1538-7755.DISP13-B22

One-unit versus two-unit cord-blood transplantation for hematologic cancers.

Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation.Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival.Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit.We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; ClinicalTrials.gov number, NCT00412360.).

Authors
Wagner, JE; Eapen, M; Carter, S; Wang, Y; Schultz, KR; Wall, DA; Bunin, N; Delaney, C; Haut, P; Margolis, D; Peres, E; Verneris, MR; Walters, M; Horowitz, MM; Kurtzberg, J
MLA Citation
Wagner, JE, Eapen, M, Carter, S, Wang, Y, Schultz, KR, Wall, DA, Bunin, N, Delaney, C, Haut, P, Margolis, D, Peres, E, Verneris, MR, Walters, M, Horowitz, MM, and Kurtzberg, J. "One-unit versus two-unit cord-blood transplantation for hematologic cancers." The New England journal of medicine 371.18 (October 2014): 1685-1694.
PMID
25354103
Source
epmc
Published In
The New England journal of medicine
Volume
371
Issue
18
Publish Date
2014
Start Page
1685
End Page
1694
DOI
10.1056/nejmoa1405584

Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort.

Epigenetic mechanisms are proposed to link maternal concentrations of methyl group donor nutrients with the risk of low birth weight. However, empirical data are lacking. We have examined the association between maternal folate and birth weight and assessed the mediating role of DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes in these associations. Compared with newborns of women with folate levels in the lowest quartile, birth weight was higher in newborns of mothers in the second (β = 143.2, se = 63.2, P = 0.02), third (β = 117.3, se = 64.0, P = 0.07), and fourth (β = 133.9, se = 65.2, P = 0.04) quartiles, consistent with a threshold effect. This pattern of association did not vary by race/ethnicity but was more apparent in newborns of non-obese women. DNA methylation at the PLAGL1, SGCE, DLK1/MEG3 and IGF2/H19 DMRs was associated with maternal folate levels and also birth weight, suggestive of threshold effects. MEG3 DMR methylation mediated the association between maternal folate levels and birth weight (P =0.06). While the small sample size and partial scope of examined DMRs limit our conclusions, our data suggest that, with respect to birth weight, no additional benefits may be derived from increased maternal folate concentrations, especially in non-obese women. These data also support epigenetic plasticity as a key mechanistic response to folate availability during early fetal development.

Authors
Hoyo, C; Daltveit, AK; Iversen, E; Benjamin-Neelon, SE; Fuemmeler, B; Schildkraut, J; Murtha, AP; Overcash, F; Vidal, AC; Wang, F; Huang, Z; Kurtzberg, J; Seewaldt, V; Forman, M; Jirtle, RL; Murphy, SK
MLA Citation
Hoyo, C, Daltveit, AK, Iversen, E, Benjamin-Neelon, SE, Fuemmeler, B, Schildkraut, J, Murtha, AP, Overcash, F, Vidal, AC, Wang, F, Huang, Z, Kurtzberg, J, Seewaldt, V, Forman, M, Jirtle, RL, and Murphy, SK. "Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort." Epigenetics 9.8 (August 2014): 1120-1130.
PMID
24874916
Source
epmc
Published In
Epigenetics : official journal of the DNA Methylation Society
Volume
9
Issue
8
Publish Date
2014
Start Page
1120
End Page
1130
DOI
10.4161/epi.29332

Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: a report from the Children's Oncology Group.

To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL).From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy.Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase.Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.

Authors
Tower, RL; Jones, TL; Camitta, BM; Asselin, BL; Bell, BA; Chauvenet, A; Devidas, M; Halperin, EC; Pullen, J; Shuster, JJ; Winick, N; Kurtzberg, J
MLA Citation
Tower, RL, Jones, TL, Camitta, BM, Asselin, BL, Bell, BA, Chauvenet, A, Devidas, M, Halperin, EC, Pullen, J, Shuster, JJ, Winick, N, and Kurtzberg, J. "Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: a report from the Children's Oncology Group." Journal of pediatric hematology/oncology 36.5 (July 2014): 353-361.
PMID
24608079
Source
epmc
Published In
Journal of Pediatric Hematology/Oncology
Volume
36
Issue
5
Publish Date
2014
Start Page
353
End Page
361
DOI
10.1097/mph.0000000000000131

Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment.

Delayed hematopoietic recovery is a major drawback of umbilical cord blood (UCB) transplantation. Transplantation of ex vivo-expanded UCB shortens time to hematopoietic recovery, but long-term, robust engraftment by the expanded unit has yet to be demonstrated. We tested the hypothesis that a UCB-derived cell product consisting of stem cells expanded for 21 days in the presence of nicotinamide and a noncultured T cell fraction (NiCord) can accelerate hematopoietic recovery and provide long-term engraftment.In a phase I trial, 11 adults with hematologic malignancies received myeloablative bone marrow conditioning followed by transplantation with NiCord and a second unmanipulated UCB unit. Safety, hematopoietic recovery, and donor engraftment were assessed and compared with historical controls.No adverse events were attributable to the infusion of NiCord. Complete or partial neutrophil and T cell engraftment derived from NiCord was observed in 8 patients, and NiCord engraftment remained stable in all patients, with a median follow-up of 21 months. Two patients achieved long-term engraftment with the unmanipulated unit. Patients transplanted with NiCord achieved earlier median neutrophil recovery (13 vs. 25 days, P < 0.001) compared with that seen in historical controls. The 1-year overall and progression-free survival rates were 82% and 73%, respectively.UCB-derived hematopoietic stem and progenitor cells expanded in the presence of nicotinamide and transplanted with a T cell-containing fraction contain both short-term and long-term repopulating cells. The results justify further study of NiCord transplantation as a single UCB graft. If long-term safety is confirmed, NiCord has the potential to broaden accessibility and reduce the toxicity of UCB transplantation.Clinicaltrials.gov NCT01221857.Gamida Cell Ltd.

Authors
Horwitz, ME; Chao, NJ; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; McDonald, C; Waters-Pick, B; Stiff, P; Wease, S; Peled, A; Snyder, D; Cohen, EG; Shoham, H; Landau, E; Friend, E; Peleg, I; Aschengrau, D; Yackoubov, D; Kurtzberg, J; Peled, T
MLA Citation
Horwitz, ME, Chao, NJ, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, McDonald, C, Waters-Pick, B, Stiff, P, Wease, S, Peled, A, Snyder, D, Cohen, EG, Shoham, H, Landau, E, Friend, E, Peleg, I, Aschengrau, D, Yackoubov, D, Kurtzberg, J, and Peled, T. "Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment." The Journal of clinical investigation 124.7 (July 2014): 3121-3128.
PMID
24911148
Source
epmc
Published In
Journal of Clinical Investigation
Volume
124
Issue
7
Publish Date
2014
Start Page
3121
End Page
3128
DOI
10.1172/jci74556

Outcome of transplantation for acute lymphoblastic leukemia in children with Down syndrome.

We report on 27 patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic cell transplantation (HCT) between 2000 and 2009. Seventy-eight percent of patients received myeloablative conditioning and 52% underwent transplantation in second remission. Disease-free survival (DFS) was 24% at a median of 3 years. Post-transplant leukemic relapse was more frequent than expected for children with DS-ALL (54%) than for non-DS ALL. These data suggest leukemic relapse rather than transplant toxicity is the most important cause of treatment failure. Advancements in leukemia control are especially needed for improvement in HCT outcomes for DS-ALL.

Authors
Hitzler, JK; He, W; Doyle, J; Cairo, M; Camitta, BM; Chan, KW; Diaz Perez, MA; Fraser, C; Gross, TG; Horan, JT; Kennedy-Nasser, AA; Kitko, C; Kurtzberg, J; Lehmann, L; O'Brien, T; Pulsipher, MA; Smith, FO; Zhang, M-J; Eapen, M; Carpenter, PA; CIBMTR Pediatric Cancer Working Committee,
MLA Citation
Hitzler, JK, He, W, Doyle, J, Cairo, M, Camitta, BM, Chan, KW, Diaz Perez, MA, Fraser, C, Gross, TG, Horan, JT, Kennedy-Nasser, AA, Kitko, C, Kurtzberg, J, Lehmann, L, O'Brien, T, Pulsipher, MA, Smith, FO, Zhang, M-J, Eapen, M, Carpenter, PA, and CIBMTR Pediatric Cancer Working Committee, . "Outcome of transplantation for acute lymphoblastic leukemia in children with Down syndrome." Pediatr Blood Cancer 61.6 (June 2014): 1126-1128.
PMID
24391118
Source
pubmed
Published In
Pediatric Blood & Cancer
Volume
61
Issue
6
Publish Date
2014
Start Page
1126
End Page
1128
DOI
10.1002/pbc.24918

Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy.

OBJECTIVE: To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells. RESULTS: Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85. CONCLUSIONS: Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.

Authors
Cotten, CM; Murtha, AP; Goldberg, RN; Grotegut, CA; Smith, PB; Goldstein, RF; Fisher, KA; Gustafson, KE; Waters-Pick, B; Swamy, GK; Rattray, B; Tan, S; Kurtzberg, J
MLA Citation
Cotten, CM, Murtha, AP, Goldberg, RN, Grotegut, CA, Smith, PB, Goldstein, RF, Fisher, KA, Gustafson, KE, Waters-Pick, B, Swamy, GK, Rattray, B, Tan, S, and Kurtzberg, J. "Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy." J Pediatr 164.5 (May 2014): 973-979.e1.
PMID
24388332
Source
pubmed
Published In
The Journal of Pediatrics
Volume
164
Issue
5
Publish Date
2014
Start Page
973
End Page
979.e1
DOI
10.1016/j.jpeds.2013.11.036

EXPERIENCE IN A PUBLIC CORD BLOOD BANK USING A SEGMENT-BASED ALDEHYDE DEHYDROGENASE ASSAY AS A BIOMARKER FOR UMBILICAL CORD BLOOD POTENCY

Authors
Shoulars, K; Troy, JD; Gentry, T; Noldner, P; Page, K; Balber, A; Kurtzberg, J
MLA Citation
Shoulars, K, Troy, JD, Gentry, T, Noldner, P, Page, K, Balber, A, and Kurtzberg, J. "EXPERIENCE IN A PUBLIC CORD BLOOD BANK USING A SEGMENT-BASED ALDEHYDE DEHYDROGENASE ASSAY AS A BIOMARKER FOR UMBILICAL CORD BLOOD POTENCY." CYTOTHERAPY 16.4 (April 2014): S59-S59.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
16
Issue
4
Publish Date
2014
Start Page
S59
End Page
S59

DUOC-01, A CANDIDATE CELL THERAPY PRODUCT DERIVED FROM BANKED CORD BLOOD, ACCELERATES BRAIN REMYELINATION IN NSG MICE FOLLOWING CUPRIZONE FEEDING

Authors
Saha, A; Buntz, S; Patel, S; Matsushima, GK; Wollish, A; Kurtzberg, J; Balber, A
MLA Citation
Saha, A, Buntz, S, Patel, S, Matsushima, GK, Wollish, A, Kurtzberg, J, and Balber, A. "DUOC-01, A CANDIDATE CELL THERAPY PRODUCT DERIVED FROM BANKED CORD BLOOD, ACCELERATES BRAIN REMYELINATION IN NSG MICE FOLLOWING CUPRIZONE FEEDING." CYTOTHERAPY 16.4 (April 2014): S61-S62.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
16
Issue
4
Publish Date
2014
Start Page
S61
End Page
S62

NEURONAL AND GLIAL CELL COMPOSITION IN A MOUSE BRAIN SLICE CULTURE MODEL IS USEFUL IN DEVELOPING HUMAN CORD BLOOD DERIVED CELLULAR THERAPIES FOR NEONATAL HYPOXIC-ISCHEMIC BRAIN INJURY

Authors
Patel, S; Saha, A; Buntz, S; Kurtzberg, J; Balber, A
MLA Citation
Patel, S, Saha, A, Buntz, S, Kurtzberg, J, and Balber, A. "NEURONAL AND GLIAL CELL COMPOSITION IN A MOUSE BRAIN SLICE CULTURE MODEL IS USEFUL IN DEVELOPING HUMAN CORD BLOOD DERIVED CELLULAR THERAPIES FOR NEONATAL HYPOXIC-ISCHEMIC BRAIN INJURY." CYTOTHERAPY 16.4 (April 2014): S61-S61.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
16
Issue
4
Publish Date
2014
Start Page
S61
End Page
S61

PRECLINICAL CHARACTERIZATION OF DUOC-01, A CANDIDATE CELL THERAPY PRODUCT DERIVED FROM HUMAN BANKED UMBILICAL CORD BLOOD INTENDED FOR USE IN TREATMENT OF DEMYELINATING DISEASES

Authors
Kurtzberg, J; Buntz, S; Gentry, T; Storms, R; Wenger, DA; Noldner, P; Zhou, J; Ozamiz, A; Rusche, B; Balber, A
MLA Citation
Kurtzberg, J, Buntz, S, Gentry, T, Storms, R, Wenger, DA, Noldner, P, Zhou, J, Ozamiz, A, Rusche, B, and Balber, A. "PRECLINICAL CHARACTERIZATION OF DUOC-01, A CANDIDATE CELL THERAPY PRODUCT DERIVED FROM HUMAN BANKED UMBILICAL CORD BLOOD INTENDED FOR USE IN TREATMENT OF DEMYELINATING DISEASES." CYTOTHERAPY 16.4 (April 2014): S16-S17.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
16
Issue
4
Publish Date
2014
Start Page
S16
End Page
S17

TISSUE DISTRIBUTION OF A CORD BLOOD-DERIVED CELL PRODUCT FOLLOWING INTRATHECAL TRANSPLANTATION

Authors
Storms, R; Liu, C; Gentry, T; Zhou, J; Ozamiz, A; Rusche, B; Balber, A; Kurtzberg, J
MLA Citation
Storms, R, Liu, C, Gentry, T, Zhou, J, Ozamiz, A, Rusche, B, Balber, A, and Kurtzberg, J. "TISSUE DISTRIBUTION OF A CORD BLOOD-DERIVED CELL PRODUCT FOLLOWING INTRATHECAL TRANSPLANTATION." CYTOTHERAPY 16.4 (April 2014): S63-S63.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
16
Issue
4
Publish Date
2014
Start Page
S63
End Page
S63

PROTECTION OF BRAIN CELLS IN ORGANOTYPIC SLICE CULTURES EXPOSED TO OXYGEN AND GLUCOSE DEPRIVATION IS SPECIFICALLY MEDIATED BY CORD BLOOD CD14+CELLS

Authors
Saha, A; Buntz, S; Kurtzberg, J; Balber, A
MLA Citation
Saha, A, Buntz, S, Kurtzberg, J, and Balber, A. "PROTECTION OF BRAIN CELLS IN ORGANOTYPIC SLICE CULTURES EXPOSED TO OXYGEN AND GLUCOSE DEPRIVATION IS SPECIFICALLY MEDIATED BY CORD BLOOD CD14+CELLS." CYTOTHERAPY 16.4 (April 2014): S61-S61.
Source
wos-lite
Published In
Cytotherapy (Informa)
Volume
16
Issue
4
Publish Date
2014
Start Page
S61
End Page
S61

A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases

Reduced-intensity conditioning (RIC) regimens have the potential to decrease transplantation-related morbidity and mortality. However, engraftment failure has been prohibitively high after RIC unrelated umbilical cord blood transplantation (UCBT) in chemotherapy-naïve children with nonmalignant diseases (NMD). Twenty-two children with a median age of 2.8years, many with severe comorbidities and prior viral infections, were enrolled in a novel RIC protocol consisting of hydroxyurea, alemtuzumab, fludarabine, melphalan, and thiotepa followed by single UCBT. Patients underwent transplantation for inherited metabolic disorders (n=8), primary immunodeficiencies (n=9), hemoglobinopathies (n=4) and Diamond Blackfan anemia (n=1). Most umbilical cord blood (UCB) units were HLA-mismatched with median infused total nucleated cell dose of 7.9× 107/kg. No serious organ toxicities were attributable to the regimen. The cumulative incidence of neutrophil engraftment was 86.4% (95% confidence interval [CI], 65% to 100%) in a median of 20days, with the majority sustaining>95% donor chimerism at 1year. Cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV by day 180 was 27.3% (95% CI, 8.7% to 45.9%) and 13.6% (95 CI, 0% to 27.6%), respectively. Cumulative incidence of extensive chronic GVHD was 9.1% (95% CI, 0% to 20.8%). The primary causes of death were viral infections (n=3), acute GVHD (n=1) and transfusion reaction (n=1). One-year overall and event-free survivals were 77.3% (95% CI, 53.7% to 89.8%) and 68.2% (95% CI, 44.6% to 83.4%) with 31months median follow-up. This is the first RIC protocol demonstrating durable UCB engraftment in children with NMD. Future risk-based modifications of this regimen could decrease the incidence of viral infections. (www.clinicaltrials.gov/NCT00744692). © 2014 American Society for Blood and Marrow Transplantation.

Authors
Parikh, SH; Mendizabal, A; Benjamin, CL; Komanduri, KV; Antony, J; Petrovic, A; Hale, G; Driscoll, TA; Martin, PL; Page, KM; Flickinger, K; Moffet, J; Niedzwiecki, D; Kurtzberg, J; Szabolcs, P
MLA Citation
Parikh, SH, Mendizabal, A, Benjamin, CL, Komanduri, KV, Antony, J, Petrovic, A, Hale, G, Driscoll, TA, Martin, PL, Page, KM, Flickinger, K, Moffet, J, Niedzwiecki, D, Kurtzberg, J, and Szabolcs, P. "A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases." Biology of Blood and Marrow Transplantation 20.3 (March 1, 2014): 326-336.
Source
scopus
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
3
Publish Date
2014
Start Page
326
End Page
336
DOI
10.1016/j.bbmt.2013.11.021

A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases.

Reduced-intensity conditioning (RIC) regimens have the potential to decrease transplantation-related morbidity and mortality. However, engraftment failure has been prohibitively high after RIC unrelated umbilical cord blood transplantation (UCBT) in chemotherapy-naïve children with nonmalignant diseases (NMD). Twenty-two children with a median age of 2.8 years, many with severe comorbidities and prior viral infections, were enrolled in a novel RIC protocol consisting of hydroxyurea, alemtuzumab, fludarabine, melphalan, and thiotepa followed by single UCBT. Patients underwent transplantation for inherited metabolic disorders (n = 8), primary immunodeficiencies (n = 9), hemoglobinopathies (n = 4) and Diamond Blackfan anemia (n = 1). Most umbilical cord blood (UCB) units were HLA-mismatched with median infused total nucleated cell dose of 7.9 × 10(7)/kg. No serious organ toxicities were attributable to the regimen. The cumulative incidence of neutrophil engraftment was 86.4% (95% confidence interval [CI], 65% to 100%) in a median of 20 days, with the majority sustaining > 95% donor chimerism at 1 year. Cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV by day 180 was 27.3% (95% CI, 8.7% to 45.9%) and 13.6% (95 CI, 0% to 27.6%), respectively. Cumulative incidence of extensive chronic GVHD was 9.1% (95% CI, 0% to 20.8%). The primary causes of death were viral infections (n = 3), acute GVHD (n = 1) and transfusion reaction (n = 1). One-year overall and event-free survivals were 77.3% (95% CI, 53.7% to 89.8%) and 68.2% (95% CI, 44.6% to 83.4%) with 31 months median follow-up. This is the first RIC protocol demonstrating durable UCB engraftment in children with NMD. Future risk-based modifications of this regimen could decrease the incidence of viral infections. (www.clinicaltrials.gov/NCT00744692).

Authors
Parikh, SH; Mendizabal, A; Benjamin, CL; Komanduri, KV; Antony, J; Petrovic, A; Hale, G; Driscoll, TA; Martin, PL; Page, KM; Flickinger, K; Moffet, J; Niedzwiecki, D; Kurtzberg, J; Szabolcs, P
MLA Citation
Parikh, SH, Mendizabal, A, Benjamin, CL, Komanduri, KV, Antony, J, Petrovic, A, Hale, G, Driscoll, TA, Martin, PL, Page, KM, Flickinger, K, Moffet, J, Niedzwiecki, D, Kurtzberg, J, and Szabolcs, P. "A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases." Biol Blood Marrow Transplant 20.3 (March 2014): 326-336.
PMID
24296492
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
3
Publish Date
2014
Start Page
326
End Page
336
DOI
10.1016/j.bbmt.2013.11.021

Optimizing donor selection for public cord blood banking: Influence of maternal, infant, and collection characteristics on cord blood unit quality

Background Banked unrelated donor umbilical cord blood (CB) has improved access to hematopoietic stem cell transplantation for patients without a suitably matched donor. In a resource-limited environment, ensuring that the public inventory is enriched with high-quality cord blood units (CBUs) addressing the needs of a diverse group of patients is a priority. Identification of donor characteristics correlating with higher CBU quality could guide operational strategies to increase the yield of banked high-quality CBUs. Study Design and Methods Characteristics of 5267 CBUs donated to the Carolinas Cord Blood Bank, a public bank participating in the National Cord Blood Inventory, were retrospectively analyzed. Eligible CBUs, collected by trained personnel, were processed using standard procedures. Routine quality and potency metrics (postprocessing total nucleated cell count [post-TNCC], CD34+, colony-forming units [CFUs]) were correlated with maternal, infant, and collection characteristics. Results High-quality CBUs were defined as those with higher post-TNCC (>1.25 × 109) with CD34+ and CFUs in the upper quartile. Factors associated with higher CD34+ or CFU content included a shorter interval from collection to processing (<10 hr), younger gestational age (34-37 weeks; CD34+ and CFUs), Caucasian race, higher birthweight (>3500 g), and larger collection volumes (>80 mL). Conclusions We describe characteristics identifying high-quality CBUs, which can be used to inform strategies for CBU collection for public banks. Efforts should be made to prioritize collections from larger babies born before 38 weeks of gestation. CBUs should be rapidly transported to the processing laboratory. The lower quality of CBUs from non-Caucasian donors highlights the challenges of building a racially diverse public CB inventory. © 2013 American Association of Blood Banks.

Authors
Page, KM; Mendizabal, A; Betz-Stablein, B; Wease, S; Shoulars, K; Gentry, T; Prasad, VK; Sun, J; Carter, S; Balber, AE; Kurtzberg, J
MLA Citation
Page, KM, Mendizabal, A, Betz-Stablein, B, Wease, S, Shoulars, K, Gentry, T, Prasad, VK, Sun, J, Carter, S, Balber, AE, and Kurtzberg, J. "Optimizing donor selection for public cord blood banking: Influence of maternal, infant, and collection characteristics on cord blood unit quality." Transfusion 54.2 (February 1, 2014): 340-352.
Source
scopus
Published In
Transfusion
Volume
54
Issue
2
Publish Date
2014
Start Page
340
End Page
352
DOI
10.1111/trf.12257

In reply.

Authors
Page, KM; Kurtzberg, J
MLA Citation
Page, KM, and Kurtzberg, J. "In reply." Transfusion 54.2 (February 2014): 496-.
PMID
24517135
Source
epmc
Published In
Transfusion
Volume
54
Issue
2
Publish Date
2014
Start Page
496
DOI
10.1111/trf.12465

Unrelated Umbilical Cord Blood Transplant for Diamond-Blackfan Anemia

Authors
McFarren, A; Page, K; Parikh, S; Martin, PL; Driscoll, TA; Kurtzberg, J; Prasad, VK
MLA Citation
McFarren, A, Page, K, Parikh, S, Martin, PL, Driscoll, TA, Kurtzberg, J, and Prasad, VK. "Unrelated Umbilical Cord Blood Transplant for Diamond-Blackfan Anemia." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S177
End Page
S177

Interplay of Recipient-Donor Matching for HLA, Race/Ethnicity and Gender on Long Term Outcomes in 365 Pediatric Recipients of Single 4/6 Matched Unrelated Cord Blood Transplantation (UCBT) after Myeloablative Therapy

Authors
Prasad, VK; Mendizabal, A; Page, K; Parikh, S; Wishnew, J; Driscoll, TA; Martin, PL; Kurtzberg, J
MLA Citation
Prasad, VK, Mendizabal, A, Page, K, Parikh, S, Wishnew, J, Driscoll, TA, Martin, PL, and Kurtzberg, J. "Interplay of Recipient-Donor Matching for HLA, Race/Ethnicity and Gender on Long Term Outcomes in 365 Pediatric Recipients of Single 4/6 Matched Unrelated Cord Blood Transplantation (UCBT) after Myeloablative Therapy." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S87
End Page
S88

Brincidofovir (CMX001) Is Well Tolerated in Highly Immunocompromised Pediatric Patients

Authors
Prasad, VK; Grimley, M; Papanicolaou, G; Yu, LC; Florescu, DF; Brundage, TM; Mommeja-Marin, H; Kurtzberg, J
MLA Citation
Prasad, VK, Grimley, M, Papanicolaou, G, Yu, LC, Florescu, DF, Brundage, TM, Mommeja-Marin, H, and Kurtzberg, J. "Brincidofovir (CMX001) Is Well Tolerated in Highly Immunocompromised Pediatric Patients." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S93
End Page
S93

Predictors of Long-Term Clinical Outcome in Hurler Syndrome Patients after Successful Hematopoietic Cell Transplantation: An International Study

Authors
Aldenhoven, M; Orchard, P; Kurtzberg, J; Wynn, R; O'Meara, A; Veys, P; Fischer, A; Valayannopoulos, V; Neven, B; Rovelli, A; Prasad, VK; Tolar, J; Shapiro, E; Jones, S; Parini, R; Renard, M; Bordon, V; Poe, M; de Koning, T; Wraith, E; Escolar, M; Boelens, J-J
MLA Citation
Aldenhoven, M, Orchard, P, Kurtzberg, J, Wynn, R, O'Meara, A, Veys, P, Fischer, A, Valayannopoulos, V, Neven, B, Rovelli, A, Prasad, VK, Tolar, J, Shapiro, E, Jones, S, Parini, R, Renard, M, Bordon, V, Poe, M, de Koning, T, Wraith, E, Escolar, M, and Boelens, J-J. "Predictors of Long-Term Clinical Outcome in Hurler Syndrome Patients after Successful Hematopoietic Cell Transplantation: An International Study." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S78
End Page
S79

Twice-Weekly Brincidofovir (CMX001) Shows Promising Antiviral Activity in Immunocompromised Transplant Recipients with Asymptomatic Adenovirus Viremia

Authors
Grimley, M; Prasad, VK; Kurtzberg, J; Chemaly, RF; Brundage, TM; Wilson, C; Mommeja-Marin, H
MLA Citation
Grimley, M, Prasad, VK, Kurtzberg, J, Chemaly, RF, Brundage, TM, Wilson, C, and Mommeja-Marin, H. "Twice-Weekly Brincidofovir (CMX001) Shows Promising Antiviral Activity in Immunocompromised Transplant Recipients with Asymptomatic Adenovirus Viremia." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S93
End Page
S93

Experience in a Public Cord Blood Bank Using a Segment-Based Aldehyde Dehydrogenase Assay As a Biomarker for Umbilical Cord Blood Potency

Authors
Shoulars, K; Troy, JD; Noldner, P; Gentry, T; Page, K; Storms, R; Balber, AE; Kurtzberg, J
MLA Citation
Shoulars, K, Troy, JD, Noldner, P, Gentry, T, Page, K, Storms, R, Balber, AE, and Kurtzberg, J. "Experience in a Public Cord Blood Bank Using a Segment-Based Aldehyde Dehydrogenase Assay As a Biomarker for Umbilical Cord Blood Potency." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S187
End Page
S188

Late Effects in Infants and Young Children Following Umbilical Cord Blood Transplant Using Busulfan-Based, Myeloablative Non-TBI Conditioning Regimens

Authors
Allewelt, HB; Martin, PL; Prasad, VK; Page, K; Kurtzberg, J
MLA Citation
Allewelt, HB, Martin, PL, Prasad, VK, Page, K, and Kurtzberg, J. "Late Effects in Infants and Young Children Following Umbilical Cord Blood Transplant Using Busulfan-Based, Myeloablative Non-TBI Conditioning Regimens." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S63
End Page
S63

Repeated Dosing of Autologous Cord Blood Is Safe and Feasible in Babies with Congenital Hydrocephalus

Authors
Sun, J; Allison, J; McLaughlin, C; Fitzgerald, RA; Waters-Pick, B; Kurtzberg, J
MLA Citation
Sun, J, Allison, J, McLaughlin, C, Fitzgerald, RA, Waters-Pick, B, and Kurtzberg, J. "Repeated Dosing of Autologous Cord Blood Is Safe and Feasible in Babies with Congenital Hydrocephalus." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S181
End Page
S181

Increase the quality of banked cord blood units without limiting HLA diversity: how cord blood banks could face this dilemma

Authors
Magalon, J; Gamerre, M; Picard, C; Chabannon, C
MLA Citation
Magalon, J, Gamerre, M, Picard, C, and Chabannon, C. "Increase the quality of banked cord blood units without limiting HLA diversity: how cord blood banks could face this dilemma." Transfusion 54.2 (February 2014): 495-496.
Source
crossref
Published In
Transfusion
Volume
54
Issue
2
Publish Date
2014
Start Page
495
End Page
496
DOI
10.1111/trf.12439

Optimizing donor selection for public cord blood banking: influence of maternal, infant, and collection characteristics on cord blood unit quality.

BACKGROUND: Banked unrelated donor umbilical cord blood (CB) has improved access to hematopoietic stem cell transplantation for patients without a suitably matched donor. In a resource-limited environment, ensuring that the public inventory is enriched with high-quality cord blood units (CBUs) addressing the needs of a diverse group of patients is a priority. Identification of donor characteristics correlating with higher CBU quality could guide operational strategies to increase the yield of banked high-quality CBUs. STUDY DESIGN AND METHODS: Characteristics of 5267 CBUs donated to the Carolinas Cord Blood Bank, a public bank participating in the National Cord Blood Inventory, were retrospectively analyzed. Eligible CBUs, collected by trained personnel, were processed using standard procedures. Routine quality and potency metrics (postprocessing total nucleated cell count [post-TNCC], CD34+, colony-forming units [CFUs]) were correlated with maternal, infant, and collection characteristics. RESULTS: High-quality CBUs were defined as those with higher post-TNCC (>1.25 × 10(9)) with CD34+ and CFUs in the upper quartile. Factors associated with higher CD34+ or CFU content included a shorter interval from collection to processing (<10 hr), younger gestational age (34-37 weeks; CD34+ and CFUs), Caucasian race, higher birthweight (>3500 g), and larger collection volumes (>80 mL). CONCLUSIONS: We describe characteristics identifying high-quality CBUs, which can be used to inform strategies for CBU collection for public banks. Efforts should be made to prioritize collections from larger babies born before 38 weeks of gestation. CBUs should be rapidly transported to the processing laboratory. The lower quality of CBUs from non-Caucasian donors highlights the challenges of building a racially diverse public CB inventory.

Authors
Page, KM; Mendizabal, A; Betz-Stablein, B; Wease, S; Shoulars, K; Gentry, T; Prasad, VK; Sun, J; Carter, S; Balber, AE; Kurtzberg, J
MLA Citation
Page, KM, Mendizabal, A, Betz-Stablein, B, Wease, S, Shoulars, K, Gentry, T, Prasad, VK, Sun, J, Carter, S, Balber, AE, and Kurtzberg, J. "Optimizing donor selection for public cord blood banking: influence of maternal, infant, and collection characteristics on cord blood unit quality." Transfusion 54.2 (February 2014): 340-352.
PMID
23711284
Source
pubmed
Published In
Transfusion
Volume
54
Issue
2
Publish Date
2014
Start Page
340
End Page
352
DOI
10.1111/trf.12257

Allogeneic human mesenchymal stem cell therapy (remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients.

Severe steroid-refractory acute graft-versus-host disease (aGVHD) is related to significant mortality and morbidity after allogeneic stem cell transplantation. Early clinical trials of therapy with human mesenchymal stem cells (hMSCs) in pediatric patients with severe aGVHD resistant to multiple immunosuppressive agents showed promising results. In this study, we evaluated the risk/benefit profile of remestemcel-L (Prochymal), a third-party, off-the-shelf source of hMSCs, as a rescue agent for treatment-resistant aGVHD in pediatric patients. Children with grade B-D aGVHD failing steroids and, in most cases, other immunosuppressive agents were eligible for enrollment. Patients received 8 biweekly i.v. infusions of 2 × 10(6) hMSCs/kg for 4 weeks, with an additional 4 weekly infusions after day +28 for patients who achieved either a partial or mixed response. The enrolled patients compose a very challenging population with severe disease that was nonresponsive to the standard of care, with 88% of the patients experiencing severe aGVHD (grade C or D). Seventy-five patients (median age, 8 yr; 58.7% male; and 61.3% Caucasian) were treated in this study. Sixty-four patients (85.3%) had received an unrelated hematopoietic stem cell graft, and 28 patients (37.3%) had received a cord blood graft. At baseline, the distribution of aGVHD grades B, C, and D was 12.0%, 28.0%, and 60.0%, respectively. The median duration of aGVHD before enrollment was 30 d (range, 2 to 1639 d), and patients failed a median of 3 immunosuppressive agents. Organ involvement at baseline was 86.7% gastrointestinal, 54.7% skin, and 36.0% liver. Thirty-six patients (48.0%) had 2 organs involved, and 11 patients (14.7%) had all 3 organs involved. When stratified by aGVHD grade at baseline, the rate of overall response (complete and partial response) at day +28 was 66.7% for aGVHD grade B, 76.2% for grade C, and 53.3% for grade D. Overall response for individual organs at day +28 was 58.5% for the gastrointestinal system, 75.6% for skin, and 44.4% for liver. Collectively, overall response at day +28 for patients treated for severe refractory aGVHD was 61.3%, and this response was correlated with statistically significant improved survival at day +100 after hMSC infusion. Patients who responded to therapy by day +28 had a higher Kaplan-Meier estimated probability of 100-d survival compared with patients who did not respond (78.1% versus 31.0%; P < .001). Prochymal infusions were generally well tolerated, with no evidence of ectopic tissue formation.

Authors
Kurtzberg, J; Prockop, S; Teira, P; Bittencourt, H; Lewis, V; Chan, KW; Horn, B; Yu, L; Talano, J-A; Nemecek, E; Mills, CR; Chaudhury, S
MLA Citation
Kurtzberg, J, Prockop, S, Teira, P, Bittencourt, H, Lewis, V, Chan, KW, Horn, B, Yu, L, Talano, J-A, Nemecek, E, Mills, CR, and Chaudhury, S. "Allogeneic human mesenchymal stem cell therapy (remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients." Biol Blood Marrow Transplant 20.2 (February 2014): 229-235.
PMID
24216185
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
229
End Page
235
DOI
10.1016/j.bbmt.2013.11.001

Outcome of transplantation for acute lymphoblastic leukemia in children with down syndrome

We report on 27 patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic cell transplantation (HCT) between 2000 and 2009. Seventy-eight percent of patients received myeloablative conditioning and 52% underwent transplantation in second remission. Disease-free survival (DFS) was 24% at a median of 3 years. Post-transplant leukemic relapse was more frequent than expected for children with DS-ALL (54%) than for non-DS ALL. These data suggest leukemic relapse rather than transplant toxicity is the most important cause of treatment failure. Advancements in leukemia control are especially needed for improvement in HCT outcomes for DS-ALL. Pediatr Blood Cancer 2014;61:1126-1128. © 2014 Wiley Periodicals, Inc.

Authors
Hitzler, JK; He, W; Doyle, J; Cairo, M; Camitta, BM; Chan, KW; Perez, MAD; Fraser, C; Gross, TG; Horan, JT; Kennedy-Nasser, AA; Kitko, C; Kurtzberg, J; Lehmann, L; O'Brien, T; Pulsipher, MA; Smith, FO; Zhang, MJ; Eapen, M; Carpenter, PA
MLA Citation
Hitzler, JK, He, W, Doyle, J, Cairo, M, Camitta, BM, Chan, KW, Perez, MAD, Fraser, C, Gross, TG, Horan, JT, Kennedy-Nasser, AA, Kitko, C, Kurtzberg, J, Lehmann, L, O'Brien, T, Pulsipher, MA, Smith, FO, Zhang, MJ, Eapen, M, and Carpenter, PA. "Outcome of transplantation for acute lymphoblastic leukemia in children with down syndrome." Pediatric Blood and Cancer 61.6 (January 1, 2014): 1126-1128.
Source
scopus
Published In
Pediatric Blood & Cancer
Volume
61
Issue
6
Publish Date
2014
Start Page
1126
End Page
1128
DOI
10.1002/pbc.24918

Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy

Objective To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE). Study design We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10 7 cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, III edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells. Results Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85. Conclusions Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed. © 2014 The Authors.

Authors
Cotten, CM; Murtha, AP; Goldberg, RN; Grotegut, CA; Smith, PB; Goldstein, RF; Fisher, KA; Gustafson, KE; Waters-Pick, B; Swamy, GK; Rattray, B; Tan, S; Kurtzberg, J
MLA Citation
Cotten, CM, Murtha, AP, Goldberg, RN, Grotegut, CA, Smith, PB, Goldstein, RF, Fisher, KA, Gustafson, KE, Waters-Pick, B, Swamy, GK, Rattray, B, Tan, S, and Kurtzberg, J. "Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy." Journal of Pediatrics 164.5 (January 1, 2014).
Source
scopus
Published In
The Journal of Pediatrics
Volume
164
Issue
5
Publish Date
2014
DOI
10.1016/j.jpeds.2013.11.036

Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: A report from the children's oncology group

PURPOSE: To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy. RESULTS: Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase. CONCLUSIONS: Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy. Copyright © 2014 by Lippincott Williams & Wilkins.

Authors
Tower, RL; Jones, TL; Camitta, BM; Asselin, BL; Bell, BA; Chauvenet, A; Devidas, M; Halperin, EC; Pullen, J; Shuster, JJ; Winick, N; Kurtzberg, J
MLA Citation
Tower, RL, Jones, TL, Camitta, BM, Asselin, BL, Bell, BA, Chauvenet, A, Devidas, M, Halperin, EC, Pullen, J, Shuster, JJ, Winick, N, and Kurtzberg, J. "Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: A report from the children's oncology group." Journal of Pediatric Hematology/Oncology 36.5 (January 1, 2014): 353-361.
Source
scopus
Published In
Journal of Pediatric Hematology/Oncology
Volume
36
Issue
5
Publish Date
2014
Start Page
353
End Page
361
DOI
10.1097/MPH.0000000000000131

Outcomes after Hematopoietic Stem Cell Transplantation for Children with I-Cell Disease

© 2014 American Society for Blood and Marrow Transplantation.Mucolipidosis type II (MLII), or I-cell disease, is a rare but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplantation (HSCT) has been used to successfully treat some lysosomal storage diseases, only 2 cases have been reported on the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, overall survival was low, with only 6 patients (27%) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development and often required complex medical support, such as gastrostomy tubes for nutrition and tracheostomy with mechanical ventilation. Although HSCT has demonstrated efficacy in treating some lysosomal storage disorders, the neurologic outcome and survival for patents with MLII were poor. Therefore, new medical and cellular therapies should be sought for these patients.

Authors
Lund, TC; Cathey, SS; Miller, WP; Eapen, M; Andreansky, M; Dvorak, CC; Davis, JH; Dalal, JD; Devine, SM; Eames, GM; Ferguson, WS; Giller, RH; He, W; Kurtzberg, J; Krance, R; Katsanis, E; Lewis, VA; Sahdev, I; Orchard, PJ
MLA Citation
Lund, TC, Cathey, SS, Miller, WP, Eapen, M, Andreansky, M, Dvorak, CC, Davis, JH, Dalal, JD, Devine, SM, Eames, GM, Ferguson, WS, Giller, RH, He, W, Kurtzberg, J, Krance, R, Katsanis, E, Lewis, VA, Sahdev, I, and Orchard, PJ. "Outcomes after Hematopoietic Stem Cell Transplantation for Children with I-Cell Disease." Biology of Blood and Marrow Transplantation 20.11 (January 1, 2014): 1847-1851.
Source
scopus
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
11
Publish Date
2014
Start Page
1847
End Page
1851
DOI
10.1016/j.bbmt.2014.06.019

Multi-site evaluation of the BD Stem Cell Enumeration Kit for CD34+ cell enumeration on the BD FACSCanto II and BD FACSCalibur flow cytometers

© 2014 International Society for Cellular Therapy.Background aims: Evaluation of the BD Stem Cell Enumeration Kit was conducted at four clinical sites with flow cytometry CD34+ enumeration to assess agreement between two investigational methods: (i) the BD FACSCanto II and BD FACSCalibur systems and (ii) the predicate method (Beckman Coulter StemKit and StemTrol, Immunotech SAS, Beckman Coulter, Marseille Cedex 9, France). Methods: Leftover and delinked specimens (. n= 1032) from clinical flow cytometry testing were analyzed on the BD FACSCanto II (. n= 918) and BD FACSCalibur (. n= 905) in normal and mobilized blood, frozen and thawed bone marrow and leucopheresis and cord blood anticoagulated with citrate phosphate dextrose, anticoagulant citrate dextrose-solution A, heparin and ethylenediaminetetraacetate, alone or in combination. Fresh leucopheresis analysis addressed site equivalency for sample preparation, testing and analysis. Results: The mean relative bias showed agreement within predefined parameters for the BD FACSCanto II (-2.81 to 4.31 ±7.1) and BD FACSCalibur (-2.69 to 5.2 ±7.9). Results are reported as absolute and relative differences compared with the predicate for viable CD34+, percentage of CD34+ in CD45+ and viable CD45+ populations (or gates). Bias analyses of the distribution of the predicate low, mid and high bin values were done using BD FACSCanto II optimal gating and BD FACSCalibur manual gating for viable CD34+, percentage of CD34+ in CD45+ and viable CD45+. Bias results from both investigational methods show agreement. Deming regression analyses showed a linear relationship with R2 > 0.92 for both investigational methods. Discussion: In conclusion, the results from both investigational methods demonstrated agreement and equivalence with the predicate method for enumeration of absolute viable CD34+, percentage of viable CD34+ in CD45+ and absolute viable CD45+ populations.

Authors
Preti, RA; Chan, WS; Kurtzberg, J; Dornsife, RE; Wallace, PK; Furlage, R; Lin, A; Omana-Zapata, I; Bonig, H; Tonn, T
MLA Citation
Preti, RA, Chan, WS, Kurtzberg, J, Dornsife, RE, Wallace, PK, Furlage, R, Lin, A, Omana-Zapata, I, Bonig, H, and Tonn, T. "Multi-site evaluation of the BD Stem Cell Enumeration Kit for CD34+ cell enumeration on the BD FACSCanto II and BD FACSCalibur flow cytometers." Cytotherapy 16.11 (January 1, 2014): 1558-1574.
Source
scopus
Published In
Cytotherapy (Informa)
Volume
16
Issue
11
Publish Date
2014
Start Page
1558
End Page
1574
DOI
10.1016/j.jcyt.2014.03.006

Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans.

In infants exposed to maternal stress in utero, phenotypic plasticity through epigenetic events may mechanistically explain increased risk of preterm birth (PTB), which confers increased risk for neurodevelopmental disorders, cardiovascular disease, and cancers in adulthood. We examined associations between prenatal maternal stress and PTB, evaluating the role of DNA methylation at imprint regulatory regions. We enrolled women from prenatal clinics in Durham, NC. Stress was measured in 537 women at 12 weeks of gestation using the Perceived Stress Scale. DNA methylation at differentially methylated regions (DMRs) associated with H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 was measured from peripheral and cord blood using bisulfite pyrosequencing in a sub-sample of 79 mother-infant pairs. We examined associations between PTB and stress and evaluated differences in DNA methylation at each DMR by stress. Maternal stress was not associated with PTB (OR = 0.98; 95% CI, 0.40-2.40; P = 0.96), after adjustment for maternal body mass index (BMI), income, and raised blood pressure. However, elevated stress was associated with higher infant DNA methylation at the MEST DMR (2.8% difference, P < 0.01) after adjusting for PTB. Maternal stress may be associated with epigenetic changes at MEST, a gene relevant to maternal care and obesity. Reduced prenatal stress may support the epigenomic profile of a healthy infant.

Authors
Vidal, AC; Benjamin Neelon, SE; Liu, Y; Tuli, AM; Fuemmeler, BF; Hoyo, C; Murtha, AP; Huang, Z; Schildkraut, J; Overcash, F; Kurtzberg, J; Jirtle, RL; Iversen, ES; Murphy, SK
MLA Citation
Vidal, AC, Benjamin Neelon, SE, Liu, Y, Tuli, AM, Fuemmeler, BF, Hoyo, C, Murtha, AP, Huang, Z, Schildkraut, J, Overcash, F, Kurtzberg, J, Jirtle, RL, Iversen, ES, and Murphy, SK. "Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans." Genetics & epigenetics 6 (January 2014): 37-44.
PMID
25512713
Source
epmc
Published In
Genetics and Epigenetics
Volume
6
Publish Date
2014
Start Page
37
End Page
44
DOI
10.4137/geg.s18067

A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases

Authors
Parikh, SH; Mendizabal, A; Benjamin, CL; Komanduri, KV; Antony, J; Petrovic, A; Hale, G; Driscoll, TA; Martin, PL; Page, KM; Flickinger, K; Moffet, J; Niedzwiecki, D; Kurtzberg, J; Szabolcs, P
MLA Citation
Parikh, SH, Mendizabal, A, Benjamin, CL, Komanduri, KV, Antony, J, Petrovic, A, Hale, G, Driscoll, TA, Martin, PL, Page, KM, Flickinger, K, Moffet, J, Niedzwiecki, D, Kurtzberg, J, and Szabolcs, P. "A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases." Biology of Blood and Marrow Transplantation 20.3 (2014): 326-336.
Source
scopus
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
3
Publish Date
2014
Start Page
326
End Page
336

Hematopoietic stem cell gene therapy with lentiviral vector in 4 patients with cerebral X-linked adrenoleukodystrophy: long-term outcome and comparison of efficacy with allogeneic hematopoietic stem cell transplantation

Authors
Orchard, P; Cartier, N; Hacein-Bey-Abina, S; Kurtzberg, J; Escolar, M; Tolar, J; Baruchel, A; Dalle, J-H; Michel, G; Blanche, S; Bartholomae, C; Schmidt, M; Bougneres, P; Von Kalle, C; Cavazzana-Calvo, M; Fischer, A; Aubourg, P
MLA Citation
Orchard, P, Cartier, N, Hacein-Bey-Abina, S, Kurtzberg, J, Escolar, M, Tolar, J, Baruchel, A, Dalle, J-H, Michel, G, Blanche, S, Bartholomae, C, Schmidt, M, Bougneres, P, Von Kalle, C, Cavazzana-Calvo, M, Fischer, A, and Aubourg, P. "Hematopoietic stem cell gene therapy with lentiviral vector in 4 patients with cerebral X-linked adrenoleukodystrophy: long-term outcome and comparison of efficacy with allogeneic hematopoietic stem cell transplantation." December 1, 2013.
Source
wos-lite
Published In
Human Gene Therapy
Volume
24
Issue
12
Publish Date
2013
Start Page
A21
End Page
A21

Analysis of risk factors influencing outcomes after cord blood transplantation in children with juvenile myelomonocytic leukemia: a EUROCORD, EBMT, EWOG-MDS, CIBMTR study.

We retrospectively analyzed 110 patients with juvenile myelomonocytic leukemia, given single-unit, unrelated donor umbilical cord blood transplantation. Median age at diagnosis and at transplantation was 1.4 years (age range, 0.1-6.4 years) and 2.2 years (age range, 0.5-7.4 years), respectively. Before transplantation, 88 patients received chemotherapy; splenectomy was performed in 24 patients. Monosomy of chromosome 7 was the most frequent cytogenetic abnormality, found in 24% of patients. All but 8 patients received myeloablative conditioning; cyclosporine plus steroids was the most common graft-versus-host disease prophylaxis. Sixteen percent of units were HLA-matched with the recipient, whereas 43% and 35% had either 1 or 2 to 3 HLA disparities, respectively. The median number of nucleated cells infused was 7.1 × 10(7)/kg (range, 1.7-27.6 × 10(7)/kg). With a median follow-up of 64 months (range, 14-174 months), the 5-year cumulative incidences of transplantation-related mortality and relapse were 22% and 33%, respectively. The 5-year disease-free survival rate was 44%. In multivariate analysis, factors predicting better disease-free survival were age younger than 1.4 years at diagnosis (hazard ratio [HR], 0.42; P = .005), 0 to 1 HLA disparities in the donor/recipient pair (HR, 0.4; P = .009), and karyotype other than monosomy 7 (HR, 0.5; P = .02). Umbilical cord blood transplantation may cure a relevant proportion of children with juvenile myelomonocytic leukemia. Because disease recurrence remains the major cause of treatment failure, strategies to reduce incidence of relapse are warranted.

Authors
Locatelli, F; Crotta, A; Ruggeri, A; Eapen, M; Wagner, JE; Macmillan, ML; Zecca, M; Kurtzberg, J; Bonfim, C; Vora, A; Díaz de Heredia, C; Teague, L; Stein, J; O'Brien, TA; Bittencourt, H; Madureira, A; Strahm, B; Peters, C; Niemeyer, C; Gluckman, E; Rocha, V
MLA Citation
Locatelli, F, Crotta, A, Ruggeri, A, Eapen, M, Wagner, JE, Macmillan, ML, Zecca, M, Kurtzberg, J, Bonfim, C, Vora, A, Díaz de Heredia, C, Teague, L, Stein, J, O'Brien, TA, Bittencourt, H, Madureira, A, Strahm, B, Peters, C, Niemeyer, C, Gluckman, E, and Rocha, V. "Analysis of risk factors influencing outcomes after cord blood transplantation in children with juvenile myelomonocytic leukemia: a EUROCORD, EBMT, EWOG-MDS, CIBMTR study." Blood 122.12 (September 19, 2013): 2135-2141.
PMID
23926304
Source
pubmed
Published In
Blood
Volume
122
Issue
12
Publish Date
2013
Start Page
2135
End Page
2141
DOI
10.1182/blood-2013-03-491589

Comparative cost-effectiveness analysis of voriconazole and fluconazole for prevention of invasive fungal infection in patients receiving allogeneic hematopoietic cell transplants.

PURPOSE: The cost-effectiveness of voriconazole versus fluconazole prophylaxis against fungal infections in hematopoietic cell transplant (HCT) recipients is investigated. METHODS: A decision-analytic model was developed to estimate the drug costs associated with planned or supplemental prophylaxis and empirical therapy and the costs of treating suspected or documented invasive fungal infections (IFIs) in HCT recipients. Published clinical trial data on 599 patients who received 100-180 days of prophylactic therapy with voriconazole or fluconazole were used to model specified IFI-prevention and mortality outcomes; 6-month, 12-month, and lifetime incremental cost-effectiveness ratios (ICERs) were estimated, with a bootstrap analysis performed to reffect the uncertainty of the clinical trial data. RESULTS: Estimated mean total prophylaxis and IFI-related costs associated with voriconazole versus fluconazole prophylaxis over 12 months were higher in the entire study population and among patients receiving HCT for diagnoses other than acute myeloid leukemia (AML) but were not significantly different for patients with AML. The cost per IFI avoided ($66,919) and the cost per life-year gained ($5,453) were lower among patients with AML who received voriconazole relative to the full study population. ICERs were more favorable for voriconazole over a 6-month time frame and when modeling was conducted using generic price data. Assuming a threshold value of $50,000 for one year of life gained, the calculated probability of voriconazole being cost-effective was 33% for the full study population and 85% for the AML subgroup. CONCLUSION: The decision model indicated that voriconazole prophylaxis was cost-effective for patients undergoing allogeneic HCT for AML.

Authors
Mauskopf, J; Chirila, C; Graham, J; Gersten, ID; Leather, H; Maziarz, RT; Baden, LR; Bolaños-Meade, J; Brown, JMY; Walsh, TJ; Horowitz, MH; Kurtzberg, J; Marr, KA; Wingard, JR
MLA Citation
Mauskopf, J, Chirila, C, Graham, J, Gersten, ID, Leather, H, Maziarz, RT, Baden, LR, Bolaños-Meade, J, Brown, JMY, Walsh, TJ, Horowitz, MH, Kurtzberg, J, Marr, KA, and Wingard, JR. "Comparative cost-effectiveness analysis of voriconazole and fluconazole for prevention of invasive fungal infection in patients receiving allogeneic hematopoietic cell transplants." Am J Health Syst Pharm 70.17 (September 1, 2013): 1518-1527.
PMID
23943184
Source
pubmed
Published In
American Journal of Health-System Pharmacy
Volume
70
Issue
17
Publish Date
2013
Start Page
1518
End Page
1527
DOI
10.2146/ajhp120599

ADOPTIVE LYMPHOCYTE THERAPY (ALT) PLUS DENDRITIC CELL VACCINATION (DCV) AFTER MYELOABLATIVE (MA) OR NON-MYELOABLATIVE (NMA) CONDITIONING IN PATIENTS WITH RECURRENT CENTRAL PNET (C-PNET)

Authors
Gururangan, S; Grant, GA; Driscoll, T; Archer, G; Sayour, EJ; II, HJE; Friedman, HS; Kurtzberg, J; Bigner, DD; Sampson, JH; Mitchell, DA
MLA Citation
Gururangan, S, Grant, GA, Driscoll, T, Archer, G, Sayour, EJ, II, HJE, Friedman, HS, Kurtzberg, J, Bigner, DD, Sampson, JH, and Mitchell, DA. "ADOPTIVE LYMPHOCYTE THERAPY (ALT) PLUS DENDRITIC CELL VACCINATION (DCV) AFTER MYELOABLATIVE (MA) OR NON-MYELOABLATIVE (NMA) CONDITIONING IN PATIENTS WITH RECURRENT CENTRAL PNET (C-PNET)." PEDIATRIC BLOOD & CANCER 60 (September 2013): 13-13.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
60
Publish Date
2013
Start Page
13
End Page
13

Outcomes of allogeneic hematopoietic cell transplantation in patients with dyskeratosis congenita.

We describe outcomes after allogeneic transplantation in 34 patients with dyskeratosis congenita who underwent transplantation between 1981 and 2009. The median age at transplantation was 13 years (range, 2 to 35). Approximately 50% of transplantations were from related donors. Bone marrow was the predominant source of stem cells (24 of 34). The day-28 probability of neutrophil recovery was 73% and the day-100 platelet recovery was 72%. The day-100 probability of grade II to IV acute GVHD and the 3-year probability of chronic graft-versus-host disease were 24% and 37%, respectively. The 10-year probability of survival was 30%; 14 patients were alive at last follow-up. Ten deaths occurred within 4 months from transplantation because of graft failure (n = 6) or other transplantation-related complications; 9 of these patients had undergone transplantation from mismatched related or from unrelated donors. Another 10 deaths occurred after 4 months; 6 of them occurred more than 5 years after transplantation, and 4 of these were attributed to pulmonary failure. Transplantation regimen intensity and transplantations from mismatched related or unrelated donors were associated with early mortality. Transplantation of grafts from HLA-matched siblings with cyclophosphamide-containing nonradiation regimens was associated with early low toxicity. Late mortality was attributed mainly to pulmonary complications and likely related to the underlying disease.

Authors
Gadalla, SM; Sales-Bonfim, C; Carreras, J; Alter, BP; Antin, JH; Ayas, M; Bodhi, P; Davis, J; Davies, SM; Deconinck, E; Deeg, HJ; Duerst, RE; Fasth, A; Ghavamzadeh, A; Giri, N; Goldman, FD; Kolb, EA; Krance, R; Kurtzberg, J; Leung, WH; Srivastava, A; Or, R; Richman, CM; Rosenberg, PS; Toledo Codina, JSD; Shenoy, S; Socié, G; Tolar, J; Williams, KM; Eapen, M; Savage, SA
MLA Citation
Gadalla, SM, Sales-Bonfim, C, Carreras, J, Alter, BP, Antin, JH, Ayas, M, Bodhi, P, Davis, J, Davies, SM, Deconinck, E, Deeg, HJ, Duerst, RE, Fasth, A, Ghavamzadeh, A, Giri, N, Goldman, FD, Kolb, EA, Krance, R, Kurtzberg, J, Leung, WH, Srivastava, A, Or, R, Richman, CM, Rosenberg, PS, Toledo Codina, JSD, Shenoy, S, Socié, G, Tolar, J, Williams, KM, Eapen, M, and Savage, SA. "Outcomes of allogeneic hematopoietic cell transplantation in patients with dyskeratosis congenita." Biol Blood Marrow Transplant 19.8 (August 2013): 1238-1243.
PMID
23751955
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
8
Publish Date
2013
Start Page
1238
End Page
1243
DOI
10.1016/j.bbmt.2013.05.021

Rescuing the neonatal brain from hypoxic injury with autologous cord blood.

Brain injury resulting from perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of acute mortality in infants and chronic neurologic disability in surviving children. Recent multicenter clinical trials demonstrated the effectiveness of hypothermia initiated within the first 6 postnatal hours to reduce the risk of death or major neurological disabilities among neonates with HIE. However, in these trials, approximately 40% of cooled infants died or survived with significant impairments. Therefore, adjunct therapies are required to improve the outcome in neonates with HIE. Cord blood (CB) is a rich source of stem cells. Administration of human CB cells in animal models of HIE has generally resulted in improved outcomes and multiple mechanisms have been suggested including anti-inflammation, release of neurotrophic factors and stimulation of endogenous neurogenesis. Investigators at Duke are conducting studies of autologous CB infusion in neonates with HIE and in children with cerebral palsy. These pilot studies indicate no added risk from the regimens used, but results of ongoing placebo-controlled trials are needed to assess efficacy. Meanwhile, further investigations are warranted to determine the best strategies, that is, timing, dosing, route of delivery, choice of stem cells and ex vivo modulations, to attain long-term benefits of CB stem cell therapy.

Authors
Liao, Y; Cotten, M; Tan, S; Kurtzberg, J; Cairo, MS
MLA Citation
Liao, Y, Cotten, M, Tan, S, Kurtzberg, J, and Cairo, MS. "Rescuing the neonatal brain from hypoxic injury with autologous cord blood." Bone Marrow Transplant 48.7 (July 2013): 890-900. (Review)
PMID
22964590
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
48
Issue
7
Publish Date
2013
Start Page
890
End Page
900
DOI
10.1038/bmt.2012.169

Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment.

High fevers and/or rashes prior to neutrophil engraftment are frequently observed after umbilical cord blood (UCB) transplantation, and the condition is referred to as pre-engraftment syndrome (PES). Few studies have evaluated the risk factors for and treatment response to PES. Therefore, we retrospectively characterized PES in 57 consecutive engrafted patients (≥ 12 years old) who received myeloablative dual UCB transplantation. All patients received TBI (≥ 13.2 Gy)-based myeloablative conditioning. Tacrolimus (n=35) or CYA (n=22) combined with mycophenolate mofetil was used as GVHD prophylaxis. PES was defined as the presence of non-infectious fever (≥ 38.5 °C) and/or rash prior to or on the day of neutrophil engraftment. The incidence (95% confidence interval) of PES was 77% (66-88%). The incidence of PES was significantly higher in patients who received CYA as a GVHD prophylaxis than those who received tacrolimus (P<0.001), and this association was confirmed in the multivariate analysis. The occurrence of PES did not impact OS or tumor relapse, although it may have increased non-relapse mortality (P=0.071). The incidence of acute GHVD or treatment-related mortality was not influenced by the choice to use corticosteroids to treat PES. This study suggests that use of CYA for GVHD prophylaxis increases the risk of PES following dual UCB transplantation.

Authors
Kanda, J; Kaynar, L; Kanda, Y; Prasad, VK; Parikh, SH; Lan, L; Shen, T; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; Winkel, S; McPherson, J; Kurtzberg, J; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Kaynar, L, Kanda, Y, Prasad, VK, Parikh, SH, Lan, L, Shen, T, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, Winkel, S, McPherson, J, Kurtzberg, J, Chao, NJ, and Horwitz, ME. "Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment." Bone Marrow Transplant 48.7 (July 2013): 926-931.
PMID
23334274
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
48
Issue
7
Publish Date
2013
Start Page
926
End Page
931
DOI
10.1038/bmt.2012.279

Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring.

OBJECTIVES: Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations. METHODS: Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions. RESULTS: After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight. CONCLUSION: We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.

Authors
Vidal, AC; Murphy, SK; Murtha, AP; Schildkraut, JM; Soubry, A; Huang, Z; Neelon, SEB; Fuemmeler, B; Iversen, E; Wang, F; Kurtzberg, J; Jirtle, RL; Hoyo, C
MLA Citation
Vidal, AC, Murphy, SK, Murtha, AP, Schildkraut, JM, Soubry, A, Huang, Z, Neelon, SEB, Fuemmeler, B, Iversen, E, Wang, F, Kurtzberg, J, Jirtle, RL, and Hoyo, C. "Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring." Int J Obes (Lond) 37.7 (July 2013): 907-913.
PMID
23609933
Source
pubmed
Published In
International Journal of Obesity
Volume
37
Issue
7
Publish Date
2013
Start Page
907
End Page
913
DOI
10.1038/ijo.2013.47

Hematopoietic Stem Cell Gene Therapy with Lentiviral Vector in 4 Patients with Cerebral X-Linked Adrenoleukodystrophy: Long-Term Outcome and Comparison of Efficacy with Allogeneic Hematopoietic Stem Cell Transplantation

Authors
Orchard, P; Cartier, N; Hacein-Bey-Abina, S; Kurtzberg, J; Escolar, M; Tolar, J; Baruchel, A; Dalle, J-H; Michel, G; Blanche, S; Bartholomae, C; Schmidt, M; Bougneres, P; van Kalle, C; Cavazzana-Calvo, M; Fischer, A; Aubourg, P
MLA Citation
Orchard, P, Cartier, N, Hacein-Bey-Abina, S, Kurtzberg, J, Escolar, M, Tolar, J, Baruchel, A, Dalle, J-H, Michel, G, Blanche, S, Bartholomae, C, Schmidt, M, Bougneres, P, van Kalle, C, Cavazzana-Calvo, M, Fischer, A, and Aubourg, P. "Hematopoietic Stem Cell Gene Therapy with Lentiviral Vector in 4 Patients with Cerebral X-Linked Adrenoleukodystrophy: Long-Term Outcome and Comparison of Efficacy with Allogeneic Hematopoietic Stem Cell Transplantation." June 2013.
Source
wos-lite
Published In
Molecular Therapy
Volume
21
Publish Date
2013
Start Page
S25
End Page
S26

Outcome of transplantation for acute myelogenous leukemia in children with Down syndrome.

Data on outcomes of allogeneic transplantation in children with Down syndrome and acute myelogenous leukemia (DS-AML) are scarce and conflicting. Early reports stress treatment-related mortality as the main barrier; a recent case series points to posttransplantation relapse. We reviewed outcome data for 28 patients with DS-AML reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2009 and performed a first matched-pair analysis of 21 patients with DS-AML and 80 non-DS AML controls. The median age at transplantation for DS-AML was 3 years, and almost half of the cohort was in second remission. The 3-year probability of overall survival was only 19%. In multivariate analysis, adjusting for interval from diagnosis to transplantation, risks of relapse (hazard ratio [HR], 2.84; P < .001; 62% versus 37%) and transplant-related mortality (HR, 2.52; P = .04; 24% versus 15%) were significantly higher for DS-AML compared to non-DS AML. Overall mortality risk (HR, 2.86; P < .001; 21% versus 52%) was significantly higher for DS-AML. Both transplant-related mortality and relapse contribute to higher mortality. Excess mortality in DS-AML patients can only effectively be addressed through an international multicenter effort to pilot strategies aimed at lowering both transplant-related mortality and relapse risks.

Authors
Hitzler, JK; He, W; Doyle, J; Cairo, M; Camitta, BM; Chan, KW; Diaz Perez, MA; Fraser, C; Gross, TG; Horan, JT; Kennedy-Nasser, AA; Kitko, C; Kurtzberg, J; Lehmann, L; O'Brien, T; Pulsipher, MA; Smith, FO; Zhang, M-J; Eapen, M; Carpenter, PA; CIBMTR Pediatric Cancer Working Committee,
MLA Citation
Hitzler, JK, He, W, Doyle, J, Cairo, M, Camitta, BM, Chan, KW, Diaz Perez, MA, Fraser, C, Gross, TG, Horan, JT, Kennedy-Nasser, AA, Kitko, C, Kurtzberg, J, Lehmann, L, O'Brien, T, Pulsipher, MA, Smith, FO, Zhang, M-J, Eapen, M, Carpenter, PA, and CIBMTR Pediatric Cancer Working Committee, . "Outcome of transplantation for acute myelogenous leukemia in children with Down syndrome." Biol Blood Marrow Transplant 19.6 (June 2013): 893-897.
PMID
23467128
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
6
Publish Date
2013
Start Page
893
End Page
897
DOI
10.1016/j.bbmt.2013.02.017

Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning.

We report transplantation outcomes of 258 children with Hurler syndrome (HS) after a myeloablative conditioning regimen from 1995 to 2007. Median age at transplant was 16.7 months and median follow-up was 57 months. The cumulative incidence of neutrophil recovery at day 60 was 91%, acute graft-versus-host disease (GVHD) (grade II-IV) at day 100 was 25%, and chronic GVHD and 5 years was 16%. Overall survival and event-free survival (EFS) at 5 years were 74% and 63%, respectively. EFS after HLA-matched sibling donor (MSD) and 6/6 matched unrelated cord blood (CB) donor were similar at 81%, 66% after 10/10 HLA-matched unrelated donor (UD), and 68% after 5/6 matched CB donor. EFS was lower after transplantation in 4/6 matched unrelated CB (UCB) (57%; P = .031) and HLA-mismatched UD (41%; P = .007). Full-donor chimerism (P = .039) and normal enzyme levels (P = .007) were higher after CB transplantation (92% and 98%, respectively) compared with the other grafts sources (69% and 59%, respectively). In conclusion, results of allogeneic transplantation for HS are encouraging, with similar EFS rates after MSD, 6/6 matched UCB, 5/6 UCB, and 10/10 matched UD. The use of mismatched UD and 4/6 matched UCB was associated with lower EFS.

Authors
Boelens, JJ; Aldenhoven, M; Purtill, D; Ruggeri, A; Defor, T; Wynn, R; Wraith, E; Cavazzana-Calvo, M; Rovelli, A; Fischer, A; Tolar, J; Prasad, VK; Escolar, M; Gluckman, E; O'Meara, A; Orchard, PJ; Veys, P; Eapen, M; Kurtzberg, J; Rocha, V; Eurocord, ; Inborn Errors Working Party of European Blood and Marrow Transplant group, ; Duke University Blood and Marrow Transplantation Program, ; Centre for International Blood and Marrow Research,
MLA Citation
Boelens, JJ, Aldenhoven, M, Purtill, D, Ruggeri, A, Defor, T, Wynn, R, Wraith, E, Cavazzana-Calvo, M, Rovelli, A, Fischer, A, Tolar, J, Prasad, VK, Escolar, M, Gluckman, E, O'Meara, A, Orchard, PJ, Veys, P, Eapen, M, Kurtzberg, J, Rocha, V, Eurocord, , Inborn Errors Working Party of European Blood and Marrow Transplant group, , Duke University Blood and Marrow Transplantation Program, , and Centre for International Blood and Marrow Research, . "Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning." Blood 121.19 (May 9, 2013): 3981-3987.
PMID
23493783
Source
pubmed
Published In
Blood
Volume
121
Issue
19
Publish Date
2013
Start Page
3981
End Page
3987
DOI
10.1182/blood-2012-09-455238

Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an inherited demyelinating disease that causes progressive neurologic deterioration, leading to severe motor disability, developmental regression, seizures, blindness, deafness, and death. The disease presents as a late-infantile, juvenile, or adult form. Hematopoietic stem cell transplantation has been shown to slow disease progression. The purpose of this longitudinal study was to evaluate long-term treatment outcomes after unrelated donor umbilical cord blood (UCB) transplantation in pediatric patients according to disease burden and age at onset (ie, late-infantile versus juvenile). Engraftment, survival, treatment-related toxicity, graft-versus-host disease, neurophysiologic measures, and neurodevelopmental function were assessed. To evaluate whether signal intensity abnormalities on magnetic resonance imaging (ie, modified Loes scores) predict post-transplant cognitive and gross motor development, a general linear mixed model was fit to the data. Twenty-seven patients underwent transplantation after myeloablative chemotherapy; 24 patients engrafted after the initial transplantation. Seven patients died of infection, regimen-related toxicity, or disease progression. Twenty patients (6 with late-infantile onset and 14 with juvenile onset) were followed for a median of 5.1 years (range, 2.4 to 14.7). We found that patients with motor function symptoms at the time of transplant did not improve after transplantation. Brainstem auditory evoked responses, visual evoked potentials, electroencephalogram, and/or peripheral nerve conduction velocities stabilized or improved in juvenile patients but continued to worsen in most patients with the late-infantile presentation. Pretransplant modified Loes scores were highly correlated with developmental outcomes and predictive of cognitive and motor function. Children who were asymptomatic at the time of transplantation benefited most from the procedure. Children with juvenile onset and minimal symptoms showed stabilization or deterioration of motor skills but maintained cognitive skills. Overall, children with juvenile onset had better outcomes than those with late-infantile onset. As in other leukodystrophies, early intervention correlated with optimal outcomes. We conclude that UCB transplantation benefits children with presymptomatic late-infantile MLD or minimally symptomatic juvenile MLD.

Authors
Martin, HR; Poe, MD; Provenzale, JM; Kurtzberg, J; Mendizabal, A; Escolar, ML
MLA Citation
Martin, HR, Poe, MD, Provenzale, JM, Kurtzberg, J, Mendizabal, A, and Escolar, ML. "Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy." Biol Blood Marrow Transplant 19.4 (April 2013): 616-624.
PMID
23348427
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
4
Publish Date
2013
Start Page
616
End Page
624
DOI
10.1016/j.bbmt.2013.01.010

A PHASE I/II STUDY OF ADOPTIVE T-CELL THERAPY (ALT) AND DC VACCINATION (DCV) DURING RECOVERY FROM MYELOABLATIVE CHEMOTHERAPY AND HEMATOPOIETIC STEM CELL TRANSPLANTATION (HDC plus ASCR) OR NON-MYELOABLATIVE CONDITIONING (NMA) IN PATIENTS (PTS) WITH RECURRENT CENTRAL PNETS (RE-MATCH PROTOCOL)

Authors
Gururangan, S; Grant, G; Driscoll, T; Archer, G; Herndon, J; Friedman, H; Kurtzberg, J; Bigner, D; Sampson, J; Mitchell, D
MLA Citation
Gururangan, S, Grant, G, Driscoll, T, Archer, G, Herndon, J, Friedman, H, Kurtzberg, J, Bigner, D, Sampson, J, and Mitchell, D. "A PHASE I/II STUDY OF ADOPTIVE T-CELL THERAPY (ALT) AND DC VACCINATION (DCV) DURING RECOVERY FROM MYELOABLATIVE CHEMOTHERAPY AND HEMATOPOIETIC STEM CELL TRANSPLANTATION (HDC plus ASCR) OR NON-MYELOABLATIVE CONDITIONING (NMA) IN PATIENTS (PTS) WITH RECURRENT CENTRAL PNETS (RE-MATCH PROTOCOL)." April 2013.
Source
wos-lite
Published In
Neuro-Oncology
Volume
15
Publish Date
2013
Start Page
46
End Page
47

NiCord (R) expanded haematopoietic progenitor cells are capable of outcompeting the unmanipulated cord blood unit following myeloablative dual umbilical cord blood transplantation

Authors
Horwitz, M; Stiff, P; Chao, N; Rizzieri, D; Long, G; Sullivan, K; Gasparetto, C; Chute, J; Morris, A; McDonald, C; Wease, S; Snyder, D; Shoham, H; Cohen, EG; Friend, E; Landau, E; Kurtzberg, J; Peled, P
MLA Citation
Horwitz, M, Stiff, P, Chao, N, Rizzieri, D, Long, G, Sullivan, K, Gasparetto, C, Chute, J, Morris, A, McDonald, C, Wease, S, Snyder, D, Shoham, H, Cohen, EG, Friend, E, Landau, E, Kurtzberg, J, and Peled, P. "NiCord (R) expanded haematopoietic progenitor cells are capable of outcompeting the unmanipulated cord blood unit following myeloablative dual umbilical cord blood transplantation." April 2013.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
48
Publish Date
2013
Start Page
S32
End Page
S33

Hematopoietic cell transplantation with cord blood for cure of HIV infections.

Hematopoietic cell transplantation (HCT) using CCR5-Δ32/Δ32 stem cells from an adult donor has resulted in the only known cure of human immunodeficiency virus (HIV) infection. However, it is not feasible to repeat this procedure except rarely because of the low incidence of the CCR5-Δ32 allele, the availability of only a small number of potential donors for most patients, and the need for a very close human leukocyte antigen (HLA) match between adult donors and recipients. In contrast, cord blood (CB) transplantations require significantly less stringent HLA matching. Therefore, our hypothesis is that cure of HIV infections by HCT can be accomplished much more readily using umbilical CB stem cells obtained from a modestly sized inventory of cryopreserved CCR5-Δ32/Δ32 CB units. To test this hypothesis, we developed a screening program for CB units and are developing an inventory of CCR5-Δ32/Δ32 cryopreserved units available for HCT. Three hundred such units are projected to provide for white pediatric patients a 73.6% probability of finding an adequately HLA matched unit with a cell dose of ≥2.5 × 10(7) total nucleated cells (TNCs)/kg and a 27.9% probability for white adults. With a cell dose of ≥1 × 10(7) TNCs/kg, the corresponding projected probabilities are 85.6% and 82.1%. The projected probabilities are lower for ethnic minorities. Impetus for using CB HCT was provided by a transplantation of an adult with acute myelogenous leukemia who was not HIV infected. The HCT was performed with a CCR5-Δ32/Δ32 CB unit, and posttransplantation in vitro studies indicated that the patient's peripheral blood mononuclear cells were resistant to HIV infection.

Authors
Petz, LD; Redei, I; Bryson, Y; Regan, D; Kurtzberg, J; Shpall, E; Gutman, J; Querol, S; Clark, P; Tonai, R; Santos, S; Bravo, A; Spellman, S; Gragert, L; Rossi, J; Li, S; Li, H; Senitzer, D; Zaia, J; Rosenthal, J; Forman, S; Chow, R
MLA Citation
Petz, LD, Redei, I, Bryson, Y, Regan, D, Kurtzberg, J, Shpall, E, Gutman, J, Querol, S, Clark, P, Tonai, R, Santos, S, Bravo, A, Spellman, S, Gragert, L, Rossi, J, Li, S, Li, H, Senitzer, D, Zaia, J, Rosenthal, J, Forman, S, and Chow, R. "Hematopoietic cell transplantation with cord blood for cure of HIV infections." Biol Blood Marrow Transplant 19.3 (March 2013): 393-397.
PMID
23089564
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
3
Publish Date
2013
Start Page
393
End Page
397
DOI
10.1016/j.bbmt.2012.10.017

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort.

BACKGROUND: Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene. METHODS: We examined DNA from umbilical cord blood leukocytes from 79 newborns, born between July 2005 and November 2006 at Duke University Hospital, Durham, NC. Their mothers participated in the Newborn Epigenetics Study (NEST) during pregnancy. Parental characteristics were obtained via standardized questionnaires and medical records. DNA methylation patterns at two DMRs were analyzed by bisulfite pyrosequencing; one DMR upstream of IGF2 (IGF2 DMR), and one DMR upstream of the neighboring H19 gene (H19 DMR). Multiple regression models were used to determine potential associations between the offspring's DNA methylation patterns and parental obesity before conception. Obesity was defined as body mass index (BMI) ≥30 kg/m². RESULTS: Hypomethylation at the IGF2 DMR was associated with paternal obesity. Even after adjusting for several maternal and newborn characteristics, we observed a persistent inverse association between DNA methylation in the offspring and paternal obesity (β-coefficient was -5.28, P = 0.003). At the H19 DMR, no significant associations were detected between methylation patterns and paternal obesity. Our data suggest an increase in DNA methylation at the IGF2 and H19 DMRs among newborns from obese mothers, but a larger study is warranted to further explore the potential effects of maternal obesity or lifestyle on the offspring's epigenome. CONCLUSIONS: While our small sample size is limited, our data indicate a preconceptional impact of paternal obesity on the reprogramming of imprint marks during spermatogenesis. Given the biological importance of imprinting fidelity, our study provides evidence for transgenerational effects of paternal obesity that may influence the offspring's future health status.

Authors
Soubry, A; Schildkraut, JM; Murtha, A; Wang, F; Huang, Z; Bernal, A; Kurtzberg, J; Jirtle, RL; Murphy, SK; Hoyo, C
MLA Citation
Soubry, A, Schildkraut, JM, Murtha, A, Wang, F, Huang, Z, Bernal, A, Kurtzberg, J, Jirtle, RL, Murphy, SK, and Hoyo, C. "Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort. (Published online)" BMC Med 11 (February 6, 2013): 29-.
PMID
23388414
Source
pubmed
Published In
BMC Medicine
Volume
11
Publish Date
2013
Start Page
29
DOI
10.1186/1741-7015-11-29

Superior Survival After Single Unit Umbilical Cord Blood Transplantation (UCBT) in Children with Hematological Malignancies Treated on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0501 Relative to the Cord Blood Transplantation (COBLT)

Authors
Kurtzberg, J; Carter, SL; Mendizabal, A; Wall, DA; Schultz, KR; Kernan, NA; Eapen, M; Wagner, JE
MLA Citation
Kurtzberg, J, Carter, SL, Mendizabal, A, Wall, DA, Schultz, KR, Kernan, NA, Eapen, M, and Wagner, JE. "Superior Survival After Single Unit Umbilical Cord Blood Transplantation (UCBT) in Children with Hematological Malignancies Treated on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0501 Relative to the Cord Blood Transplantation (COBLT)." February 2013.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
2
Publish Date
2013
Start Page
S121
End Page
S121

Nicord (R) Expanded Hematopoietic Progenitor Cells (HPC) Are Capable of Outcompeting the Unmanipulated (UM) Cord Blood Unit and of Prolonged Myeloid and Lymphoid Engraftment Following Myeloablative Dual Umbilical Cord Blood (UCB) Transplantation

Authors
Horwitz, ME; Stiff, PJ; Chao, NJ; Rizzieri, D; Long, G; Sullivan, K; Gasparetto, C; Chute, J; Morris, A; McDonald, C; Wease, S; Snyder, D; Galamidi-Cohen, E; Shoham, H; Landau, E; Friend, E; Kurtzberg, J; Peled, T
MLA Citation
Horwitz, ME, Stiff, PJ, Chao, NJ, Rizzieri, D, Long, G, Sullivan, K, Gasparetto, C, Chute, J, Morris, A, McDonald, C, Wease, S, Snyder, D, Galamidi-Cohen, E, Shoham, H, Landau, E, Friend, E, Kurtzberg, J, and Peled, T. "Nicord (R) Expanded Hematopoietic Progenitor Cells (HPC) Are Capable of Outcompeting the Unmanipulated (UM) Cord Blood Unit and of Prolonged Myeloid and Lymphoid Engraftment Following Myeloablative Dual Umbilical Cord Blood (UCB) Transplantation." February 2013.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
2
Publish Date
2013
Start Page
S118
End Page
S118

Why Do Umbilical Cord Blood Units Fail to Qualify for Public Banking?

Authors
Wishnew, J; Wease, S; Hemandez, J; Page, K; Kurtzberg, J
MLA Citation
Wishnew, J, Wease, S, Hemandez, J, Page, K, and Kurtzberg, J. "Why Do Umbilical Cord Blood Units Fail to Qualify for Public Banking?." February 2013.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
2
Publish Date
2013
Start Page
S316
End Page
S316

Associations between birth and one year anthropometric measurements and IGF2 and IGF2R genetic variants in African American and Caucasian American infants.

Insulin-like growth factor 2 receptor (IGF2R) and insulin-like growth factor 2 (IGF2) genetic variants have been inconsistently associated with low birth weight and birth length in Caucasian and Asian infants, however few studies have included African Americans (AA). Generalized linear models and logistic regression models were used to examine associations between IGF2R single nucleotide polymorphisms (SNP) rs629849 and rs8191754, and IGF2 SNP rs680 and infant anthropometric measurements, in a racially diverse birth cohort in Durham County, North Carolina. Caucasian American (CA) carriers of the IGF2R SNP rs629849 were heavier (P = 0.02) and longer (P = 0.003) at birth, however body size at age 1 yr was similar to that of AA. Birth length significantly differed between carriers and non-carriers of the IGF2 rs680 variant in both AA (P = 0.04) and CA infants (P = 0.03). Both AA and CA carriers were 1 cm shorter at birth compared to non-carriers. We found no evidence for an association between rs8191754 and infant anthropometric measurements. Associations between SNPs andone year weight gain were only observed for rs680; CA infant carriers of rs680 variants weighed less than non-carriers at year one (P = 0.03); however, no associations were found in AA infants at year one. Larger studies using ancestral markers are required to disentangle these associations.

Authors
Vidal, AC; Overcash, F; Murphy, SK; Murtha, AP; Schildkraut, JM; Forman, MR; Demark-Wahnefried, W; Kurtzberg, J; Skaar, D; Jirtle, RL; Hoyo, C
MLA Citation
Vidal, AC, Overcash, F, Murphy, SK, Murtha, AP, Schildkraut, JM, Forman, MR, Demark-Wahnefried, W, Kurtzberg, J, Skaar, D, Jirtle, RL, and Hoyo, C. "Associations between birth and one year anthropometric measurements and IGF2 and IGF2R genetic variants in African American and Caucasian American infants." Journal of pediatric genetics 2.3 (January 2013).
PMID
26045971
Source
epmc
Published In
Journal of Pediatric Genetics
Volume
2
Issue
3
Publish Date
2013
DOI
10.3233/pge-13064

Extensive haplotype diversity in African American mothers and their cord blood units.

HLA-A, -B, -C, -DRB1, -DQB1 assignments were obtained for 374 pairs of African American mothers and their umbilical cord blood units (CBU) by DNA sequencing. An algorithm developed by the National Marrow Donor Program was used to assign 1122 haplotypes by segregation. Seventy percent of the haplotypes carried assignments at all five loci. In the remainder, alleles at various loci, most often DQB1 in 48% of the haplotypes with a missing assignment, could not be assigned due to sharing of both alleles by mother and CBU. There were 652 haplotypes carrying a unique combination of alleles at the five loci; the majority (74%) were singletons. Novel B∼C and DRB1~DQB1 associations were observed. The results show the genetic diversity in this population and provide validation for a publically available tool for pedigree analysis. Our observations underscore the need for procurement of increased numbers of units in the national cord blood inventory in order to identify matching donors for all patients requiring hematopoietic stem cell transplantation.

Authors
Tu, B; Leahy, N; Yang, R; Cha, N; Kariyawasam, K; Hou, L; Xiao, Y; Masaberg, C; Pulse-Earle, D; Maiers, M; Ng, J; Kurtzberg, J; Hurley, CK
MLA Citation
Tu, B, Leahy, N, Yang, R, Cha, N, Kariyawasam, K, Hou, L, Xiao, Y, Masaberg, C, Pulse-Earle, D, Maiers, M, Ng, J, Kurtzberg, J, and Hurley, CK. "Extensive haplotype diversity in African American mothers and their cord blood units." Tissue Antigens 81.1 (January 2013): 28-34.
PMID
23163897
Source
pubmed
Published In
Tissue Antigens
Volume
81
Issue
1
Publish Date
2013
Start Page
28
End Page
34
DOI
10.1111/tan.12035

Impact of Selection of Cord Blood Units from the United States and Swiss Registries on the Cost of Banking Operations

Authors
Bart, T; Boo, M; Balabanova, S; Fischer, Y; Nicoloso, G; Foeken, L; Oudshoorn, M; Passweg, J; Tichelli, A; Kindler, V; Kurtzberg, J; Price, T; Regan, D; Shpall, EJ; Schwabe, R
MLA Citation
Bart, T, Boo, M, Balabanova, S, Fischer, Y, Nicoloso, G, Foeken, L, Oudshoorn, M, Passweg, J, Tichelli, A, Kindler, V, Kurtzberg, J, Price, T, Regan, D, Shpall, EJ, and Schwabe, R. "Impact of Selection of Cord Blood Units from the United States and Swiss Registries on the Cost of Banking Operations." TRANSFUSION MEDICINE AND HEMOTHERAPY 40.1 (2013): 14-20.
PMID
23637645
Source
wos-lite
Published In
Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie
Volume
40
Issue
1
Publish Date
2013
Start Page
14
End Page
20
DOI
10.1159/000345690

Hematopoietic Cell Transplantation with Cord Blood for Cure of HIV Infections

Hematopoietic cell transplantation (HCT) using CCR5-Δ32/Δ32 stem cells from an adult donor has resulted in the only known cure of human immunodeficiency virus (HIV) infection. However, it is not feasible to repeat this procedure except rarely because of the low incidence of the CCR5-Δ32 allele, the availability of only a small number of potential donors for most patients, and the need for a very close human leukocyte antigen (HLA) match between adult donors and recipients. In contrast, cord blood (CB) transplantations require significantly less stringent HLA matching. Therefore, our hypothesis is that cure of HIV infections by HCT can be accomplished much more readily using umbilical CB stem cells obtained from a modestly sized inventory of cryopreserved CCR5-Δ32/Δ32 CB units. To test this hypothesis, we developed a screening program for CB units and are developing an inventory of CCR5-Δ32/Δ32 cryopreserved units available for HCT. Three hundred such units are projected to provide for white pediatric patients a 73.6% probability of finding an adequately HLA matched unit with a cell dose of ≥2.5 × 107 total nucleated cells (TNCs)/kg and a 27.9% probability for white adults. With a cell dose of ≥1 × 107 TNCs/kg, the corresponding projected probabilities are 85.6% and 82.1%. The projected probabilities are lower for ethnic minorities. Impetus for using CB HCT was provided by a transplantation of an adult with acute myelogenous leukemia who was not HIV infected. The HCT was performed with a CCR5-Δ32/Δ32 CB unit, and posttransplantation in vitro studies indicated that the patient's peripheral blood mononuclear cells were resistant to HIV infection. © 2013 American Society for Blood and Marrow Transplantation.

Authors
Petz, LD; Redei, I; Bryson, Y; Regan, D; Kurtzberg, J; Shpall, E; Gutman, J; Querol, S; Clark, P; Tonai, R; Santos, S; Bravo, A; Spellman, S; Gragert, L; Rossi, J; Li, S; Li, H; Senitzer, D; Zaia, J; Rosenthal, J; Forman, S; Chow, R
MLA Citation
Petz, LD, Redei, I, Bryson, Y, Regan, D, Kurtzberg, J, Shpall, E, Gutman, J, Querol, S, Clark, P, Tonai, R, Santos, S, Bravo, A, Spellman, S, Gragert, L, Rossi, J, Li, S, Li, H, Senitzer, D, Zaia, J, Rosenthal, J, Forman, S, and Chow, R. "Hematopoietic Cell Transplantation with Cord Blood for Cure of HIV Infections." Biology of Blood and Marrow Transplantation 19.3 (2013): 393-397.
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
3
Publish Date
2013
Start Page
393
End Page
397
DOI
10.1016/j.bbmt.2012.10.017

Diffuse reduction of white matter connectivity in cerebral palsy with specific vulnerability of long range fiber tracts

Cerebral palsy (CP) is a heterogeneous group of non-progressive motor disorders caused by injury to the developing fetal or infant brain. Although the defining feature of CP is motor impairment, numerous other neurodevelopmental disabilities are associated with CP and contribute greatly to its morbidity. The relationship between brain structure and neurodevelopmental outcomes in CP is complex, and current evidence suggests that motor and developmental outcomes are related to the spatial pattern and extent of brain injury. Given that multiple disabilities are frequently associated with CP, and that there is increasing burden of neurodevelopmental disability with increasing motor severity, global white matter (WM) connectivity was examined in a cohort of 17 children with bilateral CP to test the hypothesis that increased global WM damage will be seen in the group of severely affected (Gross Motor Function Classification Scale (GMFCS) level of IV) as compared to moderately affected (GMFCS of II or III) individuals. Diffusion tensor tractography was performed and the resulting fibers between anatomically defined brain regions were quantified and analyzed in relation to GMFCS levels. Overall, a reduction in total WM connectivity throughout the brain in severe versus moderate CP was observed, including but not limited to regions associated with the sensorimotor system. Our results also show a diffuse and significant reduction in global inter-regional connectivity between severity groups, represented by inter-regional fiber count, throughout the brain. Furthermore, it was also observed that there is a significant difference (p = 0.02) in long-range connectivity in patients with severe CP as compared to those with moderate CP, whereas short-range connectivity was similar between groups. This new finding, which has not been previously reported in the CP literature, demonstrates that CP may involve distributed, network-level structural disruptions. © 2013 The Authors.

Authors
Englander, ZA; Pizoli, CE; Batrachenko, A; Sun, J; Worley, G; Mikati, MA; Kurtzberg, J; Song, AW
MLA Citation
Englander, ZA, Pizoli, CE, Batrachenko, A, Sun, J, Worley, G, Mikati, MA, Kurtzberg, J, and Song, AW. "Diffuse reduction of white matter connectivity in cerebral palsy with specific vulnerability of long range fiber tracts." NeuroImage: Clinical 2.1 (2013): 440-447.
PMID
24179798
Source
scival
Published In
NeuroImage: Clinical
Volume
2
Issue
1
Publish Date
2013
Start Page
440
End Page
447
DOI
10.1016/j.nicl.2013.03.006

Maternal BMI, IGF-I Levels, and Birth Weight in African American and White Infants.

At birth, elevated IGF-I levels have been linked to birth weight extremes; high birth weight and low birth weight are risk factors for adult-onset chronic diseases including obesity, cardiovascular disease, and type 2 diabetes. We examined associations between plasma IGF-I levels and birth weight among infants born to African American and White obese and nonobese women. Prepregnancy weight and height were assessed among 251 pregnant women and anthropometric measurements of full term infants (≥37 weeks of gestation) were taken at birth. Circulating IGF-I was measured by ELISA in umbilical cord blood plasma. Linear regression models were utilized to examine associations between birth weight and high IGF-I, using the bottom two tertiles as referents. Compared with infants with lower IGF-I levels (≤3rd tertile), those with higher IGF-I levels (>3rd tertile) were 130 g heavier at birth, (β-coefficient = 230, se = 58.0, P = 0.0001), after adjusting for gender, race/ethnicity, gestational age, delivery route, maternal BMI and smoking. Stratified analyses suggested that these associations are more pronounced in infants born to African American women and women with BMI ≥30 kg/m(2); the cross product term for IGF-I and maternal BMI was statistically significant (P ≤ 0.0004). Our findings suggest that the association between IGF-I levels and birth weight depends more on maternal obesity than African American race/ethnicity.

Authors
Vidal, AC; Murtha, AP; Murphy, SK; Fortner, K; Overcash, F; Henry, N; Schildkraut, JM; Forman, MR; Demark-Wahnefried, W; Kurtzberg, J; Jirtle, R; Hoyo, C
MLA Citation
Vidal, AC, Murtha, AP, Murphy, SK, Fortner, K, Overcash, F, Henry, N, Schildkraut, JM, Forman, MR, Demark-Wahnefried, W, Kurtzberg, J, Jirtle, R, and Hoyo, C. "Maternal BMI, IGF-I Levels, and Birth Weight in African American and White Infants." Int J Pediatr 2013 (2013): 191472-.
PMID
23861689
Source
pubmed
Published In
International Journal of Pediatrics
Volume
2013
Publish Date
2013
Start Page
191472
DOI
10.1155/2013/191472

Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: Risk factors and response to treatment

High fevers and/or rashes prior to neutrophil engraftment are frequently observed after umbilical cord blood (UCB) transplantation, and the condition is referred to as pre-engraftment syndrome (PES). Few studies have evaluated the risk factors for and treatment response to PES. Therefore, we retrospectively characterized PES in 57 consecutive engrafted patients (≥12 years old) who received myeloablative dual UCB transplantation. All patients received TBI (≥13.2 Gy)-based myeloablative conditioning. Tacrolimus (n=35) or CYA (n=22) combined with mycophenolate mofetil was used as GVHD prophylaxis. PES was defined as the presence of non-infectious fever (≥38.5 °C) and/or rash prior to or on the day of neutrophil engraftment. The incidence (95% confidence interval) of PES was 77% (66-88%). The incidence of PES was significantly higher in patients who received CYA as a GVHD prophylaxis than those who received tacrolimus (P<0.001), and this association was confirmed in the multivariate analysis. The occurrence of PES did not impact OS or tumor relapse, although it may have increased non-relapse mortality (P=0.071). The incidence of acute GHVD or treatment-related mortality was not influenced by the choice to use corticosteroids to treat PES. This study suggests that use of CYA for GVHD prophylaxis increases the risk of PES following dual UCB transplantation. © 2013 Macmillan Publishers Limited All rights reserved.

Authors
Kanda, J; Kaynar, L; Kanda, Y; Prasad, VK; Parikh, SH; Lan, L; Shen, T; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; Winkel, S; McPherson, J; Kurtzberg, J; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Kaynar, L, Kanda, Y, Prasad, VK, Parikh, SH, Lan, L, Shen, T, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, Winkel, S, McPherson, J, Kurtzberg, J, Chao, NJ, and Horwitz, ME. "Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: Risk factors and response to treatment." Bone Marrow Transplantation 48.7 (2013): 926-931.
Source
scival
Published In
Bone Marrow Transplantation
Volume
48
Issue
7
Publish Date
2013
Start Page
926
End Page
931
DOI
10.1038/bmt.2012.279

Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring

Objectives: Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations. Methods: Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions. Results: After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight. Conclusion: We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations. © 2013 Macmillan Publishers Limited.

Authors
Vidal, AC; Murphy, SK; Murtha, AP; Schildkraut, JM; Soubry, A; Huang, Z; Neelon, SEB; Fuemmeler, B; Iversen, E; Wang, F; Kurtzberg, J; Jirtle, RL; Hoyo, C
MLA Citation
Vidal, AC, Murphy, SK, Murtha, AP, Schildkraut, JM, Soubry, A, Huang, Z, Neelon, SEB, Fuemmeler, B, Iversen, E, Wang, F, Kurtzberg, J, Jirtle, RL, and Hoyo, C. "Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring." International Journal of Obesity 37.7 (2013): 907-913.
Source
scival
Published In
International Journal of Obesity
Volume
37
Issue
7
Publish Date
2013
Start Page
907
End Page
913
DOI
10.1038/ijo.2013.47

Rescuing the neonatal brain from hypoxic injury with autologous cord blood

Brain injury resulting from perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of acute mortality in infants and chronic neurologic disability in surviving children. Recent multicenter clinical trials demonstrated the effectiveness of hypothermia initiated within the first 6 postnatal hours to reduce the risk of death or major neurological disabilities among neonates with HIE. However, in these trials, approximately 40% of cooled infants died or survived with significant impairments. Therefore, adjunct therapies are required to improve the outcome in neonates with HIE. Cord blood (CB) is a rich source of stem cells. Administration of human CB cells in animal models of HIE has generally resulted in improved outcomes and multiple mechanisms have been suggested including anti-inflammation, release of neurotrophic factors and stimulation of endogenous neurogenesis. Investigators at Duke are conducting studies of autologous CB infusion in neonates with HIE and in children with cerebral palsy. These pilot studies indicate no added risk from the regimens used, but results of ongoing placebo-controlled trials are needed to assess efficacy. Meanwhile, further investigations are warranted to determine the best strategies, that is, timing, dosing, route of delivery, choice of stem cells and ex vivo modulations, to attain long-term benefits of CB stem cell therapy. © 2013 Macmillan Publishers Limited All rights reserved.

Authors
Liao, Y; Cotten, M; Tan, S; Kurtzberg, J; Cairo, MS
MLA Citation
Liao, Y, Cotten, M, Tan, S, Kurtzberg, J, and Cairo, MS. "Rescuing the neonatal brain from hypoxic injury with autologous cord blood." Bone Marrow Transplantation 48.7 (2013): 890-900.
Source
scival
Published In
Bone Marrow Transplantation
Volume
48
Issue
7
Publish Date
2013
Start Page
890
End Page
900
DOI
10.1038/bmt.2012.169

Effect of HLA-matching recipients to donor noninherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for hematologic malignancy.

Transplantation-related mortality (TRM) is high after HLA-mismatched umbilical cord blood (UCB) transplantation (UCBT). In utero, exposure to noninherited maternal antigen (NIMA) is recognized by the fetus, which induces T regulator cells to that haplotype. It is plausible that UCBTs in which recipients are matched to donor NIMAs may alleviate some of the excess mortality associated with this treatment. To explore this concept, we used marginal matched-pair Cox regression analysis to compare outcomes in 48 NIMA-matched UCBTs (ie, the NIMA of the donor UCB unit matched to the patient) and in 116 non-NIMA-matched UCBTs. All patients had a hematologic malignancy and received a single UCB unit. Cases and controls were matched on age, disease, disease status, transplantation-conditioning regimen, HLA match, and infused cell dose. TRM was lower after NIMA-matched UCBTs compared with NIMA-mismatched UCBTs (relative risk, 0.48; P = .05; 18% versus 32% at 5 years posttransplantation). Consequently, overall survival was higher after NIMA-matched UCBT. The 5-year probability of overall survival was 55% after NIMA-matched UCBTs versus 38% after NIMA-mismatched UCBTs (P = .04). When faced with the choice of multiple HLA-mismatched UCB units containing adequate cell doses, selecting an NIMA-matched UCB unit may improve survival after mismatched UCBT.

Authors
Rocha, V; Spellman, S; Zhang, M-J; Ruggeri, A; Purtill, D; Brady, C; Baxter-Lowe, LA; Baudoux, E; Bergamaschi, P; Chow, R; Freed, B; Koegler, G; Kurtzberg, J; Larghero, J; Lecchi, L; Nagler, A; Navarrette, C; Prasad, V; Pouthier, F; Price, T; Ratanatharathorn, V; van Rood, JJ; Horowitz, MM; Gluckman, E; Eapen, M; Eurocord-European Blood and Marrow Transplant Group and the Center for International Blood and Marrow Transplant Research,
MLA Citation
Rocha, V, Spellman, S, Zhang, M-J, Ruggeri, A, Purtill, D, Brady, C, Baxter-Lowe, LA, Baudoux, E, Bergamaschi, P, Chow, R, Freed, B, Koegler, G, Kurtzberg, J, Larghero, J, Lecchi, L, Nagler, A, Navarrette, C, Prasad, V, Pouthier, F, Price, T, Ratanatharathorn, V, van Rood, JJ, Horowitz, MM, Gluckman, E, Eapen, M, and Eurocord-European Blood and Marrow Transplant Group and the Center for International Blood and Marrow Transplant Research, . "Effect of HLA-matching recipients to donor noninherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for hematologic malignancy." Biol Blood Marrow Transplant 18.12 (December 2012): 1890-1896.
PMID
22814031
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
12
Publish Date
2012
Start Page
1890
End Page
1896
DOI
10.1016/j.bbmt.2012.07.010

Long Term Outcomes of Hematopoietic Stem Cell Transplantation in Patients with Severe Phenotype Hurler Syndrome: an International Multi-Center Study

Authors
Aldenhoven, M; Escolar, M; Wynn, R; Wraith, E; O'Meara, A; Veys, P; Mahlaoui, N; Poe, M; Orchard, P; Kurtzberg, J; Boelens, JJ
MLA Citation
Aldenhoven, M, Escolar, M, Wynn, R, Wraith, E, O'Meara, A, Veys, P, Mahlaoui, N, Poe, M, Orchard, P, Kurtzberg, J, and Boelens, JJ. "Long Term Outcomes of Hematopoietic Stem Cell Transplantation in Patients with Severe Phenotype Hurler Syndrome: an International Multi-Center Study." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Outcome of Transplantation for Acute Leukemia in Down Syndrome

Authors
Hitzler, JK; He, W; Doyle, JJ; Bitan, M; Cairo, MS; Camitta, B; Chan, KW; Angel Diaz, M; Fraser, C; Gross, T; Horan, JT; Kasow, KA; Kennedy-Nasser, A; Kitko, C; Kurtzberg, J; Lehmann, LE; Mitchell, D; O'Brien, T; Pulsipher, MA; Smith, FO; Yu, LC; Zhang, M-J; Eapen, M; Carpenter, PA
MLA Citation
Hitzler, JK, He, W, Doyle, JJ, Bitan, M, Cairo, MS, Camitta, B, Chan, KW, Angel Diaz, M, Fraser, C, Gross, T, Horan, JT, Kasow, KA, Kennedy-Nasser, A, Kitko, C, Kurtzberg, J, Lehmann, LE, Mitchell, D, O'Brien, T, Pulsipher, MA, Smith, FO, Yu, LC, Zhang, M-J, Eapen, M, and Carpenter, PA. "Outcome of Transplantation for Acute Leukemia in Down Syndrome." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

No Survival Advantage After Double Umbilical Cord Blood (UCB) Compared to Single UCB Transplant in Children with Hematological Malignancy: Results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0501) Randomized Trial

Authors
Wagner, JE; Eapen, M; Carter, SL; Haut, PR; Peres, E; Schultz, KR; Thompson, J; Wall, DA; Kurtzberg, J
MLA Citation
Wagner, JE, Eapen, M, Carter, SL, Haut, PR, Peres, E, Schultz, KR, Thompson, J, Wall, DA, and Kurtzberg, J. "No Survival Advantage After Double Umbilical Cord Blood (UCB) Compared to Single UCB Transplant in Children with Hematological Malignancy: Results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0501) Randomized Trial." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

No Survival Advantage After Double Umbilical Cord Blood (UCB) Compared to Single UCB Transplant in Children with Hematological Malignancy: Results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0501) Randomized Trial

Authors
Wagner, JE; Eapen, M; Carter, SL; Haut, PR; Peres, E; Schultz, KR; Thompson, J; Wall, DA; Kurtzberg, J
MLA Citation
Wagner, JE, Eapen, M, Carter, SL, Haut, PR, Peres, E, Schultz, KR, Thompson, J, Wall, DA, and Kurtzberg, J. "No Survival Advantage After Double Umbilical Cord Blood (UCB) Compared to Single UCB Transplant in Children with Hematological Malignancy: Results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0501) Randomized Trial." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

ADOPTIVE CELLULAR THERAPY TARGETING RECURRENT MEDULLOBLASTOMA AND PRIMITIVE NEUROECTODERMAL TUMORS AFTER MYELOABLATIVE AND NON-MYELOABLATIVE CONDITIONING

Authors
Mitchell, DA; Gururangan, SG; Grant, G; Driscoll, T; Archer, G; King, J; Boczkowski, D; Xie, W; Nair, S; Perry, B; Fuchs, H; Kurtzberg, J; Friedman, H; Bigner, D; Sampson, J
MLA Citation
Mitchell, DA, Gururangan, SG, Grant, G, Driscoll, T, Archer, G, King, J, Boczkowski, D, Xie, W, Nair, S, Perry, B, Fuchs, H, Kurtzberg, J, Friedman, H, Bigner, D, and Sampson, J. "ADOPTIVE CELLULAR THERAPY TARGETING RECURRENT MEDULLOBLASTOMA AND PRIMITIVE NEUROECTODERMAL TUMORS AFTER MYELOABLATIVE AND NON-MYELOABLATIVE CONDITIONING." October 2012.
Source
wos-lite
Published In
Neuro-Oncology
Volume
14
Publish Date
2012
Start Page
49
End Page
49

Myeloablative transplantation using either cord blood or bone marrow leads to immune recovery, high long-term donor chimerism and excellent survival in chronic granulomatous disease.

The curative potential of hematopoietic stem cell transplantation in patients with chronic granulomatous disease depends on availability of a suitable donor, successful donor engraftment, and maintenance of long-term donor chimerism. Twelve consecutive children (median age, 59.5 months; range, 8-140 months) with severe chronic granulomatous disease (serious bacterial/fungal infections pretransplantation; median, 3; range, 2-9) received myeloablative hematopoietic stem cell transplantation using sibling bone marrow ([SibBM]; n = 5), unrelated cord blood (UCB; n = 6), and sibling cord blood (n = 1) at our center between 1997 and 2010. SibBM and sibling cord blood were HLA matched at 6/6, whereas UCB were 5/6 (n = 5) or 6/6 (n = 1). Recipients of SibBM were conditioned with busulfan and cyclophosphamide ± anti-thymocyte globulin (ATG), whereas 6 of 7 cord blood recipients received fludarabine/busulfan/cyclophosphamide/ATG. Seven patients received granulocyte-colony stimulating factor-mobilized granulocyte transfusions from directed donors. The first 2 UCB recipients had primary graft failure but successfully underwent retransplantation with UCB. Highest acute graft-versus-host disease was grade III (n = 1). Extensive chronic graft-vs-host disease developed in 3 patients. All patients are alive with median follow-up of 70.5 months (range, 12-167 months) with high donor chimerism (>98%, n = 10; 94%, n = 1; and 92%, n = 1). Myeloablative hematopoietic stem cell transplantation led to correction of neutrophil dysfunction, durable donor chimerism, excellent survival, good quality of life, and low incidence of graft-vs-host disease regardless of graft source.

Authors
Tewari, P; Martin, PL; Mendizabal, A; Parikh, SH; Page, KM; Driscoll, TA; Malech, HL; Kurtzberg, J; Prasad, VK
MLA Citation
Tewari, P, Martin, PL, Mendizabal, A, Parikh, SH, Page, KM, Driscoll, TA, Malech, HL, Kurtzberg, J, and Prasad, VK. "Myeloablative transplantation using either cord blood or bone marrow leads to immune recovery, high long-term donor chimerism and excellent survival in chronic granulomatous disease." Biol Blood Marrow Transplant 18.9 (September 2012): 1368-1377.
PMID
22326631
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
9
Publish Date
2012
Start Page
1368
End Page
1377
DOI
10.1016/j.bbmt.2012.02.002

Long-term survival and late deaths after hematopoietic cell transplantation for primary immunodeficiency diseases and inborn errors of metabolism.

It is uncertain whether late mortality rates after hematopoietic cell transplantation for severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency diseases (non-SCID PIDD), and inborn errors of metabolism (IEM) return to rates observed in the general population, matched for age, sex, and nationality. We studied patients with SCID (n = 201), non-SCID PIDD (n = 405), and IEM (n = 348) who survived for at least 2 years after transplantation with normal T cell function (SCID) or >95% donor chimerism (non-SCID PIDD and IEM). Importantly, mortality rate was significantly higher in these patients compared with the general population for several years after transplantation. The rate decreased toward the normal rate in patients with SCID and non-SCID PIDD beyond 6 years after transplantation, but not in patients with IEM. Active chronic graft-versus-host disease at 2 years was associated with increased risk of late mortality for all diseases (hazard ratio [HR], 1.87; P = .05). In addition, late mortality was higher in patients with non-SCID PIDD who received T cell-depleted grafts (HR 4.16; P = .007) and in patients with IEM who received unrelated donor grafts (HR, 2.72; P = .03) or mismatched related donor grafts (HR, 3.76; P = .01). The finding of higher mortality rates in these long-term survivors for many years after transplantation confirms the need for long-term surveillance.

Authors
Eapen, M; Ahn, KW; Orchard, PJ; Cowan, MJ; Davies, SM; Fasth, A; Hassebroek, A; Ayas, M; Bonfim, C; O'Brien, TA; Gross, TG; Horwitz, M; Horwitz, E; Kapoor, N; Kurtzberg, J; Majhail, N; Ringden, O; Szabolcs, P; Veys, P; Baker, KS
MLA Citation
Eapen, M, Ahn, KW, Orchard, PJ, Cowan, MJ, Davies, SM, Fasth, A, Hassebroek, A, Ayas, M, Bonfim, C, O'Brien, TA, Gross, TG, Horwitz, M, Horwitz, E, Kapoor, N, Kurtzberg, J, Majhail, N, Ringden, O, Szabolcs, P, Veys, P, and Baker, KS. "Long-term survival and late deaths after hematopoietic cell transplantation for primary immunodeficiency diseases and inborn errors of metabolism." Biol Blood Marrow Transplant 18.9 (September 2012): 1438-1445.
PMID
22430083
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
9
Publish Date
2012
Start Page
1438
End Page
1445
DOI
10.1016/j.bbmt.2012.03.003

Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children.

OBJECTIVE: To determine whether aberrant DNA methylation at differentially methylated regions (DMRs) regulating insulin-like growth factor 2 (IGF2) expression in umbilical cord blood is associated with overweight or obesity in a multiethnic cohort. STUDY DESIGN: Umbilical cord blood leukocytes of 204 infants born between 2005 and 2009 in Durham, North Carolina, were analyzed for DNA methylation at two IGF2 DMRs by using pyrosequencing. Anthropometric and feeding data were collected at age 1 year. Methylation differences were compared between children >85th percentile of the Centers for Disease Control and Prevention growth charts weight-for-age (WFA) and children ≤ 85th percentile of WFA at 1 year by using generalized linear models, adjusting for post-natal caloric intake, maternal cigarette smoking, and race/ethnicity. RESULTS: The methylation percentages at the H19 imprint center DMR was higher in infants with WFA >85th percentile (62.7%; 95% CI, 59.9%-65.5%) than in infants with WFA ≤ 85th percentile (59.3%; 95% CI, 58.2%-60.3%; P = .02). At the intragenic IGF2 DMR, methylation levels were comparable between infants with WFA ≤ 85th percentile and infants with WFA >85th percentile. CONCLUSIONS: Our findings suggest that IGF2 plasticity may be mechanistically important in early childhood overweight or obese status. If confirmed in larger studies, these findings suggest aberrant DNA methylation at sequences regulating imprinted genes may be useful identifiers of children at risk for the development of early obesity.

Authors
Perkins, E; Murphy, SK; Murtha, AP; Schildkraut, J; Jirtle, RL; Demark-Wahnefried, W; Forman, MR; Kurtzberg, J; Overcash, F; Huang, Z; Hoyo, C
MLA Citation
Perkins, E, Murphy, SK, Murtha, AP, Schildkraut, J, Jirtle, RL, Demark-Wahnefried, W, Forman, MR, Kurtzberg, J, Overcash, F, Huang, Z, and Hoyo, C. "Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children." J Pediatr 161.1 (July 2012): 31-39.
PMID
22341586
Source
pubmed
Published In
The Journal of Pediatrics
Volume
161
Issue
1
Publish Date
2012
Start Page
31
End Page
39
DOI
10.1016/j.jpeds.2012.01.015

Depression in pregnancy, infant birth weight and DNA methylation of imprint regulatory elements.

Depressed mood in pregnancy has been linked to low birth weight (LBW, < 2,500 g), a risk factor for adult-onset chronic diseases in offspring. We examined maternal depressed mood in relation to birth weight and evaluated the role of DNA methylation at regulatory sequences of imprinted genes in this association. We measured depressed mood among 922 pregnant women using the CES-D scale and obtained birth weight data from hospital records. Using bisulfite pyrosequencing of cord blood DNA from 508 infants, we measured methylation at differentially methylated regions (DMRs) regulating imprinted genes IGF2/H19, DLK1/MEG3, MEST, PEG3, PEG10/SGCE, NNAT and PLAGL1. Multiple regression models were used to examine the relationship between depressed mood, birth weight and DMR methylation levels. Depressed mood was associated with a more that 3-fold higher risk of LBW, after adjusting for delivery mode, parity, education, cigarette smoking, folic acid use and preterm birth. The association may be more pronounced in offspring of black women and female infants. Compared with infants of women without depressed mood, infants born to women with severe depressed mood had a 2.4% higher methylation at the MEG3 DMR. Whereas LBW infants had 1.6% lower methylation at the IGF2 DMR, high birth weight (> 4,500 g) infants had 5.9% higher methylation at the PLAGL1 DMR compared with normal birth weight infants. Our findings confirm that severe maternal depressed mood in pregnancy is associated with LBW, and that MEG3 and IGF2 plasticity may play important roles.

Authors
Liu, Y; Murphy, SK; Murtha, AP; Fuemmeler, BF; Schildkraut, J; Huang, Z; Overcash, F; Kurtzberg, J; Jirtle, R; Iversen, ES; Forman, MR; Hoyo, C
MLA Citation
Liu, Y, Murphy, SK, Murtha, AP, Fuemmeler, BF, Schildkraut, J, Huang, Z, Overcash, F, Kurtzberg, J, Jirtle, R, Iversen, ES, Forman, MR, and Hoyo, C. "Depression in pregnancy, infant birth weight and DNA methylation of imprint regulatory elements." Epigenetics 7.7 (July 2012): 735-746.
PMID
22677950
Source
pubmed
Published In
Epigenetics : official journal of the DNA Methylation Society
Volume
7
Issue
7
Publish Date
2012
Start Page
735
End Page
746
DOI
10.4161/epi.20734

THE NEW BD STEM CELL ENUMERATION METHOD BY FLOW CYTOMETRY SHOWS CONCORDANT RESULTS ACROSS FOUR STUDY SITES

Authors
Omana-Zapata, I; Segurado, O; Kurtzberg, J; Dornsife, R; Preti, R; Chan, W-S; Wallace, PK; Furlage, R; Tonn, T; Bonig, H
MLA Citation
Omana-Zapata, I, Segurado, O, Kurtzberg, J, Dornsife, R, Preti, R, Chan, W-S, Wallace, PK, Furlage, R, Tonn, T, and Bonig, H. "THE NEW BD STEM CELL ENUMERATION METHOD BY FLOW CYTOMETRY SHOWS CONCORDANT RESULTS ACROSS FOUR STUDY SITES." INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY 34 (June 2012): 55-55.
Source
wos-lite
Published In
International Journal of Laboratory Hematology
Volume
34
Publish Date
2012
Start Page
55
End Page
55

Relationship of race/ethnicity and survival after single umbilical cord blood transplantation for adults and children with leukemia and myelodysplastic syndromes.

The relationship of race/ethnicity with outcomes of umbilical cord blood transplantation (UCBT) is not well known. We analyzed the association between race/ethnicity and outcomes of unrelated single UCBT for leukemia and myelodysplastic syndromes. Our retrospective cohort study consisted of 885 adults and children (612 whites, 145 blacks, and 128 Hispanics) who received unrelated single UCBT for leukemia and myelodysplastic syndromes between 1995 and 2006 and were reported to the Center for International Blood and Marrow Transplant Research. A 5-6/6 HLA-matched unit with a total nucleated cell count infused of ≥2.5 × 10(7)/kg was given to 40% white and 42% Hispanic, but only 21% black patients. Overall survival at 2 years was 44% for whites, 34% for blacks, and 46% for Hispanics (P = .008). In multivariate analysis adjusting for patient, disease, and treatment factors (including HLA match and cell dose), blacks had inferior overall survival (relative risk of death, 1.31; P = .02), whereas overall survival of Hispanics was similar (relative risk, 1.03; P = .81) to that of whites. For all patients, younger age, early-stage disease, use of units with higher cell dose, and performance status ≥80 were independent predictors of improved survival. Black patients and white patients infused with well-matched cords had comparable survival; similarly, black and white patients receiving units with adequate cell dose had similar survival. These results suggest that blacks have inferior survival to whites after single UCBT, but outcomes are improved when units with a higher cell dose are used.

Authors
Ballen, KK; Klein, JP; Pedersen, TL; Bhatla, D; Duerst, R; Kurtzberg, J; Lazarus, HM; LeMaistre, CF; McCarthy, P; Mehta, P; Palmer, J; Setterholm, M; Wingard, JR; Joffe, S; Parsons, SK; Switzer, GE; Lee, SJ; Rizzo, JD; Majhail, NS
MLA Citation
Ballen, KK, Klein, JP, Pedersen, TL, Bhatla, D, Duerst, R, Kurtzberg, J, Lazarus, HM, LeMaistre, CF, McCarthy, P, Mehta, P, Palmer, J, Setterholm, M, Wingard, JR, Joffe, S, Parsons, SK, Switzer, GE, Lee, SJ, Rizzo, JD, and Majhail, NS. "Relationship of race/ethnicity and survival after single umbilical cord blood transplantation for adults and children with leukemia and myelodysplastic syndromes." Biol Blood Marrow Transplant 18.6 (June 2012): 903-912.
PMID
22062801
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
6
Publish Date
2012
Start Page
903
End Page
912
DOI
10.1016/j.bbmt.2011.10.040

Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections in immunocompromised patients.

No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥ 4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥ 1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.

Authors
Florescu, DF; Pergam, SA; Neely, MN; Qiu, F; Johnston, C; Way, S; Sande, J; Lewinsohn, DA; Guzman-Cottrill, JA; Graham, ML; Papanicolaou, G; Kurtzberg, J; Rigdon, J; Painter, W; Mommeja-Marin, H; Lanier, R; Anderson, M; van der Horst, C
MLA Citation
Florescu, DF, Pergam, SA, Neely, MN, Qiu, F, Johnston, C, Way, S, Sande, J, Lewinsohn, DA, Guzman-Cottrill, JA, Graham, ML, Papanicolaou, G, Kurtzberg, J, Rigdon, J, Painter, W, Mommeja-Marin, H, Lanier, R, Anderson, M, and van der Horst, C. "Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections in immunocompromised patients." Biol Blood Marrow Transplant 18.5 (May 2012): 731-738.
PMID
21963623
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
5
Publish Date
2012
Start Page
731
End Page
738
DOI
10.1016/j.bbmt.2011.09.007

Novel stem cell enumeration method by flow cytometry shows concordant results across four study sites

Authors
Kurtzberg, J; Dornsife, R; Preti, R; Chan, W-S; Wallace, PK; Furlage, R; Tonn, T; Boenig, H; Omana-Zapata, I; Segurado, O
MLA Citation
Kurtzberg, J, Dornsife, R, Preti, R, Chan, W-S, Wallace, PK, Furlage, R, Tonn, T, Boenig, H, Omana-Zapata, I, and Segurado, O. "Novel stem cell enumeration method by flow cytometry shows concordant results across four study sites." April 2012.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
47
Publish Date
2012
Start Page
S284
End Page
S285

Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight.

PURPOSE: Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns. METHODS: Questionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels. RESULTS: Lower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (β = -9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m(2), β = -20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR. CONCLUSION: Our data suggest that variation in IGF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.

Authors
Hoyo, C; Fortner, K; Murtha, AP; Schildkraut, JM; Soubry, A; Demark-Wahnefried, W; Jirtle, RL; Kurtzberg, J; Forman, MR; Overcash, F; Huang, Z; Murphy, SK
MLA Citation
Hoyo, C, Fortner, K, Murtha, AP, Schildkraut, JM, Soubry, A, Demark-Wahnefried, W, Jirtle, RL, Kurtzberg, J, Forman, MR, Overcash, F, Huang, Z, and Murphy, SK. "Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight." Cancer Causes Control 23.4 (April 2012): 635-645.
PMID
22392079
Source
pubmed
Published In
Cancer Causes & Control
Volume
23
Issue
4
Publish Date
2012
Start Page
635
End Page
645
DOI
10.1007/s10552-012-9932-y

NiCord (R) expanded haematopoietic progenitor cells are capable of prolonged myeloid and lymphoid engraftment following myeloablative dual umbilical cord blood transplantation

Authors
Horwitz, M; Chao, J; Rizzieri, A; Long, D; Sullivan, M; Gasparetto, C; Chute, P; Morris, A; McDonald, C; Snyder, D; Galamidi, E; Srur-Kidron, O; Shoham, H; Landau, E; Friend, E; Kurtzberg, J; Peled, T
MLA Citation
Horwitz, M, Chao, J, Rizzieri, A, Long, D, Sullivan, M, Gasparetto, C, Chute, P, Morris, A, McDonald, C, Snyder, D, Galamidi, E, Srur-Kidron, O, Shoham, H, Landau, E, Friend, E, Kurtzberg, J, and Peled, T. "NiCord (R) expanded haematopoietic progenitor cells are capable of prolonged myeloid and lymphoid engraftment following myeloablative dual umbilical cord blood transplantation." April 2012.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
47
Publish Date
2012
Start Page
S57
End Page
S58

Allogeneic hematopoietic SCT for alpha-mannosidosis: an analysis of 17 patients.

Alpha-mannosidosis is a rare lysosomal storage disease. Hematopoietic SCT (HSCT) is usually recommended as a therapeutic option though reports are anecdotal to date. This retrospective multi institutional analysis describes 17 patients that were diagnosed at a median of 2.5 (1.1-23) years and underwent HSCT at a median of 3.6 (1.3-23.1) years. In all, 15 patients are alive (88%) after a median follow-up of 5.5 (2.1-12.6) years. Two patients died within the first 5 months after HSCT. Of the survivors, two developed severe acute GvHD (>=grade II) and six developed chronic GvHD. Three patients required re-transplantation because of graft failure. All 15 showed stable engraftment. The extent of the patients' developmental delay before HSCT varied over a wide range. After HSCT, patients made developmental progress, although normal development was not achieved. Hearing ability improved in some, but not in all patients. We conclude that HSCT is a feasible therapeutic option that may promote mental development in alpha-mannosidosis.

Authors
Mynarek, M; Tolar, J; Albert, MH; Escolar, ML; Boelens, JJ; Cowan, MJ; Finnegan, N; Glomstein, A; Jacobsohn, DA; Kühl, JS; Yabe, H; Kurtzberg, J; Malm, D; Orchard, PJ; Klein, C; Lücke, T; Sykora, K-W
MLA Citation
Mynarek, M, Tolar, J, Albert, MH, Escolar, ML, Boelens, JJ, Cowan, MJ, Finnegan, N, Glomstein, A, Jacobsohn, DA, Kühl, JS, Yabe, H, Kurtzberg, J, Malm, D, Orchard, PJ, Klein, C, Lücke, T, and Sykora, K-W. "Allogeneic hematopoietic SCT for alpha-mannosidosis: an analysis of 17 patients." Bone Marrow Transplant 47.3 (March 2012): 352-359.
PMID
21552297
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
47
Issue
3
Publish Date
2012
Start Page
352
End Page
359
DOI
10.1038/bmt.2011.99

National Cancer Institute, National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplantation Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: the need for pediatric-specific long-term follow-up guidelines.

Existing standards for screening and management of late effects occurring in children who have undergone hematopoietic cell transplantation (HCT) include recommendations from pediatric cancer networks and consensus guidelines from adult-oriented transplantation societies applicable to all HCT recipients. Although these approaches have significant merit, they are not pediatric HCT-focused, and they do not address post-HCT challenges faced by children with complex nonmalignant disorders. In this article we discuss the strengths and weaknesses of current published recommendations and conclude that pediatric-specific guidelines for post-HCT screening and management would be beneficial to the long-term health of these patients and would promote late effects research in this field. Our panel of late effects experts also provides recommendations for follow-up and therapy of selected post-HCT organ and endocrine complications in pediatric patients.

Authors
Pulsipher, MA; Skinner, R; McDonald, GB; Hingorani, S; Armenian, SH; Cooke, KR; Gracia, C; Petryk, A; Bhatia, S; Bunin, N; Nieder, ML; Dvorak, CC; Sung, L; Sanders, JE; Kurtzberg, J; Baker, KS
MLA Citation
Pulsipher, MA, Skinner, R, McDonald, GB, Hingorani, S, Armenian, SH, Cooke, KR, Gracia, C, Petryk, A, Bhatia, S, Bunin, N, Nieder, ML, Dvorak, CC, Sung, L, Sanders, JE, Kurtzberg, J, and Baker, KS. "National Cancer Institute, National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplantation Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: the need for pediatric-specific long-term follow-up guidelines." Biol Blood Marrow Transplant 18.3 (March 2012): 334-347.
PMID
22248713
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
3
Publish Date
2012
Start Page
334
End Page
347
DOI
10.1016/j.bbmt.2012.01.003

INCIDENCE OF ADRENAL INSUFFICIENCY IN CHILDREN WITH SANFILIPPO SYNDROME TYPE A FOLLOWING UUCB TRANSPLANT - A RETROSPECTIVE STUDY

Authors
Moffet, J; Parikh, S; Driscoll, T; Szabolcs, P; Kurtzberg, J
MLA Citation
Moffet, J, Parikh, S, Driscoll, T, Szabolcs, P, and Kurtzberg, J. "INCIDENCE OF ADRENAL INSUFFICIENCY IN CHILDREN WITH SANFILIPPO SYNDROME TYPE A FOLLOWING UUCB TRANSPLANT - A RETROSPECTIVE STUDY." February 2012.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
2
Publish Date
2012
Start Page
S396
End Page
S396

QUALIFICATION OF CORD BLOOD UNITS FOR AN AUTOLOGOUS INFUSION PROGRAM FOR PEDIATRIC PATIENTS WITH ACQUIRED BRAIN INJURIES

Authors
Allison-Thacker, J; Fitzgerald, A; Sun, J; McLaughlin, C; Waters-Pick, B; Vinesett, R; Kurtzberg, J
MLA Citation
Allison-Thacker, J, Fitzgerald, A, Sun, J, McLaughlin, C, Waters-Pick, B, Vinesett, R, and Kurtzberg, J. "QUALIFICATION OF CORD BLOOD UNITS FOR AN AUTOLOGOUS INFUSION PROGRAM FOR PEDIATRIC PATIENTS WITH ACQUIRED BRAIN INJURIES." February 2012.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
2
Publish Date
2012
Start Page
S251
End Page
S252

BUILDING A LEGACY

Authors
Bain, ME; Kurtzberg, J; Cash, J; Martin, PM
MLA Citation
Bain, ME, Kurtzberg, J, Cash, J, and Martin, PM. "BUILDING A LEGACY." February 2012.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
2
Publish Date
2012
Start Page
S322
End Page
S322

NURSING COORDINATION OF A LIFE-SAVING CADAVERIC TANDEM LUNG AND BONE MARROW TRANSPLANT IN A PEDIATRIC PATIENT WITH CONGENITAL IMMUNODEFICIENCY AND PULMONARY FAILURE

Authors
Cash, J; Rich, L; Moffet, J; Ciocci, G; Zaas, D; Kurtzberg, J; Szabolcs, P
MLA Citation
Cash, J, Rich, L, Moffet, J, Ciocci, G, Zaas, D, Kurtzberg, J, and Szabolcs, P. "NURSING COORDINATION OF A LIFE-SAVING CADAVERIC TANDEM LUNG AND BONE MARROW TRANSPLANT IN A PEDIATRIC PATIENT WITH CONGENITAL IMMUNODEFICIENCY AND PULMONARY FAILURE." February 2012.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
2
Publish Date
2012
Start Page
S394
End Page
S394

RELATIONSHIPS AMONG COMMONLY USED MEASURES OF CORD BLOOD POTENCY, ALDHBR CELL CONTENT, AND COLONY FORMING CELL CONTENT IN CORD BLOOD UNITS PRIOR TO CRYOPRESERVATION: TOWARDS AN IMPROVED METRIC FOR POTENCY OF BANKED CORD BLOOD

Authors
Page, K; Betz-Stablein, B; Mendizabal, A; Wease, S; Shoulars, K; Gentry, T; Balber, AE; Kurtzberg, J
MLA Citation
Page, K, Betz-Stablein, B, Mendizabal, A, Wease, S, Shoulars, K, Gentry, T, Balber, AE, and Kurtzberg, J. "RELATIONSHIPS AMONG COMMONLY USED MEASURES OF CORD BLOOD POTENCY, ALDHBR CELL CONTENT, AND COLONY FORMING CELL CONTENT IN CORD BLOOD UNITS PRIOR TO CRYOPRESERVATION: TOWARDS AN IMPROVED METRIC FOR POTENCY OF BANKED CORD BLOOD." February 2012.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
2
Publish Date
2012
Start Page
S261
End Page
S262

The Cord Blood Apgar: a novel scoring system to optimize selection of banked cord blood grafts for transplantation (CME).

BACKGROUND: Engraftment failure and delays, likely due to diminished cord blood unit (CBU) potency, remain major barriers to the overall success of unrelated umbilical cord blood transplantation (UCBT). To address this problem, we developed and retrospectively validated a novel scoring system, the Cord Blood Apgar (CBA), which is predictive of engraftment after UCBT. STUDY DESIGN AND METHODS: In a single-center retrospective study, utilizing a database of 435 consecutive single cord myeloablative UCBTs performed between January 1, 2000, to December 31, 2008, precryopreservation and postthaw graft variables (total nucleated cell, CD34+, colony-forming units, mononuclear cell content, and volume) were initially correlated with neutrophil engraftment. Subsequently, based on the magnitude of hazard ratios (HRs) in univariate analysis, a weighted scoring system to predict CBU potency was developed using a randomly selected training data set and internally validated on the remaining data set. RESULTS: The CBA assigns transplanted CBUs three scores: a precryopreservation score (PCS), a postthaw score (PTS), and a composite score (CS), which incorporates the PCS and PTS values. CBA-PCS scores, which could be used for initial unit selection, were predictive of neutrophil (CBA-PCS ≥ 7.75 vs. <7.75, HR 3.5; p < 0.0001) engraftment. Likewise, CBA-PTS and CS scores were strongly predictive of Day 42 neutrophil engraftment (CBA-PTS ≥ 9.5 vs. <9.5, HR 3.16, p < 0.0001; CBA-CS ≥ 17.75 vs. <17.75, HR 4.01, p < 0.0001). CONCLUSION: The CBA is strongly predictive of engraftment after UCBT and shows promise for optimizing screening of CBU donors for transplantation. In the future, a segment could be assayed for the PTS score providing data to apply the CS for final CBU selection.

Authors
Page, KM; Zhang, L; Mendizabal, A; Wease, S; Carter, S; Shoulars, K; Gentry, T; Balber, AE; Kurtzberg, J
MLA Citation
Page, KM, Zhang, L, Mendizabal, A, Wease, S, Carter, S, Shoulars, K, Gentry, T, Balber, AE, and Kurtzberg, J. "The Cord Blood Apgar: a novel scoring system to optimize selection of banked cord blood grafts for transplantation (CME)." Transfusion 52.2 (February 2012): 272-283.
PMID
21810098
Source
pubmed
Published In
Transfusion
Volume
52
Issue
2
Publish Date
2012
Start Page
272
End Page
283
DOI
10.1111/j.1537-2995.2011.03278.x

UNRELATED CORD BLOOD TRANSPLANTATION (CBT) OF 101 HEMOGLOBINOPATHY (HGB) PATIENTS

Authors
Chow, RY; Jaing, T-H; Chan, LL; Tan, P; Lin, H-P; Graham, M; Rosenthal, J; Karanes, C; Nademanee, A; Wang, BC; Yen, L; Chow, MR; Dang, T; Kurtzberg, J; Petz, LD
MLA Citation
Chow, RY, Jaing, T-H, Chan, LL, Tan, P, Lin, H-P, Graham, M, Rosenthal, J, Karanes, C, Nademanee, A, Wang, BC, Yen, L, Chow, MR, Dang, T, Kurtzberg, J, and Petz, LD. "UNRELATED CORD BLOOD TRANSPLANTATION (CBT) OF 101 HEMOGLOBINOPATHY (HGB) PATIENTS." February 2012.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
2
Publish Date
2012
Start Page
S268
End Page
S268

CORD BLOOD TRANSPLANTATION FOR LONG TERM MANAGEMENT OR POSSIBLE CURE OF HIV INFECTION

Authors
Petz, L; Tonai, R; Redei, I; Li, S; Li, H; Bryson, Y; Regan, D; Spellman, S; Gragert, L; Boo, M; Gutman, J; Armitage, S; Shpall, E; Lin, A; Rosenthal, J; Zaia, J; Rossi, J; Kurtzberg, J; Forman, S; Chow, R
MLA Citation
Petz, L, Tonai, R, Redei, I, Li, S, Li, H, Bryson, Y, Regan, D, Spellman, S, Gragert, L, Boo, M, Gutman, J, Armitage, S, Shpall, E, Lin, A, Rosenthal, J, Zaia, J, Rossi, J, Kurtzberg, J, Forman, S, and Chow, R. "CORD BLOOD TRANSPLANTATION FOR LONG TERM MANAGEMENT OR POSSIBLE CURE OF HIV INFECTION." February 2012.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
2
Publish Date
2012
Start Page
S215
End Page
S216

USE OF CYCLOSPORINE IS ASSOCIATED WITH THE INCREASE IN PRE-ENGRAFTMENT SYNDROME AFTER MYELOABLATIVE DUAL CORD BLOOD TRANSPLANTATION

Authors
Kanda, J; Kaynar, L; Kanda, Y; Prasad, VK; Parikh, SH; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; Winkel, S; McPherson, J; Kurtzberg, J; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Kaynar, L, Kanda, Y, Prasad, VK, Parikh, SH, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, Winkel, S, McPherson, J, Kurtzberg, J, Chao, NJ, and Horwitz, ME. "USE OF CYCLOSPORINE IS ASSOCIATED WITH THE INCREASE IN PRE-ENGRAFTMENT SYNDROME AFTER MYELOABLATIVE DUAL CORD BLOOD TRANSPLANTATION." February 2012.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
2
Publish Date
2012
Start Page
S332
End Page
S332

NiCORD (R) EXPANDED HEMATOPOIETIC PROGENITOR CELLS (HPC) ARE CAPABLE OF PROLONGED MYELOID AND LYMPHOID ENGRAFTMENT FOLLOWING MYELOABLATIVE DUAL UMBILICAL CORD BLOOD (UCB) TRANSPLANTATION

Authors
Horwitz, M; Chao, N; Rizzieri, D; Long, G; Sullivan, K; Gasparetto, C; Chute, J; Morris, A; McDonald, C; Snyder, D; Galamidi, E; Srur-Kidron, O; Shoham, H; Landau, E; Friend, E; Kurtzberg, J; Peled, T
MLA Citation
Horwitz, M, Chao, N, Rizzieri, D, Long, G, Sullivan, K, Gasparetto, C, Chute, J, Morris, A, McDonald, C, Snyder, D, Galamidi, E, Srur-Kidron, O, Shoham, H, Landau, E, Friend, E, Kurtzberg, J, and Peled, T. "NiCORD (R) EXPANDED HEMATOPOIETIC PROGENITOR CELLS (HPC) ARE CAPABLE OF PROLONGED MYELOID AND LYMPHOID ENGRAFTMENT FOLLOWING MYELOABLATIVE DUAL UMBILICAL CORD BLOOD (UCB) TRANSPLANTATION." February 2012.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
2
Publish Date
2012
Start Page
S326
End Page
S326

GENETIC DIVERSITY WITHIN THE US POPULATION: 67% OF HAPLOTYPES IDENTIFIED BY SEGREGATION ARE SINGLETONS.

Authors
Tu, B; Leahy, N; Yang, R; Cha, N; Kariyawasam, K; Tvrdy, E; Pulse-Earle, D; Maiers, M; Ng, J; Kurtzberg, J; Hurley, CK
MLA Citation
Tu, B, Leahy, N, Yang, R, Cha, N, Kariyawasam, K, Tvrdy, E, Pulse-Earle, D, Maiers, M, Ng, J, Kurtzberg, J, and Hurley, CK. "GENETIC DIVERSITY WITHIN THE US POPULATION: 67% OF HAPLOTYPES IDENTIFIED BY SEGREGATION ARE SINGLETONS." 2012.
Source
wos-lite
Published In
Human Immunology
Volume
73
Publish Date
2012
Start Page
115
End Page
115

Polyethylene Glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children's Oncology Group Study (POG 8866).

BACKGROUND: Administration of L-asparaginase is limited by hypersensitivity reactions mediated by anti-asparaginase antibodies. To overcome this problem, native Escherichia coli L-asparaginase was conjugated to polyethylene glycol (PEG) to formulate PEG-L-asparaginase, a preparation with decreased immunogenicity and increased circulating half-life. In early trials, PEG-L-asparaginase was tolerated by patients known to be hypersensitive to the native E. coli product. METHODS: The Pediatric Oncology Group conducted a phase II, randomized trial to compare the efficacy and toxicity of PEG-L-asparaginase compared with native E. coli asparaginase in children with acute lymphoblastic leukemia in second bone marrow relapse. All patients (n=76) received standard doses of vincristine and prednisone. Nonhypersensitive patients (n=34) were randomized to receive either PEG-L-asparaginase of 2500 IU/m/dose intramuscularly on days 1 and 15 (treatment I) or native E. coli asparaginase of 10,000 IU/m/dose intramuscularly on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 (treatment II). Patients with a clinical history of an allergic reaction to unmodified asparaginase were directly assigned to treatment with PEG-L-asparaginase (n=42). Asparaginase levels and anti-asparaginase antibody titers were monitored in all patients. Response and toxicity were scored using conventional criteria. RESULTS: The complete response rate for the total study population was 41%. There was no difference in complete response between patients randomized to PEG (47%) and native asparaginase (41%). PEG was well tolerated even in patients with prior allergic reactions to native asparaginase. PEG half-life was shorter in patients with prior allergy. CONCLUSIONS: PEG asparaginase is a useful agent in patients with allergic reactions to native asparaginase.

Authors
Kurtzberg, J; Asselin, B; Bernstein, M; Buchanan, GR; Pollock, BH; Camitta, BM
MLA Citation
Kurtzberg, J, Asselin, B, Bernstein, M, Buchanan, GR, Pollock, BH, and Camitta, BM. "Polyethylene Glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children's Oncology Group Study (POG 8866)." J Pediatr Hematol Oncol 33.8 (December 2011): 610-616.
PMID
22042277
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
33
Issue
8
Publish Date
2011
Start Page
610
End Page
616
DOI
10.1097/MPH.0b013e31822d4d4e

Relationships Among Commonly Used Measures of Cord Blood Potency, ALDH(br) Cell Content, and Colony Forming Cell Content in Cord Blood Units Prior to Cryopreservation: Towards An Improved Metric for Potency of Banked Cord Blood

Authors
Page, KM; Betz-Stablein, B; Mendizabal, AM; Wease, S; Gentry, T; Shoulars, K; Balber, AE; Kurtzberg, J
MLA Citation
Page, KM, Betz-Stablein, B, Mendizabal, AM, Wease, S, Gentry, T, Shoulars, K, Balber, AE, and Kurtzberg, J. "Relationships Among Commonly Used Measures of Cord Blood Potency, ALDH(br) Cell Content, and Colony Forming Cell Content in Cord Blood Units Prior to Cryopreservation: Towards An Improved Metric for Potency of Banked Cord Blood." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1731
End Page
1732

What Clinical Characteristics of Mothers and Babies Favorably Influence Cord Blood Potency? Defining Parameters That Can Guide Public Cord Blood Collection

Authors
Page, KM; Betz-Stablein, B; Mendizabal, AM; Wease, S; Gentry, T; Shoulars, K; Balber, AE; Kurtzberg, J
MLA Citation
Page, KM, Betz-Stablein, B, Mendizabal, AM, Wease, S, Gentry, T, Shoulars, K, Balber, AE, and Kurtzberg, J. "What Clinical Characteristics of Mothers and Babies Favorably Influence Cord Blood Potency? Defining Parameters That Can Guide Public Cord Blood Collection." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
225
End Page
226

Family-directed umbilical cord blood banking.

Umbilical cord blood transplantation from HLA-identical siblings provides good results in children. These results support targeted efforts to bank family cord blood units that can be used for a sibling diagnosed with a disease which can be cured by allogeneic hematopoietic stem cell transplantation or for research that investigates the use of allogeneic or autologous cord blood cells. Over 500 patients transplanted with related cord blood units have been reported to the Eurocord registry with a 4-year overall survival of 91% for patients with non-malignant diseases and 56% for patients with malignant diseases. Main hematologic indications in children are leukemia, hemoglobinopathies or inherited hematologic, immunological or metabolic disorders. However, family-directed cord blood banking is not widely promoted; many cord blood units used in sibling transplantation have been obtained from private banks that do not meet the necessary criteria required to store these units. Marketing by private banks who predominantly store autologous cord blood units has created public confusion. There are very few current validated indications for autologous storage but some new indications might appear in the future. Little effort is devoted to provide unbiased information and to educate the public as to the distinction between the different types of banking, economic models and standards involved in such programs. In order to provide a better service for families in need, directed-family cord blood banking activities should be encouraged and closely monitored with common standards, and better information on current and future indications should be made available.

Authors
Gluckman, E; Ruggeri, A; Rocha, V; Baudoux, E; Boo, M; Kurtzberg, J; Welte, K; Navarrete, C; van Walraven, SM; Eurocord, Netcord, World Marrow Donor Association and National Marrow Donor Program,
MLA Citation
Gluckman, E, Ruggeri, A, Rocha, V, Baudoux, E, Boo, M, Kurtzberg, J, Welte, K, Navarrete, C, van Walraven, SM, Eurocord, Netcord, and World Marrow Donor Association and National Marrow Donor Program, . "Family-directed umbilical cord blood banking." Haematologica 96.11 (November 2011): 1700-1707. (Review)
PMID
21750089
Source
pubmed
Published In
Haematologica
Volume
96
Issue
11
Publish Date
2011
Start Page
1700
End Page
1707
DOI
10.3324/haematol.2011.047050

The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring.

In utero exposures to environmental factors may result in persistent epigenetic modifications affecting normal development and susceptibility to chronic diseases in later life. We explored the relationship between exposure of the growing fetus to maternal depression or antidepressants and DNA methylation at two differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene. Aberrant DNA methylation at the IGF2 and neighboring H19 DMRs has been associated with deregulated IGF2 expression, childhood cancers and several chronic diseases during adulthood. Our study population is comprised of pregnant mothers and their newborns (n = 436), as part of the Newborn Epigenetics Study (NEST). A standardized questionnaire was completed and medical record data were abstracted to ascertain maternal depression and antidepressive drug use. DMR methylation levels in umbilical cord blood leukocytes were quantified using pyrosequencing. From the 436 newborns, laboratory data were obtained for 356 individuals at the IGF2 DMRs, and for 411 individuals at the H19 DMRs; about half of each group was African American or Caucasian. While overall no association between depression and methylation profiles was found, we observed a significant hypermethylation of the H19 DMRs in newborns of African American (n = 177) but not Caucasian (n = 168) mothers who reported the use of antidepressive drugs during pregnancy (β = +6.89, p = 0.01). Of note, our data reveal a race-independent association between smoking during pregnancy and methylation at the IGF2 DMR (+3.05%, p = 0.01). In conclusion, our findings suggest a race-dependent response related to maternal use of antidepressants at one of the IGF2 DMRs in the offspring.

Authors
Soubry, A; Murphy, S; Huang, Z; Murtha, A; Schildkraut, J; Jirtle, R; Wang, F; Kurtzberg, J; Demark-Wahnefried, W; Forman, M; Hoyo, C
MLA Citation
Soubry, A, Murphy, S, Huang, Z, Murtha, A, Schildkraut, J, Jirtle, R, Wang, F, Kurtzberg, J, Demark-Wahnefried, W, Forman, M, and Hoyo, C. "The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring. (Published online)" Clin Epigenetics 3 (October 26, 2011): 2-.
PMID
22414206
Source
pubmed
Published In
Clinical Epigenetics
Volume
3
Publish Date
2011
Start Page
2
DOI
10.1186/1868-7083-3-2

NCI, NHLBI first international consensus conference on late effects after pediatric hematopoietic cell transplantation: state of the science, future directions.

Authors
Baker, KS; Bhatia, S; Bunin, N; Nieder, M; Dvorak, CC; Sung, L; Sanders, JE; Kurtzberg, J; Pulsipher, MA
MLA Citation
Baker, KS, Bhatia, S, Bunin, N, Nieder, M, Dvorak, CC, Sung, L, Sanders, JE, Kurtzberg, J, and Pulsipher, MA. "NCI, NHLBI first international consensus conference on late effects after pediatric hematopoietic cell transplantation: state of the science, future directions." Biol Blood Marrow Transplant 17.10 (October 2011): 1424-1427.
PMID
21723224
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
10
Publish Date
2011
Start Page
1424
End Page
1427
DOI
10.1016/j.bbmt.2011.06.007

Umbilical cord blood: a guide for primary care physicians.

Umbilical cord blood stem cell transplants are used to treat a variety of oncologic, genetic, hematologic, and immunodeficiency disorders. Physicians have an important role in educating, counseling, and offering umbilical cord blood donation and storage options to patients. Parents may donate their infant's cord blood to a public bank, pay to store it in a private bank, or have it discarded. The federal government and many state governments have passed laws and issued regulations regarding umbilical cord blood, and some states require physicians to discuss cord blood options with pregnant women. Five prominent medical organizations have published recommendations about cord blood donation and storage. Current guidelines recommend donation of umbilical cord blood to public banks when possible, or storage through the Related Donor Cord Blood Program when a sibling has a disease that may require a stem cell transplant. Experts do not currently recommend private banking for unidentified possible future use. Step-by-step guidance and electronic resources are available to physicians whose patients are considering saving or donating their infant's umbilical cord blood.

Authors
Martin, PL; Kurtzberg, J; Hesse, B
MLA Citation
Martin, PL, Kurtzberg, J, and Hesse, B. "Umbilical cord blood: a guide for primary care physicians." Am Fam Physician 84.6 (September 15, 2011): 661-666. (Review)
PMID
21916391
Source
pubmed
Published In
American family physician
Volume
84
Issue
6
Publish Date
2011
Start Page
661
End Page
666

Creation of a Segment-Based Aldehyde Dehydrogenase Assay as a Biomarker for Umbilical Cord Blood Potency

Authors
Shoulars, K; Page, K; Gentry, T; Balber, A; Kurtzberg, J
MLA Citation
Shoulars, K, Page, K, Gentry, T, Balber, A, and Kurtzberg, J. "Creation of a Segment-Based Aldehyde Dehydrogenase Assay as a Biomarker for Umbilical Cord Blood Potency." September 2011.
Source
wos-lite
Published In
Transfusion
Volume
51
Publish Date
2011
Start Page
221A
End Page
221A

Partial splenectomy but not total splenectomy preserves immunoglobulin M memory B cells in mice.

PURPOSE: The mechanism by which partial splenectomy preserves splenic immune function is unknown. Immunoglobulin (Ig) M memory B cells are critical for the immune response against encapsulated bacteria and are reduced in asplenic patients, although it is unknown whether partial splenectomy can preserve memory B cells. We hypothesized that IgM memory B cells (murine B-1a cells) would be preserved after partial splenectomy but not after total splenectomy in mice. METHODS: We performed total splenectomy (n = 17), partial splenectomy (n = 10), or sham laparotomy (n = 16) on C57BL/6J mice. Mice were killed on postoperative day 10 or 30, and peritoneal washings were analyzed by multiparameter flow cytometry for expression of murine B-1a cells (IgM(pos)IgD(dull)CD5(pos)B220(dull)). RESULTS: We found that B-1a cells were significantly reduced after both total and partial splenectomies compared with sham laparotomy in the early postoperative period, although normal levels of B-1a cells returned by postoperative day 30 in mice undergoing partial splenectomy but not total splenectomy. CONCLUSION: Partial splenectomy but not total splenectomy preserves the B-1a B-cell population in mice within 30 days after surgery. Maintenance of these critical B cells may contribute to the preservation of a splenic-dependent immune response after partial splenectomy.

Authors
Tracy, ET; Haas, KM; Gentry, T; Danko, M; Roberts, JL; Kurtzberg, J; Rice, HE
MLA Citation
Tracy, ET, Haas, KM, Gentry, T, Danko, M, Roberts, JL, Kurtzberg, J, and Rice, HE. "Partial splenectomy but not total splenectomy preserves immunoglobulin M memory B cells in mice." J Pediatr Surg 46.9 (September 2011): 1706-1710.
PMID
21929978
Source
pubmed
Published In
Journal of Pediatric Surgery
Volume
46
Issue
9
Publish Date
2011
Start Page
1706
End Page
1710
DOI
10.1016/j.jpedsurg.2011.04.020

Total colony-forming units are a strong, independent predictor of neutrophil and platelet engraftment after unrelated umbilical cord blood transplantation: a single-center analysis of 435 cord blood transplants.

Graft failure occurs in approximately 20% of patients after unrelated umbilical cord blood transplantation (UCBT). This could be because of inadequate potency of the cord blood unit (CBU). To this end, we investigated the impact of graft characteristics on engraftment and survival of 435 primarily pediatric (median age: 5.3 years) patients receiving a single-unit unrelated UCBT after myeloablative conditioning from 2000 to 2008. Pre-cryopreservation (pre-cryo) graft characteristics were provided by the banks. Post-thaw parameters were measured on dextran/albumin-washed grafts. Post-thaw recovery of the colony-forming unit (CFU), a biological assay reflecting functional viability of the cord blood cells was the lowest percent age (median 21.2%, mean 36.5%) of the pre-cryo value, regardless of the bank of origin. The cumulative incidences of neutrophil and platelet engraftment were 76.9% (95%, confidence interval [CI], 71.3%-82.5%) and 55% (95% CI, 49.3%-60.7%), respectively. Univariate and separate multivariate models using pre-cryo and post-thaw datasets including clinical parameters identified predictors of engraftment and survival. In multivariate modeling, higher CFU dosing was the only pre-cryo graft characteristic predictive of neutrophil (P = .0024) and platelet engraftment (P = .0063). In the post-thaw model, CFU dose best predicted neutrophil and platelet engraftment (both P < .0001). Comparatively, CD34(+) and total nucleated cell (TNC) were only weakly predictive in post-thaw neutrophil and platelet engraftment models, respectively. In conclusion, CFU dose is a strong independent predictor of engraftment after unrelated UCBT and should be used to assess potency when selecting CBUs for transplantation.

Authors
Page, KM; Zhang, L; Mendizabal, A; Wease, S; Carter, S; Gentry, T; Balber, AE; Kurtzberg, J
MLA Citation
Page, KM, Zhang, L, Mendizabal, A, Wease, S, Carter, S, Gentry, T, Balber, AE, and Kurtzberg, J. "Total colony-forming units are a strong, independent predictor of neutrophil and platelet engraftment after unrelated umbilical cord blood transplantation: a single-center analysis of 435 cord blood transplants." Biol Blood Marrow Transplant 17.9 (September 2011): 1362-1374.
PMID
21277377
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
9
Publish Date
2011
Start Page
1362
End Page
1374
DOI
10.1016/j.bbmt.2011.01.011

Umbilical cord blood transplantation for children with thalassemia and sickle cell disease.

We examined the efficacy of unrelated cord blood (CB) transplantation in children with thalassemia (n = 35) and sickle cell disease (n = 16), using data reported to 3 registries. Donor-recipient pairs were matched at HLA-A and -B (antigen level) and DRB1 (allele level) in 7 or HLA mismatched at 1 (n = 18), 2 (n = 25), or 3 loci (n = 1). Transplant conditioning was myeloablative (n = 39) or reduced intensity (n = 12). Neutrophil recovery with donor chimerism was documented in 24 patients; 11 patients developed grade II-IV acute graft-versus-host disease (aGVHD) and 10 patients, chronic GVHD (cGVHD). Overall survival (OS) and disease-free survival (DFS) were 62% and 21% for thalassemia and 94% and 50% for sickle cell disease (SCD), respectively. In multivariate analysis, engraftment rate (hazard ratio [HR] 2.2, P = .05) and DFS (HR 0.4, P = .01) were higher with cell dose >5 × 10(7)/kg. The 2-year probability of DFS was 45% in patients who received grafts with cell dose >5 × 10(7)/kg and 13% with lower cell dose. Primary graft failure was the predominant cause of treatment failure occurring in 20 patients with thalassemia and 7 patients with SCD. Primary graft failure was fatal in 5 patients with thalassemia. These results suggest that only CB units containing an expected infused cell dose >5 × 10(7)/kg should be considered for transplantation for hemoglobinopathy.

Authors
Ruggeri, A; Eapen, M; Scaravadou, A; Cairo, MS; Bhatia, M; Kurtzberg, J; Wingard, JR; Fasth, A; Lo Nigro, L; Ayas, M; Purtill, D; Boudjedir, K; Chaves, W; Walters, MC; Wagner, J; Gluckman, E; Rocha, V; Eurocord Registry, ; Center for International Blood and Marrow Transplant Research, ; New York Blood Center,
MLA Citation
Ruggeri, A, Eapen, M, Scaravadou, A, Cairo, MS, Bhatia, M, Kurtzberg, J, Wingard, JR, Fasth, A, Lo Nigro, L, Ayas, M, Purtill, D, Boudjedir, K, Chaves, W, Walters, MC, Wagner, J, Gluckman, E, Rocha, V, Eurocord Registry, , Center for International Blood and Marrow Transplant Research, , and New York Blood Center, . "Umbilical cord blood transplantation for children with thalassemia and sickle cell disease." Biol Blood Marrow Transplant 17.9 (September 2011): 1375-1382.
PMID
21277376
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
9
Publish Date
2011
Start Page
1375
End Page
1382
DOI
10.1016/j.bbmt.2011.01.012

Guidelines for the development and validation of new potency assays for the evaluation of umbilical cord blood.

The following commentary was developed by the National Marrow Donor Program Cord Blood Advisory Group and is intended to provide an overview of umbilical cord blood (UCB) processing, summarize the current state of potency assays used to characterize UCB, and define limitations of the assays and future needs of the cord blood banking and transplant community. The UCB banking industry is eager to participate in the development of standardized assays to uniformly characterize cellular therapy products that are manufactured in a variety of ways. This paper describes the desired qualities of these assays and how the industry proposes to co-operate with developers to bring relevant assays to market. To that end, the National Marrow Donor Program (NMDP) Cord Blood Bank Network is available to serve as a resource for UCB testing material, research and development consulting, and product/assay testing in an accredited UCB manufacturing environment.

Authors
Spellman, S; Hurley, CK; Brady, C; Phillips-Johnson, L; Chow, R; Laughlin, M; McMannis, J; Reems, J-A; Regan, D; Rubinstein, P; Kurtzberg, J; National Marrow Donor Program Cord Blood Advisory Group,
MLA Citation
Spellman, S, Hurley, CK, Brady, C, Phillips-Johnson, L, Chow, R, Laughlin, M, McMannis, J, Reems, J-A, Regan, D, Rubinstein, P, Kurtzberg, J, and National Marrow Donor Program Cord Blood Advisory Group, . "Guidelines for the development and validation of new potency assays for the evaluation of umbilical cord blood." Cytotherapy 13.7 (August 2011): 848-855.
PMID
21449685
Source
pubmed
Published In
Cytotherapy (Informa)
Volume
13
Issue
7
Publish Date
2011
Start Page
848
End Page
855
DOI
10.3109/14653249.2011.571249

Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy.

Folic acid (FA) supplementation before and during pregnancy has been associated with decreased risk of neural tube defects although recent reports suggest it may also increase the risk of other chronic diseases. We evaluated exposure to maternal FA supplementation before and during pregnancy in relation to aberrant DNA methylation at two differentially methylated regions (DMRs) regulating Insulin-like Growth Factor 2 (IGF2) expression in infants. Aberrant methylation at these regions has been associated with IGF2 deregulation and increased susceptibility to several chronic diseases. Using a self-administered questionnaire, we assessed FA intake before and during pregnancy in 438 pregnant women. Pyrosequencing was used to measure methylation at two IGF2 DMRs in umbilical cord blood leukocytes. Mixed models were used to determine relationships between maternal FA supplementation before or during pregnancy and DNA methylation levels at birth. Average methylation at the H19 DMR was 61.2%. Compared to infants born to women reporting no FA intake before or during pregnancy, methylation levels at the H19 DMR decreased with increasing FA intake (2.8%, p=0.03, and 4.9%, p=0.04, for intake before and during pregnancy, respectively). This methylation decrease was most pronounced in male infants (p=0.01). Methylation alterations at the H19 DMR are likely an important mechanism by which FA risks and/or benefits are conferred in utero. Because stable methylation marks at DMRs regulating imprinted genes are acquired before gastrulation, they may serve as archives of early exposures with the potential to improve our understanding of developmental origins of adult disease.

Authors
Hoyo, C; Murtha, AP; Schildkraut, JM; Jirtle, RL; Demark-Wahnefried, W; Forman, MR; Iversen, ES; Kurtzberg, J; Overcash, F; Huang, Z; Murphy, SK
MLA Citation
Hoyo, C, Murtha, AP, Schildkraut, JM, Jirtle, RL, Demark-Wahnefried, W, Forman, MR, Iversen, ES, Kurtzberg, J, Overcash, F, Huang, Z, and Murphy, SK. "Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy." Epigenetics 6.7 (July 2011): 928-936.
PMID
21636975
Source
pubmed
Published In
Epigenetics : official journal of the DNA Methylation Society
Volume
6
Issue
7
Publish Date
2011
Start Page
928
End Page
936

Isolation and expansion of oligodendrocyte progenitor cells from cryopreserved human umbilical cord blood.

BACKGROUND AIMS: Oligodendrocyte precursor cells (OPC) hold promise as a cellular therapy for demyelinating diseases. The feasibility of using OPC-based therapies in humans depends upon a reliable, readily available source. We have previously described the isolation, expansion and characterization of oligodendrocyte-like cells from fresh human umbilical cord blood (UCB). We now describe the isolation and expansion of OPC from thawed, cryopreserved UCB. METHODS: We thawed cryopreserved UCB units employing a standard clinical protocol, then isolated and plated mononuclear cells under previously established culture conditions. All OPC cultures were trypsinized at 21 days, counted, then characterized by flow cytometry after fixation, permeablization and labeling with the following antibodies: anti-oligodendrocyte marker 4 (O4), anti-oligodendrocyte marker 1 (O1) and anti-myelin basic protein (MBP). OPC were also placed in co-culture with shiverer mouse neuronal cells then stained in situ for beta tubulin III (BT3) and MBP as a functional assay of myelination. RESULTS: The average OPC yield per cryopreserved UCB unit was 64% of that seen with fresh UCB. On flow cytometric analysis, 74% of thawed UCB units yielded cells with an O4-expression level of at least 20% of total events, compared with 95% of fresh UCB units. We observed myelination of shiverer neurons in our functional assay, which could be used as a potency assay for release of OPC cells in phase I human clinical trials. CONCLUSIONS: Our results demonstrate that OPC can be derived reliably from thawed, cryopreserved UCB units, and support the feasibility of using these cells in human clinical trials.

Authors
Tracy, ET; Zhang, CY; Gentry, T; Shoulars, KW; Kurtzberg, J
MLA Citation
Tracy, ET, Zhang, CY, Gentry, T, Shoulars, KW, and Kurtzberg, J. "Isolation and expansion of oligodendrocyte progenitor cells from cryopreserved human umbilical cord blood." Cytotherapy 13.6 (July 2011): 722-729.
PMID
21341973
Source
pubmed
Published In
Cytotherapy (Informa)
Volume
13
Issue
6
Publish Date
2011
Start Page
722
End Page
729
DOI
10.3109/14653249.2011.553592

Allogeneic transplantation for patients with high-risk or refractory neuroblastoma.

Authors
Driscoll, TA; Martin, PL; Moffet, J; Daniel, M; Page, K; Parikh, S; Prasad, V; Szabolcs, P; Kurtzberg, J
MLA Citation
Driscoll, TA, Martin, PL, Moffet, J, Daniel, M, Page, K, Parikh, S, Prasad, V, Szabolcs, P, and Kurtzberg, J. "Allogeneic transplantation for patients with high-risk or refractory neuroblastoma." JOURNAL OF CLINICAL ONCOLOGY 29.15 (May 20, 2011).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
15
Publish Date
2011

Allogeneic transplantation for patients with high-risk or refractory neuroblastoma.

9552 Background: While the survival of high-risk neuroblastoma patients has improved with myeloablative chemotherapy (MAC) and 13-cis retinoic acid, 60% of children fail this approach, thus other strategies are needed. As a potential platform for future immunologic-based therapies, we report a retrospective, single-center experience using allogeneic hematopoietic stem cell transplantation (allo-HSCT) following MAC for high risk or recurrent neuroblastoma (NB).Between June 1994 and November 2007, 17 pediatric patients with high risk or recurrent NB underwent allo-HSCT: allograft sources were related bone marrow (MRD) in 10 patients (pts) and unrelated umbilical cord blood (UCB) in 7 pts. At initial diagnosis the median age was 3.5 years, 16 pts had stage 4 and 1 patient had stage 3 disease. N-myc was amplified in 4 of the 12 pts with available N-myc status. Prior to allo-HSCT, 4 pts were in CR and 7 pts had failed autologous HSCT. Median time from NB diagnosis to allo-HSCT was 14.9 months. Regarding MAC, 7 pts received total body irradiation (TBI)-based regimens: (5 TBI/melphalan (Mel) and 2 TBI/thiotepa), 6 pts received cyclophosphamide (Cy)-based regimens (5 Cy/Mel and 1 Cy-thiotepa), 1 received carboplatin /etoposide/melphalan (CEM), and 3 pts received therapeutic I-131MIBG based regimens (MIBG /CEM in 1, MIBG /campath /Mel in 1, and MIBG/TBI/Mel in 1).The median day to neutrophil engraftment (ANC > 500) was 10.5 days for MRD BMT and 22 days for UCBT. The median day to platelet engraftment (plt >20k) for MRD BMT was 29.5 days and for UCBT was 62 days. Acute GVHD (grades I-IV) was seen in 6 patients: 3 grade-I skin, 1 grade-II skin, and 2 grade-III involving both skin and gut. Eleven pts (65%) died at a median of 377 days post-allo-HSCT: 2 infections (PCP pneumonia, Pseudomonal sepsis), 2 MSOF, 1 leukemic relapse (child with recurrent NB and secondary AML) and 6 NB progression. Six patients (5 MRD, 1 UCB) are long-term survivors with overall survival of 35% at 10 years.Allo-HSCT provided durable remission in a very high risk group of NB patients. Therefore a strategy that incorporates early allografting with targeted immunologic therapy should be investigated for refractory or ultra-high risk NB patients.

Authors
Driscoll, TA; Martin, PL; Moffet, J; Daniel, M; Page, K; Parikh, S; Prasad, V; Szabolcs, P; Kurtzberg, J
MLA Citation
Driscoll, TA, Martin, PL, Moffet, J, Daniel, M, Page, K, Parikh, S, Prasad, V, Szabolcs, P, and Kurtzberg, J. "Allogeneic transplantation for patients with high-risk or refractory neuroblastoma." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.15_suppl (May 2011): 9552-.
PMID
28019759
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
15_suppl
Publish Date
2011
Start Page
9552

MYELOABLATIVE (MAC) AUTOLOGOUS STEM-CELL TRANSPLANTATION (AUTOSCT) FOLLOWED BY REDUCED INTENSITY (RIC) ALLOGENEIC STEM-CELL TRANSPLANTATION (ALLOSCT) IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS (CAYA) WITH POOR RISK HODGKIN LYMPHOMA (HL): INDUCTION OF LONG-TERM GVHL EFFECT

Authors
Satwani, P; Harrison, L; Bhatia, M; Bradley, MB; Jr, GJH; George, D; Martin, P; Kurtzberg, J; Schwartz, J; Baxter-Lowe, LA; Cairo, MS
MLA Citation
Satwani, P, Harrison, L, Bhatia, M, Bradley, MB, Jr, GJH, George, D, Martin, P, Kurtzberg, J, Schwartz, J, Baxter-Lowe, LA, and Cairo, MS. "MYELOABLATIVE (MAC) AUTOLOGOUS STEM-CELL TRANSPLANTATION (AUTOSCT) FOLLOWED BY REDUCED INTENSITY (RIC) ALLOGENEIC STEM-CELL TRANSPLANTATION (ALLOSCT) IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS (CAYA) WITH POOR RISK HODGKIN LYMPHOMA (HL): INDUCTION OF LONG-TERM GVHL EFFECT." PEDIATRIC BLOOD & CANCER 56.5 (May 2011): 890-891.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
56
Issue
5
Publish Date
2011
Start Page
890
End Page
891

Abstract 2754: Maternal use of antidepressants in pregnancy is associated with hypermethylation at the IGF2 imprinted control regions in the offspring in a race-dependent fashion

Authors
Soubry, A; Murphy, SK; Huang, Z; Murtha, A; Schildkraut, JM; Jirtle, RL; Wang, F; Kurtzberg, J; Demark-Wahnefried, W; Forman, M; Hoyo, C
MLA Citation
Soubry, A, Murphy, SK, Huang, Z, Murtha, A, Schildkraut, JM, Jirtle, RL, Wang, F, Kurtzberg, J, Demark-Wahnefried, W, Forman, M, and Hoyo, C. "Abstract 2754: Maternal use of antidepressants in pregnancy is associated with hypermethylation at the IGF2 imprinted control regions in the offspring in a race-dependent fashion." Cancer Research 71.8 Supplement (April 15, 2011): 2754-2754.
Source
crossref
Published In
Cancer Research
Volume
71
Issue
8 Supplement
Publish Date
2011
Start Page
2754
End Page
2754
DOI
10.1158/1538-7445.AM2011-2754

Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal™) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study.

Preliminary studies using directed-donor ex vivo expanded human mesenchymal stem cells (hMSCs) have shown promise in the treatment of acute graft-versus-host disease (aGVHD). However, their production is cumbersome and standardization is difficult. We describe the first experience of using a premanufactured, universal donor, formulation of hMSCs (Prochymal) in children (n = 12; 10 boys; 9 Caucasian; age range: 0.4-15 years) with treatment-resistant grade III and IV aGVHD who received therapy on compassionate use basis between July 2005 and June 2007 at 5 transplant centers. All patients had stage III or IV gut (GI) symptoms and half had additional liver and/or skin involvement. Disease was refractory to steroids in all cases and additionally to a median of 3 other immunosuppressive therapies. The hMSCs (8 × 10(6)cells/kg/dose in 2 patients and 2 × 10(6)cells/kg/dose in the rest) were infused intravenously over 1 hour twice a week for 4 weeks. Partial and mixed responders received subsequent weekly therapy for 4 weeks. HLA or other matching was not needed. The hMSCs were started at a median of 98 days (range: 45-237) posttransplant. A total of 124 doses were administered, with a median of 8 doses (range: 2-21) per patient. Overall, 7 (58%) patients had complete response, 2 (17%) partial response, and 3 (25%) mixed response. Complete resolution of GI symptoms occurred in 9 (75%) patients. Two patients relapsed after initial response and showed partial response to retreatment. The cumulative incidence of survival at 100 days from the initiation of Prochymal therapy was 58%. Five of 12 patients (42%) were still alive after a median follow-up of 611 days (range: 427-1111) in surviving patients. No infusional or other identifiable acute toxicity was seen in any patient. Multiple infusions of hMSCs were well tolerated and appeared to be safe in children. Clinical responses, particularly in the GI system, were seen in the majority of children with severe refractory aGVHD. Given the favorable results observed in a patient population with an otherwise grave prognosis, we conclude that hMSCs hold potential for the treatment of aGVHD, and should be further studied in phase III trials in pediatric and adult patients.

Authors
Prasad, VK; Lucas, KG; Kleiner, GI; Talano, JAM; Jacobsohn, D; Broadwater, G; Monroy, R; Kurtzberg, J
MLA Citation
Prasad, VK, Lucas, KG, Kleiner, GI, Talano, JAM, Jacobsohn, D, Broadwater, G, Monroy, R, and Kurtzberg, J. "Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal™) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study." Biol Blood Marrow Transplant 17.4 (April 2011): 534-541.
PMID
20457269
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
4
Publish Date
2011
Start Page
534
End Page
541
DOI
10.1016/j.bbmt.2010.04.014

Impact of matching at non-inherited maternal antigens on outcomes after 5/6 or 4/6 HLA mismatched unrelated cord blood transplantation for malignant haematological diseases. A matched pair analysis on behalf of Eurocord, Netcord, NMDP, IBMTR

Authors
Rocha, V; Purtill, D; Zhang, M; Spellman, S; Ruggeri, A; Prasad, V; Navarette, C; Koegler, G; Baudoux, E; Lecchi, L; Baxter-Lowe, LA; Horowitz, M; van Rood, JJ; Kurtzberg, J; Gluckman, E; Eapen, M
MLA Citation
Rocha, V, Purtill, D, Zhang, M, Spellman, S, Ruggeri, A, Prasad, V, Navarette, C, Koegler, G, Baudoux, E, Lecchi, L, Baxter-Lowe, LA, Horowitz, M, van Rood, JJ, Kurtzberg, J, Gluckman, E, and Eapen, M. "Impact of matching at non-inherited maternal antigens on outcomes after 5/6 or 4/6 HLA mismatched unrelated cord blood transplantation for malignant haematological diseases. A matched pair analysis on behalf of Eurocord, Netcord, NMDP, IBMTR." April 2011.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
46
Publish Date
2011
Start Page
S2
End Page
S2

Analysis of risk factors influencing outcomes after unrelated cord blood transplantation in children with juvenile myelomonocytic leukaemia. An Eurocord, EBMT, EWOG-MDS, CIBMTR Study

Authors
Crotta, A; Rocha, V; Eapen, M; Wagner, JE; MacMillan, ML; Zecca, M; Kurtzberg, J; Bonfim, C; Vora, A; Diaz de Heredia, C; Mohty, M; Teague, L; Stein, J; O'Brien, TA; Bittencourt, H; Madureira, A; Peters, C; Niemeyer, C; Gluckman, E; Locatelli, F
MLA Citation
Crotta, A, Rocha, V, Eapen, M, Wagner, JE, MacMillan, ML, Zecca, M, Kurtzberg, J, Bonfim, C, Vora, A, Diaz de Heredia, C, Mohty, M, Teague, L, Stein, J, O'Brien, TA, Bittencourt, H, Madureira, A, Peters, C, Niemeyer, C, Gluckman, E, and Locatelli, F. "Analysis of risk factors influencing outcomes after unrelated cord blood transplantation in children with juvenile myelomonocytic leukaemia. An Eurocord, EBMT, EWOG-MDS, CIBMTR Study." April 2011.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
46
Publish Date
2011
Start Page
S15
End Page
S15

What's up with 2 cord transplantation?

Authors
Kurtzberg, J
MLA Citation
Kurtzberg, J. "What's up with 2 cord transplantation?." Blood 117.12 (March 24, 2011): 3248-3249.
PMID
21436075
Source
pubmed
Published In
Blood
Volume
117
Issue
12
Publish Date
2011
Start Page
3248
End Page
3249
DOI
10.1182/blood-2011-01-327320

Quality of Life Project – An Oral Presentation

Authors
Caraher, RBJ; Little, K; Kurtzberg, J; Guess, C; Barfield, R; Saini, S; Paul, ML
MLA Citation
Caraher, RBJ, Little, K, Kurtzberg, J, Guess, C, Barfield, R, Saini, S, and Paul, ML. "Quality of Life Project – An Oral Presentation." February 2011.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S368
End Page
S369
DOI
10.1016/j.bbmt.2010.12.648

Through the Lens: Engaging School-Age Children and Adolescent SCT Patients in an Academic Photography Project

Authors
Cash, JV; Moses, JW; Kalbacker, ME; Kurtzberg, J
MLA Citation
Cash, JV, Moses, JW, Kalbacker, ME, and Kurtzberg, J. "Through the Lens: Engaging School-Age Children and Adolescent SCT Patients in an Academic Photography Project." February 2011.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S367
End Page
S367
DOI
10.1016/j.bbmt.2010.12.642

Experience With CMX001, a Novel Antiviral Drug, for Cytomegalovirus infections in Stem Cell Transplant Patients

Authors
Papanicolau, G; Kurtzberg, J; Westervelt, P; Gea-Banacloche, J; Warlick, E; Lanier, R; Anderson, M; Painter, W
MLA Citation
Papanicolau, G, Kurtzberg, J, Westervelt, P, Gea-Banacloche, J, Warlick, E, Lanier, R, Anderson, M, and Painter, W. "Experience With CMX001, a Novel Antiviral Drug, for Cytomegalovirus infections in Stem Cell Transplant Patients." February 2011.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S273
End Page
S274
DOI
10.1016/j.bbmt.2010.12.364

Fast Facts Flip Chart – A Quick Accessible Reference Guide for Busy Nurses

Authors
Mckinney, TE; Little, K; Kurtzberg, J; Caraher, BJ
MLA Citation
Mckinney, TE, Little, K, Kurtzberg, J, and Caraher, BJ. "Fast Facts Flip Chart – A Quick Accessible Reference Guide for Busy Nurses." February 2011.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S368
End Page
S368
DOI
10.1016/j.bbmt.2010.12.647

Eighth Annual International Umbilical Cord Blood Transplantation Symposium, San Francisco, California, June 3-5, 2010.

Authors
Laughlin, M; Kurtzberg, J; McMannis, J; Petz, L
MLA Citation
Laughlin, M, Kurtzberg, J, McMannis, J, and Petz, L. "Eighth Annual International Umbilical Cord Blood Transplantation Symposium, San Francisco, California, June 3-5, 2010." Biol Blood Marrow Transplant 17.2 (February 2011): 176-189.
PMID
20951820
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
176
End Page
189
DOI
10.1016/j.bbmt.2010.10.007

CORD BLOOD (CB) APGAR SCORE MAY BE PREDICTIVE OF TRANSPLANT RELATED MORTALITY (TRM), OVERALL SURVIVAL (OS) AND DISEASE-FREE SURVIVAL (DFS) FOR PLASMA DEPLETED/REDUCED CB PRODUCTS

Authors
Chow, R; Wang, BC; Chow, M; Chou, D; Wu, T; Lin, A; Petz, LD; Kurtzberg, J
MLA Citation
Chow, R, Wang, BC, Chow, M, Chou, D, Wu, T, Lin, A, Petz, LD, and Kurtzberg, J. "CORD BLOOD (CB) APGAR SCORE MAY BE PREDICTIVE OF TRANSPLANT RELATED MORTALITY (TRM), OVERALL SURVIVAL (OS) AND DISEASE-FREE SURVIVAL (DFS) FOR PLASMA DEPLETED/REDUCED CB PRODUCTS." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S157
End Page
S157
DOI
10.1016/j.bbmt.2010.12.022

CORD BLOOD (CB) APGAR SCORE IS PREDICTIVE OF NEUTROPHIL ENGRAFTMENT AND GRAFT FAILURE PROBABILITIES FOR PLASMA DEPLETED/REDUCED CB PRODUCTS

Authors
Chow, R; Wang, BC; Chou, D; Chow, M; Wu, T; Kang, J; Petz, LD; Kurtzberg, J
MLA Citation
Chow, R, Wang, BC, Chou, D, Chow, M, Wu, T, Kang, J, Petz, LD, and Kurtzberg, J. "CORD BLOOD (CB) APGAR SCORE IS PREDICTIVE OF NEUTROPHIL ENGRAFTMENT AND GRAFT FAILURE PROBABILITIES FOR PLASMA DEPLETED/REDUCED CB PRODUCTS." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S170
End Page
S170
DOI
10.1016/j.bbmt.2010.12.057

VITAMIN D DEFICIENCY IN CHILDREN UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION

Authors
Desai, SR; Tewari, P; Whelan, M; Kurtzberg, J; Prasad, VK
MLA Citation
Desai, SR, Tewari, P, Whelan, M, Kurtzberg, J, and Prasad, VK. "VITAMIN D DEFICIENCY IN CHILDREN UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S274
End Page
S274
DOI
10.1016/j.bbmt.2010.12.366

DIFFERENTIAL IMPACT OF HLA-A, -B, AND-DRB1 MISMATCHING IN RELATION TO OTHER VARIABLES ON THE OUTCOMES OF MYELOABLATIVE UNRELATED SINGLE DONOR UMBILICAL CORD BLOOD TRANSPLANTATION FROM 4/6 MATCHED UNITS IN CHILDREN AND YOUNG ADULTS

Authors
Prasad, VK; Mendizabal, A; Tewari, P; Page, K; Parikh, SH; Szabolcs, P; Driscoll, TA; Martin, PL; Kurtzberg, J
MLA Citation
Prasad, VK, Mendizabal, A, Tewari, P, Page, K, Parikh, SH, Szabolcs, P, Driscoll, TA, Martin, PL, and Kurtzberg, J. "DIFFERENTIAL IMPACT OF HLA-A, -B, AND-DRB1 MISMATCHING IN RELATION TO OTHER VARIABLES ON THE OUTCOMES OF MYELOABLATIVE UNRELATED SINGLE DONOR UMBILICAL CORD BLOOD TRANSPLANTATION FROM 4/6 MATCHED UNITS IN CHILDREN AND YOUNG ADULTS." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S185
End Page
S186
DOI
10.1016/j.bbmt.2010.12.100

A PROSPECTIVE STUDY OF REDUCED INTENSITY CONDITIONING (RIC) IN CHILDREN UNDERGOING UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION (UCBT) FOR NON-MALIGNANT DISEASES: PRELIMINARY RESULTS DEMONSTRATE A HIGH RATE OF ENGRAFTMENT AND LOW INCIDENCE OF GVHD

Authors
Parikh, SH; Martin, PL; Driscoll, TA; Baker, J; Piersol, K; Moffet, J; Stokhuyzen, A; Cash, J; Kurtzberg, J; Szabolcs, P
MLA Citation
Parikh, SH, Martin, PL, Driscoll, TA, Baker, J, Piersol, K, Moffet, J, Stokhuyzen, A, Cash, J, Kurtzberg, J, and Szabolcs, P. "A PROSPECTIVE STUDY OF REDUCED INTENSITY CONDITIONING (RIC) IN CHILDREN UNDERGOING UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION (UCBT) FOR NON-MALIGNANT DISEASES: PRELIMINARY RESULTS DEMONSTRATE A HIGH RATE OF ENGRAFTMENT AND LOW INCIDENCE OF GVHD." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S265
End Page
S266
DOI
10.1016/j.bbmt.2010.12.338

DURABLE ENGRAFTMENT AND CORRECTION OF GENETIC DEFECT IN CHILDREN WITH CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA FOLLOWING MYELOABLATIVE UMBILICAL CORD BLOOD TRANSPLANTATION

Authors
Mahadeo, KM; Parikh, SH; Driscoll, TA; Page, K; Szabolcs, P; Martin, PL; Kurtzberg, J; Prasad, VK
MLA Citation
Mahadeo, KM, Parikh, SH, Driscoll, TA, Page, K, Szabolcs, P, Martin, PL, Kurtzberg, J, and Prasad, VK. "DURABLE ENGRAFTMENT AND CORRECTION OF GENETIC DEFECT IN CHILDREN WITH CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA FOLLOWING MYELOABLATIVE UMBILICAL CORD BLOOD TRANSPLANTATION." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S256
End Page
S256
DOI
10.1016/j.bbmt.2010.12.312

EDUCATING PEDIATRIC OUTPATIENT NURSES TO THE UNIQUE CHALLENGES OF REDUCED INTENSITY TRANSPLANT CONDITIONING (RIC) REGIMEN IN CHILDREN WITH NON-MALIGNANT DISORDERS

Authors
Hollowell, RM; Cash, JV; Stokhuyzen, AR; Szabolcs, P; Kurtzberg, J; Parikh, SH
MLA Citation
Hollowell, RM, Cash, JV, Stokhuyzen, AR, Szabolcs, P, Kurtzberg, J, and Parikh, SH. "EDUCATING PEDIATRIC OUTPATIENT NURSES TO THE UNIQUE CHALLENGES OF REDUCED INTENSITY TRANSPLANT CONDITIONING (RIC) REGIMEN IN CHILDREN WITH NON-MALIGNANT DISORDERS." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S370
End Page
S370
DOI
10.1016/j.bbmt.2010.12.653

TIME SENSITIVE PARAMETERS OF IMMUNE RECONSTITUTION MEASURED BETWEEN DAY 100 AND 1 YEAR PREDICT SURVIVAL AFTER UNRELATED CORD BLOOD TRANSPLANT (UCBT): THE DYNAMIC IMPACT OF DENDRITIC CELLS, TREGS, AND THYMIC RECOVERY

Authors
Szabolcs, P; Mendizabal, AM; Wilfret, DA; Reese, M; Vinesette, R; Page, KM; Parikh, SH; Kurtzberg, J
MLA Citation
Szabolcs, P, Mendizabal, AM, Wilfret, DA, Reese, M, Vinesette, R, Page, KM, Parikh, SH, and Kurtzberg, J. "TIME SENSITIVE PARAMETERS OF IMMUNE RECONSTITUTION MEASURED BETWEEN DAY 100 AND 1 YEAR PREDICT SURVIVAL AFTER UNRELATED CORD BLOOD TRANSPLANT (UCBT): THE DYNAMIC IMPACT OF DENDRITIC CELLS, TREGS, AND THYMIC RECOVERY." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S229
End Page
S229
DOI
10.1016/j.bbmt.2010.12.233

MPS I: Age at transplant is associated with better long-term developmental outcomes

Authors
Yin, H; Poe, M; Kurtzberg, J; Escolar, M
MLA Citation
Yin, H, Poe, M, Kurtzberg, J, and Escolar, M. "MPS I: Age at transplant is associated with better long-term developmental outcomes." February 2011.
Source
wos-lite
Published In
Molecular Genetics and Metabolism
Volume
102
Issue
2
Publish Date
2011
Start Page
S35
End Page
S35
DOI
10.1016/j.ymgme.2010.11.119

MEETING THE CHALLENGE: DEVELOPING A MODEL TO CARE FOR AN ADOLESCENT PATIENT WITH LEUKEMIA AND SEVERE AUTISM

Authors
Bain, ME; Martin, PL; Kojis, S; Trout, SB; Kurtzberg, J
MLA Citation
Bain, ME, Martin, PL, Kojis, S, Trout, SB, and Kurtzberg, J. "MEETING THE CHALLENGE: DEVELOPING A MODEL TO CARE FOR AN ADOLESCENT PATIENT WITH LEUKEMIA AND SEVERE AUTISM." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S283
End Page
S283
DOI
10.1016/j.bbmt.2010.12.391

MPS II: developmental outcomes after hematopoietic stem cell transplantation

Authors
Escolar, M; Holt, J; Poe, M; Prasad, V; Parikh, S; Kurtzberg, J; Szabolcs, P
MLA Citation
Escolar, M, Holt, J, Poe, M, Prasad, V, Parikh, S, Kurtzberg, J, and Szabolcs, P. "MPS II: developmental outcomes after hematopoietic stem cell transplantation." February 2011.
Source
wos-lite
Published In
Molecular Genetics and Metabolism
Volume
102
Issue
2
Publish Date
2011
Start Page
S35
End Page
S36
DOI
10.1016/j.ymgme.2010.11.120

SUPPORTIVE CARE

Authors
Tewari, P; Allison, J; Waters-Pick, B; Cash, JV; Kurtzberg, J; Prasad, VK
MLA Citation
Tewari, P, Allison, J, Waters-Pick, B, Cash, JV, Kurtzberg, J, and Prasad, VK. "SUPPORTIVE CARE." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S272
End Page
S272
DOI
10.1016/j.bbmt.2010.12.360

Folic acid supplementation before and during pregnancy in the Newborn Epigenetics STudy (NEST).

BACKGROUND: Folic acid (FA) added to foods during fortification is 70-85% bioavailable compared to 50% of folate occurring naturally in foods. Thus, if FA supplements also are taken during pregnancy, both mother and fetus can be exposed to FA exceeding the Institute of Medicine's recommended tolerable upper limit (TUL) of 1,000 micrograms per day (μg/d) for adult pregnant women. The primary objective is to estimate the proportion of women taking folic acid (FA) doses exceeding the TUL before and during pregnancy, and to identify correlates of high FA use. METHODS: During 2005-2008, pre-pregnancy and pregnancy-related data on dietary supplementation were obtained by interviewing 539 pregnant women enrolled at two obstetrics-care facilities in Durham County, North Carolina. RESULTS: Before pregnancy, 51% of women reported FA supplementation and 66% reported this supplementation during pregnancy. Before pregnancy, 11.9% (95% CI = 9.2%-14.6%) of women reported supplementation with FA doses above the TUL of 1,000 μg/day, and a similar proportion reported this intake prenatally. Before pregnancy, Caucasian women were more likely to take FA doses above the TUL (OR = 2.99; 95% = 1.28-7.00), compared to African American women, while women with chronic conditions were less likely to take FA doses above the TUL (OR = 0.48; 95%CI = 0.21-0.97). Compared to African American women, Caucasian women were also more likely to report FA intake in doses exceeding the TUL during pregnancy (OR = 5.09; 95%CI = 2.07-12.49). CONCLUSIONS: Fifty-one percent of women reported some FA intake before and 66% during pregnancy, respectively, and more than one in ten women took FA supplements in doses that exceeded the TUL. Caucasian women were more likely to report high FA intake. A study is ongoing to identify possible genetic and non-genotoxic effects of these high doses.

Authors
Hoyo, C; Murtha, AP; Schildkraut, JM; Forman, MR; Calingaert, B; Demark-Wahnefried, W; Kurtzberg, J; Jirtle, RL; Murphy, SK
MLA Citation
Hoyo, C, Murtha, AP, Schildkraut, JM, Forman, MR, Calingaert, B, Demark-Wahnefried, W, Kurtzberg, J, Jirtle, RL, and Murphy, SK. "Folic acid supplementation before and during pregnancy in the Newborn Epigenetics STudy (NEST). (Published online)" BMC Public Health 11.1 (January 21, 2011): 46-.
PMID
21255390
Source
pubmed
Published In
BMC Public Health
Volume
11
Issue
1
Publish Date
2011
Start Page
46
DOI
10.1186/1471-2458-11-46

Influence of nucleated cell dose on overall survival of unrelated cord blood transplantation for patients with severe acquired aplastic anemia: a study by eurocord and the aplastic anemia working party of the European group for blood and marrow transplantation.

Information is scarce on outcomes after unrelated cord blood transplantation (UCBT) for patients with severe aplastic anemia (SAA). We retrospectively analyzed 71 patients (median age, 13 years; 28 adults) with SAA (9 with paroxysmal nocturnal hemoglobinuria [PNH]) who received a single-unit (n = 57; 79%) or double-unit UCBT (n = 14; 19%) in 32 centers between 1996 and 2009. A reduced-intensity conditioning regimen was provided in 68% of the patients. The cumulative incidence (CI) of neutrophil recovery was 51% ± 6% at day 60, with significantly better engraftment seen in recipients of higher prefreezing total nucleated cell (TNC) dose (>3.9 10(7)/kg; hazard ratio [HR], 1.5; P = .05). The CI of platelet engraftment at day 180 posttransplantation was 37% ± 7%, that of grade II-IV acute GVHD was 20% ± 5%, and that of chronic GVHD at 3 years was 18% ± 5%. At a median follow-up of 35 months (range, 3-83 months), the estimated probability of 3-year overall survival (OS) was 38% ± 6%. Significantly improved OS was seen in recipients of >3.9 10(7) TNCs/kg prefreezing (45%, compared with 18% for recipients of ≤ 3.9 10(7) TNC/kg; HR, 0.4; P = .007). These results highlight the fundamental role of cell dose for both engraftment and OS in patients with SAA undergoing UCBT.

Authors
Peffault de Latour, R; Purtill, D; Ruggeri, A; Sanz, G; Michel, G; Gandemer, V; Maury, S; Kurtzberg, J; Bonfim, C; Aljurf, M; Gluckman, E; Socié, G; Passweg, J; Rocha, V
MLA Citation
Peffault de Latour, R, Purtill, D, Ruggeri, A, Sanz, G, Michel, G, Gandemer, V, Maury, S, Kurtzberg, J, Bonfim, C, Aljurf, M, Gluckman, E, Socié, G, Passweg, J, and Rocha, V. "Influence of nucleated cell dose on overall survival of unrelated cord blood transplantation for patients with severe acquired aplastic anemia: a study by eurocord and the aplastic anemia working party of the European group for blood and marrow transplantation." Biol Blood Marrow Transplant 17.1 (January 2011): 78-85.
PMID
20561593
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
1
Publish Date
2011
Start Page
78
End Page
85
DOI
10.1016/j.bbmt.2010.06.011

Influence of nucleated cell dose on overall survival of unrelated cord blood transplantation for patients with severe acquired aplastic anemia: A study by eurocord and the aplastic anemia working party of the european group for blood and marrow transplantation

Information is scarce on outcomes after unrelated cord blood transplantation (UCBT) for patients with severe aplastic anemia (SAA). We retrospectively analyzed 71 patients (median age, 13 years; 28 adults) with SAA (9 with paroxysmal nocturnal hemoglobinuria [PNH]) who received a single-unit (n = 57; 79%) or double-unit UCBT (n = 14; 19%) in 32 centers between 1996 and 2009. A reduced-intensity conditioning regimen was provided in 68% of the patients. The cumulative incidence (CI) of neutrophil recovery was 51%6 6% at day 60, with significantly better engraftment seen in recipients of higher prefreezing total nucleated cell (TNC) dose (>3.9 10 7/kg; hazard ratio [HR], 1.5; P5.05). The CI of platelet engraftment at day 180 posttransplantation was 37%±67%, that of grade II-IV acuteGVHD was 20%±65%, and that of chronic GVHD at 3 years was 18%±65%. At a median follow-up of 35 months (range, 3-83 months), the estimated probability of 3-year overall survival (OS) was 38% 6 6%. Significantly improved OS was seen in recipients of ≤3.9 10 7 TNCs/kg prefreezing (45%, compared with 18% for recipients of #3.9 107 TNC/kg; HR, 0.4; P 5 .007). These results highlight the fundamental role of cell dose for both engraftment and OS in patients with SAA undergoing UCBT. © 2011 American Society for Blood and Marrow Transplantation.

Authors
Latour, RPD; Purtill, D; Ruggeri, A; Sanz, G; Michel, G; Gandemer, V; Maury, S; Kurtzberg, J; Bonfim, C; Aljurf, M; Gluckman, E; Socié, G; Passweg, J; Rocha, V
MLA Citation
Latour, RPD, Purtill, D, Ruggeri, A, Sanz, G, Michel, G, Gandemer, V, Maury, S, Kurtzberg, J, Bonfim, C, Aljurf, M, Gluckman, E, Socié, G, Passweg, J, and Rocha, V. "Influence of nucleated cell dose on overall survival of unrelated cord blood transplantation for patients with severe acquired aplastic anemia: A study by eurocord and the aplastic anemia working party of the european group for blood and marrow transplantation." Biology of Blood and Marrow Transplantation 17.1 (2011): 78-85.
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
1
Publish Date
2011
Start Page
78
End Page
85
DOI
10.1016/j.bbmt.2010.06.011

Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation.

Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P = .09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and overall survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803.

Authors
Wingard, JR; Carter, SL; Walsh, TJ; Kurtzberg, J; Small, TN; Baden, LR; Gersten, ID; Mendizabal, AM; Leather, HL; Confer, DL; Maziarz, RT; Stadtmauer, EA; Bolaños-Meade, J; Brown, J; Dipersio, JF; Boeckh, M; Marr, KA; Blood and Marrow Transplant Clinical Trials Network,
MLA Citation
Wingard, JR, Carter, SL, Walsh, TJ, Kurtzberg, J, Small, TN, Baden, LR, Gersten, ID, Mendizabal, AM, Leather, HL, Confer, DL, Maziarz, RT, Stadtmauer, EA, Bolaños-Meade, J, Brown, J, Dipersio, JF, Boeckh, M, Marr, KA, and Blood and Marrow Transplant Clinical Trials Network, . "Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation." Blood 116.24 (December 9, 2010): 5111-5118.
PMID
20826719
Source
pubmed
Published In
Blood
Volume
116
Issue
24
Publish Date
2010
Start Page
5111
End Page
5118
DOI
10.1182/blood-2010-02-268151

Clinical outcome of cerebrospinal fluid shunting for communicating hydrocephalus in mucopolysaccharidoses I, II, and III: a retrospective analysis of 13 patients.

BACKGROUND: Intracranial pathology is a well-documented feature of mucopolysaccharidoses (MPSs), including communicating hydrocephalus (CH). Neither the success nor the complications of cerebrospinal fluid shunting in MPS patients have been well documented. OBJECTIVE: To retrospectively analyze 13 children with communicating hydrocephalus and MPS at our institution between 1998 and 2006. METHODS: Thirteen patients diagnosed with MPS I, II, or III presenting for stem cell transplantation were retrospectively analyzed. Patients underwent a rigorous pretransplantation workup, including magnetic resonance imaging of the brain. If imaging revealed ventriculomegaly, a lumbar puncture was performed. If intracranial pressure was >20 cm H20 or the patient demonstrated clinical signs of hydrocephalus or evidence of clinical decline with increasing ventricular size on imaging, a ventriculoperitoneal shunt (VPS) was placed. Clinical outcomes were analyzed after dividing the patients into 2 groups: patients who underwent VPS before (group A) and after (Group B) stem cell transplantation. RESULTS: There were 8 patients in group A and 5 in group B. Group B patients developed more severe complications, including 2 patients who required VPS early after transplantation, one who died secondary to intracerebral hemorrhage and another who developed a subdural empyema. Of the 8 patients in group A, 5 had complications, including 2 shunt infections, a punctate intracerebral hematoma, shunt tube migration, and 3 shunt failures. CONCLUSION: This is the largest review of MPS patients with communicating hydrocephalus. It demonstrates that VPS is an effective treatment. MPS patients need to be evaluated for hydrocephalus before stem cell transplantation because pretransplantation shunting appears to have the most favorable risk/benefit ratio.

Authors
Aliabadi, H; Reynolds, R; Powers, CJ; Grant, G; Fuchs, H; Kurtzberg, J
MLA Citation
Aliabadi, H, Reynolds, R, Powers, CJ, Grant, G, Fuchs, H, and Kurtzberg, J. "Clinical outcome of cerebrospinal fluid shunting for communicating hydrocephalus in mucopolysaccharidoses I, II, and III: a retrospective analysis of 13 patients." Neurosurgery 67.6 (December 2010): 1476-1481.
PMID
21107178
Source
pubmed
Published In
Neurosurgery
Volume
67
Issue
6
Publish Date
2010
Start Page
1476
End Page
1481
DOI
10.1227/NEU.0b013e3181f8c11d

Analysis of Risk Factors Influencing Outcomes After Unrelated Cord Blood Transplantation In Children with Juvenile Myelomonocytic Leukemia. An Eurocord, EBMT, EWOG-MDS, CIBMTR Study

Authors
Crotta, A; Rocha, V; Eapen, M; Wagner, JE; MacMillan, ML; Zecca, M; Kurtzberg, J; Bonfim, C; Vora, AJ; Diaz de Heredia, C; Mohty, M; Teague, L; Stein, J; O'Brien, TA; Bittencourt, H; Madureira, ABM; Peters, C; Niemeyer, CM; Gluckman, E; Locatelli, F
MLA Citation
Crotta, A, Rocha, V, Eapen, M, Wagner, JE, MacMillan, ML, Zecca, M, Kurtzberg, J, Bonfim, C, Vora, AJ, Diaz de Heredia, C, Mohty, M, Teague, L, Stein, J, O'Brien, TA, Bittencourt, H, Madureira, ABM, Peters, C, Niemeyer, CM, Gluckman, E, and Locatelli, F. "Analysis of Risk Factors Influencing Outcomes After Unrelated Cord Blood Transplantation In Children with Juvenile Myelomonocytic Leukemia. An Eurocord, EBMT, EWOG-MDS, CIBMTR Study." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
237
End Page
238

Relationship of Race/Ethnicity and Survival After Single Umbilical Cord Blood Transplantation

Authors
Ballen, KK; Klein, JP; Pedersen, TL; Kurtzberg, J; Lazarus, HM; LeMaistre, CF; Mehta, P; Palmer, J; Setterholm, M; Wingard, JR; Joffe, S; Parsons, SK; Switzer, GE; Lee, SJ; Rizzo, JD; Majhail, NS; CIBMTR, HPWC
MLA Citation
Ballen, KK, Klein, JP, Pedersen, TL, Kurtzberg, J, Lazarus, HM, LeMaistre, CF, Mehta, P, Palmer, J, Setterholm, M, Wingard, JR, Joffe, S, Parsons, SK, Switzer, GE, Lee, SJ, Rizzo, JD, Majhail, NS, and CIBMTR, HPWC. "Relationship of Race/Ethnicity and Survival After Single Umbilical Cord Blood Transplantation." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
104
End Page
105

Chronic Graft-Versus-Host Disease and Its Association with Treatment-Related Mortality, Relapse, Leukemia-Free and Overall Survival After Umbilical Cord Blood Transplantation (UCBT) In Children and Adolescents with Acute Leukemia

Authors
Eapen, M; Wang, T; Kurtzberg, J; Lee, SJ; Duerst, R; Arora, M; Bonfim, C; Duval, M; Eames, G; Tiedemann, K; Weisdorf, DJ; Wagner, JE
MLA Citation
Eapen, M, Wang, T, Kurtzberg, J, Lee, SJ, Duerst, R, Arora, M, Bonfim, C, Duval, M, Eames, G, Tiedemann, K, Weisdorf, DJ, and Wagner, JE. "Chronic Graft-Versus-Host Disease and Its Association with Treatment-Related Mortality, Relapse, Leukemia-Free and Overall Survival After Umbilical Cord Blood Transplantation (UCBT) In Children and Adolescents with Acute Leukemia." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
98
End Page
99

Validation of the Cord Blood (CB) APGAR Score System to Predict Neutrophil Engraftment of Plasma Depleted CB Products

Authors
Chow, R; Wang, BC; Chou, D; Lin, A; Kang, J; Chow, M; Petz, LD; Kurtzberg, J
MLA Citation
Chow, R, Wang, BC, Chou, D, Lin, A, Kang, J, Chow, M, Petz, LD, and Kurtzberg, J. "Validation of the Cord Blood (CB) APGAR Score System to Predict Neutrophil Engraftment of Plasma Depleted CB Products." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1459
End Page
1460

Reduced Intensity Conditioning In Children Undergoing Unrelated Umbilical Cord Blood Transplantation for Non-Malignant Diseases: Preliminary Results Demonstrate a High Rate of Engraftment and Low Incidence of Gvhd.

Authors
Parikh, SH; Martin, PL; Driscoll, TA; Baker, J; Piersol, K; Moffet, J; Stokhuyzen, A; Kurtzberg, J; Szabolcs, P
MLA Citation
Parikh, SH, Martin, PL, Driscoll, TA, Baker, J, Piersol, K, Moffet, J, Stokhuyzen, A, Kurtzberg, J, and Szabolcs, P. "Reduced Intensity Conditioning In Children Undergoing Unrelated Umbilical Cord Blood Transplantation for Non-Malignant Diseases: Preliminary Results Demonstrate a High Rate of Engraftment and Low Incidence of Gvhd." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1453
End Page
1454

A Novel Scoring System, the Cord Blood Apgar, Predicts Engraftment After Cord Blood Transplantation: Optimization of Selection of Cord Blood Units (CBUs) for Transplantation

Authors
Page, KM; Zhang, L; Mendizabal, AM; Gentry, T; Balber, A; Kurtzberg, J
MLA Citation
Page, KM, Zhang, L, Mendizabal, AM, Gentry, T, Balber, A, and Kurtzberg, J. "A Novel Scoring System, the Cord Blood Apgar, Predicts Engraftment After Cord Blood Transplantation: Optimization of Selection of Cord Blood Units (CBUs) for Transplantation." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
158
End Page
158

Differences in quality between privately and publicly banked umbilical cord blood units: a pilot study of autologous cord blood infusion in children with acquired neurologic disorders.

BACKGROUND: A pilot study was conducted to determine the safety and feasibility of intravenous administration of autologous umbilical cord blood (CB) in young children with acquired neurologic disorders. Most CB units (CBUs) were electively stored in private CB banks. Unlike public banks, which utilize specific criteria and thresholds for banking, private banks generally store all collected CBUs. STUDY DESIGN AND METHODS: CBUs of eligible patients containing more than 1 × 10⁷ cells/kg were shipped to Duke from the banks of origin after confirming identity by HLA typing. On the day of infusion, CBUs were thawed and washed in dextran-albumin and infused intravenously. Patients were medicated with acetaminophen, diphenhydramine, and methylprednisolone before transfusion. Data regarding patients, infusions, and CBUs were collected retrospectively. Characteristics of CBUs were compared to existing data from CBUs publicly banked at the Carolinas Cord Blood Bank. RESULTS: From March 2004 to December 2009, 184 children received 198 CB infusions. Three patients had infusion reactions, all responsive to medical therapy and stopping the infusion. Median precryopreservation volume (60 mL vs. 89 mL, p < 0.0001), total nucleated cell count (4.7 × 10⁸ vs. 10.8 × 10⁸, p < 0.0001), and CD34 count (1.8 × 10⁶ vs. 3.0 × 10⁶, p < 0.0001) were significantly lower than publicly stored CBUs. Postthaw sterility cultures were positive in 7.6% of infused CBUs. CONCLUSION: IV infusion of autologous CB is safe and feasible in young children with neurologic injuries. Quality parameters of privately banked CBUs are inferior to those stored in public banks. If efficacy of autologous CB is established clinically, the quality of autologous units should be held to the same standards as those stored in public banks.

Authors
Sun, J; Allison, J; McLaughlin, C; Sledge, L; Waters-Pick, B; Wease, S; Kurtzberg, J
MLA Citation
Sun, J, Allison, J, McLaughlin, C, Sledge, L, Waters-Pick, B, Wease, S, and Kurtzberg, J. "Differences in quality between privately and publicly banked umbilical cord blood units: a pilot study of autologous cord blood infusion in children with acquired neurologic disorders." Transfusion 50.9 (September 2010): 1980-1987.
PMID
20546200
Source
pubmed
Published In
Transfusion
Volume
50
Issue
9
Publish Date
2010
Start Page
1980
End Page
1987
DOI
10.1111/j.1537-2995.2010.02720.x

Donor cell leukemia in umbilical cord blood transplant patients: a case study and literature review highlighting the importance of molecular engraftment analysis.

Donor cell neoplasms are rare complications of treatment regimens that involve stem cell transplantation for hematological malignancies, myelodysplastic processes, or certain genetic or metabolic disorders. We report a case of donor cell leukemia in a pediatric patient with a history of acute myeloid leukemia that manifested as recurrent AML FAB type M5 fourteen months after umbilical cord blood transplantation. Although there was some immunophenotypic drift from the patient's original AML and their posttransplant presentation, the initial pathological impression was of recurrent disease. Bone marrow engraftment analysis by multiplex PCR of short tandem repeat markers performed on the patient's diagnostic specimen showed complete engraftment by donor cells, with a loss of heterozygosity in the donor alleles on chromosome 7. This led to the reinterpretation of this patient's disease as donor-derived leukemia. This interpretation was supported by a routine karyotype and fluorescence in situ hybridization analysis showing loss of chromosome 7 and a male (donor) chromosome complement in this female patient. Also noted was a loss of the patient's presenting chromosomal abnormality, t(11;19)(q23;p13). This case highlights the need for close coordination between all aspects of clinical testing for the transplant patient, including molecular engraftment studies, when distinguishing the very common complication of recurrent disease from the exceedingly rare complication of donor cell leukemia.

Authors
Crow, J; Youens, K; Michalowski, S; Perrine, G; Emhart, C; Johnson, F; Gerling, A; Kurtzberg, J; Goodman, BK; Sebastian, S; Rehder, CW; Datto, MB
MLA Citation
Crow, J, Youens, K, Michalowski, S, Perrine, G, Emhart, C, Johnson, F, Gerling, A, Kurtzberg, J, Goodman, BK, Sebastian, S, Rehder, CW, and Datto, MB. "Donor cell leukemia in umbilical cord blood transplant patients: a case study and literature review highlighting the importance of molecular engraftment analysis." J Mol Diagn 12.4 (July 2010): 530-537. (Review)
PMID
20431036
Source
pubmed
Published In
The Journal of molecular diagnostics : JMD
Volume
12
Issue
4
Publish Date
2010
Start Page
530
End Page
537
DOI
10.2353/jmoldx.2010.090215

Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial.

Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for > or =14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day +100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day +100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD.

Authors
Richardson, PG; Soiffer, RJ; Antin, JH; Uno, H; Jin, Z; Kurtzberg, J; Martin, PL; Steinbach, G; Murray, KF; Vogelsang, GB; Chen, AR; Krishnan, A; Kernan, NA; Avigan, DE; Spitzer, TR; Shulman, HM; Di Salvo, DN; Revta, C; Warren, D; Momtaz, P; Bradwin, G; Wei, LJ; Iacobelli, M; McDonald, GB; Guinan, EC
MLA Citation
Richardson, PG, Soiffer, RJ, Antin, JH, Uno, H, Jin, Z, Kurtzberg, J, Martin, PL, Steinbach, G, Murray, KF, Vogelsang, GB, Chen, AR, Krishnan, A, Kernan, NA, Avigan, DE, Spitzer, TR, Shulman, HM, Di Salvo, DN, Revta, C, Warren, D, Momtaz, P, Bradwin, G, Wei, LJ, Iacobelli, M, McDonald, GB, and Guinan, EC. "Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial." Biol Blood Marrow Transplant 16.7 (July 2010): 1005-1017.
PMID
20167278
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
16
Issue
7
Publish Date
2010
Start Page
1005
End Page
1017
DOI
10.1016/j.bbmt.2010.02.009

Inefficient dystrophin expression after cord blood transplantation in Duchenne muscular dystrophy.

We report a boy who received two allogeneic stem cell transplantations from umbilical cord donors to treat chronic granulomatous disease (CGD). The CGD was cured after the second transplantation, but 2.5 years later he was diagnosed with Duchenne muscular dystrophy (DMD). Examinations of his DNA, muscle tissue, and myoblast cultures derived from muscle tissue were performed to determine whether any donor dystrophin was being expressed. The boy was found to have a large-scale deletion on the X chromosome that spanned the loci for CYBB and DMD. The absence of dystrophin led to muscle histology characteristic of DMD. Analysis of myofibers demonstrated no definite donor cell engraftment. This case suggests that umbilical cord-derived hematopoietic stem cell transplantation will not be efficacious in the therapy of DMD without additional interventions that induce engraftment of donor cells in skeletal muscle.

Authors
Kang, PB; Lidov, HGW; White, AJ; Mitchell, M; Balasubramanian, A; Estrella, E; Bennett, RR; Darras, BT; Shapiro, FD; Bambach, BJ; Kurtzberg, J; Gussoni, E; Kunkel, LM
MLA Citation
Kang, PB, Lidov, HGW, White, AJ, Mitchell, M, Balasubramanian, A, Estrella, E, Bennett, RR, Darras, BT, Shapiro, FD, Bambach, BJ, Kurtzberg, J, Gussoni, E, and Kunkel, LM. "Inefficient dystrophin expression after cord blood transplantation in Duchenne muscular dystrophy." Muscle Nerve 41.6 (June 2010): 746-750.
PMID
20513101
Source
pubmed
Published In
Muscle and Nerve
Volume
41
Issue
6
Publish Date
2010
Start Page
746
End Page
750
DOI
10.1002/mus.21702

Splenectomy and partial splenectomy improve hematopoietic stem cell engraftment in hypersplenic mice.

BACKGROUND: Hematopoietic stem cell (HSC) engraftment is delayed after transplantation in children with hypersplenism, increasing the morbidity and costs of care. Preliminary clinical data suggest that splenectomy before HSC transplantation may improve HSC engraftment, although this observation has not been tested in an animal model. METHODS: We performed total splenectomy (n = 22), partial splenectomy (n = 16), or sham laparotomy (n = 21) on erythrocyte protein 4.2 knockout mice, a murine model of hereditary spherocytosis with hypersplenism. After 10 days, we lethally irradiated the mice, transplanted 3 x 10(6) allogeneic bone marrow cells, and then assessed engraftment using serial complete blood counts. Successful engraftment was defined as recovery of hemoglobin, neutrophil, or platelet counts. We compared engraftment rate using chi(2) test and time to engraftment using Student's t test analysis, with significance defined as P < .05. RESULTS: Total splenectomy increased the rate of successful HSC engraftment and decreased the interval to HSC engraftment compared with controls. Similarly, partial splenectomy decreased the interval to HSC engraftment, with a nonsignificant trend toward improved overall rate of successful HSC engraftment. CONCLUSION: Partial or total splenectomy before HSC transplantation improves HSC engraftment in hypersplenic mice. This model supports consideration of splenic resection in hypersplenic children requiring HSC transplantation.

Authors
Tracy, ET; Talbot, LJ; Kurtzberg, J; Rice, HE
MLA Citation
Tracy, ET, Talbot, LJ, Kurtzberg, J, and Rice, HE. "Splenectomy and partial splenectomy improve hematopoietic stem cell engraftment in hypersplenic mice." J Pediatr Surg 45.6 (June 2010): 1365-1369.
PMID
20620346
Source
pubmed
Published In
Journal of Pediatric Surgery
Volume
45
Issue
6
Publish Date
2010
Start Page
1365
End Page
1369
DOI
10.1016/j.jpedsurg.2010.02.114

OUTCOMES OF UNRELATED CORD BLOOD TRANSPLANT IN PATIENTS WITH HEMOGLOBINOPATHIES

Authors
Ruggeri, A; Eapen, M; Scaradavou, A; Purtill, D; Cairo, M; Bhatia, M; Kurtzberg, J; Wagner, J; Fasth, A; Lo Nigro, L; Chaves, W; Walters, M; Gluckman, E; Rocha, V
MLA Citation
Ruggeri, A, Eapen, M, Scaradavou, A, Purtill, D, Cairo, M, Bhatia, M, Kurtzberg, J, Wagner, J, Fasth, A, Lo Nigro, L, Chaves, W, Walters, M, Gluckman, E, and Rocha, V. "OUTCOMES OF UNRELATED CORD BLOOD TRANSPLANT IN PATIENTS WITH HEMOGLOBINOPATHIES." June 2010.
Source
wos-lite
Published In
Haematologica
Volume
95
Publish Date
2010
Start Page
246
End Page
246

Stem cell transplantation rare genetic disease consortium for allogeneic transplantation in RDEB

Authors
Christiano, A; McGrath, I; Paller, A; Arbuckle, A; Norris, D; Roop, D; Hall, R; Prose, N; Morel, K; Geyer, M; Morris, E; Baxter-Lowe, L; Kurtzberg, J; Chaudhary, S; Giller, R; Shah, A; Ishida-Yamamoto, A; Keene, D; Uitto, J; Chen, M; Woodley, D; Cairo, M
MLA Citation
Christiano, A, McGrath, I, Paller, A, Arbuckle, A, Norris, D, Roop, D, Hall, R, Prose, N, Morel, K, Geyer, M, Morris, E, Baxter-Lowe, L, Kurtzberg, J, Chaudhary, S, Giller, R, Shah, A, Ishida-Yamamoto, A, Keene, D, Uitto, J, Chen, M, Woodley, D, and Cairo, M. "Stem cell transplantation rare genetic disease consortium for allogeneic transplantation in RDEB." April 2010.
Source
wos-lite
Published In
Journal of Investigative Dermatology
Volume
130
Publish Date
2010
Start Page
S57
End Page
S57

Treatment of steroid-refractory acute GvHD with mesenchymal stem cells improves outcomes in paediatric patients. Results of the paediatric subset in a phase III randomized, placebo-controlled study

Authors
Szabolcs, P; Visani, G; Locatelli, F; Kleiner, G; Talano, J; Nemecek, ER; Kurtzberg, J
MLA Citation
Szabolcs, P, Visani, G, Locatelli, F, Kleiner, G, Talano, J, Nemecek, ER, and Kurtzberg, J. "Treatment of steroid-refractory acute GvHD with mesenchymal stem cells improves outcomes in paediatric patients. Results of the paediatric subset in a phase III randomized, placebo-controlled study." March 2010.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
45
Publish Date
2010
Start Page
S18
End Page
S18

Allogeneic haematopoietic stem cell transplantation in patients with alpha-mannosidosis: analysis of 13 patients

Authors
Mynarek, M; Tolar, J; Albert, M; Boelens, JJ; Cowan, MJ; Escolar, ML; Glomstein, A; Kuehl, JS; Malm, D; Orchard, PJ; Luecke, T; Kurtzberg, J; Sykora, KW
MLA Citation
Mynarek, M, Tolar, J, Albert, M, Boelens, JJ, Cowan, MJ, Escolar, ML, Glomstein, A, Kuehl, JS, Malm, D, Orchard, PJ, Luecke, T, Kurtzberg, J, and Sykora, KW. "Allogeneic haematopoietic stem cell transplantation in patients with alpha-mannosidosis: analysis of 13 patients." March 2010.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
45
Publish Date
2010
Start Page
S313
End Page
S313

Survey of outcomes of unrelated cord blood transplant in patients with haemoglobinopathies: a retrospective study on behalf of CIBMTR, NYCB and EUROCORD

Authors
Ruggeri, A; Eapen, M; Scaravadou, A; Purtill, D; Cairo, M; Bhatia, M; Kurtzberg, J; Wagner, J; Fasth, A; Chaves, W; Walters, M; Gluckman, E; Rocha, V
MLA Citation
Ruggeri, A, Eapen, M, Scaravadou, A, Purtill, D, Cairo, M, Bhatia, M, Kurtzberg, J, Wagner, J, Fasth, A, Chaves, W, Walters, M, Gluckman, E, and Rocha, V. "Survey of outcomes of unrelated cord blood transplant in patients with haemoglobinopathies: a retrospective study on behalf of CIBMTR, NYCB and EUROCORD." March 2010.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
45
Publish Date
2010
Start Page
S73
End Page
S73

Allogeneic human mesenchymal stem cell therapy (Prochymal (R)) as a rescue agent for severe treatment resistant GvHD in paediatric patients

Authors
Kurtzberg, J; Prasad, V; Grimley, MS; Horn, B; Carpenter, PA; Jacobsohn, D; Prockop, S
MLA Citation
Kurtzberg, J, Prasad, V, Grimley, MS, Horn, B, Carpenter, PA, Jacobsohn, D, and Prockop, S. "Allogeneic human mesenchymal stem cell therapy (Prochymal (R)) as a rescue agent for severe treatment resistant GvHD in paediatric patients." March 2010.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
45
Publish Date
2010
Start Page
S125
End Page
S125

Stem cell source and outcome after hematopoietic stem cell transplantation (HSCT) in children and adolescents with acute leukemia.

Allogeneic hematopoietic stem cell transplantation from siblings, unrelated donors or HLA mismatched family members has become an important procedure to offer a chance of cure to children and adolescents with acute leukemia at high risk of relapse and those with certain genetic diseases. Bone marrow (BM) was the only stem cell source for many years. During the past 15 years, peripheral blood stem cells from granulocyte colony-stimulating factor (G-CSF) mobilized healthy donors, or umbilical cord blood from related or unrelated donors, have become available. Each stem cell source has different risks/benefits for patients and donors, the choice depending not only on availability, but also on HLA compatibility and urgency of the HSCT. This review will analyze the advantages and limitations of each of these options, and the main criteria which can be applied when choosing the appropriate stem cell source for pediatric transplant recipients with acute leukemia.

Authors
Peters, C; Cornish, JM; Parikh, SH; Kurtzberg, J
MLA Citation
Peters, C, Cornish, JM, Parikh, SH, and Kurtzberg, J. "Stem cell source and outcome after hematopoietic stem cell transplantation (HSCT) in children and adolescents with acute leukemia." Pediatr Clin North Am 57.1 (February 2010): 27-46. (Review)
PMID
20307710
Source
pubmed
Published In
Pediatric Clinics of North America
Volume
57
Issue
1
Publish Date
2010
Start Page
27
End Page
46
DOI
10.1016/j.pcl.2010.01.004

Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directions.

Progressive degeneration of the central nervous system leading to the loss of neuromotor, neurophysiological and cognitive abilities is the fundamental clinical problem in patients with many inherited metabolic diseases (IMD). Worldwide experience shows that morbidity, quality of life, and survival in these patients can be improved by allogeneic haematopoietic stem cell transplantation (HSCT), particularly when performed early in the course of the disease. At present, while available for some conditions, exogenous enzyme replacement therapy is unable to correct cognitive and central nervous system disease because of its inability to cross the blood-brain barrier. In contrast, HSCT allows donor-derived, enzyme-producing cells to migrate to the brain and other organs providing a permanent enzyme replacement therapy. HSCT may also mediate non-hematopoietic cell regeneration or repair. Traditionally, bone marrow has been the graft source for IMD patients. However, in the last 5 years many studies utilizing unrelated donor umbilical cord blood (UCB) as a graft source have demonstrated that UCB provides rapid and increased access to transplantation with favourable outcomes. This review describes preclinical studies and past and present clinical treatment approaches and discusses current controversies and future directions of this promising field.

Authors
Prasad, VK; Kurtzberg, J
MLA Citation
Prasad, VK, and Kurtzberg, J. "Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directions." Br J Haematol 148.3 (February 2010): 356-372. (Review)
PMID
19919654
Source
pubmed
Published In
British Journal of Haematology
Volume
148
Issue
3
Publish Date
2010
Start Page
356
End Page
372
DOI
10.1111/j.1365-2141.2009.07974.x

Umbilical cord blood transplantation

© Cambridge University Press 2013.Overview. Over the past several decades, hematopoietic stem cell transplantation has emerged as an effective approach to curative therapy for both pediatric and adult patients with aggressive or recurrent malignancies, congenital immunodeficiency diseases, some genetic diseases, including inborn errors of metabolism and hemoglobinopathies, and congenital and acquired bone marrow failure syndromes. Traditionally, autologous or allogeneic stem and progenitor cells have been obtained from bone marrow or mobilized peripheral blood. More recently, banked umbilical cord blood (UCB) has emerged as an alternative source of stem and progenitor cells for transplantation. Cord blood is readily available and can be transplanted across partially mismatched human leukocyte antigen (HLA) barriers, increasing the availability of allogeneic stem cell donors for patients lacking traditional HLA-matched related and unrelated donors. Additional applications of stem cell therapies envisioned in the next decade, including regenerative therapies for non-hematopoietic tissues damaged by injury or disease are currently unproven and the subject of ongoing preclinical and clinical research. A major limitation to stem cell transplantation therapy is donor availability. Only 20%-25% of patients in need of a transplant will have an HLA-matched relative who can serve as their donor. Of those lacking a related donor, approximately 25% of Caucasian patients will identify an HLA-matched unrelated living bone-marrow donor through the National Marrow Donor Program and other donor registries, but less than 10% of patients of ethnic minority backgrounds will find a suitably matched unrelated marrow donor. For the remaining patients, a fully matched unrelated stem cell donor cannot be identified.

Authors
Sun, JM; Kurtzberg, J
MLA Citation
Sun, JM, and Kurtzberg, J. "Umbilical cord blood transplantation." Neonatal Hematology: Pathogenesis, Diagnosis, and Management of Hematologic Problems, Second Edition. January 1, 2010. 328-336.
Source
scopus
Publish Date
2010
Start Page
328
End Page
336
DOI
10.1017/CBO9780511978135.021

Transplant outcomes in mucopolysaccharidoses.

The mucopolysaccharidoses (MPSs) are inherited metabolic disorders (IMDs) caused by single-gene defects leading to progressive cellular accumulation of glycosaminoglycans (GAGs) and damage to multiple organs, including the central nervous, musculoskeletal, cardiorespiratory, and other systems. Hurler syndrome (MPS IH), the most severe form, is the prototypical model. Enzyme replacement therapy (ERT), available for MPS I, II, and VI, is beneficial in some patients. However, ERT does not improve neurocognitive function because of its inability to cross the blood-brain barrier. In contrast, allogeneic hematopoietic stem cell transplantation (HSCT) allows donor-derived, enzyme-producing cells to migrate to the brain and other organs to provide permanent enzyme therapy and thus help somatic organs, improve neurocognitive function and quality of life, and prolong survival, particularly when performed early in the course of the disease. Bone marrow has been the graft source in the past. However, in the last 5 years many patients have been treated with unrelated donor (URD) umbilical cord blood transplant (UCBT), allowing rapid and increased access to transplantation with favorable outcomes. This review describes published and our institutional clinical experiences, discusses the current status of the field, and provides therapy guidelines for patients with MPS.

Authors
Prasad, VK; Kurtzberg, J
MLA Citation
Prasad, VK, and Kurtzberg, J. "Transplant outcomes in mucopolysaccharidoses." Semin Hematol 47.1 (January 2010): 59-69. (Review)
PMID
20109613
Source
pubmed
Published In
Seminars in Hematology
Volume
47
Issue
1
Publish Date
2010
Start Page
59
End Page
69
DOI
10.1053/j.seminhematol.2009.10.008

Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling

The clinical manifestations of Fanconi's anemia, an autosomal recessive disorder, include progressive pancyto-penia, a predisposition to neoplasia, and nonhematopoietic developmental anomalies [1-3]. Hypersensitivity to the clastogenic effect of DNA-cross-linking agents such as diepoxybutane acts as a diagnostic indicator of the genotype of Fanconi's anemia, both prenatally and postnatally [3-6]. Prenatal HLA typing has made it possible to ascertain whether a fetus is HLA-identical to an affected sibling [7]. We report here on hematopoietic reconstitution in a boy with severe Fanconi's anemia who received cryo-pre-served umbilical-cord blood from a sister shown by prenatal testing to be unaffected by the disorder, to have a normal karyotype, and to be HLA-identical to the patient. We used a pretransplantation conditioning procedure developed specifcally for the treatment of such patients [8]; this technique makes use of the hypersensitivity of the abnormal cells to alkylating agents that cross-link DNA [9,10] and to irradiation [11] In this case, the availability of cord blood obviated the need for obtaining bone marrow from the infant sibling. This use of cord blood followed the suggestion of one of us that blood retrieved from umbilical cord at delivery, usually discarded, might restore hematopoiesis - a proposal supported by preparatory studies by some of us [12] and consistent with reports on the presence of hematopoietic stem and multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in human umbilical-cord blood (see the references cited by Broxmeyer et al. [12]). © 1989 Massachusetts Medical Society. All rights reserved.

Authors
Gluckman, E; Broxmeyer, HE; Auerbach, AD; Friedman, HS; Douglas, GW; Devergie, A; Esperou, H; Thierry, D; Socie, G; Lehn, P; Cooper, S; English, D; Kurtzberg, J; Bard, J; Boyse, EA
MLA Citation
Gluckman, E, Broxmeyer, HE, Auerbach, AD, Friedman, HS, Douglas, GW, Devergie, A, Esperou, H, Thierry, D, Socie, G, Lehn, P, Cooper, S, English, D, Kurtzberg, J, Bard, J, and Boyse, EA. "Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling." Cellular Therapy and Transplantation 2.7 (2010).
Source
scival
Published In
Cellular Therapy and Transplantation
Volume
2
Issue
7
Publish Date
2010
DOI
10.3205/ctt-2010-en-000079.01

Epigenetic orchestration of circulating insulin-like growth factor-2 levels in cord blood

Authors
Fortner, K; Murtha, A; Hoyo, C; Overcash, F; Huang, Z; Schildkraut, J; Kurtzberg, J; Jirtle, R; Forman, M; Murphy, S
MLA Citation
Fortner, K, Murtha, A, Hoyo, C, Overcash, F, Huang, Z, Schildkraut, J, Kurtzberg, J, Jirtle, R, Forman, M, and Murphy, S. "Epigenetic orchestration of circulating insulin-like growth factor-2 levels in cord blood." December 2009.
Source
wos-lite
Published In
American Journal of Obstetrics & Gynecology
Volume
201
Issue
6
Publish Date
2009
Start Page
S39
End Page
S39

Impact of Nucleated Cell Dose On Engraftment and Survival After Unrelated Cord Blood Transplantation for Severe Aplastic Anemia: A Retrospective Study On Behalf of Eurocord and the EBMT SAA WP

Authors
de Latour, RP; Purtill, D; Ruggeri, A; Sanz, G; Michel, G; Gandemer, V; Maury, S; Kurtzberg, J; Bonfim, C; Aljurf, M; Gluckman, E; Socie, G; Passweg, JR; Rocha, V
MLA Citation
de Latour, RP, Purtill, D, Ruggeri, A, Sanz, G, Michel, G, Gandemer, V, Maury, S, Kurtzberg, J, Bonfim, C, Aljurf, M, Gluckman, E, Socie, G, Passweg, JR, and Rocha, V. "Impact of Nucleated Cell Dose On Engraftment and Survival After Unrelated Cord Blood Transplantation for Severe Aplastic Anemia: A Retrospective Study On Behalf of Eurocord and the EBMT SAA WP." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1240
End Page
1241

Long-Term Survival and Late Deaths After Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency Diseases and Inborn Errors of Metabolism

Authors
Eapen, M; Ahn, KW; Orchard, P; Cowan, MJ; Davies, SM; Fasth, A; Hassebroek, A; Ayas, MF; Bonfim, C; O'Brien, T; Gross, T; Horowitz, MM; Horwitz, M; Horwitz, EM; Kapoor, N; Kurtzberg, J; Majhail, NS; Ringden, O; Szabolcs, P; Veys, PA; Baker, KS
MLA Citation
Eapen, M, Ahn, KW, Orchard, P, Cowan, MJ, Davies, SM, Fasth, A, Hassebroek, A, Ayas, MF, Bonfim, C, O'Brien, T, Gross, T, Horowitz, MM, Horwitz, M, Horwitz, EM, Kapoor, N, Kurtzberg, J, Majhail, NS, Ringden, O, Szabolcs, P, Veys, PA, and Baker, KS. "Long-Term Survival and Late Deaths After Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency Diseases and Inborn Errors of Metabolism." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1287
End Page
1288

Creation of a Segment-Based Aldehyde Dehydrogenase Assay as a Biomarker for Cord Blood Potency.

Authors
Shoulars, K; Gentry, T; Page, KM; Balber, A; Kurtzberg, J
MLA Citation
Shoulars, K, Gentry, T, Page, KM, Balber, A, and Kurtzberg, J. "Creation of a Segment-Based Aldehyde Dehydrogenase Assay as a Biomarker for Cord Blood Potency." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1246
End Page
1247

Thymic Recovery and De Novo T Cell Production During the First Year After Unrelated Cord Blood Transplant (UCBT) Predicts Overall Survival: A Multivariate Analysis of 93 Patients Following Myeloablative Conditioning and a Single Unit Graft.

Authors
Wilfret, DA; Mendizabal, A; Page, KM; Reese, M; Vinesett, R; Kurtzberg, J; Szabolcs, P
MLA Citation
Wilfret, DA, Mendizabal, A, Page, KM, Reese, M, Vinesett, R, Kurtzberg, J, and Szabolcs, P. "Thymic Recovery and De Novo T Cell Production During the First Year After Unrelated Cord Blood Transplant (UCBT) Predicts Overall Survival: A Multivariate Analysis of 93 Patients Following Myeloablative Conditioning and a Single Unit Graft." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
481
End Page
482

Use of Aldehyde Dehydrogenase Content to Predict Dominating Cord in Double Cord Blood Transplant

Authors
Page, KM; Gentry, T; Shoulars, K; Horwitz, M; Herrmann, N; Meadows, N; Philipps, B; Balber, A; Kurtzberg, J
MLA Citation
Page, KM, Gentry, T, Shoulars, K, Horwitz, M, Herrmann, N, Meadows, N, Philipps, B, Balber, A, and Kurtzberg, J. "Use of Aldehyde Dehydrogenase Content to Predict Dominating Cord in Double Cord Blood Transplant." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
847
End Page
848

Transplantation Following Myeloablative Cytoreduction Results in Excellent Survival, Long-Term Engraftment, and Donor Chimerism in Children with Chronic Granulomatous Disease Across Donor and Graft Sources

Authors
Tewari, P; Wood, S; Martin, PL; Parikh, SH; Szabolcs, P; Page, KM; Driscoll, T; Kurtzberg, J; Prasad, VK
MLA Citation
Tewari, P, Wood, S, Martin, PL, Parikh, SH, Szabolcs, P, Page, KM, Driscoll, T, Kurtzberg, J, and Prasad, VK. "Transplantation Following Myeloablative Cytoreduction Results in Excellent Survival, Long-Term Engraftment, and Donor Chimerism in Children with Chronic Granulomatous Disease Across Donor and Graft Sources." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1319
End Page
1319

ALDH(br) Hematopoietic Progenitors Promote Short-Term Engraftment in Experimental Models for Cord Blood Transplantation.

Authors
Storms, RW; Liu, C; Tracy, ET; Gentry, T; Balber, A; Kurtzberg, J
MLA Citation
Storms, RW, Liu, C, Tracy, ET, Gentry, T, Balber, A, and Kurtzberg, J. "ALDH(br) Hematopoietic Progenitors Promote Short-Term Engraftment in Experimental Models for Cord Blood Transplantation." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
960
End Page
961

Umbilical cord blood transplantation for non-malignant diseases.

Many factors, including lower risk of GVHD, rapid availability of 4/6-6/6 matched cord blood (CB) units and incremental gains in the outcomes, have led to an increasing use of CB transplantation (CBT) to treat many patients who lack fully matched adult BM donors. A large electronically searchable worldwide inventory of publicly banked CB units allows for quicker donor identification and selection. In this review, we examine the current status and cumulative experience of related and unrelated donor CBT for the treatment of non-malignant diseases, including hemoglobinopathies, BM failure syndromes, primary immunodeficiency diseases (PIDs) and inherited metabolic disorders (IMDs), and conclude that CBT offers a promising and effective therapy for these diseases. Future strategies to facilitate earlier diagnosis and to decrease transplant-related risks should further improve the short- and long-term outcomes. Every effort should be made to perform transplantation early in the course of disease before extensive damage to various tissues and organs ensues.

Authors
Prasad, VK; Kurtzberg, J
MLA Citation
Prasad, VK, and Kurtzberg, J. "Umbilical cord blood transplantation for non-malignant diseases." Bone Marrow Transplant 44.10 (November 2009): 643-651. (Review)
PMID
19802020
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
44
Issue
10
Publish Date
2009
Start Page
643
End Page
651
DOI
10.1038/bmt.2009.290

Unrelated donor umbilical cord blood transplantation in pediatric myelodysplastic syndrome: a single-center experience.

Myelodysplastic syndromes (MDS) respond poorly to chemotherapy. Between 1995 and 2006, 23 pediatric patients with MDS were transplanted with unrelated donor umbilical cord blood (UUCB) at our center. The median age was 11.1 years (range: 1.1-19.7), median weight was 38.6 kg (range: 9.6-62.6), 61% of patients were male, and median time from diagnosis to transplant was 6.6 months (range: 2.0-61.4). Patients were followed for a median of 5.3 years (range: 1.6-12.4 years) posttransplant. MDS stage was refractory anemia (RA) in 12, refractory anemia with excess blasts (RAEB) in 8, and refractory anemia with excess blasts in transformation (RAEB-T) in 3 patients; 18 (78%) patients had primary MDS. Monosomy 7 was present in 17(74%) patients. Patients with acute myelogenous leukemia (AML) were excluded. Preparative regimen was total body irradiation (TBI) based in 18 (78%) patients. Graft-versus-host-disease (GVHD) prophylaxis was cyclosporine (CsA)/steroids (19 patients) or CsA/mycophenolate mofetil (MMF; 4 patients). Grafts were HLA matched at Class I (A and B) at low resolution and Class II (DRB1) at the allelic level, resulting in 16 (70%) 4/6 and 7 (30%) 5/6 matched transplants. The grafts contained a median of 4.0 x 10(7) (range: 1.7-12.6) total nucleated cells (TNC)/kg precryopreservation; 3.6 x 10(7) (range: 1.0-12.0) TNC/kg and 1.7 x 10(5) (range: 0.2-28.5) CD34+ cells/kg were infused. Cumulative incidence of neutrophil engraftment (absolute neutrophil count [ANC] >500/microL) at day 42 and day 100 was 73.9% (95% confidence interval [CI] 55.1%-92.7%) and 91.3% (95% CI 71.3%-100.0%) respectively, and that of platelet engraftment (50 K) at 180 days was 69.6% (95% CI 49.8%-89.4%). Three patients had graft failure whereas 3 patients (13%) engrafted slowly (after day 42). Three patients developed acute GVHD (aGVHD) grades II-IV with a cumulative incidence at 100 days of 13% (95% CI 0.0%-27.1.0%). Four patients relapsed with a cumulative incidence of relapse at 3 years of 13.0% (95% CI 0.0%-27.1%). Cumulative incidence of nonrelapse mortality (NRM) at 1 year was 27% (95% CI 8.0%-46.0%). Ten patients died: 3 graft failure, 4 relapse, 2 infections (1 adenovirus, 1 toxoplasmosis), and 1 Epstein-Barr virus (EBV) lymphoproliferative disorder. Probabilities of event-free survival (EFS) at 1 and 3 years were 69.6% (95% CI 46.6%-84.2%) and 60.9% (95% CI 38.3%-77.4%), respectively. Factors associated with better EFS were age < or = 11 years (P = .05) and weight < or = 38 kg (P = .03). These results, especially in younger patients with monosomy 7 positive MDS, are equivalent to published matched allogeneic bone marrow data. UUCB should be actively considered for pediatric MDS patients lacking matched related or unrelated adult donors.

Authors
Parikh, SH; Mendizabal, A; Martin, PL; Prasad, VK; Szabolcs, P; Driscoll, TA; Kurtzberg, J
MLA Citation
Parikh, SH, Mendizabal, A, Martin, PL, Prasad, VK, Szabolcs, P, Driscoll, TA, and Kurtzberg, J. "Unrelated donor umbilical cord blood transplantation in pediatric myelodysplastic syndrome: a single-center experience." Biol Blood Marrow Transplant 15.8 (August 2009): 948-955.
PMID
19589484
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
8
Publish Date
2009
Start Page
948
End Page
955
DOI
10.1016/j.bbmt.2009.04.010

Umbilical cord stem cell transplantation.

OBJECTIVES: To discuss the history, current state, and future directions of umbilical cord blood (UCB) transplantation as it relates to the emerging field of cellular therapies. DATA SOURCES: Research studies, articles, and personal experiences. CONCLUSION: Transplantation using hematopoietic stem cells from UCB is a life-saving option for patients with select oncologic and immunologic diseases, bone marrow failure, hemoglobinopathies, and inborn errors of metabolism.

Authors
Frey, MA; Guess, C; Allison, J; Kurtzberg, J
MLA Citation
Frey, MA, Guess, C, Allison, J, and Kurtzberg, J. "Umbilical cord stem cell transplantation." Semin Oncol Nurs 25.2 (May 2009): 115-119. (Review)
PMID
19411014
Source
pubmed
Published In
Seminars in Oncology Nursing
Volume
25
Issue
2
Publish Date
2009
Start Page
115
End Page
119
DOI
10.1016/j.soncn.2009.03.005

Risk factor analysis of outcomes after unrelated cord blood transplantation in patients with hurler syndrome.

Allogeneic stem cell transplantation (SCT) is considered effective in preventing disease progression in patients with Hurler syndrome (HS). Unrelated umbilical cord blood (UCB) grafts are suggested as an alternative to bone marrow (BM) or peripheral blood stem cells (PBSC). We studied 93 HS patients receiving an UCB graft to analyze risk factors for outcomes. The median time from diagnosis to transplant was 4.6 months, median follow-up was 29 months, and median number of nucleated CB cells infused was 7.6 x 10(7)/kg. Most of the patients received 1 or 2 HLA disparate grafts, and the most frequently used conditioning regimen was cyclophosphamide + busulfan (Bu/Cy). All patients received anti-T cell antibody. At post transplant day +60, the cumulative incidence of neutrophil engraftment was 85%. A younger age at transplant and a higher CD34(+) dose at infusion were favorably associated with engraftment. With the exception of 2 patients, all engrafted patients achieved full and sustained donor chimerism. The 3-year event-free survival (EFS) and 3-year overall survival (OS) rates were 70% and 77%, respectively. In a multivariate analyses, use of Bu/Cy and a shorter interval from diagnosis to transplant were predictors for improved EFS rate (82% for patients transplanted within 4.6 months after diagnosis compared to 57% for the rest). Improved outcomes from early transplantation and immediate availability of CB unit lead us to conclude that CB transplantation is a beneficial option, which should be considered expediently for children with HS.

Authors
Boelens, JJ; Rocha, V; Aldenhoven, M; Wynn, R; O'Meara, A; Michel, G; Ionescu, I; Parikh, S; Prasad, VK; Szabolcs, P; Escolar, M; Gluckman, E; Cavazzana-Calvo, M; Kurtzberg, J; EUROCORD, Inborn error Working Party of EBMT and Duke University,
MLA Citation
Boelens, JJ, Rocha, V, Aldenhoven, M, Wynn, R, O'Meara, A, Michel, G, Ionescu, I, Parikh, S, Prasad, VK, Szabolcs, P, Escolar, M, Gluckman, E, Cavazzana-Calvo, M, Kurtzberg, J, EUROCORD, and Inborn error Working Party of EBMT and Duke University, . "Risk factor analysis of outcomes after unrelated cord blood transplantation in patients with hurler syndrome." Biol Blood Marrow Transplant 15.5 (May 2009): 618-625.
PMID
19361754
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
5
Publish Date
2009
Start Page
618
End Page
625
DOI
10.1016/j.bbmt.2009.01.020

Diffusion tensor imaging detects abnormalities in the corticospinal tracts of neonates with infantile Krabbe disease.

BACKGROUND AND PURPOSE: It is not possible to determine if neonates diagnosed with Krabbe disease through statewide neonate screening programs will develop the disease as infants, juveniles, or adults. The only available treatment for this fatal neurodegenerative condition is unrelated umbilical cord transplantation, but this treatment is only effective before clinical symptoms appear. Therefore, a marker of disease progression is needed. The purpose of this study was to evaluate the use of diffusion tensor imaging (DTI) with fiber tracking in identifying early changes in major motor tracts of asymptomatic neonates with infantile Krabbe disease. MATERIALS AND METHODS: Six neonates with infantile Krabbe disease identified because of family history underwent brain MR imaging within the first 4 weeks of life. Six-direction DTI and quantitative tractography of the corticospinal tracts were performed. Hypothesis tests, 1 for each hemisphere, were used to determine whether the fractional anisotropy (FA) ratio of the neonates with infantile Krabbe disease was significantly different from that of 45 age- and sex-matched controls. RESULTS: The average FA ratio for patients with Krabbe disease was 0.89 and 0.87 for left and right tracts, respectively (P = .002 and < .001). After adjusting for gestational age, gestational age at birth, birth weight, sex, and race, the 6 patients with Krabbe disease had significantly lower FA values than the controls (P < .001). CONCLUSIONS: DTI with quantitative tractography detected significant differences in the corticospinal tracts of asymptomatic neonates who had the early-onset form of Krabbe disease. Once standardized and validated, this tool has the potential to be used as a marker of disease progression in neonates diagnosed through statewide neonate screening programs.

Authors
Escolar, ML; Poe, MD; Smith, JK; Gilmore, JH; Kurtzberg, J; Lin, W; Styner, M
MLA Citation
Escolar, ML, Poe, MD, Smith, JK, Gilmore, JH, Kurtzberg, J, Lin, W, and Styner, M. "Diffusion tensor imaging detects abnormalities in the corticospinal tracts of neonates with infantile Krabbe disease." AJNR Am J Neuroradiol 30.5 (May 2009): 1017-1021.
PMID
19386732
Source
pubmed
Published In
American Journal of Neuroradiology
Volume
30
Issue
5
Publish Date
2009
Start Page
1017
End Page
1021
DOI
10.3174/ajnr.A1476

Unintended changes in cognition, mood, and behavior arising from cell-based interventions for neurological conditions: ethical challenges.

The prospect of using cell-based interventions (CBIs) to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior-brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment.

Authors
Duggan, PS; Siegel, AW; Blass, DM; Bok, H; Coyle, JT; Faden, R; Finkel, J; Gearhart, JD; Greely, HT; Hillis, A; Hoke, A; Johnson, R; Johnston, M; Kahn, J; Kerr, D; King, P; Kurtzberg, J; Liao, SM; McDonald, JW; McKhann, G; Nelson, KB; Rao, M; Regenberg, A; Smith, K; Solter, D; Song, H; Sugarman, J; Traystman, RJ; Vescovi, A; Yanofski, J; Young, W; Mathews, DJH
MLA Citation
Duggan, PS, Siegel, AW, Blass, DM, Bok, H, Coyle, JT, Faden, R, Finkel, J, Gearhart, JD, Greely, HT, Hillis, A, Hoke, A, Johnson, R, Johnston, M, Kahn, J, Kerr, D, King, P, Kurtzberg, J, Liao, SM, McDonald, JW, McKhann, G, Nelson, KB, Rao, M, Regenberg, A, Smith, K, Solter, D, Song, H, Sugarman, J, Traystman, RJ, Vescovi, A, Yanofski, J, Young, W, and Mathews, DJH. "Unintended changes in cognition, mood, and behavior arising from cell-based interventions for neurological conditions: ethical challenges." Am J Bioeth 9.5 (May 2009): 31-36.
PMID
19396681
Source
pubmed
Published In
American Journal of Bioethics
Volume
9
Issue
5
Publish Date
2009
Start Page
31
End Page
36
DOI
10.1080/15265160902788645

Newborn screening for Krabbe disease: the New York State model.

Krabbe disease is a rare inherited neurologic disorder affecting the central and peripheral nervous systems. The disease has four phenotypes: early infantile, later onset, adolescent, and adult. The only known treatment is hematopoietic stem cell transplantation, which is, in the early infantile form of the disease, most beneficial if performed before onset of clinical symptoms. In August 2006, New York State began screening all newborns for Krabbe disease. A rapid and accurate technique for assessing galactocerebrosidase activity and performing DNA mutation analysis had been developed. Interpreting these results was limited, however, because neither enzyme activity nor genetic mutation reliably predicts phenotype. A series of initiatives were therefore developed by a multidisciplinary group of neurologists, geneticists, metabolic pediatricians, neurodevelopmental pediatricians, and transplant physicians (the Krabbe Consortium of New York State) to enhance the effectiveness of the newborn screening program. A standardized clinical evaluation protocol was designed based on the available literature, criteria for transplantation for the early infantile phenotype were formulated, a clinical database and registry was developed, and a study of developmental and functional outcomes was instituted. This multidisciplinary standardized approach to evaluating infants who have positive results on newborn screening may serve as a model for other states as they begin the process of screening for Krabbe disease and other lysosomal storage disorders.

Authors
Duffner, PK; Caggana, M; Orsini, JJ; Wenger, DA; Patterson, MC; Crosley, CJ; Kurtzberg, J; Arnold, GL; Escolar, ML; Adams, DJ; Andriola, MR; Aron, AM; Ciafaloni, E; Djukic, A; Erbe, RW; Galvin-Parton, P; Helton, LE; Kolodny, EH; Kosofsky, BE; Kronn, DF; Kwon, JM; Levy, PA; Miller-Horn, J; Naidich, TP; Pellegrino, JE; Provenzale, JM; Rothman, SJ; Wasserstein, MP
MLA Citation
Duffner, PK, Caggana, M, Orsini, JJ, Wenger, DA, Patterson, MC, Crosley, CJ, Kurtzberg, J, Arnold, GL, Escolar, ML, Adams, DJ, Andriola, MR, Aron, AM, Ciafaloni, E, Djukic, A, Erbe, RW, Galvin-Parton, P, Helton, LE, Kolodny, EH, Kosofsky, BE, Kronn, DF, Kwon, JM, Levy, PA, Miller-Horn, J, Naidich, TP, Pellegrino, JE, Provenzale, JM, Rothman, SJ, and Wasserstein, MP. "Newborn screening for Krabbe disease: the New York State model." Pediatr Neurol 40.4 (April 2009): 245-252.
PMID
19302934
Source
pubmed
Published In
Pediatric Neurology
Volume
40
Issue
4
Publish Date
2009
Start Page
245
End Page
252
DOI
10.1016/j.pediatrneurol.2008.11.010

Umbilical Cord Blood: A Reliable Source of Stem and Progenitor Cells for Human Transplantation

Authors
Parikh, SH; Kurtzberg, J
MLA Citation
Parikh, SH, and Kurtzberg, J. "Umbilical Cord Blood: A Reliable Source of Stem and Progenitor Cells for Human Transplantation." Rossi's Principles of Transfusion Medicine: Fourth Edition. March 5, 2009. 559-565.
Source
scopus
Publish Date
2009
Start Page
559
End Page
565
DOI
10.1002/9781444303513.ch36

PLASMACYTOID CD123+DENDRITIC CELL RECOVERY AND REDUCED ACTIVATION STATE OF CIRCULATING CD8+T CELLS PREDICT SURVIVAL AFTER UNRELATED CORD BLOOD TRANSPLANT (UCBT)

Authors
Wilfret, DA; Mendizabal, AM; Reese, M; Vinsett, R; Kurtzberg, J; Szabolcs, P
MLA Citation
Wilfret, DA, Mendizabal, AM, Reese, M, Vinsett, R, Kurtzberg, J, and Szabolcs, P. "PLASMACYTOID CD123+DENDRITIC CELL RECOVERY AND REDUCED ACTIVATION STATE OF CIRCULATING CD8+T CELLS PREDICT SURVIVAL AFTER UNRELATED CORD BLOOD TRANSPLANT (UCBT)." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15.2 (February 2009): 136-136.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
2
Publish Date
2009
Start Page
136
End Page
136

DEVELOPMENT OF A SEGMENT-BASED ALDEHYDE DEHYDROGENASE ASSAY TO DETERMINE UMBILICAL CORD BLOOD UNIT (CBU) POTENCY

Authors
Shoulars, KW; Gentry, T; Tracy, ET; Page, K; Sun, J; Winstead, L; Balber, AE; Kurtzberg, J
MLA Citation
Shoulars, KW, Gentry, T, Tracy, ET, Page, K, Sun, J, Winstead, L, Balber, AE, and Kurtzberg, J. "DEVELOPMENT OF A SEGMENT-BASED ALDEHYDE DEHYDROGENASE ASSAY TO DETERMINE UMBILICAL CORD BLOOD UNIT (CBU) POTENCY." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15.2 (February 2009): 44-44.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
2
Publish Date
2009
Start Page
44
End Page
44

ISOLATION AND EXPANSION OF OLIGODENDROCYTES FROM THAWED, CRYOPRESERVED HUMAN UMBLILICAL CORD BLOOD

Authors
Tracy, E; Gentry, T; Shoulars, K; Hughes, M; Kurtzberg, J
MLA Citation
Tracy, E, Gentry, T, Shoulars, K, Hughes, M, and Kurtzberg, J. "ISOLATION AND EXPANSION OF OLIGODENDROCYTES FROM THAWED, CRYOPRESERVED HUMAN UMBLILICAL CORD BLOOD." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15.2 (February 2009): 86-86.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
2
Publish Date
2009
Start Page
86
End Page
86

Update on umbilical cord blood transplantation.

PURPOSE OF REVIEW: 2008 marks the 20th anniversary of the first use of umbilical cord blood (UCB) as a source of donor cells for hematopoietic stem cell transplantation. In those early days, there was great doubt and skepticism about the utility of UCB as a source of hematopoietic stem cells. Doubts about whether UCB, containing 10-20x fewer cells than bone marrow, had sufficient cells to durably engraft a myeloablated patient and, after demonstration that engraftment occurred with less graft-versus-host disease, whether it would confer graft-versus-leukemia activity were raised. RECENT FINDINGS: Transplantation with UCB is effective in the treatment of children with hematological malignancies, marrow failure, immunodeficiencies, hemoglobinopathies and inherited metabolic diseases. Transplantation without full human leukocyte antigen matching is possible and, despite a lower incidence of graft-versus-host disease, graft-versus-leukemia is preserved. The number of cells in a single UCB can be limiting, but the use of two UCBs for a single transplant shows promise to overcome this obstacle. SUMMARY: Cord blood transplantation is now an established field with enormous potential. UCB increases access to transplantation therapy for many patients unable to identify a fully matched adult donor. In the future, it may emerge as a source of cells for cellular therapies focused on tissue repair and regeneration.

Authors
Kurtzberg, J
MLA Citation
Kurtzberg, J. "Update on umbilical cord blood transplantation." Curr Opin Pediatr 21.1 (February 2009): 22-29. (Review)
PMID
19253461
Source
pubmed
Published In
Current Opinion in Pediatrics
Volume
21
Issue
1
Publish Date
2009
Start Page
22
End Page
29

PERICARDIAL EFFUSION FOLLOWING UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION: ANALYSIS IN A COHORT OF 423 PEDIATRIC PATIENTS TRANSPLANTED AT A SINGLE CENTER

Authors
Hwang, EI; Camitta, MGW; Vinesett, R; Mendizabal, A; Wood, S; Semmel, D; Page, K; Driscoll, TA; Parikh, SH; Szabolcs, P; Kurtzberg, J; Prasad, VK
MLA Citation
Hwang, EI, Camitta, MGW, Vinesett, R, Mendizabal, A, Wood, S, Semmel, D, Page, K, Driscoll, TA, Parikh, SH, Szabolcs, P, Kurtzberg, J, and Prasad, VK. "PERICARDIAL EFFUSION FOLLOWING UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION: ANALYSIS IN A COHORT OF 423 PEDIATRIC PATIENTS TRANSPLANTED AT A SINGLE CENTER." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15.2 (February 2009): 73-74.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
2
Publish Date
2009
Start Page
73
End Page
74

NEGATIVE IMPACT OF POST-THAW WASHING ON THE OVERALL SURVIVAL (OS) AND DISEASE FREE SURVIVAL (DFS) OF PATIENTS RECEIVING PLASMA DEPLETED (PD) CORD BLOOD (CB) TRANSPLANTATION

Authors
Chow, R; Law, P; Wang, B; Rosenthal, J; Nademanee, A; Karanes, C; Jaing, T-H; Graham, ML; Delaney, C; Gjertson, D; Petz, L; Kurtzberg, J
MLA Citation
Chow, R, Law, P, Wang, B, Rosenthal, J, Nademanee, A, Karanes, C, Jaing, T-H, Graham, ML, Delaney, C, Gjertson, D, Petz, L, and Kurtzberg, J. "NEGATIVE IMPACT OF POST-THAW WASHING ON THE OVERALL SURVIVAL (OS) AND DISEASE FREE SURVIVAL (DFS) OF PATIENTS RECEIVING PLASMA DEPLETED (PD) CORD BLOOD (CB) TRANSPLANTATION." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15.2 (February 2009): 17-17.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
2
Publish Date
2009
Start Page
17
End Page
17

UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION FROM A SINGLE 4/6 MATCHED UNIT IS AN EFFECTIVE THERAPY FOR CHILDREN WITH MALIGNANT AND NON-MALIGNANT DIAGNOSES: GOOD SURVIVAL, LOW GRAFT FAILURE AND GRAFT-VS-HOST DISEASE IN A SINGLE CENTER ANALYSIS OF 314 PATIENTS

Authors
Prasad, VK; Mendizabal, A; Gill, P; Parikh, SH; Szabolcs, P; Driscoll, TA; Page, K; Wood, S; Semmel, D; Martin, PL; Carter, S; Kurtzberg, J
MLA Citation
Prasad, VK, Mendizabal, A, Gill, P, Parikh, SH, Szabolcs, P, Driscoll, TA, Page, K, Wood, S, Semmel, D, Martin, PL, Carter, S, and Kurtzberg, J. "UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION FROM A SINGLE 4/6 MATCHED UNIT IS AN EFFECTIVE THERAPY FOR CHILDREN WITH MALIGNANT AND NON-MALIGNANT DIAGNOSES: GOOD SURVIVAL, LOW GRAFT FAILURE AND GRAFT-VS-HOST DISEASE IN A SINGLE CENTER ANALYSIS OF 314 PATIENTS." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15.2 (February 2009): 27-27.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
2
Publish Date
2009
Start Page
27
End Page
27

OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN PEDIATRIC PATIENTS WITH PRIMARY AND SECONDARY MYELODYSPLASTIC SYNDROMES

Authors
Parikh, SH; Mendizabal, A; Betz-Stablein, B; Martin, PL; Szabolcs, P; Prasad, VK; Driscoll, TA; Kurtzberg, J
MLA Citation
Parikh, SH, Mendizabal, A, Betz-Stablein, B, Martin, PL, Szabolcs, P, Prasad, VK, Driscoll, TA, and Kurtzberg, J. "OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN PEDIATRIC PATIENTS WITH PRIMARY AND SECONDARY MYELODYSPLASTIC SYNDROMES." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15.2 (February 2009): 72-72.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
2
Publish Date
2009
Start Page
72
End Page
72

DTI with quantitative tractography as a marker of disease progression in newborns with Krabbe disease

Authors
Escolar, ML; Poe, MD; Smith, K; Lin, W; Kurtzberg, J; Styner, M
MLA Citation
Escolar, ML, Poe, MD, Smith, K, Lin, W, Kurtzberg, J, and Styner, M. "DTI with quantitative tractography as a marker of disease progression in newborns with Krabbe disease." MOLECULAR GENETICS AND METABOLISM 96.2 (February 2009): S23-S24.
Source
wos-lite
Published In
Molecular Genetics and Metabolism
Volume
96
Issue
2
Publish Date
2009
Start Page
S23
End Page
S24
DOI
10.1016/j.ymgme.2008.11.054

The role of animal models in evaluating reasonable safety and efficacy for human trials of cell-based interventions for neurologic conditions.

Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.

Authors
Regenberg, A; Mathews, DJH; Blass, DM; Bok, H; Coyle, JT; Duggan, P; Faden, R; Finkel, J; Gearhart, JD; Hillis, A; Hoke, A; Johnson, R; Johnston, M; Kahn, J; Kerr, D; King, P; Kurtzberg, J; Liao, SM; McDonald, JW; McKhann, G; Nelson, KB; Rao, M; Siegel, AW; Smith, K; Solter, D; Song, H; Sugarman, J; Vescovi, A; Young, W; Greely, HT; Traystman, RJ
MLA Citation
Regenberg, A, Mathews, DJH, Blass, DM, Bok, H, Coyle, JT, Duggan, P, Faden, R, Finkel, J, Gearhart, JD, Hillis, A, Hoke, A, Johnson, R, Johnston, M, Kahn, J, Kerr, D, King, P, Kurtzberg, J, Liao, SM, McDonald, JW, McKhann, G, Nelson, KB, Rao, M, Siegel, AW, Smith, K, Solter, D, Song, H, Sugarman, J, Vescovi, A, Young, W, Greely, HT, and Traystman, RJ. "The role of animal models in evaluating reasonable safety and efficacy for human trials of cell-based interventions for neurologic conditions." J Cereb Blood Flow Metab 29.1 (January 2009): 1-9. (Review)
PMID
18728679
Source
pubmed
Published In
Journal of Cerebral Blood Flow and Metabolism
Volume
29
Issue
1
Publish Date
2009
Start Page
1
End Page
9
DOI
10.1038/jcbfm.2008.98

Correlation of neurodevelopmental features and MRI findings in infantile Krabbe's disease.

OBJECTIVE: The purpose of our study was to compare MRI findings with neurobehavioral development in infants with Krabbe's disease. MATERIALS AND METHODS: Nine infants with Krabbe's disease underwent a total of 19 MR studies during the first year of life as well as tests of mental development, gross motor skills, and fine motor skills (score range: 0-100) within 1 month of imaging. MR scans were scored using the Loes severity scale based on signal abnormality and atrophy, ranging from 0 (best) to 32. We performed three comparisons (Student's t test): each test versus total brain Loes score, fine motor and gross motor tests versus Loes score for the pyramidal tract, and fine motor and gross motor tests versus Loes score for the internal capsule. RESULTS: Mean test results were 65+/-31 for mental development, 48+/-39 for gross motor score, 57+/-35 for fine motor score, and mean total brain score was 7.79+/-6.20. Correlations for total Loes score were -0.78 (p=0.003) for mental development, -0.74 (p=0.003) for gross motor function, and -0.80 (p<0.001) for fine motor function. Correlations for pyramidal system Loes scores were -0.73 (p=0.003) for fine motor function and -0.58 (p=0.028) for gross motor function. Correlation between Loes scores for internal capsule and fine motor function was -0.38 (p>0.05) and between Loes scores for internal capsule and gross motor function was -0.35 (p>0.05). CONCLUSION: The very good correlation between testing results and Loes scores for the entire brain and moderately good correlation between test results and scores for specific brain regions indicate the Loes scoring system likely provides a reasonable means for assessing prognosis and therapeutic response for infants with Krabbe's disease.

Authors
Provenzale, JM; Peddi, S; Kurtzberg, J; Poe, MD; Mukundan, S; Escolar, M
MLA Citation
Provenzale, JM, Peddi, S, Kurtzberg, J, Poe, MD, Mukundan, S, and Escolar, M. "Correlation of neurodevelopmental features and MRI findings in infantile Krabbe's disease." AJR Am J Roentgenol 192.1 (January 2009): 59-65.
PMID
19098180
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
192
Issue
1
Publish Date
2009
Start Page
59
End Page
65
DOI
10.2214/ajr.192.5_supplement.0a59

Isolation and Expansion of Oligodendrocytes from Thawed, Cryopreserved Human Umblilical Cord Blood

Authors
Tracy, E; Gentry, T; Hughes, M; Kurtzberg, J
MLA Citation
Tracy, E, Gentry, T, Hughes, M, and Kurtzberg, J. "Isolation and Expansion of Oligodendrocytes from Thawed, Cryopreserved Human Umblilical Cord Blood." BLOOD 112.11 (November 16, 2008): 1193-1193.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
1193
End Page
1193

Encoraging Results after Alternative Donor Transplantation for Myelodysplastic Syndrome

Authors
Locatelli, F; Moreno-Madureira, A; Teira, P; Eapen, M; Zhang, M-J; Davies, SM; Picardi, A; Woolfrey, AE; Chan, KW; Socie, G; Vora, AJ; Bertrand, Y; Kurtzberg, J; Bonfim, C; Gluckman, E; Niemeyer, CM; Rocha, V
MLA Citation
Locatelli, F, Moreno-Madureira, A, Teira, P, Eapen, M, Zhang, M-J, Davies, SM, Picardi, A, Woolfrey, AE, Chan, KW, Socie, G, Vora, AJ, Bertrand, Y, Kurtzberg, J, Bonfim, C, Gluckman, E, Niemeyer, CM, and Rocha, V. "Encoraging Results after Alternative Donor Transplantation for Myelodysplastic Syndrome." BLOOD 112.11 (November 16, 2008): 685-686.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
685
End Page
686

Plasmacytoid CD123+Dendritic Cell Recovery Is An Independent Predictor of Survival after Unrelated Cord Blood Transplant (UCBT)

Authors
Wilfret, DA; Mendizabai, A; Reese, M; Vinesett, R; Kurtzberg, J; Szabolcs, P
MLA Citation
Wilfret, DA, Mendizabai, A, Reese, M, Vinesett, R, Kurtzberg, J, and Szabolcs, P. "Plasmacytoid CD123+Dendritic Cell Recovery Is An Independent Predictor of Survival after Unrelated Cord Blood Transplant (UCBT)." BLOOD 112.11 (November 16, 2008): 777-777.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
777
End Page
777

Single Donor 4/6 Matched Banked Unrelated Cord Blood Is An Effective Graft Source for Children Undergoing Myeloablative Transplantation for Malignant and Nonmalignant Disorders: Single Center Analysis of 318 Patients

Authors
Prasad, VK; Gill, P; Vinesett, R; Parikh, SH; Szabolcs, P; Driscoll, TA; Page, KM; Wood, S; Semmel, D; Martin, PL; Kurtzberg, J
MLA Citation
Prasad, VK, Gill, P, Vinesett, R, Parikh, SH, Szabolcs, P, Driscoll, TA, Page, KM, Wood, S, Semmel, D, Martin, PL, and Kurtzberg, J. "Single Donor 4/6 Matched Banked Unrelated Cord Blood Is An Effective Graft Source for Children Undergoing Myeloablative Transplantation for Malignant and Nonmalignant Disorders: Single Center Analysis of 318 Patients." BLOOD 112.11 (November 16, 2008): 690-690.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
690
End Page
690

Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies.

Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching at enrollment was 6/6 (n = 17), 5/6 (n = 58), 4/6 (n = 111), or 3/6 (n = 5) by low-resolution HLA-A, -B, and high-resolution (HR) DRB1. Retrospectively, 179 pairs were HLA typed by HR. The median precryopreservation total nucleated cell (TNC) dose was 5.1 x 10(7) TNC/kg (range, 1.5-23.7) with 3.9 x 10(7) TNC/kg (range, 0.8-22.8) infused. The median time to engraftment (absolute neutrophil count > 500/mm(3) and platelets 50 000/muL) was 27 and 174 days. The cumulative incidence of neutrophil engraftment by day 42 was 79.9% (95% confidence interval [CI], 75.1%-85.2%); acute grades III/IV GVHD by day 100 was 19.5% (95% CI, 13.9%-25.5%); and chronic GVHD at 2 years was 20.8% (95% CI, 14.8%-27.7%). HR matching decreased the probability of severe acute GVHD. The cumulative incidence of relapse at 2 years was 19.9% (95% CI, 14.8%-25.7%). The probabilities of 6-month and 2-year survivals were 67.4% and 49.5%. Unrelated donor cord blood transplantation from partially HLA-mismatched units can cure many children with leukemias. The study was registered at www.clinicaltrials.gov as #NCT00000603.

Authors
Kurtzberg, J; Prasad, VK; Carter, SL; Wagner, JE; Baxter-Lowe, LA; Wall, D; Kapoor, N; Guinan, EC; Feig, SA; Wagner, EL; Kernan, NA; COBLT Steering Committee,
MLA Citation
Kurtzberg, J, Prasad, VK, Carter, SL, Wagner, JE, Baxter-Lowe, LA, Wall, D, Kapoor, N, Guinan, EC, Feig, SA, Wagner, EL, Kernan, NA, and COBLT Steering Committee, . "Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies." Blood 112.10 (November 15, 2008): 4318-4327.
PMID
18723429
Source
pubmed
Published In
Blood
Volume
112
Issue
10
Publish Date
2008
Start Page
4318
End Page
4327
DOI
10.1182/blood-2007-06-098020

Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes.

Outcomes of 159 young patients with inherited metabolic disorders (IMDs) undergoing transplantation with partially HLA-mismatched unrelated donor umbilical cord blood were studied to investigate the impact of graft and patient characteristics on engraftment, overall survival (OS), and graft-versus-host disease (GVHD). Patients received myeloablative chemotherapy (busulfan, cyclophosphamide, ATG) and cyclosporine-based GVHD prophylaxis. Infused cell doses were high (7.57 x 10(7)/kg) because of the patients' young age (median, 1.5 years) and small size (median, 12 kg). Median follow-up was 4.2 years (range, 1-11 years). The cumulative incidences of neutrophil and platelet engraftment were 87.1% (95% confidence interval [CI], 81.8%-92.4%) and 71.0% (95% CI, 63.7%-78.3%). A total of 97% achieved high (> 90%) donor chimerism. Serum enzyme normalized in 97% of patients with diseases for which testings exist. Grade III/IV acute GVHD occurred in 10.3% (95% CI, 5.4%-15.2%) of patients. Extensive chronic GVHD occurred in 10.8% (95% CI, 5.7%-15.9%) of patients by 1 year. OS at 1 and 5 years was 71.8% (95% CI, 64.7%-78.9%) and 58.2% (95% CI, 49.7%-66.6%) in all patients and 84.5% (95% CI, 77.0%-92.0%) and 75.7% (95% CI, 66.1%-85.3%) in patients with high (80-100) performance score. In multivariate analysis, favorable factors for OS were high pretransplantation performance status, matched donor/recipient ethnicity, and higher infused colony forming units.

Authors
Prasad, VK; Mendizabal, A; Parikh, SH; Szabolcs, P; Driscoll, TA; Page, K; Lakshminarayanan, S; Allison, J; Wood, S; Semmel, D; Escolar, ML; Martin, PL; Carter, S; Kurtzberg, J
MLA Citation
Prasad, VK, Mendizabal, A, Parikh, SH, Szabolcs, P, Driscoll, TA, Page, K, Lakshminarayanan, S, Allison, J, Wood, S, Semmel, D, Escolar, ML, Martin, PL, Carter, S, and Kurtzberg, J. "Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes." Blood 112.7 (October 1, 2008): 2979-2989.
PMID
18587012
Source
pubmed
Published In
Blood
Volume
112
Issue
7
Publish Date
2008
Start Page
2979
End Page
2989
DOI
10.1182/blood-2008-03-140830

Posttransplant autoimmune hemolytic anemia and other autoimmune cytopenias are increased in very young infants undergoing unrelated donor umbilical cord blood transplantation.

Autoimmune cytopenias are a recognized complication of hematopoietic stem cell transplant (HSCT), and are considered to be a feature of chronic graft-versus-host disease (cGVHD). We report on a cohort of very young infants (< or =3 months of age) receiving HSCT from unrelated donor umbilical cord blood for genetic disorders who developed posttransplant autoimmune cytopenias at an increased rate compared to older aged controls. These infants received a conditioning regimen consisting of busulfan, cyclophosphamide, and antithymocyte globulin (ATG). All infants received HLA mismatched unrelated umbilical cord blood as graft source. GVHD prophylaxis was either cyclosporine + methylprednisolone (n = 16) or cyclosporine + mycophenolate mofetil (n = 3). Engraftment, acute GVHD (aGVHD) and cGVHD, survival, treatment-related mortality (TRM), and deaths were evaluated. Ten patients developed cGVHD manifesting as autoimmune cytopenias at a median 247 days posttransplant with a cumulative incidence of 44% (95% confidence interval [CI] 21%-68%) and 56% (95% CI 32%-80%) at 1 and 2 years, respectively. In 6 of 10 patients developing autoimmune cytopenias, cGVHD presented as autoimmune cytopenia de novo. The cytopenias observed included anemia (n = 4), thrombocytopenia (n = 1), anemia with thrombocytopenia (n = 3), and pancytopenia (n = 2). No graft factors were identified as being significant to development of cGVHD. All patients responded to treatment with methylprednisolone, azithioprine +/- rituximab. One patient required splenectomy. We hypothesize that posttransplant immunosuppression interferes with normal immune ontogeny creating immune dysregulation and graft directed cell destruction. Alternative strategies to prevent GVHD should be considered for this unique patient population.

Authors
Page, KM; Mendizabal, AM; Prasad, VK; Martin, PL; Parikh, S; Wood, S; Sempowski, GD; Szabolcs, P; Kurtzberg, J
MLA Citation
Page, KM, Mendizabal, AM, Prasad, VK, Martin, PL, Parikh, S, Wood, S, Sempowski, GD, Szabolcs, P, and Kurtzberg, J. "Posttransplant autoimmune hemolytic anemia and other autoimmune cytopenias are increased in very young infants undergoing unrelated donor umbilical cord blood transplantation." Biol Blood Marrow Transplant 14.10 (October 2008): 1108-1117.
PMID
18804040
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
10
Publish Date
2008
Start Page
1108
End Page
1117
DOI
10.1016/j.bbmt.2008.07.006

Efficacy of high-dose chemotherapy or standard salvage therapy in patients with recurrent medulloblastoma.

The efficacy of high-dose chemotherapy (HDC) or standard salvage therapy was evaluated in patients with recurrent medulloblastoma (MBL) using retrospective chart review of all patients with recurrent MBL treated at Duke University Medical Center between 1995 and 2005 and who had undergone HDC with or without radiotherapy (RT) or standard salvage therapy after relapse. A total of 30 patients were diagnosed with recurrent MBL after standard RT alone or chemotherapy with RT. Nineteen patients (7 who received no RT before recurrence [group A] and 12 who received definitive RT before recurrence [group B]) underwent surgery and/or induction chemotherapy followed by HDC plus autologous stem-cell rescue. Eleven patients (group C) underwent standard salvage therapy. Six of seven group A patients also received standard RT just before or after recovery from HDC, and 5 of 12 group B patients received adjuvant palliative focal RT post-HDC. At a median follow-up of 28 months, three of seven patients in group A are alive and disease-free at >or=34, >or=110, and >or=116 months, respectively, post-HDC. All patients in groups B and C have died of tumor, at a median of 35 months and 26 months from HDC and standard salvage therapy, respectively. HDC or standard salvage therapy was ineffective in our patients with recurrent MBL who had received standard RT before recurrence. The favorable impact of HDC on disease control in the two long-term survivors cannot be clearly established due to the cofounding effect of definitive RT postrecurrence.

Authors
Gururangan, S; Krauser, J; Watral, MA; Driscoll, T; Larrier, N; Reardon, DA; Rich, JN; Quinn, JA; Vredenburgh, JJ; Desjardins, A; McLendon, RE; Fuchs, H; Kurtzberg, J; Friedman, HS
MLA Citation
Gururangan, S, Krauser, J, Watral, MA, Driscoll, T, Larrier, N, Reardon, DA, Rich, JN, Quinn, JA, Vredenburgh, JJ, Desjardins, A, McLendon, RE, Fuchs, H, Kurtzberg, J, and Friedman, HS. "Efficacy of high-dose chemotherapy or standard salvage therapy in patients with recurrent medulloblastoma." Neuro Oncol 10.5 (October 2008): 745-751.
PMID
18755919
Source
pubmed
Published In
Neuro-Oncology
Volume
10
Issue
5
Publish Date
2008
Start Page
745
End Page
751
DOI
10.1215/15228517-2008-044

Avoidance of post-thaw washing prior to transplantation of plasma depleted umbilical cord blood improves outcome in a matched pair audited analysis of 258 patients

Authors
Chow, R; Jaing, T-H; Rosenthai, J; Nademanee, A; Karanes, C; Graham, M; Law, P; Wang, B; Gjertson, DW; Petz, L; Kurtzberg, J
MLA Citation
Chow, R, Jaing, T-H, Rosenthai, J, Nademanee, A, Karanes, C, Graham, M, Law, P, Wang, B, Gjertson, DW, Petz, L, and Kurtzberg, J. "Avoidance of post-thaw washing prior to transplantation of plasma depleted umbilical cord blood improves outcome in a matched pair audited analysis of 258 patients." September 2008.
Source
wos-lite
Published In
Transfusion
Volume
48
Issue
2
Publish Date
2008
Start Page
17A
End Page
18A

Cell-based interventions for neurologic conditions: ethical challenges for early human trials.

BACKGROUND: Attempts to translate basic stem cell research into treatments for neurologic diseases and injury are well under way. With a clinical trial for one such treatment approved and in progress in the United States, and additional proposals under review, we must begin to address the ethical issues raised by such early forays into human clinical trials for cell-based interventions for neurologic conditions. METHODS: An interdisciplinary working group composed of experts in neuroscience, cell biology, bioethics, law, and transplantation, along with leading disease researchers, was convened twice over 2 years to identify and deliberate on the scientific and ethical issues raised by the transition from preclinical to clinical research of cell-based interventions for neurologic conditions. RESULTS: While the relevant ethical issues are in many respects standard challenges of human subjects research, they are heightened in complexity by the novelty of the science, the focus on the CNS, and the political climate in which the science is proceeding. CONCLUSIONS: Distinctive challenges confronting US scientists, administrators, institutional review boards, stem cell research oversight committees, and others who will need to make decisions about work involving stem cells and their derivatives and evaluate the ethics of early human trials include evaluating the risks, safety, and benefits of these trials, determining and evaluating cell line provenance, and determining inclusion criteria, informed consent, and the ethics of conducting early human trials in the public spotlight. Further study and deliberation by stakeholders is required to move toward professional and institutional policies and practices governing this research.

Authors
Mathews, DJH; Sugarman, J; Bok, H; Blass, DM; Coyle, JT; Duggan, P; Finkel, J; Greely, HT; Hillis, A; Hoke, A; Johnson, R; Johnston, M; Kahn, J; Kerr, D; Kurtzberg, J; Liao, SM; McDonald, JW; McKhann, G; Nelson, KB; Rao, M; Regenberg, A; Siegel, AW; Smith, K; Solter, D; Song, H; Vescovi, A; Young, W; Gearhart, JD; Faden, R
MLA Citation
Mathews, DJH, Sugarman, J, Bok, H, Blass, DM, Coyle, JT, Duggan, P, Finkel, J, Greely, HT, Hillis, A, Hoke, A, Johnson, R, Johnston, M, Kahn, J, Kerr, D, Kurtzberg, J, Liao, SM, McDonald, JW, McKhann, G, Nelson, KB, Rao, M, Regenberg, A, Siegel, AW, Smith, K, Solter, D, Song, H, Vescovi, A, Young, W, Gearhart, JD, and Faden, R. "Cell-based interventions for neurologic conditions: ethical challenges for early human trials." Neurology 71.4 (July 22, 2008): 288-293. (Review)
PMID
18463365
Source
pubmed
Published In
Neurology
Volume
71
Issue
4
Publish Date
2008
Start Page
288
End Page
293
DOI
10.1212/01.wnl.0000316436.13659.80

A pilot study of myeloablative (MA) autologous stem cell (AutoSCT) followed by reduced intensity allogeneic transplantation (RI AlloSCT) in children with poor risk Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL)

Authors
Satwani, P; Bradley, B; Harrison, L; Tallamy, B; Baldinger, L; Garvin, J; George, D; Bhatia, M; Martin, P; Kurtzberg, J; Cairo, MS
MLA Citation
Satwani, P, Bradley, B, Harrison, L, Tallamy, B, Baldinger, L, Garvin, J, George, D, Bhatia, M, Martin, P, Kurtzberg, J, and Cairo, MS. "A pilot study of myeloablative (MA) autologous stem cell (AutoSCT) followed by reduced intensity allogeneic transplantation (RI AlloSCT) in children with poor risk Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL)." June 2008.
Source
wos-lite
Published In
Annals of Oncology
Volume
19
Publish Date
2008
Start Page
140
End Page
140

Isolation of oligodendrocyte-like cells from human umbilical cord blood.

Background As human umbilical cord blood (UCB) is known to be a rich source of progenitor cells, the prospect of isolating a subset of these cells that could differentiate into cells of non-hematopoietic lineages suggests a therapeutic use for patients with inherited lysosomal and peroxisomal storage diseases currently treated with UCB transplantation. Methods Oligodendrocyte-like cells were isolated from UCB by density-gradient centrifugation and expanded using selective media. We then characterized this population of cells using standard immunohistochemical staining methods for neural cell proteins and polymerase chain reaction (PCR) to detect RNA sequences for myelin basic protein (MBP). We also developed a functional assay demonstrating myelination of neurons in vitro. Results Cells with oligodendrocyte-like morphology were reproducibly cultured ex vivo from fresh human UCB. Cells stained positively for multiple oligodendria cell markers (O1, MBP and CNPase) via immunohistochemical staining and flow cytometry. PCR confirmed the presence of MBP and CNPase mRNA. A further in vitro functional assay demonstrated the myelination of mature neuronal cells from the brain of a myelin-deficient murine model co-cultured with the oligodendrocyte-like cells. Discussion After human UCB transplant, donor-derived cells have been noted to migrate to the brain over time. Although is not known whether these cells solely deliver enzyme replacement or a subset engrafts and differentiates into mature neural cells, the clinical improvements noted in these patients suggest a potential role for targeted cellular therapy. Oligodendrocyte-like cells isolated ex vivo and expanded from human UCB could provide a potential cellular therapy for patients with demyelinating or dismyelinating diseases.

Authors
Tracy, E; Aldrink, J; Panosian, J; Beam, D; Thacker, J; Reese, M; Kurtzberg, J
MLA Citation
Tracy, E, Aldrink, J, Panosian, J, Beam, D, Thacker, J, Reese, M, and Kurtzberg, J. "Isolation of oligodendrocyte-like cells from human umbilical cord blood." Cytotherapy (June 2008): 1-8. (Academic Article)
Source
manual
Published In
Cytotherapy (Informa)
Publish Date
2008
Start Page
1
End Page
8

A prospective longitudinal multicenter study of coagulation in pediatric patients undergoing allogeneic stem cell transplantation.

BACKGROUND: Thrombotic complications occur in adult patients undergoing stem cell transplantation (SCT), especially following high dose chemo-radiotherapy. There is little published information in children on the impact of SCT on coagulation, as well as potential correlations between altered coagulation and SCT-associated thrombosis and organ failure. PROCEDURE: Forty three pediatric subjects who underwent allogeneic SCT were prospectively evaluated for congenital thrombophilia, anticoagulant levels, coagulation activation, and fibrinolysis at pre-established set points encompassing the period from the 2 to 4 weeks prior to conditioning to 28 days post-transplantation. RESULTS: A significant decrease of protein C and antithrombin levels was found in 39% and 31% of subjects respectively, between SCT days +6 and +7. A peak in plasminogen activator inhibitor-1 levels in 31% of subjects was noted between days +9 and +10. No subject experienced a thrombotic event or other SCT-related organ failure. Antithrombin deficiency correlated with underlying malignancy, donor HLA-mismatch, and TBI, whereas decreased PC activity demonstrated a trend of association with lack of T-cell depletion and TBI. Prophylactic heparin did not influence the pattern of acquired hemostatic abnormalities observed in this cohort. CONCLUSIONS: Children undergoing allogeneic SCT develop a state of acquired thrombophilia in the early post-transplantation period. Although no SCT-related thromboembolic events were observed, our results provide new information about the hemostatic changes in children undergoing allogeneic SCT and their potential clinical triggers. The significance of these findings requires further prospective evaluation in a larger cohort of patients.

Authors
Brandão, LR; Kletzel, M; Boulad, F; Kurtzberg, J; Maloney, K; Fligman, I; Sison, CP; Dimichele, D
MLA Citation
Brandão, LR, Kletzel, M, Boulad, F, Kurtzberg, J, Maloney, K, Fligman, I, Sison, CP, and Dimichele, D. "A prospective longitudinal multicenter study of coagulation in pediatric patients undergoing allogeneic stem cell transplantation." Pediatr Blood Cancer 50.6 (June 2008): 1240-1246.
PMID
18273869
Source
pubmed
Published In
Pediatric Blood & Cancer
Volume
50
Issue
6
Publish Date
2008
Start Page
1240
End Page
1246
DOI
10.1002/pbc.21473

Prospective analysis of TEL gene rearrangements in childhood acute lymphoblastic leukemia: a Children's Oncology Group study.

PURPOSE: To prospectively determine the prognostic significance of the TEL-AML1 fusion in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: TEL gene status was determined for 926 patients with B-precursor ALL enrolled on the Pediatric Oncology Group ALinC 16 trials and patients were observed for a median time of 8 years. RESULTS: Rearrangements of the TEL gene were detected in 244 patients (26%). The estimated 5-year event-free survival rate (+/- SE) for patients with TEL rearrangements was 86% +/- 2%, compared with 72% +/- 2% for those with germline TEL (P < .0001). TEL rearrangements were associated with a superior outcome among patients with standard-risk ALL, high-risk ALL, and rapid early responses to therapy. In a multivariate analysis that included risk group, sex, and day 15 marrow status, TEL status was an independent predictor of outcome (P = .0002). CONCLUSION: We conclude that TEL gene status should be incorporated into risk classification schemes and suggest that patients who have standard-risk features, the TEL-AML1 fusion, and rapid early responses to therapy, should be treated with antimetabolite-based therapy designed to maintain their high cure rates and avoid late effects.

Authors
Rubnitz, JE; Wichlan, D; Devidas, M; Shuster, J; Linda, SB; Kurtzberg, J; Bell, B; Hunger, SP; Chauvenet, A; Pui, C-H; Camitta, B; Pullen, J; Children's Oncology Group,
MLA Citation
Rubnitz, JE, Wichlan, D, Devidas, M, Shuster, J, Linda, SB, Kurtzberg, J, Bell, B, Hunger, SP, Chauvenet, A, Pui, C-H, Camitta, B, Pullen, J, and Children's Oncology Group, . "Prospective analysis of TEL gene rearrangements in childhood acute lymphoblastic leukemia: a Children's Oncology Group study." J Clin Oncol 26.13 (May 1, 2008): 2186-2191.
PMID
18445843
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
13
Publish Date
2008
Start Page
2186
End Page
2191
DOI
10.1200/JCO.2007.14.3552

Interleukin-7 promotes ex vivo expansion and maturation of cord blood T-cells. An essential step towards adoptive immunotherapy?

Authors
Davis, C; Kurtzberg, J; Bonyhadi, M; Szabolcs, P
MLA Citation
Davis, C, Kurtzberg, J, Bonyhadi, M, and Szabolcs, P. "Interleukin-7 promotes ex vivo expansion and maturation of cord blood T-cells. An essential step towards adoptive immunotherapy?." March 2008.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
41
Publish Date
2008
Start Page
S328
End Page
S329

Risk factor analysis of outcomes after unrelated cord blood transplantation for children with Hurler's Syndrome. A Eurocord-Duke University collaborative study

Authors
Boelens, J; Rocha, V; Aldenhoven, M; Wynn, R; O'Meara, A; Ionescu, I; Parikh, S; Prasad, V; Cavazzana-Calvo, M; Escolar, M; Gluckman, E; Kurtzberg, J
MLA Citation
Boelens, J, Rocha, V, Aldenhoven, M, Wynn, R, O'Meara, A, Ionescu, I, Parikh, S, Prasad, V, Cavazzana-Calvo, M, Escolar, M, Gluckman, E, and Kurtzberg, J. "Risk factor analysis of outcomes after unrelated cord blood transplantation for children with Hurler's Syndrome. A Eurocord-Duke University collaborative study." March 2008.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
41
Publish Date
2008
Start Page
S27
End Page
S27

105: Augmentation of Standard Umbilical Cord Blood Transplantation with ALDHbr Cells: Results of a Phase I Study in Pediatric Patients

Authors
Kurtzberg, J; Mendizabal, A; Carter, S; Reese, M; Kaestner, A; Hickerson, D; Winstead, L; Fiordalisi, M; Waters-Pick, B; Balber, A
MLA Citation
Kurtzberg, J, Mendizabal, A, Carter, S, Reese, M, Kaestner, A, Hickerson, D, Winstead, L, Fiordalisi, M, Waters-Pick, B, and Balber, A. "105: Augmentation of Standard Umbilical Cord Blood Transplantation with ALDHbr Cells: Results of a Phase I Study in Pediatric Patients." February 2008.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
41
End Page
41
DOI
10.1016/j.bbmt.2007.12.114

Indications and donor selections for allogeneic stem cell transplantation in children with hematologic malignancies.

Allogeneic stem cell transplantation (SCT) is the only curative approach for many patients with advanced or high-risk leukemia. Advances in supportive care and management of graft-versus-host disease have resulted in improvements in outcomes of related and unrelated donor SCT, creating controversies as to which strategy might be the optimal therapy for individual patients. This article discusses the indications and donor selection strategies for SCT in patients with malignant hematologic disease.

Authors
Handgretinger, R; Kurtzberg, J; Egeler, RM
MLA Citation
Handgretinger, R, Kurtzberg, J, and Egeler, RM. "Indications and donor selections for allogeneic stem cell transplantation in children with hematologic malignancies." Pediatr Clin North Am 55.1 (February 2008): 71-x. (Review)
PMID
18242316
Source
pubmed
Published In
Pediatric Clinics of North America
Volume
55
Issue
1
Publish Date
2008
Start Page
71
End Page
x
DOI
10.1016/j.pcl.2007.10.013

A NOVEL METHOD TO REDUCE RATES OF EXTENSIVE CHRONIC GVHD (cGvHD) WITHOUT INCREASED RELAPSE FOR CORD BLOOD TRANSPLANT

Authors
Chow, R; Wang, B; Rosenthal, J; Nademanee, A; Karanes, C; Jaing, T-H; Graham, M; Delaney, C; Gjertson, D; Petz, L; Forman, S; Kurtzberg, J
MLA Citation
Chow, R, Wang, B, Rosenthal, J, Nademanee, A, Karanes, C, Jaing, T-H, Graham, M, Delaney, C, Gjertson, D, Petz, L, Forman, S, and Kurtzberg, J. "A NOVEL METHOD TO REDUCE RATES OF EXTENSIVE CHRONIC GVHD (cGvHD) WITHOUT INCREASED RELAPSE FOR CORD BLOOD TRANSPLANT." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
11
End Page
11
DOI
10.1016/j.bbmt.2007.12.031

THE USE, SAFETY, AND EFFICACY OF DACLIZUMAB FOR STEROID REFRACTORY GRAFT-VERSUS-HOST-DISEASE (GVHD) AFTER UNRELATED CORD BLOOD TRANSPLANTATION (UCBT)

Authors
Mohamed, A; Niedzwiecki, D; Baker, JH; Vinesett, R; Martin, PL; Driscoll, TA; Prasad, VK; Parikh, S; Kurtzberg, J; Szabolcs, P
MLA Citation
Mohamed, A, Niedzwiecki, D, Baker, JH, Vinesett, R, Martin, PL, Driscoll, TA, Prasad, VK, Parikh, S, Kurtzberg, J, and Szabolcs, P. "THE USE, SAFETY, AND EFFICACY OF DACLIZUMAB FOR STEROID REFRACTORY GRAFT-VERSUS-HOST-DISEASE (GVHD) AFTER UNRELATED CORD BLOOD TRANSPLANTATION (UCBT)." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
77
End Page
77
DOI
10.1016/j.bbmt.2007.12.217

OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN PEDIATRIC PATIENTS WITH MYELODYSPLASTIC SYNDROME

Authors
Parikh, SH; Mendizabal, A; Martin, PL; Szabolcs, P; Prasad, VK; Driscoll, TA; Kurtzberg, J
MLA Citation
Parikh, SH, Mendizabal, A, Martin, PL, Szabolcs, P, Prasad, VK, Driscoll, TA, and Kurtzberg, J. "OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN PEDIATRIC PATIENTS WITH MYELODYSPLASTIC SYNDROME." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
83
End Page
84
DOI
10.1016/j.bbmt.2007.12.233

OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN 159 YOUNG PATIENTS WITH PEROXISOMAL AND LYSOSOMAL STORAGE DISORDERS AT A SINGLE CENTER

Authors
Prasad, VK; Mendizabal, A; Parikh, SH; Szabolcs, P; Driscoll, T; Page, K; Lakshbinarayanan, S; Allison, J; Wood, S; Semmel, D; Escolar, ML; Martin, PL; Carter, S; Kurtzberg, J
MLA Citation
Prasad, VK, Mendizabal, A, Parikh, SH, Szabolcs, P, Driscoll, T, Page, K, Lakshbinarayanan, S, Allison, J, Wood, S, Semmel, D, Escolar, ML, Martin, PL, Carter, S, and Kurtzberg, J. "OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN 159 YOUNG PATIENTS WITH PEROXISOMAL AND LYSOSOMAL STORAGE DISORDERS AT A SINGLE CENTER." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
26
End Page
26
DOI
10.1016/j.bbmt.2007.12.071

Long-term developmental follow-up of babies treated for infantile Krabbe disease with unrelated cord blood transplantation

Authors
Escolar, ML; Poe, MD; Yelin, K; Kurtzberg, J
MLA Citation
Escolar, ML, Poe, MD, Yelin, K, and Kurtzberg, J. "Long-term developmental follow-up of babies treated for infantile Krabbe disease with unrelated cord blood transplantation." February 2008.
Source
wos-lite
Published In
Molecular Genetics and Metabolism
Volume
93
Issue
2
Publish Date
2008
Start Page
S21
End Page
S21
DOI
10.1016/j.ymgme.2007.10.042

PASS IT ON

Authors
Harris, LN; Guess, CW; Frey, MA; Kurtzberg, J
MLA Citation
Harris, LN, Guess, CW, Frey, MA, and Kurtzberg, J. "PASS IT ON." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
156
End Page
156
DOI
10.1016/j.bbmt.2007.12.449

SUCCESSFUL COMBINED UNRELATED UMBILICAL CORD BLOOD HAPLOIDENTICAL TRANSPLANT IN NON MALIGNANT DISEASE

Authors
Kleiner, GI; Barredo, J; Shariatmadar, S; Khan, A; Pabwa, R; Rodriguez, M; Willumsen, S; Podda, A; Fernandes, C; Alvarez, O; Kritzer-Cheren, M; Tzakis, A; Rubinstein, P; Kurtzberg, J
MLA Citation
Kleiner, GI, Barredo, J, Shariatmadar, S, Khan, A, Pabwa, R, Rodriguez, M, Willumsen, S, Podda, A, Fernandes, C, Alvarez, O, Kritzer-Cheren, M, Tzakis, A, Rubinstein, P, and Kurtzberg, J. "SUCCESSFUL COMBINED UNRELATED UMBILICAL CORD BLOOD HAPLOIDENTICAL TRANSPLANT IN NON MALIGNANT DISEASE." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
89
End Page
89
DOI
10.1016/j.bbmt.2007.12.250

POST THAW COLONY FORMING UNITS (CFU) IS A STRONG INDEPENDENT PREDICTOR OF ENGRAFTMENT AFTER UNRELATED DONOR UMBILICAL CORD BLOOD TRANSPLANTATION (UCBT)

Authors
Page, KM; Mendizabel, A; Waters-Pick, B; Avrutsky, S; Reese, M; Prasad, VK; Kurtzberg, J
MLA Citation
Page, KM, Mendizabel, A, Waters-Pick, B, Avrutsky, S, Reese, M, Prasad, VK, and Kurtzberg, J. "POST THAW COLONY FORMING UNITS (CFU) IS A STRONG INDEPENDENT PREDICTOR OF ENGRAFTMENT AFTER UNRELATED DONOR UMBILICAL CORD BLOOD TRANSPLANTATION (UCBT)." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
41
End Page
42
DOI
10.1016/j.bbmt.2007.12.116

UNRELATED DONOR UMBILICAL CORD BLOOD TRANSPLANT FOR HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)

Authors
Kelly, SS; Shahlaee, A; Szabolcs, P; Driscoll, T; Eslin, D; Kurtzberg, J; Martin, PL
MLA Citation
Kelly, SS, Shahlaee, A, Szabolcs, P, Driscoll, T, Eslin, D, Kurtzberg, J, and Martin, PL. "UNRELATED DONOR UMBILICAL CORD BLOOD TRANSPLANT FOR HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
75
End Page
75

RISK FACTOR ANALYSIS OF OUTCOMES AFTER UNRELATED CORD BLOOD TRANSPLANTATION FOR CHILDREN WITH HURLERS SYNDROME. AN EUROCORD-DUKE UNIVERSITY COLLABORATIVE STUDY

Authors
Boelens, JJ; Rocha, V; Aldenhoven, M; Wynn, R; Ionescu, I; Parikh, S; Prasad, V; Escolar, M; Cacazzana-Calvo, M; Gluckman, E; Kurtzberg, J; O'Meara, A
MLA Citation
Boelens, JJ, Rocha, V, Aldenhoven, M, Wynn, R, Ionescu, I, Parikh, S, Prasad, V, Escolar, M, Cacazzana-Calvo, M, Gluckman, E, Kurtzberg, J, and O'Meara, A. "RISK FACTOR ANALYSIS OF OUTCOMES AFTER UNRELATED CORD BLOOD TRANSPLANTATION FOR CHILDREN WITH HURLERS SYNDROME. AN EUROCORD-DUKE UNIVERSITY COLLABORATIVE STUDY." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
24
End Page
24

Emerging trends in transplantation of inherited metabolic diseases.

Allogeneic hematopoietic stem cell transplantation (HSCT) can prolong life and improve its quality in patients with inherited metabolic diseases. HSCT offers a permanent source of enzyme replacement therapy and also might mediate nonhematopoietic cell regeneration or repair. Unrelated cord blood is an exciting newer graft source for treatment of patients with these fatal disorders, providing increased access to donors and significant clinical efficacy, particularly when transplantation is performed in early stages. Pre-transplant performance status is highly predictive of overall survival.

Authors
Prasad, VK; Kurtzberg, J
MLA Citation
Prasad, VK, and Kurtzberg, J. "Emerging trends in transplantation of inherited metabolic diseases." Bone Marrow Transplant 41.2 (January 2008): 99-108. (Review)
PMID
18176609
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
41
Issue
2
Publish Date
2008
Start Page
99
End Page
108
DOI
10.1038/sj.bmt.1705970

Isolation of oligodendrocyte-like cells from human umbilical cord blood.

BACKGROUND: As human umbilical cord blood (UCB) is known to be a rich source of progenitor cells, the prospect of isolating a subset of these cells that could differentiate into cells of non-hematopoietic lineages suggests a therapeutic use for patients with inherited lysosomal and peroxisomal storage diseases currently treated with UCB transplantation. METHODS: Oligodendrocyte-like cells were isolated from UCB by density-gradient centrifugation and expanded using selective media. We then characterized this population of cells using standard immunohistochemical staining methods for neural cell proteins and polymerase chain reaction (PCR) to detect RNA sequences for myelin basic protein (MBP). We also developed a functional assay demonstrating myelination of neurons in vitro. RESULTS: Cells with oligodendrocyte-like morphology were reproducibly cultured ex vivo from fresh human UCB. Cells stained positively for multiple oligodendria cell markers (O1, MBP and CNPase) via immunohistochemical staining and flow cytometry. PCR confirmed the presence of MBP and CNPase mRNA. A further in vitro functional assay demonstrated the myelination of mature neuronal cells from the brain of a myelin-deficient murine model co-cultured with the oligodendrocyte-like cells. DISCUSSION: After human UCB transplant, donor-derived cells have been noted to migrate to the brain over time. Although is not known whether these cells solely deliver enzyme replacement or a subset engrafts and differentiates into mature neural cells, the clinical improvements noted in these patients suggest a potential role for targeted cellular therapy. Oligodendrocyte-like cells isolated ex vivo and expanded from human UCB could provide a potential cellular therapy for patients with demyelinating or dismyelinating diseases.

Authors
Tracy, E; Aldrink, J; Panosian, J; Beam, D; Thacker, J; Reese, M; Kurtzberg, J
MLA Citation
Tracy, E, Aldrink, J, Panosian, J, Beam, D, Thacker, J, Reese, M, and Kurtzberg, J. "Isolation of oligodendrocyte-like cells from human umbilical cord blood." Cytotherapy 10.5 (2008): 518-525.
PMID
18608351
Source
pubmed
Published In
Cytotherapy (Informa)
Volume
10
Issue
5
Publish Date
2008
Start Page
518
End Page
525
DOI
10.1080/14653240802154586

Correction of chronic granulomatous disease after second unrelated-donor umbilical cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for chronic granulomatous disease (CGD), but many patients lack a suitably matched related donor. We report successful outcomes after mismatched, unrelated-donor umbilical cord blood transplantation (uUCBT) in two boys with X-linked CGD. Both patients experienced autologous recovery after first transplants, required second transplants to achieve durable donor engraftment, and are alive 27 and 15 months post-transplant. Both had invasive fungal disease and received granulocyte transfusions. In conclusion, uUCBT is effective in children with CGD, but immunosuppression in the conditioning regimen may need to be increased to decrease the risk of graft rejection.

Authors
Parikh, SH; Szabolcs, P; Prasad, VK; Lakshminarayanan, S; Martin, PL; Driscoll, TA; Kurtzberg, J
MLA Citation
Parikh, SH, Szabolcs, P, Prasad, VK, Lakshminarayanan, S, Martin, PL, Driscoll, TA, and Kurtzberg, J. "Correction of chronic granulomatous disease after second unrelated-donor umbilical cord blood transplantation." Pediatr Blood Cancer 49.7 (December 2007): 982-984.
PMID
17941061
Source
pubmed
Published In
Pediatric Blood & Cancer
Volume
49
Issue
7
Publish Date
2007
Start Page
982
End Page
984
DOI
10.1002/pbc.21365

Avoidance of post-thaw wash prior to transplantation of plasma depleted cord blood (PD CB) is associated with improved engraftment & decreased severity of chronic GvHD (cGvHD) without increased relapse

Authors
Chow, R; Wang, B; Rosenthal, J; Nademanee, A; Karanes, C; Jaing, T-H; Graham, M; Delaney, C; Gjertson, D; Petz, L; Forman, S; Kurtzberg, J
MLA Citation
Chow, R, Wang, B, Rosenthal, J, Nademanee, A, Karanes, C, Jaing, T-H, Graham, M, Delaney, C, Gjertson, D, Petz, L, Forman, S, and Kurtzberg, J. "Avoidance of post-thaw wash prior to transplantation of plasma depleted cord blood (PD CB) is associated with improved engraftment & decreased severity of chronic GvHD (cGvHD) without increased relapse." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
494A
End Page
494A

Analysis of the cellular components of the graft and clinical characteristics of 159 children with lysosomal and peroxisomal disorders (LSD) undergoing unrelated umbilical cord blood transplantation at a single center

Authors
Prasad, VK; Medizabal, A; Parikh, SH; Szaboles, P; Driscoll, TA; Page, K; Lakshminarayan, S; Allison, J; Wood, S; Semmell, D; Escolar, ML; Martin, PL; Carter, S; Kurtzberg, J
MLA Citation
Prasad, VK, Medizabal, A, Parikh, SH, Szaboles, P, Driscoll, TA, Page, K, Lakshminarayan, S, Allison, J, Wood, S, Semmell, D, Escolar, ML, Martin, PL, Carter, S, and Kurtzberg, J. "Analysis of the cellular components of the graft and clinical characteristics of 159 children with lysosomal and peroxisomal disorders (LSD) undergoing unrelated umbilical cord blood transplantation at a single center." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
106A
End Page
106A

Risk factor analysis of outcomes after unrelated cord blood transplantation for children with Hurler's syndrome. An Eurocord-Duke University Collaborative Study

Authors
Boelens, JJ; Rocha, V; Aldenhoven, M; Wynn, R; O'Meara, A; Cavazzana-Calvo, M; Ionescu, I; Parikh, S; Prasad, V; Escolar, M; Gluckman, E; Kurtzberg, J
MLA Citation
Boelens, JJ, Rocha, V, Aldenhoven, M, Wynn, R, O'Meara, A, Cavazzana-Calvo, M, Ionescu, I, Parikh, S, Prasad, V, Escolar, M, Gluckman, E, and Kurtzberg, J. "Risk factor analysis of outcomes after unrelated cord blood transplantation for children with Hurler's syndrome. An Eurocord-Duke University Collaborative Study." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
350B
End Page
350B

Post transplant autoimmune hemolytic anemia and other cytopenias are increased in very young babies after unrelated donor umbilical cord blood transplantation

Authors
Page, KM; Mendizabal, A; Szabolcs, P; Wood, S; Prasad, V; Kurtzberg, J
MLA Citation
Page, KM, Mendizabal, A, Szabolcs, P, Wood, S, Prasad, V, and Kurtzberg, J. "Post transplant autoimmune hemolytic anemia and other cytopenias are increased in very young babies after unrelated donor umbilical cord blood transplantation." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
319A
End Page
319A

Use of mesenchymal stem cells to treat pediatric patients with severe (Grade III-IV) acute graft versus host disease refractory to steroid and other agents on a compassionate use basis

Authors
Prasad, VK; Lucas, KG; Kleiner, GI; Talano, J-AM; Jacobsohn, D; Szaboles, P; Monroy, R; Kurtzberg, J
MLA Citation
Prasad, VK, Lucas, KG, Kleiner, GI, Talano, J-AM, Jacobsohn, D, Szaboles, P, Monroy, R, and Kurtzberg, J. "Use of mesenchymal stem cells to treat pediatric patients with severe (Grade III-IV) acute graft versus host disease refractory to steroid and other agents on a compassionate use basis." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
872A
End Page
873A

Post thaw colony forming units (CFU) is a strong independent predictor of engraftment after unrelated donor umbilical cord blood transplantation (UCBT)

Authors
Page, KM; Mendizabal, A; Waters-Pick, B; Rurtsky, SA; Reese, M; Prasad, V; Kurtzberg, J
MLA Citation
Page, KM, Mendizabal, A, Waters-Pick, B, Rurtsky, SA, Reese, M, Prasad, V, and Kurtzberg, J. "Post thaw colony forming units (CFU) is a strong independent predictor of engraftment after unrelated donor umbilical cord blood transplantation (UCBT)." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
964A
End Page
964A

Ethical and policy issues relating to progenitor-cell-based strategies for prevention of atherosclerosis.

OBJECTIVE: To examine important ethical and societal issues relating to the use of progenitor-cell-based strategies for disease prevention, particularly atherosclerosis. BACKGROUND: Several nascent lines of evidence suggest the feasibility of using progenitor cells to reverse the health consequence of atherosclerosis. Such potential uses of progenitor cells are scientifically exciting, yet they raise important ethical and societal issues. METHOD: The Working Group on Ethics of Progenitor Cell-based Strategies for Disease Prevention met to discuss the relevant issues. Several drafts of a report were then circulated to the entire Working Group for comments until a consensus was reached. RESULTS: Scientific evidence suggests the appropriateness of using progenitor-cell-based strategies for some rare conditions involving atherosclerosis, but additional preclinical data are needed for other, more prevalent conditions before human trials begin. All such trials raise a set of ethical issues, especially since trials aimed at prevention rather than treatment may involve persons who do not yet have disease but will be exposed to the risks of interventions. In addition, enrolment in prevention trials may be hazardous and harmful if participants erroneously believe experimental interventions will necessarily prevent disease. Finally, given the high prevalence of atherosclerosis, there are some important public policy implications of taking such an approach to prevention, including the sources of progenitor cells for such interventions as well as the allocation of health resources. CONCLUSION: Potential uses of progenitor-cell-based strategies for preventing atherosclerosis must be considered in the context of a range of social and ethical issues.

Authors
Liao, SM; Goldschmidt-Clermont, PJ; Sugarman, J; Working Group on Ethics of Progenitor Cell-based Strategies for Disease Prevention,
MLA Citation
Liao, SM, Goldschmidt-Clermont, PJ, Sugarman, J, and Working Group on Ethics of Progenitor Cell-based Strategies for Disease Prevention, . "Ethical and policy issues relating to progenitor-cell-based strategies for prevention of atherosclerosis." J Med Ethics 33.11 (November 2007): 643-646.
PMID
17971466
Source
pubmed
Published In
Journal of medical ethics
Volume
33
Issue
11
Publish Date
2007
Start Page
643
End Page
646
DOI
10.1136/jme.2006.017251

Unrelated cord blood transplantation in children with sickle cell disease: review of four-center experience.

UCBT was performed in seven children with SCD and stroke (HLA match 4/6 n=5; 5/6 n=2). Four received myeloablative regimens (BU, CY, ATG plus FLU in one patient). One had primary graft failure, three had sustained engraftment, two with grade III-IV GVHD (one died, one developed chronic GVHD), one with stable mixed chimerism. Three patients treated with reduced-intensity regimens (FLU, BU or CY, ATG, TLI) failed to engraft; one engrafted after second UCBT (HU, TT, RXA, ALZ, TBI). Four patients (57%) developed viral infections. Engraftment, GVHD, and infection remain challenges.

Authors
Adamkiewicz, TV; Szabolcs, P; Haight, A; Baker, KS; Staba, S; Kedar, A; Chiang, KY; Krishnamurti, L; Boyer, MW; Kurtzberg, J; Wagner, JE; Wingard, JR; Yeager, AM
MLA Citation
Adamkiewicz, TV, Szabolcs, P, Haight, A, Baker, KS, Staba, S, Kedar, A, Chiang, KY, Krishnamurti, L, Boyer, MW, Kurtzberg, J, Wagner, JE, Wingard, JR, and Yeager, AM. "Unrelated cord blood transplantation in children with sickle cell disease: review of four-center experience." Pediatr Transplant 11.6 (September 2007): 641-644.
PMID
17663687
Source
pubmed
Published In
Pediatric Transplantation
Volume
11
Issue
6
Publish Date
2007
Start Page
641
End Page
644
DOI
10.1111/j.1399-3046.2007.00725.x

Results of unrelated cord blood transplant in fanconi anemia patients: risk factor analysis for engraftment and survival.

We retrospectively analyzed results of unrelated cord blood transplantation (UCBT) in 93 Fanconi anemia (FA) patients. Median age at transplantation was 8.6 years (1-45). The units transplanted were HLA-A, -B, or -DRB1 identical in 12 cases, 1 HLA mismatch in 35 cases, and 2 or 3 HLA differences in 45 cases. The median number of nucleated cells (NC) and CD34+ cells infused of recipient weight was 4.9x10(7)/kg and 1.9x10(5)/kg, respectively. Participating centers selected the preparative regimen of their choice, in 57 patients (61%), it included Fludarabine. Graft-versus-host disease (GVHD) prophylaxis consisted mostly of cyclosporine with prednisone. Cumulative incidence (CI) of neutrophil recovery was 60+/-5% at day +60. In multivariate analysis, Fludarabine containing regimen and NC infused>or=4.9x10(7)/kg were associated with higher probability of recovery. CI of grade II-IV acute and of chronic GVHD (aGVHD, cGVHD) was 32%+/-5% and 16%+/-4%, respectively. Overall survival (OS) was 40%+/-5%. In multivariate analysis, factors associated with favorable outcome were use of Fludarabine in the conditioning regimen, number of NC infused>or=4.9x10(7)/kg, and negative cytomegalovirus (CMV) serology in the recipient. In conclusion, factors easily modifiable such as donor selection and a Fludarabine-containing regimen can considerably improve survival in FA patients given a UCBT. These data are the basis for designing prospective protocols.

Authors
Gluckman, E; Rocha, V; Ionescu, I; Bierings, M; Harris, RE; Wagner, J; Kurtzberg, J; Champagne, MA; Bonfim, C; Bittencourt, M; Darbyshire, P; Fernandez, M-N; Locatelli, F; Pasquini, R; Eurocord-Netcord and EBMT,
MLA Citation
Gluckman, E, Rocha, V, Ionescu, I, Bierings, M, Harris, RE, Wagner, J, Kurtzberg, J, Champagne, MA, Bonfim, C, Bittencourt, M, Darbyshire, P, Fernandez, M-N, Locatelli, F, Pasquini, R, and Eurocord-Netcord and EBMT, . "Results of unrelated cord blood transplant in fanconi anemia patients: risk factor analysis for engraftment and survival." Biol Blood Marrow Transplant 13.9 (September 2007): 1073-1082.
PMID
17697970
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
9
Publish Date
2007
Start Page
1073
End Page
1082
DOI
10.1016/j.bbmt.2007.05.015

Allergic reactions to E. coli L-asparaginase do not affect outcome in childhood B-precursor acute lymphoblastic leukemia: a Children's Oncology Group Study.

We describe the outcome of children with B-precursor acute lymphoblastic leukemia registered on Pediatric Oncology Group 8602 who switched to Erwinia asparaginase (ASP) due to an allergy to the Escherichia coli product. Between February 1986 and January 1991, children in complete remission after induction that included intramuscular E. coli ASP (6000 U/m2x6) were randomized for consolidation. One regimen included intensive weekly intramuscular E. coli ASP (25,000 U/m2/wkx24). In case of an allergic reaction to E. coli ASP, Erwinia ASP was substituted at the same dose and schedule. Of the 540 eligible patients, 408 switched to Erwinia ASP due to an allergic reaction. Allergic reactions were significantly associated with younger age, white race, and standard-risk acute lymphoblastic leukemia. Multivariate Cox analysis adjusting for these factors demonstrated no correlation between the switch per se or the timing of the switch and event-free survival.

Authors
Wacker, P; Land, VJ; Camitta, BM; Kurtzberg, J; Pullen, J; Harris, MB; Shuster, JJ; Children's Oncology Study Group,
MLA Citation
Wacker, P, Land, VJ, Camitta, BM, Kurtzberg, J, Pullen, J, Harris, MB, Shuster, JJ, and Children's Oncology Study Group, . "Allergic reactions to E. coli L-asparaginase do not affect outcome in childhood B-precursor acute lymphoblastic leukemia: a Children's Oncology Group Study." J Pediatr Hematol Oncol 29.9 (September 2007): 627-632.
PMID
17805038
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
29
Issue
9
Publish Date
2007
Start Page
627
End Page
632
DOI
10.1097/MPH.0b013e3181483df1

Antimetabolite therapy for lesser-risk B-lineage acute lymphoblastic leukemia of childhood: a report from Children's Oncology Group Study P9201.

Pediatric Oncology Group (POG) protocol 9201 enrolled children with lesser-risk B-lineage acute lymphoblastic leukemia (ALL) defined by age (1-9), white blood cell count (WBC) less than 50 x 10(9)/L (50,000/microL), DNA findings of trisomies 4 and 10 (or DNA index > 1.16), and lack of overt central nervous system (CNS) leukemia. After vincristine, prednisone, and asparaginase induction, 650 of 653 eligible patients attained remission (3 induction deaths) and received 6 courses of intravenous methotrexate (1 g/m(2)) with daily mercaptopurine. Weekly intramuscular methotrexate was added during maintenance; pulses of vincristine and prednisone were administered with periodic intrathecal chemotherapy. Treatment duration was 2.5 years. No alkylators, epipodophylotoxins, anthracyclines, or radiation were given. The 6-year event-free survival (EFS) was 86.6% with overall survival (OS) of 97.2%. Patients with less than 5% marrow blasts on induction day 15 had superior EFS. A difference not reaching conventional statistical significance (P = .068) was noted for superior outcomes in patients with trisomies of chromosomes 4 and 10 versus those lacking double trisomies. Sex, ethnicity, CNS status, and WBC were not predictive. This indicates the great majority of children with lesser-risk B-lineage ALL are curable without agents with substantial late effects.

Authors
Chauvenet, AR; Martin, PL; Devidas, M; Linda, SB; Bell, BA; Kurtzberg, J; Pullen, J; Pettenati, MJ; Carroll, AJ; Shuster, JJ; Camitta, B
MLA Citation
Chauvenet, AR, Martin, PL, Devidas, M, Linda, SB, Bell, BA, Kurtzberg, J, Pullen, J, Pettenati, MJ, Carroll, AJ, Shuster, JJ, and Camitta, B. "Antimetabolite therapy for lesser-risk B-lineage acute lymphoblastic leukemia of childhood: a report from Children's Oncology Group Study P9201." Blood 110.4 (August 15, 2007): 1105-1111.
PMID
17442849
Source
pubmed
Published In
Blood
Volume
110
Issue
4
Publish Date
2007
Start Page
1105
End Page
1111
DOI
10.1182/blood-2006-12-061689

Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study.

BACKGROUND: Although umbilical cord blood is an accepted alternative to bone marrow for transplantation, allele-matched bone marrow is generally regarded as the preferred graft source. Our aim was to assess leukaemia-free survival after transplantations of these alternatives compared with present HLA-matching practices, and to assess the relative effect of cell dose and HLA match, and their potential interaction on leukaemia-free survival after cord-blood transplantation. METHODS: Outcomes of 503 children (<16 years) with acute leukaemia and transplanted with umbilical cord blood were compared with outcomes of 282 bone-marrow recipients. All transplantation took place in the USA. Recipients of umbilical cord blood were transplanted with grafts that were HLA-matched (n=35) or HLA-mismatched for one (n=201) or two antigens (n=267) (typing at antigen level for HLA-A and HLA-B, and allele level for HLA-DRB1). Bone-marrow recipients were transplanted with grafts that were matched at the allele level for HLA-A, HLA-B, HLA-C, and HLA-DRB (n=116), or mismatched (n=166). The primary endpoint was 5-year leukaemia-free survival. FINDINGS: In comparison with allele-matched bone-marrow transplants, 5-year leukaemia-free survival was similar to that after transplants of umbilical cord blood mismatched for either one or two antigens and possibly higher after transplants of HLA-matched umbilical cord blood. Transplant-related mortality rates were higher after transplants of two-antigen HLA-mismatched umbilical cord blood (relative risk 2.31, p=0.0003) and possibly after one-antigen HLA-mismatched low-cell-dose umbilical-cord-blood transplants (1.88, p=0.0455). Relapse rates were lower after two-antigen HLA-mismatched umbilical-cord-blood transplants (0.54, p=0.0045). INTERPRETATION: These data support the use of HLA-matched and one- or two-antigen HLA-mismatched umbilical cord blood in children with acute leukaemia who need transplantation. Because better HLA matching and higher cell doses significantly decrease the risk of transplant-related mortality after umbilical-cord-blood transplantation, greater investment in large-scale banking is needed to increase HLA diversity.

Authors
Eapen, M; Rubinstein, P; Zhang, M-J; Stevens, C; Kurtzberg, J; Scaradavou, A; Loberiza, FR; Champlin, RE; Klein, JP; Horowitz, MM; Wagner, JE
MLA Citation
Eapen, M, Rubinstein, P, Zhang, M-J, Stevens, C, Kurtzberg, J, Scaradavou, A, Loberiza, FR, Champlin, RE, Klein, JP, Horowitz, MM, and Wagner, JE. "Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study." Lancet 369.9577 (June 9, 2007): 1947-1954.
PMID
17560447
Source
pubmed
Published In
The Lancet
Volume
369
Issue
9577
Publish Date
2007
Start Page
1947
End Page
1954
DOI
10.1016/S0140-6736(07)60915-5

Intensified PEG-L-asparaginase and antimetabolite-based therapy for treatment of higher risk precursor-B acute lymphoblastic leukemia: a report from the Children's Oncology Group.

The Pediatric Oncology Group 9203 pilot protocol was designed to determine the feasibility of delivering 29 biweekly doses of polyethylene glycol (PEG)-L-asparaginase, on a backbone of intensive multiagent antimetabolite-based consolidation and maintenance in higher risk B-precursor acute lymphoblastic leukemia. Between June 1992 and August 1993, 34 patients were enrolled on this limited institution pilot. The 5-year event-free survival (+/-standard error) and overall survival (+/-standard error) were 68+/-8% and 76+/-7%, respectively. Excessive toxicities attributed to PEG-L-asparaginase and myelosuppression associated with cytosine arabinoside were encountered during consolidation resulting in early study closure and modification of therapy for those already enrolled. Ninety-two percent of methotrexate/cytosine arabinoside cycles were associated with grades 3 to 4 myelosuppression, and 24% resulted in delays in therapy of more than 7 days. Fifteen PEG-L-asparaginase related toxicities occurred in 13 patients (8 allergy, 4 pancreas, 2 central nervous system, and 1 hemorrhage). Intensification of therapy with PEG-L-asparaginase resulted in event-free survival and overall survival comparable to other studies of the same time period without the use of agents associated with long-term complications, such as anthracyclines, epipodophyllotoxins, and alkylating agents. However, excessive toxicity occurred with intensified PEG-L-asparaginase and antimetabolite based therapy delivered on this schedule.

Authors
Salzer, WL; Devidas, M; Shuster, JJ; Wang, C; Chauvenet, A; Asselin, BL; Camitta, BM; Kurtzberg, J; Children's Oncology Group,
MLA Citation
Salzer, WL, Devidas, M, Shuster, JJ, Wang, C, Chauvenet, A, Asselin, BL, Camitta, BM, Kurtzberg, J, and Children's Oncology Group, . "Intensified PEG-L-asparaginase and antimetabolite-based therapy for treatment of higher risk precursor-B acute lymphoblastic leukemia: a report from the Children's Oncology Group." J Pediatr Hematol Oncol 29.6 (June 2007): 369-375.
PMID
17551397
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
29
Issue
6
Publish Date
2007
Start Page
369
End Page
375
DOI
10.1097/MPH.0b013e3180640d54

Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. However, many patients lack suitable HLA- matched related donors and must rely on unmatched donors for a source of stem cells. The purpose of this study was to evaluate outcomes of unrelated donor umbilical cord blood transplantation after chemotherapy-based myeloablative conditioning and retrospectively determine if baseline studies correlate and help predict outcome. Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who lacked HL- matched related donors were referred to Duke University Medical Center for transplantation. These children were conditioned with myeloablative therapy including busulfan, cyclophosphamide, and antithymocyte globulin before receiving umbilical cord-blood transplants from unrelated donors. Baseline studies of neurophysiologic, neuroimaging, and neurodevelopmental status were performed and patients were subsequently evaluated for survival, engraftment, graft-versus-host disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline neuroimaging and neurophysiologic studies correlated with cognitive and motor function and if these studies were predictive of posttransplantation outcomes. The umbilical cord blood grafts had normal levels of very long chain fatty acids. They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil engraftment occurred at a median of 22.9 days after transplantation. Three patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic graft-versus-host disease. Cumulative incidence of overall survival of the group at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was 3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow transplantation, symptomatic patients faired poorly with lower survival and rapid deterioration of neurologic function. This study included 3 patients transplanted at a very young age (2.6-3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3-5 years posttransplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiologic studies failed to show statistically significant differences. Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.

Authors
Beam, D; Poe, MD; Provenzale, JM; Szabolcs, P; Martin, PL; Prasad, V; Parikh, S; Driscoll, T; Mukundan, S; Kurtzberg, J; Escolar, ML
MLA Citation
Beam, D, Poe, MD, Provenzale, JM, Szabolcs, P, Martin, PL, Prasad, V, Parikh, S, Driscoll, T, Mukundan, S, Kurtzberg, J, and Escolar, ML. "Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy." Biol Blood Marrow Transplant 13.6 (June 2007): 665-674.
PMID
17531776
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
6
Publish Date
2007
Start Page
665
End Page
674
DOI
10.1016/j.bbmt.2007.01.082

Comparison of the Digene Hybrid Capture System Cytomegalovirus (CMV) DNA (version 2.0), Roche CMV UL54 analyte-specific reagent, and QIAGEN RealArt CMV LightCycler PCR reagent tests using AcroMetrix OptiQuant CMV DNA quantification panels and specimens from allogeneic-stem-cell transplant recipients.

The Digene Hybrid Capture system cytomegalovirus (CMV) DNA (version 2.0), Roche CMV UL54 analyte-specific reagent, and QIAGEN RealArt CMV LightCycler PCR reagent tests were compared using whole-virus standards and plasma specimens collected from allogeneic-stem-cell transplant recipients. PCR assays showed better speed, sensitivity, and specificity.

Authors
Hanson, KE; Reller, LB; Kurtzberg, J; Horwitz, M; Long, G; Alexander, BD
MLA Citation
Hanson, KE, Reller, LB, Kurtzberg, J, Horwitz, M, Long, G, and Alexander, BD. "Comparison of the Digene Hybrid Capture System Cytomegalovirus (CMV) DNA (version 2.0), Roche CMV UL54 analyte-specific reagent, and QIAGEN RealArt CMV LightCycler PCR reagent tests using AcroMetrix OptiQuant CMV DNA quantification panels and specimens from allogeneic-stem-cell transplant recipients." J Clin Microbiol 45.6 (June 2007): 1972-1973.
PMID
17314226
Source
pubmed
Published In
Journal of clinical microbiology
Volume
45
Issue
6
Publish Date
2007
Start Page
1972
End Page
1973
DOI
10.1128/JCM.02515-06

Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511.

CALGB 9511 used pegaspargase (PEG-ASP) in lieu of the native enzyme. The aim was to compare differences in overall survival (OS) and disease-free survival (DFS) between patients who did and did not achieve asparagine depletion, defined by enzyme levels greater than 0.03 U/mL plasma for 14 consecutive days after at least 1 of 4 planned PEG-ASP administrations. Samples were available from 85 eligible patients. On univariate analyses, the 22 patients who did not achieve asparagine depletion had inferior OS (P = .002; hazard ratio [HR] = 2.37; 95% CI = 1.38-4.09) and DFS (P = .012; HR = 2.21; 95% CI = 1.19-4.13). After adjusting for age, performance status, leukocyte count, and karyotype in a proportional hazards model, both the OS and DFS HRs decreased to 1.8 (P = .056; 95% CI = 1.0-3.2 and P = .084; 95% CI = 0.9-3.6, respectively). We conclude that effective asparagine depletion with PEG-ASP is feasible as part of an intensive multiagent therapeutic regimen in adult acute lymphoblastic leukemia and appears associated with improved outcomes.

Authors
Wetzler, M; Sanford, BL; Kurtzberg, J; DeOliveira, D; Frankel, SR; Powell, BL; Kolitz, JE; Bloomfield, CD; Larson, RA
MLA Citation
Wetzler, M, Sanford, BL, Kurtzberg, J, DeOliveira, D, Frankel, SR, Powell, BL, Kolitz, JE, Bloomfield, CD, and Larson, RA. "Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511." Blood 109.10 (May 15, 2007): 4164-4167.
PMID
17264295
Source
pubmed
Published In
Blood
Volume
109
Issue
10
Publish Date
2007
Start Page
4164
End Page
4167
DOI
10.1182/blood-2006-09-045351

Use of MR Imaging Severity Scale to Estimate Neurobehavioral Function in Krabbe Disease

Authors
Provenzale, JM; Peddi, S; Poe, M; Mukundan, S; Kurtzberg, J; Escolar, M
MLA Citation
Provenzale, JM, Peddi, S, Poe, M, Mukundan, S, Kurtzberg, J, and Escolar, M. "Use of MR Imaging Severity Scale to Estimate Neurobehavioral Function in Krabbe Disease." AMERICAN JOURNAL OF ROENTGENOLOGY 188.5 (May 2007).
Source
wos-lite
Published In
AJR. American journal of roentgenology
Volume
188
Issue
5
Publish Date
2007

Hematopoietic cell transplantation for Chediak-Higashi syndrome.

We reviewed outcomes after allogeneic hematopoietic cell transplantation (HCT) in 35 children with Chediak-Higashi syndrome (CHS). Twenty-two patients had a history of the life-threatening accelerated phase of CHS before HCT and 11 were in accelerated phase at transplantation. Thirteen patients received their allograft from an human leukocyte antigen (HLA)-matched sibling, 10 from an alternative related donor and 12 from an unrelated donor. Eleven recipients of HLA-matched sibling donor, three recipients of alternative related donor and eight recipients of unrelated donor HCT are alive. With a median follow-up of 6.5 years, the 5-year probability of overall survival is 62%. Mortality was highest in those with accelerated phase disease at transplantation and after alternative related donor HCT. Only four of 11 patients with active disease at transplantation are alive. Seven recipients of alternative related donor HCT had active disease at transplantation and this may have influenced the poor outcome in this group. Although numbers are limited, HCT appears to be effective therapy for correcting and preventing hematologic and immunologic complications of CHS, and an unrelated donor may be a suitable alternative for patients without an HLA-matched sibling. Early referral and transplantation in remission after accelerated phase disease may improve disease-free survival.

Authors
Eapen, M; DeLaat, CA; Baker, KS; Cairo, MS; Cowan, MJ; Kurtzberg, J; Steward, CG; Veys, PA; Filipovich, AH
MLA Citation
Eapen, M, DeLaat, CA, Baker, KS, Cairo, MS, Cowan, MJ, Kurtzberg, J, Steward, CG, Veys, PA, and Filipovich, AH. "Hematopoietic cell transplantation for Chediak-Higashi syndrome." Bone Marrow Transplant 39.7 (April 2007): 411-415.
PMID
17293882
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
39
Issue
7
Publish Date
2007
Start Page
411
End Page
415
DOI
10.1038/sj.bmt.1705600

Improving skin care of the pediatric blood and marrow tranplant patient.

Authors
Smith, M; Frey, M; Kurtzberg, J
MLA Citation
Smith, M, Frey, M, and Kurtzberg, J. "Improving skin care of the pediatric blood and marrow tranplant patient." ONCOLOGY NURSING FORUM 34.2 (March 2007): 546-546.
Source
wos-lite
Published In
Oncology Nursing Forum
Volume
34
Issue
2
Publish Date
2007
Start Page
546
End Page
546

172: Post transplant autoimmune hemolytic anemia and other cytopenias are increased in young babies undergoing unrelated donor umbilical cord blood transplantation

Authors
Page, KM; Wood, S; Prasad, V; Szabolcs, P; Kurtzberg, J
MLA Citation
Page, KM, Wood, S, Prasad, V, Szabolcs, P, and Kurtzberg, J. "172: Post transplant autoimmune hemolytic anemia and other cytopenias are increased in young babies undergoing unrelated donor umbilical cord blood transplantation." February 2007.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
64
End Page
64
DOI
10.1016/j.bbmt.2006.12.176

372: Educating the pediatric blood and marrow transplant patients and families with diagnoses of genetic versus malignant diagnoses

Authors
Allison-Thacker, J; Robinette, D; Kurtzberg, J
MLA Citation
Allison-Thacker, J, Robinette, D, and Kurtzberg, J. "372: Educating the pediatric blood and marrow transplant patients and families with diagnoses of genetic versus malignant diagnoses." February 2007.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
136
End Page
136
DOI
10.1016/j.bbmt.2007.01.002

109: A pilot trial of unrelated donor umbilical cord blood transplanation (UCBT) augmented with cytokine-primed aldehyde dehydrogenase-bright (ALDHbr) cells

Authors
Kurtzberg, J; Balber, A; Mendizabal, A; Reese, M; Kaestner, A; Gentry, T; Hickerson, D; Allen, C; Sledge, LS; Deibert, E; Allison, J; Baker, J; Haley, NR
MLA Citation
Kurtzberg, J, Balber, A, Mendizabal, A, Reese, M, Kaestner, A, Gentry, T, Hickerson, D, Allen, C, Sledge, LS, Deibert, E, Allison, J, Baker, J, and Haley, NR. "109: A pilot trial of unrelated donor umbilical cord blood transplanation (UCBT) augmented with cytokine-primed aldehyde dehydrogenase-bright (ALDHbr) cells." February 2007.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
42
End Page
43
DOI
10.1016/j.bbmt.2006.12.113

23: Early hematopoietic cells, including megakaryocyte progenitors, are recovered in ALDH bright cell populations isolated by cell sorting from previously frozen umbilical cord blood

Authors
Deibert, E; Gentry, T; Foster, SJ; Kurtzberg, J; Balber, AE
MLA Citation
Deibert, E, Gentry, T, Foster, SJ, Kurtzberg, J, and Balber, AE. "23: Early hematopoietic cells, including megakaryocyte progenitors, are recovered in ALDH bright cell populations isolated by cell sorting from previously frozen umbilical cord blood." February 2007.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
11
End Page
11
DOI
10.1016/j.bbmt.2006.12.026

396: Nursing care of the child receiving inhaled ribavirin for the treatment of RSV in the peritransplant period

Authors
Murphy, C; Frey, M; Kurtzberg, J
MLA Citation
Murphy, C, Frey, M, and Kurtzberg, J. "396: Nursing care of the child receiving inhaled ribavirin for the treatment of RSV in the peritransplant period." February 2007.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
143
End Page
143
DOI
10.1016/j.bbmt.2007.01.026

Outcomes of unrelated umbilical cord blood transplantation in pediatric patients with myelodysplastic syndrome

Authors
Parikh, SH; Mendizabal, A; Martin, PL; Szaboles, P; Prasad, VK; Driscoll, TA; Kurtzberg, J
MLA Citation
Parikh, SH, Mendizabal, A, Martin, PL, Szaboles, P, Prasad, VK, Driscoll, TA, and Kurtzberg, J. "Outcomes of unrelated umbilical cord blood transplantation in pediatric patients with myelodysplastic syndrome." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
64
End Page
65

Chronic graft-versus host disease (GVHD) in children with mucopolysacharidoses (MPS) two years after unrelated donor umbilical cord blood transplantation (UCBT)

Authors
Szaboles, P; Martin, RL; Parikh, S; Prasad, VK; Vinesett, R; Escolar, ML; Kurtzberg, J
MLA Citation
Szaboles, P, Martin, RL, Parikh, S, Prasad, VK, Vinesett, R, Escolar, ML, and Kurtzberg, J. "Chronic graft-versus host disease (GVHD) in children with mucopolysacharidoses (MPS) two years after unrelated donor umbilical cord blood transplantation (UCBT)." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
67
End Page
67
DOI
10.1016/j.bbmt.2006.12.184

Treatment of acute graft vs. host disease after unrelated donor umbilical cord blood transplantation in pediatric patients

Authors
Baker, EJ; Frey, MA; Kurtzberg, J
MLA Citation
Baker, EJ, Frey, MA, and Kurtzberg, J. "Treatment of acute graft vs. host disease after unrelated donor umbilical cord blood transplantation in pediatric patients." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
137
End Page
137
DOI
10.1016/j.bbmt.2007.01.006

Fly me to the moon

Authors
Caraher, R; Ahmed, S; Frey, MA; Jordan, LE; Kurtzberg, J
MLA Citation
Caraher, R, Ahmed, S, Frey, MA, Jordan, LE, and Kurtzberg, J. "Fly me to the moon." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
138
End Page
138
DOI
10.1016/j.bbmt.2007.01.009

Prophylaxis of pneumocystis carinii pneumonia (PCP) with inhaled pentamidine in pediatric patients undergoing hematopoietic stem cell transplantation

Authors
Zelko, VS; Frey, MA; Kurtzberg, J
MLA Citation
Zelko, VS, Frey, MA, and Kurtzberg, J. "Prophylaxis of pneumocystis carinii pneumonia (PCP) with inhaled pentamidine in pediatric patients undergoing hematopoietic stem cell transplantation." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
150
End Page
151
DOI
10.1016/j.bbmt.2007.01.053

Engraftment syndrome: A complication of hematopoietic stem cell transplantation

Authors
Summers, E; Frey, MA; Kurtzberg, J
MLA Citation
Summers, E, Frey, MA, and Kurtzberg, J. "Engraftment syndrome: A complication of hematopoietic stem cell transplantation." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
148
End Page
148
DOI
10.1016/j.bbmt.2007.01.044

The duke pediatric blood and marrow transplant nursing graduate integration program

Authors
Stewart, RM; Frey, MA; Stanton, T; Guess, C; Kurtzberg, J
MLA Citation
Stewart, RM, Frey, MA, Stanton, T, Guess, C, and Kurtzberg, J. "The duke pediatric blood and marrow transplant nursing graduate integration program." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
148
End Page
148
DOI
10.1016/j.bbmt.2007.01.043

Outcomes of pediatric patients transplanted a second time after experiencing graft failure with unrelated donor umbilical cord blood transplantation

Authors
Baker, JH; Martin, PL; Driscoll, T; Szabolcs, P; Allison, J; Gurganus, K; Ciocci, G; Parikh, S; Prasad, V; Kurtzberg, J
MLA Citation
Baker, JH, Martin, PL, Driscoll, T, Szabolcs, P, Allison, J, Gurganus, K, Ciocci, G, Parikh, S, Prasad, V, and Kurtzberg, J. "Outcomes of pediatric patients transplanted a second time after experiencing graft failure with unrelated donor umbilical cord blood transplantation." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
137
End Page
137
DOI
10.1016/j.bbmt.2007.01.007

The long and winding road of the clinical development of Nelarabine.

Authors
Kurtzberg, J
MLA Citation
Kurtzberg, J. "The long and winding road of the clinical development of Nelarabine." Leuk Lymphoma 48.1 (January 2007): 1-2.
PMID
17325839
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
48
Issue
1
Publish Date
2007
Start Page
1
End Page
2
DOI
10.1080/10428190601135447

Isolation of early hematopoietic cells, including megakaryocyte progenitors, in the ALDH-bright cell population of cryopreserved, banked UC blood.

BACKGROUND: ALDH-bright (ALDH(br)) cell populations sorted from freshly collected umbilical cord blood (UCB) on the basis of their high aldehyde dehydrogenase (ALDH) activity are highly enriched for HPC. HPC with low ALDH activity (ALDH(dim)) are primarily short-term progenitors, whereas progenitors that initiate long-term cultures or establish long-term grafts in xenograft models are ALDH(br). We examined the multilineage hematopoietic and platelet progenitor activities of ALDH(br) cells recovered from cryopreserved UCB units typically employed in the practice of clinical transplantation. METHODS: Frozen UCB units were thawed, washed, immunomagnetically depleted of cells expressing glycophorin A and CD14, reacted for flow cytometric detection of ALDH, and sorted to yield ALDH(br) and ALDH(dim) populations. We measured surface Ag expression and viability of cells in the ALDH(br) and ALDH(dim) populations by flow cytometry and hematopoietic (CFC-H) and megakaryocytic (CFC-Mk) colony-forming cells in each population. RESULTS: ALDH(br) populations isolated from thawed UCB cells were highly enriched for CD34(+) and CD133(+) cells. Flow-sorted ALDH(br) populations were enriched 1116-fold in CFC-H, 10-fold in multilineage GEMM colonies and 2015-fold in CFC-Mk compared with the ALDH(dim) population. All progenitors giving rise to large Mk colonies were derived from ALDH(br) populations. DISCUSSION: ALDH(br) populations recovered from thawed, banked UCB with the method we describe have HPC activity and may be useful in the clinic to facilitate reconstitution of erythroid, myeloid and megakaryocytic blood elements.

Authors
Gentry, T; Deibert, E; Foster, SJ; Haley, R; Kurtzberg, J; Balber, AE
MLA Citation
Gentry, T, Deibert, E, Foster, SJ, Haley, R, Kurtzberg, J, and Balber, AE. "Isolation of early hematopoietic cells, including megakaryocyte progenitors, in the ALDH-bright cell population of cryopreserved, banked UC blood." Cytotherapy 9.6 (2007): 569-576.
PMID
17882722
Source
pubmed
Published In
Cytotherapy (Informa)
Volume
9
Issue
6
Publish Date
2007
Start Page
569
End Page
576
DOI
10.1080/14653240701466347

Modification of a commercial cell sorter to support efficient and reliable preparation of ALDH-bright cells for clinical use.

BACKGROUND: Cell populations manufactured by conventional commercial cell sorters have been safely infused into patients, but reliably sterilizing these instruments remains challenging. We are developing clinical protocols involving use of ALDH bright cells manufactured by cell sorting in patients. However, we encountered problems when we attempted to reliably sterilize the FACSAria cell sorter using standard methods. RESULTS: We have identified and modified potential sources of microbial contamination in several FACSAria systems. We added new filter systems to the sheath and sample air lines, to the wet cart fluid supply, and to the sample line. Sheath was provided from an external sterile, disposable bag through sterile disposable tubing sets. The plenum reservoirs were modified in several ways to allow efficient decontamination of internal surfaces. A new bubble filter assembly was added and one valve was eliminated from the sample pathway to improve flow cell sterilization. A new cleaning and sterilization protocol was developed and validated. All cell products manufactured using the modified instrument and validated cleaning protocol have met lot release criteria for prevention of microbial contamination and safe clinical use. DISCUSSION: The instrument modification and cleaning protocol described enable reliable manufacture of ALDH bright cell populations that are suitable for clinical trials. We have manufactured nineteen consecutive samples that meet all clinical release criteria in an on-going Phase 1 human trial.

Authors
Hickerson, D; Fiordalisi, M; Reese, M; Deibert, E; Balber, AE; Kurtzberg, J; Haley, NR
MLA Citation
Hickerson, D, Fiordalisi, M, Reese, M, Deibert, E, Balber, AE, Kurtzberg, J, and Haley, NR. "Modification of a commercial cell sorter to support efficient and reliable preparation of ALDH-bright cells for clinical use." Cytotherapy 9.6 (2007): 562-568.
PMID
17882721
Source
pubmed
Published In
Cytotherapy (Informa)
Volume
9
Issue
6
Publish Date
2007
Start Page
562
End Page
568
DOI
10.1080/14653240701466321

Cord blood banking for potential future transplantation

In recent years, umbilical cord blood, which contains a rich source of hematopoietic stem and progenitor cells, has been used successfully as an alternative allogeneic donor source to treat a variety of pediatric genetic, hematologic, immunologic, and oncologic disorders. Because there is diminished risk of graft-versus-host disease after transplantation of cord stem cells using matched related donors, the use of less-than-completely matched HLA cord blood stem cells may incur less risk of graft-versus-host disease than mismatched cells from either a related or unrelated "walking" donor, although this remains to be proven. Gene-therapy research involving modification of autologous cord blood stem cells for the treatment of childhood genetic disorders, although experimental at the present time, may prove to be of value. These scientific advances have resulted in the establishment of not-for-profit and for-profit cord blood-banking programs for allogeneic and autologous cord blood transplantation. Many issues confront institutions that wish to establish or participate in such programs. Parents often seek information from their physicians about this new biotechnology option. This document is intended to provide information to guide physicians in responding to parents' questions about cord blood donation and banking and the types and quality of cord blood banks. Provided also are recommendations about appropriate ethical and operational standards, including informed consent policies, financial disclosures, and conflict-of-interest policies for physicians, institutions, and organizations that operate or have a relationship with cord blood-banking programs. Copyright © 2007 by the American Academy of Pediatrics.

Authors
Cairo, MS; Kurtzberg, J; Lubin, BH; Shearer, WT; Feig, SA; Corrigan, JJ; Gamis, AS; Kodish, ED; Lane, PA; Hutter, JJ; Berkow, RL; Lubin, NL; Forman, EN; Laskosz, L; Williams, PV; Chipps, BE; Fasano, MB; Lester, MR; Sicherer, SH; Virant, FS; Bahna, SL; Welch, MJ; Rachelefsky, GS; Mahr, TA; Kanda, PT
MLA Citation
Cairo, MS, Kurtzberg, J, Lubin, BH, Shearer, WT, Feig, SA, Corrigan, JJ, Gamis, AS, Kodish, ED, Lane, PA, Hutter, JJ, Berkow, RL, Lubin, NL, Forman, EN, Laskosz, L, Williams, PV, Chipps, BE, Fasano, MB, Lester, MR, Sicherer, SH, Virant, FS, Bahna, SL, Welch, MJ, Rachelefsky, GS, Mahr, TA, and Kanda, PT. "Cord blood banking for potential future transplantation." Pediatrics 119.1 (2007): 165-170.
PMID
17200285
Source
scival
Published In
Pediatrics
Volume
119
Issue
1
Publish Date
2007
Start Page
165
End Page
170
DOI
10.1542/peds.2006-2901

Antigen-specific T-lymphocyte function after cord blood transplantation.

It has not been possible to determine the singular contribution of naive T lymphocytes to antigen-specific immunity after hematopoietic stem cell transplantation (HSCT), because of the confounding effects of donor-derived antigen-specific T lymphocytes present in most hematopoietic stem cell (HSC) products. Because umbilical cord blood contains only naive T lymphocytes, we longitudinally evaluated the recipients of unrelated cord blood transplantation (UCBT) for the presence of T lymphocytes with specificity for herpesviruses, to determine the contribution of the naive T lymphocytes to antigen-specific immune reconstitution after HSCT. Antigen-specific T lymphocytes were detected early after UCBT (herpes simplex virus on day 29; cytomegalovirus on day 44; varicella zoster virus on day 94). Overall, 66 of 153 UCBT recipients developed antigen-specific T lymphocytes to 1 or more herpesviruses during the evaluation period. The likelihood of developing antigen-specific T lymphocyte function was not associated with immunophenotypic T lymphocyte reconstitution, transplant cell dose, primary disease, or acute and chronic graft-versus-host disease. These results indicate that naive T lymphocytes present in the HSC inoculum can contribute to the generation of antigen-specific T-lymphocyte immunity early after transplantation.

Authors
Cohen, G; Carter, SL; Weinberg, KI; Masinsin, B; Guinan, E; Kurtzberg, J; Wagner, JE; Kernan, NA; Parkman, R
MLA Citation
Cohen, G, Carter, SL, Weinberg, KI, Masinsin, B, Guinan, E, Kurtzberg, J, Wagner, JE, Kernan, NA, and Parkman, R. "Antigen-specific T-lymphocyte function after cord blood transplantation." Biol Blood Marrow Transplant 12.12 (December 2006): 1335-1342.
PMID
17162216
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
12
Publish Date
2006
Start Page
1335
End Page
1342
DOI
10.1016/j.bbmt.2006.08.036

Outcomes of 122 diverse adult and pediatric cord blood transplant recipients from a large cord blood bank.

BACKGROUND: Umbilical cord blood is a useful stem cell source for some patients. The American Red Cross Cord Blood Program was established as a national network of cord blood banks. Nine thousand cord blood units were cryopreserved for transplant use. STUDY DESIGN AND METHODS: This report summarizes the experience with the first 125 cord blood units that have been distributed for transplant for 122 patients at 36 different transplant centers worldwide. Patients were treated with a variety of conditioning regimens. RESULTS: Most patients had acute myelogeneous leukemia (21%), genetic disorders (22%), or acute lymphoblastic leukemia (18%). The median age of the patients was 11 years with a range of 2 months to 63 years. The patients ranged in size from 3 to 120 kg (median, 39 kg). The median number of days to neutrophil engraftment was 22, and the median number of days to platelet engraftment was 63. Thirty percent of patients experienced Grades III to IV acute graft-versus-host disease (GVHD). Survival at 1 year after transplant was 35 percent, with recurrent disease the major cause of death. In multivariate analysis, only age less than 18 years was a significant predictor for improved survival. Forty-two percent of patients were non-Caucasian. Engraftment, GVHD, survival, and disease-free survival were similar among Caucasian and non-Caucasian patients. CONCLUSION: Umbilical cord blood serves as a satisfactory stem cell source for a diverse group of pediatric and adult patients.

Authors
Ballen, KK; Haley, NR; Kurtzberg, J; Lane, TA; Lindgren, BR; Miller, JP; Newman, B; McCullough, J
MLA Citation
Ballen, KK, Haley, NR, Kurtzberg, J, Lane, TA, Lindgren, BR, Miller, JP, Newman, B, and McCullough, J. "Outcomes of 122 diverse adult and pediatric cord blood transplant recipients from a large cord blood bank." Transfusion 46.12 (December 2006): 2063-2070.
PMID
17176317
Source
pubmed
Published In
Transfusion
Volume
46
Issue
12
Publish Date
2006
Start Page
2063
End Page
2070
DOI
10.1111/j.1537-2995.2006.01032.x

Transplantation of a child with sickle cell anemia with an unrelated cord blood unit after reduced intensity conditioning.

Sickle cell disease can be corrected by hematopoietic cell transplantation but success is limited by low availability of matched related/unrelated donors and comorbidities leading to the increased transplant-related morbidity/mortality. There is a need for expanded donor pools and reduced intensity regimens. We describe a case of a second unrelated cord blood transplant after a novel preparative regimen in a child with sickle cell disease related stroke and liver fibrosis. Hydroxyurea, rituximab, and alemtuzumab were followed by thiotepa and low dose total body irradiation before unrelated cord blood transplant. Rapid full donor chimerism and improved performance status was achieved and sustained over 2 years after transplant.

Authors
Mazur, M; Kurtzberg, J; Halperin, E; Ciocci, G; Szabolcs, P
MLA Citation
Mazur, M, Kurtzberg, J, Halperin, E, Ciocci, G, and Szabolcs, P. "Transplantation of a child with sickle cell anemia with an unrelated cord blood unit after reduced intensity conditioning." J Pediatr Hematol Oncol 28.12 (December 2006): 840-844.
PMID
17164657
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
28
Issue
12
Publish Date
2006
Start Page
840
End Page
844
DOI
10.1097/MPH.0b013e31802d3e53

Preliminary results of a pilot trial of unrelated umbilical cord blood transplantation (UCBT) augmented with cytolkine-primed aldehyde dehydrogenase-bright (ALDHbr) cells.

Authors
Kurtzberg, J; Balber, A; Mendizabal, A; Reese, M; Kaestner, A; Gentry, T; Hickerson, D; Allen, C; Sledge, LS; Deibert, E; Allison, J; Baker, J; Rebecca Haley, N
MLA Citation
Kurtzberg, J, Balber, A, Mendizabal, A, Reese, M, Kaestner, A, Gentry, T, Hickerson, D, Allen, C, Sledge, LS, Deibert, E, Allison, J, Baker, J, and Rebecca Haley, N. "Preliminary results of a pilot trial of unrelated umbilical cord blood transplantation (UCBT) augmented with cytolkine-primed aldehyde dehydrogenase-bright (ALDHbr) cells." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
1040A
End Page
1040A

Unrelated donor hematopoietic stem cell transplantation (HSCT) in children with acute leukemia: Risks and benefits of umbilical cord blood (CB) versus HLAA, B, C, DRB1 allele-matched bone marrow (BM).

Authors
Eapen, M; Rubinstein, P; Zhang, M-J; Stevens, C; Kurtzberg, J; Scaradavou, A; Horowitz, MM; Wagner, JE
MLA Citation
Eapen, M, Rubinstein, P, Zhang, M-J, Stevens, C, Kurtzberg, J, Scaradavou, A, Horowitz, MM, and Wagner, JE. "Unrelated donor hematopoietic stem cell transplantation (HSCT) in children with acute leukemia: Risks and benefits of umbilical cord blood (CB) versus HLAA, B, C, DRB1 allele-matched bone marrow (BM)." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
133A
End Page
133A

Prospective analysis of TEL and MLL gene rearrangements in childhood acute lymphoblastic leukemia: A Children's Oncology Group study.

Authors
Rubnitz, J; Wichlan, D; Devidas, M; Shuster, J; Kurtzberg, J; Bell, B; Hungers, S; Chauvenet, A; Pui, C-H; Camitta, B; Pullen, J
MLA Citation
Rubnitz, J, Wichlan, D, Devidas, M, Shuster, J, Kurtzberg, J, Bell, B, Hungers, S, Chauvenet, A, Pui, C-H, Camitta, B, and Pullen, J. "Prospective analysis of TEL and MLL gene rearrangements in childhood acute lymphoblastic leukemia: A Children's Oncology Group study." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
68A
End Page
69A

Testicular relapse in lesser, standard, and high risk patients treated with frontline therapy for childhood ALL. Pediatric oncology group protocols 9201, 9405, 9605, and 9406.

Authors
Harrison, M; Bell, B; Chauvenet, A; Kurtzberg, J; Camitta, B; Devidas, M
MLA Citation
Harrison, M, Bell, B, Chauvenet, A, Kurtzberg, J, Camitta, B, and Devidas, M. "Testicular relapse in lesser, standard, and high risk patients treated with frontline therapy for childhood ALL. Pediatric oncology group protocols 9201, 9405, 9605, and 9406." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
528A
End Page
528A

Dosing of post-thaw colony forming units (CFU) and CD34 cells predict engraftment and survival in recipients of banked unrelated donor umbilical cord blood (UCB) for allogeneic transplantation.

Authors
Kurtzberg, J; Mendizabal, A; Carter, S; Allison, J; Avrutsky, S; Stephens, C; Waters-Pick, B
MLA Citation
Kurtzberg, J, Mendizabal, A, Carter, S, Allison, J, Avrutsky, S, Stephens, C, and Waters-Pick, B. "Dosing of post-thaw colony forming units (CFU) and CD34 cells predict engraftment and survival in recipients of banked unrelated donor umbilical cord blood (UCB) for allogeneic transplantation." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
912A
End Page
913A

Acute graft versus host disease (GVHD) is increased in patients receiving cyclosporine/celicept as frontline prophylaxis against GVKD in pediatric patients undergoing allogeneic stem cell transplantation.

Authors
Lakshminarayanan, S; Szabolcs, P; Prasad, V; Parikh, S; Wood, S; Ciocci, G; Stafford, L; Boyd, L; Driscoll, T; Martin, PL; Kurtzberg, J
MLA Citation
Lakshminarayanan, S, Szabolcs, P, Prasad, V, Parikh, S, Wood, S, Ciocci, G, Stafford, L, Boyd, L, Driscoll, T, Martin, PL, and Kurtzberg, J. "Acute graft versus host disease (GVHD) is increased in patients receiving cyclosporine/celicept as frontline prophylaxis against GVKD in pediatric patients undergoing allogeneic stem cell transplantation." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
820A
End Page
820A

Melphalan containing cytoreduction results in a good overall survival (OS) in pediatric patients with relapse or refractory AML undergoing unrelated umbilical cord blood transplantation (UCBT).

Authors
Prasad, VK; Wu, J; Martin, PL; Driscoll, TA; Parikh, SH; Semmel, D; Moffet, J; Stafford, L; Shonkwiler, A; Carter, S; Szabolcs, P; Kurtzberg, J
MLA Citation
Prasad, VK, Wu, J, Martin, PL, Driscoll, TA, Parikh, SH, Semmel, D, Moffet, J, Stafford, L, Shonkwiler, A, Carter, S, Szabolcs, P, and Kurtzberg, J. "Melphalan containing cytoreduction results in a good overall survival (OS) in pediatric patients with relapse or refractory AML undergoing unrelated umbilical cord blood transplantation (UCBT)." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
899A
End Page
899A

Defibrotide (DF) for the treatment of severe veno-occlusive disease (sVOD) and multi-organ failure (MOF) post SCT: Final results of a multi-center, randomized, dose-finding trial.

Authors
Richardson, P; Soiffer, RJ; Antin, JH; Jin, Z; Kurtzberg, J; Martin, PL; Steinbach, G; Murray, KF; Vogelsang, GB; Chen, A; Krishnan, A; Kernan, NA; Avigan, D; Spitzer, TR; Warren, D; Revta, C; Wei, LJ; Iacobelli, M; McDonald, GB; Guinan, EC
MLA Citation
Richardson, P, Soiffer, RJ, Antin, JH, Jin, Z, Kurtzberg, J, Martin, PL, Steinbach, G, Murray, KF, Vogelsang, GB, Chen, A, Krishnan, A, Kernan, NA, Avigan, D, Spitzer, TR, Warren, D, Revta, C, Wei, LJ, Iacobelli, M, McDonald, GB, and Guinan, EC. "Defibrotide (DF) for the treatment of severe veno-occlusive disease (sVOD) and multi-organ failure (MOF) post SCT: Final results of a multi-center, randomized, dose-finding trial." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
17A
End Page
18A

The addition of fludarabine to a conventional Busulfan/Melphalan/Anti-Thymocyte globulin (Flu/Bu/Mel/ATG) preparative regimen increased engraftment without additional toxicity.

Authors
Lakshminarayanan, S; Mendizabal, A; Prasad, V; Parikh, S; Szabolcs, P; Driscoll, T; Schweitzer, M; Kassmann, B; Paden, M; Robinette, D; Martin, PL; Kurtzberg, J
MLA Citation
Lakshminarayanan, S, Mendizabal, A, Prasad, V, Parikh, S, Szabolcs, P, Driscoll, T, Schweitzer, M, Kassmann, B, Paden, M, Robinette, D, Martin, PL, and Kurtzberg, J. "The addition of fludarabine to a conventional Busulfan/Melphalan/Anti-Thymocyte globulin (Flu/Bu/Mel/ATG) preparative regimen increased engraftment without additional toxicity." BLOOD 108.11 (November 16, 2006): 833A-834A.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
833A
End Page
834A

Multivariate analysis of patient and graft specific factors among 330 recipients of unrelated cord blood transplant (UCBT) to predict risk of death from opportunistic infections in the first 6 months after UCBT.

Authors
Szabolcs, P; Peterson, BL; Niedzwiecki, D; Chao, N; Kurtzberg, J
MLA Citation
Szabolcs, P, Peterson, BL, Niedzwiecki, D, Chao, N, and Kurtzberg, J. "Multivariate analysis of patient and graft specific factors among 330 recipients of unrelated cord blood transplant (UCBT) to predict risk of death from opportunistic infections in the first 6 months after UCBT." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
810A
End Page
810A

In vitro priming and expansion of cytomegalovirus-specific Th1 and Tc1 T cells from naive cord blood lymphocytes.

Adoptive transfer of CMV-specific cytotoxic T cells (CTLs) expanded in vitro from memory donor T cells can reduce the incidence of CMV disease in allogeneic transplant recipients. However, this approach has been unavailable in the cord blood (CB) transplantation setting because CB T cells are antigen naive and biased toward Th2/Tc2 function. We developed a protocol to in vitro prime and expand CMV-specific CTLs from CB. T cells were primed with cytokines to trigger skewing toward Th1/Tc1 lineage before encountering monocyte and CD34+ progenitor-derived dendritic cells loaded with CMV antigen and its immune complex. CMV-pulsed cultures expanded significantly more over 4 to 6 weeks than CMV cultures despite identical cytokine milieu. T cells isolated from CMV+ cultures showed a preferential expansion of CD45RA-/RO+/CD27+ T cells compared to CMV- cultures. CMV-specific IFN-gamma- and TNF-alpha-producing CD4+ (Th1) and CD8+ (Tc1) T cells were enriched after 3 to 4 weeks and CMV-specific cytotoxicity developed 1 to 2 weeks later.

Authors
Park, K-D; Marti, L; Kurtzberg, J; Szabolcs, P
MLA Citation
Park, K-D, Marti, L, Kurtzberg, J, and Szabolcs, P. "In vitro priming and expansion of cytomegalovirus-specific Th1 and Tc1 T cells from naive cord blood lymphocytes." Blood 108.5 (September 1, 2006): 1770-1773.
PMID
16675712
Source
pubmed
Published In
Blood
Volume
108
Issue
5
Publish Date
2006
Start Page
1770
End Page
1773
DOI
10.1182/blood-2005-10-006536

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.

Authors
Parkman, R; Cohen, G; Carter, SL; Weinberg, KI; Masinsin, B; Guinan, E; Kurtzberg, J; Wagner, JE; Kernan, NA
MLA Citation
Parkman, R, Cohen, G, Carter, SL, Weinberg, KI, Masinsin, B, Guinan, E, Kurtzberg, J, Wagner, JE, and Kernan, NA. "Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation." Biol Blood Marrow Transplant 12.9 (September 2006): 919-927.
PMID
16920557
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
9
Publish Date
2006
Start Page
919
End Page
927
DOI
10.1016/j.bbmt.2006.05.008

Neurophysiologic assessment of mucopolysaccharidosis III.

OBJECTIVE: To describe finding of various neurophysiologic tests in patients with mucopolysaccharidosis III (MPS III) early in the disease course. METHODS: Patients were evaluated with flash visual evoked potentials (VEP), brainstem auditory evoked potentials (BAEP), electroencephalography (EEG), and nerve conduction studies (NCS) before they underwent hematopoietic stem cell transplantation (HSCT). RESULTS: Thirteen children underwent at least one neurophysiologic test before HSCT. The mean age at testing was 2.7 years. Ten of 11 (91%) patients had a normal flash VEP, and all 9 who had BAEP had normal central conduction. EEG was normal in 7/13 (54%), with the others showing diffuse slowing. NCS was normal in 10/11 (91%) patients. CONCLUSIONS: Despite extensive central nervous system involvement in MPS III, flash VEP and BAEP are almost always normal. EEG is often abnormal early in the disease. SIGNIFICANCE: This is the first report of neurophysiologic tests in a large series of MPS III patients.

Authors
Husain, AM; Escolar, ML; Kurtzberg, J
MLA Citation
Husain, AM, Escolar, ML, and Kurtzberg, J. "Neurophysiologic assessment of mucopolysaccharidosis III." Clin Neurophysiol 117.9 (September 2006): 2059-2063.
PMID
16884953
Source
pubmed
Published In
Clinical Neurophysiology
Volume
117
Issue
9
Publish Date
2006
Start Page
2059
End Page
2063
DOI
10.1016/j.clinph.2006.05.031

A staging system for infantile Krabbe disease to predict outcome after unrelated umbilical cord blood transplantation.

OBJECTIVE: Infantile Krabbe disease, a rare neurodegenerative disorder that leads to rapid demyelination, dysmyelination, and death in the first 2 years of life, is responsive to treatment with umbilical cord blood transplantation provided that the patient is treated in the first weeks of life. At present, family history is the only way to identify patients that are asymptomatic with most patients being diagnosed after onset of symptoms. We hypothesized that a staging system based on clinical indicators and neurophysiological and neuroimaging measures can predict posttreatment variation in patients diagnosed with infantile Krabbe disease. METHODS: A retrospective review of pretransplant clinical indicators and neurodevelopmental, brain imaging and neurophysiological measures was performed in 42 patients being considered for treatment with umbilical cord blood transplantation. Based on these evaluations, an expert system approach was used to develop a staging system for infantile Krabbe disease. Another set of analyses in the subset of patients who were transplanted (n = 29) evaluated the association between pretransplant stage of disease and posttransplant neurodevelopmental outcomes. RESULTS: A staging algorithm for infants with infantile Krabbe disease was developed and tested for predicting neurodevelopmental outcome after umbilical cord blood transplantation. Standard neurophysiological and neuroimaging tests were not useful in the staging algorithm. Clinical indicators were found to best classify stage of disease. Pretransplant stage was found to be predictive of neurodevelopmental outcome. CONCLUSIONS: We conclude that the clinical staging system based solely on signs and symptoms of disease can be used to predict outcomes after umbilical cord blood transplantation. This staging system can be used prospectively to guide physicians unfamiliar with the disorder in evaluating, monitoring, and counseling families about treatment outcomes. The staging will be useful for both patients diagnosed with infantile Krabbe disease because of clinical symptoms and those identified through neonatal screening programs.

Authors
Escolar, ML; Poe, MD; Martin, HR; Kurtzberg, J
MLA Citation
Escolar, ML, Poe, MD, Martin, HR, and Kurtzberg, J. "A staging system for infantile Krabbe disease to predict outcome after unrelated umbilical cord blood transplantation." Pediatrics 118.3 (September 2006): e879-e889.
PMID
16923928
Source
pubmed
Published In
Pediatrics
Volume
118
Issue
3
Publish Date
2006
Start Page
e879
End Page
e889
DOI
10.1542/peds.2006-0747

Characterization of cord blood natural killer and lymphokine activated killer lymphocytes following ex vivo cellular engineering.

Cord blood (CB) natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic cells are poorly characterized but might be used to treat minimal residual and/or recurrent malignant disease. Currently, there is no mechanism to use CB for adoptive cancer cellular immunotherapy after CB transplantation (CBT). Recognizing this as a deficiency, we hypothesized that CB aliquots could be engineered ex vivo for potential donor lymphocyte infusion after CBT. Cryopreserved CB aliquots were thawed, depleted of monocytes, and cultured in serum-free medium alone or serum-free medium with anti-CD3 and interleukins 2, 7, and 12 combined with antibody/cytokines for 48 hours. Immunophenotyping, cytotoxicity, and proliferation were evaluated. A significant expansion of CD3+ was seen, in addition to increases in lymphocyte subsets of CD8+, CD8+/CD25+, and CD3+/45RO+ versus medium alone. A significant enhancement of CD3 proliferation (P<.001), NK cytotoxicity, NK subset expansion, LAK cytotoxicity, and T-helper 1 subset expansion was also demonstrated. Significant enrichment was seen in NK CD16+/CD56+bright, CD16+/CD56+dim, CD56+bright and CD56+dim/KIR3DL1+, CD56+bright and CD56+dim/KIR2DL1+, CD56+bright and CD56+dim/KIR2DL2+ and CD94+/NKG2a+ subsets. These increases in CB NK subsets were in part secondary to augmentation of cell survival. Further, survival of NOD-SCID mice xenografted with human K562 cells and treated with CB cells expanded with antibody/cytokines was significantly higher than that in animals that received no treatment (phosphate buffered saline) and those that were treated with CB ex vivo expanded in medium alone (P<.005, respectively). These data suggest that cryopreserved CB cells could be ex vivo engineered for potential use as adoptive cancer cellular immunotherapy for donor lymphocyte infusion after CBT.

Authors
Ayello, J; van de Ven, C; Fortino, W; Wade-Harris, C; Satwani, P; Baxi, L; Simpson, LL; Sanger, W; Pickering, D; Kurtzberg, J; Cairo, MS
MLA Citation
Ayello, J, van de Ven, C, Fortino, W, Wade-Harris, C, Satwani, P, Baxi, L, Simpson, LL, Sanger, W, Pickering, D, Kurtzberg, J, and Cairo, MS. "Characterization of cord blood natural killer and lymphokine activated killer lymphocytes following ex vivo cellular engineering." Biol Blood Marrow Transplant 12.6 (June 2006): 608-622.
PMID
16737934
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
6
Publish Date
2006
Start Page
608
End Page
622
DOI
10.1016/j.bbmt.2006.01.009

Response to letter regarding article "Atherosclerosis 2005: Recent discoveries and novel hypotheses"

Authors
Goldschmidt-Clermont, PJ; Lam, GKW; Dzau, VJ; Dong, C; Kurtzberg, J; Creager, MA; Losordo, DW; Wassef, M
MLA Citation
Goldschmidt-Clermont, PJ, Lam, GKW, Dzau, VJ, Dong, C, Kurtzberg, J, Creager, MA, Losordo, DW, and Wassef, M. "Response to letter regarding article "Atherosclerosis 2005: Recent discoveries and novel hypotheses"." CIRCULATION 113.21 (May 30, 2006): E783-E783.
Source
wos-lite
Published In
Circulation
Volume
113
Issue
21
Publish Date
2006
Start Page
E783
End Page
E783
DOI
10.1161/CIRCULATIONHA.106.176126

Ectopic expression of the proto-oncogene Mer in pediatric T-cell acute lymphoblastic leukemia.

PURPOSE: The Mer receptor tyrosine kinase, cloned from a B-lymphoblastoid library, is the mammalian orthologue of the chicken retroviral oncogene v-eyk and sends antiapoptotic and transforming signals when activated. To determine if Mer expression is ectopic in T-cell acute lymphoblastic leukemia (ALL) and potentially important in leukemogenesis, we analyzed Mer expression in normal human thymocytes and lymphocytes and in pediatric ALL patient samples. EXPERIMENTAL DESIGN: Reverse transcription-PCR, flow cytometry, and immunohistochemistry were used to determine expression of Mer in sorted human thymocyte populations, lymphocytes, and lymphocytes activated by phytohemagglutinin or phorbol 12-myristate 13-acetate/ionophore. Mer expression in 34 T-cell ALL (T-ALL) patient samples was evaluated by reverse transcription-PCR, and Mer protein expression in a separate cohort of 16 patient samples was assayed by flow cytometry and Western blot. RESULTS: Mer expression was absent in normal thymocytes or lymphocytes, and in T cells activated with phytohemagglutinin or phorbol 12-myristate 13-acetate/ionophore. In contrast, Jurkat cells and T-ALL patient samples expressed unique 180 to 185 kDa Mer protein glycoforms. Substantial Mer RNA levels were principally observed in a subset of T-ALL patient samples that expressed B220 (P = 0.004) but lacked surface expression of CD3 (P = 0.02) and CD4 (P = 0.006), a phenotypic profile consistent with immature lymphoblasts. In addition, 8 of 16 T-ALL patient samples had Mer protein detected by flow cytometry and Western blot. CONCLUSIONS: Transforming Mer signals may contribute to T-cell leukemogenesis, and abnormal Mer expression may be a novel therapeutic target in pediatric ALL therapy.

Authors
Graham, DK; Salzberg, DB; Kurtzberg, J; Sather, S; Matsushima, GK; Keating, AK; Liang, X; Lovell, MA; Williams, SA; Dawson, TL; Schell, MJ; Anwar, AA; Snodgrass, HR; Earp, HS
MLA Citation
Graham, DK, Salzberg, DB, Kurtzberg, J, Sather, S, Matsushima, GK, Keating, AK, Liang, X, Lovell, MA, Williams, SA, Dawson, TL, Schell, MJ, Anwar, AA, Snodgrass, HR, and Earp, HS. "Ectopic expression of the proto-oncogene Mer in pediatric T-cell acute lymphoblastic leukemia." Clin Cancer Res 12.9 (May 1, 2006): 2662-2669.
PMID
16675557
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
12
Issue
9
Publish Date
2006
Start Page
2662
End Page
2669
DOI
10.1158/1078-0432.CCR-05-2208

Activation and enhancement of ex vivo (EvE) expanded cryopreserved Cord Blood (CB) Natural Killer (NK) cells, cytolytic potential, and NK receptor (NKR) expression: Potential role for CB NK in Adoptive Cellular Immunotherapy (ACI)

Authors
Ayello, J; Satwani, P; Lomazow, W; van de Ven, C; Roman, E; Shereck, E; Baxi, L; Kurtzberg, J; Cairo, MS
MLA Citation
Ayello, J, Satwani, P, Lomazow, W, van de Ven, C, Roman, E, Shereck, E, Baxi, L, Kurtzberg, J, and Cairo, MS. "Activation and enhancement of ex vivo (EvE) expanded cryopreserved Cord Blood (CB) Natural Killer (NK) cells, cytolytic potential, and NK receptor (NKR) expression: Potential role for CB NK in Adoptive Cellular Immunotherapy (ACI)." February 2006.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
103
End Page
104
DOI
10.1016/j.bbmt.2005.11.318

Recipient outcomes data collection and reporting for cord blood bank follow-up and quality assurance purposes: The National Marrow Donor Program® experience

Authors
Halet, M; Confer, D; Welte, K; Matlack, M; King, R; Boo, M; Kurtzberg, J
MLA Citation
Halet, M, Confer, D, Welte, K, Matlack, M, King, R, Boo, M, and Kurtzberg, J. "Recipient outcomes data collection and reporting for cord blood bank follow-up and quality assurance purposes: The National Marrow Donor Program® experience." February 2006.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
44
End Page
44
DOI
10.1016/j.bbmt.2005.11.137

Compassion fatigue: Care for the caring

Authors
Blackstock, J; Frey, M; Kurtzberg, J
MLA Citation
Blackstock, J, Frey, M, and Kurtzberg, J. "Compassion fatigue: Care for the caring." February 2006.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
159
End Page
159
DOI
10.1016/j.bbmt.2005.11.494

Expansion of umbilical cord blood derived oligodendrocytes

Authors
Beam, DT; Thacker, J; Kurtzberg, J
MLA Citation
Beam, DT, Thacker, J, and Kurtzberg, J. "Expansion of umbilical cord blood derived oligodendrocytes." February 2006.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
133
End Page
133
DOI
10.1016/j.bbmt.2005.11.409

Umbilical cord blood transplantation in pediatric patients: Results of the prospective, multi-institutional Cord Blood Transplantation Study (COBLT)

Authors
Kernan, NA; Carter, SL; Wagner, JE; Baxter-Lowe, L; Wall, D; Kapoor, N; Guinan, E; Wagner, E; Geller, N; Kurtzberg, J
MLA Citation
Kernan, NA, Carter, SL, Wagner, JE, Baxter-Lowe, L, Wall, D, Kapoor, N, Guinan, E, Wagner, E, Geller, N, and Kurtzberg, J. "Umbilical cord blood transplantation in pediatric patients: Results of the prospective, multi-institutional Cord Blood Transplantation Study (COBLT)." February 2006.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
14
End Page
15
DOI
10.1016/j.bbmt.2005.11.048

Rapid in vivo acquisition of effector Tc1 phenotype prior to myeloid engraftment predicts opportunistic infections in unrelated cord blood transplant recipients

Authors
Szabolcs, P; Lee, YA; Reese, M; Chao, N; Kurtzberg, J
MLA Citation
Szabolcs, P, Lee, YA, Reese, M, Chao, N, and Kurtzberg, J. "Rapid in vivo acquisition of effector Tc1 phenotype prior to myeloid engraftment predicts opportunistic infections in unrelated cord blood transplant recipients." February 2006.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
83
End Page
84
DOI
10.1016/j.bbmt.2005.11.259

Nursing care of the granulocyte donor for pediatric stem cell transplant patients

Authors
Stanton, TJ; Marconi, AL; Allison, J; Kurtzberg, J
MLA Citation
Stanton, TJ, Marconi, AL, Allison, J, and Kurtzberg, J. "Nursing care of the granulocyte donor for pediatric stem cell transplant patients." February 2006.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
155
End Page
156
DOI
10.1016/j.bbmt.2005.11.481

Implementation of discharge videos for pediatric patients undergoing blood and marrow transplantation: Bridging the gap between inpatient and outpatient care

Authors
Kokoszka, A; Talbert, G; Yarwood, K; Garmhausen, L; Kurtzberg, J
MLA Citation
Kokoszka, A, Talbert, G, Yarwood, K, Garmhausen, L, and Kurtzberg, J. "Implementation of discharge videos for pediatric patients undergoing blood and marrow transplantation: Bridging the gap between inpatient and outpatient care." February 2006.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
159
End Page
159
DOI
10.1016/j.bbmt.2005.11.493

Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases.

The Cord Blood Transplantation Study (COBLT), sponsored by the National Heart, Lung, and Blood Institute, is a phase II multicenter study designed to evaluate the use of cord blood in allogeneic transplantation. In this report, we evaluated the outcomes of cord blood transplantation in 69 patients with lysosomal and peroxisomal storage diseases. Patients with mucopolysaccharidoses I to III, mucolipidoses (ML) II (n = 36), adrenoleukodystrophy (n = 8), metachromatic leukodystrophy (n = 6), Krabbe disease (n = 16), and Tay-Sachs disease (n = 3) were enrolled between August 1999 and June 2004. All patients received the same preparative regimen, graft-versus-host disease (GVHD) prophylaxis, and supportive care. End points included survival, engraftment, GVHD, and toxicity. Sixty-nine patients (64% men; 81% white) with a median age of 1.8 years underwent transplantation with a median cell dose of 8.7 x 10(7)/kg. One-year survival was 72% (95% confidence interval, 61%-83%). The cumulative incidence of neutrophil engraftment by day 42 was 78% (95% confidence interval, 67%-87%) at a median of 25 days. Grade II to IV acute GVHD occurred in 36% of patients. Cord blood donors are readily available for rapid transplantation. Cord blood transplantation should be considered as frontline therapy for young patients with lysosomal and peroxisomal storage diseases.

Authors
Martin, PL; Carter, SL; Kernan, NA; Sahdev, I; Wall, D; Pietryga, D; Wagner, JE; Kurtzberg, J
MLA Citation
Martin, PL, Carter, SL, Kernan, NA, Sahdev, I, Wall, D, Pietryga, D, Wagner, JE, and Kurtzberg, J. "Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases." Biol Blood Marrow Transplant 12.2 (February 2006): 184-194.
PMID
16443516
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
184
End Page
194
DOI
10.1016/j.bbmt.2005.09.016

Graves' disease following unrelated umbilical cord blood transplantation in pediatric patients

Authors
Driscoll, TA; Ciocci, GH; Kurtzberg, J
MLA Citation
Driscoll, TA, Ciocci, GH, and Kurtzberg, J. "Graves' disease following unrelated umbilical cord blood transplantation in pediatric patients." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
111
End Page
111
DOI
10.1016/j.bbmt.2005.11.342

Busulfan/melphalan is an effective and well tolerated conditioning regimen for pediatric AML and MDS patients receiving a matched sibling bmt

Authors
Martin, PL; Driscoll, TA; Szabolcs, P; Parikh, SH; Prasad, VK; Kurtzberg, J
MLA Citation
Martin, PL, Driscoll, TA, Szabolcs, P, Parikh, SH, Prasad, VK, and Kurtzberg, J. "Busulfan/melphalan is an effective and well tolerated conditioning regimen for pediatric AML and MDS patients receiving a matched sibling bmt." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
127
End Page
127
DOI
10.1016/j.bbmt.2005.11.389

Single center experience of unrelated umbilical cord blood transplantation (UCBDT) for acute myeloid leukemia (AML) in 97 pediatric patients: Impact of disease status and cytoreductive regimen

Authors
Prasad, VK; Wu, J; Parikh, SH; Driscoll, TA; Szabolcs, P; Martin, PL; Carter, S; Kurtzberg, J
MLA Citation
Prasad, VK, Wu, J, Parikh, SH, Driscoll, TA, Szabolcs, P, Martin, PL, Carter, S, and Kurtzberg, J. "Single center experience of unrelated umbilical cord blood transplantation (UCBDT) for acute myeloid leukemia (AML) in 97 pediatric patients: Impact of disease status and cytoreductive regimen." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
124
End Page
124
DOI
10.1016/j.bbmt.2005.11.381

Neonatal umbilical cord blood transplantation favorably alters the neurodevelopmental outcome and survival of babies with infantile Krabbe disease

Authors
Wood, SJ; Allison, J; Escolar, ML; Provenzale, JM; Kurtzberg, J
MLA Citation
Wood, SJ, Allison, J, Escolar, ML, Provenzale, JM, and Kurtzberg, J. "Neonatal umbilical cord blood transplantation favorably alters the neurodevelopmental outcome and survival of babies with infantile Krabbe disease." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
153
End Page
154
DOI
10.1016/j.bbmt.2005.11.476

Patient controlled analgesia by proxy

Authors
Guess, C; Frey, MA; Martin, PL; Kurtzberg, J
MLA Citation
Guess, C, Frey, MA, Martin, PL, and Kurtzberg, J. "Patient controlled analgesia by proxy." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
159
End Page
160
DOI
10.1016/j.bbmt.2005.11.495

Cellcept/cyclosporine as prophylaxis against graft- versus-host disease in pediatric patients undergoing allogeneic stem cell transplantation

Authors
Lakshminarayanan, S; Martin, PL; Szabolcs, P; Driscoll, T; Parikh, S; Prasad, V; Kurtzberg, J
MLA Citation
Lakshminarayanan, S, Martin, PL, Szabolcs, P, Driscoll, T, Parikh, S, Prasad, V, and Kurtzberg, J. "Cellcept/cyclosporine as prophylaxis against graft- versus-host disease in pediatric patients undergoing allogeneic stem cell transplantation." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
67
End Page
68
DOI
10.1016/j.bbmt.2005.11.212

Neurobehavioral outcome in children with MPS III (Sanfilippo syndrome) after unrelated donor umbilical cord blood transplantation (UCBT)

Authors
Escolar, M; Lakshminayanaran, S; Szabolcs, P; Poe, M; Prasad, V; Parikh, S; Allison, J; Wood, S; Kurtzberg, J
MLA Citation
Escolar, M, Lakshminayanaran, S, Szabolcs, P, Poe, M, Prasad, V, Parikh, S, Allison, J, Wood, S, and Kurtzberg, J. "Neurobehavioral outcome in children with MPS III (Sanfilippo syndrome) after unrelated donor umbilical cord blood transplantation (UCBT)." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
125
End Page
125
DOI
10.1016/j.bbmt.2005.11.384

Vend occulsive disease: A potentially life threatening complication of hematopoietic stem cell transplantation

Authors
Summers, E; Edmisten, J; Martin, PL; Frey, M; Kurtzberg, J
MLA Citation
Summers, E, Edmisten, J, Martin, PL, Frey, M, and Kurtzberg, J. "Vend occulsive disease: A potentially life threatening complication of hematopoietic stem cell transplantation." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
161
End Page
161
DOI
10.1016/j.bbmt.2005.11.500

Comparable long-term survival after unrelated and HLA-matched sibling donor hematopoietic stem cell transplantations for acute leukemia in children younger than 18 months.

PURPOSE: To describe outcomes after unrelated donor stem cell transplantation (HCT) in children (< 18 months at diagnosis) with acute leukemia and compare these with outcomes after human leukocyte antigen (HLA)-matched sibling donor HCT. PATIENTS AND METHODS: We compared the results of unrelated donor HCT with bone marrow (n = 85) or cord blood grafts (n = 81) and HLA-matched sibling donor HCT with bone marrow grafts (n = 101) for acute myeloid or acute lymphoblastic leukemia using Cox proportional hazards models. Unrelated donor HCT recipients were younger, more likely to have MLL gene rearrangement, to have advanced leukemia, and to receive irradiation before HCT. RESULTS: Treatment-related mortality rates were 6%, 15%, and 31% after matched sibling, unrelated donor bone marrow, and cord blood HCT, respectively. Risks of relapse, overall and leukemia-free survival were significantly associated with disease status at transplantation. Though leukemia recurrence was lowest after unrelated donor HCT in first clinical remission (CR), overall survival, and leukemia-free survival rates were similar after matched sibling and unrelated donor HCT, after adjustment for disease status. Relapse, overall and leukemia-free survival did not differ by graft type (bone marrow v cord blood) or type of leukemia. Three-year probabilities of leukemia-free survival were 49% and 54% after HLA-matched sibling and unrelated donor transplantation in first CR, respectively. Corresponding rates for those with advanced leukemia were 20% and 30%. CONCLUSION: Unrelated donor HCT should be considered for infants with acute leukemia in first CR using the same eligibility criteria as are currently used for those with HLA matched sibling donors.

Authors
Eapen, M; Rubinstein, P; Zhang, M-J; Camitta, BM; Stevens, C; Cairo, MS; Davies, SM; Doyle, JJ; Kurtzberg, J; Pulsipher, MA; Ortega, JJ; Scaradavou, A; Horowitz, MM; Wagner, JE
MLA Citation
Eapen, M, Rubinstein, P, Zhang, M-J, Camitta, BM, Stevens, C, Cairo, MS, Davies, SM, Doyle, JJ, Kurtzberg, J, Pulsipher, MA, Ortega, JJ, Scaradavou, A, Horowitz, MM, and Wagner, JE. "Comparable long-term survival after unrelated and HLA-matched sibling donor hematopoietic stem cell transplantations for acute leukemia in children younger than 18 months." J Clin Oncol 24.1 (January 1, 2006): 145-151.
PMID
16382124
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
1
Publish Date
2006
Start Page
145
End Page
151
DOI
10.1200/JCO.2005.02.4612

Response to letter regarding article "Atherosclerosis 2005: Recent discoveries and novel hypotheses" [2]

Authors
Goldschmidt-Clermont, PJ; Lam, GKW; Dzau, VJ; Dong, C; Kurtzberg, J; Creager, MA; Losordo, DW; Wassef, M
MLA Citation
Goldschmidt-Clermont, PJ, Lam, GKW, Dzau, VJ, Dong, C, Kurtzberg, J, Creager, MA, Losordo, DW, and Wassef, M. "Response to letter regarding article "Atherosclerosis 2005: Recent discoveries and novel hypotheses" [2]." Circulation 113.21 (2006): e783-.
Source
scival
Published In
Circulation
Volume
113
Issue
21
Publish Date
2006
Start Page
e783
DOI
10.1161/CIRCULATIONAHA.106.617068

Is it time to expand the use of cord blood donor transplantation in relapsed ALL?

Authors
Kurtzberg, J
MLA Citation
Kurtzberg, J. "Is it time to expand the use of cord blood donor transplantation in relapsed ALL?." Pediatr Blood Cancer 45.7 (December 2005): 874-875.
PMID
16187299
Source
pubmed
Published In
Pediatric Blood & Cancer
Volume
45
Issue
7
Publish Date
2005
Start Page
874
End Page
875
DOI
10.1002/pbc.20664

Quantitative analysis of diffusion tensor imaging data in serial assessment of Krabbe disease.

Krabbe disease is a rare autosomal recessive pediatric white matter (WM) disorder that is due to deficiency of a specific enzyme, beta-galactocerebrosidase. This report reviews our experience with use of diffusion tensor imaging (DTI) in serial assessment of WM changes in Krabbe disease following stem cell transplantation. DTI appears to be a sensitive means to monitor effects of stem cell transplantation on WM development in Krabbe disease. The group of early transplantation infants was clearly distinguishable from the group of late transplantation infants based on anisotropy measurements. Good correlation also was seen between neurodevelopmental scores and anisotropy measurements. The work described here in Krabbe disease may serve as a model for application of DTI to other therapies in various WM disorders such as multiple sclerosis and dysmyelinating disorders of childhood.

Authors
Provenzale, JM; Escolar, M; Kurtzberg, J
MLA Citation
Provenzale, JM, Escolar, M, and Kurtzberg, J. "Quantitative analysis of diffusion tensor imaging data in serial assessment of Krabbe disease." Ann N Y Acad Sci 1064 (December 2005): 220-229. (Review)
PMID
16394159
Source
pubmed
Published In
Annals of the New York Academy of Sciences
Volume
1064
Publish Date
2005
Start Page
220
End Page
229
DOI
10.1196/annals.1340.040

A report of the event free survival (EFS) for children with newly diagnosed standard risk acute lymphoblastic leukemia (ALL) treated on pediatric oncology group (POG) protocol 9605.

Authors
Bell, BA; Abish, SB; Chauvenet, A; Kurtzberg, J; Pullen, J; Devidas, M; Shuster, J; Camitta, BM
MLA Citation
Bell, BA, Abish, SB, Chauvenet, A, Kurtzberg, J, Pullen, J, Devidas, M, Shuster, J, and Camitta, BM. "A report of the event free survival (EFS) for children with newly diagnosed standard risk acute lymphoblastic leukemia (ALL) treated on pediatric oncology group (POG) protocol 9605." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
257A
End Page
257A

Rapid in vivo acquisition of effector Tc1 phenotype even before myeloid engraftment predicts opportunistic infections (OI) in unrelated cord blood transplant recipients.

Authors
Szabolcs, P; Lee, YA; Reese, M; Chao, N; Kurtzberg, J
MLA Citation
Szabolcs, P, Lee, YA, Reese, M, Chao, N, and Kurtzberg, J. "Rapid in vivo acquisition of effector Tc1 phenotype even before myeloid engraftment predicts opportunistic infections (OI) in unrelated cord blood transplant recipients." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
409A
End Page
409A

A report of the event-free survival (EFS) and neurotoxicity for children with newly diagnosed standard risk acute lymphoblastic leukemia (ALL) on pediatric oncology group (POG) protocol 9405.

Authors
Rodes, S; Bell, BA; Abish, SB; Pullen, J; Chauvenet, A; Kurtzberg, J; Devidas, M; Shuster, J; Camitta, BM
MLA Citation
Rodes, S, Bell, BA, Abish, SB, Pullen, J, Chauvenet, A, Kurtzberg, J, Devidas, M, Shuster, J, and Camitta, BM. "A report of the event-free survival (EFS) and neurotoxicity for children with newly diagnosed standard risk acute lymphoblastic leukemia (ALL) on pediatric oncology group (POG) protocol 9405." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
259A
End Page
259A

Unique reversible but serious adverse events in very young infants undergoing unrelated donor umbilical cord blood transplantation for non-malignant conditions: Increased autoimmune cytopenias and hypertrophic cardiomyopathy.

Authors
Lakshminarayanan, S; Szabolcs, P; Parikh, S; Wood, SJ; Allison, J; Kurtzberg, J
MLA Citation
Lakshminarayanan, S, Szabolcs, P, Parikh, S, Wood, SJ, Allison, J, and Kurtzberg, J. "Unique reversible but serious adverse events in very young infants undergoing unrelated donor umbilical cord blood transplantation for non-malignant conditions: Increased autoimmune cytopenias and hypertrophic cardiomyopathy." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
451B
End Page
451B

Post-thaw colony forming unit (CFU) counts and yield are the most important predictors of engraftment and survival following unrelated donor cord blood transplantation (CBT): A COBLT study report.

Authors
Wall, DA; Wagner, EL; Carter, SL; Mendizabal, AM; Cairo, MS; Kernan, NA; Laughlin, M; Kurtzberg, J
MLA Citation
Wall, DA, Wagner, EL, Carter, SL, Mendizabal, AM, Cairo, MS, Kernan, NA, Laughlin, M, and Kurtzberg, J. "Post-thaw colony forming unit (CFU) counts and yield are the most important predictors of engraftment and survival following unrelated donor cord blood transplantation (CBT): A COBLT study report." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
579A
End Page
579A

Antigen-specific T lymphocyte function following unrelated cord blood transplantation (UCBT).

Authors
Parkman, R; Cohen, G; Carter, SL; Weinberg, KI; Masinsin, B; Guinan, EC; Kurtzberg, J; Wagner, JE; Kernan, NA
MLA Citation
Parkman, R, Cohen, G, Carter, SL, Weinberg, KI, Masinsin, B, Guinan, EC, Kurtzberg, J, Wagner, JE, and Kernan, NA. "Antigen-specific T lymphocyte function following unrelated cord blood transplantation (UCBT)." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
849A
End Page
849A

Ex vivo expansion of umbilical cord blood T cells for adoptive immunotherapy.

Authors
Mazur, MA; Lee, YA; Kurtzberg, J; Szabolcs, P
MLA Citation
Mazur, MA, Lee, YA, Kurtzberg, J, and Szabolcs, P. "Ex vivo expansion of umbilical cord blood T cells for adoptive immunotherapy." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
15A
End Page
15A

Thrombotic and hemorrhagic events for patients on pediatric oncology group (POG) protocols 9201, 9605, 9406.

Authors
Rice, MA; Bell, BA; Chauvenet, A; Kurtzberg, J; Abish, SB; Pullen, J; Devidas, M; Camitta, BM
MLA Citation
Rice, MA, Bell, BA, Chauvenet, A, Kurtzberg, J, Abish, SB, Pullen, J, Devidas, M, and Camitta, BM. "Thrombotic and hemorrhagic events for patients on pediatric oncology group (POG) protocols 9201, 9605, 9406." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
258A
End Page
259A

Transplant outcomes and stabilization of neurological function in young children with MPS III (Sanfilippo syndrome) after unrelated donor umbilical cord blood transplantation.

Authors
Lakshminarayanan, S; Szabolcs, P; Prasad, VK; Parikh, S; Allison, J; Wood, SJ; Escolar, M; Kurtzberg, J
MLA Citation
Lakshminarayanan, S, Szabolcs, P, Prasad, VK, Parikh, S, Allison, J, Wood, SJ, Escolar, M, and Kurtzberg, J. "Transplant outcomes and stabilization of neurological function in young children with MPS III (Sanfilippo syndrome) after unrelated donor umbilical cord blood transplantation." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
580A
End Page
580A

Defibrotide (DF) for the treatment of Veno-Occlusive Disease (VOD) and multi-system organ failure (MOF) post SCT: Analysis of response and survival according to degree and type of MOV.

Authors
Richardson, PG; Soiffer, RJ; Antin, JH; Jin, Z; Kurtzberg, J; Martin, PL; Hockenbery, D; Murray, KF; Vogelsang, GB; Chen, A; Krishnan, A; Kernan, NA; Avigan, D; Spitzer, TR; Warren, D; Momtaz, P; Revta, C; Wei, LJ; Iacobelli, M; McDonald, GB; Guinan, EC
MLA Citation
Richardson, PG, Soiffer, RJ, Antin, JH, Jin, Z, Kurtzberg, J, Martin, PL, Hockenbery, D, Murray, KF, Vogelsang, GB, Chen, A, Krishnan, A, Kernan, NA, Avigan, D, Spitzer, TR, Warren, D, Momtaz, P, Revta, C, Wei, LJ, Iacobelli, M, McDonald, GB, and Guinan, EC. "Defibrotide (DF) for the treatment of Veno-Occlusive Disease (VOD) and multi-system organ failure (MOF) post SCT: Analysis of response and survival according to degree and type of MOV." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
120A
End Page
120A

Comparison of cytomegalovirus polymerase chain reaction and serology for screening umbilical cord blood components.

BACKGROUND: Recipients of umbilical cord blood (UCB) transplants are susceptible to opportunistic infections, including cytomegalovirus (CMV). To prevent CMV transmission from UCB donors, most laboratories perform serology on corresponding maternal samples and quarantine units when the mother has immunoglobulin M (IgM) anti-CMV. STUDY DESIGN AND METHODS: UCB units and associated samples (UCB plasma and red cell pellet; maternal whole blood and serum) from two cord blood banks were tested with two validated CMV polymerase chain reaction assays (UL54 and UL93 targets). Results were compared with maternal CMV serology (IgG and IgM). RESULTS: Only 4 of 48 (8.3%) quarantined CMV IgM-positive units were also CMV nucleic acid testing (NAT)-positive (651-68,600 copies/mL). In contrast, 1 of 200 "CMV-safe" UCB units (CMV IgM-equivocal or -negative) had CMV DNA (0.5%). The corresponding maternal samples were CMV NAT-negative. Positive maternal IgM serology demonstrates only modest sensitivity (80%) and specificity (82%) and poor positive predictive value (8%), when correlated with the presence of CMV DNA in UCB units. CONCLUSION: CMV NAT may be a useful adjunct to serologic screening, potentially reducing wastage of IgM-positive and NAT-negative units while also detecting potentially infectious units that would pass serologic screening. A prospective clinical trial to further evaluate the role of CMV NAT in UCB transplantation appears warranted.

Authors
Roback, JD; Caliendo, AM; Newman, JL; Sgan, SL; Saakadze, N; Gillespie, TW; Lane, TA; Kurtzberg, J; Hillyer, CD
MLA Citation
Roback, JD, Caliendo, AM, Newman, JL, Sgan, SL, Saakadze, N, Gillespie, TW, Lane, TA, Kurtzberg, J, and Hillyer, CD. "Comparison of cytomegalovirus polymerase chain reaction and serology for screening umbilical cord blood components." Transfusion 45.11 (November 2005): 1722-1728.
PMID
16271096
Source
pubmed
Published In
Transfusion
Volume
45
Issue
11
Publish Date
2005
Start Page
1722
End Page
1728
DOI
10.1111/j.1537-2995.2005.00596.x

Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood.

Since the first successful transplantation of umbilical cord blood in 1988, cord blood has become an important source of hematopoietic stem and progenitor cells for the treatment of blood and genetic disorders. Significant progress has been accompanied by challenges for scientists, ethicists, and health policy makers. With the recent recognition of the need for a national system for the collection, banking, distribution, and use of cord blood and the increasing focus on cord blood as an alternative to embryos as a source of tissue for regenerative medicine, cord blood has garnered significant attention. We review the development of cord blood banking and transplantation and then discuss the scientific and ethical issues influencing both established and investigational practices surrounding cord blood collection, banking, and use.

Authors
Kurtzberg, J; Lyerly, AD; Sugarman, J
MLA Citation
Kurtzberg, J, Lyerly, AD, and Sugarman, J. "Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood." J Clin Invest 115.10 (October 2005): 2592-2597. (Review)
PMID
16200191
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
115
Issue
10
Publish Date
2005
Start Page
2592
End Page
2597
DOI
10.1172/JCI26690

Establishing an external proficiency testing program for cord blood banks: A national marrow donor program cord blood committee study

Authors
Creer, MH; Wofford, JD; Kurtzberg, J; Reems, J; Wall, D
MLA Citation
Creer, MH, Wofford, JD, Kurtzberg, J, Reems, J, and Wall, D. "Establishing an external proficiency testing program for cord blood banks: A national marrow donor program cord blood committee study." September 2005.
Source
wos-lite
Published In
Transfusion
Volume
45
Issue
3
Publish Date
2005
Start Page
9A
End Page
9A

Recurrent hemophagocytic lymphohistiocytosis syndrome (HLH) in a patient with common variable immune deficiency.

Authors
Kleiner, G; Gordon, P; Toledano, S; Rodriguez, M; Lederhandler, J; Byrnes, G; Rodriguez, M; Prasad, V; Kurtzberg, J
MLA Citation
Kleiner, G, Gordon, P, Toledano, S, Rodriguez, M, Lederhandler, J, Byrnes, G, Rodriguez, M, Prasad, V, and Kurtzberg, J. "Recurrent hemophagocytic lymphohistiocytosis syndrome (HLH) in a patient with common variable immune deficiency." September 2005.
Source
wos-lite
Published In
Clinical Immunology
Volume
116
Issue
3
Publish Date
2005
Start Page
290
End Page
290

Busulfan/melphalan/antithymocyte globulin followed by unrelated donor cord blood transplantation for treatment of infant leukemia and leukemia in young children: the Cord Blood Transplantation study (COBLT) experience.

A non-total body irradiation-containing preparative regimen was studied in young children (<4 years old) undergoing unrelated donor cord blood transplantation as part of the Cord Blood Transplantation trial for the treatment of acute lymphoblastic leukemia (n = 14), acute myeloid leukemia (n = 13), undifferentiated leukemia (n = 1), juvenile myelomonocytic leukemia (n = 2), and myelodysplastic syndromes (n = 2). Donor/recipient HLA matching based on low-/intermediate-resolution molecular typing for HLA-A and -B and high-resolution HLA-DRB1 typing was 5/6 or 6/6 (n = 21) or 4/6 (n = 11). The preparative therapy consisted of busulfan, melphalan, and antithymocyte globulin, with cyclosporine and corticosteroids for graft-versus-host disease (GVHD) prophylaxis. The median age was 1.6 years (range, 0.5-3.9 years), and the median weight was 10.5 kg (range, 5.8-19.5 kg). Cord blood grafts contained a median of 10.7 x 10 7 nucleated cells per kilogram (range, 4.6-29.2) and 2.6 x 10(5) CD34+ cells per kilogram (range, 0.7-8.3). The cumulative incidence (CINC) of neutrophil recovery (absolute neutrophil count >500/microL) at day 42 was 0.59 (95% confidence interval [CI], 0.44-0.78) at a median of 31 days (range, 23-55 days). The CINC and Kaplan-Meier estimates of platelet engraftment at day 180 were 0.53 (95% CI, 0.34-0.69) and 0.82 (95% CI, 0.61-1.00), respectively. CINC estimates of grade III/IV acute GVHD at day 100 and chronic GVHD at 1 year were 0.25 (95% CI, 0.09-0.41) and 0.26 (95% CI, 0.09-0.44), respectively. The CINC estimate of relapse was 0.31 (95% CI, 0.16-0.47) at 2 years. With a median follow-up of 27.8 months (range, 23.4-46.7 months), the probability of survival at 1 year was 0.47 (95% CI, 0.30-0.64). A preparative regimen containing a busulfan/melphalan/antithymocyte globulin preparative regimen is well tolerated in the setting of unrelated donor cord blood transplantation for childhood leukemia and can serve as a platform preparative regimen for intensifying host immunosuppression and antileukemic therapy to allow for improved engraftment and improved relapse-free survival.

Authors
Wall, DA; Carter, SL; Kernan, NA; Kapoor, N; Kamani, NR; Brochstein, JA; Frangoul, H; Goyal, RK; Horan, JT; Pietryga, D; Wagner, JE; Kurtzberg, J; COBLT Steering Committee,
MLA Citation
Wall, DA, Carter, SL, Kernan, NA, Kapoor, N, Kamani, NR, Brochstein, JA, Frangoul, H, Goyal, RK, Horan, JT, Pietryga, D, Wagner, JE, Kurtzberg, J, and COBLT Steering Committee, . "Busulfan/melphalan/antithymocyte globulin followed by unrelated donor cord blood transplantation for treatment of infant leukemia and leukemia in young children: the Cord Blood Transplantation study (COBLT) experience." Biol Blood Marrow Transplant 11.8 (August 2005): 637-646.
PMID
16041314
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
8
Publish Date
2005
Start Page
637
End Page
646
DOI
10.1016/j.bbmt.2005.05.003

Rapid in vivo acquisition of effector Tc1 phenotype before myeloid engraftment predicts opportunistic infections (OI) in cord blood transplant recipients

Authors
Szabolcs, P; Lee, Y; Reese, M; Kurtzberg, J
MLA Citation
Szabolcs, P, Lee, Y, Reese, M, and Kurtzberg, J. "Rapid in vivo acquisition of effector Tc1 phenotype before myeloid engraftment predicts opportunistic infections (OI) in cord blood transplant recipients." July 2005.
Source
wos-lite
Published In
Experimental Hematology
Volume
33
Issue
7
Publish Date
2005
Start Page
48
End Page
48

Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements--initial experience.

PURPOSE: To prospectively compare diffusion-tensor magnetic resonance (MR) imaging anisotropy measurements of white matter (WM) regions in early and late treatment groups of Krabbe disease patients treated with stem cell transplantation. MATERIALS AND METHODS: The study was approved by the Institutional Review Board and was compliant with Health Insurance Portability and Accountability Act; informed consent was obtained from the families of all patients. Patients with early-onset Krabbe disease (four girls and three boys) underwent diffusion-tensor MR imaging before and after stem cell transplantation. Fractional anisotropy (FA) values from serial studies were compared in patients who underwent transplantation at less than 1 month (early group, two girls and one boy) and those who underwent transplantation at 5-8 months (late group, two girls and two boys). FA values were measured in the genu and splenium of the corpus callosum, the frontal WM, and the internal capsule; were compared with those of five age-matched children in the comparison group (normal MR images and no proved neurologic disease); and were expressed as a ratio. Images obtained after transplantation were evaluated at approximately 1 (n = 7), 2 (n = 6), 3 (n = 1), and 4 (n = 1) years. RESULTS: Before transplantation, mean FA ratios in the early group for all four WM regions ranged between 97% and 117%. At 1 year, mean FA ratios at all locations were either 92% or 93%. At 2 years after transplantation, mean FA ratios were between 83% and 92%. In one patient imaged at 3 years, the mean FA ratio was 97%; in another patient imaged at 4 years, the mean FA ratio was 77%. Before transplantation, mean FA ratios in the late group ranged between 55% and 74%. Mean FA ratios were between 37% and 50% at 1 year after transplantation and between 36% and 39% at 2 years. CONCLUSION: All patients had decreases in FA ratios over time. The early group had higher initial FA ratios and lower subsequent decreases, which may indicate amelioration of the dysmyelinating process.

Authors
McGraw, P; Liang, L; Escolar, M; Mukundan, S; Kurtzberg, J; Provenzale, JM
MLA Citation
McGraw, P, Liang, L, Escolar, M, Mukundan, S, Kurtzberg, J, and Provenzale, JM. "Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements--initial experience." Radiology 236.1 (July 2005): 221-230.
PMID
15987975
Source
pubmed
Published In
Radiology
Volume
236
Issue
1
Publish Date
2005
Start Page
221
End Page
230
DOI
10.1148/radiol.2353040716

Results of the cord blood transplantation (COBLT) study unrelated donor banking program.

BACKGROUND: The goals of the Cord Blood Transplantation (COBLT) Study banking program initiated in 1996 were to develop standard operating procedures (SOPs) for cord blood (CB) donor recruitment and banking and to build an ethnically diverse unrelated CB bank to support a transplantation protocol. STUDY DESIGN AND METHODS: The program included collection centers, three banks, a steering committee, and a medical coordinating center (MCC) that developed and validated SOPs and a Web-based data collection system. External oversight was performed by the National Heart, Lung, and Blood Institute and the MCC. RESULTS: A total of 34,799 potential donors were screened and 20,710 consented. A total of 17,207 ethnically diverse units were collected between 1998 and 2001. A total of 11,077 (64%) units were cryopreserved and quarantined. Of these, 79 percent met eligibility criteria and were HLA-typed and entered into the search registry. Higher CB volumes and cell counts were obtained from cesarean sections compared to vaginal deliveries. Units from African American persons contained lower cell counts per volume compared to other ethnicities. Birth weight correlated with volume and cell content. External oversight was accomplished through custom reports generated by the data collection system and periodic site visits. During maintenance, a breach in the SOPs was detected during a site visit at one of the banks. These units were designated for future use in nonclinical research. CONCLUSION: The COBLT Study demonstrated that SOPs and data collection can be implemented in multiple banks coordinated by one MCC. Relationships between donor demographics and CB content may be useful in the development of other CB banking programs.

Authors
Kurtzberg, J; Cairo, MS; Fraser, JK; Baxter-Lowe, L; Cohen, G; Carter, SL; Kernan, NA
MLA Citation
Kurtzberg, J, Cairo, MS, Fraser, JK, Baxter-Lowe, L, Cohen, G, Carter, SL, and Kernan, NA. "Results of the cord blood transplantation (COBLT) study unrelated donor banking program." Transfusion 45.6 (June 2005): 842-855.
PMID
15934981
Source
pubmed
Published In
Transfusion
Volume
45
Issue
6
Publish Date
2005
Start Page
842
End Page
855
DOI
10.1111/j.1537-2995.2005.04428.x

Characterization of banked umbilical cord blood hematopoietic progenitor cells and lymphocyte subsets and correlation with ethnicity, birth weight, sex, and type of delivery: a Cord Blood Transplantation (COBLT) Study report.

BACKGROUND: The Cord Blood Transplantation (COBLT) Study banking program was initiated in 1996. The study goals were to develop standard operating procedures for cord blood (CB) donor recruitment and banking and to build an ethnically diverse unrelated CB bank to support a transplantation protocol. STUDY DESIGN AND METHODS: The hematopoietic progenitor cell (HPC) and lymphocyte subset (LS) content of approximately 8000 CB units were characterized, and these results were correlated with donor ethnicity, birth weight, gestational age, sex, and type of delivery. RESULTS: There was a significant correlation of CD34+ cell count with colony-forming unit (CFU)-granulocyte-macrophage (r=0.68, p<0.001), CFU-granulocyte-erythroid-macrophage-megakaryocyte (r=0.52, p<0.001), burst-forming unit-erythroid (BFU-E; r=0.61, p<0.001), and total CFUs (r=0.67, p<0.001). Nucleated red blood cell count was significantly correlated with total CD34+ (r=0.56, p<0.001), total CFU (r=0.50, p<0.001), BFU-E (r=0.48, p<0.001), and counts of CD34+ subsets (p<0.001). Caucasian ethnicity was significantly correlated with higher CD3+/CD4+, CD19+, and CD16+/CD56+ LSs. Furthermore, CD34+/CD38- and CD34+/CD61+ CB units (HPC-C) were significantly lower in African American and Asian persons compared to Caucasian and Hispanic persons. Male sex was associated with significantly fewer CD3+/CD4+, CD19+, and CD16+/CD56+ but increased CD3+/CD8+ LSs (p<0.001). Finally, cesarean section was associated with significantly higher total CFU and CD16+/CD56+ but lower CD3+/CD4+, CD3+/CD8+, and CD19+ LSs. CONCLUSION: These results provide a standard and range for uniformly processed HPC-C progenitor cells and LSs. CB progenitor cells and/or LSs may in the future predict for rapidity of engraftment, incidence of graft-versus-host disease, speed and quality of immunore- constitution, graft-versus-tumor effects, and/or success of gene transfection after CB transplantation.

Authors
Cairo, MS; Wagner, EL; Fraser, J; Cohen, G; van de Ven, C; Carter, SL; Kernan, NA; Kurtzberg, J
MLA Citation
Cairo, MS, Wagner, EL, Fraser, J, Cohen, G, van de Ven, C, Carter, SL, Kernan, NA, and Kurtzberg, J. "Characterization of banked umbilical cord blood hematopoietic progenitor cells and lymphocyte subsets and correlation with ethnicity, birth weight, sex, and type of delivery: a Cord Blood Transplantation (COBLT) Study report." Transfusion 45.6 (June 2005): 856-866.
PMID
15934982
Source
pubmed
Published In
Transfusion
Volume
45
Issue
6
Publish Date
2005
Start Page
856
End Page
866
DOI
10.1111/j.1537-2995.2005.04429.x

Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group.

PURPOSE: Nelarabine (compound 506U78), a water soluble prodrug of 9-b-d-arabinofuranosylguanine, is converted to ara-GTP in T lymphoblasts. We sought to define the response rate of nelarabine in children and young adults with refractory or recurrent T-cell disease. PATIENTS AND METHODS: We performed a phase II study with patients stratified as follows: stratum 1: > or = 25% bone marrow blasts in first relapse; stratum 2: > or = 25% bone marrow blasts in > or = second relapse; stratum 3: positive CSF; stratum 4: extramedullary (non-CNS) relapse. The initial nelarabine dose was 1.2 g/m2 daily for 5 consecutive days every 3 weeks. There were two dose de-escalations due to neurotoxicity on this or other studies. The final dose was 650 mg/m2/d for strata 1 and two patients and 400 mg/m2/d for strata 3 and four patients. RESULTS: We enrolled 121 patients (106 assessable for response) at the final dose levels. Complete plus partial response rates at the final dose levels were: 55% in stratum 1; 27% in stratum 2; 33% in stratum 3; and 14% in stratum 4. There were 31 episodes of > or = grade 3 neurologic adverse events in 27 patients (18% of patients). CONCLUSION: Nelarabine is active as a single agent in recurrent T-cell leukemia, with a response rate more than 50% in first bone marrow relapse. The most significant adverse events associated with nelarabine administration are neurologic. Further studies are planned to determine whether the addition of nelarabine to front-line therapy for T-cell leukemia in children will improve survival.

Authors
Berg, SL; Blaney, SM; Devidas, M; Lampkin, TA; Murgo, A; Bernstein, M; Billett, A; Kurtzberg, J; Reaman, G; Gaynon, P; Whitlock, J; Krailo, M; Harris, MB; Children's Oncology Group,
MLA Citation
Berg, SL, Blaney, SM, Devidas, M, Lampkin, TA, Murgo, A, Bernstein, M, Billett, A, Kurtzberg, J, Reaman, G, Gaynon, P, Whitlock, J, Krailo, M, Harris, MB, and Children's Oncology Group, . "Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group." J Clin Oncol 23.15 (May 20, 2005): 3376-3382.
PMID
15908649
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
15
Publish Date
2005
Start Page
3376
End Page
3382
DOI
10.1200/JCO.2005.03.426

Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies.

PURPOSE: A phase I study was conducted to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics of a novel purine nucleoside, nelarabine, a soluble prodrug of 9-beta-D-arabinosylguanine (araG; Nelarabine), in pediatric and adult patients with refractory hematologic malignancies. PATIENTS AND METHODS: Between April 1994 and April 1997, 93 patients with refractory hematologic malignancies were treated with one to 16 cycles of study drug. Nelarabine was administered daily, as a 1-hour intravenous infusion for 5 consecutive days, every 21 to 28 days. First-cycle pharmacokinetic data, including plasma nelarabine and araG levels, were obtained on all patients treated. Intracellular phosphorylation of araG was studied in samples of leukemic blasts from selected patients. RESULTS: The MTDs were defined at 60 mg/kg/dose and 40 mg/kg/dose daily x 5 days in children and adults, respectively. Dose-limiting toxicity (DLT) was neurologic in both children and adults. Myelosuppression and other significant organ toxicities did not occur. Pharmacokinetic parameters were similar in children and adults. Accumulation of araGTP in leukemic blasts was correlated with cytotoxic activity. The overall response rate was 31%. Major responses were seen in patients with T-cell malignancies, with 54% of patients with T-lineage acute lymphoblastic leukemia achieving a complete or partial response after one to two courses of drug. CONCLUSION: Nelarabine is a novel nucleoside with significant cytotoxic activity against malignant T cells. DLT is neurologic. Phase II and III trials in patients with T-cell malignancies are encouraged.

Authors
Kurtzberg, J; Ernst, TJ; Keating, MJ; Gandhi, V; Hodge, JP; Kisor, DF; Lager, JJ; Stephens, C; Levin, J; Krenitsky, T; Elion, G; Mitchell, BS
MLA Citation
Kurtzberg, J, Ernst, TJ, Keating, MJ, Gandhi, V, Hodge, JP, Kisor, DF, Lager, JJ, Stephens, C, Levin, J, Krenitsky, T, Elion, G, and Mitchell, BS. "Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies." J Clin Oncol 23.15 (May 20, 2005): 3396-3403.
PMID
15908652
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
15
Publish Date
2005
Start Page
3396
End Page
3403
DOI
10.1200/JCO.2005.03.199

Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease.

BACKGROUND: Infantile Krabbe's disease produces progressive neurologic deterioration and death in early childhood. We hypothesized that transplantation of umbilical-cord blood from unrelated donors before the development of symptoms would favorably alter the natural history of the disease among newborns in whom the disease was diagnosed because of a family history. We compared the outcomes among these newborns with the outcomes among infants who underwent transplantation after the development of symptoms and with the outcomes in an untreated cohort of affected children. METHODS: Eleven asymptomatic newborns (age range, 12 to 44 days) and 14 symptomatic infants (age range, 142 to 352 days) with infantile Krabbe's disease underwent transplantation of umbilical-cord blood from unrelated donors after myeloablative chemotherapy. Engraftment, survival, and neurodevelopmental function were evaluated longitudinally for four months to six years. RESULTS: The rates of donor-cell engraftment and survival were 100 percent and 100 percent, respectively, among the asymptomatic newborns (median follow-up, 3.0 years) and 100 percent and 43 percent, respectively, among the symptomatic infants (median follow-up, 3.4 years). Surviving patients showed durable engraftment of donor-derived hematopoietic cells with restoration of normal blood galactocerebrosidase levels. Infants who underwent transplantation before the development of symptoms showed progressive central myelination and continued gains in developmental skills, and most had age-appropriate cognitive function and receptive language skills, but a few had mild-to-moderate delays in expressive language and mild-to-severe delays in gross motor function. Children who underwent transplantation after the onset of symptoms had minimal neurologic improvement. CONCLUSIONS: Transplantation of umbilical-cord blood from unrelated donors in newborns with infantile Krabbe's disease favorably altered the natural history of the disease. Transplantation in babies after symptoms had developed did not result in substantive neurologic improvement.

Authors
Escolar, ML; Poe, MD; Provenzale, JM; Richards, KC; Allison, J; Wood, S; Wenger, DA; Pietryga, D; Wall, D; Champagne, M; Morse, R; Krivit, W; Kurtzberg, J
MLA Citation
Escolar, ML, Poe, MD, Provenzale, JM, Richards, KC, Allison, J, Wood, S, Wenger, DA, Pietryga, D, Wall, D, Champagne, M, Morse, R, Krivit, W, and Kurtzberg, J. "Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease." N Engl J Med 352.20 (May 19, 2005): 2069-2081.
PMID
15901860
Source
pubmed
Published In
The New England journal of medicine
Volume
352
Issue
20
Publish Date
2005
Start Page
2069
End Page
2081
DOI
10.1056/NEJMoa042604

Results of the cord blood transplantation study (COBLT): Clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with inborn errors of metabolism

Authors
Kurtzberg, J; Carter, SL; Sahdev, I; Wall, D; Pietryga, D; Wagner, JE; Kernan, NA
MLA Citation
Kurtzberg, J, Carter, SL, Sahdev, I, Wall, D, Pietryga, D, Wagner, JE, and Kernan, NA. "Results of the cord blood transplantation study (COBLT): Clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with inborn errors of metabolism." February 2005.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
2
Publish Date
2005
Start Page
82
End Page
82
DOI
10.1016/j.bbmt.2004.12.242

Results of the Cord Blood Transplantation Study (COBLT): Clinical outcomes of 193 unrelated donor umbilical cord blood transplantation in pediatric patients with malignant conditions

Authors
Kurtzberg, J; Carter, SL; Baxter-Lowe, LA; Feig, SA; Guinan, EC; Kamani, NR; Kapoor, N; Delaney, C; Haut, PR; Wall, D; Kernan, NA
MLA Citation
Kurtzberg, J, Carter, SL, Baxter-Lowe, LA, Feig, SA, Guinan, EC, Kamani, NR, Kapoor, N, Delaney, C, Haut, PR, Wall, D, and Kernan, NA. "Results of the Cord Blood Transplantation Study (COBLT): Clinical outcomes of 193 unrelated donor umbilical cord blood transplantation in pediatric patients with malignant conditions." February 2005.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
2
Publish Date
2005
Start Page
2
End Page
2
DOI
10.1016/j.bbmt.2004.12.007

Establishment of a National Cord Blood Banking Network through the National Marrow Donor Program

Authors
Kurtzberg, J; Creer, M; Halet, M; Welte, K; Boo, M; Confer, D; Chell, J
MLA Citation
Kurtzberg, J, Creer, M, Halet, M, Welte, K, Boo, M, Confer, D, and Chell, J. "Establishment of a National Cord Blood Banking Network through the National Marrow Donor Program." February 2005.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
2
Publish Date
2005
Start Page
39
End Page
39
DOI
10.1016/j.bbmt.2004.12.114

Efficient enrichment and flow sorting of aldehyde dehydrogenase bright hematopoietic progenitor cells from thawed, banked umbilical cord blood

Authors
Gentry, TL; Balber, AE; Baucom, C; Deibert, E; Haley, NR; Pritchard, C; Hickerson, D; Carawan, H; Kaestner, A; Kurtzberg, J
MLA Citation
Gentry, TL, Balber, AE, Baucom, C, Deibert, E, Haley, NR, Pritchard, C, Hickerson, D, Carawan, H, Kaestner, A, and Kurtzberg, J. "Efficient enrichment and flow sorting of aldehyde dehydrogenase bright hematopoietic progenitor cells from thawed, banked umbilical cord blood." February 2005.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
2
Publish Date
2005
Start Page
68
End Page
68
DOI
10.1016/j.bbmt.2004.12.204

Single center experience with collection and administration of G-CSF–mobilized, irradiated granulocyte transfusions from directed donors to support patients at high risk for infections undergoing unrelated donor blood and marrow transplantation

Authors
Allison, J; Stephens, C; Waters-Pick, B; Bradshaw, T; Whitlock, P; Kurtzberg, J
MLA Citation
Allison, J, Stephens, C, Waters-Pick, B, Bradshaw, T, Whitlock, P, and Kurtzberg, J. "Single center experience with collection and administration of G-CSF–mobilized, irradiated granulocyte transfusions from directed donors to support patients at high risk for infections undergoing unrelated donor blood and marrow transplantation." February 2005.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
2
Publish Date
2005
Start Page
90
End Page
90
DOI
10.1016/j.bbmt.2004.12.265

Treatment of pediatric patients with Sanfilippo syndrome (MPS IIIA and IIIB) with unrelated umbilical cord blood transplantation

Authors
Kurtzberg, J; Szabolcs, P; Wood, S; Ciocci, G; Driscoll, T; Prasad, V; Parikh, S; Martin, PL; Allison, J; Escolar, ML
MLA Citation
Kurtzberg, J, Szabolcs, P, Wood, S, Ciocci, G, Driscoll, T, Prasad, V, Parikh, S, Martin, PL, Allison, J, and Escolar, ML. "Treatment of pediatric patients with Sanfilippo syndrome (MPS IIIA and IIIB) with unrelated umbilical cord blood transplantation." February 2005.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
2
Publish Date
2005
Start Page
83
End Page
84
DOI
10.1016/j.bbmt.2004.12.246

Treatment options and nursing care for the pediatric aplastic anemia patient requriring bone marrow or stem cell transplantation

Authors
Baker, JH; Frey, MA; Kurtzberg, J
MLA Citation
Baker, JH, Frey, MA, and Kurtzberg, J. "Treatment options and nursing care for the pediatric aplastic anemia patient requriring bone marrow or stem cell transplantation." February 2005.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
2
Publish Date
2005
Start Page
98
End Page
98
DOI
10.1016/j.bbmt.2004.12.291

Dendritic cell and T-cell subsets correlate with the development and site of acute GVHD following unrelated cord blood transplantation in children: A multivariate analysis

Authors
Szabolcs, P; Park, KD; Niedzwiecki, D; Sanders, L; Lee, YA; Marti, L; Reese, MI; Kurtzberg, J
MLA Citation
Szabolcs, P, Park, KD, Niedzwiecki, D, Sanders, L, Lee, YA, Marti, L, Reese, MI, and Kurtzberg, J. "Dendritic cell and T-cell subsets correlate with the development and site of acute GVHD following unrelated cord blood transplantation in children: A multivariate analysis." February 2005.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
2
Publish Date
2005
Start Page
81
End Page
81
DOI
10.1016/j.bbmt.2004.12.240

Outcomes of unrelated umbilical cord blood transplantation in pediatric patients with myelodysplastic syndrome

Authors
Parikh, SH; Martin, PL; Szabolcs, P; Ann, S; Prasad, V; Driscoll, T; Kurtzberg, J
MLA Citation
Parikh, SH, Martin, PL, Szabolcs, P, Ann, S, Prasad, V, Driscoll, T, and Kurtzberg, J. "Outcomes of unrelated umbilical cord blood transplantation in pediatric patients with myelodysplastic syndrome." February 2005.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
2
Publish Date
2005
Start Page
80
End Page
80
DOI
10.1016/j.bbmt.2004.12.236

Partial splenectomy before a hematopoietic stem cell transplantation in children.

UNLABELLED: Hematopoietic stem cell (HSC) engraftment is delayed in children with hypersplenism, and splenectomy may improve HSC engraftment. However, the use of total splenectomy in children is limited because of concerns for postsplenectomy sepsis. In this study, the authors sought to assess the role of partial splenectomy for children with hypersplenism undergoing HSC transplantation. METHODS: Five children with a variety of conditions and associated hypersplenism underwent partial splenectomy before an HSC transplantation at the authors' institution between 2000 and 2003. Primary outcome measures were rates of neutrophil and platelet engraftment. Secondary outcome measures included perioperative complications, splenic regrowth, graft-versus-host disease, and infection rate. All outcomes were compared with recipients of an HSC transplant from both age-matched nonsplenectomized children (n = 497) and hypersplenic children who underwent total splenectomy (n = 10). Outcomes were compared using Wilcoxon's rank sum test. RESULTS: The rate of both neutrophil and platelet engraftment was faster in children who underwent either partial or total splenectomy as compared with nonsplenectomized children (mean rates of neutrophil engraftment were 26, 19, and 19 days for the nonsplenectomy, total splenectomy, and partial splenectomy groups, respectively; mean rates of platelet engraftment were 97, 37, and 45 days for the nonsplenectomy, total splenectomy, and partial splenectomy groups, respectively). Graft-versus-host disease rates were similar between the 3 groups. The mean percentage of splenic regrowth after partial splenectomy was 39%. There were no perioperative complications. CONCLUSIONS: Partial splenectomy may be safely performed before HSC transplantation and, similar to total splenectomy, may improve the rate of HSC engraftment. Although this series has a limited number of patients, the use of partial splenectomy appears to be safe and may allow for splenic salvage to minimize the risk of postsplenectomy sepsis.

Authors
Hall, JG; Kurtzberg, J; Szabolcs, P; Skinner, MA; Rice, HE
MLA Citation
Hall, JG, Kurtzberg, J, Szabolcs, P, Skinner, MA, and Rice, HE. "Partial splenectomy before a hematopoietic stem cell transplantation in children." J Pediatr Surg 40.1 (January 2005): 221-227.
PMID
15868588
Source
pubmed
Published In
Journal of Pediatric Surgery
Volume
40
Issue
1
Publish Date
2005
Start Page
221
End Page
227
DOI
10.1016/j.jpedsurg.2004.09.047

Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations.

Globoid cell leukodystrophy is an inherited metabolic disorder of the central nervous system caused by deficiency of the lysosomal enzyme galactocerebrosidase. Haematopoietic stem cell transplantation is the only available effective treatment. The engraftment from normal donors provides competent cells able to correct the metabolic defect. Umbilical cord blood cells have proved to significantly decrease complications and improve engraftment rate compared to adult marrow cells in haematopoietic stem cell transplantation. Umbilical cord blood cells must be of sufficient activity to provide central nervous system recovery after engraftment is obtained. Galactocerebrosidase activity is known to be affected by two polymorphic alleles found at nucleotides 502 and 1637 of the cDNA for this gene. This enzyme activity and the polymorphic alleles noted above were analysed in 83 random samples of umbilical cord blood. The activity, assayed with the fluorogenic substrate 6-hexadecanoylamino-4-methylumbelliferyl-beta-galactopyranoside, in those with neither polymorphic allele was 4.6 +/- 1.7 units (nmol/h per mg protein). This optimal choice of cord blood was found in only 24% of specimens. Homozygotes for 1637T > C with activity of only 1.5 +/- 0.4 units represented 16% of the samples. Those heterozygous for 1637T > C with slightly better activity (2.3 +/- 0.7 units) represented 52% of the samples. Choice of umbilical cord blood for haematopoietic stem cell transplantation, therefore, requires consideration not only of cell quantity and HLA compatibility but also selection for normal alleles to obtain maximal enzymatic activity for central nervous system correction.

Authors
Raghavan, S; Zeng, B; Torres, PA; Pastores, GM; Kolodny, EH; Kurtzberg, J; Krivit, W
MLA Citation
Raghavan, S, Zeng, B, Torres, PA, Pastores, GM, Kolodny, EH, Kurtzberg, J, and Krivit, W. "Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations." J Inherit Metab Dis 28.6 (2005): 1005-1009.
PMID
16435193
Source
pubmed
Published In
Journal of Inherited Metabolic Disease
Volume
28
Issue
6
Publish Date
2005
Start Page
1005
End Page
1009
DOI
10.1007/s10545-005-4138-z

Cord blood transplantation for lysosomal storage diseases demonstrates the potential of cord blood cells for future cellular therapies

Authors
Kurtzberg, J; Krivit, W
MLA Citation
Kurtzberg, J, and Krivit, W. "Cord blood transplantation for lysosomal storage diseases demonstrates the potential of cord blood cells for future cellular therapies." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
979A
End Page
980A

Recryopreserved and rethawed aliquots with anti-CD3, IL-2, IL12 significantly expands NKT cells, NKT KIR substes and NK cytotoxicity compared to short-term expansion: Potential for CB adoptive cellular immunotherapy (ACI).

Authors
Ayello, J; Satwani, P; van de Ven, C; Roman, E; O'Neill, A; Shutran, M; Greenhawt, M; Baxi, L; Simpson, L; Kurtzberg, J; Cairo, MS
MLA Citation
Ayello, J, Satwani, P, van de Ven, C, Roman, E, O'Neill, A, Shutran, M, Greenhawt, M, Baxi, L, Simpson, L, Kurtzberg, J, and Cairo, MS. "Recryopreserved and rethawed aliquots with anti-CD3, IL-2, IL12 significantly expands NKT cells, NKT KIR substes and NK cytotoxicity compared to short-term expansion: Potential for CB adoptive cellular immunotherapy (ACI)." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
778A
End Page
778A

Immunophenotype and analysis of allo-reactivity of umbilical cord blood (UCB)-derived T-cells following ex-vivo expansion

Authors
Staba, SL; Reese, M; Kurtzberg, J
MLA Citation
Staba, SL, Reese, M, and Kurtzberg, J. "Immunophenotype and analysis of allo-reactivity of umbilical cord blood (UCB)-derived T-cells following ex-vivo expansion." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
118A
End Page
118A

High expression of granzymes and perforin along with increased T cell cycling in vivo predicts the development of opportunistic infections (OI) following unrelated cord blood transplantation (UCBT).

Authors
Szabolcs, P; Lee, YA; Marti, L; Reese, M; Kurtzberg, J
MLA Citation
Szabolcs, P, Lee, YA, Marti, L, Reese, M, and Kurtzberg, J. "High expression of granzymes and perforin along with increased T cell cycling in vivo predicts the development of opportunistic infections (OI) following unrelated cord blood transplantation (UCBT)." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
615A
End Page
615A

Establishment of the NMDP cord blood banking network.

Authors
Kurtzberg, J; Creer, M; Halet, M; Welte, K; Wagner, JE; Boo, M; Confer, DL; Chell, J
MLA Citation
Kurtzberg, J, Creer, M, Halet, M, Welte, K, Wagner, JE, Boo, M, Confer, DL, and Chell, J. "Establishment of the NMDP cord blood banking network." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
382B
End Page
382B

Cord blood (CB) bank log CD34(+) and CD34(+) subsets (CD38(-)CD61(+)CD90(+)) are significantly correlated to log total CFU, CFU-GEMM, CFU-GM and BFU-E: A report from the COBLT program

Authors
Cairo, MS; Wagner, E; Cohen, G; Fraser, J; Jensen, LA; Carter, S; van de Ven, C; Kernan, NA; Kurtzberg, J
MLA Citation
Cairo, MS, Wagner, E, Cohen, G, Fraser, J, Jensen, LA, Carter, S, van de Ven, C, Kernan, NA, and Kurtzberg, J. "Cord blood (CB) bank log CD34(+) and CD34(+) subsets (CD38(-)CD61(+)CD90(+)) are significantly correlated to log total CFU, CFU-GEMM, CFU-GM and BFU-E: A report from the COBLT program." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
119A
End Page
119A

Defibrotide (DF) for the treatment of severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post SCT: Final results of a phase II, multicenter, randomized study and preliminary analyses of surrogate markers and ultrasound findings

Authors
Richardson, PG; Soiffer, RJ; Antin, JH; Voss, SD; Jin, Z; Kurtzberg, J; Martin, PL; Hockenbery, D; Murray, KF; Vogelsang, GB; Chen, A; Krishnan, A; Kernan, NA; Avigan, D; Spitzer, TR; Iannone, R; Giralt, S; Warren, D; Momtaz, P; Bradwin, G; Iacobelli, M; McDonald, GB; Guinan, EC
MLA Citation
Richardson, PG, Soiffer, RJ, Antin, JH, Voss, SD, Jin, Z, Kurtzberg, J, Martin, PL, Hockenbery, D, Murray, KF, Vogelsang, GB, Chen, A, Krishnan, A, Kernan, NA, Avigan, D, Spitzer, TR, Iannone, R, Giralt, S, Warren, D, Momtaz, P, Bradwin, G, Iacobelli, M, McDonald, GB, and Guinan, EC. "Defibrotide (DF) for the treatment of severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post SCT: Final results of a phase II, multicenter, randomized study and preliminary analyses of surrogate markers and ultrasound findings." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
103A
End Page
104A

Dendritic and T cell subsets correlate with the development and site of acute GVHD following unrelated cord blood transplantation. A multivariate analysis of host, graft, and day+50 immune profile.

Authors
Szabolcs, P; Park, KD; Marti, L; Lee, YA; Reese, M; Sanders, L; Niedzwiecki, D; Kurtzberg, J
MLA Citation
Szabolcs, P, Park, KD, Marti, L, Lee, YA, Reese, M, Sanders, L, Niedzwiecki, D, and Kurtzberg, J. "Dendritic and T cell subsets correlate with the development and site of acute GVHD following unrelated cord blood transplantation. A multivariate analysis of host, graft, and day+50 immune profile." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
281A
End Page
281A

Purine nucleoside phosphorylase deficiency (PNP-def) presenting with lymphopenia and developmental delay: successful correction with umbilical cord blood transplantation.

Purine nucleoside phosphorylase deficiency is a primary immunodeficiency syndrome characterized by the triad of recurrent infection, neurologic dysfunction, and autoimmunity. This patient presented atypically with few infections and normal T-cell function. Progressive lymphopenia, ataxia, and developmental delay led to diagnosis. Umbilical cord blood transplantation corrected the immunodeficiency.

Authors
Myers, LA; Hershfield, MS; Neale, WT; Escolar, M; Kurtzberg, J
MLA Citation
Myers, LA, Hershfield, MS, Neale, WT, Escolar, M, and Kurtzberg, J. "Purine nucleoside phosphorylase deficiency (PNP-def) presenting with lymphopenia and developmental delay: successful correction with umbilical cord blood transplantation." J Pediatr 145.5 (November 2004): 710-712.
PMID
15520787
Source
pubmed
Published In
The Journal of Pediatrics
Volume
145
Issue
5
Publish Date
2004
Start Page
710
End Page
712
DOI
10.1016/j.jpeds.2004.06.075

Cord blood transplantation in genetic disorders

Authors
Kurtzberg, J
MLA Citation
Kurtzberg, J. "Cord blood transplantation in genetic disorders." October 2004.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Issue
10
Publish Date
2004
Start Page
735
End Page
736
DOI
10.1016/j.bbmt.2004.06.021

High resolution class I sequence-based typing of cord blood samples reveals high rate of new allele detection in ethnic minorities

Authors
Sidebottom, D; Lai, J; Peng, L; Kurtzberg, J; Baxter-Lowe, LA
MLA Citation
Sidebottom, D, Lai, J, Peng, L, Kurtzberg, J, and Baxter-Lowe, LA. "High resolution class I sequence-based typing of cord blood samples reveals high rate of new allele detection in ethnic minorities." September 2004.
Source
crossref
Published In
Human Immunology
Volume
65
Issue
9-10
Publish Date
2004
Start Page
S96
End Page
S96
DOI
10.1016/j.humimm.2004.07.181

Isolation of oligodendrocyte precursors from umbilical cord blood for the repair of spinal cord injury

Authors
Hall, JG; Crapnell, K; Staba, S; Kurtzberg, J; Rice, H
MLA Citation
Hall, JG, Crapnell, K, Staba, S, Kurtzberg, J, and Rice, H. "Isolation of oligodendrocyte precursors from umbilical cord blood for the repair of spinal cord injury." September 2004.
Source
wos-lite
Published In
Journal of The American College of Surgeons
Volume
199
Issue
3
Publish Date
2004
Start Page
S46
End Page
S46

The incidence of testicular recurrence in boys with acute leukemia treated with total body and testicular irradiation and stem cell transplantation.

BACKGROUND: The incidence of testicular recurrence of childhood acute leukemia after total body irradiation (TBI) in conjunction with stem cell transplantation (SCT) has been reported to be as high as 24%. The authors studied the incidence of testicular failure in a large series of male patients who underwent SCT using either TBI and a testicular irradiation boost or chemotherapy alone. METHODS: One hundred thirty-one boys with either acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) were treated with SCT with either TBI with testicular boost (n = 94 patients), TBI without testicular boost (n = 1 patient), or chemotherapy alone (n = 36 patients) between 1991 and 1999. RESULTS: The median follow-up was 26.5 months (range, 0.6-99.5 months) from the date of bone marrow infusion. Two patients in the study had a primary testicular failure after TBI with testicular boost followed by an umbilical cord blood transplantation. The first patient had ALL, did not engraft, and was rescued with autologous cells. He developed disease in the testicle 15 months afterward and subsequently died. The second patient had Philadelphia chromosome-positive ALL and developed a testicular recurrence 26 months after SCT. He was treated with orchiectomy, further testicular irradiation, and chemotherapy and remained in complete remission > 3 year after his failure. The incidence of testicular failure in boys who received TBI and testicular irradiation who survived > or = 1 year was 4.2%. There were no primary testicular failures reported in boys who received chemotherapy alone. CONCLUSIONS: Boys with AML or ALL had a low incidence of primary testicular failure when they were treated with TBI plus a testicular boost or with chemotherapy alone.

Authors
Quaranta, BP; Halperin, EC; Kurtzberg, J; Clough, R; Martin, PL
MLA Citation
Quaranta, BP, Halperin, EC, Kurtzberg, J, Clough, R, and Martin, PL. "The incidence of testicular recurrence in boys with acute leukemia treated with total body and testicular irradiation and stem cell transplantation." Cancer 101.4 (August 15, 2004): 845-850.
PMID
15305418
Source
pubmed
Published In
Cancer
Volume
101
Issue
4
Publish Date
2004
Start Page
845
End Page
850
DOI
10.1002/cncr.20413

Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations

Authors
Krivit, WC; Kurtzberg, J; Zeng, B; Torres, P; Pastores, G; Raghavan, S
MLA Citation
Krivit, WC, Kurtzberg, J, Zeng, B, Torres, P, Pastores, G, and Raghavan, S. "Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations." August 2004.
Source
wos-lite
Published In
Journal of Neurochemistry
Volume
90
Publish Date
2004
Start Page
95
End Page
95

Utility of end consolidation bone marrow aspirates in childhood acute lymphoblastic leukemia [ALL]: A Pediatric Oncology Group study [POG].

Authors
Hull, KJ; Bell, BB; Chauvenet, AR; Kurtzberg, J; Sterikoff, S; Devidas, M; Camitta, BM
MLA Citation
Hull, KJ, Bell, BB, Chauvenet, AR, Kurtzberg, J, Sterikoff, S, Devidas, M, and Camitta, BM. "Utility of end consolidation bone marrow aspirates in childhood acute lymphoblastic leukemia [ALL]: A Pediatric Oncology Group study [POG]." July 15, 2004.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
22
Issue
14
Publish Date
2004
Start Page
815S
End Page
815S

Cord blood (CB) hematopoietic progenitor cell (HPC) characterization and correlation with ethnicity: A report from the COBLT/NHLBI program

Authors
Cairo, MS; Cohen, G; Wagner, E; Fraser, J; Jensen, L; Carter, S; Kernan, N; Kurtzberg, J
MLA Citation
Cairo, MS, Cohen, G, Wagner, E, Fraser, J, Jensen, L, Carter, S, Kernan, N, and Kurtzberg, J. "Cord blood (CB) hematopoietic progenitor cell (HPC) characterization and correlation with ethnicity: A report from the COBLT/NHLBI program." July 2004.
Source
wos-lite
Published In
Experimental Hematology
Volume
32
Issue
7
Publish Date
2004
Start Page
57
End Page
57

A novel approach for expansion and activation of natural killer cell subsets in previously cryopreserved cord blood (CB) with anti-CD3, IL-2, IL-7 and IL-12: Implication for adoptive cellular immunotherapy post cord blood transplantation (CBT)

Authors
Ayello, J; Satwani, P; van de Ven, C; Kurtzberg, J; Baxi, L; Simpson, LL; Cairo, MS
MLA Citation
Ayello, J, Satwani, P, van de Ven, C, Kurtzberg, J, Baxi, L, Simpson, LL, and Cairo, MS. "A novel approach for expansion and activation of natural killer cell subsets in previously cryopreserved cord blood (CB) with anti-CD3, IL-2, IL-7 and IL-12: Implication for adoptive cellular immunotherapy post cord blood transplantation (CBT)." July 2004.
Source
wos-lite
Published In
Experimental Hematology
Volume
32
Issue
7
Publish Date
2004
Start Page
77
End Page
77

Unrelated cord blood (CB) banking, immune lymphocyte subsets and nucleated RBC characterization and correlation with ethnicity, birthweight, sex and type of delivery: A report from the COBLT/NHLBI program

Authors
Cairo, MS; Cohen, G; Wagner, E; Fraser, J; Jensen, L; Carter, S; Kernan, N; Kurtzberg, J
MLA Citation
Cairo, MS, Cohen, G, Wagner, E, Fraser, J, Jensen, L, Carter, S, Kernan, N, and Kurtzberg, J. "Unrelated cord blood (CB) banking, immune lymphocyte subsets and nucleated RBC characterization and correlation with ethnicity, birthweight, sex and type of delivery: A report from the COBLT/NHLBI program." July 2004.
Source
wos-lite
Published In
Experimental Hematology
Volume
32
Issue
7
Publish Date
2004
Start Page
80
End Page
80

Utility of end consolidation bone marrow aspirates in childhood acute lymphoblastic leukemia [ALL]: A Pediatric Oncology Group study [POG].

8564 Background: There is little information on the value of bone marrow aspirates (BMA) as a guide to treatment in pediatric ALL. Although BMA morphology provides useful information at diagnosis, end of induction, and end of therapy, its value when performed at the end of consolidation is not known. During the conduct of several POG protocols, a decision was made to discontinue end of consolidation BMA. This provided an opportunity to study the value of BMA at that time point.We reviewed end of consolidation BMA morphology from four POG protocols, (POG 9201 Pilot for good-risk ALL; POG 9201, phase III study for good-risk ALL; and POG 9405/9605, phase III study for standard-risk ALL). Patients were stratified into low-, standard-, and high-risk groups according to NIH criteria (age, white count, CNS involvement), DNA index, and cytogenetics. POG 9201 Pilot, 9201, and 9605 defined the end of consolidation as week 25, and POG 9405 as week 28. 2086 study coordinator charts were reviewed: 697 [POG 9201 Pilot/9201], 301 [POG 9405], and 1088 [POG 9605]. Remission was defined as: M1: 0-5% blasts; M2: > 5-25%; M3: > 25%, with at least 200 cells counted. High-risk patients were not reviewed.776 patients (330/697, 66/301 and 380/1088) had complete information, including differential count, on the end of consolidation marrow (reflects study amendment to discontinue BMA). 773 of 776 (99.6%) of patients with end of consolidation BMA had M1 marrow. Two of 3 who had M2 marrow relapsed (28 and 45 months after achieving remission), and the third is continuously disease free (60 months).Routine BMA at the end of consolidation is not of prognostic or therapeutic value and should be restricted to protocols in which randomization to different treatments is after that time point. Traditional morphologic review will likely be supplanted by more sensitive measures of minimal residual disease, such as cytogenetics, flow cytometry, or molecular markers. No significant financial relationships to disclose.

Authors
Hull, KJ; Bell, BB; Chauvenet, AR; Kurtzberg, J; Sterikoff, S; Devidas, M; Camitta, BM
MLA Citation
Hull, KJ, Bell, BB, Chauvenet, AR, Kurtzberg, J, Sterikoff, S, Devidas, M, and Camitta, BM. "Utility of end consolidation bone marrow aspirates in childhood acute lymphoblastic leukemia [ALL]: A Pediatric Oncology Group study [POG]." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 22.14_suppl (July 2004): 8564-.
PMID
28013875
Source
epmc
Published In
Journal of Clinical Oncology
Volume
22
Issue
14_suppl
Publish Date
2004
Start Page
8564

Unrelated umbilical cord blood transplantation for an infant with beta-thalassemia major.

BACKGROUND: beta-thalassemia major, one of the most prevalent hemoglobinopathies throughout the world, can be cured by allogeneic stem cell transplantation therapy. Many patients, however, lack a suitably matched related donor. Unrelated umbilical cord blood can be used as an alternative stem cell source for some of these patients. This report describes the successful transplantation of a 2-month-old infant with beta-thalassemia major using partially HLA-matched unrelated umbilical cord blood. METHODS: After cytoreduction with busulfan, cyclophosphamide, and antithymocyte globulin (ATG), the patient underwent transplantation at the age of 2 months with a 4/6 HLA matching umbilical cord blood unit from an unrelated donor. RESULTS: The patient engrafted promptly with 100% donor chimerism. His only major complication was an autoimmune hemolytic anemia that resolved 2 years after transplantation. He is currently surviving, event-free, 5 years after transplantation with normal growth and cognitive development and full donor chimerism without evidence of beta-thalassemia. CONCLUSIONS: Umbilical cord blood transplantation from related and unrelated donors should be considered for patients with beta-thalassemia major who lack traditional bone marrow donors. As most newborns undergo screening for hemoglobinopathies, those with disease could be transplanted early in life before experiencing the morbidity and mortality caused by transfusion therapy, alloimmunization, and iron overload, increasing the likelihood of successful transplantation therapy.

Authors
Hall, JG; Martin, PL; Wood, S; Kurtzberg, J
MLA Citation
Hall, JG, Martin, PL, Wood, S, and Kurtzberg, J. "Unrelated umbilical cord blood transplantation for an infant with beta-thalassemia major." J Pediatr Hematol Oncol 26.6 (June 2004): 382-385.
PMID
15167353
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
26
Issue
6
Publish Date
2004
Start Page
382
End Page
385

Cord-blood transplants from unrelated donors in patients with Hurler's syndrome.

BACKGROUND: Hurler's syndrome (the most severe form of mucopolysaccharidosis type I) causes progressive deterioration of the central nervous system and death in childhood. Allogeneic bone marrow transplantation before the age of two years halts disease progression and prolongs life, but many children lack a bone marrow donor. We investigated the feasibility of using cord-blood transplants from unrelated donors and a myeloablative preparative regimen that did not involve total-body irradiation in young children with Hurler's syndrome. METHODS: Between December 1995 and October 2002, 20 consecutive children with Hurler's syndrome received busulfan, cyclophosphamide, and antithymocyte globulin before receiving cord-blood transplants from unrelated donors. The children were subsequently evaluated for engraftment, adverse effects, and effects on disease symptoms. RESULTS: Cord-blood donors had normal alpha-L-iduronidase activity (mean number of cells, 10.53x10(7) per kilogram of body weight) and were discordant for up to three of six HLA markers. Neutrophil engraftment occurred a median of 24 days after transplantation. Five patients had grade II or grade III acute graft-versus-host disease; none had extensive chronic graft-versus-host disease. Seventeen of the 20 children were alive a median of 905 days after transplantation, with complete donor chimerism and normal peripheral-blood alpha-L-iduronidase activity (event-free survival rate, 85 percent). Transplantation improved neurocognitive performance and decreased somatic features of Hurler's syndrome. CONCLUSIONS: Cord blood from unrelated donors appears to be an excellent source of stem cells for transplantation in patients with Hurler's syndrome. Sustained engraftment can be achieved without total-body irradiation. Cord-blood transplantation favorably altered the natural history of Hurler's syndrome and thus may be important to consider in young children with this form of the disease.

Authors
Staba, SL; Escolar, ML; Poe, M; Kim, Y; Martin, PL; Szabolcs, P; Allison-Thacker, J; Wood, S; Wenger, DA; Rubinstein, P; Hopwood, JJ; Krivit, W; Kurtzberg, J
MLA Citation
Staba, SL, Escolar, ML, Poe, M, Kim, Y, Martin, PL, Szabolcs, P, Allison-Thacker, J, Wood, S, Wenger, DA, Rubinstein, P, Hopwood, JJ, Krivit, W, and Kurtzberg, J. "Cord-blood transplants from unrelated donors in patients with Hurler's syndrome." N Engl J Med 350.19 (May 6, 2004): 1960-1969.
PMID
15128896
Source
pubmed
Published In
The New England journal of medicine
Volume
350
Issue
19
Publish Date
2004
Start Page
1960
End Page
1969
DOI
10.1056/NEJMoa032613

Proof of principle: Globoid cell leukodystrophy late onset: Effective therapeutic intervention in disease course by use of hematopoietic stem cell transplantation

Authors
Krivit, W; Van Coster, R; Kurtzberg, J; Bunin, N; Kaplan, P; Peters, C
MLA Citation
Krivit, W, Van Coster, R, Kurtzberg, J, Bunin, N, Kaplan, P, and Peters, C. "Proof of principle: Globoid cell leukodystrophy late onset: Effective therapeutic intervention in disease course by use of hematopoietic stem cell transplantation." April 2004.
Source
wos-lite
Published In
Pediatric Research
Volume
55
Issue
4
Publish Date
2004
Start Page
35A
End Page
35A

Racial diversity with high nucleated cell counts and CD34 counts achieved in a national network of cord blood banks.

Banked, unrelated, partially HLA-matched, umbilical cord blood is an alternative stem cell source for patients in need of transplantation therapy who lack traditionally matched donors. A presumed advantage of cord blood is the ability to increase recruitment of donors of minority ethnic backgrounds. The American Red Cross Cord Blood Program was established in 1999 with 6 banks and 10 collection sites throughout the country. Cord blood donors self-report racial designations on questionnaires, and donor race was collected from each site. Postprocessing nucleated cell counts and CD34(+) counts were obtained on the cord blood units, and results from each racial group (white, black, Asian, Hispanic, and Native American) were compared in the natural logarithmic scale by using analysis of variance. A total of 18878 donors consented: 64% white, 16% black, 12% Hispanic, 4% Asian, 1% Native American, and 3% other. The Detroit area consented the highest percentage of black donors (87%), San Diego consented the highest percentage of Hispanic donors (59%), and Oakland consented the highest percentage of Asian donors (15%). Seven thousand eight hundred sixty-six cord blood units have been banked for transplantation. The mean preprocessing nucleated cell count was 1220 x 10(6) (range, 327-7300 x 10(6)). There was no difference among racial groups when controlled for site (P =.395). The mean CD34(+) count was 3.28 x 10(6). Blacks had a significantly lower CD34(+) count than the other racial/ethnic groups in the Midwest, Northwest, and North Carolina collection sites. A racially diverse cord blood bank can be achieved. Nucleated cell counts were similar among the different racial/ethnic groups. CD34(+) counts were lower for blacks in some collection sites.

Authors
Ballen, KK; Kurtzberg, J; Lane, TA; Lindgren, BR; Miller, JP; Nagan, D; Newman, B; Rupp, N; Haley, NR
MLA Citation
Ballen, KK, Kurtzberg, J, Lane, TA, Lindgren, BR, Miller, JP, Nagan, D, Newman, B, Rupp, N, and Haley, NR. "Racial diversity with high nucleated cell counts and CD34 counts achieved in a national network of cord blood banks." Biol Blood Marrow Transplant 10.4 (April 2004): 269-275.
PMID
15077225
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Issue
4
Publish Date
2004
Start Page
269
End Page
275
DOI
10.1016/j.bbmt.2003.12.003

Immune reconstitution and the risk of opportunistic infections after unrelated cord blood transplantation. A multivariate analysis

Authors
Szaboles, P; Park, KD; Reese, M; Marti, L; Sanders, L; Niedzwiecki, D; Lee, Y; DeOliveira, D; Kurtzberg, J
MLA Citation
Szaboles, P, Park, KD, Reese, M, Marti, L, Sanders, L, Niedzwiecki, D, Lee, Y, DeOliveira, D, and Kurtzberg, J. "Immune reconstitution and the risk of opportunistic infections after unrelated cord blood transplantation. A multivariate analysis." March 24, 2004.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
18
Issue
5
Publish Date
2004
Start Page
A829
End Page
A829

Elevated chitotriosidase activity in CSF in patients with tay-Sachs disease: a surrogate marker of disease progression?

Authors
Tifft, CJ; Kurtzberg, J; Proia, RL
MLA Citation
Tifft, CJ, Kurtzberg, J, and Proia, RL. "Elevated chitotriosidase activity in CSF in patients with tay-Sachs disease: a surrogate marker of disease progression?." March 2004.
Source
wos-lite
Published In
Molecular Genetics and Metabolism
Volume
81
Issue
3
Publish Date
2004
Start Page
182
End Page
182

Elevated chitotriosidase activity in CSF in patients with GM1 and GM2 gangliosidosis: a surrogate marker of disease progression?

Authors
Tifft, CJ; Kurtzberg, J; Proia, RL
MLA Citation
Tifft, CJ, Kurtzberg, J, and Proia, RL. "Elevated chitotriosidase activity in CSF in patients with GM1 and GM2 gangliosidosis: a surrogate marker of disease progression?." March 2004.
Source
wos-lite
Published In
Molecular Genetics and Metabolism
Volume
81
Issue
3
Publish Date
2004
Start Page
181
End Page
182

Ex vivo expansion of immature and mature T cells derived from umbilical cord blood (UCB)

Authors
Staba, SL; Crapnell, KB; Hall, JG; Reese, M; Kurtzberg, J
MLA Citation
Staba, SL, Crapnell, KB, Hall, JG, Reese, M, and Kurtzberg, J. "Ex vivo expansion of immature and mature T cells derived from umbilical cord blood (UCB)." February 2004.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Publish Date
2004
Start Page
16
End Page
16
DOI
10.1016/j.bbmt.2003.12.056

Umbilical cord blood cells engraft and differentiate in cardiac tissues after human tranplantation

Authors
Crapnell, KB; Turner, K; Hall, J; Staba, S; Kurtzberg, J
MLA Citation
Crapnell, KB, Turner, K, Hall, J, Staba, S, and Kurtzberg, J. "Umbilical cord blood cells engraft and differentiate in cardiac tissues after human tranplantation." February 2004.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Publish Date
2004
Start Page
83
End Page
84
DOI
10.1016/j.bbmt.2003.12.158

Isolation of oligodendrocyte precursors from umbilical cord blood

Authors
Hall, JG; Crapnell, KB; Staba, S; Kurtzberg, J
MLA Citation
Hall, JG, Crapnell, KB, Staba, S, and Kurtzberg, J. "Isolation of oligodendrocyte precursors from umbilical cord blood." February 2004.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Publish Date
2004
Start Page
67
End Page
67
DOI
10.1016/j.bbmt.2003.12.057

A novel approach for ex-vivo expansion (EvE) of NK CD3−/CD16+/56+bright/dim subsets expressing increased inhibitory receptors from cryopreserved/thawed/expanded/recryopreserved/rethawed (CTECT) and cryopreserved/thawed/recryopreserved/rethawed/expanded (CTCTE) umbilical cord blood (UCB) using anti-CD3, IL-2, IL-7 and IL-12 (AB/CY)

Authors
Ayello, J; Satwani, P; van de Ven, C; Simpson, LL; Kurtzberg, J; Cairo, MS
MLA Citation
Ayello, J, Satwani, P, van de Ven, C, Simpson, LL, Kurtzberg, J, and Cairo, MS. "A novel approach for ex-vivo expansion (EvE) of NK CD3−/CD16+/56+bright/dim subsets expressing increased inhibitory receptors from cryopreserved/thawed/expanded/recryopreserved/rethawed (CTECT) and cryopreserved/thawed/recryopreserved/rethawed/expanded (CTCTE) umbilical cord blood (UCB) using anti-CD3, IL-2, IL-7 and IL-12 (AB/CY)." February 2004.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Publish Date
2004
Start Page
16
End Page
16
DOI
10.1016/j.bbmt.2003.12.054

Results of the cord blood transplantation study (COBLT) unrelated donor banking program

Authors
Kurtzberg, J; Wagner, EL; Fraser, JK; Cairo, MS; Jensen, L; Cohen, G; Carter, SL; Kernan, NA
MLA Citation
Kurtzberg, J, Wagner, EL, Fraser, JK, Cairo, MS, Jensen, L, Cohen, G, Carter, SL, and Kernan, NA. "Results of the cord blood transplantation study (COBLT) unrelated donor banking program." February 2004.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Publish Date
2004
Start Page
21
End Page
21
DOI
10.1016/j.bbmt.2003.12.082

Unrelated umbilical cord blood transplantation for familial erythrophagocytic lymphohistiocytosis

Authors
Archambault, BL; Driscoll, TA; Stafford, LA; Szabolcs, P; Kurtzberg, J; Martin, PL
MLA Citation
Archambault, BL, Driscoll, TA, Stafford, LA, Szabolcs, P, Kurtzberg, J, and Martin, PL. "Unrelated umbilical cord blood transplantation for familial erythrophagocytic lymphohistiocytosis." February 2004.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Issue
2
Publish Date
2004
Start Page
79
End Page
80
DOI
10.1016/j.bbmt.2003.12.132

Continuous platelet drip: A unique approach in the treatment of severe/refractory thrombocytopenia in the pediatric stem cell transplant population

Authors
Talbert, G; Zbylut, C; Chelf, K; Frey, MA; Martin, P; Kurtzberg, J
MLA Citation
Talbert, G, Zbylut, C, Chelf, K, Frey, MA, Martin, P, and Kurtzberg, J. "Continuous platelet drip: A unique approach in the treatment of severe/refractory thrombocytopenia in the pediatric stem cell transplant population." February 2004.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Issue
2
Publish Date
2004
Start Page
101
End Page
102
DOI
10.1016/j.bbmt.2003.12.270

Second hematopoietic stem cell transplant using unrelated donor umbilical cord blood cures 50% of pediatric patients with leukemia relapsing after prior allogeneic transplant from a matched related sibling

Authors
Staba, SL; Szabolcs, P; Driscoll, T; Martin, PL; Kurtzberg, J
MLA Citation
Staba, SL, Szabolcs, P, Driscoll, T, Martin, PL, and Kurtzberg, J. "Second hematopoietic stem cell transplant using unrelated donor umbilical cord blood cures 50% of pediatric patients with leukemia relapsing after prior allogeneic transplant from a matched related sibling." February 2004.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Issue
2
Publish Date
2004
Start Page
38
End Page
38
DOI
10.1016/j.bbmt.2003.12.179

Transplantation of boys with X-linked adrenoleukodystrophy with unrelated-donor, partially HLA-mismatched banked umbilical cord blood

Authors
Allison, J; Martin, PL; Szabolcs, P; Driscoll, T; Parikh, S; Wood, S; Kurtzberg, J
MLA Citation
Allison, J, Martin, PL, Szabolcs, P, Driscoll, T, Parikh, S, Wood, S, and Kurtzberg, J. "Transplantation of boys with X-linked adrenoleukodystrophy with unrelated-donor, partially HLA-mismatched banked umbilical cord blood." February 2004.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Issue
2
Publish Date
2004
Start Page
74
End Page
74
DOI
10.1016/j.bbmt.2003.12.100

Cord-blood transplants from unrelated donors in Hurler's syndrome [1]

Authors
Fujisaki, G; Kami, M; Kishi, Y; Staba, SL; Kurtzberg, J
MLA Citation
Fujisaki, G, Kami, M, Kishi, Y, Staba, SL, and Kurtzberg, J. "Cord-blood transplants from unrelated donors in Hurler's syndrome [1]." New England Journal of Medicine 351.5 (2004): 506-507.
PMID
15282360
Source
scival
Published In
New England Journal of Medicine
Volume
351
Issue
5
Publish Date
2004
Start Page
506
End Page
507
DOI
10.1056/NEJM200407293510518

Unrelated umbilical cord blood transplantation in adult patients.

Since January 1996, we have administered myeloablative therapy followed by infusion of unrelated umbilical cord blood cells in 57 adult patients with high-risk disease. The median age was 31 years (range, 18-58 years), and the median weight was 70 kg (range, 46-110 kg). Two patients were treated for genetic disorders and 55 for advanced hematologic malignancies. The preparative regimens were total body irradiation or busulfan based, both with antithymocyte globulin. HLA matching between donor and recipient was 3 of 6 in 3 patients, 4 of 6 in 44 patients, 5 of 6 in 8 patients, and 6 of 6 in 2 patients. The median nucleated cell dose was 1.50 x 10(7)/kg (range, 0.54-2.78 x 10(7)/kg), and the median CD34(+) cell dose was 1.37 x 10(5)/kg (range, 0.02-12.45 x 10(5)/kg). All patients received granulocyte colony-stimulating factor after transplantation until neutrophil recovery. Graft-versus-host disease prophylaxis consisted of cyclosporine and steroids. The median number of days to an absolute neutrophil count of 500/microL was 26 (range, 12-55 days). The median time to an untransfused platelet count of >20000/microL was 84 days (range, 35-167 days). Seventeen patients developed grade II to IV acute GVHD. The median survival of the entire group was 91 days (range, 10-2251 days). Eleven patients were alive at a median follow-up of 1670 days (range, 67-2251 days), 1 with autologous recovery and 1 with relapsed lymphoma. The actuarial projected 3-year survival is 19%. Infection was the primary cause of death. These results suggest that unrelated umbilical cord blood transplantation is a viable option for adult patients and should be explored in patients with earlier-stage disease.

Authors
Long, GD; Laughlin, M; Madan, B; Kurtzberg, J; Gasparetto, C; Morris, A; Rizzieri, D; Smith, C; Vredenburgh, J; Halperin, EC; Broadwater, G; Niedzwiecki, D; Chao, NJ
MLA Citation
Long, GD, Laughlin, M, Madan, B, Kurtzberg, J, Gasparetto, C, Morris, A, Rizzieri, D, Smith, C, Vredenburgh, J, Halperin, EC, Broadwater, G, Niedzwiecki, D, and Chao, NJ. "Unrelated umbilical cord blood transplantation in adult patients." Biol Blood Marrow Transplant 9.12 (December 2003): 772-780.
PMID
14677117
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
9
Issue
12
Publish Date
2003
Start Page
772
End Page
780
DOI
10.1016/j.bbmt.2003.08.007

Results of the cord blood transplantation study (COBLT) unrelated donor banking program from donor screening to characterization of banked units.

Authors
Kurtzberg, J; Wagner, EL; Fraser, JK; Cairo, MS; Jensen, LA; Cohen, G; Carter, SL; Kernan, NA
MLA Citation
Kurtzberg, J, Wagner, EL, Fraser, JK, Cairo, MS, Jensen, LA, Cohen, G, Carter, SL, and Kernan, NA. "Results of the cord blood transplantation study (COBLT) unrelated donor banking program from donor screening to characterization of banked units." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
461A
End Page
461A

Isolation of oligodendrocyte precursors from umbilical cord blood.

Authors
Hall, JG; Crapnell, KB; Staba, S; Kurtzberg, J
MLA Citation
Hall, JG, Crapnell, KB, Staba, S, and Kurtzberg, J. "Isolation of oligodendrocyte precursors from umbilical cord blood." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
965A
End Page
966A

A novel method for ex-vivo expansion of NKCD3-/CD16+/56(+bright/dim) subjects expressing increased inhibitory receptors from cryopreserved/thawed/expanded/recryopreserved (CTECT) umbilical cord blood (UCB) using anti-CD3, IL-2, IL-7, and IL-12 (AB/CY): Implications for adoptive cellular immunotherapy (ACI) post umbilical cord blood transplantation (UCBT)

Authors
Satwani, P; Ayello, J; van de Ven, C; Kurtzberg, J; Cairo, MS
MLA Citation
Satwani, P, Ayello, J, van de Ven, C, Kurtzberg, J, and Cairo, MS. "A novel method for ex-vivo expansion of NKCD3-/CD16+/56(+bright/dim) subjects expressing increased inhibitory receptors from cryopreserved/thawed/expanded/recryopreserved (CTECT) umbilical cord blood (UCB) using anti-CD3, IL-2, IL-7, and IL-12 (AB/CY): Implications for adoptive cellular immunotherapy (ACI) post umbilical cord blood transplantation (UCBT)." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
963A
End Page
964A

Umbilical cord blood cells engraft and differentiate in cardiac tissues after human transplantation.

Authors
Crapnell, KB; Turner, K; Hall, J; Staba, S; Kurtzberg, J
MLA Citation
Crapnell, KB, Turner, K, Hall, J, Staba, S, and Kurtzberg, J. "Umbilical cord blood cells engraft and differentiate in cardiac tissues after human transplantation." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
153B
End Page
153B

Outcomes of 138 adult and pediatric patients undergoing cord blood transplantation from large cord blood bank.

Authors
Ballen, KK; Haley, NR; Kurtzberg, J; Lane, TA; Lindgren, BR; Miller, JP; Newman, BH; McCullough, J
MLA Citation
Ballen, KK, Haley, NR, Kurtzberg, J, Lane, TA, Lindgren, BR, Miller, JP, Newman, BH, and McCullough, J. "Outcomes of 138 adult and pediatric patients undergoing cord blood transplantation from large cord blood bank." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
479A
End Page
479A

Ex vivo expansion of umbilical cord blood (UCB) derived immature and mature T cells.

Authors
Staba, SL; Crapnell, KB; Hall, JG; Reese, M; Kurtzberg, J
MLA Citation
Staba, SL, Crapnell, KB, Hall, JG, Reese, M, and Kurtzberg, J. "Ex vivo expansion of umbilical cord blood (UCB) derived immature and mature T cells." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
965A
End Page
965A

Activity of compound 506U78 in patients with refractory T-cell malignancies: A POG/CCG intergroup phase 2 study.

Authors
Berg, SL; Blaney, SM; Bernstein, M; Kurtzberg, J; Devidas, M; Lampkin, T; Murgo, AJ; Harris, MB
MLA Citation
Berg, SL, Blaney, SM, Bernstein, M, Kurtzberg, J, Devidas, M, Lampkin, T, Murgo, AJ, and Harris, MB. "Activity of compound 506U78 in patients with refractory T-cell malignancies: A POG/CCG intergroup phase 2 study." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
226A
End Page
226A

Unrelated donor umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

Authors
Kurtzberg, J; Szabolcs, P; Martin, PL; Driscoll, T; Kelly, T; Ciocci, G; Escolar, ML
MLA Citation
Kurtzberg, J, Szabolcs, P, Martin, PL, Driscoll, T, Kelly, T, Ciocci, G, and Escolar, ML. "Unrelated donor umbilical cord blood transplantation for X-linked adrenoleukodystrophy." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
479B
End Page
479B

Preliminary results of unrelated umbilical cord blood transplantation for Sanfilippo syndrome (MPS III).

Authors
Staba, SL; Escolar, ML; Provenzale, JM; Wood, S; Allison, J; Cash, J; Szabolcs, P; Kurtzberg, J
MLA Citation
Staba, SL, Escolar, ML, Provenzale, JM, Wood, S, Allison, J, Cash, J, Szabolcs, P, and Kurtzberg, J. "Preliminary results of unrelated umbilical cord blood transplantation for Sanfilippo syndrome (MPS III)." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
481A
End Page
481A

TEPA augments the ex-vivo and in-vivo potential of cord blood derived CD34+cells: From basic science to clinical trials.

Authors
Peled, T; Rubinstein, P; Kurtzberg, J; Nagler, A; Fibach, E; Shpall, EJ
MLA Citation
Peled, T, Rubinstein, P, Kurtzberg, J, Nagler, A, Fibach, E, and Shpall, EJ. "TEPA augments the ex-vivo and in-vivo potential of cord blood derived CD34+cells: From basic science to clinical trials." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
961A
End Page
961A

Splenectomy prior to umbilical cord blood (UCB) transplantation facilitates hematologic engraftment in pediatric and adult patients.

Authors
Hall, JG; Rice, HE; Skinner, MA; Szabolcs, P; Kurtzberg, J
MLA Citation
Hall, JG, Rice, HE, Skinner, MA, Szabolcs, P, and Kurtzberg, J. "Splenectomy prior to umbilical cord blood (UCB) transplantation facilitates hematologic engraftment in pediatric and adult patients." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
470A
End Page
471A

Defibrotide (DF) is effective in the treatment of severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post stem cell transplantation (SCT): Results of a phase II, multicenter, randomized study.

Authors
Richardson, P; Soiffer, RJ; Antin, JH; Jin, Z; Vredenburgh, JJ; Kurtzberg, J; Martin, PL; Hockenbery, D; Steinbach, G; Murray, KF; Vogelsang, GB; Chen, A; Krishnan, A; Prasad, VK; Warren, DL; Momtaz, P; Batchelder, A; Wei, LJ; Rifai, N; Bradwin, G; Iacobelli, M; McDonald, GB; Guinan, EC
MLA Citation
Richardson, P, Soiffer, RJ, Antin, JH, Jin, Z, Vredenburgh, JJ, Kurtzberg, J, Martin, PL, Hockenbery, D, Steinbach, G, Murray, KF, Vogelsang, GB, Chen, A, Krishnan, A, Prasad, VK, Warren, DL, Momtaz, P, Batchelder, A, Wei, LJ, Rifai, N, Bradwin, G, Iacobelli, M, McDonald, GB, and Guinan, EC. "Defibrotide (DF) is effective in the treatment of severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post stem cell transplantation (SCT): Results of a phase II, multicenter, randomized study." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
193A
End Page
193A

Coexistent naïve phenotype and higher cycling rate of cord blood T cells as compared to adult peripheral blood.

OBJECTIVE: Umbilical cord blood (UCB) T cells are predominantly CD45RA(+), secrete less cytokines, and have diminished cytotoxicity compared to adult peripheral blood (PB). We hypothesized that the functional impairment of bulk UCB cells results from the relative dominance of immature lymphocyte subsets. In this study we established the physiologic ranges of lymphocyte subsets in UCB, and contrasted those with adult PB. MATERIALS AND METHODS: Four-color FACS was utilized to characterize surface and intracellular protein expression on lymphocyte subsets from fresh unmanipulated UCB and adult PB. RESULTS: We found that UCB contain significantly higher absolute numbers of T cells, NK cells, and B cells than adult PB (p<0.0001). UCB also contains more "naïve" cells not only among CD4(+) and CD8(+) T cells but also among B lymphocytes (p=0.003). Most UCB T cells are CD45RA(+)/CD62L(+) "recent thymic emigrants" with smaller TCRgammadelta (p<0.0001) and CD25(+) subsets (p=0.0068). Fewer UCB T cells display HLA-DR and CCR-5 activation markers (p<0.0001) while the CD8(+)/CD57(+)/CD28(-) "suppressor," CD8(+)/CD45RA(+)/CD27(-) "cytotoxic," and skin homing CLA(+) T-cell subsets are absent altogether. Compared with adult PB, more cord blood T cells progress through cell cycle (p<0.0001) and enter apoptosis (p=0.0003). Unlike in adult PB, the majority of proliferating Ki-67(+) T cells in UCB retain a CD45RA(+)/RO(-), CD69(-), CD25(-), HLA-DR(-) "resting" phenotype (p=0.0002). CONCLUSION: Most T and B lymphocytes express a nai;ve phenotype in cord blood while "suppressor" and "cytotoxic" T-cell subsets are absent. Cycling UCB T cells retain a nai;ve immunophenotype that may represent homeostatic expansion rather than antigen-driven proliferation.

Authors
Szabolcs, P; Park, K-D; Reese, M; Marti, L; Broadwater, G; Kurtzberg, J
MLA Citation
Szabolcs, P, Park, K-D, Reese, M, Marti, L, Broadwater, G, and Kurtzberg, J. "Coexistent naïve phenotype and higher cycling rate of cord blood T cells as compared to adult peripheral blood." Exp Hematol 31.8 (August 2003): 708-714.
PMID
12901976
Source
pubmed
Published In
Experimental Hematology
Volume
31
Issue
8
Publish Date
2003
Start Page
708
End Page
714

Cerebral phaeohyphomycosis in an immunodeficient child treated medically with combination antifungal therapy.

Cerebral phaeohyphomycosis is a rare fungal infection with a poor prognosis when using conventional antifungal therapy in the absence of neurosurgical intervention. We present a case of a pediatric patient with inoperable Cladophialophora bantiana cerebral abscesses. To our knowledge, this child's case is the first reported to be treated with the combination of the newer triazole voriconazole and the new echinocandin caspofungin. Although our patient subsequently died, the natural rapid progression of the disease seemed to be altered by the antifungal combination alone, in the absence of surgery. Despite the fatal outcome for our patient, we encourage other clinicians to try unique medical approaches for this historically life-threatening infection when adjunctive surgery is impossible.

Authors
Trinh, JV; Steinbach, WJ; Schell, WA; Kurtzberg, J; Giles, SS; Perfect, JR
MLA Citation
Trinh, JV, Steinbach, WJ, Schell, WA, Kurtzberg, J, Giles, SS, and Perfect, JR. "Cerebral phaeohyphomycosis in an immunodeficient child treated medically with combination antifungal therapy." Med Mycol 41.4 (August 2003): 339-345.
PMID
12964727
Source
pubmed
Published In
Medical Mycology (Informa)
Volume
41
Issue
4
Publish Date
2003
Start Page
339
End Page
345

A Phase I-II trial of polyethylene glycol-conjugated L-asparaginase in patients with multiple myeloma.

BACKGROUND: Multiple myeloma remains an incurable disease. New agents are needed to improve therapy for patients with this disease. Previous investigators evaluated in vitro sensitivity of myeloma cells to polyethylene glycol-conjugated L-asparaginase (PEG-L-asparaginase) using the human tumor clonogenic assay. Of the 19 myeloma samples evaluated, 63% were inhibited at 0.075 IU/mL, and 74% were inhibited at 0.75 IU/mL. PEG-L-asparaginase is a form of Escherichia coli-derived L-asparaginase that is bound covalently to polyethylene glycol. Compared with the native form, it has a longer half-life and is less likely to cause allergic reactions. METHODS: The authors conducted a Phase I-II trial using PEG-L-asparaginase as a single agent in patients with recurrent and/or refractory multiple myeloma. RESULTS: Twenty-two patients received a median of two doses of PEG-L-asparaginase. In the 17 patients who are evaluable for response, a complete response was observed in one patient after four doses, and stable disease was observed in eight patients. Progression of disease was the reason for termination from study in the remaining eight patients. The median survival was 31.7 months, with four patients who were alive at 72 months after the start of therapy. Grade 3-4 toxicity was noted by the PEG-L-asparaginase 2000 mg/m(2) level. Severe allergic reactions were noted only at the highest dose level. CONCLUSIONS: Current data suggest that the maximal tolerated dose for single agent PEG-L-asparaginase in relapse/refractory multiple myeloma patients is 1000 mg/m(2) every 4 weeks. We could not identify any correlation between dose, plasma level and response. In this advanced group of patients we noted stable disease and/or response in 52% of evaluable patients. PEG-L-asparaginase has lower tolerance when used in the standard dosage as a single agent in this group of patients. We therefore recommend further studying of PEG-L-asparaginase dose of 1000 mg/m(2) on alternate weeks with steroids and/or other immune modulators.

Authors
Agrawal, NR; Bukowski, RM; Rybicki, LA; Kurtzberg, J; Cohen, LJ; Hussein, MA
MLA Citation
Agrawal, NR, Bukowski, RM, Rybicki, LA, Kurtzberg, J, Cohen, LJ, and Hussein, MA. "A Phase I-II trial of polyethylene glycol-conjugated L-asparaginase in patients with multiple myeloma." Cancer 98.1 (July 1, 2003): 94-99.
PMID
12833461
Source
pubmed
Published In
Cancer
Volume
98
Issue
1
Publish Date
2003
Start Page
94
End Page
99
DOI
10.1002/cncr.11480

Ex vivo expansion of umbilical cord blood (UCB) derived immature and mature T cells for adoptive immunotherapy

Authors
Staba, S; Crapnell, K; Hall, J; Reese, M; Kurtzberg, J
MLA Citation
Staba, S, Crapnell, K, Hall, J, Reese, M, and Kurtzberg, J. "Ex vivo expansion of umbilical cord blood (UCB) derived immature and mature T cells for adoptive immunotherapy." July 2003.
Source
wos-lite
Published In
Experimental Hematology
Volume
31
Issue
7
Publish Date
2003
Start Page
207
End Page
207

Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell System.

Allogeneic stem cell transplantation with umbilical cord blood (UCB) cells is limited by the cell dose a single unit provides recipients. Ex vivo expansion is one strategy to increase the number of cells available for transplantation. Aastrom Biosciences developed an automated continuous perfusion culture device for expansion of hematopoietic stem cells (HSCs). Cells are expanded in media supplemented with fetal bovine serum, horse serum, PIXY321, flt-3 ligand, and erythropoietin. We performed a phase 1 trial augmenting conventional UCB transplants with ex vivo-expanded cells. The 28 patients were enrolled on the trial between October 8, 1997 and September 30, 1998. UCB cells were expanded in the device, then administered as a boost to the conventional graft on posttransplantation day 12. While expansion of total cells and colony-forming units (CFUs) occurred in all cases, the magnitude of expansion varied considerably. The median fold increase was 2.4 (range, 1.0-8.5) in nucleated cells, 82 (range, 4.6-266.4) in CFU granulocyte-macrophages, and 0.5 (range, 0.09-2.45) in CD34+ lineage negative (lin-) cells. CD3+ cells did not expand under these conditions. Clinical-scale ex vivo expansion of UCB is feasible, and the administration of ex vivo-expanded cells is well tolerated. Augmentation of UCB transplants with ex vivo-expanded cells did not alter the time to myeloid, erythroid, or platelet engraftment in 21 evaluable patients. Recipients of ex vivo-expanded cells continue to have durable engraftment with a median follow-up of 47 months (range, 41-51 months). A randomized phase 2 study will determine whether augmenting UCB transplants with ex vivo-expanded UCB cells is beneficial.

Authors
Jaroscak, J; Goltry, K; Smith, A; Waters-Pick, B; Martin, PL; Driscoll, TA; Howrey, R; Chao, N; Douville, J; Burhop, S; Fu, P; Kurtzberg, J
MLA Citation
Jaroscak, J, Goltry, K, Smith, A, Waters-Pick, B, Martin, PL, Driscoll, TA, Howrey, R, Chao, N, Douville, J, Burhop, S, Fu, P, and Kurtzberg, J. "Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell System." Blood 101.12 (June 15, 2003): 5061-5067.
PMID
12595310
Source
pubmed
Published In
Blood
Volume
101
Issue
12
Publish Date
2003
Start Page
5061
End Page
5067
DOI
10.1182/blood-2001-12-0290

High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas.

PURPOSE: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). PATIENTS AND METHODS: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR. RESULTS: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. CONCLUSION: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma.

Authors
Gururangan, S; McLaughlin, C; Quinn, J; Rich, J; Reardon, D; Halperin, EC; Herndon, J; Fuchs, H; George, T; Provenzale, J; Watral, M; McLendon, RE; Friedman, A; Friedman, HS; Kurtzberg, J; Vredenbergh, J; Martin, PL
MLA Citation
Gururangan, S, McLaughlin, C, Quinn, J, Rich, J, Reardon, D, Halperin, EC, Herndon, J, Fuchs, H, George, T, Provenzale, J, Watral, M, McLendon, RE, Friedman, A, Friedman, HS, Kurtzberg, J, Vredenbergh, J, and Martin, PL. "High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas." J Clin Oncol 21.11 (June 1, 2003): 2187-2191.
PMID
12775745
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
21
Issue
11
Publish Date
2003
Start Page
2187
End Page
2191
DOI
10.1200/JCO.2003.10.096

Human umbilical cord cells (UCCS) distribute themselves throughout the degenerating human brain but do not transdifferentiate into neural cells.

Authors
Kosaras, B; Kurtzberg, J; Sidman, RL; Wenger, D; Bianchi, D; Snyder, EY
MLA Citation
Kosaras, B, Kurtzberg, J, Sidman, RL, Wenger, D, Bianchi, D, and Snyder, EY. "Human umb