You are here

Rizzieri, David Alan

Overview:

My research interests focus on the care of patients with hematologic malignancies, both with and without the use of bone marrow or stem cell transplantation. I focus my research efforts on new approaches to manipulate minimal residual disease.

Recent endeavors have included:


Phase one trials with novel anti-cancer agents targeting aurora kinases, tyrosine kinases, mtor, VEGF, and raf/ras pathways 
New monoclonal antibodies targeting tumor stroma rather than cellular antigens 
Investigating new antibody targets, i.e. CD123, endoglin, or tenascin for hematologic malignancies 
Aggressive therapy and transplantation for mantle cell lymphoma 
Antiangiogenesis therapy for patients with NHL 
Nonablative allogeneic transplantation therapy with matched or mismatched donors followed by immune modulation

Positions:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1991

M.D. — University of Rochester

Medical Resident, Medicine

Duke University

Fellow In Hematology/Oncology, Medicine

Duke University

Grants:

AG-120

Administered By
Duke Cancer Institute
AwardedBy
Agios Pharmaceuticals, Inc.
Role
Principal Investigator
Start Date
September 06, 2017
End Date
September 10, 2022

Venetoclax (ABT-199/GDC-0199) in combination with Azacitidine

Administered By
Duke Cancer Institute
AwardedBy
AbbVie Inc.
Role
Principal Investigator
Start Date
July 20, 2017
End Date
August 31, 2022

Phase I/II Study of Lintuzumab-Ac225 AML

Administered By
Duke Cancer Institute
AwardedBy
Actinium Pharmaceuticals, Inc.
Role
Principal Investigator
Start Date
April 14, 2017
End Date
July 31, 2022

A Phase 3 Multicenter, Randomized, Open Label study of Guadecitabine

Administered By
Duke Cancer Institute
AwardedBy
Astex Therapeutics Ltd.
Role
Principal Investigator
Start Date
July 17, 2017
End Date
June 30, 2022

Postdoctoral training in genomic medicine research

Administered By
Duke Center for Applied Genomics and Precision Medicine
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
June 14, 2017
End Date
May 31, 2022

Phase 1 Study of ABBV-075

Administered By
Duke Cancer Institute
AwardedBy
AbbVie Inc.
Role
Principal Investigator
Start Date
February 21, 2017
End Date
April 02, 2022

Phase 3 Guadecitabine (SGI-110-07)

Administered By
Duke Cancer Institute
AwardedBy
Astex Therapeutics Ltd.
Role
Principal Investigator
Start Date
January 01, 2017
End Date
December 31, 2021

Phase I study of ADCT-301 in CD25+ AML

Administered By
Duke Cancer Institute
AwardedBy
ADC Therapeutics Sarl
Role
Principal Investigator
Start Date
January 01, 2016
End Date
December 31, 2021

Phase 2 of SY-1425

Administered By
Duke Cancer Institute
AwardedBy
SYROS PHARMACEUTICALS
Role
Principal Investigator
Start Date
November 01, 2016
End Date
October 31, 2021

TPI-ALV-201

Administered By
Duke Cancer Institute
AwardedBy
Tolero Pharmaceuticals, Inc
Role
Principal Investigator
Start Date
October 24, 2017
End Date
September 30, 2021

Efficacy study of Inecalitol in combination with Decitabine in Acute Myeloid Patients unfit for standard chemotherapy

Administered By
Duke Cancer Institute
AwardedBy
Hybrigenics
Role
Principal Investigator
Start Date
October 01, 2016
End Date
September 30, 2021

MEDI D4190C00023

Administered By
Duke Cancer Institute
AwardedBy
MedImmune, Inc.
Role
Principal Investigator
Start Date
October 01, 2016
End Date
September 30, 2021

Randomized Phase II study of CX-01 combined with standard induction therapy for newly diagnosed AML

Administered By
Duke Cancer Institute
AwardedBy
Cantex Pharmaceuticals, Inc.
Role
Principal Investigator
Start Date
October 01, 2016
End Date
September 30, 2021

Transfusion Medicine and Hematology

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Preceptor
Start Date
July 01, 1975
End Date
June 30, 2021

A phase 3 study of SGI-110 vs Treatment Choice for AML patients not candidates for chemotherapy

Administered By
Duke Cancer Institute
AwardedBy
Astex Therapeutics Ltd.
Role
Principal Investigator
Start Date
January 01, 2016
End Date
December 31, 2020

Phase III study of ASP2215 vs Salvage Chemo in pts with R/R AML with FLT3 mutation

Administered By
Duke Cancer Institute
AwardedBy
Astellas Pharma Global Development, Inc
Role
Principal Investigator
Start Date
January 01, 2016
End Date
December 31, 2020

Quizartinib AC220-007

Administered By
Duke Cancer Institute
AwardedBy
Ambit Biosciences
Role
Principal Investigator
Start Date
September 11, 2015
End Date
September 10, 2020

AC220-A-U302 trial

Administered By
Duke Clinical Research Institute
AwardedBy
Daiichi Sankyo Inc
Role
Principal Investigator
Start Date
July 01, 2016
End Date
August 07, 2020

Phase 1/1b, First-in-Human FLX925 for R/R AML

Administered By
Duke Cancer Institute
AwardedBy
Flexus Biosciences, Inc
Role
Principal Investigator
Start Date
July 20, 2015
End Date
July 19, 2020

Pathological B Cells: Novel Strategies to Prevent and Treat Chronic GVHD

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
August 15, 2015
End Date
June 30, 2020

Phase II study of SINE (KPT-330) vs SOC in patients with R/R AML

Administered By
Duke Cancer Institute
AwardedBy
Karyopharm Therapeutics
Role
Principal Investigator
Start Date
July 01, 2015
End Date
June 30, 2020

A Phase 1 Dose Escalation Study of MDG006 in Patients with Relapsed or Refractory AML

Administered By
Duke Cancer Institute
AwardedBy
MacroGenics, Inc.
Role
Principal Investigator
Start Date
February 27, 2015
End Date
February 26, 2020

Stemline Phase II

Administered By
Duke Cancer Institute
AwardedBy
Stemline Therapeutics, Inc
Role
Principal Investigator
Start Date
February 09, 2015
End Date
February 08, 2020

Phase I Study of ABT-199 in comb w/ Aza or Dec with AML patients ho are > 65 y/o

Administered By
Duke Cancer Institute
AwardedBy
AbbVie Inc.
Role
Principal Investigator
Start Date
December 01, 2014
End Date
November 30, 2019

Phase I/II Pri-724 for Advanced Myeloid Malignancies

Administered By
Duke Cancer Institute
AwardedBy
PRISM Pharma Co., Ltd
Role
Principal Investigator
Start Date
May 01, 2014
End Date
April 30, 2019

SL-401 with AML patients

Administered By
Duke Cancer Institute
AwardedBy
Stemline Therapeutics, Inc
Role
Principal Investigator
Start Date
April 01, 2014
End Date
March 31, 2019

Phase I study of L-asparaginase encapsulated in red blood cells (ERYASP)

Administered By
Duke Cancer Institute
AwardedBy
ERYTECH Pharma
Role
Principal Investigator
Start Date
March 01, 2014
End Date
February 28, 2019

Development of the Phase I study involving ET190L1-Artemis in CD19 positive blood malignancies

Administered By
Duke Cancer Institute
AwardedBy
Eureka Therapeutics, Inc.
Role
Principal Investigator
Start Date
September 01, 2016
End Date
August 31, 2018

Selection of Allogeneic Hematopoietic Cell Donor Based on KIR and HLA Genotypes

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
Memorial Sloan Kettering Cancer Center
Role
Principal Investigator
Start Date
May 01, 2017
End Date
April 30, 2018

Improving Outcomes of Older and Medically Infirm Patients with AML

Administered By
Duke Cancer Institute
AwardedBy
Fred Hutchinson Cancer Research Center
Role
Principal Investigator
Start Date
October 28, 2015
End Date
December 31, 2017

Phase 2, Randomized, Double-Blind, Placebo-Controlled study of Azacitidine with or without Birinapant

Administered By
Duke Cancer Institute
AwardedBy
Novella Clinical
Role
Principal Investigator
Start Date
September 21, 2014
End Date
October 11, 2017

A Multicenter Phase III Rand, open-Label, study of Bosutinib vs Imatinib in adults with newly diagnosed CPCML

Administered By
Duke Cancer Institute
AwardedBy
Pfizer, Inc.
Role
Principal Investigator
Start Date
December 01, 2014
End Date
October 03, 2017

Kalobios Ph1/2 KB004 for EphA3-Expressing Hematologic Malignancies (KB004-01)

Administered By
Duke Cancer Institute
AwardedBy
KaloBios Pharmaceuticals, Inc
Role
Principal Investigator
Start Date
July 17, 2015
End Date
September 19, 2016

Cancer Biology Training Grant

Administered By
Pharmacology & Cancer Biology
AwardedBy
National Cancer Institute
Role
Mentor
Start Date
July 01, 1993
End Date
March 31, 2016

Clinical Oncology Research Career Development Program

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co-Mentor
Start Date
September 29, 2009
End Date
July 31, 2015

Mechanisms of lung injury following autologous BMT

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
August 01, 2003
End Date
June 30, 2007

Mentored Patient-Oriented Research Career Dev Award

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 2000
End Date
August 31, 2005
Show More

Publications:

Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States

Authors
Muffly, L; Pasquini, MC; Martens, M; Brazauskas, R; Zhu, X; Adekola, K; Aljurf, M; Ballen, KK; Bajel, A; Baron, F; Battiwalla, M; Beitinjaneh, A; Cahn, J-Y; Carabasi, M; Chen, Y-B; Chhabra, S; Ciurea, S; Copelan, E; D’Souza, A; Edwards, J; Foran, J; Freytes, CO; Fung, HC; Gale, RP; Giralt, S; Hashmi, SK; Hildebrandt, GC; Ho, V; Jakubowski, A; Lazarus, H; Luskin, MR; Martino, R; Maziarz, R; McCarthy, P; Nishihori, T; Olin, R; Olsson, RF; Pawarode, A; Peres, E; Rezvani, AR; Rizzieri, D et al.
MLA Citation
Muffly, L, Pasquini, MC, Martens, M, Brazauskas, R, Zhu, X, Adekola, K, Aljurf, M, Ballen, KK, Bajel, A, Baron, F, Battiwalla, M, Beitinjaneh, A, Cahn, J-Y, Carabasi, M, Chen, Y-B, Chhabra, S, Ciurea, S, Copelan, E, D’Souza, A, Edwards, J, Foran, J, Freytes, CO, Fung, HC, Gale, RP, Giralt, S, Hashmi, SK, Hildebrandt, GC, Ho, V, Jakubowski, A, Lazarus, H, Luskin, MR, Martino, R, Maziarz, R, McCarthy, P, Nishihori, T, Olin, R, Olsson, RF, Pawarode, A, Peres, E, Rezvani, AR, and Rizzieri, D et al. "Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States." Blood 130.9 (August 31, 2017): 1156-1164.
Source
crossref
Published In
Blood
Volume
130
Issue
9
Publish Date
2017
Start Page
1156
End Page
1164
DOI
10.1182/blood-2017-03-772368

A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma.

Deregulation of histone deacetylase (HDAC) is important in the pathogenesis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Mocetinostat, an isotype-selective HDAC inhibitor, induces accumulation of acetylated histones, cell cycle arrest and apoptosis in several cancers. This phase 2 study evaluated mocetinostat in patients with relapsed/refractory (R/R) DLBCL and FL. Seventy-two patients received mocetinostat (starting doses: 70-110 mg TIW, 4-week cycles). The best overall response rate (95% CI) was 18·9% (7·2, 32·2) for the DLBCL cohort (n = 41), and 11·5% (1·7, 20·7) for the FL cohort (n = 31). Responses were durable (≥90 days in 7 of 10 responses). Overall, 54·1% and 73·1% of patients derived clinical benefit (response or stable disease) from mocetinostat in the DLBCL and FL cohorts, respectively. Progression-free survival ranged from 1·8 to 22·8 months and 11·8 to 26·3 months in responders with DLBCL and FL, respectively. The most frequent treatment-related adverse events were fatigue (75·0%), nausea (69·4%) and diarrhoea (61·1%). Although mocetinostat had limited single-agent activity in R/R DLBCL and FL, patients with clinical benefit had long-term disease control. The safety profile was acceptable. This drug class warrants further investigation, including identifying patients more likely to respond to this agent, or in combination with other agents.

Authors
Batlevi, CL; Crump, M; Andreadis, C; Rizzieri, D; Assouline, SE; Fox, S; van der Jagt, RHC; Copeland, A; Potvin, D; Chao, R; Younes, A
MLA Citation
Batlevi, CL, Crump, M, Andreadis, C, Rizzieri, D, Assouline, SE, Fox, S, van der Jagt, RHC, Copeland, A, Potvin, D, Chao, R, and Younes, A. "A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma." British journal of haematology 178.3 (August 2017): 434-441.
PMID
28440559
Source
epmc
Published In
British Journal of Haematology
Volume
178
Issue
3
Publish Date
2017
Start Page
434
End Page
441
DOI
10.1111/bjh.14698

Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy.

Manganese porphyrins are redox-active drugs and superoxide dismutase mimics, which have been shown to chemosensitize lymphoma, a cancer which frequently occurs in dogs. This study aimed to identify critical information regarding the pharmacokinetics and toxicity of Mn(III) meso-tetrakis (N-n-butoxyetylpyridium-2-yl) porphyrin, (MnTnBuOE-2-PyP5+, MnBuOE) in dogs as a prelude to a clinical trial in canine lymphoma patients.A single-dose pharmacokinetic (PK) study in normal dogs was performed to determine the plasma half-life (t 1/2) of MnBuOE. A dose reduction study was performed to establish the maximum tolerated dose (MTD) of MnBuOE. The safety and PK of a multi-dosing protocol was assessed.Peak plasma drug concentration occurred 30 min post-injection. The t 1/2 was defined as 7 h. MnBuOE induced an anaphylactic reaction and prolonged tachycardia. The MTD was defined as 0.25 mg/kg. The dogs were given MTD 3×/week for 2-3 weeks. The highest recorded tissue drug levels were in the lymph nodes (4-6 μM), followed by kidney and liver (2.5, 2.0 uM, respectively).We obtained critical information regarding the PK and toxicity of MnBuOE in dogs. The acute drug reaction and tachycardia post-injection have not been described in other species and may be specific to canines. The high tissue drug levels in lymph nodes have not been previously reported. MnBuOE accumulation in lymph nodes has important implications for the utility of adjuvant MnBuOE to treat lymphoma. With MnBuOE lymph node accumulation, reduction in the dose and/or administration frequency could be possible, leading to reduced toxicity.

Authors
Boss, MK; Dewhirst, MW; Sampaio, RS; Bennett, A; Tovmasyan, A; Berman, KG; Beaven, AW; Rizzieri, DA; Batinic-Haberle, I; Hauck, ML; Spasojevic, I
MLA Citation
Boss, MK, Dewhirst, MW, Sampaio, RS, Bennett, A, Tovmasyan, A, Berman, KG, Beaven, AW, Rizzieri, DA, Batinic-Haberle, I, Hauck, ML, and Spasojevic, I. "Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy." Cancer chemotherapy and pharmacology 80.2 (August 2017): 421-431.
PMID
28685347
Source
epmc
Published In
Cancer Chemotherapy and Pharmacology
Volume
80
Issue
2
Publish Date
2017
Start Page
421
End Page
431
DOI
10.1007/s00280-017-3372-z

Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial

Authors
Kantarjian, HM; Roboz, GJ; Kropf, PL; Yee, KWL; O'Connell, CL; Tibes, R; Walsh, KJ; Podoltsev, NA; Griffiths, EA; Jabbour, E; Garcia-Manero, G; Rizzieri, D; Stock, W; Savona, MR; Rosenblat, TL; Berdeja, JG; Ravandi, F; Rock, EP; Hao, Y; Azab, M; Issa, J-PJ
MLA Citation
Kantarjian, HM, Roboz, GJ, Kropf, PL, Yee, KWL, O'Connell, CL, Tibes, R, Walsh, KJ, Podoltsev, NA, Griffiths, EA, Jabbour, E, Garcia-Manero, G, Rizzieri, D, Stock, W, Savona, MR, Rosenblat, TL, Berdeja, JG, Ravandi, F, Rock, EP, Hao, Y, Azab, M, and Issa, J-PJ. "Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial." The Lancet Oncology (August 2017).
Source
crossref
Published In
The Lancet Oncology
Publish Date
2017
DOI
10.1016/S1470-2045(17)30576-4

Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization.

Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit.

Authors
Anand, S; Thomas, S; Hyslop, T; Adcock, J; Corbet, K; Gasparetto, C; Lopez, R; Long, GD; Morris, AK; Rizzieri, DA; Sullivan, KM; Sung, AD; Sarantopoulos, S; Chao, NJ; Horwitz, ME
MLA Citation
Anand, S, Thomas, S, Hyslop, T, Adcock, J, Corbet, K, Gasparetto, C, Lopez, R, Long, GD, Morris, AK, Rizzieri, DA, Sullivan, KM, Sung, AD, Sarantopoulos, S, Chao, NJ, and Horwitz, ME. "Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 23.7 (July 2017): 1151-1157.
PMID
28392378
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
23
Issue
7
Publish Date
2017
Start Page
1151
End Page
1157
DOI
10.1016/j.bbmt.2017.04.001

Cytogenetic risk determines outcomes after allogeneic transplantation in older patients with acute myeloid leukemia in their second complete remission: A Center for International Blood and Marrow Transplant Research cohort analysis.

Allogeneic hematopoietic cell transplantation (HCT) offers curative potential to a number of older patients with acute myeloid leukemia (AML) in their first complete remission. However, there are limited data in the literature concerning post-HCT outcomes for older patients in their second complete remission (CR2).The purpose of the current study was to retrospectively investigate within the Center for International Blood and Marrow Transplant Research database parameters influencing posttransplant outcomes for patients 60 years of age or older undergoing HCT for AML in CR2.In total, 196 patients from 78 centers were identified; the median age was 64 years (range, 60-78 years). Seventy-one percent had a Karnofsky performance status ≥ 90 at the time of HCT. Reduced-intensity conditioning regimens were used in 159 patients (81%). A univariate analysis demonstrated a 3-year overall survival (OS) rate of 42% (95% confidence interval [CI], 35%-49%), a leukemia-free survival rate of 37% (95% CI, 30%-44%), a cumulative incidence of nonrelapse mortality of 25% (95% CI, 19%-32%), and a cumulative incidence of relapse (CIR) of 38% (95% CI, 31%-45%). A multivariate analysis demonstrated that cytogenetic risk was the only independent risk factor for OS (P = .023) with a hazard ratio (HR) of 1.14 (95% CI, 0.59-2.19) for intermediate-risk cytogenetics and an HR of 2.32 (95% CI, 1.05-5.14) for unfavorable-risk cytogenetics. For CIR, cytogenetic risk was also the only independent prognostic factor (P = .01) with an HR of 1.10 (95% CI, 0.47-2.56) for intermediate-risk cytogenetics and an HR of 2.98 (95% CI, 1.11-8.00) for unfavorable-risk cytogenetics.Allogeneic HCT is a curative treatment option for older patients with AML in CR2, particularly for those with favorable or intermediate cytogenetic risk. Cancer 2017;123:2035-2042. © 2017 American Cancer Society.

Authors
Michelis, FV; Gupta, V; Zhang, M-J; Wang, H-L; Aljurf, M; Bacher, U; Beitinjaneh, A; Chen, Y-B; DeFilipp, Z; Gale, RP; Kebriaei, P; Kharfan-Dabaja, M; Lazarus, HM; Nishihori, T; Olsson, RF; Oran, B; Rashidi, A; Rizzieri, DA; Tallman, MS; de Lima, M; Khoury, HJ; Sandmaier, BM; Weisdorf, D; Saber, W et al.
MLA Citation
Michelis, FV, Gupta, V, Zhang, M-J, Wang, H-L, Aljurf, M, Bacher, U, Beitinjaneh, A, Chen, Y-B, DeFilipp, Z, Gale, RP, Kebriaei, P, Kharfan-Dabaja, M, Lazarus, HM, Nishihori, T, Olsson, RF, Oran, B, Rashidi, A, Rizzieri, DA, Tallman, MS, de Lima, M, Khoury, HJ, Sandmaier, BM, Weisdorf, D, and Saber, W et al. "Cytogenetic risk determines outcomes after allogeneic transplantation in older patients with acute myeloid leukemia in their second complete remission: A Center for International Blood and Marrow Transplant Research cohort analysis." Cancer 123.11 (June 2017): 2035-2042.
PMID
28117898
Source
epmc
Published In
Cancer
Volume
123
Issue
11
Publish Date
2017
Start Page
2035
End Page
2042
DOI
10.1002/cncr.30567

Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation.

To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation.We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT.The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P = 0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR] = 0.97; 95% CI, 0.95-0.99; P = 0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P = 0.002).Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant depression represent a population that is at risk for post-transplant complications. Cancer 2017;123:1828-1838. © 2017 American Cancer Society.

Authors
El-Jawahri, A; Chen, Y-B; Brazauskas, R; He, N; Lee, SJ; Knight, JM; Majhail, N; Buchbinder, D; Schears, RM; Wirk, BM; Wood, WA; Ahmed, I; Aljurf, M; Szer, J; Beattie, SM; Battiwalla, M; Dandoy, C; Diaz, M-A; D'Souza, A; Freytes, CO; Gajewski, J; Gergis, U; Hashmi, SK; Jakubowski, A; Kamble, RT; Kindwall-Keller, T; Lazarus, HM; Malone, AK; Marks, DI; Meehan, K; Savani, BN; Olsson, RF; Rizzieri, D; Steinberg, A; Speckhart, D; Szwajcer, D; Schoemans, H; Seo, S; Ustun, C; Atsuta, Y; Dalal, J et al.
MLA Citation
El-Jawahri, A, Chen, Y-B, Brazauskas, R, He, N, Lee, SJ, Knight, JM, Majhail, N, Buchbinder, D, Schears, RM, Wirk, BM, Wood, WA, Ahmed, I, Aljurf, M, Szer, J, Beattie, SM, Battiwalla, M, Dandoy, C, Diaz, M-A, D'Souza, A, Freytes, CO, Gajewski, J, Gergis, U, Hashmi, SK, Jakubowski, A, Kamble, RT, Kindwall-Keller, T, Lazarus, HM, Malone, AK, Marks, DI, Meehan, K, Savani, BN, Olsson, RF, Rizzieri, D, Steinberg, A, Speckhart, D, Szwajcer, D, Schoemans, H, Seo, S, Ustun, C, Atsuta, Y, and Dalal, J et al. "Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation." Cancer 123.10 (May 2017): 1828-1838.
PMID
28102896
Source
epmc
Published In
Cancer
Volume
123
Issue
10
Publish Date
2017
Start Page
1828
End Page
1838
DOI
10.1002/cncr.30546

Allogeneic Hematopoietic Cell Transplantation for Adult Chronic Myelomonocytic Leukemia

Authors
Liu, HD; Ahn, KW; Hu, Z-H; Hamadani, M; Nishihori, T; Wirk, B; Beitinjaneh, A; Rizzieri, D; Grunwald, MR; Sabloff, M; Olsson, RF; Bajel, A; Bredeson, C; Daly, A; Inamoto, Y; Majhail, N; Saad, A; Gupta, V; Gerds, A; Malone, A; Tallman, M; Reshef, R; Marks, DI; Copelan, E; Gergis, U; Savoie, ML; Ustun, C; Litzow, MR; Cahn, J-Y; Kindwall-Keller, T; Akpek, G; Savani, BN; Aljurf, M; Rowe, JM; Wiernik, PH; Hsu, JW; Cortes, J; Kalaycio, M; Maziarz, R; Sobecks, R; Popat, U; Alyea, E; Saber, W
MLA Citation
Liu, HD, Ahn, KW, Hu, Z-H, Hamadani, M, Nishihori, T, Wirk, B, Beitinjaneh, A, Rizzieri, D, Grunwald, MR, Sabloff, M, Olsson, RF, Bajel, A, Bredeson, C, Daly, A, Inamoto, Y, Majhail, N, Saad, A, Gupta, V, Gerds, A, Malone, A, Tallman, M, Reshef, R, Marks, DI, Copelan, E, Gergis, U, Savoie, ML, Ustun, C, Litzow, MR, Cahn, J-Y, Kindwall-Keller, T, Akpek, G, Savani, BN, Aljurf, M, Rowe, JM, Wiernik, PH, Hsu, JW, Cortes, J, Kalaycio, M, Maziarz, R, Sobecks, R, Popat, U, Alyea, E, and Saber, W. "Allogeneic Hematopoietic Cell Transplantation for Adult Chronic Myelomonocytic Leukemia." Biology of Blood and Marrow Transplantation 23.5 (May 2017): 767-775.
Source
crossref
Published In
Biology of Blood and Marrow Transplantation
Volume
23
Issue
5
Publish Date
2017
Start Page
767
End Page
775
DOI
10.1016/j.bbmt.2017.01.078

Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma.

Comprehensive recommendations for maintenance therapy after autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared with lenalidomide in the post-ASCT setting are limited. Therefore, we retrospectively analyzed the outcomes of 102 patients with MM who received maintenance therapy with bortezomib after ASCT at Duke University's adult bone marrow transplant clinic between 2005 and 2015. Maintenance with bortezomib was initiated between 60 and 90 days after ASCT as a single agent 1.3 mg/m2 once every 2 weeks (n = 92) or in combination with lenalidomide (10 mg/day) (n = 10). The median age at ASCT was 64 (range, 31 to 78). Of the 99 patients with molecular data available, 42% had high-risk cytogenetics (including d17p, t(4;14), +1q, and t(14;16) by fluorescein in situ hybridization). Overall, 46% of patients experienced side effects from maintenance therapy, with 31% of all patients experiencing peripheral neuropathy. In total, 2% of patients required discontinuation of bortezomib maintenance because of adverse events. No secondary malignancies were reported from the therapy. The median progression-free survival (PFS) for patients receiving maintenance therapy with bortezomib after ASCT was 36.5 months (95% confidence interval [CI], 21.3 to not available) and median overall survival was 72.7 months (95% CI, 63.9 to not available). The PFS of patients with high-risk cytogenetics was not statistically significantly different from those with standard-risk cytogenetics, suggesting that maintenance with bortezomib may help overcome the impact of high-risk cytogenetics on early progression. These results indicate that maintenance therapy with bortezomib represents a safe, well-tolerated, and efficacious option for patients with high-risk cytogenetics, renal insufficiency, an inability to tolerate lenalidomide, or a previous history of another cancer.

Authors
Sivaraj, D; Green, MM; Li, Z; Sung, AD; Sarantopoulos, S; Kang, Y; Long, GD; Horwitz, ME; Lopez, RD; Sullivan, KM; Rizzieri, DA; Chao, NJ; Gasparetto, C
MLA Citation
Sivaraj, D, Green, MM, Li, Z, Sung, AD, Sarantopoulos, S, Kang, Y, Long, GD, Horwitz, ME, Lopez, RD, Sullivan, KM, Rizzieri, DA, Chao, NJ, and Gasparetto, C. "Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 23.2 (February 2017): 262-268.
PMID
27856369
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
23
Issue
2
Publish Date
2017
Start Page
262
End Page
268
DOI
10.1016/j.bbmt.2016.11.010

Efficacy and safety of high-dose chemotherapy with autologous stem cell transplantation in senior versus younger adults with newly diagnosed multiple myeloma.

We retrospectively studied 340 fit patients with multiple myeloma (MM) who underwent autologous stem cell transplantation (ASCT). We hypothesized that progression-free survival (PFS) of older patients was non-inferior to that of younger patients after ASCT. Our null hypothesis was that the PFS hazard ratio (HR) for a 5-year increase in age was ≥1.05; the alternative (non-inferiority) hypothesis was that the HR was ≤1. The observed HR was 0.94 (95% confidence interval [CI] 0.86-1.03); since the CI upper bound was <1.05, we reject the null hypothesis and conclude that PFS in older patients was at least as good as in younger patients. We cannot reject an analogous null hypothesis for overall survival (HR 1.06 [95% CI 0.94-1.19]), since the CI upper bound >1.05. Toxicity was similar across ages and transplant-related mortality was minimal. 28% of subjects <65 versus 45% of those ≥65 received maintenance therapy. In summary, ASCT prolongs PFS equally well in older vs. younger adults. Although we cannot exclude maintenance as a confounder, these data support ASCT for fit seniors with MM.

Authors
Huang, L-W; Bacon, W; Cirrincione, C; Peterson, B; Long, G; Rizzieri, D; Sullivan, KM; Corbet, K; Horwitz, M; Chao, N; Gasparetto, C; Tuchman, SA
MLA Citation
Huang, L-W, Bacon, W, Cirrincione, C, Peterson, B, Long, G, Rizzieri, D, Sullivan, KM, Corbet, K, Horwitz, M, Chao, N, Gasparetto, C, and Tuchman, SA. "Efficacy and safety of high-dose chemotherapy with autologous stem cell transplantation in senior versus younger adults with newly diagnosed multiple myeloma." Hematological oncology (January 19, 2017).
PMID
28105753
Source
epmc
Published In
Hematological Oncology
Publish Date
2017
DOI
10.1002/hon.2379

Treatment of blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4+CD56+CD123+lineage-MPO-, although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies. Chromosomal aberrations are frequent, and the mutational landscape of BPDCN is being rapidly characterized although no obvious molecular target for chemoimmunotherapy has been identified. Chemotherapy regimens developed for acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome have all been used to treat BPDCN. Relapse is frequent, and overall survival is quite poor. Allogeneic transplantation offers a chance at prolonged remission and possible cure for those who are eligible; unfortunately, relapse remains high ranging from 30% to 40%. Novel therapies such as SL-401, a diphtheria toxin conjugated to interleukin-3 (IL-3) is commonly overexpressed in BPDCN and other aggressive myeloid malignancies and has shown considerable promise in ongoing clinical trials. Future work with SL-401 will define its place in treating relapsed or refractory disease as well as its role as a first-line therapy or bridge to transplantation.

Authors
Sullivan, JM; Rizzieri, DA
MLA Citation
Sullivan, JM, and Rizzieri, DA. "Treatment of blastic plasmacytoid dendritic cell neoplasm." Hematology. American Society of Hematology. Education Program 2016.1 (December 2016): 16-23. (Review)
PMID
27913457
Source
epmc
Published In
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
Volume
2016
Issue
1
Publish Date
2016
Start Page
16
End Page
23
DOI
10.1182/asheducation-2016.1.16

CD98-Mediated Adhesive Signaling Enables the Establishment and Propagation of Acute Myelogenous Leukemia.

Acute myelogenous leukemia (AML) is an aggressive disease associated with drug resistance and relapse. To improve therapeutic strategies, it is critical to better understand the mechanisms that underlie AML progression. Here we show that the integrin binding glycoprotein CD98 plays a central role in AML. CD98 promotes AML propagation and lethality by driving engagement of leukemia cells with their microenvironment and maintaining leukemic stem cells. Further, delivery of a humanized anti-CD98 antibody blocks growth of patient-derived AML, highlighting the importance of this pathway in human disease. These findings indicate that microenvironmental interactions are key regulators of AML and that disrupting these signals with targeted inhibitors such as CD98 antibodies may be a valuable therapeutic approach for adults and children with this disease.

Authors
Bajaj, J; Konuma, T; Lytle, NK; Kwon, HY; Ablack, JN; Cantor, JM; Rizzieri, D; Chuah, C; Oehler, VG; Broome, EH; Ball, ED; van der Horst, EH; Ginsberg, MH; Reya, T
MLA Citation
Bajaj, J, Konuma, T, Lytle, NK, Kwon, HY, Ablack, JN, Cantor, JM, Rizzieri, D, Chuah, C, Oehler, VG, Broome, EH, Ball, ED, van der Horst, EH, Ginsberg, MH, and Reya, T. "CD98-Mediated Adhesive Signaling Enables the Establishment and Propagation of Acute Myelogenous Leukemia." Cancer cell 30.5 (November 2016): 792-805.
PMID
27908736
Source
epmc
Published In
Cancer Cell
Volume
30
Issue
5
Publish Date
2016
Start Page
792
End Page
805
DOI
10.1016/j.ccell.2016.10.003

Myeloablative conditioning with total body irradiation for AML: Balancing survival and pulmonary toxicity.

The purpose of this study was to compare leukemia-free survival (LFS) and other clinical outcomes in patients with acute myelogenous leukemia who underwent a myeloablative allogeneic stem cell transplant with and without total body irradiation (TBI).Adult patients with acute myelogenous leukemia undergoing myeloablative allogeneic stem cell transplant at Duke University Medical Center between 1995 and 2012 were included. The primary endpoint was LFS. Secondary outcomes included overall survival (OS), nonrelapse mortality, and the risk of pulmonary toxicity. Kaplan-Meier survival estimates and Cox proportional hazards multivariate analyses were performed.A total of 206 patients were evaluated: 90 received TBI-based conditioning regimens and 116 received chemotherapy alone. Median follow-up was 36 months. For all patients, 2-year LFS and OS were 36% (95% confidence interval [CI], 29-43) and 39% (95% CI, 32-46), respectively. After adjusting for known prognostic factors using a multivariate analysis, TBI was associated with improved LFS (hazard ratio: 0.63; 95% CI: 0.44-0.91) and OS (hazard ratio: 0.63; 95% CI, 0.43-0.91). There was no difference in nonrelapse mortality between cohorts, but pulmonary toxicity was significantly more common with TBI (2-year incidence 42% vs 12%, P < .001). High-grade pulmonary toxicity predominated with both conditioning strategies (70% and 93% of cases were grade 3-5 with TBI and chemotherapy alone, respectively).TBI-based regimens were associated with superior LFS and OS but at the cost of increased pulmonary toxicity.

Authors
Stephens, SJ; Thomas, S; Rizzieri, DA; Horwitz, ME; Chao, NJ; Engemann, AM; Lassiter, M; Kelsey, CR
MLA Citation
Stephens, SJ, Thomas, S, Rizzieri, DA, Horwitz, ME, Chao, NJ, Engemann, AM, Lassiter, M, and Kelsey, CR. "Myeloablative conditioning with total body irradiation for AML: Balancing survival and pulmonary toxicity." October 2016.
PMID
28740897
Source
epmc
Published In
Advances in Radiation Oncology
Volume
1
Issue
4
Publish Date
2016
Start Page
272
End Page
280
DOI
10.1016/j.adro.2016.07.001

Zevalin(®) (ibritumomab tiuxetan): After more than a decade of treatment experience, what have we learned?

Non-Hodgkin's lymphoma (NHL) comprises a clinically and biologically heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer (NK) cells. The disease course may range from indolent to aggressive. Zevalin(®) (ibritumomab tiuxetan) is a radioactive drug product, which is the combination of a β-emitting isotope, (90)Y, linked to the anti-CD20 monoclonal antibody (mAb), rituximab. It has demonstrated therapeutic efficacy with durable responses and allows delivery of ionizing radiation directly to the tumor site, while minimizing toxicity to normal tissue. Ibritumomab tiuxetan is indicated for treatment of patients with relapsed or refractory low-grade, follicular NHL, including patients who are refractory to rituximab, and as consolidation therapy in previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapy. Despite the efficacy and acceptable safety profile of ibritumomab tiuxetan, utilization has not been broadly adopted in practice due to a number of factors. This manuscript will review the literature available for ibritumomab tiuxetan, including several new trials that are currently being studied, and discuss the rationale for use of ibritumomab tiuxetan in NHL.

Authors
Rizzieri, D
MLA Citation
Rizzieri, D. "Zevalin(®) (ibritumomab tiuxetan): After more than a decade of treatment experience, what have we learned?." Critical reviews in oncology/hematology 105 (September 2016): 5-17. (Review)
PMID
27497027
Source
epmc
Published In
Critical Reviews in Oncology/Hematology
Volume
105
Publish Date
2016
Start Page
5
End Page
17
DOI
10.1016/j.critrevonc.2016.07.008

An open-label phase 2 study of glycogen synthase kinase-3 inhibitor LY2090314 in patients with acute leukemia.

This open-label, Phase-2 study investigated the safety of LY2090314 (GSK-3 inhibitor) in AML patients. Twenty patients received 40-mg LY2090314 (50-mg ranitidine pretreatment) as follows: Cohort 1 - days 1, 8, and 15 of a 28-d cycle (n = 7); Cohort 2 - days 1, 5, and 9 of a 21-d cycle (n = 6); Cohort 3 - days 1, 5, 9, and 12 of a 21-d cycle (n = 7). Decreased appetite (n = 7) and nausea (n = 4) were the most frequently reported possibly drug-related non-hematologic treatment-emergent adverse events (TEAEs). Hematologic TEAEs included febrile neutropenia (n = 2), thrombocytopenia (n = 1), and anemia (n = 1). Atrial flutter (n = 1), QT interval prolongation (n = 3), and visual disturbances (n = 2) were observed, but were not clinically significant (investigator assessed). Although β-catenin levels indicated an on-target effect, no complete or partial remissions were observed. Pharmacokinetics were consistent with a previous Phase 1 study. These data suggest that single-agent LY2090314 has acceptable safety but limited clinical benefit in AML patients at the dose/frequencies investigated.

Authors
Rizzieri, DA; Cooley, S; Odenike, O; Moonan, L; Chow, KH; Jackson, K; Wang, X; Brail, L; Borthakur, G
MLA Citation
Rizzieri, DA, Cooley, S, Odenike, O, Moonan, L, Chow, KH, Jackson, K, Wang, X, Brail, L, and Borthakur, G. "An open-label phase 2 study of glycogen synthase kinase-3 inhibitor LY2090314 in patients with acute leukemia." Leukemia & lymphoma 57.8 (August 2016): 1800-1806.
PMID
26735141
Source
epmc
Published In
Leukemia & Lymphoma (Informa)
Volume
57
Issue
8
Publish Date
2016
Start Page
1800
End Page
1806
DOI
10.3109/10428194.2015.1122781

Scoring System Prognostic of Outcome in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome.

To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS).We examined 2,133 patients with MDS undergoing HLA-matched (n = 1,728) or -mismatched (n = 405) allo HCT from 2000 to 2012. We used a Cox multivariable model to identify factors prognostic of mortality in a training subset (n = 1,151) of the HLA-matched cohort. A weighted score using these factors was assigned to the remaining patients undergoing HLA-matched allo HCT (validation cohort; n = 577) as well as to patients undergoing HLA-mismatched allo HCT.Blood blasts greater than 3% (hazard ratio [HR], 1.41; 95% CI, 1.08 to 1.85), platelets 50 × 10(9)/L or less at transplantation (HR, 1.37; 95% CI, 1.18 to 1.61), Karnofsky performance status less than 90% (HR, 1.25; 95% CI, 1.06 to 1.28), comprehensive cytogenetic risk score of poor or very poor (HR, 1.43; 95% CI, 1.14 to 1.80), and age 30 to 49 years (HR, 1.60; 95% CI, 1.09 to 2.35) were associated with increased hazard of death and assigned 1 point in the scoring system. Monosomal karyotype (HR, 2.01; 95% CI, 1.65 to 2.45) and age 50 years or older (HR, 1.93; 95% CI, 1.36 to 2.83) were assigned 2 points. The 3-year overall survival after transplantation in patients with low (0 to 1 points), intermediate (2 to 3), high (4 to 5) and very high (≥ 6) scores was 71% (95% CI, 58% to 85%), 49% (95% CI, 42% to 56%), 41% (95% CI, 31% to 51%), and 25% (95% CI, 4% to 46%), respectively (P < .001). Increasing score was predictive of increased relapse (P < .001) and treatment-related mortality (P < .001) in the HLA-matched set and relapse (P < .001) in the HLA-mismatched cohort.The proposed system is prognostic of outcome in patients undergoing HLA-matched and -mismatched allo HCT for MDS.

Authors
Shaffer, BC; Ahn, KW; Hu, Z-H; Nishihori, T; Malone, AK; Valcárcel, D; Grunwald, MR; Bacher, U; Hamilton, B; Kharfan-Dabaja, MA; Saad, A; Cutler, C; Warlick, E; Reshef, R; Wirk, BM; Sabloff, M; Fasan, O; Gerds, A; Marks, D; Olsson, R; Wood, WA; Costa, LJ; Miller, AM; Cortes, J; Daly, A; Kindwall-Keller, TL; Kamble, R; Rizzieri, DA; Cahn, J-Y; Gale, RP; William, B; Litzow, M; Wiernik, PH; Liesveld, J; Savani, BN; Vij, R; Ustun, C; Copelan, E; Popat, U; Kalaycio, M; Maziarz, R; Alyea, E et al.
MLA Citation
Shaffer, BC, Ahn, KW, Hu, Z-H, Nishihori, T, Malone, AK, Valcárcel, D, Grunwald, MR, Bacher, U, Hamilton, B, Kharfan-Dabaja, MA, Saad, A, Cutler, C, Warlick, E, Reshef, R, Wirk, BM, Sabloff, M, Fasan, O, Gerds, A, Marks, D, Olsson, R, Wood, WA, Costa, LJ, Miller, AM, Cortes, J, Daly, A, Kindwall-Keller, TL, Kamble, R, Rizzieri, DA, Cahn, J-Y, Gale, RP, William, B, Litzow, M, Wiernik, PH, Liesveld, J, Savani, BN, Vij, R, Ustun, C, Copelan, E, Popat, U, Kalaycio, M, Maziarz, R, and Alyea, E et al. "Scoring System Prognostic of Outcome in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.16 (June 2016): 1864-1871.
PMID
27044940
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
16
Publish Date
2016
Start Page
1864
End Page
1871
DOI
10.1200/jco.2015.65.0515

Efficacy of Autologous Stem Cell Transplantation in Older Multiple Myeloma Patients

Authors
Huang, L-W; Bacon, W; Cirrincione, C; Peterson, B; Long, GD; Rizzieri, DA; Horwitz, ME; Sullivan, K; Corbet, K; Chao, NJ; Gasparetto, C; Tuchman, S
MLA Citation
Huang, L-W, Bacon, W, Cirrincione, C, Peterson, B, Long, GD, Rizzieri, DA, Horwitz, ME, Sullivan, K, Corbet, K, Chao, NJ, Gasparetto, C, and Tuchman, S. "Efficacy of Autologous Stem Cell Transplantation in Older Multiple Myeloma Patients." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S223
End Page
S223

Clinical and Immunomodulatiory Outcomes of Microtransplantation for AML

Authors
Rizzieri, DA; Rao, AV; Beaven, A; Brander, D; DeCastro, C; Diehl, L; LeBlanc, TW; Long, GD; McKinney, M; Toaso, B; Chao, NJ; Sung, AD
MLA Citation
Rizzieri, DA, Rao, AV, Beaven, A, Brander, D, DeCastro, C, Diehl, L, LeBlanc, TW, Long, GD, McKinney, M, Toaso, B, Chao, NJ, and Sung, AD. "Clinical and Immunomodulatiory Outcomes of Microtransplantation for AML." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S207
End Page
S208

Increasing Use of Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients Age 70 Years and Older: A CIBMTR Study of Trends and Outcomes

Authors
Muffly, L; Pasquini, MC; Martens, M; Brazauskas, R; Zhu, X; Adekola, K; Aljurf, MD; Artz, AS; Bajel, A; Ballen, KK; Battiwalla, M; Beitinjaneh, A; Cahn, J-Y; Carabasi, M; Chen, Y-B; Chhabra, S; Ciurea, SO; Copelan, EA; D'Souza, A; Edwards, J; Freytes, CO; Fung, HC; Gale, RP; Giralt, SA; Hashmi, SK; Hematti, P; Hildebrandt, GC; Ho, VT; Jakubowski, AA; Lazarus, HM; McCarthy, PL; Olin, RL; Olsson, R; Rezvani, A; Rizzieri, DA; Seftel, M; Seo, S; Sorror, ML; Szer, J; Wood, WA
MLA Citation
Muffly, L, Pasquini, MC, Martens, M, Brazauskas, R, Zhu, X, Adekola, K, Aljurf, MD, Artz, AS, Bajel, A, Ballen, KK, Battiwalla, M, Beitinjaneh, A, Cahn, J-Y, Carabasi, M, Chen, Y-B, Chhabra, S, Ciurea, SO, Copelan, EA, D'Souza, A, Edwards, J, Freytes, CO, Fung, HC, Gale, RP, Giralt, SA, Hashmi, SK, Hematti, P, Hildebrandt, GC, Ho, VT, Jakubowski, AA, Lazarus, HM, McCarthy, PL, Olin, RL, Olsson, R, Rezvani, A, Rizzieri, DA, Seftel, M, Seo, S, Sorror, ML, Szer, J, and Wood, WA. "Increasing Use of Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients Age 70 Years and Older: A CIBMTR Study of Trends and Outcomes." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S68
End Page
S69

Haploidentical Hematopoietic Stem Cell Transplantation: Expanding the Horizon for Hematologic Disorders.

Despite the advent of targeted therapies and novel agents, allogeneic hematopoietic stem cell transplantation remains the only curative modality in the management of hematologic disorders. The necessity to find an HLA-matched related donor is a major obstacle that compromises the widespread application and development of this field. Matched unrelated donors and umbilical cord blood have emerged as alternative sources of donor stem cells; however, the cost of maintaining donor registries and cord blood banks is very high and even impractical in developing countries. Almost every patient has an HLA haploidentical relative in the family, meaning that haploidentical donors are potential sources of stem cells, especially in situations where cord blood or matched unrelated donors are not easily available. Due to the high rates of graft failure and graft-versus-host disease, haploidentical transplant was not considered a feasible option up until the late 20th century, when strategies such as "megadose stem cell infusions" and posttransplantation immunosuppression with cyclophosphamide showed the ability to overcome the HLA disparity barrier and significantly improve the rates of engraftment and reduce the incidence and severity of graft-versus-host disease. Newer technologies of graft manipulation have also yielded the same effects in addition to preserving the antileukemic cells in the donor graft.

Authors
Zahid, MF; Rizzieri, DA
MLA Citation
Zahid, MF, and Rizzieri, DA. "Haploidentical Hematopoietic Stem Cell Transplantation: Expanding the Horizon for Hematologic Disorders." Advances in hematology 2016 (January 2016): 1423493-. (Review)
PMID
26949395
Source
epmc
Published In
Advances in Hematology
Volume
2016
Publish Date
2016
Start Page
1423493
DOI
10.1155/2016/1423493

Targeting the Human Notch 2-BCR Axis: A Driver of B-Cell Hyper-Responsiveness in Active Chronic Graft-Versus Host Disease (cGVHD)

Authors
Poe, JC; Jia, W; Li, Z; Hakim, FT; Pavletic, SZ; Rose, JJ; Rizzieri, DA; Yang, Y; Chen, BJ; Green, M; Anand, S; Siebel, CW; Maillard, I; Chao, NJ; Sarantopoulos, S
MLA Citation
Poe, JC, Jia, W, Li, Z, Hakim, FT, Pavletic, SZ, Rose, JJ, Rizzieri, DA, Yang, Y, Chen, BJ, Green, M, Anand, S, Siebel, CW, Maillard, I, Chao, NJ, and Sarantopoulos, S. "Targeting the Human Notch 2-BCR Axis: A Driver of B-Cell Hyper-Responsiveness in Active Chronic Graft-Versus Host Disease (cGVHD)." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

A Phase I-II Study of the Combination of Bendamustine and Pomalidomide with Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma.

Authors
Gasparetto, C; Green, M; Srinivasan, A; Kang, Y; Rizzieri, DA; Decastro, C; Diehl, LF; Beaven, A; Li, Z; Rao, AV; Garrett, A; Tuchman, S; Long, GD
MLA Citation
Gasparetto, C, Green, M, Srinivasan, A, Kang, Y, Rizzieri, DA, Decastro, C, Diehl, LF, Beaven, A, Li, Z, Rao, AV, Garrett, A, Tuchman, S, and Long, GD. "A Phase I-II Study of the Combination of Bendamustine and Pomalidomide with Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

Long-Term Follow-up Results: A Phase 2 Trial of Imatinib Mesylate As Maintenance Therapy for Patients with Newly Diagnosed c-Kit Positive Acute Myeloid Leukemia (AML)

Authors
Advani, AS; Tse, W; Jia, X; Elson, P; Cooper, B; Ali-Osman, F; Park, J; Rao, AV; Rizzieri, DA; Wang, ES; Cotta, CV; Kalaycio, M; Sobecks, RM; Rouphail, B; Maciejewski, JP; Fensterl, J; Bailey, L; Carew, JS; Foster, B; Rush, ML; Adams, D; Griffiths, EA; Sekeres, MA
MLA Citation
Advani, AS, Tse, W, Jia, X, Elson, P, Cooper, B, Ali-Osman, F, Park, J, Rao, AV, Rizzieri, DA, Wang, ES, Cotta, CV, Kalaycio, M, Sobecks, RM, Rouphail, B, Maciejewski, JP, Fensterl, J, Bailey, L, Carew, JS, Foster, B, Rush, ML, Adams, D, Griffiths, EA, and Sekeres, MA. "Long-Term Follow-up Results: A Phase 2 Trial of Imatinib Mesylate As Maintenance Therapy for Patients with Newly Diagnosed c-Kit Positive Acute Myeloid Leukemia (AML)." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

Lead-in Stage Results of a Pivotal Trial of SL-401, an Interleukin-3 Receptor (IL-3R) Targeting Biologic, in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) or Acute Myeloid Leukemia (AML)

Authors
Sweet, KL; Pemmaraju, N; Lane, AA; Stein, AS; Vasu, S; Blum, W; Rizzieri, DA; Wang, ES; Rowinsky, EK; Szarek, M; Brooks, CL; Disalvatore, S; Liu, D; Duvic, M; Schwartz, JD; Konopleva, M
MLA Citation
Sweet, KL, Pemmaraju, N, Lane, AA, Stein, AS, Vasu, S, Blum, W, Rizzieri, DA, Wang, ES, Rowinsky, EK, Szarek, M, Brooks, CL, Disalvatore, S, Liu, D, Duvic, M, Schwartz, JD, and Konopleva, M. "Lead-in Stage Results of a Pivotal Trial of SL-401, an Interleukin-3 Receptor (IL-3R) Targeting Biologic, in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) or Acute Myeloid Leukemia (AML)." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

ENESTnext Final Results: Deep Molecular Response (MR) with Nilotinib (NIL) in Patients (pts) with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

Authors
Berdeja, JG; Heinrich, M; Dakhil, S; Goldberg, SL; Wadleigh, M; Catchatourian, R; Kuriakose, P; Cortes, JE; Radich, JP; Rizzieri, DA; Bonifacio, G; Dautaj, I; Warsi, G; Mauro, MJ
MLA Citation
Berdeja, JG, Heinrich, M, Dakhil, S, Goldberg, SL, Wadleigh, M, Catchatourian, R, Kuriakose, P, Cortes, JE, Radich, JP, Rizzieri, DA, Bonifacio, G, Dautaj, I, Warsi, G, and Mauro, MJ. "ENESTnext Final Results: Deep Molecular Response (MR) with Nilotinib (NIL) in Patients (pts) with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP)." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

A Phase 1 Study of the DOT1L Inhibitor, Pinometostat (EPZ-5676), in Adults with Relapsed or Refractory Leukemia: Safety, Clinical Activity, Exposure and Target Inhibition

Authors
Stein, EM; Garcia-Manero, G; Rizzieri, DA; Tibes, R; Berdeja, JG; Jongen-Lavrencic, M; Altman, JK; Dohner, H; Thomson, B; Blakemore, SJ; Daigle, S; Fine, G; Waters, NJ; Krivstov, AV; Koche, R; Armstrong, SA; Ho, PT; Lowenberg, B; Tallman, MS
MLA Citation
Stein, EM, Garcia-Manero, G, Rizzieri, DA, Tibes, R, Berdeja, JG, Jongen-Lavrencic, M, Altman, JK, Dohner, H, Thomson, B, Blakemore, SJ, Daigle, S, Fine, G, Waters, NJ, Krivstov, AV, Koche, R, Armstrong, SA, Ho, PT, Lowenberg, B, and Tallman, MS. "A Phase 1 Study of the DOT1L Inhibitor, Pinometostat (EPZ-5676), in Adults with Relapsed or Refractory Leukemia: Safety, Clinical Activity, Exposure and Target Inhibition." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen.

The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.

Authors
Urbano-Ispizua, A; Pavletic, SZ; Flowers, ME; Klein, JP; Zhang, M-J; Carreras, J; Montoto, S; Perales, M-A; Aljurf, MD; Akpek, G; Bredeson, CN; Costa, LJ; Dandoy, C; Freytes, CO; Fung, HC; Gale, RP; Gibson, J; Hamadani, M; Hayashi, RJ; Inamoto, Y; Inwards, DJ; Lazarus, HM; Maloney, DG; Martino, R; Munker, R; Nishihori, T; Olsson, RF; Rizzieri, DA; Reshef, R; Saad, A; Savani, BN; Schouten, HC; Smith, SM; Socié, G; Wirk, B; Yu, LC; Saber, W
MLA Citation
Urbano-Ispizua, A, Pavletic, SZ, Flowers, ME, Klein, JP, Zhang, M-J, Carreras, J, Montoto, S, Perales, M-A, Aljurf, MD, Akpek, G, Bredeson, CN, Costa, LJ, Dandoy, C, Freytes, CO, Fung, HC, Gale, RP, Gibson, J, Hamadani, M, Hayashi, RJ, Inamoto, Y, Inwards, DJ, Lazarus, HM, Maloney, DG, Martino, R, Munker, R, Nishihori, T, Olsson, RF, Rizzieri, DA, Reshef, R, Saad, A, Savani, BN, Schouten, HC, Smith, SM, Socié, G, Wirk, B, Yu, LC, and Saber, W. "The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 21.10 (October 2015): 1746-1753.
PMID
25981509
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
21
Issue
10
Publish Date
2015
Start Page
1746
End Page
1753
DOI
10.1016/j.bbmt.2015.05.010

A multicenter, phase II study of maintenance azacitidine in older patients with acute myeloid leukemia in complete remission after induction chemotherapy.

Older patients with acute myeloid leukemia (AML) have poor outcomes, with median durations of complete remission lasting less than 1 year. Increased toxicity in older patients limits the delivery of standard consolidation therapies, such as allogeneic stem cell transplant or high-dose cytarabine. Azacitidine, a nucleoside analog/DNA methyltransferase inhibitor, has demonstrated significant activity and favorable tolerability in patients unable to tolerate intensive induction chemotherapy; however, the role of azacitidine in the maintenance setting has not been fully evaluated. We undertook a pilot study of low-dose subcutaneous azacitidine [50 mg/(m(2) day)] for 5 days every 4 weeks) in AML patients ≥60 years of age in first remission following standard induction therapy. The primary objective was to determine the 1-year disease-free survival (DFS); secondary objectives were to determine safety and tolerability. We enrolled 24 patients (median age 68, range 62-81 years), the majority of whom received anthracycline-cytarabine induction regimens. From the time of first complete remission, the estimated 1-year DFS was 50% and the median overall survival was 20.4 months. Thrombocytopenia and neutropenia were the most common grade 3/4 toxicities (50 and 58%, respectively). In our study population, maintenance therapy with subcutaneous azacitidine was safe and well tolerated.

Authors
Griffin, PT; Komrokji, RS; De Castro, CM; Rizzieri, DA; Melchert, M; List, AF; Lancet, JE
MLA Citation
Griffin, PT, Komrokji, RS, De Castro, CM, Rizzieri, DA, Melchert, M, List, AF, and Lancet, JE. "A multicenter, phase II study of maintenance azacitidine in older patients with acute myeloid leukemia in complete remission after induction chemotherapy." American journal of hematology 90.9 (September 2015): 796-799.
PMID
26089240
Source
epmc
Published In
American Journal of Hematology
Volume
90
Issue
9
Publish Date
2015
Start Page
796
End Page
799
DOI
10.1002/ajh.24087

Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study.

Hypomethylating agents are used to treat cancers driven by aberrant DNA methylation, but their short half-life might limit their activity, particularly in patients with less proliferative diseases. Guadecitabine (SGI-110) is a novel hypomethylating dinucleotide of decitabine and deoxyguanosine resistant to degradation by cytidine deaminase. We aimed to assess the safety and clinical activity of subcutaneously given guadecitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome.In this multicentre, open-label, phase 1 study, patients from nine North American medical centres with myelodysplastic syndrome or acute myeloid leukaemia that was refractory to or had relapsed after standard treatment were randomly assigned (1:1) to receive subcutaneous guadecitabine, either once-daily for 5 consecutive days (daily × 5), or once-weekly for 3 weeks, in a 28-day treatment cycle. Patients were stratified by disease. A 3 + 3 dose-escalation design was used in which we treated patients with guadecitabine doses of 3-125 mg/m(2) in separate dose-escalation cohorts. A twice-weekly treatment schedule was added to the study after a protocol amendment. The primary objective was to assess safety and tolerability of guadecitabine, determine the maximum tolerated and biologically effective dose, and identify the recommended phase 2 dose of guadecitabine. Safety analyses included all patients who received at least one dose of guadecitabine. Pharmacokinetic and pharmacodynamic analyses to determine the biologically effective dose included all patients for whom samples were available. This study is registered with ClinicalTrials.gov, number NCT01261312.Between Jan 4, 2011, and April 11, 2014, we enrolled and treated 93 patients: 35 patients with acute myeloid leukaemia and nine patients with myelodysplastic syndrome in the daily × 5 dose-escalation cohorts, 28 patients with acute myeloid leukaemia and six patients with myelodysplastic syndrome in the once-weekly dose-escalation cohorts, and 11 patients with acute myeloid leukaemia and four patients with myelodysplastic syndrome in the twice-weekly dose-escalation cohorts. The most common grade 3 or higher adverse events were febrile neutropenia (38 [41%] of 93 patients), pneumonia (27 [29%] of 93 patients), thrombocytopenia (23 [25%] of 93 patients), anaemia (23 [25%] of 93 patients), and sepsis (16 [17%] of 93 patients). The most common serious adverse events were febrile neutropenia (29 [31%] of 93 patients), pneumonia (26 [28%] of 93 patients), and sepsis (16 [17%] of 93 patients). Six of the 74 patients with acute myeloid leukaemia and six of the 19 patients with myelodysplastic syndrome had a clinical response to treatment. Two dose-limiting toxicities were noted in patients with myelodysplastic syndrome at 125 mg/m(2) daily × 5, thus the maximum tolerated dose in patients with myelodysplastic syndrome was 90 mg/m(2) daily × 5. The maximum tolerated dose was not reached in patients with acute myeloid leukaemia. Potent dose-related DNA demethylation occurred on the daily × 5 regimen, reaching a plateau at 60 mg/m(2) (designated as the biologically effective dose).Guadecitabine given subcutaneously at 60 mg/m(2) daily × 5 is well tolerated and is clinically and biologically active in patients with myelodysplastic syndrome and acute myeloid leukaemia. Guadecitabine 60 mg/m(2) daily × 5 is the recommended phase 2 dose, and these findings warrant further phase 2 studies.Astex Pharmaceuticals, Stand Up To Cancer.

Authors
Issa, J-PJ; Roboz, G; Rizzieri, D; Jabbour, E; Stock, W; O'Connell, C; Yee, K; Tibes, R; Griffiths, EA; Walsh, K; Daver, N; Chung, W; Naim, S; Taverna, P; Oganesian, A; Hao, Y; Lowder, JN; Azab, M; Kantarjian, H
MLA Citation
Issa, J-PJ, Roboz, G, Rizzieri, D, Jabbour, E, Stock, W, O'Connell, C, Yee, K, Tibes, R, Griffiths, EA, Walsh, K, Daver, N, Chung, W, Naim, S, Taverna, P, Oganesian, A, Hao, Y, Lowder, JN, Azab, M, and Kantarjian, H. "Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study." The Lancet. Oncology 16.9 (September 2015): 1099-1110.
PMID
26296954
Source
epmc
Published In
The Lancet Oncology
Volume
16
Issue
9
Publish Date
2015
Start Page
1099
End Page
1110
DOI
10.1016/s1470-2045(15)00038-8

Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia.

Acute Myelogenous Leukemia (AML) is an aggressive cancer that strikes both adults and children and is frequently resistant to therapy. Thus, identifying signals needed for AML propagation is a critical step toward developing new approaches for treating this disease. Here, we show that Tetraspanin 3 is a target of the RNA binding protein Musashi 2, which plays a key role in AML. We generated Tspan3 knockout mice that were born without overt defects. However, Tspan3 deletion impaired leukemia stem cell self-renewal and disease propagation and markedly improved survival in mouse models of AML. Additionally, Tspan3 inhibition blocked growth of AML patient samples, suggesting that Tspan3 is also important in human disease. As part of the mechanism, we show that Tspan3 deficiency disabled responses to CXCL12/SDF-1 and led to defects in AML localization within the niche. These identify Tspan3 as an important regulator of aggressive leukemias and highlight a role for Tspan3 in oncogenesis.

Authors
Kwon, HY; Bajaj, J; Ito, T; Blevins, A; Konuma, T; Weeks, J; Lytle, NK; Koechlein, CS; Rizzieri, D; Chuah, C; Oehler, VG; Sasik, R; Hardiman, G; Reya, T
MLA Citation
Kwon, HY, Bajaj, J, Ito, T, Blevins, A, Konuma, T, Weeks, J, Lytle, NK, Koechlein, CS, Rizzieri, D, Chuah, C, Oehler, VG, Sasik, R, Hardiman, G, and Reya, T. "Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia." Cell stem cell 17.2 (August 2015): 152-164.
PMID
26212080
Source
epmc
Published In
Cell Stem Cell
Volume
17
Issue
2
Publish Date
2015
Start Page
152
End Page
164
DOI
10.1016/j.stem.2015.06.006

Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma.

High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10(6) CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57-1.25] and 0.96 for overall survival [95% CI 0.61-1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.

Authors
Tuchman, SA; Bacon, WA; Huang, L-W; Long, G; Rizzieri, D; Horwitz, M; Chute, JP; Sullivan, K; Morris Engemann, A; Yopp, A; Li, Z; Corbet, K; Chao, N; Gasparetto, C
MLA Citation
Tuchman, SA, Bacon, WA, Huang, L-W, Long, G, Rizzieri, D, Horwitz, M, Chute, JP, Sullivan, K, Morris Engemann, A, Yopp, A, Li, Z, Corbet, K, Chao, N, and Gasparetto, C. "Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma." Journal of clinical apheresis 30.3 (June 2015): 176-182.
PMID
25293363
Source
epmc
Published In
Journal of Clinical Apheresis
Volume
30
Issue
3
Publish Date
2015
Start Page
176
End Page
182
DOI
10.1002/jca.21360

Immunotherapeutic Applications of NK Cells

Authors
Davis, C; Rizzieri, D
MLA Citation
Davis, C, and Rizzieri, D. "Immunotherapeutic Applications of NK Cells." Pharmaceuticals 8.2 (June 2015): 250-256.
Source
crossref
Published In
Pharmaceuticals
Volume
8
Issue
2
Publish Date
2015
Start Page
250
End Page
256
DOI
10.3390/ph8020250

Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia.

PURPOSE: Secondary acute myeloid leukemia (sAML), defined as AML arising after a prior myelodysplastic syndrome or after antineoplastic therapy, responds poorly to current therapies. It is often associated with adverse karyotypic abnormalities and overexpression of proteins that mediate drug resistance. We performed a phase III trial to determine whether induction therapy with cytarabine and amonafide L-malate, a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades drug resistance mechanisms, yielded a superior complete remission rate than standard therapy with cytarabine and daunorubicin in sAML. PATIENTS AND METHODS: Patients with previously untreated sAML were randomly assigned at a one-to-one ratio to cytarabine 200 mg/m(2) continuous intravenous (IV) infusion once per day on days 1 to 7 plus either amonafide 600 mg/m(2) IV over 4 hours on days 1 to 5 (A + C arm) or daunorubicin 45 mg/m(2) IV over 30 minutes once per day on days 1 to 3 (D + C arm). RESULTS: The complete remission (CR) rate was 46% (99 of 216 patients) in A + C arm and 45% (97 of 217 patients) in D + C arm (P = .81). The 30- and 60-day mortality rates were 19% and 28% in A + C arm and 13% and 21% in D + C arm, respectively. CONCLUSION: Induction treatment with A + C did not improve the CR rate compared with D + C in patients with sAML.

Authors
Stone, RM; Mazzola, E; Neuberg, D; Allen, SL; Pigneux, A; Stuart, RK; Wetzler, M; Rizzieri, D; Erba, HP; Damon, L; Jang, J-H; Tallman, MS; Warzocha, K; Masszi, T; Sekeres, MA; Egyed, M; Horst, H-A; Selleslag, D; Solomon, SR; Venugopal, P; Lundberg, AS; Powell, B
MLA Citation
Stone, RM, Mazzola, E, Neuberg, D, Allen, SL, Pigneux, A, Stuart, RK, Wetzler, M, Rizzieri, D, Erba, HP, Damon, L, Jang, J-H, Tallman, MS, Warzocha, K, Masszi, T, Sekeres, MA, Egyed, M, Horst, H-A, Selleslag, D, Solomon, SR, Venugopal, P, Lundberg, AS, and Powell, B. "Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 33.11 (April 2015): 1252-1257.
PMID
25732165
Source
epmc
Published In
Journal of Clinical Oncology
Volume
33
Issue
11
Publish Date
2015
Start Page
1252
End Page
1257
DOI
10.1200/jco.2014.57.0952

Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor

© 2015 Macmillan Publishers Limited All rights reserved. Alternative donor transplantation is increasingly used for high-risk lymphoma patients. We analyzed 1593 transplant recipients (2000-2010) and compared transplant outcomes in recipients of 8/8 allele HLA-A, -B, -C and DRB1 matched unrelated donors (MUDs; n=1176), 7/8 allele HLA mismatched unrelated donors (MMUDs; n=275) and umbilical cord blood donors (1 or 2 units UCB; n=142). Adjusted 3-year non-relapse mortality of MMUD (44%) was higher as compared with MUD (35%; P=0.004), but similar to UCB recipients (37%; P=0.19), although UCB had lower rates of neutrophil and platelet recovery compared with unrelated donor groups. With a median follow-up of 55 months, 3-year adjusted cumulative incidence of relapse was lower after MMUD compared with MUD (25% vs 33%, P=0.003) but similar between UCB and MUD (30% vs 33%; P=0.48). In multivariate analysis, UCB recipients had lower risks of acute and chronic GVHD compared with adult donor groups (UCB vs MUD: hazard ratio (HR)=0.68, P=0.05; HR=0.35; P < 0.001). Adjusted 3-year OS was comparable (43% MUD, 37% MMUD and 41% UCB). These data highlight the observation that patients with lymphoma have acceptable survival after alternative donor transplantation. MMUD and UCB can extend the curative potential of allotransplant to patients who lack suitable HLA matched sibling or MUD.

Authors
Bachanova, V; Burns, LJ; Wang, T; Carreras, J; Gale, RP; Wiernik, PH; Ballen, KK; Wirk, B; Munker, R; Rizzieri, DA; Chen, YB; Gibson, J; Akpek, G; Costa, LJ; Kamble, RT; Aljurf, MD; Hsu, JW; Cairo, MS; Schouten, HC; Bacher, U; Savani, BN; Wingard, JR; Lazarus, HM; Laport, GG; Montoto, S; Maloney, DG; Smith, SM; Brunstein, C; Saber, W
MLA Citation
Bachanova, V, Burns, LJ, Wang, T, Carreras, J, Gale, RP, Wiernik, PH, Ballen, KK, Wirk, B, Munker, R, Rizzieri, DA, Chen, YB, Gibson, J, Akpek, G, Costa, LJ, Kamble, RT, Aljurf, MD, Hsu, JW, Cairo, MS, Schouten, HC, Bacher, U, Savani, BN, Wingard, JR, Lazarus, HM, Laport, GG, Montoto, S, Maloney, DG, Smith, SM, Brunstein, C, and Saber, W. "Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor." Bone Marrow Transplantation 50.2 (February 7, 2015): 197-203.
Source
scopus
Published In
Bone Marrow Transplantation
Volume
50
Issue
2
Publish Date
2015
Start Page
197
End Page
203
DOI
10.1038/bmt.2014.259

Safety of growth factor administration for leukapheresis in those with WBC counts greater than 60,000/µl

Authors
Chen, W; Rizzieri, D; Drago, S
MLA Citation
Chen, W, Rizzieri, D, and Drago, S. "Safety of growth factor administration for leukapheresis in those with WBC counts greater than 60,000/µl." Journal of Clinical Apheresis 30.1 (February 2015): 28-31.
Source
crossref
Published In
Journal of Clinical Apheresis
Volume
30
Issue
1
Publish Date
2015
Start Page
28
End Page
31
DOI
10.1002/jca.21343

Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor.

Alternative donor transplantation is increasingly used for high-risk lymphoma patients. We analyzed 1593 transplant recipients (2000-2010) and compared transplant outcomes in recipients of 8/8 allele HLA-A, -B, -C and DRB1 matched unrelated donors (MUDs; n=1176), 7/8 allele HLA mismatched unrelated donors (MMUDs; n=275) and umbilical cord blood donors (1 or 2 units UCB; n=142). Adjusted 3-year non-relapse mortality of MMUD (44%) was higher as compared with MUD (35%; P=0.004), but similar to UCB recipients (37%; P=0.19), although UCB had lower rates of neutrophil and platelet recovery compared with unrelated donor groups. With a median follow-up of 55 months, 3-year adjusted cumulative incidence of relapse was lower after MMUD compared with MUD (25% vs 33%, P=0.003) but similar between UCB and MUD (30% vs 33%; P=0.48). In multivariate analysis, UCB recipients had lower risks of acute and chronic GVHD compared with adult donor groups (UCB vs MUD: hazard ratio (HR)=0.68, P=0.05; HR=0.35; P<0.001). Adjusted 3-year OS was comparable (43% MUD, 37% MMUD and 41% UCB). These data highlight the observation that patients with lymphoma have acceptable survival after alternative donor transplantation. MMUD and UCB can extend the curative potential of allotransplant to patients who lack suitable HLA matched sibling or MUD.

Authors
Bachanova, V; Burns, LJ; Wang, T; Carreras, J; Gale, RP; Wiernik, PH; Ballen, KK; Wirk, B; Munker, R; Rizzieri, DA; Chen, Y-B; Gibson, J; Akpek, G; Costa, LJ; Kamble, RT; Aljurf, MD; Hsu, JW; Cairo, MS; Schouten, HC; Bacher, U; Savani, BN; Wingard, JR; Lazarus, HM; Laport, GG; Montoto, S; Maloney, DG; Smith, SM; Brunstein, C; Saber, W
MLA Citation
Bachanova, V, Burns, LJ, Wang, T, Carreras, J, Gale, RP, Wiernik, PH, Ballen, KK, Wirk, B, Munker, R, Rizzieri, DA, Chen, Y-B, Gibson, J, Akpek, G, Costa, LJ, Kamble, RT, Aljurf, MD, Hsu, JW, Cairo, MS, Schouten, HC, Bacher, U, Savani, BN, Wingard, JR, Lazarus, HM, Laport, GG, Montoto, S, Maloney, DG, Smith, SM, Brunstein, C, and Saber, W. "Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor." Bone marrow transplantation 50.2 (February 2015): 197-203.
PMID
25402415
Source
epmc
Published In
Bone Marrow Transplantation
Volume
50
Issue
2
Publish Date
2015
Start Page
197
End Page
203
DOI
10.1038/bmt.2014.259

Safety of growth factor administration for leukapheresis in those with WBC counts greater than 60,000/µl.

Peripheral blood stem cell mobilization using growth factors is a common method of stem cell collection for transplantation, however, little is reported concerning safety of continued growth factor delivery in exceptional responders with very high white blood cell (WBC) counts in preparation for pheresis. We performed a retrospective study of the safety of growth factor delivery for leukapheresis in those with WBC counts greater than 60,000/µl.Allogeneic donors received 5 days of granulocyte colony-stimulating factor (G-CSF) at a daily dose of 10 or 16 µg/kg. Autologous donors received G-CSF 10 µg/kg/day +/- chemotherapy until peripheral blood CD34(+) count reached 10/µl. Granulocyte donors received 300 µg dose of G-CSF the day prior to donation.Out of 3,037 leukapheresis collections from 1998 to 2005, we identified 303 collections from 204 donors or patients who had a WBC > 60,000/µl. WBC counts were ≥100,000/µl in seven of these subjects. If inadequate stem cell dose was obtained with pheresis with WBC counts this high, patients had growth factor dosing decreased 50% but still received a dose till stem cell collection was completed. Of the 204 subjects, 122 were patients and 82 were donors. These 204 donors/patients had no serious adverse events reported other than the common reports of myalgia, bone pain, and headache associated with administration of growth factors. Pain levels ranged from mild to severe and usually were managed by over the counter analgesics.Continuing ½ the dose of neupogen to complete the pheresis process appears safe in subjects with very high white blood counts.

Authors
Chen, W; Rizzieri, D; Drago, S
MLA Citation
Chen, W, Rizzieri, D, and Drago, S. "Safety of growth factor administration for leukapheresis in those with WBC counts greater than 60,000/µl." Journal of clinical apheresis 30.1 (February 2015): 28-31.
PMID
24975628
Source
epmc
Published In
Journal of Clinical Apheresis
Volume
30
Issue
1
Publish Date
2015
Start Page
28
End Page
31
DOI
10.1002/jca.21343

Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma

© 2014 Wiley Periodicals, Inc. High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10 < sup > 6 < /sup > CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57-1.25] and 0.96 for overall survival [95% CI 0.61-1.54] ). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.

Authors
Tuchman, SA; Bacon, WA; Huang, LW; Long, G; Rizzieri, D; Horwitz, M; Chute, JP; Sullivan, K; Engemann, AM; Yopp, A; Li, Z; Corbet, K; Chao, N; Gasparetto, C
MLA Citation
Tuchman, SA, Bacon, WA, Huang, LW, Long, G, Rizzieri, D, Horwitz, M, Chute, JP, Sullivan, K, Engemann, AM, Yopp, A, Li, Z, Corbet, K, Chao, N, and Gasparetto, C. "Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma." Journal of Clinical Apheresis 30.3 (January 1, 2015): 176-182.
Source
scopus
Published In
Journal of Clinical Apheresis
Volume
30
Issue
3
Publish Date
2015
Start Page
176
End Page
182
DOI
10.1002/jca.21360

Final Clinical Results with Laboratory Correlates in the Phase I Trial of Lenalidomide Plus Plerixafor in Previously Treated Chronic Lymphocytic Leukemia (CLL)

Authors
Brander, DM; Allgood, SD; Rizzieri, DA; Stewart, T; Weinberg, JB; Lanasa, MC
MLA Citation
Brander, DM, Allgood, SD, Rizzieri, DA, Stewart, T, Weinberg, JB, and Lanasa, MC. "Final Clinical Results with Laboratory Correlates in the Phase I Trial of Lenalidomide Plus Plerixafor in Previously Treated Chronic Lymphocytic Leukemia (CLL)." December 6, 2014.
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

Deep Molecular Response in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated With Nilotinib: ENESTnext Update

Authors
Mauro, MJ; Dakhil, S; Cortes, JE; Rizzieri, DA; Keir, CH; Yi, S; Heinrich, MC; Goldberg, SL; Catchatourian, R; Kuriakose, P; Radich, JP
MLA Citation
Mauro, MJ, Dakhil, S, Cortes, JE, Rizzieri, DA, Keir, CH, Yi, S, Heinrich, MC, Goldberg, SL, Catchatourian, R, Kuriakose, P, and Radich, JP. "Deep Molecular Response in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated With Nilotinib: ENESTnext Update." December 6, 2014.
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

The DOT1L Inhibitor EPZ-5676: Safety and Activity in Relapsed/Refractory Patients with MLL-Rearranged Leukemia

Authors
Stein, EM; Garcia-Manero, G; Rizzieri, DA; Savona, M; Tibes, R; Altman, JK; Jongen-Lavrencic, M; Doehner, H; Armstrong, S; Pollock, RM; Waters, NJ; Legler, M; Thomson, B; Daigle, S; McDonald, A; Campbell, C; Olhava, E; Hedrick, EE; Lowenberg, B; Copeland, RA; Tallman, MS
MLA Citation
Stein, EM, Garcia-Manero, G, Rizzieri, DA, Savona, M, Tibes, R, Altman, JK, Jongen-Lavrencic, M, Doehner, H, Armstrong, S, Pollock, RM, Waters, NJ, Legler, M, Thomson, B, Daigle, S, McDonald, A, Campbell, C, Olhava, E, Hedrick, EE, Lowenberg, B, Copeland, RA, and Tallman, MS. "The DOT1L Inhibitor EPZ-5676: Safety and Activity in Relapsed/Refractory Patients with MLL-Rearranged Leukemia." BLOOD 124.21 (December 6, 2014).
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

Clinical potential of elacytarabine in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) has been treated for over four decades with standard induction chemotherapy including seven days of cytosine arabinoside (cytarabine, ara-C) infusion. Cytarabine, while effective in killing leukemic cells, is subject to development of several resistance mechanisms rendering the drug ineffective in many patients. Elacytarabine, a lipophilic 5'-elaidic acid ester or nucleoside analogue of cytosine arabinoside, was created with the intent of overcoming resistance mechanisms including reduced expression of the human equilibrative nucleoside transporter 1 (hENT1) required for cytarabine entry into cells, as well as increased activity of cytidine deaminase (CDA) which breaks down the active metabolite of cytarabine, ara-CTP. Elacytarabine enters cells independently of transporters, has a longer half life compared with cytarabine and is not subject to deactivation by CDA. Preclinical data were encouraging although subsequent clinical studies have failed to show superiority of elacytarabine compared with standard of care as monotherapy in patients with AML. Clinical trials utilizing elacytarabine in combination with anthracyclines are ongoing. Use of hENT1 expression as a predictive marker for cytarabine or elacytarabine response has been studied with no conclusive validation to date. Despite promising early results, the jury is still out in regards to this novel agent as an effective alternative to standard cytarabine therapy in acute leukemias, especially in combination with additional agents such as anthracyclines.

Authors
Rein, LAM; Rizzieri, DA
MLA Citation
Rein, LAM, and Rizzieri, DA. "Clinical potential of elacytarabine in patients with acute myeloid leukemia." Therapeutic advances in hematology 5.6 (December 2014): 211-220. (Review)
PMID
25469211
Source
epmc
Published In
Therapeutic Advances in Hematology
Volume
5
Issue
6
Publish Date
2014
Start Page
211
End Page
220
DOI
10.1177/2040620714552615

Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation

© 2014 American Society for Blood and Marrow Transplantation. The poor prognosis for patients with diffuse large Bcell lymphoma (DLBCL) who relapse within 1year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1year of initial diagnosis. The ERF cohort was compared with those relapsing > 1year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3years were 9% (95% confidence interval [CI] , 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P=34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P < 001) within the first 9months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.

Authors
Hamadani, M; Hari, PN; Zhang, Y; Carreras, J; Akpek, G; Aljurf, MD; Ayala, E; Bachanova, V; Chen, AI; Chen, YB; Costa, LJ; Fenske, TS; Freytes, CO; Ganguly, S; Hertzberg, MS; Holmberg, LA; Inwards, DJ; Kamble, RT; Kanfer, EJ; Lazarus, HM; Marks, DI; Nishihori, T; Olsson, R; Reddy, NM; Rizzieri, DA; Savani, BN; Solh, M; Vose, JM; Wirk, B; Maloney, DG; Smith, SM; Montoto, S; Saber, W
MLA Citation
Hamadani, M, Hari, PN, Zhang, Y, Carreras, J, Akpek, G, Aljurf, MD, Ayala, E, Bachanova, V, Chen, AI, Chen, YB, Costa, LJ, Fenske, TS, Freytes, CO, Ganguly, S, Hertzberg, MS, Holmberg, LA, Inwards, DJ, Kamble, RT, Kanfer, EJ, Lazarus, HM, Marks, DI, Nishihori, T, Olsson, R, Reddy, NM, Rizzieri, DA, Savani, BN, Solh, M, Vose, JM, Wirk, B, Maloney, DG, Smith, SM, Montoto, S, and Saber, W. "Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation." Biology of Blood and Marrow Transplantation 20.11 (November 1, 2014): 1729-1736.
Source
scopus
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
11
Publish Date
2014
Start Page
1729
End Page
1736
DOI
10.1016/j.bbmt.2014.06.036

Early failure of frontline rituximab-containing chemo-immunotherapy in diffuse large B cell lymphoma does not predict futility of autologous hematopoietic cell transplantation.

The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P <.001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.

Authors
Hamadani, M; Hari, PN; Zhang, Y; Carreras, J; Akpek, G; Aljurf, MD; Ayala, E; Bachanova, V; Chen, AI; Chen, Y-B; Costa, LJ; Fenske, TS; Freytes, CO; Ganguly, S; Hertzberg, MS; Holmberg, LA; Inwards, DJ; Kamble, RT; Kanfer, EJ; Lazarus, HM; Marks, DI; Nishihori, T; Olsson, R; Reddy, NM; Rizzieri, DA; Savani, BN; Solh, M; Vose, JM; Wirk, B; Maloney, DG; Smith, SM; Montoto, S; Saber, W; Alpdogan, O; Cashen, A; Dandoy, C; Finke, R; Gale, R; Gibson, J; Hsu, JW; Janakiraman, N; Laughlin, MJ; Lill, M et al.
MLA Citation
Hamadani, M, Hari, PN, Zhang, Y, Carreras, J, Akpek, G, Aljurf, MD, Ayala, E, Bachanova, V, Chen, AI, Chen, Y-B, Costa, LJ, Fenske, TS, Freytes, CO, Ganguly, S, Hertzberg, MS, Holmberg, LA, Inwards, DJ, Kamble, RT, Kanfer, EJ, Lazarus, HM, Marks, DI, Nishihori, T, Olsson, R, Reddy, NM, Rizzieri, DA, Savani, BN, Solh, M, Vose, JM, Wirk, B, Maloney, DG, Smith, SM, Montoto, S, Saber, W, Alpdogan, O, Cashen, A, Dandoy, C, Finke, R, Gale, R, Gibson, J, Hsu, JW, Janakiraman, N, Laughlin, MJ, and Lill, M et al. "Early failure of frontline rituximab-containing chemo-immunotherapy in diffuse large B cell lymphoma does not predict futility of autologous hematopoietic cell transplantation." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20.11 (November 2014): 1729-1736.
PMID
25008330
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
11
Publish Date
2014
Start Page
1729
End Page
1736
DOI
10.1016/j.bbmt.2014.06.036

Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis.

The metabolic profiles of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. In particular, a wide range of both solid and liquid tumors use aerobic glycolysis to supply energy and support cell growth. This metabolic program leads to high rates of glucose consumption through glycolysis with secretion of lactate even in the presence of oxygen. Identifying the limiting events in aerobic glycolysis and the response of cancer cells to metabolic inhibition is now essential to exploit this potential metabolic dependency. Here, we examine the role of glucose uptake and the glucose transporter Glut1 in the metabolism and metabolic stress response of BCR-Abl+ B-cell acute lymphoblastic leukemia cells (B-ALL). B-ALL cells were highly glycolytic and primary human B-ALL samples were dependent on glycolysis. We show B-ALL cells express multiple glucose transporters and conditional genetic deletion of Glut1 led to a partial loss of glucose uptake. This reduced glucose transport capacity, however, was sufficient to metabolically reprogram B-ALL cells to decrease anabolic and increase catabolic flux. Cell proliferation decreased and a limited degree of apoptosis was also observed. Importantly, Glut1-deficient B-ALL cells failed to accumulate in vivo and leukemic progression was suppressed by Glut1 deletion. Similarly, pharmacologic inhibition of aerobic glycolysis with moderate doses of 2-deoxyglucose (2-DG) slowed B-ALL cell proliferation, but extensive apoptosis only occurred at high doses. Nevertheless, 2-DG induced the pro-apoptotic protein Bim and sensitized B-ALL cells to the tyrosine kinase inhibitor Dasatinib in vivo. Together, these data show that despite expression of multiple glucose transporters, B-ALL cells are reliant on Glut1 to maintain aerobic glycolysis and anabolic metabolism. Further, partial inhibition of glucose metabolism is sufficient to sensitize cancer cells to specifically targeted therapies, suggesting inhibition of aerobic glycolysis as a plausible adjuvant approach for B-ALL therapies.

Authors
Liu, T; Kishton, RJ; Macintyre, AN; Gerriets, VA; Xiang, H; Liu, X; Abel, ED; Rizzieri, D; Locasale, JW; Rathmell, JC
MLA Citation
Liu, T, Kishton, RJ, Macintyre, AN, Gerriets, VA, Xiang, H, Liu, X, Abel, ED, Rizzieri, D, Locasale, JW, and Rathmell, JC. "Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis." Cell death & disease 5 (October 16, 2014): e1470-.
PMID
25321477
Source
epmc
Published In
Cell Death and Disease
Volume
5
Publish Date
2014
Start Page
e1470
DOI
10.1038/cddis.2014.431

A phase II study of elacytarabine in combination with idarubicin and of human equilibrative nucleoside transporter 1 expression in patients with acute myeloid leukemia and persistent blasts after the first induction course.

Unlike cytarabine, cellular entry of Elacytarabine, the elaidic acid ester derivative of cytarabine, is independent of the human equilibrative nucleoside transporter 1 (hENT1). This phase II study tested whether the hENT1 blast expression level can be used as a predictive marker for cytarabine response and if the efficacy of elacytarabine is independent of hENT1 expression. A total of 51 patients with acute myeloid leukemia (AML) induction failure were given elacytarabine-idarubicin as a second induction course. The hENT1 expression level was analyzed prior to first induction and/or prior to treatment with elacytarabine. The overall response rate (ORR) was 41% and the safety profile was manageable. There is a trend suggesting that hENT1 expression influences response to cytarabine, but not sufficient to support it as a biomarker for guiding treatment. Further, we conclude that the activity of elacytarabine is not significantly predicted by the hENT1 expression level.

Authors
Rizzieri, D; Vey, N; Thomas, X; Huguet-Rigal, F; Schlenk, RF; Krauter, J; Kindler, T; Gjertsen, BT; Blau, IW; Jacobsen, TF; Johansen, M; Bergeland, T; Gianella-Borradori, A; Krug, U
MLA Citation
Rizzieri, D, Vey, N, Thomas, X, Huguet-Rigal, F, Schlenk, RF, Krauter, J, Kindler, T, Gjertsen, BT, Blau, IW, Jacobsen, TF, Johansen, M, Bergeland, T, Gianella-Borradori, A, and Krug, U. "A phase II study of elacytarabine in combination with idarubicin and of human equilibrative nucleoside transporter 1 expression in patients with acute myeloid leukemia and persistent blasts after the first induction course." Leukemia & lymphoma 55.9 (September 2014): 2114-2119.
PMID
24255981
Source
epmc
Published In
Leukemia & Lymphoma (Informa)
Volume
55
Issue
9
Publish Date
2014
Start Page
2114
End Page
2119
DOI
10.3109/10428194.2013.867489

Outcomes of hematopoietic cell transplantation for diffuse large B cell lymphoma transformed from follicular lymphoma.

There are limited data on the outcomes of autologous or allogeneic hematopoietic cell transplantation (HCT) in diffuse large B cell lymphoma transformed from follicular lymphoma. We analyzed transplantation outcomes in 141 subjects with biopsy-proven diffuse large B-cell lymphoma transformed from follicular lymphoma reported to the Center for International Blood and Marrow Transplant Research between 1990 and 2009. Two groups were identified: autologous HCT (auto-HCT; n = 108) and allogeneic HCT (allo-HCT; n = 33). Fewer auto-HCTs were done for transformed follicular lymphoma in 2003 to 2009, with a shift favoring allo-HCT. Auto-HCT was associated with a 1-year nonrelapse mortality (NRM) of 8% (95% confidence interval [CI], 4% to 14%), 5-year progression-free survival of 35% (95% CI, 26% to 45%), and 5-year overall survival of 50% (95% CI, 40% to 59%). In contrast, allo-HCT was associated with a 1-year NRM of 41% (95% CI, 23% to 58%), 5-year progression-free survival of 18% (95% CI, 6% to 35%), and 5-year overall survival of 22% (95% CI, 8% to 41%). Auto-HCT for transformed follicular lymphoma achieves sustained remission in a high proportion of subjects. The high NRM of allo-HCT offset any benefit that might be associated with this transplantation modality.

Authors
Wirk, B; Fenske, TS; Hamadani, M; Zhang, M-J; Hu, Z-H; Akpek, G; Aljurf, MD; Armand, P; Ayala, E; Bachanova, V; Bolwell, B; Cairo, MS; Cashen, A; Chen, Y-B; Costa, LJ; Farhan, S; Freytes, CO; Gajewski, JL; Gibson, J; Hale, GA; Holmberg, LA; Hsu, JW; Inwards, DJ; Kamble, RT; Maharaj, D; Maziarz, RT; Munker, R; Nath, R; Reddy, NM; Reeder, CB; Rizzieri, DA; Sauter, CS; Savani, BN; Schouten, HC; Sureda, A; Vose, JM; Waller, EK; Wiernik, PH; Gale, RP; Burns, LJ; Saber, W
MLA Citation
Wirk, B, Fenske, TS, Hamadani, M, Zhang, M-J, Hu, Z-H, Akpek, G, Aljurf, MD, Armand, P, Ayala, E, Bachanova, V, Bolwell, B, Cairo, MS, Cashen, A, Chen, Y-B, Costa, LJ, Farhan, S, Freytes, CO, Gajewski, JL, Gibson, J, Hale, GA, Holmberg, LA, Hsu, JW, Inwards, DJ, Kamble, RT, Maharaj, D, Maziarz, RT, Munker, R, Nath, R, Reddy, NM, Reeder, CB, Rizzieri, DA, Sauter, CS, Savani, BN, Schouten, HC, Sureda, A, Vose, JM, Waller, EK, Wiernik, PH, Gale, RP, Burns, LJ, and Saber, W. "Outcomes of hematopoietic cell transplantation for diffuse large B cell lymphoma transformed from follicular lymphoma." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20.7 (July 2014): 951-959.
PMID
24641828
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
7
Publish Date
2014
Start Page
951
End Page
959
DOI
10.1016/j.bbmt.2014.03.014

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

Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002.

To improve long-term outcomes for Burkitt leukaemia/lymphoma (BL) or aggressive lymphomas in adults, we assessed the benefit of adding rituximab and filgrastim support to a dose-dense modified chemotherapy regimen from the Cancer and Leukemia Group B (CALGB) 9251 trial. One hundred and five patients (aged 19-79 years) were enrolled; 27% were >60 years old; 47% had high or high-intermediate risk by International Prognostic Index (IPI) criteria. Common severe toxicities included stomatitis/upper gastrointestinal toxicity (69%), renal insufficiency (10%), neurological events (25%) and pulmonary events (18%). Seven died from treatment-related causes (one central nervous system bleed, four infections, two respiratory failure); five were >60 years old. Results in this adult population are encouraging as complete response (CR) was observed in 83% and 4-year event-free (EFS) and overall survivals (OS) were 74% and 78%, respectively. Results compare favourably to our prior chemotherapy alone study (CALGB 9251) but despite this, high-risk patients still had worse outcomes. In conclusion, short duration, intensive chemo-immunotherapy is feasible and should be considered in adults with BL as it results in high remission rates and durable remissions.

Authors
Rizzieri, DA; Johnson, JL; Byrd, JC; Lozanski, G; Blum, KA; Powell, BL; Shea, TC; Nattam, S; Hoke, E; Cheson, BD; Larson, RA; Alliance for Clinical Trials In Oncology (ACTION),
MLA Citation
Rizzieri, DA, Johnson, JL, Byrd, JC, Lozanski, G, Blum, KA, Powell, BL, Shea, TC, Nattam, S, Hoke, E, Cheson, BD, Larson, RA, and Alliance for Clinical Trials In Oncology (ACTION), . "Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002." British journal of haematology 165.1 (April 2014): 102-111.
PMID
24428673
Source
epmc
Published In
British Journal of Haematology
Volume
165
Issue
1
Publish Date
2014
Start Page
102
End Page
111
DOI
10.1111/bjh.12736

Increased BCR responsiveness in B cells from patients with chronic GVHD.

Although B cells have emerged as important contributors to chronic graft-versus-host-disease (cGVHD) pathogenesis, the mechanisms responsible for their sustained activation remain unknown. We previously showed that patients with cGVHD have significantly increased B cell-activating factor (BAFF) levels and that their B cells are activated and resistant to apoptosis. Exogenous BAFF confers a state of immediate responsiveness to antigen stimulation in normal murine B cells. To address this in cGVHD, we studied B-cell receptor (BCR) responsiveness in 48 patients who were >1 year out from allogeneic hematopoietic stem cell transplantation (HSCT). We found that B cells from cGVHD patients had significantly increased proliferative responses to BCR stimulation along with elevated basal levels of the proximal BCR signaling components B cell linker protein (BLNK) and Syk. After initiation of BCR signaling, cGVHD B cells exhibited increased BLNK and Syk phosphorylation compared with B cells from patients without cGVHD. Blocking Syk kinase activity prevented relative post-HSCT BCR hyper-responsiveness of cGVHD B cells. These data suggest that a lowered BCR signaling threshold in cGVHD associates with increased B-cell proliferation and activation in response to antigen. We reveal a mechanism underpinning aberrant B-cell activation in cGVHD and suggest that therapeutic inhibition of the involved kinases may benefit these patients.

Authors
Allen, JL; Tata, PV; Fore, MS; Wooten, J; Rudra, S; Deal, AM; Sharf, A; Hoffert, T; Roehrs, PA; Shea, TC; Serody, JS; Richards, KL; Jagasia, M; Lee, SJ; Rizzieri, D; Horwitz, ME; Chao, NJ; Sarantopoulos, S
MLA Citation
Allen, JL, Tata, PV, Fore, MS, Wooten, J, Rudra, S, Deal, AM, Sharf, A, Hoffert, T, Roehrs, PA, Shea, TC, Serody, JS, Richards, KL, Jagasia, M, Lee, SJ, Rizzieri, D, Horwitz, ME, Chao, NJ, and Sarantopoulos, S. "Increased BCR responsiveness in B cells from patients with chronic GVHD." Blood 123.13 (March 2014): 2108-2115.
PMID
24532806
Source
epmc
Published In
Blood
Volume
123
Issue
13
Publish Date
2014
Start Page
2108
End Page
2115
DOI
10.1182/blood-2013-10-533562

Autologous or reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chemotherapy-sensitive mantle-cell lymphoma: analysis of transplantation timing and modality.

PURPOSE: To examine the outcomes of patients with chemotherapy-sensitive mantle-cell lymphoma (MCL) following a first hematopoietic stem-cell transplantation (HCT), comparing outcomes with autologous (auto) versus reduced-intensity conditioning allogeneic (RIC allo) HCT and with transplantation applied at different times in the disease course. PATIENTS AND METHODS: In all, 519 patients who received transplantations between 1996 and 2007 and were reported to the Center for International Blood and Marrow Transplant Research were analyzed. The early transplantation cohort was defined as those patients in first partial or complete remission with no more than two lines of chemotherapy. The late transplantation cohort was defined as all the remaining patients. RESULTS: Auto-HCT and RIC allo-HCT resulted in similar overall survival from transplantation for both the early (at 5 years: 61% auto-HCT v 62% RIC allo-HCT; P = .951) and late cohorts (at 5 years: 44% auto-HCT v 31% RIC allo-HCT; P = .202). In both early and late transplantation cohorts, progression/relapse was lower and nonrelapse mortality was higher in the allo-HCT group. Overall survival and progression-free survival were highest in patients who underwent auto-HCT in first complete response. Multivariate analysis of survival from diagnosis identified a survival benefit favoring early HCT for both auto-HCT and RIC allo-HCT. CONCLUSION: For patients with chemotherapy-sensitive MCL, the optimal timing for HCT is early in the disease course. Outcomes are particularly favorable for patients undergoing auto-HCT in first complete remission. For those unable to achieve complete remission after two lines of chemotherapy or those with relapsed disease, either auto-HCT or RIC allo-HCT may be effective, although the chance for long-term remission and survival is lower.

Authors
Fenske, TS; Zhang, M-J; Carreras, J; Ayala, E; Burns, LJ; Cashen, A; Costa, LJ; Freytes, CO; Gale, RP; Hamadani, M; Holmberg, LA; Inwards, DJ; Lazarus, HM; Maziarz, RT; Munker, R; Perales, M-A; Rizzieri, DA; Schouten, HC; Smith, SM; Waller, EK; Wirk, BM; Laport, GG; Maloney, DG; Montoto, S; Hari, PN
MLA Citation
Fenske, TS, Zhang, M-J, Carreras, J, Ayala, E, Burns, LJ, Cashen, A, Costa, LJ, Freytes, CO, Gale, RP, Hamadani, M, Holmberg, LA, Inwards, DJ, Lazarus, HM, Maziarz, RT, Munker, R, Perales, M-A, Rizzieri, DA, Schouten, HC, Smith, SM, Waller, EK, Wirk, BM, Laport, GG, Maloney, DG, Montoto, S, and Hari, PN. "Autologous or reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chemotherapy-sensitive mantle-cell lymphoma: analysis of transplantation timing and modality." J Clin Oncol 32.4 (February 1, 2014): 273-281.
PMID
24344210
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
32
Issue
4
Publish Date
2014
Start Page
273
End Page
281
DOI
10.1200/JCO.2013.49.2454

Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies.

We present a comparative study on 124 patients with hematologic malignancies who had undergone reduced-intensity conditioning and then received a transplant from an HLA-matched related (MRD), an HLA-matched unrelated (MUD), or an HLA-haploidentical related (HAPLO) donor. The conditioning regimen, which consisted of fludarabine, melphalan or busulfan, and alemtuzumab was administered to patients with lymphoid (n = 62) or myeloid disease (n = 62). Mycophenolate mofetil was used as prophylaxis for graft-versus-host disease (GVHD), and 38, 58, and 33 patients received transplants from MRD, MUD, and HAPLO donors, respectively. Only 2 patients experienced primary graft failure (GF) after melphalan-based regimen, whereas 8 of the 17 patients who received a transplant from HAPLO donors experienced a primary GF after busulfan-based regimen. The cumulative incidence of grade III to IV acute GVHD in engrafted patients who had received transplants from MRD, MUD, or HAPLO donors was 3%, 11%, and 27%, respectively, and the 2-year overall survival (OS) rates were 51%, 22%, and 23%, respectively. According to multivariate analysis, transplantation from either MUD or HAPLO donors compared with MRD were adverse factors that affected the OS (P = .006 and P = .002, respectively). In conclusion, the reduced-intensity regimen that included fludarabine, busulfan, or melphalan and alemtuzumab using only mycophenolate mofetil as the GVHD prophylaxis conferred favorable outcomes in the MRD group but lower survival rates in the MUD and HAPLO groups. The busulfan-based regimen led to a high incidence of GF in the HAPLO group, suggesting the need for modification or intensification of immunosuppression.

Authors
Kanda, J; Long, GD; Gasparetto, C; Horwitz, ME; Sullivan, KM; Chute, JP; Morris, A; Shafique, M; Li, Z; Chao, NJ; Rizzieri, DA
MLA Citation
Kanda, J, Long, GD, Gasparetto, C, Horwitz, ME, Sullivan, KM, Chute, JP, Morris, A, Shafique, M, Li, Z, Chao, NJ, and Rizzieri, DA. "Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies." Biol Blood Marrow Transplant 20.2 (February 2014): 257-263.
PMID
24269380
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
257
End Page
263
DOI
10.1016/j.bbmt.2013.11.010

Is timing everything?

Authors
Rizzieri, D
MLA Citation
Rizzieri, D. "Is timing everything?." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20.2 (February 2014): 145-146.
PMID
24342395
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
145
End Page
146
DOI
10.1016/j.bbmt.2013.12.556

Outcomes of Hematopoietic Cell Transplantation for Diffuse Large B Cell Lymphoma Transformed from Follicular Lymphoma

There are limited data on the outcomes of autologous or allogeneic hematopoietic cell transplantation (HCT) in diffuse large B cell lymphoma transformed from follicular lymphoma. We analyzed transplantation outcomes in 141 subjects with biopsy-proven diffuse large B-cell lymphoma transformed from follicular lymphoma reported to the Center for International Blood and Marrow Transplant Research between 1990 and 2009. Two groups were identified: autologous HCT (auto-HCT; n = 108) and allogeneic HCT (allo-HCT; n = 33). Fewer auto-HCTs were done for transformed follicular lymphoma in 2003 to 2009, with a shift favoring allo-HCT. Auto-HCT was associated with a 1-year nonrelapse mortality (NRM) of 8% (95% confidence interval [CI], 4% to 14%), 5-year progression-free survival of 35% (95% CI, 26% to 45%), and 5-year overall survival of 50% (95% CI, 40% to 59%). In contrast, allo-HCT was associated with a 1-year NRM of 41% (95% CI, 23% to 58%), 5-year progression-free survival of 18% (95% CI, 6% to 35%), and 5-year overall survival of 22% (95% CI, 8% to 41%). Auto-HCT for transformed follicular lymphoma achieves sustained remission in a high proportion of subjects. The high NRM of allo-HCT offset any benefit that might be associated with this transplantation modality. © 2014 American Society for Blood and Marrow Transplantation.

Authors
Wirk, B; Fenske, TS; Hamadani, M; Zhang, MJ; Hu, ZH; Akpek, G; Aljurf, MD; Armand, P; Ayala, E; Bachanova, V; Bolwell, B; Cairo, MS; Cashen, A; Chen, YB; Costa, LJ; Farhan, S; Freytes, CO; Gajewski, JL; Gibson, J; Hale, GA; Holmberg, LA; Hsu, JW; Inwards, DJ; Kamble, RT; Maharaj, D; Maziarz, RT; Munker, R; Nath, R; Reddy, NM; Reeder, CB; Rizzieri, DA; Sauter, CS; Savani, BN; Schouten, HC; Sureda, A; Vose, JM; Waller, EK; Wiernik, PH; Gale, RP; Burns, LJ; Saber, W
MLA Citation
Wirk, B, Fenske, TS, Hamadani, M, Zhang, MJ, Hu, ZH, Akpek, G, Aljurf, MD, Armand, P, Ayala, E, Bachanova, V, Bolwell, B, Cairo, MS, Cashen, A, Chen, YB, Costa, LJ, Farhan, S, Freytes, CO, Gajewski, JL, Gibson, J, Hale, GA, Holmberg, LA, Hsu, JW, Inwards, DJ, Kamble, RT, Maharaj, D, Maziarz, RT, Munker, R, Nath, R, Reddy, NM, Reeder, CB, Rizzieri, DA, Sauter, CS, Savani, BN, Schouten, HC, Sureda, A, Vose, JM, Waller, EK, Wiernik, PH, Gale, RP, Burns, LJ, and Saber, W. "Outcomes of Hematopoietic Cell Transplantation for Diffuse Large B Cell Lymphoma Transformed from Follicular Lymphoma." Biology of Blood and Marrow Transplantation 20.7 (January 1, 2014): 951-959.
Source
scopus
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
7
Publish Date
2014
Start Page
951
End Page
959
DOI
10.1016/j.bbmt.2014.03.014

Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: Cancer and Leukemia Group B study 10 002

To improve long-term outcomes for Burkitt leukaemia/lymphoma (BL) or aggressive lymphomas in adults, we assessed the benefit of adding rituximab and filgrastim support to a dose-dense modified chemotherapy regimen from the Cancer and Leukemia Group B (CALGB) 9251 trial. One hundred and five patients (aged 19-79 years) were enrolled; 27% were > 60 years old; 47% had high or high-intermediate risk by International Prognostic Index (IPI) criteria. Common severe toxicities included stomatitis/upper gastrointestinal toxicity (69%), renal insufficiency (10%), neurological events (25%) and pulmonary events (18%). Seven died from treatment-related causes (one central nervous system bleed, four infections, two respiratory failure); five were > 60 years old. Results in this adult population are encouraging as complete response (CR) was observed in 83% and 4-year event-free (EFS) and overall survivals (OS) were 74% and 78%, respectively. Results compare favourably to our prior chemotherapy alone study (CALGB 9251) but despite this, high-risk patients still had worse outcomes. In conclusion, short duration, intensive chemo-immunotherapy is feasible and should be considered in adults with BL as it results in high remission rates and durable remissions. © 2014 John Wiley & Sons Ltd.

Authors
Rizzieri, DA; Johnson, JL; Byrd, JC; Lozanski, G; Blum, KA; Powell, BL; Shea, TC; Nattam, S; Hoke, E; Cheson, BD; Larson, RA
MLA Citation
Rizzieri, DA, Johnson, JL, Byrd, JC, Lozanski, G, Blum, KA, Powell, BL, Shea, TC, Nattam, S, Hoke, E, Cheson, BD, and Larson, RA. "Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: Cancer and Leukemia Group B study 10 002." British Journal of Haematology 165.1 (January 1, 2014): 102-111.
Source
scopus
Published In
British Journal of Haematology
Volume
165
Issue
1
Publish Date
2014
Start Page
102
End Page
111
DOI
10.1111/bjh.12736

Lis1 regulates asymmetric division in hematopoietic stem cells and in leukemia

Cell fate can be controlled through asymmetric division and segregation of protein determinants, but the regulation of this process in the hematopoietic system is poorly understood. Here we show that the dynein-binding protein Lis1 is critically required for hematopoietic stem cell function and leukemogenesis. Conditional deletion of Lis1 (also known as Pafah1b1) in the hematopoietic system led to a severe bloodless phenotype, depletion of the stem cell pool and embryonic lethality. Further, real-time imaging revealed that loss of Lis1 caused defects in spindle positioning and inheritance of cell fate determinants, triggering accelerated differentiation. Finally, deletion of Lis1 blocked the propagation of myeloid leukemia and led to a marked improvement in survival, suggesting that Lis1 is also required for oncogenic growth. These data identify a key role for Lis1 in hematopoietic stem cells and mark its directed control of asymmetric division as a critical regulator of normal and malignant hematopoietic development. © 2014 Nature America, Inc. © 2014 Nature America, Inc.

Authors
Zimdahl, B; Ito, T; Blevins, A; Bajaj, J; Konuma, T; Weeks, J; Koechlein, CS; Kwon, HY; Arami, O; Rizzieri, D; Broome, HE; Chuah, C; Oehler, VG; Sasik, R; Hardiman, G; Reya, T
MLA Citation
Zimdahl, B, Ito, T, Blevins, A, Bajaj, J, Konuma, T, Weeks, J, Koechlein, CS, Kwon, HY, Arami, O, Rizzieri, D, Broome, HE, Chuah, C, Oehler, VG, Sasik, R, Hardiman, G, and Reya, T. "Lis1 regulates asymmetric division in hematopoietic stem cells and in leukemia." Nature Genetics 46.3 (January 1, 2014): 245-252.
Source
scopus
Published In
Nature Genetics
Volume
46
Issue
3
Publish Date
2014
Start Page
245
End Page
252
DOI
10.1038/ng.2889

Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis.

Authors
Liu, T; Kishton, RJ; Macintyre, AN; Gerriets, VA; Xiang, H; Liu, X; Abel, ED; Rizzieri, D; Locasale, JW; Rathmell, JC
MLA Citation
Liu, T, Kishton, RJ, Macintyre, AN, Gerriets, VA, Xiang, H, Liu, X, Abel, ED, Rizzieri, D, Locasale, JW, and Rathmell, JC. "Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis." Cell death & disease 5 (2014): e1516-.
PMID
25375381
Source
epmc
Published In
Cell Death and Disease
Volume
5
Publish Date
2014
Start Page
e1516
DOI
10.1038/cddis.2014.493

Phase II open label study of the oral vascular endothelial growth factor-receptor inhibitor PTK787/ZK222584 (vatalanib) in adult patients with refractory or relapsed diffuse large B-cell lymphoma.

PTK787/ZK222584 (vatalanib), an orally active inhibitor of vascular endothelial growth factor receptors (VEGFRs), was evaluated in this phase II study of 20 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received once-daily PTK787/ZK222584 at a target dose of 1250 mg. Eighteen patients were evaluable for response: one patient had a complete response (CR), six patients had stable disease but subsequently progressed, 10 patients had progressive disease by three cycles and one subject withdrew before response evaluation. The patient who attained a CR underwent autologous stem cell transplant and remains disease-free 76 months after study completion. There were no grade 4 toxicities. Grade 3 thrombocytopenia occurred in 20% and grade 3 hypertension occurred in 10%. There were no episodes of grade 3 proteinuria. In conclusion, PTK787/ZK222584 was well tolerated in a heavily pretreated population of patients with DLBCL, although its therapeutic potential as a single agent in DLBCL appears limited.

Authors
Brander, D; Rizzieri, D; Gockerman, J; Diehl, L; Shea, TC; Decastro, C; Moore, JO; Beaven, A
MLA Citation
Brander, D, Rizzieri, D, Gockerman, J, Diehl, L, Shea, TC, Decastro, C, Moore, JO, and Beaven, A. "Phase II open label study of the oral vascular endothelial growth factor-receptor inhibitor PTK787/ZK222584 (vatalanib) in adult patients with refractory or relapsed diffuse large B-cell lymphoma." Leuk Lymphoma 54.12 (December 2013): 2627-2630.
PMID
23488610
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
54
Issue
12
Publish Date
2013
Start Page
2627
End Page
2630
DOI
10.3109/10428194.2013.784969

Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial.

PURPOSE: The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade. PATIENTS AND METHODS: We conducted an international phase II study of pidilizumab, an anti-PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT. RESULTS: Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E-bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab. CONCLUSION: This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease.

Authors
Armand, P; Nagler, A; Weller, EA; Devine, SM; Avigan, DE; Chen, Y-B; Kaminski, MS; Holland, HK; Winter, JN; Mason, JR; Fay, JW; Rizzieri, DA; Hosing, CM; Ball, ED; Uberti, JP; Lazarus, HM; Mapara, MY; Gregory, SA; Timmerman, JM; Andorsky, D; Or, R; Waller, EK; Rotem-Yehudar, R; Gordon, LI
MLA Citation
Armand, P, Nagler, A, Weller, EA, Devine, SM, Avigan, DE, Chen, Y-B, Kaminski, MS, Holland, HK, Winter, JN, Mason, JR, Fay, JW, Rizzieri, DA, Hosing, CM, Ball, ED, Uberti, JP, Lazarus, HM, Mapara, MY, Gregory, SA, Timmerman, JM, Andorsky, D, Or, R, Waller, EK, Rotem-Yehudar, R, and Gordon, LI. "Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial." J Clin Oncol 31.33 (November 20, 2013): 4199-4206.
PMID
24127452
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
31
Issue
33
Publish Date
2013
Start Page
4199
End Page
4206
DOI
10.1200/JCO.2012.48.3685

Providing personalized prognostic information for adult leukemia survivors.

Prediction of subsequent leukemia-free survival (LFS) and chronic graft-versus-host disease (GVHD) in adults with acute leukemia who survived at least 1 year after allogeneic hematopoietic cell transplantation is difficult. We analyzed 3339 patients with acute myeloid leukemia and 1434 patients with acute lymphoblastic leukemia who received myeloablative conditioning and related or unrelated stem cells from 1990 to 2005. Most clinical factors predictive of LFS in 1-year survivors were no longer significant after 2 or more years. For acute myeloid leukemia, only disease status (beyond first complete remission) remained a significant adverse risk factor for LFS 2 or more years after transplantation. For lymphoblastic leukemia, only extensive chronic GVHD remained a significant adverse predictor of LFS in the second and subsequent years. For patients surviving for 1 year without disease relapse or extensive chronic GVHD, the risk of developing extensive chronic GVHD in the next year was 4% if no risk factors were present and higher if noncyclosporine-based GVHD prophylaxis, an HLA-mismatched donor, or peripheral blood stem cells were used. Estimates for subsequent LFS and extensive chronic GVHD can be derived for individual patients or populations using an online calculator (http://www.cibmtr.org/LeukemiaCalculators). This prognostic information is more relevant for survivors than estimates provided before transplantation.

Authors
Lee, SJ; Storer, B; Wang, H; Lazarus, HM; Waller, EK; Isola, LM; Klumpp, TR; Umejiego, JBC; Savani, BN; Loren, AW; Cairo, MS; Camitta, BM; Cutler, CS; George, B; Jean Khoury, H; Marks, DI; Rizzieri, DA; Copelan, EA; Gupta, V; Liesveld, JL; Litzow, MR; Miller, AM; Schouten, HC; Gale, RP; Cahn, J-Y; Weisdorf, DJ
MLA Citation
Lee, SJ, Storer, B, Wang, H, Lazarus, HM, Waller, EK, Isola, LM, Klumpp, TR, Umejiego, JBC, Savani, BN, Loren, AW, Cairo, MS, Camitta, BM, Cutler, CS, George, B, Jean Khoury, H, Marks, DI, Rizzieri, DA, Copelan, EA, Gupta, V, Liesveld, JL, Litzow, MR, Miller, AM, Schouten, HC, Gale, RP, Cahn, J-Y, and Weisdorf, DJ. "Providing personalized prognostic information for adult leukemia survivors." Biol Blood Marrow Transplant 19.11 (November 2013): 1600-1607.
PMID
24018394
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
11
Publish Date
2013
Start Page
1600
End Page
1607
DOI
10.1016/j.bbmt.2013.08.013

Autologous haematopoietic cell transplantation for non-Hodgkin lymphoma with secondary CNS involvement.

Pre-existing central nervous system (CNS) involvement may influence referral for autologous haematopoietic cell transplantation (AHCT) for patients with non-Hodgkin lymphoma (NHL). The outcomes of 151 adult patients with NHL with prior secondary CNS involvement (CNS(+) ) receiving an AHCT were compared to 4688 patients without prior CNS lymphoma (CNS(-) ). There were significant baseline differences between the cohorts. CNS(+) patients were more likely to be younger, have lower performance scores, higher age-adjusted international prognostic index scores, more advanced disease stage at diagnosis, more aggressive histology, more sites of extranodal disease, and a shorter interval between diagnosis and AHCT. However, no statistically significant differences were identified between the two groups by analysis of progression-free survival (PFS) and overall survival (OS) at 5 years. A matched pair comparison of the CNS(+) group with a subset of CNS(-) patients matched on propensity score also showed no differences in outcomes. Patients with active CNS lymphoma at the time of AHCT (n = 55) had a higher relapse rate and diminished PFS and OS compared with patients whose CNS lymphoma was in remission (n = 96) at the time of AHCT. CNS(+) patients can achieve excellent long-term outcomes with AHCT. Active CNS lymphoma at transplant confers a worse prognosis.

Authors
Maziarz, RT; Wang, Z; Zhang, M-J; Bolwell, BJ; Chen, AI; Fenske, TS; Freytes, CO; Gale, RP; Gibson, J; Hayes-Lattin, BM; Holmberg, L; Inwards, DJ; Isola, LM; Khoury, HJ; Lewis, VA; Maharaj, D; Munker, R; Phillips, GL; Rizzieri, DA; Rowlings, PA; Saber, W; Satwani, P; Waller, EK; Maloney, DG; Montoto, S; Laport, GG; Vose, JM; Lazarus, HM; Hari, PN
MLA Citation
Maziarz, RT, Wang, Z, Zhang, M-J, Bolwell, BJ, Chen, AI, Fenske, TS, Freytes, CO, Gale, RP, Gibson, J, Hayes-Lattin, BM, Holmberg, L, Inwards, DJ, Isola, LM, Khoury, HJ, Lewis, VA, Maharaj, D, Munker, R, Phillips, GL, Rizzieri, DA, Rowlings, PA, Saber, W, Satwani, P, Waller, EK, Maloney, DG, Montoto, S, Laport, GG, Vose, JM, Lazarus, HM, and Hari, PN. "Autologous haematopoietic cell transplantation for non-Hodgkin lymphoma with secondary CNS involvement." Br J Haematol 162.5 (September 2013): 648-656.
PMID
23829536
Source
pubmed
Published In
British Journal of Haematology
Volume
162
Issue
5
Publish Date
2013
Start Page
648
End Page
656
DOI
10.1111/bjh.12451

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

Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function

Authors
Lim, S; Saw, TY; Zhang, M; Janes, MR; Nacro, K; Hill, J; Lim, AQ; Chang, C-T; Fruman, DA; Rizzieri, DA; Tan, SY; Fan, H; Chuah, CTH; Ong, ST
MLA Citation
Lim, S, Saw, TY, Zhang, M, Janes, MR, Nacro, K, Hill, J, Lim, AQ, Chang, C-T, Fruman, DA, Rizzieri, DA, Tan, SY, Fan, H, Chuah, CTH, and Ong, ST. "Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function." PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 110.25 (June 18, 2013): E2298-E2307.
Source
wos-lite
Published In
Proceedings of the National Academy of Sciences of USA
Volume
110
Issue
25
Publish Date
2013
Start Page
E2298
End Page
E2307
DOI
10.1073/pnas.1301838110

Impact of pretransplantation conditioning regimens on outcomes of allogeneic transplantation for chemotherapy-unresponsive diffuse large B cell lymphoma and grade III follicular lymphoma.

Patients with chemorefractory non-Hodgkin lymphomas generally have a poor prognosis. We used the observational database of the Center for International Blood and Marrow Transplant Research to study the outcome of 533 patients with refractory diffuse large B cell lymphoma (DLBCL) or grade III follicular lymphoma (FL-III) who underwent allogeneic hematopoietic cell transplantation (allo-HCT) using either myeloablative (MA; n = 307) or reduced-intensity/nonmyeloablative conditioning (RIC/NST; n = 226) between 1998 and 2010. We analyzed nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Only 45% of the patients at transplantation had a Karnofsky performance score of ≥90%. Median follow-up of surviving patients after MA and RIC/NST allo-HCT is 35 months and 30 months, respectively. At 3 years, MA allo-HCT was associated with a higher NRM compared with RIC/NST (53% versus 42%; P = .03), similar PFS (19% versus 23%; P = .40), and lower OS (19% versus 28%; P = .02), respectively. On multivariate analysis, FL-III histology was associated with lower NRM (relative risk [RR], .52), reduced risk of relapse/progression (RR, .42), and superior PFS (RR, .51) and OS (RR, .53), whereas MA conditioning was associated with reduced risk of relapse/progression (RR, .66). Despite a refractory state, a small subset of DLBCL and FL-III patients can attain durable remissions after allo-HCT. Conditioning regimen intensity was not associated with PFS and OS despite a higher risk of relapse/progression with RIC/NST allo-HCT.

Authors
Hamadani, M; Saber, W; Ahn, KW; Carreras, J; Cairo, MS; Fenske, TS; Gale, RP; Gibson, J; Hale, GA; Hari, PN; Hsu, JW; Inwards, DJ; Kamble, RT; Klein, A; Maharaj, D; Marks, DI; Rizzieri, DA; Savani, BN; Schouten, HC; Waller, EK; Wirk, B; Laport, GG; Montoto, S; Maloney, DG; Lazarus, HM
MLA Citation
Hamadani, M, Saber, W, Ahn, KW, Carreras, J, Cairo, MS, Fenske, TS, Gale, RP, Gibson, J, Hale, GA, Hari, PN, Hsu, JW, Inwards, DJ, Kamble, RT, Klein, A, Maharaj, D, Marks, DI, Rizzieri, DA, Savani, BN, Schouten, HC, Waller, EK, Wirk, B, Laport, GG, Montoto, S, Maloney, DG, and Lazarus, HM. "Impact of pretransplantation conditioning regimens on outcomes of allogeneic transplantation for chemotherapy-unresponsive diffuse large B cell lymphoma and grade III follicular lymphoma." Biol Blood Marrow Transplant 19.5 (May 2013): 746-753.
PMID
23380340
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
5
Publish Date
2013
Start Page
746
End Page
753
DOI
10.1016/j.bbmt.2013.01.024

Leukemic stem cells: a review.

A small subset of cells in a patient with leukemia, termed leukemic stem cells (LSCs) have been shown to be responsible for the proliferation of disease. LSCs are thought to derive from normal hematopoietic stem cells, but are phenotypically distinguishable in that they are CD90(-), CD117(-), and CD123(+). Research in mouse models provides several potential therapeutics to target these cells in human patients. Eliminating LSCs should provide an efficient, potentially curative treatment option for leukemia patients.

Authors
O'Brien, JA; Rizzieri, DA
MLA Citation
O'Brien, JA, and Rizzieri, DA. "Leukemic stem cells: a review." Cancer Invest 31.4 (May 2013): 215-220. (Review)
PMID
23473080
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
31
Issue
4
Publish Date
2013
Start Page
215
End Page
220
DOI
10.3109/07357907.2012.700986

Allogeneic hematopoietic cell transplantation for chemotherapy-unresponsive mantle cell lymphoma: a cohort analysis from the center for international blood and marrow transplant research.

Patients with chemorefractory mantle cell lymphoma (MCL) have a poor prognosis. We used the Center for International Blood and Marrow Transplant Research database to study the outcome of 202 patients with refractory MCL who underwent allogeneic hematopoietic cell transplantation (allo-HCT) using either myeloablative (MA) or reduced-intensity/nonmyeloablative conditioning (RIC/NST), during 1998-2010. We analyzed nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS). Seventy-four patients (median age, 54 years) received MA, and 128 patients (median age, 59 years) received RIC/NST. Median follow-up after allo-HCT was 35 months in the MA group and 43 months in the RIC/NST group. At 3 years post-transplantation, no significant between-group differences were seen in terms of NRM (47% in MA versus 43% in RIC/NST; P = .68), relapse/progression (33% versus 32%; P = .89), PFS (20% versus 25%; P = .53), or OS (25% versus 30%; P = .45). Multivariate analysis also revealed no significant between-group differences in NRM, relapse, PFS, or OS; however, receipt of a bone marrow or T cell-depleted allograft was associated with an increased risk of NRM and inferior PFS and OS. Our data suggest that despite a refractory disease state, approximately 25% of patients with MCL can attain durable remission after allo-HCT, and conditioning regimen intensity does not influence outcome of allo-HCT.

Authors
Hamadani, M; Saber, W; Ahn, KW; Carreras, J; Cairo, MS; Fenske, TS; Gale, RP; Gibson, J; Hale, GA; Hari, PN; Hsu, JW; Inwards, DJ; Kamble, RT; Klein, A; Maharaj, D; Marks, DI; Rizzieri, DA; Savani, BN; Schouten, HC; Waller, EK; Wirk, B; Lazarus, HM
MLA Citation
Hamadani, M, Saber, W, Ahn, KW, Carreras, J, Cairo, MS, Fenske, TS, Gale, RP, Gibson, J, Hale, GA, Hari, PN, Hsu, JW, Inwards, DJ, Kamble, RT, Klein, A, Maharaj, D, Marks, DI, Rizzieri, DA, Savani, BN, Schouten, HC, Waller, EK, Wirk, B, and Lazarus, HM. "Allogeneic hematopoietic cell transplantation for chemotherapy-unresponsive mantle cell lymphoma: a cohort analysis from the center for international blood and marrow transplant research." Biol Blood Marrow Transplant 19.4 (April 2013): 625-631.
PMID
23333532
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
4
Publish Date
2013
Start Page
625
End Page
631
DOI
10.1016/j.bbmt.2013.01.009

A Phase I study of arsenic trioxide (Trisenox), ascorbic acid, and bortezomib (Velcade) combination therapy in patients with relapsed/refractory multiple myeloma.

PURPOSE: This Phase I study assessed the feasibility of concomitant arsenic trioxide (ATO), ascorbic acid (AA), and bortezomib (Velcade™) (AAV) for patients with relapsed/refractory multiple myeloma. EXPERIMENTAL DESIGN: ATO (0.25 mg/kg) and AA (1 g) were given with an escalating dose of bortezomib (1 mg/m(2) or 1.3 mg/m(2) IV bolus on days 1 and 8 of a 21-day cycle). RESULTS: Ten patients (median age 62 years), with a median of 3 prior regimens, were enrolled. Four (40%) patients achieved clinical benefit, with one patient achieving a durable partial response. No formal DLTs were encountered. CONCLUSION: AAV combination was feasible and demonstrated some benefits in this heavily pretreated population.

Authors
Held, LA; Rizzieri, D; Long, GD; Gockerman, JP; Diehl, LF; de Castro, CM; Moore, JO; Horwitz, ME; Chao, NJ; Gasparetto, C
MLA Citation
Held, LA, Rizzieri, D, Long, GD, Gockerman, JP, Diehl, LF, de Castro, CM, Moore, JO, Horwitz, ME, Chao, NJ, and Gasparetto, C. "A Phase I study of arsenic trioxide (Trisenox), ascorbic acid, and bortezomib (Velcade) combination therapy in patients with relapsed/refractory multiple myeloma." Cancer Invest 31.3 (March 2013): 172-176.
PMID
23406188
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
31
Issue
3
Publish Date
2013
Start Page
172
End Page
176
DOI
10.3109/07357907.2012.756109

Engineering a BCR-ABL-activated caspase for the selective elimination of leukemic cells.

Increased understanding of the precise molecular mechanisms involved in cell survival and cell death signaling pathways offers the promise of harnessing these molecules to eliminate cancer cells without damaging normal cells. Tyrosine kinase oncoproteins promote the genesis of leukemias through both increased cell proliferation and inhibition of apoptotic cell death. Although tyrosine kinase inhibitors, such as the BCR-ABL inhibitor imatinib, have demonstrated remarkable efficacy in the clinic, drug-resistant leukemias emerge in some patients because of either the acquisition of point mutations or amplification of the tyrosine kinase, resulting in a poor long-term prognosis. Here, we exploit the molecular mechanisms of caspase activation and tyrosine kinase/adaptor protein signaling to forge a unique approach for selectively killing leukemic cells through the forcible induction of apoptosis. We have engineered caspase variants that can directly be activated in response to BCR-ABL. Because we harness, rather than inhibit, the activity of leukemogenic kinases to kill transformed cells, this approach selectively eliminates leukemic cells regardless of drug-resistant mutations.

Authors
Kurokawa, M; Ito, T; Yang, C-S; Zhao, C; Macintyre, AN; Rizzieri, DA; Rathmell, JC; Deininger, MW; Reya, T; Kornbluth, S
MLA Citation
Kurokawa, M, Ito, T, Yang, C-S, Zhao, C, Macintyre, AN, Rizzieri, DA, Rathmell, JC, Deininger, MW, Reya, T, and Kornbluth, S. "Engineering a BCR-ABL-activated caspase for the selective elimination of leukemic cells." Proc Natl Acad Sci U S A 110.6 (February 5, 2013): 2300-2305.
Website
http://hdl.handle.net/10161/8388
PMID
23324740
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
110
Issue
6
Publish Date
2013
Start Page
2300
End Page
2305
DOI
10.1073/pnas.1206551110

New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation.

Minimal residual disease (MRD) is a complex topic that has been studied extensively in hematologic malignancies given its clinical implications related to prognosis. However, methods to monitor and treat MRD, especially after stem cell transplantation, are not well defined and vary in different disease processes. Alternative transplant strategies, such as reduced-intensity conditioning, have altered the way we assess and address MRD after transplantation. Development of new diagnostic tools have allowed for higher sensitivity and specificity of testing. Both targeted chemotherapeutic agents and immunotherapies have been developed to treat MRD in hopes of improving patient outcomes. This article aims to address ways to define and manipulate MRD specifically after stem cell transplantation.

Authors
Rein, LA; Sung, AD; Rizzieri, DA
MLA Citation
Rein, LA, Sung, AD, and Rizzieri, DA. "New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation." International journal of hematologic oncology 2.1 (February 2013).
PMID
24303095
Source
epmc
Published In
International Journal of Hematologic Oncology
Volume
2
Issue
1
Publish Date
2013
DOI
10.2217/ijh.13.4

Autologous and allogeneic transplantation for burkitt lymphoma outcomes and changes in utilization: a report from the center for international blood and marrow transplant research.

Trends in utilization and outcomes after autologous or allogeneic hematopoietic cell transplantation (HCT) for Burkitt lymphoma were analyzed in 241 recipients reported to the Center for International Blood and Marrow Transplant Research between 1985 and 2007. The autologous HCT cohort had a higher proportion of chemotherapy-sensitive disease, peripheral blood grafts, and HCT in first complete remission (CR1). The use of autologous HCT has declined over time, with only 19% done after 2001. Overall survival at 5 years for the autologous cohort was 83% for those in CR1 and 31% for those not in CR1. Corresponding progression-free survival (PFS) was 78% and 27%, respectively. After allogeneic HCT, overall survival at 5 years was 53% and 20% for the CR1 and non-CR1 cohorts, whereas PFS was 50% and 19%, respectively. The most common cause of death was progressive lymphoma. Allogeneic HCT performed in a higher-risk subset (per National Comprehensive Cancer Network guidelines) resulted in a 5-year PFS of 27%. Autologous HCT resulted in a 5-year PFS of 44% in those undergoing transplantation in the second CR.

Authors
Maramattom, LV; Hari, PN; Burns, LJ; Carreras, J; Arcese, W; Cairo, MS; Costa, LJ; Fenske, TS; Lill, M; Freytes, CO; Gale, RP; Gross, TG; Hale, GA; Hamadani, M; Holmberg, LA; Hsu, JW; Inwards, DJ; Lazarus, HM; Marks, DI; Maloney, DG; Maziarz, RT; Montoto, S; Rizzieri, DA; Wirk, B; Gajewski, JL
MLA Citation
Maramattom, LV, Hari, PN, Burns, LJ, Carreras, J, Arcese, W, Cairo, MS, Costa, LJ, Fenske, TS, Lill, M, Freytes, CO, Gale, RP, Gross, TG, Hale, GA, Hamadani, M, Holmberg, LA, Hsu, JW, Inwards, DJ, Lazarus, HM, Marks, DI, Maloney, DG, Maziarz, RT, Montoto, S, Rizzieri, DA, Wirk, B, and Gajewski, JL. "Autologous and allogeneic transplantation for burkitt lymphoma outcomes and changes in utilization: a report from the center for international blood and marrow transplant research." Biol Blood Marrow Transplant 19.2 (February 2013): 173-179.
PMID
23200705
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
2
Publish Date
2013
Start Page
173
End Page
179
DOI
10.1016/j.bbmt.2012.11.016

Genetic heterogeneity of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma in adults. The disease exhibits a striking heterogeneity in gene expression profiles and clinical outcomes, but its genetic causes remain to be fully defined. Through whole genome and exome sequencing, we characterized the genetic diversity of DLBCL. In all, we sequenced 73 DLBCL primary tumors (34 with matched normal DNA). Separately, we sequenced the exomes of 21 DLBCL cell lines. We identified 322 DLBCL cancer genes that were recurrently mutated in primary DLBCLs. We identified recurrent mutations implicating a number of known and not previously identified genes and pathways in DLBCL including those related to chromatin modification (ARID1A and MEF2B), NF-κB (CARD11 and TNFAIP3), PI3 kinase (PIK3CD, PIK3R1, and MTOR), B-cell lineage (IRF8, POU2F2, and GNA13), and WNT signaling (WIF1). We also experimentally validated a mutation in PIK3CD, a gene not previously implicated in lymphomas. The patterns of mutation demonstrated a classic long tail distribution with substantial variation of mutated genes from patient to patient and also between published studies. Thus, our study reveals the tremendous genetic heterogeneity that underlies lymphomas and highlights the need for personalized medicine approaches to treating these patients.

Authors
Zhang, J; Grubor, V; Love, CL; Banerjee, A; Richards, KL; Mieczkowski, PA; Dunphy, C; Choi, W; Au, WY; Srivastava, G; Lugar, PL; Rizzieri, DA; Lagoo, AS; Bernal-Mizrachi, L; Mann, KP; Flowers, C; Naresh, K; Evens, A; Gordon, LI; Czader, M; Gill, JI; Hsi, ED; Liu, Q; Fan, A; Walsh, K; Jima, D; Smith, LL; Johnson, AJ; Byrd, JC; Luftig, MA; Ni, T; Zhu, J; Chadburn, A; Levy, S; Dunson, D; Dave, SS
MLA Citation
Zhang, J, Grubor, V, Love, CL, Banerjee, A, Richards, KL, Mieczkowski, PA, Dunphy, C, Choi, W, Au, WY, Srivastava, G, Lugar, PL, Rizzieri, DA, Lagoo, AS, Bernal-Mizrachi, L, Mann, KP, Flowers, C, Naresh, K, Evens, A, Gordon, LI, Czader, M, Gill, JI, Hsi, ED, Liu, Q, Fan, A, Walsh, K, Jima, D, Smith, LL, Johnson, AJ, Byrd, JC, Luftig, MA, Ni, T, Zhu, J, Chadburn, A, Levy, S, Dunson, D, and Dave, SS. "Genetic heterogeneity of diffuse large B-cell lymphoma." Proc Natl Acad Sci U S A 110.4 (January 22, 2013): 1398-1403.
PMID
23292937
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
110
Issue
4
Publish Date
2013
Start Page
1398
End Page
1403
DOI
10.1073/pnas.1205299110

Re-induction therapy decisions based on day 14 bone marrow biopsy in acute myeloid leukemia.

PURPOSE: The decision to re-induce patients with acute myeloid leukemia (AML) based on results of the day 14 bone marrow (BM) biopsy is variable and lacks evidence based data. The aim of our review was to evaluate the accuracy of a day 14 BM biopsy in determining the need for re-induction chemotherapy. METHODS: Seventy-four patients with newly diagnosed de novo AML treated with induction chemotherapy were retrospectively reviewed for the purpose of evaluating treatment decisions and outcomes based on their day 14 BM biopsy. Response to therapy in this analysis was based on morphology alone. RESULTS: Of the 74 patients undergoing standard induction, 45 patients (61%) had no evidence of leukemia on their day 14 BM biopsy. Eighteen patients (24%) had definitive residual disease (RD), and 11 patient's (15%) were classified as indeterminate response (IR). Fifteen patients with RD and one with IR underwent re-induction chemotherapy. However, thirteen patients (3 RD and 10 IR) were observed until count recovery without any re-induction therapy. Eleven of these 13 patients who were observed eventually attained a morphologic complete remission (CR), including two patients with RD. CONCLUSIONS: A day 14 BM biopsy may have suboptimal sensitivity for the detection of residual leukemia. Some patients with an IR on day 14 may not require re-induction chemotherapy, but instead, may benefit from careful observation until count recovery to avoid the mortality and morbidity associated with re-induction chemotherapy.

Authors
Morris, TA; DeCastro, CM; Diehl, LF; Gockerman, JP; Lagoo, AS; Li, Z; Moore, JO; Rizzieri, DA; Rao, AV
MLA Citation
Morris, TA, DeCastro, CM, Diehl, LF, Gockerman, JP, Lagoo, AS, Li, Z, Moore, JO, Rizzieri, DA, and Rao, AV. "Re-induction therapy decisions based on day 14 bone marrow biopsy in acute myeloid leukemia." Leuk Res 37.1 (January 2013): 28-31.
PMID
23046833
Source
pubmed
Published In
Leukemia Research: clinical and laboratory studies
Volume
37
Issue
1
Publish Date
2013
Start Page
28
End Page
31
DOI
10.1016/j.leukres.2012.09.016

MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia.

MK-0457, an Aurora kinase and BCR-ABL inhibitor, was studied on a Phase I/II study in 77 patients with refractory hematologic malignancies. The average number of cycles per patient was 3 (range 1-21). Maximum tolerated doses for a 5-day short infusion and continuous infusion regimens were 40 mg/m(2)/h and 144 mg/m(2)/h, respectively. Drug-related adverse events (AEs) included transient mucositis and alopecia. Eight of 18 patients with BCR-ABL T315I-mutated chronic myelogenous leukemia (44%) had hematologic responses and one of three patients (33%) with Philadelphia chromosome-positive acute lymphoblastic leukemia obtained complete remission. MK-0457 has important activity in patients with leukemias expressing the highly resistant T315I BCR-ABL mutation.

Authors
Giles, FJ; Swords, RT; Nagler, A; Hochhaus, A; Ottmann, OG; Rizzieri, DA; Talpaz, M; Clark, J; Watson, P; Xiao, A; Zhao, B; Bergstrom, D; Le Coutre, PD; Freedman, SJ; Cortes, JE
MLA Citation
Giles, FJ, Swords, RT, Nagler, A, Hochhaus, A, Ottmann, OG, Rizzieri, DA, Talpaz, M, Clark, J, Watson, P, Xiao, A, Zhao, B, Bergstrom, D, Le Coutre, PD, Freedman, SJ, and Cortes, JE. "MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia." Leukemia 27.1 (January 2013): 113-117.
PMID
22772060
Source
pubmed
Published In
Leukemia
Volume
27
Issue
1
Publish Date
2013
Start Page
113
End Page
117
DOI
10.1038/leu.2012.186

Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (OPAL): a randomised open-label phase 2 study

Background: Tosedostat is a novel oral aminopeptidase inhibitor with clinical activity in a previous phase 1-2 study in elderly patients with relapsed or refractory acute myeloid leukaemia (AML). We aimed to compare two dosing regimens of tosedostat. Methods: In this randomised phase 2 study, patients aged 60 years or older with AML that had relapsed after a first complete remission lasting less than 12 months, or had achieved no previous complete remission, were randomly assigned (1:1) to receive as first salvage tosedostat 120 mg once daily for 6 months or 240 mg once daily for 2 months followed by 120 mg for 4 months. Randomisation was by block method via an interactive web response system using a randomisation schedule generated by an external vendor, with no stratification. The study was open label. The primary endpoint was the proportion of patients who obtained a complete remission or complete remission with incomplete platelet recovery. Analyses included all patients randomly assigned to treatment groups who received at least one oral dose of tosedostat. The study is registered with ClinicalTrials.gov, number NCT00780598. Findings: 38 patients were randomly assigned to receive tosedostat 120 mg and 38 to receive the tosedostat 240 mg to 120 mg regimen. 38 patients in the 120 mg group and 35 in the 240 mg to 120 mg group received tosedostat. Seven patients (10%) had complete remission or complete remission with incomplete platelet recovery: two (5%) in the 120 mg group and five (14%) in the 240 mg to 120 mg group. The most common grade 3 or worse adverse events were febrile neutropenia (11 [29%] patients in the 120 mg group and ten [29%] of the 240 mg to 120 mg group), thrombocytopenia (eight [21%] and eight [23%] patients), fatigue (seven [18%] and eight [23%] patients), dyspnoea (five [13%] and seven [20%] patients), and pneumonia (four [11%] and six [17%] patients). There were five fatal adverse events deemed to be treatment-related: three in the 120 mg group and two in the 240 mg to 120 mg group. The events were acute hepatitis, respiratory failure, pneumonia, atrial fibrillation, and left ventricular dysfunction. Interpretation: Tosedostat, at either dose schedule, has activity in older patients with relapsed or refractory AML. Additional studies of tosedostat including combination with hypomethylating agents and low-dose cytarabine in patients with high-risk myelodysplastic syndromes and AML are ongoing or planned. Funding: Chroma Therapeutics. © 2013 Elsevier Ltd. All rights reserved.

Authors
Cortes, J; Feldman, E; Yee, K; Rizzieri, D; Advani, AS; Charman, A; Spruyt, R; Toal, M; Kantarjian, H
MLA Citation
Cortes, J, Feldman, E, Yee, K, Rizzieri, D, Advani, AS, Charman, A, Spruyt, R, Toal, M, and Kantarjian, H. "Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (OPAL): a randomised open-label phase 2 study." The Lancet Oncology (2013).
PMID
23453583
Source
scival
Published In
The Lancet Oncology
Publish Date
2013
DOI
10.1016/S1470-2045(13)70037-8

MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia

MK-0457, an Aurora kinase and BCR-ABL inhibitor, was studied on a Phase I/II study in 77 patients with refractory hematologic malignancies. The average number of cycles per patient was 3 (range 1-21). Maximum tolerated doses for a 5-day short infusion and continuous infusion regimens were 40 mg/m 2/h and 144 mg/m 2/h, respectively. Drug-related adverse events (AEs) included transient mucositis and alopecia. Eight of 18 patients with BCR-ABL T315I-mutated chronic myelogenous leukemia (44%) had hematologic responses and one of three patients (33%) with Philadelphia chromosome-positive acute lymphoblastic leukemia obtained complete remission. MK-0457 has important activity in patients with leukemias expressing the highly resistant T315I BCR-ABL mutation. © 2013 Macmillan Publishers Limited All rights reserved.

Authors
Giles, FJ; Swords, RT; Nagler, A; Hochhaus, A; Ottmann, OG; Rizzieri, DA; Talpaz, M; Clark, J; Watson, P; Xiao, A; Zhao, B; Bergstrom, D; Coutre, PDL; Freedman, SJ; Cortes, JE
MLA Citation
Giles, FJ, Swords, RT, Nagler, A, Hochhaus, A, Ottmann, OG, Rizzieri, DA, Talpaz, M, Clark, J, Watson, P, Xiao, A, Zhao, B, Bergstrom, D, Coutre, PDL, Freedman, SJ, and Cortes, JE. "MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia." Leukemia 27.1 (2013): 113-117.
Source
scival
Published In
Leukemia
Volume
27
Issue
1
Publish Date
2013
Start Page
113
End Page
117
DOI
10.1038/leu.2012.186

Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (OPAL): A randomised open-label phase 2 study

Background: Tosedostat is a novel oral aminopeptidase inhibitor with clinical activity in a previous phase 1-2 study in elderly patients with relapsed or refractory acute myeloid leukaemia (AML). We aimed to compare two dosing regimens of tosedostat. Methods: In this randomised phase 2 study, patients aged 60 years or older with AML that had relapsed after a first complete remission lasting less than 12 months, or had achieved no previous complete remission, were randomly assigned (1:1) to receive as first salvage tosedostat 120 mg once daily for 6 months or 240 mg once daily for 2 months followed by 120 mg for 4 months. Randomisation was by block method via an interactive web response system using a randomisation schedule generated by an external vendor, with no stratification. The study was open label. The primary endpoint was the proportion of patients who obtained a complete remission or complete remission with incomplete platelet recovery. Analyses included all patients randomly assigned to treatment groups who received at least one oral dose of tosedostat. The study is registered with ClinicalTrials.gov, number NCT00780598. Findings: 38 patients were randomly assigned to receive tosedostat 120 mg and 38 to receive the tosedostat 240 mg to 120 mg regimen. 38 patients in the 120 mg group and 35 in the 240 mg to 120 mg group received tosedostat. Seven patients (10%) had complete remission or complete remission with incomplete platelet recovery: two (5%) in the 120 mg group and five (14%) in the 240 mg to 120 mg group. The most common grade 3 or worse adverse events were febrile neutropenia (11 [29%] patients in the 120 mg group and ten [29%] of the 240 mg to 120 mg group), thrombocytopenia (eight [21%] and eight [23%] patients), fatigue (seven [18%] and eight [23%] patients), dyspnoea (five [13%] and seven [20%] patients), and pneumonia (four [11%] and six [17%] patients). There were five fatal adverse events deemed to be treatment-related: three in the 120 mg group and two in the 240 mg to 120 mg group. The events were acute hepatitis, respiratory failure, pneumonia, atrial fibrillation, and left ventricular dysfunction. Interpretation: Tosedostat, at either dose schedule, has activity in older patients with relapsed or refractory AML. Additional studies of tosedostat including combination with hypomethylating agents and low-dose cytarabine in patients with high-risk myelodysplastic syndromes and AML are ongoing or planned. Funding: Chroma Therapeutics. © 2013 Elsevier Ltd.

Authors
Cortes, J; Feldman, E; Yee, K; Rizzieri, D; Advani, AS; Charman, A; Spruyt, R; Toal, M; Kantarjian, H
MLA Citation
Cortes, J, Feldman, E, Yee, K, Rizzieri, D, Advani, AS, Charman, A, Spruyt, R, Toal, M, and Kantarjian, H. "Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (OPAL): A randomised open-label phase 2 study." The Lancet Oncology 14.4 (2013): 354-362.
Source
scival
Published In
The Lancet Oncology
Volume
14
Issue
4
Publish Date
2013
Start Page
354
End Page
362
DOI
10.1016/S1470-2045(13)70037-8

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

Autologous haematopoietic cell transplantation for non-Hodgkin lymphoma with secondary CNS involvement

Pre-existing central nervous system (CNS) involvement may influence referral for autologous haematopoietic cell transplantation (AHCT) for patients with non-Hodgkin lymphoma (NHL). The outcomes of 151 adult patients with NHL with prior secondary CNS involvement (CNS+) receiving an AHCT were compared to 4688 patients without prior CNS lymphoma (CNS-). There were significant baseline differences between the cohorts. CNS+ patients were more likely to be younger, have lower performance scores, higher age-adjusted international prognostic index scores, more advanced disease stage at diagnosis, more aggressive histology, more sites of extranodal disease, and a shorter interval between diagnosis and AHCT. However, no statistically significant differences were identified between the two groups by analysis of progression-free survival (PFS) and overall survival (OS) at 5 years. A matched pair comparison of the CNS+ group with a subset of CNS- patients matched on propensity score also showed no differences in outcomes. Patients with active CNS lymphoma at the time of AHCT (n = 55) had a higher relapse rate and diminished PFS and OS compared with patients whose CNS lymphoma was in remission (n = 96) at the time of AHCT. CNS+ patients can achieve excellent long-term outcomes with AHCT. Active CNS lymphoma at transplant confers a worse prognosis. © 2013 John Wiley & Sons Ltd.

Authors
Maziarz, RT; Wang, Z; Zhang, M-J; Bolwell, BJ; Chen, AI; Fenske, TS; Freytes, CO; Gale, RP; Gibson, J; Hayes-Lattin, BM; Holmberg, L; Inwards, DJ; Isola, LM; Khoury, HJ; Lewis, VA; Maharaj, D; Munker, R; Phillips, GL; Rizzieri, DA; Rowlings, PA; Saber, W; Satwani, P; Waller, EK; Maloney, DG; Montoto, S; Laport, GG; Vose, JM; Lazarus, HM; Hari, PN
MLA Citation
Maziarz, RT, Wang, Z, Zhang, M-J, Bolwell, BJ, Chen, AI, Fenske, TS, Freytes, CO, Gale, RP, Gibson, J, Hayes-Lattin, BM, Holmberg, L, Inwards, DJ, Isola, LM, Khoury, HJ, Lewis, VA, Maharaj, D, Munker, R, Phillips, GL, Rizzieri, DA, Rowlings, PA, Saber, W, Satwani, P, Waller, EK, Maloney, DG, Montoto, S, Laport, GG, Vose, JM, Lazarus, HM, and Hari, PN. "Autologous haematopoietic cell transplantation for non-Hodgkin lymphoma with secondary CNS involvement." British Journal of Haematology 162.5 (2013): 648-656.
Source
scival
Published In
British Journal of Haematology
Volume
162
Issue
5
Publish Date
2013
Start Page
648
End Page
656
DOI
10.1111/bjh.12451

MDS: unraveling the mystery.

In this issue of Blood, Sekeres et al report a phase 2 study of lenalidomide and azacitidine for higher risk myelodysplastic syndromes (MDS). High overall response and duration of response supports the concept of combination, multitargeted approaches rather than traditional chemotherapeutics for this disease.

Authors
Rizzieri, DA
MLA Citation
Rizzieri, DA. "MDS: unraveling the mystery." Blood 120.25 (December 13, 2012): 4906-4908.
PMID
23243154
Source
pubmed
Published In
Blood
Volume
120
Issue
25
Publish Date
2012
Start Page
4906
End Page
4908
DOI
10.1182/blood-2012-09-452755

The genetic landscape of mutations in Burkitt lymphoma.

Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.

Authors
Love, C; Sun, Z; Jima, D; Li, G; Zhang, J; Miles, R; Richards, KL; Dunphy, CH; Choi, WWL; Srivastava, G; Lugar, PL; Rizzieri, DA; Lagoo, AS; Bernal-Mizrachi, L; Mann, KP; Flowers, CR; Naresh, KN; Evens, AM; Chadburn, A; Gordon, LI; Czader, MB; Gill, JI; Hsi, ED; Greenough, A; Moffitt, AB; McKinney, M; Banerjee, A; Grubor, V; Levy, S; Dunson, DB; Dave, SS
MLA Citation
Love, C, Sun, Z, Jima, D, Li, G, Zhang, J, Miles, R, Richards, KL, Dunphy, CH, Choi, WWL, Srivastava, G, Lugar, PL, Rizzieri, DA, Lagoo, AS, Bernal-Mizrachi, L, Mann, KP, Flowers, CR, Naresh, KN, Evens, AM, Chadburn, A, Gordon, LI, Czader, MB, Gill, JI, Hsi, ED, Greenough, A, Moffitt, AB, McKinney, M, Banerjee, A, Grubor, V, Levy, S, Dunson, DB, and Dave, SS. "The genetic landscape of mutations in Burkitt lymphoma." Nat Genet 44.12 (December 2012): 1321-1325.
PMID
23143597
Source
pubmed
Published In
Nature Genetics
Volume
44
Issue
12
Publish Date
2012
Start Page
1321
End Page
1325
DOI
10.1038/ng.2468

Phase II Study of VEGF Inhibitor, PTK787/ZK222584, in Patients with Refractory or Relapsed Diffuse Large B-Cell Lymphoma

Authors
Brander, DM; Beaven, AW; Gockerman, JP; Diehl, LF; Gasparetto, C; Shea, TC; deCastro, C; Moore, JO; Rizzieri, DA
MLA Citation
Brander, DM, Beaven, AW, Gockerman, JP, Diehl, LF, Gasparetto, C, Shea, TC, deCastro, C, Moore, JO, and Rizzieri, DA. "Phase II Study of VEGF Inhibitor, PTK787/ZK222584, in Patients with Refractory or Relapsed Diffuse Large B-Cell Lymphoma." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Pilot Study of Sorafenib for Myelodysplastic Syndrome

Authors
Rao, A; Rizzieri, DA; Vanegas, E; Moore, JO; Gockerman, JP; Diehl, LF; Adams, D; Warzecho, J; Decastro, C
MLA Citation
Rao, A, Rizzieri, DA, Vanegas, E, Moore, JO, Gockerman, JP, Diehl, LF, Adams, D, Warzecho, J, and Decastro, C. "Pilot Study of Sorafenib for Myelodysplastic Syndrome." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Phase 1 Study of Lenalidomide and Decitabine for High and Intermediate 2 Risk MDS

Authors
Rao, A; Khan, G; Rizzieri, DA; Moore, JO; Gockerman, JP; Diehl, LF; Beaven, AW; Adams, D; Warzecho, J; Decastro, C
MLA Citation
Rao, A, Khan, G, Rizzieri, DA, Moore, JO, Gockerman, JP, Diehl, LF, Beaven, AW, Adams, D, Warzecho, J, and Decastro, C. "Phase 1 Study of Lenalidomide and Decitabine for High and Intermediate 2 Risk MDS." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

ID3 Is a Novel Tumor Suppressor Gene in Burkitt Lymphom

Authors
Love, CL; Jima, D; Sun, Z; Miles, RR; Dunphy, CH; Choi, WWL; Au, WY; Srivastava, G; Lugar, P; Rizzieri, DA; Lagoo, AS; Bernal-Mizrachi, L; Mann, KP; Flowers, CR; Naresh, K; Evens, AM; Chadburn, A; Gordon, LI; Czader, M; Gill, J; Hsi, ED; Zhang, J; Grubor, V; Levy, S; Bunerjee, A; Dunson, D; Li, G; Moffitt, A; Greenough, A; McKinney, MS; Dave, SS
MLA Citation
Love, CL, Jima, D, Sun, Z, Miles, RR, Dunphy, CH, Choi, WWL, Au, WY, Srivastava, G, Lugar, P, Rizzieri, DA, Lagoo, AS, Bernal-Mizrachi, L, Mann, KP, Flowers, CR, Naresh, K, Evens, AM, Chadburn, A, Gordon, LI, Czader, M, Gill, J, Hsi, ED, Zhang, J, Grubor, V, Levy, S, Bunerjee, A, Dunson, D, Li, G, Moffitt, A, Greenough, A, McKinney, MS, and Dave, SS. "ID3 Is a Novel Tumor Suppressor Gene in Burkitt Lymphom." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

A Phase 2 Trial of Imatinib Mesylate As Maintenance Therapy for Patients with Newly Diagnosed C-Kit Positive Acute Myeloid Leukemia (AML)

Authors
Advani, A; Cooper, B; Sowunmi, O; Elson, P; Ali-Osman, F; Park, J; Rao, A; Rizzieri, DA; Wang, ES; Cotta, C; Sekeres, MA; Kalaycio, M; Sobecks, R; Rouphail, B; Maciejewski, JP; Davis, R; Bailey, L; Foster, B; Rush, ML; Adams, D; Tse, W
MLA Citation
Advani, A, Cooper, B, Sowunmi, O, Elson, P, Ali-Osman, F, Park, J, Rao, A, Rizzieri, DA, Wang, ES, Cotta, C, Sekeres, MA, Kalaycio, M, Sobecks, R, Rouphail, B, Maciejewski, JP, Davis, R, Bailey, L, Foster, B, Rush, ML, Adams, D, and Tse, W. "A Phase 2 Trial of Imatinib Mesylate As Maintenance Therapy for Patients with Newly Diagnosed C-Kit Positive Acute Myeloid Leukemia (AML)." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Results From the Dose Escalation Phase of a Randomized Phase 1-2 First-in-Human (FIH) Study of SGI-110, a Novel Low Volume Stable Subcutaneous (SQ) Second Generation Hypomethylating Agent (HMA) in Patients with Relapsed/Refractory MDS and AML

Authors
Kantarjian, HM; Roboz, GJ; Rizzieri, DA; Stock, W; O'Connell, CL; Griffiths, EA; Yee, K; Tibes, R; Garcia-Manero, G; Ravandi, F; Walsh, K; Feldman, E; Ritchie, E; Rao, A; Decastro, C; Schimmer, AD; Mesa, RA; Syed, I; Choy, G; Oganesian, A; Taverna, P; Azab, M; Chung, W; Issa, J-P
MLA Citation
Kantarjian, HM, Roboz, GJ, Rizzieri, DA, Stock, W, O'Connell, CL, Griffiths, EA, Yee, K, Tibes, R, Garcia-Manero, G, Ravandi, F, Walsh, K, Feldman, E, Ritchie, E, Rao, A, Decastro, C, Schimmer, AD, Mesa, RA, Syed, I, Choy, G, Oganesian, A, Taverna, P, Azab, M, Chung, W, and Issa, J-P. "Results From the Dose Escalation Phase of a Randomized Phase 1-2 First-in-Human (FIH) Study of SGI-110, a Novel Low Volume Stable Subcutaneous (SQ) Second Generation Hypomethylating Agent (HMA) in Patients with Relapsed/Refractory MDS and AML." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

SL-401, A Targeted Therapy Directed to the Interleukin-3 Receptor Present On Leukemia Blasts and Cancer Stem Cells, Is Active As a Single Agent in Patients with Advanced AML

Authors
Konopleva, M; Hogge, DE; Rizzieri, DA; Cirrito, TP; Kornblau, SM; Borthakur, G; Bivins, C; Garcia-Manero, G; Kadia, TM; Ravandi, F; Andreeff, M; Cortes, JE; Hoberman, K; Szarek, M; Rowinsky, E; Bergstein, I; Kantarjian, HM; Frankel, AE
MLA Citation
Konopleva, M, Hogge, DE, Rizzieri, DA, Cirrito, TP, Kornblau, SM, Borthakur, G, Bivins, C, Garcia-Manero, G, Kadia, TM, Ravandi, F, Andreeff, M, Cortes, JE, Hoberman, K, Szarek, M, Rowinsky, E, Bergstein, I, Kantarjian, HM, and Frankel, AE. "SL-401, A Targeted Therapy Directed to the Interleukin-3 Receptor Present On Leukemia Blasts and Cancer Stem Cells, Is Active As a Single Agent in Patients with Advanced AML." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

A Phase II Study of Elacytarabine/Idarubicin As Second Course Remission-Induction in Patients with Acute Myeloid Leukemia Who Failed Cytarabine/Anthracycline

Authors
Rizzieri, DA; Vey, N; Thomas, X; Huguet, F; Schlenk, RF; Krauter, J; Kindler, T; Gjertsen, B; Blau, IW; Johansen, M; Bergeland, T; Gianella-Borradori, A; Jacobsen, TF; Rao, J; Krug, U
MLA Citation
Rizzieri, DA, Vey, N, Thomas, X, Huguet, F, Schlenk, RF, Krauter, J, Kindler, T, Gjertsen, B, Blau, IW, Johansen, M, Bergeland, T, Gianella-Borradori, A, Jacobsen, TF, Rao, J, and Krug, U. "A Phase II Study of Elacytarabine/Idarubicin As Second Course Remission-Induction in Patients with Acute Myeloid Leukemia Who Failed Cytarabine/Anthracycline." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and matched unrelated donor hematopoietic cell transplantation.

Immunologic reconstitution after allogeneic hematopoietic cell transplantation is a critical component of successful outcome. Umbilical cord blood (UCB) transplantation in adult recipients is associated with slow and often inadequate immune recovery. We characterized the kinetics and extent of immune recovery in 95 adult recipients after a dual UCB (n = 29) and matched sibling donor (n = 33) or matched unrelated donor (n = 33) transplantation. All patients were treated with myeloablative conditioning. There were no differences in the immune recovery profile of matched sibling donor and matched unrelated donor recipients. Significantly lower levels of CD3+, CD4+, and CD8+ T cells were observed in UCB recipients until 6 months after transplantation. Lower levels of regulatory T cells persisted until 1 year after transplantation. Thymopoiesis as measured by TCR rearrangement excision circle was comparable among all recipients by 6 months after transplantation. In a subset of patients 1 year after transplantation with similar levels of circulating T cells and TCR rearrangement excision circle, there was no difference in TCR diversity. Compared to HLA-identical matched sibling donor and matched unrelated donor adult hematopoietic cell transplantation recipients, quantitative lymphoid recovery in UCB transplantation recipients is slower in the first 3 months, but these differences disappeared by 6 to 12 months after transplantation.

Authors
Kanda, J; Chiou, L-W; Szabolcs, P; Sempowski, GD; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; McPherson, J; Hale, J; Livingston, JA; Broadwater, G; Niedzwiecki, D; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Chiou, L-W, Szabolcs, P, Sempowski, GD, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, McPherson, J, Hale, J, Livingston, JA, Broadwater, G, Niedzwiecki, D, Chao, NJ, and Horwitz, ME. "Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and matched unrelated donor hematopoietic cell transplantation." Biol Blood Marrow Transplant 18.11 (November 2012): 1664-1676.e1.
PMID
22698485
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
11
Publish Date
2012
Start Page
1664
End Page
1676.e1
DOI
10.1016/j.bbmt.2012.06.005

Mini test dose of intravenous busulfan (busulfex(®)) in allogeneic non-myeloablative stem cell transplantation, followed by liquid chromatography tandem-mass spectrometry.

Authors
Spasojevic, I; da Costa, LRS; Horwitz, ME; Long, GD; Sullivan, KM; Chute, JP; Gasparetto, C; Morris, A; Chao, NJ; Rizzieri, DA
MLA Citation
Spasojevic, I, da Costa, LRS, Horwitz, ME, Long, GD, Sullivan, KM, Chute, JP, Gasparetto, C, Morris, A, Chao, NJ, and Rizzieri, DA. "Mini test dose of intravenous busulfan (busulfex(®)) in allogeneic non-myeloablative stem cell transplantation, followed by liquid chromatography tandem-mass spectrometry." Cancer Invest 30.9 (November 2012): 679-682.
PMID
23020519
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
30
Issue
9
Publish Date
2012
Start Page
679
End Page
682
DOI
10.3109/07357907.2012.726386

Elacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia.

Elacytarabine is a novel cytotoxic nucleoside analogue, independent of nucleoside transporters (e.g. human Equilibrative Nucleoside Transporter 1 [hENT1]) for cell uptake, and mechanisms of action similar to those of cytarabine. This Phase II study assessed the efficacy and safety of elacytarabine in patients with advanced stage acute myeloid leukaemia (AML). Patients received 2000 mg/m(2) per d continuously i.v. during days 1-5 every 3 weeks. Patients were matched by six risk factors with historical controls; remission rate (assessed after 1 or 2 cycles) and 6-month survival were compared. Sixty-one patients, median age 58 years, were enrolled; 52% had five or six risk factors. The remission rate was 18% (95% confidence interval: 9-30%) vs. 4% in controls (P < 0·0001), 6-month survival rate was 43%, median overall survival was 5·3 months (vs. 1·5 months); 10 patients (16%) were referred for stem cell transplantation after treatment. Side effects were predictable and manageable. The most common grade 3/4 non-haematological adverse events were febrile neutropenia, hypokalemia, fatigue, hyponatraemia, dyspnoea and pyrexia. Thirty-day all-cause mortality, after start of treatment, was 13% vs. 25% in controls. Elacytarabine has monotherapy activity in patients with advanced AML. This study provides proof-of-concept that lipid esterification of nucleoside analogues is clinically relevant.

Authors
O'Brien, S; Rizzieri, DA; Vey, N; Ravandi, F; Krug, UO; Sekeres, MA; Dennis, M; Venditti, A; Berry, DA; Jacobsen, TF; Staudacher, K; Bergeland, T; Giles, FJ
MLA Citation
O'Brien, S, Rizzieri, DA, Vey, N, Ravandi, F, Krug, UO, Sekeres, MA, Dennis, M, Venditti, A, Berry, DA, Jacobsen, TF, Staudacher, K, Bergeland, T, and Giles, FJ. "Elacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia." Br J Haematol 158.5 (September 2012): 581-588.
PMID
22702906
Source
pubmed
Published In
British Journal of Haematology
Volume
158
Issue
5
Publish Date
2012
Start Page
581
End Page
588
DOI
10.1111/j.1365-2141.2012.09186.x

Preemptive dosing of plerixafor given to poor stem cell mobilizers on day 5 of G-CSF administration.

Plerixafor, given on day 4 of G-CSF treatment is more effective than G-CSF alone in mobilizing hematopoietic progenitor cells. We tested a strategy of preemptive plerixafor use following assessment of the peak mobilization response to 5 days of G-CSF. Patients were eligible for plerixafor if, on day 5 of G-CSF, there were <7 circulating CD34+ cells/μL or if <1.3 × 10(6) CD34+ cells/kg were collected on the first day of apheresis. Plerixafor (0.24 mg/kg s.c.) was given on day 5 of G-CSF followed by apheresis on day 6. This was repeated for up to two additional doses of plerixafor. The primary end point of the study was the percentage of patients who collected at least 2 × 10(6) CD34+ cells/kg. Twenty candidates for auto-SCT enrolled on the trial. The circulating CD34+ cell level increased a median of 3.1 fold (range 1-8 fold) after the first dose of plerixafor and a median of 1.2 fold (range 0.3-6.5 fold) after the second dose of plerixafor. In all, 15 out of 20 (75%) patients achieved the primary end point. In conclusion, the decision to administer plerixafor can be delayed until after the peak mobilization response to G-CSF has been fully assessed.

Authors
Horwitz, ME; Chute, JP; Gasparetto, C; Long, GD; McDonald, C; Morris, A; Rizzieri, DA; Sullivan, KM; Chao, NJ
MLA Citation
Horwitz, ME, Chute, JP, Gasparetto, C, Long, GD, McDonald, C, Morris, A, Rizzieri, DA, Sullivan, KM, and Chao, NJ. "Preemptive dosing of plerixafor given to poor stem cell mobilizers on day 5 of G-CSF administration." Bone Marrow Transplant 47.8 (August 2012): 1051-1055.
PMID
22080963
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
47
Issue
8
Publish Date
2012
Start Page
1051
End Page
1055
DOI
10.1038/bmt.2011.217

Phase I and pharmacokinetic study of elacytarabine, a novel 5'-elaidic acid derivative of cytarabine, in adults with refractory hematological malignancies.

Authors
Giles, FJ; Vey, N; Rizzieri, D; Ravandi, F; Prebet, T; Borthakur, G; Jacobsen, TF; Hagen, S; Nilsson, B; O'Brien, S
MLA Citation
Giles, FJ, Vey, N, Rizzieri, D, Ravandi, F, Prebet, T, Borthakur, G, Jacobsen, TF, Hagen, S, Nilsson, B, and O'Brien, S. "Phase I and pharmacokinetic study of elacytarabine, a novel 5'-elaidic acid derivative of cytarabine, in adults with refractory hematological malignancies." Leukemia 26.7 (July 2012): 1686-1689. (Letter)
PMID
22222600
Source
pubmed
Published In
Leukemia
Volume
26
Issue
7
Publish Date
2012
Start Page
1686
End Page
1689
DOI
10.1038/leu.2012.1

Alternate donor hematopoietic cell transplantation (HCT) in non-Hodgkin lymphoma using lower intensity conditioning: a report from the CIBMTR.

We analyzed the outcomes of 248 (61% male) adult recipients of HLA-matched unrelated and HLA-mismatched related donor hematopoietic cell transplantation (HCT) for non-Hodgkin lymphoma (NHL) after reduced or lower intensity conditioning (RIC), reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1997 to 2004. Median age was 52 (range: 18-72 years); 31% had a Karnofsky performance score <90. Follicular NHL (43%) was the major histology. Incidence of grades II-IV acute graft-versus-host disease (aGVHD) was 43% at 100 days; and chronic GVHD (cGVHD) was 44% at 3 years. Treatment-related mortality (TRM) at 100 days was 24%. Three-year overall survival (OS) and progression-free survival (PFS) were 41% and 32%, respectively. In multivariate analysis, use of antithymocyte globulin (ATG) and HLA mismatch were associated with increased TRM. High-grade histology, ATG use, and chemotherapy resistance were associated with lower PFS. Older age, shorter interval from diagnosis to HCT, non-total body irridiation (TBI) conditioning regimens, ex vivo T cell depletion, and HLA-mismatched unrelated donors were associated with mortality. GVHD did not influence relapse or PFS. Older age, aggressive histology, and chemotherapy resistance correlated with poorer survival. For selected patients with NHL, lack of an available sibling donor should not be a barrier to allogeneic HCT.

Authors
Hale, GA; Shrestha, S; Le-Rademacher, J; Burns, LJ; Gibson, J; Inwards, DJ; Freytes, CO; Bolwell, BJ; Hsu, JW; Slavin, S; Isola, L; Rizzieri, DA; Gale, RP; Laport, GG; Montoto, S; Lazarus, HM; Hari, PN
MLA Citation
Hale, GA, Shrestha, S, Le-Rademacher, J, Burns, LJ, Gibson, J, Inwards, DJ, Freytes, CO, Bolwell, BJ, Hsu, JW, Slavin, S, Isola, L, Rizzieri, DA, Gale, RP, Laport, GG, Montoto, S, Lazarus, HM, and Hari, PN. "Alternate donor hematopoietic cell transplantation (HCT) in non-Hodgkin lymphoma using lower intensity conditioning: a report from the CIBMTR." Biol Blood Marrow Transplant 18.7 (July 2012): 1036-1043.e1.
PMID
22155506
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
7
Publish Date
2012
Start Page
1036
End Page
1043.e1
DOI
10.1016/j.bbmt.2011.11.026

Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR) on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors.

The impact of activating KIR (aKIR) and inhibitory KIR (iKIR) on OS, relapse-related mortality (RRM) and acute GVHD (aGVHD) was prospectively studied in 84 adults with high-risk hematologic malignancies receiving reduced intensity conditioning (RIC) T-cell depleted hematopoietic SCT (HSCT) from haploidentical related donors. In this clinical model, freedom from RRM is dependent on GVL effect. Patients were divided into myeloid (n=49) and lymphoid (n=35) malignancy groups. KIR-ligand and ligand-ligand models were studied in both GVH and rejection directions and statistically correlated with outcome measures. In the myeloid group, OS was higher (P=0.009) and RRM was lower (P=0.036) in patients missing HLA-C group2 ligand to donor iKIR. OS was higher if patients had >1 missing ligand (P=0.018). In lymphoid malignancy, missing ligand to donor KIR had no impact on OS or RRM. However, OS was better with donor aKIR 2DS2 (P=0.028). There was a trend towards shorter OS in recipient with KIR 2DS1, 2DS5 and 3DS1, although sample sizes were too small to provide inferential statistics. Findings in lymphoid malignancy patients should be further studied. These results suggest that the absence of appropriate HLA ligands in the recipient to donor iKIR may induce GVL without aGVHD in myeloid malignancy patients undergoing TCD-RIC transplants.

Authors
Chen, D-F; Prasad, VK; Broadwater, G; Reinsmoen, NL; DeOliveira, A; Clark, A; Sullivan, KM; Chute, JP; Horwitz, ME; Gasparetto, C; Long, GD; Yang, Y; Chao, NJ; Rizzieri, DA
MLA Citation
Chen, D-F, Prasad, VK, Broadwater, G, Reinsmoen, NL, DeOliveira, A, Clark, A, Sullivan, KM, Chute, JP, Horwitz, ME, Gasparetto, C, Long, GD, Yang, Y, Chao, NJ, and Rizzieri, DA. "Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR) on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors." Bone Marrow Transplant 47.6 (June 2012): 817-823.
PMID
22139069
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
47
Issue
6
Publish Date
2012
Start Page
817
End Page
823
DOI
10.1038/bmt.2011.181

Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: a CIBMTR analysis.

Allogeneic hematopoietic SCT is an effective treatment in accelerated (AP) or blast phase (BP) CML. Imatinib (IM) has transient but significant activity in advanced phases of CML, which may permit early allografting for responding patients. To identify prognostic factors in allograft recipients previously treated with IM, we analyzed 449 allogeneic hematopoietic SCTs performed from 1999 to 2004 in advanced-phase CML, using the data reported to the Center for International Blood and Marrow Transplant Research. CML patients in second chronic phase (CP2, n=184), AP (n=185) and BP (n=80) received HLA-identical sibling (27%), related (3%), or matched or mismatched unrelated donor (70%), peripheral blood (47%) or BM (53%) hematopoietic SCT after myeloablative (78%) or non-myeloablative (22%) conditioning. In all, 52% in CP2, 49% in AP and 46% in BP received IM before hematopoietic SCT. Disease-free survival was 35-40% for CP2, 26-27% for AP and 8-11% for BP. Cumulative incidence of acute and chronic GVHD and TRM were not affected by the stages of CML or pre-hematopoietic SCT IM exposure. Multivariate analyses showed that conventional prognostic indicators remain the strongest determinants of transplant outcomes. In conclusion, there are no new prognostic indicators of the outcomes of allogeneic hematopoietic SCT for advanced-phase CML in the IM era.

Authors
Khoury, HJ; Kukreja, M; Goldman, JM; Wang, T; Halter, J; Arora, M; Gupta, V; Rizzieri, DA; George, B; Keating, A; Gale, RP; Marks, DI; McCarthy, PL; Woolfrey, A; Szer, J; Giralt, SA; Maziarz, RT; Cortes, J; Horowitz, MM; Lee, SJ
MLA Citation
Khoury, HJ, Kukreja, M, Goldman, JM, Wang, T, Halter, J, Arora, M, Gupta, V, Rizzieri, DA, George, B, Keating, A, Gale, RP, Marks, DI, McCarthy, PL, Woolfrey, A, Szer, J, Giralt, SA, Maziarz, RT, Cortes, J, Horowitz, MM, and Lee, SJ. "Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: a CIBMTR analysis." Bone Marrow Transplant 47.6 (June 2012): 810-816.
PMID
21986636
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
47
Issue
6
Publish Date
2012
Start Page
810
End Page
816
DOI
10.1038/bmt.2011.194

Outcomes of a 1-day nonmyeloablative salvage regimen for patients with primary graft failure after allogeneic hematopoietic cell transplantation.

Primary graft failure after allogeneic hematopoietic cell transplantation is a life-threatening complication. A shortened conditioning regimen may reduce the risk of infection and increase the chance of survival. Here, we report the outcome of 11 patients with hematologic diseases (median age, 44; range, 25-67 years, seven males) who received a 1-day reduced-intensity preparative regimen given as a re-transplantation for primary graft failure. The salvage regimen consisted of fludarabine, cyclophosphamide, alemtuzumab and TBI, all administered 1 day before re-transplantation. All patients received T-cell replete PBSCs from the same or a different haploidentical donor (n=10) or from the same matched sibling donor (n=1). Neutrophil counts promptly increased to >500/μL for 10 of the 11 patients at a median of 13 days. Of these, none developed grade III/IV acute GVHD. At present, 8 of the 11 patients are alive with a median follow-up of 11.2 months from re-transplantation and 5 of the 8 are in remission. In conclusion, this series suggests that our 1-day preparative regimen is feasible, leads to successful engraftment in a high proportion of patients, and is appropriate for patients requiring immediate re-transplantation after primary graft failure following reduced-intensity transplantation.

Authors
Kanda, J; Horwitz, ME; Long, GD; Gasparetto, C; Sullivan, KM; Chute, JP; Morris, A; Hennig, T; Li, Z; Chao, NJ; Rizzieri, DA
MLA Citation
Kanda, J, Horwitz, ME, Long, GD, Gasparetto, C, Sullivan, KM, Chute, JP, Morris, A, Hennig, T, Li, Z, Chao, NJ, and Rizzieri, DA. "Outcomes of a 1-day nonmyeloablative salvage regimen for patients with primary graft failure after allogeneic hematopoietic cell transplantation." Bone Marrow Transplant 47.5 (May 2012): 700-705.
PMID
21804612
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
47
Issue
5
Publish Date
2012
Start Page
700
End Page
705
DOI
10.1038/bmt.2011.158

Elacytarabine, a novel 5'-elaidic acid derivative of cytarabine, and idarubicin combination is active in refractory acute myeloid leukemia.

Authors
Giles, F; Rizzieri, D; Ravandi, F; Swords, R; Jacobsen, TF; O'Brien, S
MLA Citation
Giles, F, Rizzieri, D, Ravandi, F, Swords, R, Jacobsen, TF, and O'Brien, S. "Elacytarabine, a novel 5'-elaidic acid derivative of cytarabine, and idarubicin combination is active in refractory acute myeloid leukemia." Leuk Res 36.4 (April 2012): e71-e73. (Letter)
PMID
22226018
Source
pubmed
Published In
Leukemia Research: clinical and laboratory studies
Volume
36
Issue
4
Publish Date
2012
Start Page
e71
End Page
e73
DOI
10.1016/j.leukres.2011.12.010

Phase II study of cenersen, an antisense inhibitor of p53, in combination with fludarabine, cyclophosphamide and rituximab for high-risk chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) with deletion or mutation of TP53 have exceedingly poor clinical outcomes. Cenersen, an oligonucleotide targeting TP53, has been shown to abrogate the activity of TP53 gain-of-function mutants and to increase sensitivity of lymphoma cells to cytotoxic chemotherapy in vitro. We combined cenersen with fludarabine, cyclophosphamide and rituximab (FCR) as treatment for patients with high-risk CLL. The purpose of this phase II study was to determine the overall response rate, response duration and toxicity of cenersen administered in combination with FCR. Twenty patients with relapsed or high-risk CLL were evaluated. Nineteen patients were previously treated. The complete response rate was 18%; the overall response rate was 53%. Median progression-free and overall survival was 5.3 and 10.6 months, respectively. The most common serious adverse events were neutropenia and thrombocytopenia. In this single arm phase II study, cenersen combined with FCR yielded clinical responses with acceptable toxicity in patients with high-risk CLL.

Authors
Lanasa, MC; Davis, PH; Datto, M; Li, Z; Gockerman, JP; Moore, JO; DeCastro, CM; Friedman, DR; Diehl, LF; Rehder, C; Cook, H; Daugherty, FJ; Matta, KMB; Weinberg, JB; Rizzieri, D
MLA Citation
Lanasa, MC, Davis, PH, Datto, M, Li, Z, Gockerman, JP, Moore, JO, DeCastro, CM, Friedman, DR, Diehl, LF, Rehder, C, Cook, H, Daugherty, FJ, Matta, KMB, Weinberg, JB, and Rizzieri, D. "Phase II study of cenersen, an antisense inhibitor of p53, in combination with fludarabine, cyclophosphamide and rituximab for high-risk chronic lymphocytic leukemia." Leuk Lymphoma 53.2 (February 2012): 218-224.
PMID
21827374
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
53
Issue
2
Publish Date
2012
Start Page
218
End Page
224
DOI
10.3109/10428194.2011.610012

Chemoimmunotherapy's potential to impact paroxysmal nocturnal hemoglobinuria.

Authors
Rizzieri, DA; Walsh, K
MLA Citation
Rizzieri, DA, and Walsh, K. "Chemoimmunotherapy's potential to impact paroxysmal nocturnal hemoglobinuria." Clin Adv Hematol Oncol 10.2 (February 2012): 136-137. (Review)
PMID
22402360
Source
pubmed
Published In
Clinical advances in hematology & oncology : H&O
Volume
10
Issue
2
Publish Date
2012
Start Page
136
End Page
137

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

Phase I study of dose dense induction and consolidation with gemtuzumab ozogamicin and high dose cytarabine in older adults with AML

Objective: Older adults with acute myeloid leukemia (AML) tend to have worse complete remission (CR) rates and overall survival compared to their younger counterparts. At least one reason for this is increased expression of the multidrug resistance gene (MDR1). Dose dense, high intensity chemotherapy may overcome the MDR1 effect, possibly when combined with anti-CD33 monoclonal antibody gemtuzumab ozogamicin (GO,Mylotarg™), which has been studied in older adults with relapsed AML. This phase I study was aimed at establishing safety by defining a maximum tolerated dose (MTD) by treating older AML patients with two cycles of dose-dense therapy with high dose cytarabine (HiDAC) combined with targeted therapy using GO. Materials and methods: Nine patients ≥60years with newly diagnosed, untreated CD33+ AML with adequate renal and hepatic function, and ECOG PS 0-2 were eligible. HiDAC was administered at two dose levels: 3000mg/m 2 every 12h for 6 doses (cohort 1), or 9 doses (cohort 2). GO was administered at 6mg/m 2 on days 1 and 8. Results: The MTD was HiDAC 3000mg/m 2 for six doses along with GO 6mg/m 2. All patients had grades 3-4 pancytopenia, and two patients developed reversible grade 2 neurotoxicity. There were no cases of veno-occlusive disease. Seven of nine patients had a complete response (CR or CRp). Conclusions: There was no difference in relapse-free survival in our patients when compared to historical data. However, despite high toxicity, two of nine patients treated in this dose-dense fashion remained in CR for > 60 months. © 2012 Elsevier Inc.

Authors
Rao, AV; Rizzieri, DA; DeCastro, CM; Diehl, LF; Lagoo, AS; Moore, JO; Gockerman, JP
MLA Citation
Rao, AV, Rizzieri, DA, DeCastro, CM, Diehl, LF, Lagoo, AS, Moore, JO, and Gockerman, JP. "Phase I study of dose dense induction and consolidation with gemtuzumab ozogamicin and high dose cytarabine in older adults with AML." Journal of Geriatric Oncology 3.3 (2012): 220-227.
Source
scival
Published In
Journal of Geriatric Oncology
Volume
3
Issue
3
Publish Date
2012
Start Page
220
End Page
227
DOI
10.1016/j.jgo.2012.02.002

Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: Results from the CLASSIC I trial

Purpose:To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm) with cytarabine (Ara-C arm) in patients ≥ 55 years old with refractory or relapsed acute myelogenous leukemia (AML). Patients and Methods: Patients were randomly assigned to receive either clofarabine (Clo) 40 mg/m 2 or a placebo followed by Ara-C 1 g/m 2 for five consecutive days. The primary end point was overall survival (OS). Secondary end points included event-free survival (EFS), 4-month EFS, overall remission rate (ORR; complete remission [CR] plus CR with incomplete peripheral blood count recovery), disease-free survival (DFS), duration of remission (DOR), and safety. Results: Among 320 patients with confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara-C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9% in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P <.01) and 4-month EFS (37.7% v 16.6%; P <.01) favored the Clo+Ara-C arm compared with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30-day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively), thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively), anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively). Conclusion: Although the primary end point of OS did not differ between arms, Clo+Ara-C significantly improved response rates and EFS. Study follow-up continues, and the role of clofarabine in the treatment of adult patients with AML continues to be investigated. © 2012 by American Society of Clinical Oncology.

Authors
Faderl, S; Wetzler, M; Rizzieri, D; Schiller, G; Jagasia, M; Stuart, R; Ganguly, S; Avigan, D; Craig, M; Collins, R; Maris, M; Kovacsovics, T; Goldberg, S; Seiter, K; Hari, P; Greiner, J; Vey, N; Recher, C; Ravandi, F; Wang, ES; Vasconcelles, M; Huebner, D; Kantarjian, HM
MLA Citation
Faderl, S, Wetzler, M, Rizzieri, D, Schiller, G, Jagasia, M, Stuart, R, Ganguly, S, Avigan, D, Craig, M, Collins, R, Maris, M, Kovacsovics, T, Goldberg, S, Seiter, K, Hari, P, Greiner, J, Vey, N, Recher, C, Ravandi, F, Wang, ES, Vasconcelles, M, Huebner, D, and Kantarjian, HM. "Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: Results from the CLASSIC I trial." Journal of Clinical Oncology 30.20 (2012): 2492-2499.
PMID
22585697
Source
scival
Published In
Journal of Clinical Oncology
Volume
30
Issue
20
Publish Date
2012
Start Page
2492
End Page
2499
DOI
10.1200/JCO.2011.37.9743

Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: A phase 3, multicentre, open-label, randomised trial

Background: Pixantrone dimaleate (pixantrone)-a novel aza-anthracenedione-was synthesised to reduce anthracycline-related cardiotoxicity without compromising antitumour efficacy. We aimed to assess the efficacy and safety of pixantrone versus an investigator's choice of a single-agent therapy in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma. Methods: In this phase 3, multicentre, open-label, randomised trial at 66 hospitals in Europe, India, Russia, South America, the UK, and the USA, patients with histologically confirmed aggressive non-Hodgkin lymphoma who had relapsed after two or more previous chemotherapy regimens were randomly assigned (1:1) by an interactive voice response system to treatment with pixantrone dimaleate (85 mg/m2 intravenously on days 1, 8, and 15 of a 28-day cycle, for up to six cycles) or to a comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide, mitoxantrone, or gemcitabine) given at prespecified standard doses and schedules. Patients were stratified by region, International Prognostic Index score, and previous stem-cell transplantation. Patients and investigators were not masked to treatment assignment; however, an independent assessment panel was masked. The primary endpoint was the proportion of patients with a complete or unconfirmed complete response in the intention-to-treat (ITT) population at the end of treatment. Primary analyses of efficacy were based on the independent assessment panel's data review. The study is registered at ClinicalTrials.gov, number NCT00088530. Findings: The ITT population comprised 70 patients randomly assigned to the pixantrone group and 70 to the comparator. Five patients (two in the pixantrone group and three in the comparator group) dropped out before receiving their study drug. 14 patients (20·0% [95% CI 11·4-31·3]) who received pixantrone achieved a complete or unconfirmed complete response at end of treatment compared with four patients (5·7% [1·6-14·0]) in the comparator group (p = 0·021). The most common grade 3 or 4 adverse events in patients given pixantrone were uncomplicated, non-cumulative neutropenia (28 [41·2%] of 68 patients vs 13 [19·4%] of 67 patients in the comparator group), leucopenia (16 [23·5%] vs five [7·5%]), and thrombocytopenia (eight [11·8%] vs seven [10·4%]). Interpretation: Pixantrone, given as a single-agent salvage therapy in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma, is efficacious and tolerable. It could be a treatment option for patients whose aggressive non-Hodgkin lymphoma has failed to respond to at least two previous chemotherapy regimens. Funding: Cell Therapeutics, Inc. © 2012 Elsevier Ltd.

Authors
Pettengell, R; Coiffier, B; Narayanan, G; Mendoza, FHD; Digumarti, R; Gomez, H; Zinzani, PL; Schiller, G; Rizzieri, D; Boland, G; Cernohous, P; Wang, L; Kuepfer, C; Gorbatchevsky, I; Singer, JW
MLA Citation
Pettengell, R, Coiffier, B, Narayanan, G, Mendoza, FHD, Digumarti, R, Gomez, H, Zinzani, PL, Schiller, G, Rizzieri, D, Boland, G, Cernohous, P, Wang, L, Kuepfer, C, Gorbatchevsky, I, and Singer, JW. "Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: A phase 3, multicentre, open-label, randomised trial." The Lancet Oncology 13.7 (2012): 696-706.
PMID
22652183
Source
scival
Published In
The Lancet Oncology
Volume
13
Issue
7
Publish Date
2012
Start Page
696
End Page
706
DOI
10.1016/S1470-2045(12)70212-7

Implementation of management guidelines for chronic myeloidl leukemia perspectives in the United States

Clinical practice guidelines are developed to improve the quality of care and outcomes for patients. Guidelines facilitate clinical decisions, promote efficient use of health care resources, and provide guidance to practitioners. For chronic myeloid leukemia (CML), tyrosine kinase inhibitors (TKIs) have changed the paradigm of therapy by lowering the disease burden and by providing more precise monitoring of response. These advances affect treatment guidelines for CML and inform CML clinical trial protocols. Guidelines developed by the National Comprehensive Cancer Network (NCCN) and European LeukemiaNet (ELN) synthesize the best available evidence to support decision-making in the management of CML patients. Both guidelines recognize specific milestones for treatment response. At each time point, the ELN guidelines define overall response benchmarks, and the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) provide an algorithm that specifies the timing for evaluations of cytogenetic and molecular parameters during therapy. The NCCN Guidelines also include strategies for providing supportive care and for managing toxicities. Molecular monitoring now plays a greater role in CML management. Molecular response as a milestone is currently recommended by the ELN but has not yet been adopted by the NCCN. As evidence continues to accumulate, the NCCN and ELN Guidelines are likely to evolve to reflect new data and standards of care.

Authors
Rizzieri, D; Moore, JO
MLA Citation
Rizzieri, D, and Moore, JO. "Implementation of management guidelines for chronic myeloidl leukemia perspectives in the United States." P and T 37.11 (2012): 640-648.
Source
scival
Published In
P & T : a peer-reviewed journal for formulary management
Volume
37
Issue
11
Publish Date
2012
Start Page
640
End Page
648

Comparison of reduced-intensity hematopoietic cell transplantation with chemotherapy in patients age 60-70 years with acute myelogenous leukemia in first remission.

We compared the outcomes of patients age 60-70 years with acute myelogenous leukemia receiving reduced-intensity allogeneic hematopoietic cell transplantation (HCT) in first remission (CR1) reported to the Center for International Blood and Marrow Research (n = 94) with the outcomes in patients treated with induction and postremission chemotherapy on Cancer and Leukemia Group B protocols (n = 96). All patients included had been in CR1 for at least 4 months. The HCT recipients were slightly younger than the chemotherapy patients (median age, 63 years vs 65 years; P < .001), but there were no significant between-group differences in the proportion with therapy-related leukemia or in different cytogenetic risk groups. Time from diagnosis to CR1 was longer for the HCT recipients (median, 44 days vs 38 days; P = .031). Allogeneic HCT was associated with significantly lower risk of relapse (32% vs 81% at 3 years; P < .001), higher nonrelapse mortality (36% vs 4% at 3 years; P < .001), and longer leukemia-free survival (32% vs 15% at 3 years; P = .001). Although overall survival was longer for HCT recipients, the difference was not statistically significant (37% vs 25% at 3 years; P = .08). Our findings suggest that reduced-intensity conditioning allogeneic HCT in patients age 60-70 with acute myelogenous leukemia in CR1 reduces relapse and improves leukemia-free survival. Strategies that reduce nonrelapse mortality may yield significant improvements in overall survival.

Authors
Farag, SS; Maharry, K; Zhang, M-J; Pérez, WS; George, SL; Mrózek, K; DiPersio, J; Bunjes, DW; Marcucci, G; Baer, MR; Cairo, M; Copelan, E; Cutler, CS; Isola, L; Lazarus, HM; Litzow, MR; Marks, DI; Ringdén, O; Rizzieri, DA; Soiffer, R; Larson, RA; Tallman, MS; Bloomfield, CD; Weisdorf, DJ; Acute Leukemia Committee of the Center for International Blood and Marrow Transplant Research and Cancer and Leukemia Group B,
MLA Citation
Farag, SS, Maharry, K, Zhang, M-J, Pérez, WS, George, SL, Mrózek, K, DiPersio, J, Bunjes, DW, Marcucci, G, Baer, MR, Cairo, M, Copelan, E, Cutler, CS, Isola, L, Lazarus, HM, Litzow, MR, Marks, DI, Ringdén, O, Rizzieri, DA, Soiffer, R, Larson, RA, Tallman, MS, Bloomfield, CD, Weisdorf, DJ, and Acute Leukemia Committee of the Center for International Blood and Marrow Transplant Research and Cancer and Leukemia Group B, . "Comparison of reduced-intensity hematopoietic cell transplantation with chemotherapy in patients age 60-70 years with acute myelogenous leukemia in first remission." Biol Blood Marrow Transplant 17.12 (December 2011): 1796-1803.
PMID
21699879
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
12
Publish Date
2011
Start Page
1796
End Page
1803
DOI
10.1016/j.bbmt.2011.06.005

High Complete Response Rates with Dose Dense/Dose Intense Chemotherapy Plus Radioimmunotherapy in High Risk Diffuse Large B Cell and Mantle Cell Lymphoma

Authors
Beaven, AW; Rizzieri, DA; Powell, Z; Li, Z; Alton, P; Warzecho, J; Diehl, LF; Moore, JO; III, DCCM; Gockerman, JP
MLA Citation
Beaven, AW, Rizzieri, DA, Powell, Z, Li, Z, Alton, P, Warzecho, J, Diehl, LF, Moore, JO, III, DCCM, and Gockerman, JP. "High Complete Response Rates with Dose Dense/Dose Intense Chemotherapy Plus Radioimmunotherapy in High Risk Diffuse Large B Cell and Mantle Cell Lymphoma." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1152
End Page
1152

Impact of High Dose Cyclophosphamide on the Outcome of Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma

Authors
Bacon, WA; Long, GD; Rizzieri, DA; Horwitz, ME; Chute, JP; Sullivan, KM; Yopp, A; Johns, A; Chao, NJ; Gasparetto, C
MLA Citation
Bacon, WA, Long, GD, Rizzieri, DA, Horwitz, ME, Chute, JP, Sullivan, KM, Yopp, A, Johns, A, Chao, NJ, and Gasparetto, C. "Impact of High Dose Cyclophosphamide on the Outcome of Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1765
End Page
1765

The Impact of Lymphocyte Subset Recovery At 3 Months on Progression-Free Survival After Myeloablative Allogeneic Stem Cell Transplantation

Authors
Kanda, J; Rizzieri, DA; Long, GD; Gasparetto, C; Chute, JP; Sullivan, KM; Morris, A; McPherson, J; Livingston, JA; Broadwater, G; Niedzwiecki, D; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Rizzieri, DA, Long, GD, Gasparetto, C, Chute, JP, Sullivan, KM, Morris, A, McPherson, J, Livingston, JA, Broadwater, G, Niedzwiecki, D, Chao, NJ, and Horwitz, ME. "The Impact of Lymphocyte Subset Recovery At 3 Months on Progression-Free Survival After Myeloablative Allogeneic Stem Cell Transplantation." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1736
End Page
1736

High Dose BCNU/Melphalan Preparative Regimen Doubles Event Free Survival of Myeloma Patients Undergoing Autologous Transplantation

Authors
Gasparetto, C; Bacon, WA; Doan, P; Rizzieri, DA; Horwitz, ME; Chute, JP; Sullivan, KM; Yopp, A; Li, Z; Chao, NJ; Long, GD
MLA Citation
Gasparetto, C, Bacon, WA, Doan, P, Rizzieri, DA, Horwitz, ME, Chute, JP, Sullivan, KM, Yopp, A, Li, Z, Chao, NJ, and Long, GD. "High Dose BCNU/Melphalan Preparative Regimen Doubles Event Free Survival of Myeloma Patients Undergoing Autologous Transplantation." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
879
End Page
879

Whole Genome and Exome Sequencing Reveals the Genetic Landscape of Burkitt Lymphoma

Authors
Love, CL; Jima, D; Zhang, J; Grubor, V; Miles, RR; Dunphy, CH; Richards, KL; Choi, WWL; Au, WY; Srivastava, G; Chadburn, A; Gordon, LI; Evens, AM; Hsi, ED; Czader, M; Rizzieri, DA; Lagoo, AS; Bernal-Mizrachi, L; Mann, KP; Sunay, S; Flowers, CR; Naresh, K; Thompson, MA; Gill, J; Dave, SS
MLA Citation
Love, CL, Jima, D, Zhang, J, Grubor, V, Miles, RR, Dunphy, CH, Richards, KL, Choi, WWL, Au, WY, Srivastava, G, Chadburn, A, Gordon, LI, Evens, AM, Hsi, ED, Czader, M, Rizzieri, DA, Lagoo, AS, Bernal-Mizrachi, L, Mann, KP, Sunay, S, Flowers, CR, Naresh, K, Thompson, MA, Gill, J, and Dave, SS. "Whole Genome and Exome Sequencing Reveals the Genetic Landscape of Burkitt Lymphoma." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
199
End Page
200

Re-Induction Therapy Decisions Based on Day 14 Bone Marrow Biopsy in Acute Myeloid Leukemia

Authors
Morris, TA; Rizzieri, DA; de Castro, CM; Diehl, LF; Gockerman, JP; Lagoo, AS; Moore, JO; Rao, AV
MLA Citation
Morris, TA, Rizzieri, DA, de Castro, CM, Diehl, LF, Gockerman, JP, Lagoo, AS, Moore, JO, and Rao, AV. "Re-Induction Therapy Decisions Based on Day 14 Bone Marrow Biopsy in Acute Myeloid Leukemia." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1532
End Page
1533

Targeting of a Novel MNK-eIF4E-b-Catenin Axis in Blast Crisis Chronic Myelogenous Leukemia Inhibits Leukemia Stem Cell Function

Authors
Lim, S; Saw, TY; Chang, S; Zhang, M; Janes, MR; Fruman, DA; Rizzieri, DA; Tan, S-Y; Chuah, C; Ong, ST
MLA Citation
Lim, S, Saw, TY, Chang, S, Zhang, M, Janes, MR, Fruman, DA, Rizzieri, DA, Tan, S-Y, Chuah, C, and Ong, ST. "Targeting of a Novel MNK-eIF4E-b-Catenin Axis in Blast Crisis Chronic Myelogenous Leukemia Inhibits Leukemia Stem Cell Function." November 18, 2011.
PMID
23737503
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
440
End Page
440

Results of the OPAL Study: A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of Tosedostat (CHR-2797) in Elderly Subjects with Treatment Refractory or Relapsed Acute Myeloid Leukemia

Authors
Cortes, JE; Feldman, EJ; Yee, K; Rizzieri, DA; Advani, AS; Charman, A; Toal, MJ; Kantarjian, HM
MLA Citation
Cortes, JE, Feldman, EJ, Yee, K, Rizzieri, DA, Advani, AS, Charman, A, Toal, MJ, and Kantarjian, HM. "Results of the OPAL Study: A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of Tosedostat (CHR-2797) in Elderly Subjects with Treatment Refractory or Relapsed Acute Myeloid Leukemia." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
348
End Page
348

A Phase II Study of Elacytarabine/Idarubicin As Second Course Remission-Induction in Patients with Acute Myeloid Leukemia Who Failed Cytarabine/Anthracycline, and Evaluation of the Impact of the Nucleoside Transporter hENT1 on Response

Authors
Rizzieri, DA; Vey, N; Schlenk, RF; Thomas, X; Huguet, F; Gjertsen, B; Krauter, J; Blau, IW; Johansen, M; Gianelli-Borradori, A; Jacobsen, TF; Rao, J; Krug, U
MLA Citation
Rizzieri, DA, Vey, N, Schlenk, RF, Thomas, X, Huguet, F, Gjertsen, B, Krauter, J, Blau, IW, Johansen, M, Gianelli-Borradori, A, Jacobsen, TF, Rao, J, and Krug, U. "A Phase II Study of Elacytarabine/Idarubicin As Second Course Remission-Induction in Patients with Acute Myeloid Leukemia Who Failed Cytarabine/Anthracycline, and Evaluation of the Impact of the Nucleoside Transporter hENT1 on Response." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
666
End Page
667

Significance of Prior HSCT on the Outcome of Salvage Therapy with CPX-351 or Conventional Chemotherapy Among First Relapse AML Patients

Authors
Cortes, JE; Feldman, EJ; Goldberg, SL; Rizzieri, DA; Louie, AC; Kolitz, JE
MLA Citation
Cortes, JE, Feldman, EJ, Goldberg, SL, Rizzieri, DA, Louie, AC, and Kolitz, JE. "Significance of Prior HSCT on the Outcome of Salvage Therapy with CPX-351 or Conventional Chemotherapy Among First Relapse AML Patients." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1125
End Page
1125

CPX-351: A Randomized Phase 2b Study of CPX-351 v. Intensive Salvage Therapy in '65 Yo First Relapse AML Patients: Initial Efficacy and Safety Report

Authors
Cortes, JE; Feldman, EJ; Goldberg, SL; Rizzieri, DA; Paulsen, KH; Louie, AC; Kolitz, JE
MLA Citation
Cortes, JE, Feldman, EJ, Goldberg, SL, Rizzieri, DA, Paulsen, KH, Louie, AC, and Kolitz, JE. "CPX-351: A Randomized Phase 2b Study of CPX-351 v. Intensive Salvage Therapy in '65 Yo First Relapse AML Patients: Initial Efficacy and Safety Report." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
116
End Page
116

Severe pulmonary toxicity after myeloablative conditioning using total body irradiation: an assessment of risk factors.

PURPOSE: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. METHODS AND MATERIALS: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. RESULTS: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). CONCLUSIONS: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

Authors
Kelsey, CR; Horwitz, ME; Chino, JP; Craciunescu, O; Steffey, B; Folz, RJ; Chao, NJ; Rizzieri, DA; Marks, LB
MLA Citation
Kelsey, CR, Horwitz, ME, Chino, JP, Craciunescu, O, Steffey, B, Folz, RJ, Chao, NJ, Rizzieri, DA, and Marks, LB. "Severe pulmonary toxicity after myeloablative conditioning using total body irradiation: an assessment of risk factors." Int J Radiat Oncol Biol Phys 81.3 (November 1, 2011): 812-818.
PMID
20932682
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
81
Issue
3
Publish Date
2011
Start Page
812
End Page
818
DOI
10.1016/j.ijrobp.2010.06.058

Adult dual umbilical cord blood transplantation using myeloablative total body irradiation (1350 cGy) and fludarabine conditioning.

High treatment-related mortality (TRM) and high graft failure rate are serious concerns in HLA-mismatched umbilical cord blood (UCB) transplantation with myeloablative conditioning. We conducted a prospective trial of dual UCB transplantation using modified myeloablation consisting of total-body irradiation (TBI; 1350 cGy) and fludarabine (Flu) (160 mg/m(2)). Twenty-seven patients (median age, 33 years; range: 20-58 years) with hematologic malignancies were enrolled. The median combined cryopreserved total nucleated cell (TNC) dose was 4.3 × 10(7)/kg (range: 3.2-7.7 × 10(7)/kg). The cumulative incidences of neutrophil (≥500/μL) and platelet (≥50,000/μL) engraftment were 80% (95% confidence interval [CI], 58%-91%) and 68% (95% CI, 46%-83%), respectively. Among engrafted patients, a single cord blood unit was predominant by 100 days posttransplantation. A higher cryopreserved and infused TNC dose and infused CD3(+) cell dose were significant factors associated with the predominant UCB unit (P = .032, .020, and .042, respectively). TRM and relapse rates at 2 years were 28% (95% CI, 12%-47%) and 20% (95% CI, 7%-37%), respectively. Cumulative incidences of grades II-IV and grades III-IV acute graft-versus-host disease (aGVHD) were 37% (95% CI, 20%-55%) and 11% (95% CI, 3%-26%), respectively, and that of chronic GVHD was 31% (95% CI, 15%-49%). With a median follow-up of 23 months, overall survival and disease-free survival rates at 2 years were 58% (95% CI, 34%-75%) and 52% (95% CI, 29%-70%), respectively. This study supports the use of TBI 1350 cGy/Flu as an alternative to conventional myeloablative conditioning for dual UCB transplantation.

Authors
Kanda, J; Rizzieri, DA; Gasparetto, C; Long, GD; Chute, JP; Sullivan, KM; Morris, A; Smith, CA; Hogge, DE; Nitta, J; Song, K; Niedzwiecki, D; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Rizzieri, DA, Gasparetto, C, Long, GD, Chute, JP, Sullivan, KM, Morris, A, Smith, CA, Hogge, DE, Nitta, J, Song, K, Niedzwiecki, D, Chao, NJ, and Horwitz, ME. "Adult dual umbilical cord blood transplantation using myeloablative total body irradiation (1350 cGy) and fludarabine conditioning." Biol Blood Marrow Transplant 17.6 (June 2011): 867-874.
PMID
20868761
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
6
Publish Date
2011
Start Page
867
End Page
874
DOI
10.1016/j.bbmt.2010.09.009

Histone H4 acetylation by immunohistochemistry and prognosis in relapsed acute lymphocytic leukaemia (ALL).

Histone H4 acetylation was examined by immunohistochemistry in patients with acute lymphocytic leukaemia (ALL) in first relapse. Univariate and multivariate models identified correlates of complete remission (CR) and overall survival (OS). No variables were associated with achievement of CR. In multivariate analysis, weak histone H4 acetylation [Hazard Ratio (HR) 2·20, 95% confidence interval (CI) 0·93-5·23, P=0·07], shorter interval from diagnosis to relapse (<9 vs. 9-24 vs. >24 months) (HR 1·82, 95% CI 1·20-2·75, P= 0·005), and central nervous system involvement (HR 3·43, 95% CI 1·31-8·99, P=0·01) were independent poor prognostic factors for OS. These data provide a rationale for the use of histone deacetylase inhibitors in the treatment of relapsed ALL.

Authors
Advani, AS; Gibson, S; Douglas, E; Diacovo, J; Elson, P; Kalaycio, M; Copelan, E; Sekeres, M; Sobecks, R; Sungren, S; Lagoo, A; Rizzieri, D; Hsi, E
MLA Citation
Advani, AS, Gibson, S, Douglas, E, Diacovo, J, Elson, P, Kalaycio, M, Copelan, E, Sekeres, M, Sobecks, R, Sungren, S, Lagoo, A, Rizzieri, D, and Hsi, E. "Histone H4 acetylation by immunohistochemistry and prognosis in relapsed acute lymphocytic leukaemia (ALL)." Br J Haematol 153.4 (May 2011): 504-507.
PMID
21375525
Source
pubmed
Published In
British Journal of Haematology
Volume
153
Issue
4
Publish Date
2011
Start Page
504
End Page
507
DOI
10.1111/j.1365-2141.2011.08607.x

Donor cell-derived leukemias/myelodysplastic neoplasms in allogeneic hematopoietic stem cell transplant recipients: a clinicopathologic study of 10 cases and a comprehensive review of the literature.

We report 10 cases of donor cell leukemia (DCL). All cases except the case of chronic lymphocytic leukemia had anemia, neutropenia, and/or thrombocytopenia when DCL was diagnosed. Eight cases with sex-mismatched hematopoietic stem cell transplant (HCT) showed donor gonosomal complements, suggesting DCL. Clonal cytogenetic abnormalities were detected in 8 cases: 6 were monosomy 7/del(7q). In all 10 cases, engraftment studies confirmed donor cell origin. Retrospective fluorescence in situ hybridization in archived donor cells in 4 cases showed a low level of abnormalities in 2. Of 7 patients with clinical follow-up of 5 months or more, 1 (with acute myeloid leukemia) died of disease; 6 are alive, including 1 with myelodysplastic syndrome with spontaneous remission. Similar to reported cases, we found disproportional sex-mismatched HCTs, suggesting probable underdetection of DCL in sex-matched HCTs. The latency between HCT and DCL ranged from 1 to 193 months (median, 24 months), in keeping with the literature. Analyzing our cases, pooled with reported cases, with survival models showed much shorter latency for malignancy as primary disease, for T-cell large granular lymphocyte leukemia as type of DCL, and for umbilical cord blood as stem cell source.

Authors
Wang, E; Hutchinson, CB; Huang, Q; Lu, CM; Crow, J; Wang, FF; Sebastian, S; Rehder, C; Lagoo, A; Horwitz, M; Rizzieri, D; Yu, J; Goodman, B; Datto, M; Buckley, P
MLA Citation
Wang, E, Hutchinson, CB, Huang, Q, Lu, CM, Crow, J, Wang, FF, Sebastian, S, Rehder, C, Lagoo, A, Horwitz, M, Rizzieri, D, Yu, J, Goodman, B, Datto, M, and Buckley, P. "Donor cell-derived leukemias/myelodysplastic neoplasms in allogeneic hematopoietic stem cell transplant recipients: a clinicopathologic study of 10 cases and a comprehensive review of the literature." Am J Clin Pathol 135.4 (April 2011): 525-540. (Review)
PMID
21411775
Source
pubmed
Published In
American Journal of Clinical Pathology
Volume
135
Issue
4
Publish Date
2011
Start Page
525
End Page
540
DOI
10.1309/AJCPPJUQ9DNR1GHP

Renal shielding and dosimetry for patients with severe systemic sclerosis receiving immunoablation with total body irradiation in the scleroderma: cyclophosphamide or transplantation trial.

PURPOSE: To describe renal shielding techniques and dosimetry in delivering total body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled in a hematopoietic stem cell transplant protocol. METHODS AND MATERIALS: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) protocol uses a lymphoablative preparative regimen including 800 cGy TBI delivered in two 200-cGy fractions twice a day before CD34(+) selected autologous hematopoietic stem cell transplantation. Lung and kidney doses are limited to 200 cGy to protect organs damaged by SSc. Kidney block proximity to the spinal cord was investigated, and guidelines were developed for acceptable lumbar area TBI dosing. Information about kidney size and the organ shifts from supine to standing positions were recorded using diagnostic ultrasound (US). Minimum distance between the kidney blocks (dkB) and the lumbar spine region dose was recorded, and in vivo dosimetry was performed at several locations to determine the radiation doses delivered. RESULTS: Eleven patients were treated at our center with an anteroposterior (AP)/posteroanterior (PA) TBI technique. A 10% to 20% dose inhomogeneity in the lumbar spine region was achieved with a minimum kidney block separation of 4 to 5 cm. The average lumbar spine dose was 179.6 ± 18.1 cGy, with an average dkB of 5.0 ± 1.0 cm. Kidney block shield design was accomplished using a combination of US and noncontrast computerized tomography (CT) or CT imaging alone. The renal US revealed a wide range of kidney displacement from upright to supine positions. Overall, the average in vivo dose for the kidney prescription point was 193.4 ± 5.1 cGy. CONCLUSIONS: The dose to the kidneys can be attenuated while maintaining a 10% to 20% dose inhomogeneity in the lumbar spine area. Kidneys were localized more accurately using both US and CT imaging. With this technique, renal function has been preserved, and the study continues to enroll patients.

Authors
Craciunescu, OI; Steffey, BA; Kelsey, CR; Larrier, NA; Paarz-Largay, CJ; Prosnitz, RG; Chao, N; Chute, J; Gasparetto, C; Horwitz, M; Long, G; Rizzieri, D; Sullivan, KM
MLA Citation
Craciunescu, OI, Steffey, BA, Kelsey, CR, Larrier, NA, Paarz-Largay, CJ, Prosnitz, RG, Chao, N, Chute, J, Gasparetto, C, Horwitz, M, Long, G, Rizzieri, D, and Sullivan, KM. "Renal shielding and dosimetry for patients with severe systemic sclerosis receiving immunoablation with total body irradiation in the scleroderma: cyclophosphamide or transplantation trial." Int J Radiat Oncol Biol Phys 79.4 (March 15, 2011): 1248-1255.
PMID
20800376
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
79
Issue
4
Publish Date
2011
Start Page
1248
End Page
1255
DOI
10.1016/j.ijrobp.2010.05.036

OUTCOMES OF A 1-DAY NONMYELOABLATIVE PREPARATIVE REGIMEN FOR PRIMARY GRAFT FAILURE AFTER ALLOGENEIC STEM CELL TRANSPLANTATION

Authors
Kanda, J; Horwitz, ME; Long, GD; Gasparetto, C; Sullivan, KM; Chute, JP; Morris, A; Hennig, T; Chao, NJ; Rizzieri, DA
MLA Citation
Kanda, J, Horwitz, ME, Long, GD, Gasparetto, C, Sullivan, KM, Chute, JP, Morris, A, Hennig, T, Chao, NJ, and Rizzieri, DA. "OUTCOMES OF A 1-DAY NONMYELOABLATIVE PREPARATIVE REGIMEN FOR PRIMARY GRAFT FAILURE AFTER ALLOGENEIC 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
S308
End Page
S308
DOI
10.1016/j.bbmt.2010.12.460

Feasibility of low-dose interleukin-2 therapy following T-cell-depleted nonmyeloablative allogeneic hematopoietic stem cell transplantation from HLA-matched or -mismatched family member donors.

INTRODUCTION: High relapse rates and infections remain primary causes of failure in nonmyeloablative transplantation. Interleukin-2 (IL-2) may stimulate the immune system and improve outcomes. The primary objective of this pilot study was to evaluate the feasibility of administering IL-2 following a T-cell-depleted nonmyeloablative hematopoietic stem cell transplant. METHODS: Patients received T-cell-depleted nonmyeloablative transplant from a matched or mismatched related donor. Those with allogeneic engraftment,

Authors
Rizzieri, DA; Crout, C; Storms, R; Golob, J; Long, GD; Gasparetto, C; Sullivan, KM; Horwitz, M; Chute, J; Lagoo, AS; Morris, A; Beaven, A; Yang, Y; Peterson, B; Li, Z; Chao, NJ
MLA Citation
Rizzieri, DA, Crout, C, Storms, R, Golob, J, Long, GD, Gasparetto, C, Sullivan, KM, Horwitz, M, Chute, J, Lagoo, AS, Morris, A, Beaven, A, Yang, Y, Peterson, B, Li, Z, and Chao, NJ. "Feasibility of low-dose interleukin-2 therapy following T-cell-depleted nonmyeloablative allogeneic hematopoietic stem cell transplantation from HLA-matched or -mismatched family member donors." Cancer Invest 29.1 (January 2011): 56-61.
PMID
21166499
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
29
Issue
1
Publish Date
2011
Start Page
56
End Page
61
DOI
10.3109/07357907.2010.535055

Early post transplant (F-18) 2-fluoro-2-deoxyglucose positron emission tomography does not predict outcome for patients undergoing auto-SCT in non-Hodgkin and Hodgkin lymphoma

Positron emission tomography (PET) in conjunction with computed tomography is a frequently used modality for staging patients with lymphoma. Utility of PET-computed tomography before or early following auto-SCT has not been as rigorously evaluated. We retrospectively analyzed patients who received auto-SCT for treatment of relapsed or refractory non-Hodgkins lymphoma or Hodgkins disease between the years of 1996 and 2007. Patients who had either a PET scan following salvage chemotherapy within 14 weeks of transplantation (pre-PET), and/or a PET scan 6-14 weeks following transplantation (post-PET) were included. A total of 90 patients were identified for analysis. The median follow-up time is 3.3 years, with a range of 0.13-12.0 years. The median PFS was 4.6 years, and median OS was 5.1 years. At the time of this analysis, 34 patients (37%) experienced disease relapse, and 25 (27%) of the patients died from disease progression. In multivariate Cox proportional hazards analysis, post-PET did not predict for outcome, pre-PET positivity predicted for decrease in PFS. In conclusion, post-PET scan did not predict for PFS or OS in multivariate analysis. Positive pre-PET scan did predict for PFS as seen in previous studies, and may help identify patients who would benefit from innovative post transplant therapies. © 2011 Macmillan Publishers Limited All rights reserved.

Authors
Palmer, J; Goggins, T; Broadwater, G; Chao, N; Horwitz, M; Beaven, A; Sullivan, K; Coleman, RE; Rizzieri, D
MLA Citation
Palmer, J, Goggins, T, Broadwater, G, Chao, N, Horwitz, M, Beaven, A, Sullivan, K, Coleman, RE, and Rizzieri, D. "Early post transplant (F-18) 2-fluoro-2-deoxyglucose positron emission tomography does not predict outcome for patients undergoing auto-SCT in non-Hodgkin and Hodgkin lymphoma." Bone Marrow Transplantation 46.6 (2011): 847-851.
PMID
20856212
Source
scival
Published In
Bone Marrow Transplantation
Volume
46
Issue
6
Publish Date
2011
Start Page
847
End Page
851
DOI
10.1038/bmt.2010.203

Alemtuzumab for the prevention and treatment of graft-versus-host disease.

Alemtuzumab is a humanized monoclonal antibody against the CD52 antigen, which is expressed on the surface of various hematopoietic cells such as B and T lymphocytes, and has been widely used for preventing acute graft-versus-host disease (GVHD) in allogeneic stem cell transplantation (SCT). Administration of 100 mg alemtuzumab before transplantation has resulted in a low incidence of acute GVHD in HLA-matched and mismatched transplantation from either related or unrelated donors. However, because alemtuzumab could remain in the blood at the lympholytic level 1-2 months after transplantation, immune reconstitution was substantially delayed, leading to a high incidence of viral infection and relapse. A dose reduction of alemtuzumab was attempted in a reduced-intensity conditioning setting to facilitate immune reconstitution, and this resulted in earlier immune reconstitution, but the clinical benefits were unclear. The dose of alemtuzumab and the timing of its administration should be optimized to maximize the benefit of acute GVHD suppression and minimize the risk of infection and relapse. Another strategy to facilitate immune reconstitution and augment anti-tumor effects is donor cell infusion of T and NK cells. Although there is accumulating evidence regarding the use of alemtuzumab for acute GVHD prevention, information on the salvage treatment for steroid-refractory acute and chronic GVHD is still limited.

Authors
Kanda, J; Lopez, RD; Rizzieri, DA
MLA Citation
Kanda, J, Lopez, RD, and Rizzieri, DA. "Alemtuzumab for the prevention and treatment of graft-versus-host disease." International journal of hematology 93.5 (2011): 586-593.
PMID
21369856
Source
scival
Published In
International Journal of Hematology
Volume
93
Issue
5
Publish Date
2011
Start Page
586
End Page
593
DOI
10.1007/s12185-011-0802-2

Alemtuzumab for the prevention and treatment of graft-versus-host disease

Alemtuzumab is a humanized monoclonal antibody against the CD52 antigen, which is expressed on the surface of various hematopoietic cells such as B and T lymphocytes, and has been widely used for preventing acute graft-versus-host disease (GVHD) in allogeneic stem cell transplantation (SCT). Administration of 100 mg alemtuzumab before transplantation has resulted in a low incidence of acute GVHD in HLA-matched and mismatched transplantation from either related or unrelated donors. However, because alemtuzumab could remain in the blood at the lympholytic level 1-2 months after transplantation, immune reconstitution was substantially delayed, leading to a high incidence of viral infection and relapse. A dose reduction of alemtuzumab was attempted in a reduced-intensity conditioning setting to facilitate immune reconstitution, and this resulted in earlier immune reconstitution, but the clinical benefits were unclear. The dose of alemtuzumab and the timing of its administration should be optimized to maximize the benefit of acute GVHD suppression and minimize the risk of infection and relapse. Another strategy to facilitate immune reconstitution and augment anti-tumor effects is donor cell infusion of T and NK cells. Although there is accumulating evidence regarding the use of alemtuzumab for acute GVHD prevention, information on the salvage treatment for steroid-refractory acute and chronic GVHD is still limited. © 2011 The Japanese Society of Hematology.

Authors
Kanda, J; Lopez, RD; Rizzieri, DA
MLA Citation
Kanda, J, Lopez, RD, and Rizzieri, DA. "Alemtuzumab for the prevention and treatment of graft-versus-host disease." International Journal of Hematology (2011): 1-8.
Source
scival
Published In
International Journal of Hematology
Publish Date
2011
Start Page
1
End Page
8
DOI
10.1007/s12185-011-0802-2

Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs.

A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-β pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions.

Authors
Jima, DD; Zhang, J; Jacobs, C; Richards, KL; Dunphy, CH; Choi, WWL; Au, WY; Srivastava, G; Czader, MB; Rizzieri, DA; Lagoo, AS; Lugar, PL; Mann, KP; Flowers, CR; Bernal-Mizrachi, L; Naresh, KN; Evens, AM; Gordon, LI; Luftig, M; Friedman, DR; Weinberg, JB; Thompson, MA; Gill, JI; Liu, Q; How, T; Grubor, V; Gao, Y; Patel, A; Wu, H; Zhu, J; Blobe, GC; Lipsky, PE; Chadburn, A; Dave, SS; Hematologic Malignancies Research Consortium,
MLA Citation
Jima, DD, Zhang, J, Jacobs, C, Richards, KL, Dunphy, CH, Choi, WWL, Au, WY, Srivastava, G, Czader, MB, Rizzieri, DA, Lagoo, AS, Lugar, PL, Mann, KP, Flowers, CR, Bernal-Mizrachi, L, Naresh, KN, Evens, AM, Gordon, LI, Luftig, M, Friedman, DR, Weinberg, JB, Thompson, MA, Gill, JI, Liu, Q, How, T, Grubor, V, Gao, Y, Patel, A, Wu, H, Zhu, J, Blobe, GC, Lipsky, PE, Chadburn, A, Dave, SS, and Hematologic Malignancies Research Consortium, . "Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs." Blood 116.23 (December 2, 2010): e118-e127.
PMID
20733160
Source
pubmed
Published In
Blood
Volume
116
Issue
23
Publish Date
2010
Start Page
e118
End Page
e127
DOI
10.1182/blood-2010-05-285403

A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse.

INTRODUCTION: We evaluated the complete remission (CR) rate in patients with acute myeloid leukemia (AML) in first relapse treated with fixed-dose-rate gemcitabine and mitoxantrone. In addition, we measured multidrug resistance (MDR) proteins on pretreatment bone marrows and correlated expression with outcome. PATIENTS AND METHODS: The study was performed in a 2-stage design. Pretreatment bone marrows were assayed for the MDR proteins (LRP, MDR1, MRP1, SLC28-29A1/A2, ABCC4/C5, and GSTP1) by immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Only 5 of the first 24 patients (21%) achieved CR; therefore, the study was terminated. Eleven patients (46%) had poor-risk cytogenetics and the median duration of first CR was 7.3 months. Patients had significant expression of the various MDR genes, with 70% of patients expressing moderate to high levels of GSTP1 by immunohistochemistry. Higher sum total of ABCC4 and SLC29A2 expression measured by RT-PCR was associated with not achieving CR (20.6 vs. 12.1; P = .006). In addition, there was a trend for higher expression of the sum total of the 10 MDR genes (measured by RT-PCR) and not achieving CR (P = .06). CONCLUSION: The CR rate in this study was comparable to other regimens used in poor-risk patients. Of interest, ABCC4 and SLC29A2 expression were predictive of achieving CR. The high expression of GSTP1 suggests that this may be a therapeutic target for relapsed AML. Finally, the rapidity and ease of using RT-PCR to quantify MDR in this study may have clinical utility in future trials.

Authors
Advani, AS; Shadman, M; Ali-Osman, F; Barker, A; Rybicki, L; Kalaycio, M; Sekeres, MA; de Castro, CM; Diehl, LF; Moore, JO; Beaven, A; Copelan, E; Sobecks, R; Talea, P; Rizzieri, DA
MLA Citation
Advani, AS, Shadman, M, Ali-Osman, F, Barker, A, Rybicki, L, Kalaycio, M, Sekeres, MA, de Castro, CM, Diehl, LF, Moore, JO, Beaven, A, Copelan, E, Sobecks, R, Talea, P, and Rizzieri, DA. "A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse." Clin Lymphoma Myeloma Leuk 10.6 (December 2010): 473-476.
PMID
21156465
Source
pubmed
Published In
Clinical Lymphoma, Myeloma and Leukemia
Volume
10
Issue
6
Publish Date
2010
Start Page
473
End Page
476
DOI
10.3816/CLML.2010.n.082

Adult Dual Umbilical Cord Blood Transplantation Using Myeloablative Total Body Irradiation (1350cGy) and Fludarabine Conditioning

Authors
Kanda, J; Rizzieri, DA; Gasparetto, C; Long, GD; Chute, JP; Sullivan, KM; Morris, A; Smith, CA; Hogge, DE; Nitta, J; Song, K; Niedzwiecki, D; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Rizzieri, DA, Gasparetto, C, Long, GD, Chute, JP, Sullivan, KM, Morris, A, Smith, CA, Hogge, DE, Nitta, J, Song, K, Niedzwiecki, D, Chao, NJ, and Horwitz, ME. "Adult Dual Umbilical Cord Blood Transplantation Using Myeloablative Total Body Irradiation (1350cGy) and Fludarabine Conditioning." November 19, 2010.
PMID
28729147
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1448
End Page
1448

Prospective, Biological Randomized Study of T-Cell Depleted Nonmyeloablative Allogeneic Transplantation From HLA-Matched Related, Unrelated or Haploidentical Donors for Patients with Hematologic Malignancies.

Authors
Kanda, J; Long, GD; Gasparetto, C; Horwitz, ME; Sullivan, KM; Chute, JP; Morris, A; Li, Z; Chao, NJ; Rizzieri, DA
MLA Citation
Kanda, J, Long, GD, Gasparetto, C, Horwitz, ME, Sullivan, KM, Chute, JP, Morris, A, Li, Z, Chao, NJ, and Rizzieri, DA. "Prospective, Biological Randomized Study of T-Cell Depleted Nonmyeloablative Allogeneic Transplantation From HLA-Matched Related, Unrelated or Haploidentical Donors for Patients with Hematologic Malignancies." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1456
End Page
1457

Donor Cell Leukemia: A Clinicopathological Study of 9 Cases and a Comprehensive Review of Literature

Authors
Hutchinson, CB; Crow, JH; Huang, Q; Lu, CM; Sebastain, S; Rehder, C; Lagoo, AS; Goodman, B; Horwitz, ME; Rizzieri, DA; Datto, M; Buckley, P; Wang, E
MLA Citation
Hutchinson, CB, Crow, JH, Huang, Q, Lu, CM, Sebastain, S, Rehder, C, Lagoo, AS, Goodman, B, Horwitz, ME, Rizzieri, DA, Datto, M, Buckley, P, and Wang, E. "Donor Cell Leukemia: A Clinicopathological Study of 9 Cases and a Comprehensive Review of Literature." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1423
End Page
1424

Alternative Splicing Is a Major Mechanism of Gene Regulation In Diffuse Large B Cell Lymphoma

Authors
Jacobs, CL; Patel, A; Jima, D; Liu, Q; Greenough, A; Zhang, J; Dunphy, C; Richards, K; Choi, W; Srivastava, G; Au, WY; Evens, AM; Gordon, LI; Czader, M; Rizzieri, DA; Lagoo, AS; Mann, KP; Flowers, CR; Bernal-Mizrachi, L; Naresh, K; Luftig, M; Chadburn, A; Hsi, E; Thompson, MA; Gill, J; Dave, S
MLA Citation
Jacobs, CL, Patel, A, Jima, D, Liu, Q, Greenough, A, Zhang, J, Dunphy, C, Richards, K, Choi, W, Srivastava, G, Au, WY, Evens, AM, Gordon, LI, Czader, M, Rizzieri, DA, Lagoo, AS, Mann, KP, Flowers, CR, Bernal-Mizrachi, L, Naresh, K, Luftig, M, Chadburn, A, Hsi, E, Thompson, MA, Gill, J, and Dave, S. "Alternative Splicing Is a Major Mechanism of Gene Regulation In Diffuse Large B Cell Lymphoma." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
351
End Page
352

A Phase I/II Trial of the Potent Hsp90 Inhibitor STA-9090 Administered Once Weekly In Patients with Advanced Hematologic Malignancies

Authors
Lancet, JE; Smith, BD; Bradley, R; Komrokji, RS; Teofilovici, F; Rizzieri, DA
MLA Citation
Lancet, JE, Smith, BD, Bradley, R, Komrokji, RS, Teofilovici, F, and Rizzieri, DA. "A Phase I/II Trial of the Potent Hsp90 Inhibitor STA-9090 Administered Once Weekly In Patients with Advanced Hematologic Malignancies." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1349
End Page
1350

Phase I Trial Results for SL-401, a Novel Cancer Stem Cell (CSC) Targeting Agent, Demonstrate Clinical Efficacy at Tolerable Doses In Patients with Heavily Pre-Treated AML, Poor Risk Elderly AML, and High Risk MDS

Authors
Konopleva, M; Hogge, DE; Rizzieri, DA; Cirrito, TP; Liu, JS; Kornblau, SM; Grable, M; Hwang, I-R; Borthakur, G; Mankin, A; Bivins, C; Garcia-Manero, G; Kadia, T; Harris, D; Ravandi, F; Andreeff, M; Cortes, JE; Niecestro, R; Bergstein, I; Kantarjian, HM; Frankel, AE
MLA Citation
Konopleva, M, Hogge, DE, Rizzieri, DA, Cirrito, TP, Liu, JS, Kornblau, SM, Grable, M, Hwang, I-R, Borthakur, G, Mankin, A, Bivins, C, Garcia-Manero, G, Kadia, T, Harris, D, Ravandi, F, Andreeff, M, Cortes, JE, Niecestro, R, Bergstein, I, Kantarjian, HM, and Frankel, AE. "Phase I Trial Results for SL-401, a Novel Cancer Stem Cell (CSC) Targeting Agent, Demonstrate Clinical Efficacy at Tolerable Doses In Patients with Heavily Pre-Treated AML, Poor Risk Elderly AML, and High Risk MDS." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1351
End Page
1351

Efficacy and Toxicity of Rituximab and Brief Duration, High Intensity Chemotherapy with Filgrastim Support for Burkitt or Burkitt - Like Leukemia/Lymphoma: Cancer and Leukemia Group B (Calgb) Study 10002

Authors
Rizzieri, DA; Johnson, JL; Byrd, JC; Lozanski, G; Powell, BL; Shea, TC; Nattom, S; Hoke, E; Cheson, BD; Larson, R
MLA Citation
Rizzieri, DA, Johnson, JL, Byrd, JC, Lozanski, G, Powell, BL, Shea, TC, Nattom, S, Hoke, E, Cheson, BD, and Larson, R. "Efficacy and Toxicity of Rituximab and Brief Duration, High Intensity Chemotherapy with Filgrastim Support for Burkitt or Burkitt - Like Leukemia/Lymphoma: Cancer and Leukemia Group B (Calgb) Study 10002." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
374
End Page
375

Phase 3 Trial of Pixantrone Dimaleate Compared with Other Agents as Third-Line, Single-Agent Treatment of Relapsed Aggressive Non-Hodgkin Lymphoma (EXTEND): End of Study Results

Authors
Pettengell, R; Zinzani, PL; Narayanan, G; de Mendoza, FH; Digumarti, R; Gomez, H; Coiffier, B; Schiller, G; Rizzieri, DA; Cernohous, P; Wang, L; Singer, J
MLA Citation
Pettengell, R, Zinzani, PL, Narayanan, G, de Mendoza, FH, Digumarti, R, Gomez, H, Coiffier, B, Schiller, G, Rizzieri, DA, Cernohous, P, Wang, L, and Singer, J. "Phase 3 Trial of Pixantrone Dimaleate Compared with Other Agents as Third-Line, Single-Agent Treatment of Relapsed Aggressive Non-Hodgkin Lymphoma (EXTEND): End of Study Results." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1168
End Page
1169

Comparable survival after HLA-well-matched unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis.

We compared the outcomes of unrelated donor (URD, n = 358) with human leukocyte antigen (HLA)-matched sibling donor (MSD, n = 226) transplantations in patients with acute myeloid leukemia (AML) in first complete remission (CR1) having unfavorable cytogenetics at diagnosis. Unfavorable cytogenetic abnormalities were: complex (≥ 3 abnormalities), 32%; and noncomplex involving chromosome 7, 25%; chromosome 5, 9%; 11q or MLL rearrangements, 18%; t(6;9), 5%; and other noncomplex, 10%. URDs were HLA-well-matched (n = 254; 71%) or partially-matched (n = 104; 29%). Three-year leukemia-free survival (LFS) for MSD was 42% (95% confidence interval [CI], 35%-48%) compared with 34% (95% CI, 28%-41%) for HLA-well-matched URD and 29% (95% CI, 20%-39%) for partially-matched URD (P = .08). In multivariate analysis, HLA-well-matched URD and MSD yielded similar LFS (relative risk [RR] = 1.1, 95% CI, 0.86-1.40, P = .44) and overall survival (OS; RR = 1.06, 95% CI, 0.83-1.37, P = .63). LFS and OS were significantly inferior for HLA-partially-matched URD recipients, those with prior myelodysplastic syndrome, and those older than 50 years. All cytogenetic cohorts had similar outcomes. Patients with chronic graft-versus-host disease had a significantly lower risk of relapse (RR = 0.68, 95% CI, 0.47-0.99, P = .05). Hematopoietic cell transplantation (HCT) using HLA-well-matched URD and MSD resulted in similar LFS and OS in AML patients in CR1 with unfavorable cytogenetics. Outcomes of HCT from HLA-partially- matched URD were inferior.

Authors
Gupta, V; Tallman, MS; He, W; Logan, BR; Copelan, E; Gale, RP; Khoury, HJ; Klumpp, T; Koreth, J; Lazarus, HM; Marks, DI; Martino, R; Rizzieri, DA; Rowe, JM; Sabloff, M; Waller, EK; DiPersio, JF; Bunjes, DW; Weisdorf, DJ
MLA Citation
Gupta, V, Tallman, MS, He, W, Logan, BR, Copelan, E, Gale, RP, Khoury, HJ, Klumpp, T, Koreth, J, Lazarus, HM, Marks, DI, Martino, R, Rizzieri, DA, Rowe, JM, Sabloff, M, Waller, EK, DiPersio, JF, Bunjes, DW, and Weisdorf, DJ. "Comparable survival after HLA-well-matched unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis." Blood 116.11 (September 16, 2010): 1839-1848.
PMID
20538804
Source
pubmed
Published In
Blood
Volume
116
Issue
11
Publish Date
2010
Start Page
1839
End Page
1848
DOI
10.1182/blood-2010-04-278317

Haploidentical transplantation for leukemia.

Hematopoietic stem cell transplantation from human leukocyte antigen (HLA)-haploidentical family members offers a potential cure for patients in need of allogeneic immunotherapy who have no immediate access to an HLA-matched donor. The use of ex vivo T-cell-depleted stem cells combined with immuno-myeloablative conditioning has enabled durable donor engraftment with a low incidence of acute graft-versus-host disease despite the HLA disparity. Moreover, additional transplant techniques involving in vivo T-cell depletion and reduced-intensity conditioning have further minimized the risks. However, a major drawback is delayed immune reconstitution leading to infections and high relapse rates, prompting significant research efforts focused on improving recovery in the post-transplant period. Infusions with donor lymphocytes are common, though newer manipulations with a focus on donor natural killer cells hold great promise, as do other modified donor T-cell infusions. Success of these new procedures will make haploidentical transplants safer and more effective, further broadening its appeal.

Authors
Kanda, J; Chao, NJ; Rizzieri, DA
MLA Citation
Kanda, J, Chao, NJ, and Rizzieri, DA. "Haploidentical transplantation for leukemia." Curr Oncol Rep 12.5 (September 2010): 292-301. (Review)
PMID
20602183
Source
pubmed
Published In
Current Oncology Reports
Volume
12
Issue
5
Publish Date
2010
Start Page
292
End Page
301
DOI
10.1007/s11912-010-0113-4

Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure.

PURPOSE: Patients with acute leukemia refractory to induction or reinduction chemotherapy have poor prognoses if they do not undergo hematopoietic stem-cell transplantation (HSCT). However, HSCT when a patient is not in complete remission (CR) is of uncertain benefit. We hypothesized that pretransplantation variables may define subgroups that have a better prognosis. PATIENTS AND METHODS: Overall, 2,255 patients who underwent transplantation for acute leukemia in relapse or with primary induction failure after myeloablative conditioning regimen between 1995 and 2004 were reported to the Center for International Blood and Marrow Transplant Research. The median follow-up of survivors was 61 months. We performed multivariate analysis of pretransplantation variables and developed a predictive scoring system for survival. RESULTS: The 3-year overall survival (OS) rates were 19% for acute myeloid leukemia (AML) and 16% for acute lymphoblastic leukemia (ALL). For AML, five adverse pretransplantation variables significantly influenced survival: first CR duration less than 6 months, circulating blasts, donor other than HLA-identical sibling, Karnofsky or Lansky score less than 90, and poor-risk cytogenetics. For ALL, survival was worse with the following: first refractory or second or greater relapse, > or = 25% marrow blasts, cytomegalovirus-seropositive donor, and age of 10 years or older. Patients with AML who had a predictive score of 0 had 42% OS at 3 years, whereas OS was 6% for a score > or = 3. Patients with ALL who had a score of 0 or 1 had 46% 3-year OS but only 10% OS rate for a score > or = 3. CONCLUSION: Pretransplantation variables delineate subgroups with different outcomes. HSCT during relapse can achieve long-term survival in selected patients with acute leukemia.

Authors
Duval, M; Klein, JP; He, W; Cahn, J-Y; Cairo, M; Camitta, BM; Kamble, R; Copelan, E; de Lima, M; Gupta, V; Keating, A; Lazarus, HM; Litzow, MR; Marks, DI; Maziarz, RT; Rizzieri, DA; Schiller, G; Schultz, KR; Tallman, MS; Weisdorf, D
MLA Citation
Duval, M, Klein, JP, He, W, Cahn, J-Y, Cairo, M, Camitta, BM, Kamble, R, Copelan, E, de Lima, M, Gupta, V, Keating, A, Lazarus, HM, Litzow, MR, Marks, DI, Maziarz, RT, Rizzieri, DA, Schiller, G, Schultz, KR, Tallman, MS, and Weisdorf, D. "Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure." J Clin Oncol 28.23 (August 10, 2010): 3730-3738.
PMID
20625136
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
28
Issue
23
Publish Date
2010
Start Page
3730
End Page
3738
DOI
10.1200/JCO.2010.28.8852

Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation.

Infusing natural killer (NK) cells following transplantation may allow less infections and relapse with little risk of acute graft-versus-host disease (aGVHD). We delivered 51 total NK cell-enriched donor lymphocyte infusions (DLIs) to 30 patients following a 3-6/6 HLA matched T cell-depleted nonmyeloablative allogeneic transplant. The primary endpoint of this study was feasibility and safety. Eight weeks following transplantation, donor NK cell-enriched DLIs were processed using a CD56(+) selecting column with up to 3 fresh infusions allowed. Toxicity, relapse, and survival were monitored. T cell phenotype, NK cell functional recovery, and KIR typing were assessed for association with outcomes. Fourteen matched and 16 mismatched transplanted patients received a total of 51 NK cell-enriched DLIs. Selection resulted in 96% (standard deviation [SD] 8%) purity and 83% (SD 21%) yield in the matched setting and 97% (SD 3%) purity and 77% (SD 24%) yield in the mismatched setting. The median number of CD3(-) CD56(+) NK cells infused was 10.6 (SD 7.91) x 10(6) cells/kg and 9.21 (SD 5.6) x 10(6) cells/kg, respectively. The median number of contaminating CD3(+)CD56(-) T cells infused was .53 (1.1) x 10(6) and .27 (.78) x 10(6) in the matched and mismatched setting, respectively. Only 1 patient each in the matched (n = 14) or mismatched (n = 16) setting experienced severe aGVHD with little other toxicity attributable to the infusions. Long-term responders with multiple NK cell-enriched infusions and improved T cell phenotypic recovery had improved duration of responses (p = .0045) and overall survival (OS) (P = .0058). A 1-step, high-yield process is feasible, and results in high doses of NK cells infused with little toxicity. NK cell-enriched DLIs result in improved immune recovery and outcomes for some. Future studies must assess whether the improved outcomes are the direct result of the high doses and improved NK cell function or other aspects of immune recovery.

Authors
Rizzieri, DA; Storms, R; Chen, D-F; Long, G; Yang, Y; Nikcevich, DA; Gasparetto, C; Horwitz, M; Chute, J; Sullivan, K; Hennig, T; Misra, D; Apple, C; Baker, M; Morris, A; Green, PG; Hasselblad, V; Chao, NJ
MLA Citation
Rizzieri, DA, Storms, R, Chen, D-F, Long, G, Yang, Y, Nikcevich, DA, Gasparetto, C, Horwitz, M, Chute, J, Sullivan, K, Hennig, T, Misra, D, Apple, C, Baker, M, Morris, A, Green, PG, Hasselblad, V, and Chao, NJ. "Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation." Biol Blood Marrow Transplant 16.8 (August 2010): 1107-1114.
PMID
20188202
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
16
Issue
8
Publish Date
2010
Start Page
1107
End Page
1114
DOI
10.1016/j.bbmt.2010.02.018

The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission.

We examined the efficacy of reduced-intensity conditioning (RIC) and compared outcomes of 93 patients older than 16 years after RIC with 1428 patients receiving full-intensity conditioning for allografts using sibling and unrelated donors for Philadelphia-negative acute lymphoblastic leukemia (ALL) in first or second complete remission. RIC conditioning included busulfan 9 mg/kg or less (27), melphalan 150 mg/m(2) or less (23), low-dose total body irradiation (TBI; 36), and others (7). The RIC group was older (median 45 vs 28 years, P < .001) and more received peripheral blood grafts (73% vs 43%, P < .001) but had similar other prognostic factors. The RIC versus full-intensity conditioning groups had slightly, but not significantly, less acute grade II-IV graft-versus-host disease (39% vs 46%) and chronic graft-versus-host disease (34% vs 42%), yet similar transplantation-related mortality. RIC led to slightly more relapse (35% vs 26%, P = .08) yet similar age-adjusted survival (38% vs 43%, P = .39). Multivariate analysis showed that conditioning intensity did not affect transplantation-related mortality (P = .92) or relapse risk (P = .14). Multivariate analysis demonstrated significantly improved overall survival with: Karnofsky performance status more than 80, first complete remission, lower white blood count, well-matched unrelated or sibling donors, transplantation since 2001, age younger than 30 years, and conditioning with TBI, but no independent impact of conditioning intensity. RIC merits further investigation in prospective trials of adult ALL.

Authors
Marks, DI; Wang, T; Pérez, WS; Antin, JH; Copelan, E; Gale, RP; George, B; Gupta, V; Halter, J; Khoury, HJ; Klumpp, TR; Lazarus, HM; Lewis, VA; McCarthy, P; Rizzieri, DA; Sabloff, M; Szer, J; Tallman, MS; Weisdorf, DJ
MLA Citation
Marks, DI, Wang, T, Pérez, WS, Antin, JH, Copelan, E, Gale, RP, George, B, Gupta, V, Halter, J, Khoury, HJ, Klumpp, TR, Lazarus, HM, Lewis, VA, McCarthy, P, Rizzieri, DA, Sabloff, M, Szer, J, Tallman, MS, and Weisdorf, DJ. "The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission." Blood 116.3 (July 22, 2010): 366-374.
PMID
20404137
Source
pubmed
Published In
Blood
Volume
116
Issue
3
Publish Date
2010
Start Page
366
End Page
374
DOI
10.1182/blood-2010-01-264077

Overcoming drug resistance in mantle cell lymphoma using a combination of dose-dense and intense therapy.

We present a study of the prevalence of genetic polymorphisms and expression of genes encoding the drug-resistance proteins glutathione S-transferases (GSTs) in order to gain insights into the pattern of failure evident in mantle cell lymphoma. We note a high preponderance of genetic alterations conferring resistance to standard chemotherapy in this illness. Concurrent with this investigation, we present a series of patients who were provided dose-dense and intense chemotherapy to circumvent these drug-resistance mechanisms. High responses were noted, though durable remissions were few, indicating non-traditional chemotherapy options are important to investigate in this illness.

Authors
Crout, CA; Koh, L-P; Gockerman, JP; Moore, JO; Decastro, C; Long, GD; Diehl, L; Gasparetto, C; Niedzwiecki, D; Edwards, J; Prosnitz, L; Horwitz, M; Chute, J; Morris, A; Davis, P; Beaven, A; Chao, NJ; Ali-Osman, F; Rizzieri, DA
MLA Citation
Crout, CA, Koh, L-P, Gockerman, JP, Moore, JO, Decastro, C, Long, GD, Diehl, L, Gasparetto, C, Niedzwiecki, D, Edwards, J, Prosnitz, L, Horwitz, M, Chute, J, Morris, A, Davis, P, Beaven, A, Chao, NJ, Ali-Osman, F, and Rizzieri, DA. "Overcoming drug resistance in mantle cell lymphoma using a combination of dose-dense and intense therapy." Cancer Invest 28.6 (July 2010): 654-660.
PMID
20521909
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
28
Issue
6
Publish Date
2010
Start Page
654
End Page
660
DOI
10.3109/07357901003631015

Phase I study of temozolomide and laromustine (VNP40101M) in patients with relapsed or refractory leukemia.

PURPOSE: Although alkylators are known to be effective against some myeloid leukemias, resistance is often mediated via O6-alkylguanine-DNA alkyltransferase (AGT). Temozolomide's inhibition of AGT may sensitize leukemia cells to the novel alkylator laromustine. We conducted a phase I translational study to evaluate the toxicities and estimate the maximum tolerated dose (MTD) of laromustine when administered with temozolomide (TMZ) in patients with hematologic malignancies. PATIENTS AND METHODS: TMZ was delivered twice daily for 5 doses followed by a single infusion of laromustine. The target TMZ dose was the dose that would reliably result in > 90% AGT depletion. Once the target TMZ dose was identified, the laromustine dose was escalated. A total of 35 patients with relapsed/refractory leukemia were treated. RESULTS: Treatment with TMZ 300 mg for 5 doses resulted in > 90% depletion of AGT levels in 5 of 6 patients. The MTD of the combination was established at TMZ 1500 mg and laromustine 300 mg/m2. Three of the 7 patients assayed from cohort 1 achieved > 90% depletion of AGT activity (range, 77%-100% depletion; median, 88%). Five of 6 patients enrolled in cohort 2 achieved > 90% depletion of AGT activity (range, 92%-100% depletion; median, 93.5%). This established that the 300-mg dose of TMZ (1500 mg total) would be maintained in subsequent cohorts. The majority of adverse events were primarily hematologic, with infectious and pulmonary complications also noted. Three (9%) of the patients with previous refractory disease achieved a complete remission, and 5 (14%) of the patients achieved a morphologic, leukemia-free, but persistent hypocellular bone marrow status. CONCLUSION: Laromustine in combination with TMZ is tolerable and manageable at doses that predictably suppress AGT. Reliable TMZ-induced inhibition of AGT was observed in doses that are clinically tolerable. Evidence of antitumor effect was observed with this combination, suggesting that further efficacy studies should be performed.

Authors
Rizzieri, D; LoRusso, S; Tse, W; Khan, K; Advani, A; Moore, J; Karsten, V; Cahill, A; Gerson, SL
MLA Citation
Rizzieri, D, LoRusso, S, Tse, W, Khan, K, Advani, A, Moore, J, Karsten, V, Cahill, A, and Gerson, SL. "Phase I study of temozolomide and laromustine (VNP40101M) in patients with relapsed or refractory leukemia." Clin Lymphoma Myeloma Leuk 10.3 (June 2010): 211-216.
PMID
20511167
Source
pubmed
Published In
Clinical Lymphoma, Myeloma and Leukemia
Volume
10
Issue
3
Publish Date
2010
Start Page
211
End Page
216
DOI
10.3816/CLML.2010.n.033

"Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for nontransplant candidates in patients with previously untreated multiple myeloma.

The purpose of this study was to evaluate the efficacy and safety of short-course bortezomib, melphalan, prednisone (VMP) in previously untreated multiple myeloma as frontline therapy for transplant-ineligible patients and induction prior to autologous stem cell transplantation (ASCT). Patients received up to 6 28-day cycles of bortezomib 1.3 mg/m(2), days 1, 4, 8, and 11, plus melphalan 6 mg/m(2) and prednisone 60 mg/m(2), days 1-7. After 2-6 cycles, eligible and consenting patients could proceed to ASCT. Responses were assessed by International Uniform Response Criteria. The primary endpoint was complete response (CR) rate with VMP. Forty-five patients were enrolled. Among 44 evaluable patients, response rate was 95%, including 18% >or=CR (9% stringent CR), 27% very good partial responses (VGPR), and 50% partial responses (PR). Twenty patients proceeded to ASCT. Stem cell collection was successful in all; median yield was 5.6 x 10(6) CD34(+) cells/kg. Posttransplant response rates were 30% >or=CR (10% stringent CR), 65% VGPR, and 5% PR. After median follow-up of 14.0/14.6 months, median time to progression and progression-free survival were both 19.8/27.9 months in non-ASCT/ASCT patients. Seven patients have died; 1-year survival rates were 82%/95% in non-ASCT/ASCT patients. The most common grade 3/4 toxicities were thrombocytopenia (20%), neutropenia (28%), and infection (9%). Peripheral neuropathy grade 2-4 was the most common nonhematopoietic side effect occurring 17 patients (38%), although it was typically reversible, and only 5 patients (11%) discontinued therapy as a result of it. Short-course VMP is highly effective and generally well tolerated, both as initial treatment in non-ASCT patients and induction prior to ASCT. VMP did not negatively affect stem cell collection. Longer follow-up and prospective phase III trials are required to validate these initial observations.

Authors
Gasparetto, C; Gockerman, JP; Diehl, LF; de Castro, CM; Moore, JO; Long, GD; Horwitz, ME; Keogh, G; Chute, JP; Sullivan, KM; Neuwirth, R; Davis, PH; Sutton, LM; Anderson, RD; Chao, NJ; Rizzieri, D
MLA Citation
Gasparetto, C, Gockerman, JP, Diehl, LF, de Castro, CM, Moore, JO, Long, GD, Horwitz, ME, Keogh, G, Chute, JP, Sullivan, KM, Neuwirth, R, Davis, PH, Sutton, LM, Anderson, RD, Chao, NJ, and Rizzieri, D. ""Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for nontransplant candidates in patients with previously untreated multiple myeloma." Biol Blood Marrow Transplant 16.1 (January 2010): 70-77.
PMID
19733251
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
16
Issue
1
Publish Date
2010
Start Page
70
End Page
77
DOI
10.1016/j.bbmt.2009.08.017

Age-specific differences in oncogenic pathway dysregulation and anthracycline sensitivity in patients with acute myeloid leukemia.

PURPOSE: To define the biology driving the aggressive nature of acute myeloid leukemia (AML) in elderly patients. PATIENTS AND METHODS: Clinically annotated microarray data from 425 patients with newly diagnosed de novo AML from two publicly available data sets were analyzed after age-specific cohorts (young or= 55 years; n = 144) were prospectively identified. Gene expression analysis was conducted utilizing gene set enrichment analysis, and by applying previously defined and tested signature profiles reflecting dysregulation of oncogenic signaling pathways, altered tumor environment, and signatures of chemotherapy sensitivity. RESULTS: Elderly AML patients as expected had worse overall survival and event-free survival compared with younger patients. Analysis of oncogenic pathways revealed that older patients had higher probability of RAS, Src, and tumor necrosis factor (TNF) pathway activation (all P < .0001). Older patients were also less sensitive to anthracycline compared with younger patients with AML (P < .0001). Hierarchical clustering revealed that younger AML patients in cluster 2 had clinically worse survival, with high RAS, Src, and TNF pathway activation and in turn were less sensitive to anthracycline compared with patients in cluster 1. However, among elderly patients with AML, those in cluster 1 also demonstrated high RAS, Src, and TNF pathway activation but this did not translate into differences in survival or anthracycline sensitivity. CONCLUSION: AML in the elderly represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathway variations that contributes to poor survival and anthracycline resistance. These insights should enable development and adjustments of clinically meaningful treatment strategies in the older patient population.

Authors
Rao, AV; Valk, PJM; Metzeler, KH; Acharya, CR; Tuchman, SA; Stevenson, MM; Rizzieri, DA; Delwel, R; Buske, C; Bohlander, SK; Potti, A; Löwenberg, B
MLA Citation
Rao, AV, Valk, PJM, Metzeler, KH, Acharya, CR, Tuchman, SA, Stevenson, MM, Rizzieri, DA, Delwel, R, Buske, C, Bohlander, SK, Potti, A, and Löwenberg, B. "Age-specific differences in oncogenic pathway dysregulation and anthracycline sensitivity in patients with acute myeloid leukemia." J Clin Oncol 27.33 (November 20, 2009): 5580-5586.
PMID
19858393
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
27
Issue
33
Publish Date
2009
Start Page
5580
End Page
5586
DOI
10.1200/JCO.2009.22.2547

A Comprehensive Identification of the Microrna Transcriptome and Its Application in B Cell Malignancies

Authors
Jacobs, CL; Jima, DD; Zhang, J; Dunphy, C; Richards, KL; Choi, WWL; Srivastava, G; Evens, AM; Gordon, LI; Czader, M; Rizzieri, DA; Lagoo, AS; Mann, KP; Flowers, CR; Naresh, K; Luftig, M; Friedman, DR; Weinberg, JB; Thompson, MA; Gill, J; Kahl, BS; Chadburn, A; Dave, S
MLA Citation
Jacobs, CL, Jima, DD, Zhang, J, Dunphy, C, Richards, KL, Choi, WWL, Srivastava, G, Evens, AM, Gordon, LI, Czader, M, Rizzieri, DA, Lagoo, AS, Mann, KP, Flowers, CR, Naresh, K, Luftig, M, Friedman, DR, Weinberg, JB, Thompson, MA, Gill, J, Kahl, BS, Chadburn, A, and Dave, S. "A Comprehensive Identification of the Microrna Transcriptome and Its Application in B Cell Malignancies." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
948
End Page
949

Cenersen, An Antisense Inhibitor of p53, in Combination with Fludarabine, Cyclophosphamide, and Rituximab Shows Clinical Activity in High Risk CLL.

Authors
Lanasa, MC; Davis, PH; Datto, M; Cook, H; Rizzieri, DA
MLA Citation
Lanasa, MC, Davis, PH, Datto, M, Cook, H, and Rizzieri, DA. "Cenersen, An Antisense Inhibitor of p53, in Combination with Fludarabine, Cyclophosphamide, and Rituximab Shows Clinical Activity in High Risk CLL." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1332
End Page
1332

Immunocompromised Status of Patients with Hematologic and Solid Tumor Malignancies: Construction of a Practical Algorithm

Authors
Tran, TN; Ray, GT; Saddier, P; Trigg, M; Hayes, N; Li, Y; Rizzieri, DA; Stein, A; Weber, D; Serody, J; Raasch, R; Habel, L
MLA Citation
Tran, TN, Ray, GT, Saddier, P, Trigg, M, Hayes, N, Li, Y, Rizzieri, DA, Stein, A, Weber, D, Serody, J, Raasch, R, and Habel, L. "Immunocompromised Status of Patients with Hematologic and Solid Tumor Malignancies: Construction of a Practical Algorithm." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
980
End Page
980

A Phase II Multicentre Study with Elacytarabine as Second Salvage Therapy in Patients with AML.

Authors
O'Brien, S; Rizzieri, DA; Vey, N; Ravandi, F; Krug, UO; Sekeres, MA; Dennis, M; Venditti, A; Jacobsen, TF; Staudacher, K; Nilsson, BI; Giles, FJ
MLA Citation
O'Brien, S, Rizzieri, DA, Vey, N, Ravandi, F, Krug, UO, Sekeres, MA, Dennis, M, Venditti, A, Jacobsen, TF, Staudacher, K, Nilsson, BI, and Giles, FJ. "A Phase II Multicentre Study with Elacytarabine as Second Salvage Therapy in Patients with AML." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
431
End Page
431

Efficacy and Safety of Nilotinib in Elderly Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia (CML) in Chronic Phase (CP): A Sub-Analysis of the ENACT (Expanding Nilotinib Access in Clinical Trials) Study

Authors
le Coutre, PD; Turkina, A; Kim, D-W; Ceglarek, B; Alimena, G; Al-Ali, HK; Shen, Z; Jootar, S; Smith, G; De Souza, CA; Dorlhiac-Llacer, PE; Rizzieri, DA; Szczudlo, T; Berton, M; Wang, J; Wang, S-T; Nicolini, FE
MLA Citation
le Coutre, PD, Turkina, A, Kim, D-W, Ceglarek, B, Alimena, G, Al-Ali, HK, Shen, Z, Jootar, S, Smith, G, De Souza, CA, Dorlhiac-Llacer, PE, Rizzieri, DA, Szczudlo, T, Berton, M, Wang, J, Wang, S-T, and Nicolini, FE. "Efficacy and Safety of Nilotinib in Elderly Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia (CML) in Chronic Phase (CP): A Sub-Analysis of the ENACT (Expanding Nilotinib Access in Clinical Trials) Study." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1272
End Page
1273

Pralatrexate Induces Responses in Patients with Highly Refractory Peripheral T-Cell Lymphoma (PTCL).

Authors
Pettengell, R; Coiffier, B; Narayanan, G; Hurtado de Mendoza, F; Digumarti, R; Gomez, H; Zinzani, PL; Schiller, GJ; Rizzieri, DA; Cernohous, P; Wang, L; Singer, JW
MLA Citation
Pettengell, R, Coiffier, B, Narayanan, G, Hurtado de Mendoza, F, Digumarti, R, Gomez, H, Zinzani, PL, Schiller, GJ, Rizzieri, DA, Cernohous, P, Wang, L, and Singer, JW. "Pralatrexate Induces Responses in Patients with Highly Refractory Peripheral T-Cell Lymphoma (PTCL)." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
669
End Page
669

PI3K Inhibitors Inhibit Lymphoma Growth by Downregulation of MYC-Dependent Proliferation.

Authors
Walsh, KJ; Fan, S; Patel, A; Jacobs, CL; Smith, JL; Liu, Q; Rizzieri, DA; Dave, S
MLA Citation
Walsh, KJ, Fan, S, Patel, A, Jacobs, CL, Smith, JL, Liu, Q, Rizzieri, DA, and Dave, S. "PI3K Inhibitors Inhibit Lymphoma Growth by Downregulation of MYC-Dependent Proliferation." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
676
End Page
676

Monosomal Karyotype Is Predictive of Poor Response to Therapy and Worse Overall Survival in Secondary Acute Myeloid Leukemia (sAML); Analysis of a Multi-Center Phase II Study of Amonafide and Cytarabine Induction Therapy

Authors
Downie, BJ; Erba, HP; Stone, RM; Rizzieri, DA; Foran, JM
MLA Citation
Downie, BJ, Erba, HP, Stone, RM, Rizzieri, DA, and Foran, JM. "Monosomal Karyotype Is Predictive of Poor Response to Therapy and Worse Overall Survival in Secondary Acute Myeloid Leukemia (sAML); Analysis of a Multi-Center Phase II Study of Amonafide and Cytarabine Induction Therapy." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
819
End Page
820

Nilotinib Responses and Tolerability Confirmed in North American Patients with Chronic Myeloid Leukemia (CML) From ENACT (Expanding Nilotinib Access in Clinical Trials)

Authors
Powell, BL; Khoury, HJ; Lipton, JH; Rizzieri, DA; Williams, D; Turner, AR
MLA Citation
Powell, BL, Khoury, HJ, Lipton, JH, Rizzieri, DA, Williams, D, and Turner, AR. "Nilotinib Responses and Tolerability Confirmed in North American Patients with Chronic Myeloid Leukemia (CML) From ENACT (Expanding Nilotinib Access in Clinical Trials)." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1277
End Page
1277

Amonafide L-Malate (AS1413) in Combination with Cytarabine Is Equally Effective in Older and Younger Patients with Secondary Acute Myeloid Leukemia (AML); Final Data From a Phase II Study.

Authors
Erba, HP; O'Donnell, M; Allen, SL; Baer, MR; Powell, BL; Stone, RM; Bennett, JM; Lundberg, AS; Capizzi, RL; Rizzieri, DA
MLA Citation
Erba, HP, O'Donnell, M, Allen, SL, Baer, MR, Powell, BL, Stone, RM, Bennett, JM, Lundberg, AS, Capizzi, RL, and Rizzieri, DA. "Amonafide L-Malate (AS1413) in Combination with Cytarabine Is Equally Effective in Older and Younger Patients with Secondary Acute Myeloid Leukemia (AML); Final Data From a Phase II Study." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
433
End Page
434

Patterns and Management of Selected Adverse Events of Adult Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia (CML) From the ENACT (Expanding Nilotinib Access in Clinical Trials) Study.

Authors
le Coutre, PD; Ceglarek, B; Turkina, A; Kim, D-W; Alimena, G; Al-Ali, HK; Shen, Z; Jootar, S; Smith, G; De Souza, CA; Rizzieri, DA; Szczudlo, T; Berton, M; Wang, J; Dial, E; Nicolini, FE
MLA Citation
le Coutre, PD, Ceglarek, B, Turkina, A, Kim, D-W, Alimena, G, Al-Ali, HK, Shen, Z, Jootar, S, Smith, G, De Souza, CA, Rizzieri, DA, Szczudlo, T, Berton, M, Wang, J, Dial, E, and Nicolini, FE. "Patterns and Management of Selected Adverse Events of Adult Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia (CML) From the ENACT (Expanding Nilotinib Access in Clinical Trials) Study." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
457
End Page
458

Impact of Prior Therapy and Suboptimal Response to Imatinib On the Efficacy and Safety of Nilotinib Among 1,422 Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia (CML) in Chronic Phase (CP): Sub-Analyses of the ENACT (Expanding Nilotinib Access in Clinical Trials) Study

Authors
Nicolini, FE; Kim, D-W; Ceglarek, B; Turkina, A; Alimena, G; Al-Ali, HK; Shen, Z; Jootar, S; Smith, G; De Souza, CA; Dorlhiac-Llacer, PE; Rizzieri, DA; Szczudlo, T; Berton, M; Wang, J; Bieri, C; le Coutre, PD
MLA Citation
Nicolini, FE, Kim, D-W, Ceglarek, B, Turkina, A, Alimena, G, Al-Ali, HK, Shen, Z, Jootar, S, Smith, G, De Souza, CA, Dorlhiac-Llacer, PE, Rizzieri, DA, Szczudlo, T, Berton, M, Wang, J, Bieri, C, and le Coutre, PD. "Impact of Prior Therapy and Suboptimal Response to Imatinib On the Efficacy and Safety of Nilotinib Among 1,422 Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia (CML) in Chronic Phase (CP): Sub-Analyses of the ENACT (Expanding Nilotinib Access in Clinical Trials) Study." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
866
End Page
867

Maintenance Therapy with Low-Dose Subcutaneous 5-Azacitidine in Older Patients with AML in 1st Remission.

Authors
Lancet, JE; Komrokji, RS; Lin, H; de Castro, CM; Rizzieri, DA; Melchert, M; List, AF
MLA Citation
Lancet, JE, Komrokji, RS, Lin, H, de Castro, CM, Rizzieri, DA, Melchert, M, and List, AF. "Maintenance Therapy with Low-Dose Subcutaneous 5-Azacitidine in Older Patients with AML in 1st Remission." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
425
End Page
426

Histone Deacetylase Inhibition Using LBH589 Is Effective in Lymphoma and Results in Down-Regulation of the NF-KB Pathway

Authors
Smith, JL; Patel, A; Fan, S; Jacobs, CL; Walsh, KJ; Liu, Q; Rizzieri, DA; Dave, S
MLA Citation
Smith, JL, Patel, A, Fan, S, Jacobs, CL, Walsh, KJ, Liu, Q, Rizzieri, DA, and Dave, S. "Histone Deacetylase Inhibition Using LBH589 Is Effective in Lymphoma and Results in Down-Regulation of the NF-KB Pathway." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1436
End Page
1437

Outcomes of patients who undergo aggressive induction therapy for secondary acute myeloid leukemia.

BACKGROUND: Response and survival in 96 patients with secondary acute myeloid leukemia (sAML) who received aggressive induction chemotherapy was reviewed. METHODS: The median follow-up of survivors was 2.3 years. A total of 70 (73%) patients achieved a morphologic complete remission (CR) confirmed by absence of leukemic blasts by flow cytometry. RESULTS: For all 96 patients, the median event-free survival (EFS) was 8 months, and overall survival (OS) was 13.6 months (range, 1-119 months). Eight patients died shortly after induction therapy because of disease or side effects, and 13 are currently in continuous first remission. The median disease-free survival (DFS) for all 70 patients who achieved a morphologic CR was 9 months (range, 1-51 months), with a 64% chance of surviving 1 year. Patients with AML after previous chemotherapy or radiation therapy had a higher morphologic remission rate compared with those arising from myelodysplastic syndrome or myeloproliferative disease (82% vs 62%; P = .027). However, among the patients from the 2 groups who attained a morphologic remission, there was no difference in terms of CR rate (P = .94), DFS, EFS, or OS (P = .55, .83, and .71, respectively). This is a similar DFS to the group of 7 patients who went directly to ablative allogeneic transplant rather than having induction therapy first. In this population of patients who received aggressive chemotherapy, Charlson comorbidity index or a higher number of factors recognized as high risk in leukemia patients did not affect the chance of OS, DFS, and EFS, although having more recognized leukemia risk factors was related to a lower chance of surviving 1 year. However, it is important to note that those with higher comorbidity indexes were underrepresented in this aggressively treated cohort. CONCLUSIONS: The data from the current study demonstrate that many patients with sAML can tolerate aggressive induction therapy and attain remission, but duration of response and the chance of long-term survival remain poor.

Authors
Rizzieri, DA; O'Brien, JA; Broadwater, G; Decastro, CM; Dev, P; Diehl, L; Beaven, A; Lagoo, A; Gockerman, JP; Chao, NJ; Moore, JO
MLA Citation
Rizzieri, DA, O'Brien, JA, Broadwater, G, Decastro, CM, Dev, P, Diehl, L, Beaven, A, Lagoo, A, Gockerman, JP, Chao, NJ, and Moore, JO. "Outcomes of patients who undergo aggressive induction therapy for secondary acute myeloid leukemia." Cancer 115.13 (July 1, 2009): 2922-2929.
PMID
19452542
Source
pubmed
Published In
Cancer
Volume
115
Issue
13
Publish Date
2009
Start Page
2922
End Page
2929
DOI
10.1002/cncr.24379

EXPANDING NILOTINIB ACCESS IN CLINICAL TRIALS (ENACT) STUDY IN ADULT PATIENTS (PTS) WITH IMATINIB-RESISTANT OR -INTOLERANT CHRONIC MYELOID LEUKEMIA (CML): SUBGROUP ANALYSIS OF PATIENTS WHO FAILED PRIOR DASATINIB THERAPY

Authors
Nicolini, FE; Alimena, G; Al-Ali, HK; Turkina, AT; Shen, Z; Jootar, S; Smith, G; Conchon, M; Wang, J; Berton, M; Szczudlo, T; Rizzieri, DA
MLA Citation
Nicolini, FE, Alimena, G, Al-Ali, HK, Turkina, AT, Shen, Z, Jootar, S, Smith, G, Conchon, M, Wang, J, Berton, M, Szczudlo, T, and Rizzieri, DA. "EXPANDING NILOTINIB ACCESS IN CLINICAL TRIALS (ENACT) STUDY IN ADULT PATIENTS (PTS) WITH IMATINIB-RESISTANT OR -INTOLERANT CHRONIC MYELOID LEUKEMIA (CML): SUBGROUP ANALYSIS OF PATIENTS WHO FAILED PRIOR DASATINIB THERAPY." HAEMATOLOGICA-THE HEMATOLOGY JOURNAL 94 (June 2009): 257-257.
Source
wos-lite
Published In
Haematologica
Volume
94
Publish Date
2009
Start Page
257
End Page
257

FINAL SAFETY ANALYSIS OF 1,793 CML PATIENTS FROM ENACT (EXPANDING NILOTINIB ACCESS IN CLINICAL TRIALS) STUDY IN ADULT PATIENTS WITH IMATINIB-RESISTANT OR -INTOLERANT CHRONIC MYELOID LEUKEMIA

Authors
Nicolini, FE; Alimena, G; Al-Ali, HK; Turkina, AT; Shen, Z; Jootar, S; Smith, G; De Souza, C; Wang, J; Berton, M; Szczudlo, T; Rizzieri, DA
MLA Citation
Nicolini, FE, Alimena, G, Al-Ali, HK, Turkina, AT, Shen, Z, Jootar, S, Smith, G, De Souza, C, Wang, J, Berton, M, Szczudlo, T, and Rizzieri, DA. "FINAL SAFETY ANALYSIS OF 1,793 CML PATIENTS FROM ENACT (EXPANDING NILOTINIB ACCESS IN CLINICAL TRIALS) STUDY IN ADULT PATIENTS WITH IMATINIB-RESISTANT OR -INTOLERANT CHRONIC MYELOID LEUKEMIA." HAEMATOLOGICA-THE HEMATOLOGY JOURNAL 94 (June 2009): 255-256.
Source
wos-lite
Published In
Haematologica
Volume
94
Publish Date
2009
Start Page
255
End Page
256

Age-specific differences in oncogenic pathway deregulation and chemosensitivity in patients with acute myeloid leukemia: Strategies to maximize response to induction chemotherapy

Authors
Rao, AV; Valk, P; Metzeler, KH; Acharya, C; Rizzieri, DA; Delwel, R; Bohlander, SH; Buske, C; Potti, A; Lowenberg, B
MLA Citation
Rao, AV, Valk, P, Metzeler, KH, Acharya, C, Rizzieri, DA, Delwel, R, Bohlander, SH, Buske, C, Potti, A, and Lowenberg, B. "Age-specific differences in oncogenic pathway deregulation and chemosensitivity in patients with acute myeloid leukemia: Strategies to maximize response to induction chemotherapy." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

A phase II study with CP-4055 in patients with second salvage AML

Authors
Giles, FG; O'Brien, S; Rizzieri, DA; Vey, N; Krug, U; Sekeres, M; Jacobsen, TF; Nilsson, BI; Staudacher, K
MLA Citation
Giles, FG, O'Brien, S, Rizzieri, DA, Vey, N, Krug, U, Sekeres, M, Jacobsen, TF, Nilsson, BI, and Staudacher, K. "A phase II study with CP-4055 in patients with second salvage AML." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Patterns of microRNA expression characterize stages of human B-cell differentiation.

Mature B-cell differentiation provides an important mechanism for the acquisition of adaptive immunity. Malignancies derived from mature B cells constitute the majority of leukemias and lymphomas. These malignancies often maintain the characteristics of the normal B cells that they are derived from, a feature that is frequently used in their diagnosis. The role of microRNAs in mature B cells is largely unknown. Through concomitant microRNA and mRNA profiling, we demonstrate a potential regulatory role for microRNAs at every stage of the mature B-cell differentiation process. In addition, we have experimentally identified a direct role for the microRNA regulation of key transcription factors in B-cell differentiation: LMO2 and PRDM1 (Blimp1). We also profiled the microRNA of B-cell tumors derived from diffuse large B-cell lymphoma, Burkitt lymphoma, and chronic lymphocytic leukemia. We found that, in contrast to many other malignancies, common B-cell malignancies do not down-regulate microRNA expression. Although these tumors could be distinguished from each other with use of microRNA expression, each tumor type maintained the expression of the lineage-specific microRNAs. Expression of these lineage-specific microRNAs could correctly predict the lineage of B-cell malignancies in more than 95% of the cases. Thus, our data demonstrate that microRNAs may be important in maintaining the mature B-cell phenotype in normal and malignant B cells.

Authors
Zhang, J; Jima, DD; Jacobs, C; Fischer, R; Gottwein, E; Huang, G; Lugar, PL; Lagoo, AS; Rizzieri, DA; Friedman, DR; Weinberg, JB; Lipsky, PE; Dave, SS
MLA Citation
Zhang, J, Jima, DD, Jacobs, C, Fischer, R, Gottwein, E, Huang, G, Lugar, PL, Lagoo, AS, Rizzieri, DA, Friedman, DR, Weinberg, JB, Lipsky, PE, and Dave, SS. "Patterns of microRNA expression characterize stages of human B-cell differentiation." Blood 113.19 (May 7, 2009): 4586-4594.
PMID
19202128
Source
pubmed
Published In
Blood
Volume
113
Issue
19
Publish Date
2009
Start Page
4586
End Page
4594
DOI
10.1182/blood-2008-09-178186

Vascular endothelial growth factor inhibition is not an effective therapeutic strategy for relapsed or refractory multiple myeloma: a phase 2 study of pazopanib (GW786034).

Authors
Prince, HM; Hönemann, D; Spencer, A; Rizzieri, DA; Stadtmauer, EA; Roberts, AW; Bahlis, N; Tricot, G; Bell, B; Demarini, DJ; Benjamin Suttle, A; Baker, KL; Pandite, LN
MLA Citation
Prince, HM, Hönemann, D, Spencer, A, Rizzieri, DA, Stadtmauer, EA, Roberts, AW, Bahlis, N, Tricot, G, Bell, B, Demarini, DJ, Benjamin Suttle, A, Baker, KL, and Pandite, LN. "Vascular endothelial growth factor inhibition is not an effective therapeutic strategy for relapsed or refractory multiple myeloma: a phase 2 study of pazopanib (GW786034)." Blood 113.19 (May 7, 2009): 4819-4820. (Letter)
PMID
19423744
Source
pubmed
Published In
Blood
Volume
113
Issue
19
Publish Date
2009
Start Page
4819
End Page
4820
DOI
10.1182/blood-2009-02-207209

Sequential high-dose ifosfamide, carboplatin and etoposide with rituximab for relapsed Hodgkin and large B-cell non-Hodgkin lymphoma: increased toxicity without improvement in progression-free survival.

Non-cross resistant drugs given at high-dose intensity may maximise tumor cell kill leading to improved patient outcomes. We investigated the feasibility and efficacy of administering ifosfamide, carboplatin and etoposide +/- rituximab as sequential high-dose single agents. Twenty-two patients with relapsed/refractory Hodgkin lymphoma (n = 9) or non-Hodgkin (n = 13) lymphoma (NHL) were included. Therapy included: cycle 1 ifosfamide (15 g/m(2)), cycle 2 etoposide (900 mg/m(2)) and cycle 3 carboplatin (area under the curve 15). Patients with NHL received rituximab (375 mg/m(2)) with cycles 1 and 2. Blood stem cell collection was performed after etoposide. Primary endpoints were overall response (complete response (CR) + PR) and ability to mobilise stem cells after etoposide. Secondary endpoints were to assess the toxicity of the regimen and to evaluate the ability of patients to proceed to stem cell transplant (SCT). Overall response rate was 54% with CR in 4/22 (18%) subjects and PR in 8/22 (36%). Median progression-free survival was 15 months and overall survival has not been reached at 40 months. Thirteen participants proceeded to SCT. Grade 3/4 thrombocytopenia and neutropenia occurred in 58% of cycles and 91% of subjects respectively. Forty-five percent of patients required hospitalisation for toxicity and two patients died from complications of therapy. Sequential dose intense ifosfamide, etoposide, carboplatin +/- rituximab was more toxic and no more effective than the same drugs given in a conventional fashion.

Authors
Shea, TC; Beaven, AW; Moore, DT; Serody, JS; Gabriel, DA; Chao, N; Gockerman, JP; Garcia, RA; Rizzieri, DA
MLA Citation
Shea, TC, Beaven, AW, Moore, DT, Serody, JS, Gabriel, DA, Chao, N, Gockerman, JP, Garcia, RA, and Rizzieri, DA. "Sequential high-dose ifosfamide, carboplatin and etoposide with rituximab for relapsed Hodgkin and large B-cell non-Hodgkin lymphoma: increased toxicity without improvement in progression-free survival." Leuk Lymphoma 50.5 (May 2009): 741-748.
PMID
19358012
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
50
Issue
5
Publish Date
2009
Start Page
741
End Page
748
DOI
10.1080/10428190902853136

Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia.

Although the role of Hedgehog (Hh) signalling in embryonic pattern formation is well established, its functions in adult tissue renewal and maintenance remain unclear, and the relationship of these functions to cancer development has not been determined. Here we show that the loss of Smoothened (Smo), an essential component of the Hh pathway, impairs haematopoietic stem cell renewal and decreases induction of chronic myelogenous leukaemia (CML) by the BCR-ABL1 oncoprotein. Loss of Smo causes depletion of CML stem cells--the cells that propagate the leukaemia--whereas constitutively active Smo augments CML stem cell number and accelerates disease. As a possible mechanism for Smo action, we show that the cell fate determinant Numb, which depletes CML stem cells, is increased in the absence of Smo activity. Furthermore, pharmacological inhibition of Hh signalling impairs not only the propagation of CML driven by wild-type BCR-ABL1, but also the growth of imatinib-resistant mouse and human CML. These data indicate that Hh pathway activity is required for maintenance of normal and neoplastic stem cells of the haematopoietic system and raise the possibility that the drug resistance and disease recurrence associated with imatinib treatment of CML might be avoided by targeting this essential stem cell maintenance pathway.

Authors
Zhao, C; Chen, A; Jamieson, CH; Fereshteh, M; Abrahamsson, A; Blum, J; Kwon, HY; Kim, J; Chute, JP; Rizzieri, D; Munchhof, M; VanArsdale, T; Beachy, PA; Reya, T
MLA Citation
Zhao, C, Chen, A, Jamieson, CH, Fereshteh, M, Abrahamsson, A, Blum, J, Kwon, HY, Kim, J, Chute, JP, Rizzieri, D, Munchhof, M, VanArsdale, T, Beachy, PA, and Reya, T. "Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia." Nature 458.7239 (April 9, 2009): 776-779.
PMID
19169242
Source
pubmed
Published In
Nature
Volume
458
Issue
7239
Publish Date
2009
Start Page
776
End Page
779
DOI
10.1038/nature07737

Response and toxicity of donor lymphocyte infusions following T-cell depleted non-myeloablative allogeneic hematopoietic SCT from 3-6/6 HLA matched donors.

We report the outcome of early donor lymphocyte infusions (DLIs) after T-cell depleted non-myeloablative transplantation using stem cells from HLA-matched or mismatched donors. Sixty-nine patients with high-risk hematologic malignancies received DLI following fludarabine, CY and alemtuzumab with infusion of stem cells from a matched sibling (52) or partially matched family member donor (17). Patients received the first infusion at a median of 50 days after transplant, and doses ranged from 1 x 10(4) CD3+ cells/kg to 3.27 x 10(8) CD3+ cells/kg, depending on clinical status and the physician's discretion. A median cell dose of 1 x 10(5) CD3+ cells/kg in the mismatched setting and 1 x 10(6) CD3+ cells/kg in the matched sibling setting appears safe with only 1 of 7 (14%) and 4 of 31 patients (13%), respectively, experiencing severe acute GVHD at these doses. Importantly, 38% of patients with persistent disease before DLI attained a remission after infusion. Nine of the 69 patients remain alive and disease-free 32-71 months after the first DLI. In conclusion, low doses of DLI can be safely provided soon after T-cell depleted non-myeloablative therapy and provide a chance of remission. However, long-term survival still remains poor, primarily because of relapse in these patients.

Authors
Rizzieri, DA; Dev, P; Long, GD; Gasparetto, C; Sullivan, KM; Horwitz, M; Chute, J; Chao, NJ
MLA Citation
Rizzieri, DA, Dev, P, Long, GD, Gasparetto, C, Sullivan, KM, Horwitz, M, Chute, J, and Chao, NJ. "Response and toxicity of donor lymphocyte infusions following T-cell depleted non-myeloablative allogeneic hematopoietic SCT from 3-6/6 HLA matched donors." Bone Marrow Transplant 43.4 (February 2009): 327-333.
PMID
18850014
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
43
Issue
4
Publish Date
2009
Start Page
327
End Page
333
DOI
10.1038/bmt.2008.321

P134 A phase II pilot study of sorafenib in patients with myelodysplastic syndromes

Authors
Castro, CD; Adams, D; Rizzieri, D; Moore, J; Gockerman, J; Diehl, L; Horwitz, M; Edmonds, E; Warzecho, J
MLA Citation
Castro, CD, Adams, D, Rizzieri, D, Moore, J, Gockerman, J, Diehl, L, Horwitz, M, Edmonds, E, and Warzecho, J. "P134 A phase II pilot study of sorafenib in patients with myelodysplastic syndromes." Leukemia Research 33.SUPPL. 1 (2009): S137-.
Source
scival
Published In
Leukemia Research
Volume
33
Issue
SUPPL. 1
Publish Date
2009
Start Page
S137
DOI
10.1016/S0145-2126(09)70215-2

P129 A pilot study of decitabine in combination with arsenic trioxide for patients with myelodysplastic syndromes

Authors
Castro, CD; Adams, D; Rizzieri, D; Moore, J; Gockerman, J; Diehl, L; Horwitz, M; Edmonds, E; Warzecho, J
MLA Citation
Castro, CD, Adams, D, Rizzieri, D, Moore, J, Gockerman, J, Diehl, L, Horwitz, M, Edmonds, E, and Warzecho, J. "P129 A pilot study of decitabine in combination with arsenic trioxide for patients with myelodysplastic syndromes." Leukemia Research 33.SUPPL. 1 (2009): S134-.
Source
scival
Published In
Leukemia Research
Volume
33
Issue
SUPPL. 1
Publish Date
2009
Start Page
S134
DOI
10.1016/S0145-2126(09)70210-3

Erratum: Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia (Cancer Cell) (2008) 14 (238-249) DOI:10.1038/nature08255)

Authors
Zhao, C; Chen, A; Jamieson, CH; Fereshteh, M; Abrahamsson, A; Blum, J; Kwon, HY; Kim, J; Chute, JP; Rizzieri, D; Munchhof, M; Vanarsdale, T; Beachy, PA; Reya, T
MLA Citation
Zhao, C, Chen, A, Jamieson, CH, Fereshteh, M, Abrahamsson, A, Blum, J, Kwon, HY, Kim, J, Chute, JP, Rizzieri, D, Munchhof, M, Vanarsdale, T, Beachy, PA, and Reya, T. "Erratum: Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia (Cancer Cell) (2008) 14 (238-249) DOI:10.1038/nature08255)." Nature 460.7255 (2009): 652--.
Source
scival
Published In
Nature
Volume
460
Issue
7255
Publish Date
2009
Start Page
652-
DOI
10.1038/nature08255

Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia.

Survival of chronic lymphocytic leukemia (CLL) cells requires sustained activation of the antiapoptotic PI-3-K/Akt pathway, and many therapies for CLL cause leukemia cell death by triggering apoptosis. Blood lipoprotein particles are either pro- or antiapoptotic. High-density lipoprotein particles are antiapoptotic through sphingosine-1-phosphate receptor 3-mediated activation of the PI-3-K/Akt pathway. Apolipoprotein E4 (apoE4)-very low density lipoproteins (VLDL) increase apoptosis, but the apoE2-VLDL and apoE3-VLDL isoforms do not. As increased B-cell apoptosis favors longer survival of CLL patients, we hypothesized that APOE4 genotype would beneficially influence the clinical course of CLL. We report here that women (but not men) with an APOE4 genotype had markedly longer survival than non-APOE4 patients. VLDL is metabolized to low-density lipoprotein through lipoprotein lipase. Higher levels of lipoprotein lipase mRNA in these CLL patients correlated with shorter survival. The beneficial effect of APOE4 in CLL survival is likely mediated through APOE4 allele-specific regulation of leukemia cell apoptosis. The APOE allele and genotype distribution in these CLL patients is the same as in unaffected control populations, suggesting that although APOE genotype influences CLL outcome and response to therapy, it does not alter susceptibility to developing this disease.

Authors
Weinberg, JB; Volkheimer, AD; Mihovilovic, M; Jiang, N; Chen, Y; Bond, K; Moore, JO; Gockerman, JP; Diehl, LF; de Castro, CM; Rizzieri, DA; Levesque, MC; Dekroon, R; Strittmatter, WJ
MLA Citation
Weinberg, JB, Volkheimer, AD, Mihovilovic, M, Jiang, N, Chen, Y, Bond, K, Moore, JO, Gockerman, JP, Diehl, LF, de Castro, CM, Rizzieri, DA, Levesque, MC, Dekroon, R, and Strittmatter, WJ. "Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia." Leukemia 22.12 (December 2008): 2184-2192.
PMID
18784741
Source
pubmed
Published In
Leukemia
Volume
22
Issue
12
Publish Date
2008
Start Page
2184
End Page
2192
DOI
10.1038/leu.2008.241

MicroRNAs Regulate Mature B Cell Differentiation

Authors
Zhang, J; Jima, DD; Jacobs, CL; Gottwein, E; Huang, G; Lugar, PL; Lagoo, AS; Rizzieri, DA; Lipsky, PE; Dave, SS
MLA Citation
Zhang, J, Jima, DD, Jacobs, CL, Gottwein, E, Huang, G, Lugar, PL, Lagoo, AS, Rizzieri, DA, Lipsky, PE, and Dave, SS. "MicroRNAs Regulate Mature B Cell Differentiation." BLOOD 112.11 (November 16, 2008): 262-262.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
262
End Page
262

Safety Trial of NK Cell Enhanced Donor Lymphocyte Infusions from a 3-5/6 HLA Matched Family Member Following Nonmyeloablative Allogeneic Stem Cell Transplantation

Authors
Rizzieri, DA; Storms, R; Nikcevich, D; Peterson, B; Misra, D; Apple, C; Baker, M; Gasparetto, C; Horwitz, M; Chute, J; Morris, A; Chao, NJ
MLA Citation
Rizzieri, DA, Storms, R, Nikcevich, D, Peterson, B, Misra, D, Apple, C, Baker, M, Gasparetto, C, Horwitz, M, Chute, J, Morris, A, and Chao, NJ. "Safety Trial of NK Cell Enhanced Donor Lymphocyte Infusions from a 3-5/6 HLA Matched Family Member Following Nonmyeloablative Allogeneic Stem Cell Transplantation." BLOOD 112.11 (November 16, 2008): 133-134.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
133
End Page
134

Differential Impact of Inhibitory and Activating Killer Ig-Like Receptors and HLA Ligand on Outcomes of Transplantation for Myeloid and Lymphoid Malignancies

Authors
Prasad, VK; Chen, D-F; Broadwater, G; Reinsmoen, NL; Clark, A; Chao, NJ; Rizzieri, DA
MLA Citation
Prasad, VK, Chen, D-F, Broadwater, G, Reinsmoen, NL, Clark, A, Chao, NJ, and Rizzieri, DA. "Differential Impact of Inhibitory and Activating Killer Ig-Like Receptors and HLA Ligand on Outcomes of Transplantation for Myeloid and Lymphoid Malignancies." BLOOD 112.11 (November 16, 2008): 1118-1118.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
1118
End Page
1118

Gene Expression Profiles with Signatures of Tumor Biology and Chemotherapy Sensitivity May Provide a Novel Approach to Maximize Response to Induction Therapy in Patients with Acute Myeloid Leukemia

Authors
Rao, AV; Tuchman, SA; Potti, A; Rizzieri, DA; Mano, H; Delwel, R; Valk, P; Lowenberg, B
MLA Citation
Rao, AV, Tuchman, SA, Potti, A, Rizzieri, DA, Mano, H, Delwel, R, Valk, P, and Lowenberg, B. "Gene Expression Profiles with Signatures of Tumor Biology and Chemotherapy Sensitivity May Provide a Novel Approach to Maximize Response to Induction Therapy in Patients with Acute Myeloid Leukemia." BLOOD 112.11 (November 16, 2008): 785-786.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
785
End Page
786

A Phase I/II Study with CP-4055 in Patients with Haematologic Malignancies.

Authors
O'Brien, S; Rizzieri, DA; Vey, N; Kantarjian, HM; Jacobsen, TF; Nilsson, BI; Staudacher, K; Giles, F
MLA Citation
O'Brien, S, Rizzieri, DA, Vey, N, Kantarjian, HM, Jacobsen, TF, Nilsson, BI, Staudacher, K, and Giles, F. "A Phase I/II Study with CP-4055 in Patients with Haematologic Malignancies." BLOOD 112.11 (November 16, 2008): 350-350.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
350
End Page
350

Secondary Acute Myeloid Leukemia (sAML) Treated with Amonafide (AS1413) + Cytarabine: Durable Responses in Poor-Risk AML

Authors
Allen, SL; Erba, HP; Rizzieri, DA; O'Donnell, M; Powell, B; Lundberg, AS; Bennett, JM; Capizzi, RL
MLA Citation
Allen, SL, Erba, HP, Rizzieri, DA, O'Donnell, M, Powell, B, Lundberg, AS, Bennett, JM, and Capizzi, RL. "Secondary Acute Myeloid Leukemia (sAML) Treated with Amonafide (AS1413) + Cytarabine: Durable Responses in Poor-Risk AML." BLOOD 112.11 (November 16, 2008): 1019-1020.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
1019
End Page
1020

Bortezomib Plus Melphalan and Prednisone as Induction Prior to Transplant or as Frontline Therapy for Non-Transplant Candidates in Patients with Previously Untreated Multiple Myeloma

Authors
Gasparet, C; Gockerman, JP; Diehl, LF; III, DCC; Moore, J; Long, GD; Horwitz, M; Chute, J; Sullivan, KM; Netuwirth, R; Davis, PH; Sutton, LM; Anderson, RD; Chao, N; Rizzieri, DA
MLA Citation
Gasparet, C, Gockerman, JP, Diehl, LF, III, DCC, Moore, J, Long, GD, Horwitz, M, Chute, J, Sullivan, KM, Netuwirth, R, Davis, PH, Sutton, LM, Anderson, RD, Chao, N, and Rizzieri, DA. "Bortezomib Plus Melphalan and Prednisone as Induction Prior to Transplant or as Frontline Therapy for Non-Transplant Candidates in Patients with Previously Untreated Multiple Myeloma." BLOOD 112.11 (November 16, 2008): 1142-1142.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
1142
End Page
1142

Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia.

Imatinib mesylate (IM, Gleevec) has largely supplanted allogeneic hematopoietic cell transplantation (HCT) as first line therapy for chronic myeloid leukemia (CML). Nevertheless, many people with CML eventually undergo HCT, raising the question of whether prior IM therapy impacts HCT success. Data from the Center for International Blood and Marrow Transplant Research on 409 subjects treated with IM before HCT (IM(+)) and 900 subjects who did not receive IM before HCT (IM(-)) were analyzed. Among patients in first chronic phase, IM therapy before HCT was associated with better survival but no statistically significant differences in treatment-related mortality, relapse, and leukemia-free survival. Better HLA-matched donors, use of bone marrow, and transplantation within one year of diagnosis were also associated with better survival. A matched-pairs analysis was performed and confirmed a higher survival rate among first chronic phase patients receiving IM. Among patients transplanted with advanced CML, use of IM before HCT was not associated with treatment-related mortality, relapse, leukemia-free survival, or survival. Acute graft-versus-host disease rates were similar between IM(+) and IM(-) groups regardless of leukemia phase. These results should be reassuring to patients receiving IM before HCT.

Authors
Lee, SJ; Kukreja, M; Wang, T; Giralt, SA; Szer, J; Arora, M; Woolfrey, AE; Cervantes, F; Champlin, RE; Gale, RP; Halter, J; Keating, A; Marks, DI; McCarthy, PL; Olavarria, E; Stadtmauer, EA; Abecasis, M; Gupta, V; Khoury, HJ; George, B; Hale, GA; Liesveld, JL; Rizzieri, DA; Antin, JH; Bolwell, BJ; Carabasi, MH; Copelan, E; Ilhan, O; Litzow, MR; Schouten, HC; Zander, AR; Horowitz, MM; Maziarz, RT
MLA Citation
Lee, SJ, Kukreja, M, Wang, T, Giralt, SA, Szer, J, Arora, M, Woolfrey, AE, Cervantes, F, Champlin, RE, Gale, RP, Halter, J, Keating, A, Marks, DI, McCarthy, PL, Olavarria, E, Stadtmauer, EA, Abecasis, M, Gupta, V, Khoury, HJ, George, B, Hale, GA, Liesveld, JL, Rizzieri, DA, Antin, JH, Bolwell, BJ, Carabasi, MH, Copelan, E, Ilhan, O, Litzow, MR, Schouten, HC, Zander, AR, Horowitz, MM, and Maziarz, RT. "Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia." Blood 112.8 (October 15, 2008): 3500-3507.
PMID
18664621
Source
pubmed
Published In
Blood
Volume
112
Issue
8
Publish Date
2008
Start Page
3500
End Page
3507
DOI
10.1182/blood-2008-02-141689

Phase I evaluation of gemcitabine, mitoxantrone, and their effect on plasma disposition of fludarabine in patients with relapsed or refractory acute myeloid leukemia.

Our aim was to estimate the duration of maximum tolerated dose (MTD) duration for gemcitabine given as a continuous infusion in combination with fludarabine and mitoxantrone and to evaluate potential pharmacokinetic (PK) interactions in 17 patients with refractory or relapsed acute myeloid leukaemia (AML). Gemcitabine was administered at 10 mg/m(2)/min for 3-15 h, fludarabine at 25 mg/m(2) daily for days 1-5 and mitoxantrone at 10 mg/m(2) daily on days 1-3. PK studies revealed that fludarabine clearance was not affected by gemcitabine but mean terminal half-life and volume of distribution of fludarabine were slightly increased. The duration of MTD for gemcitabine was 12 h. Our previous in vitro work has demonstrated the binary combination of gemcitabine + fludarabine is most synergistic at a molar ratio around 0.002. However, with MTD dosing this drug ratio is not optimal to produce synergy and future studies using ratiometric dosing are required to confirm these findings.

Authors
Rao, AV; Younis, IR; Sand, GJ; Spasojevic, I; Adams, DJ; Decastro, CM; Gockerman, JP; Peterson, BL; Petros, WP; Moore, JO; Rizzieri, DA
MLA Citation
Rao, AV, Younis, IR, Sand, GJ, Spasojevic, I, Adams, DJ, Decastro, CM, Gockerman, JP, Peterson, BL, Petros, WP, Moore, JO, and Rizzieri, DA. "Phase I evaluation of gemcitabine, mitoxantrone, and their effect on plasma disposition of fludarabine in patients with relapsed or refractory acute myeloid leukemia." Leuk Lymphoma 49.8 (August 2008): 1523-1529.
PMID
18766965
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
49
Issue
8
Publish Date
2008
Start Page
1523
End Page
1529
DOI
10.1080/10428190802210700

A phase I study with CP-4055 in patients with hematologic malignancies

Authors
O'Brien, SM; Vey, N; Rizzieri, DA; Kantarjian, HM; Prebet, T; Ravandi, F; Jacobsen, TF; Nilsson, BI; Staudacher, K; Giles, FJ
MLA Citation
O'Brien, SM, Vey, N, Rizzieri, DA, Kantarjian, HM, Prebet, T, Ravandi, F, Jacobsen, TF, Nilsson, BI, Staudacher, K, and Giles, FJ. "A phase I study with CP-4055 in patients with hematologic malignancies." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Expanding Nilotinib Access in Clinical Trials (ENACT) study in adult patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph plus ) chronic myelogenous leukemia (CML) in chronic phase (CP), accelerated phase (AP), or blast crisis (BC): Updated safety analysis

Authors
Nicolini, FE; Alimena, G; Al-Ali, H; Zaritskey, AY; Shen, Z; Jootar, S; Smith, G; Hsu, Y; Veronese, ML; Rizzieri, DA
MLA Citation
Nicolini, FE, Alimena, G, Al-Ali, H, Zaritskey, AY, Shen, Z, Jootar, S, Smith, G, Hsu, Y, Veronese, ML, and Rizzieri, DA. "Expanding Nilotinib Access in Clinical Trials (ENACT) study in adult patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph plus ) chronic myelogenous leukemia (CML) in chronic phase (CP), accelerated phase (AP), or blast crisis (BC): Updated safety analysis." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Amonafide plus ara-C in secondary acute myeloid leukemia (sAML): Consistent efficacy in poor risk populations

Authors
Rizzieri, DA; Erba, HP; O'Donnell, M; Powell, BL; Lundberg, AS; Bennett, JM; Capizzi, RL
MLA Citation
Rizzieri, DA, Erba, HP, O'Donnell, M, Powell, BL, Lundberg, AS, Bennett, JM, and Capizzi, RL. "Amonafide plus ara-C in secondary acute myeloid leukemia (sAML): Consistent efficacy in poor risk populations." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies.

PURPOSE: Deforolimus (AP23573), a novel non-prodrug rapamycin analogue, inhibits the mammalian target of rapamycin, a downstream effector of the phosphatidylinositol 3-kinase/Akt and nutrient-sensing pathways. A phase 2 trial was conducted to determine the efficacy and safety of single-agent deforolimus in patients with relapsed or refractory hematologic malignancies. EXPERIMENTAL DESIGN: Eligible patients were assigned to one of five disease-specific, parallel cohorts and given 12.5 mg deforolimus as a 30-minute infusion once daily for 5 days every 2 weeks. A Simon two-stage design was used for each cohort. Safety, pharmacokinetics, pharmacodynamics, and antitumor response were assessed. RESULTS: Fifty-five patients received deforolimus as follows: cohort 1 23 acute myelogenous leukemia, two myelodysplastic syndrome and one chronic myelogenous leukemia in nonlymphoid blast phase; cohort 2, one acute lymphocytic leukemia; cohort 3, nine agnogenic myeloid metaplasia; cohort 4, eight chronic lymphocytic leukemia; cohort 5, nine mantle cell lymphoma and two T-cell leukemia/lymphoma. Most patients were heavily pretreated. Of the 52 evaluable patients, partial responses were noted in five (10%), two of seven agnogenic myeloid metaplasia and three of nine mantle cell lymphoma. Hematologic improvement/stable disease was observed in 21 (40%). Common treatment-related adverse events, which were generally mild and reversible, were mouth sores, fatigue, nausea, and thrombocytopenia. Decreased levels of phosphorylated 4E-BP1 in 9 of 11 acute myelogenous leukemia/myelodysplastic syndrome patients after therapy showed mammalian target of rapamycin inhibition by deforolimus. CONCLUSIONS: Deforolimus was well-tolerated in patients with heavily pretreated hematologic malignancies, and antitumor activity was observed. Further investigation of deforolimus alone and in combination with other therapeutic agents is warranted in patients with selected hematologic malignancies.

Authors
Rizzieri, DA; Feldman, E; Dipersio, JF; Gabrail, N; Stock, W; Strair, R; Rivera, VM; Albitar, M; Bedrosian, CL; Giles, FJ
MLA Citation
Rizzieri, DA, Feldman, E, Dipersio, JF, Gabrail, N, Stock, W, Strair, R, Rivera, VM, Albitar, M, Bedrosian, CL, and Giles, FJ. "A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies." Clin Cancer Res 14.9 (May 1, 2008): 2756-2762.
PMID
18451242
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
14
Issue
9
Publish Date
2008
Start Page
2756
End Page
2762
DOI
10.1158/1078-0432.CCR-07-1372

Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients.

The efficacy of once-daily intravenous busulfan with fludarabine as a preparative regimen for partially matched umbilical cord blood transplantation has not been formally studied. We randomized 10 adult patients with myeloid malignancies to receive either concurrent or sequential administration of intravenous busulfan 130 mg/m(2) once daily x 4 days and fludarabine 40 mg/m(2) daily x 4 days, followed by dual umbilical cord blood transplantation. The median combined cryopreserved total nucleated cell dose was 3.6 x 10(7)/kg recipient body weight (range: 2.8-4.5 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was provided by tacrolimus and mycophenolate mofetil (MMF). Donor-derived neutrophil recovery was observed in only 2 of 10 patients, resulting in premature closure of the study as per graft failure stopping rules. We conclude that the myeloablative conditioning regimen of once-daily intravenous busulfan with fludarabine provides insufficient immunosuppression to allow for engraftment of partially matched, dual umbilical cord blood grafts.

Authors
Horwitz, ME; Morris, A; Gasparetto, C; Sullivan, K; Long, G; Chute, J; Rizzieri, D; McPherson, J; Chao, N
MLA Citation
Horwitz, ME, Morris, A, Gasparetto, C, Sullivan, K, Long, G, Chute, J, Rizzieri, D, McPherson, J, and Chao, N. "Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients." Biol Blood Marrow Transplant 14.5 (May 2008): 591-594.
PMID
18410902
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
5
Publish Date
2008
Start Page
591
End Page
594
DOI
10.1016/j.bbmt.2008.02.016

Anti proliferative activity of ELACY (CP-4055) in combination with cloretazine (VNP40101M), idarubicin, gemcitabine, irinotecan and topotecan in human leukemia and lymphoma cells.

This study evaluated combination drug partners for CP-4055, the C18:1(Delta9,trans) unsaturated fatty acid ester of cytarabine in HL-60 and U937 cells. Growth inhibition was assessed by ATP assay and drug interaction by the combination index and three dimensional methods. Synergy was observed in HL-60 cells for simultaneous combinations of CP-4055 with gemcitabine, irinotecan and topotecan, while combinations with cloretazine (VNP40101M) and idarubicin were additive. In U937 cells, synergy was observed with gemcitabine and additivity for the other drugs. In HL-60, the IC50 concentration of CP-4055 could be reduced 10-fold and that of gemcitabine 3-fold in combination versus the agents alone, an interaction that was independent of drug sequence, ratio and exposure time. In contrast, interactions of CP-4055 with the topoisomerase inhibitors became antagonistic when the drugs were administered 24 h prior to CP-4055 and at certain drug ratios, particularly in U937 cells. In summary, CP-4055 produced additive to synergistic anti proliferative activity when combined simultaneously with drugs from four mechanistic classes in cell culture models of human leukemia and lymphoma. The impact of drug sequence and ratio on the interactions argues for incorporation of these parameters into the design of combination chemotherapy regimens.

Authors
Adams, DJ; Sandvold, ML; Myhren, F; Jacobsen, TF; Giles, F; Rizzieri, DA
MLA Citation
Adams, DJ, Sandvold, ML, Myhren, F, Jacobsen, TF, Giles, F, and Rizzieri, DA. "Anti proliferative activity of ELACY (CP-4055) in combination with cloretazine (VNP40101M), idarubicin, gemcitabine, irinotecan and topotecan in human leukemia and lymphoma cells." Leuk Lymphoma 49.4 (April 2008): 786-797.
PMID
18398748
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
49
Issue
4
Publish Date
2008
Start Page
786
End Page
797
DOI
10.1080/10428190801935752

Expanding nilotinib access in clinical trials (ENACT) study in adult patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myelogenous leukaemia (CML) in chronic phase (CP), accelerated phase (AP), or blast crisis (BC): updated safety analysis

Authors
Smith, G; Rizzieri, DA; Alimena, G; Al-Ali, H-K; Zaritskey, A; Shen, Z; Jootar, S; Hsu, Y; Veronese, ML; Nicolini, FE
MLA Citation
Smith, G, Rizzieri, DA, Alimena, G, Al-Ali, H-K, Zaritskey, A, Shen, Z, Jootar, S, Hsu, Y, Veronese, ML, and Nicolini, FE. "Expanding nilotinib access in clinical trials (ENACT) study in adult patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myelogenous leukaemia (CML) in chronic phase (CP), accelerated phase (AP), or blast crisis (BC): updated safety analysis." April 2008.
Source
wos-lite
Published In
British Journal of Haematology
Volume
141
Publish Date
2008
Start Page
34
End Page
35

Outcomes of a second non-myeloablative allogeneic stem cell transplantation following graft rejection.

Following initial graft rejection, a second attempt at allogeneic immunotherapy is often contemplated, but data on the success is limited. We therefore report on 11 patients with hematologic malignancies, renal cell cancer or marrow failure who underwent a second reduced-intensity regimen for primary or secondary graft failure. Nine of the 11 patients initially engrafted with the second attempt including two of four who used the same donor. One of the patients engrafted after the third attempt using a different donor and conditioning regimen. There were two treatment-related deaths. Four patients died from progressive disease 1-9 months after the second transplant. Two patients are still in recovery phase less than 1 year from the second transplant. Long-term remission is possible and three patients are alive in complete remission.

Authors
Byrne, BJ; Horwitz, M; Long, GD; Gasparetto, C; Sullivan, KM; Chute, J; Chao, NJ; Rizzieri, DA
MLA Citation
Byrne, BJ, Horwitz, M, Long, GD, Gasparetto, C, Sullivan, KM, Chute, J, Chao, NJ, and Rizzieri, DA. "Outcomes of a second non-myeloablative allogeneic stem cell transplantation following graft rejection." Bone Marrow Transplant 41.1 (January 2008): 39-43.
PMID
17982503
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
41
Issue
1
Publish Date
2008
Start Page
39
End Page
43
DOI
10.1038/sj.bmt.1705882

Detailed analysis of cytomegalovirus (CMV)-specific T cells expanded for adoptive immunotherapy of CMV infection following allogeneic stem cell transplantation for malignant disease.

BACKGROUND: Cytomegalovirus (CMV) infection and its treatment causes significant morbidity following allogeneic stem cell transplantation (SCT) for malignancies. We studied the phenotype, function and growth kinetics of CMV pp65 antigen (Ag)-specific T cells expanded in a short-term culture for adoptive therapy. METHODS: Peripheral blood mononuclear cells (PBMC) from CMV-seropositive donors were cultured in various conditions with CMV pp65((495-503)) peptide to determine the most effective method for generating CMV-specific T cells. CMV-expanded cultures were tested for frequency, phenotype and functionality using peptide-MHC tetramer analysis, cytokine flow cytometry and cytolytic assays. A patient undergoing allogeneic SCT was administered CMV pp65-specific T cells generated from the donor based on these data, and recipient PBMC were analyzed following T-cell infusion. RESULTS: CMV pp65-specific T cells were consistently generated from CMV-seropositive donors at high frequencies (20-40% of CD8+ T cells), secreted interferon-gamma (IFN-gamma) in response to CMV peptide and had lytic activity against CMV peptide-expressing targets. Cultured CMV-specific T cells were infused into a SCT recipient without toxicity. DISCUSSION: Stimulating donor PBMC to generate functional, Ag-specific T cells for infusion into SCT recipients was accomplished consistently using readily available technology. We observed no toxicity in one patient receiving T cells and were able to monitor infused cells. These findings support further study of this approach as a prophylaxis against the risk of infection in patients receiving allogeneic transplantation from CMV-seropositive donors.

Authors
Hobeika, A; Osada, T; Serra, D; Peplinski, S; Hanson, K; Tanaka, Y; Niedzwiecki, D; Chao, N; Rizzieri, D; Lyerly, H; Clay, T; Morse, M
MLA Citation
Hobeika, A, Osada, T, Serra, D, Peplinski, S, Hanson, K, Tanaka, Y, Niedzwiecki, D, Chao, N, Rizzieri, D, Lyerly, H, Clay, T, and Morse, M. "Detailed analysis of cytomegalovirus (CMV)-specific T cells expanded for adoptive immunotherapy of CMV infection following allogeneic stem cell transplantation for malignant disease." Cytotherapy 10.3 (2008): 289-302.
PMID
18418774
Source
pubmed
Published In
Cytotherapy (Informa)
Volume
10
Issue
3
Publish Date
2008
Start Page
289
End Page
302
DOI
10.1080/14653240801927040

Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: A phase II trial of the Cancer and Leukemia Group B

Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide. © 2008 The Authors.

Authors
Smith, SM; Grinblatt, D; Johnson, JL; Niedzwiecki, D; Rizzieri, D; Bartlett, NL; Cheson, BD
MLA Citation
Smith, SM, Grinblatt, D, Johnson, JL, Niedzwiecki, D, Rizzieri, D, Bartlett, NL, and Cheson, BD. "Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: A phase II trial of the Cancer and Leukemia Group B." British Journal of Haematology 140.3 (2008): 313-319.
PMID
18217897
Source
scival
Published In
British Journal of Haematology
Volume
140
Issue
3
Publish Date
2008
Start Page
313
End Page
319
DOI
10.1111/j.1365-2141.2007.06937.x

Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia

DT388IL3 fusion protein containing the catalytic and translocation domains of diphtheria toxin fused to human interleukin 3 was administered in an inter-patient dose escalation trial by 15 min i.v. infusions every other day for up to 6 doses to patients with chemo-refractory acute myeloid leukemia (AML) and myelodysplasia (MDS). The maximal tolerated dose was & 12.5 μg/kg/dose. Transient grade 3 transaminasemia and grade 2 fevers, chills, hypoalbuminemia, and hypotension occurred. Peak DT388IL3 levels correlated with dose and day of administration but not antibody titer. Anti-DT388IL3 antibodies developed in most patients between day 15 and 30. Of 40 evaluable AML patients, 1 had a CR (8 months) and 1 had PR (3 months). Of 5 MDS patients, 1 had a PR (4 months). Because of the prolonged infusion schedule, many patients failed to receive six doses. DT388IL3 produces remissions in patients with relapsed/ refractory AML and MDS with minimal toxicities, and alternate schedules of administration are needed to enhance the response rate.

Authors
Frankel, A; Liu, J-S; Rizzieri, D; Hogge, D
MLA Citation
Frankel, A, Liu, J-S, Rizzieri, D, and Hogge, D. "Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia." Leukemia and Lymphoma 49.3 (2008): 543-553.
PMID
18297533
Source
scival
Published In
Leukemia & Lymphoma (Informa)
Volume
49
Issue
3
Publish Date
2008
Start Page
543
End Page
553
DOI
10.1080/10428190701799035

RELEVANCE OF INHIBITORY AND ACTIVATING KIR AND HLA LIGAND ON OUTCOMES IN REDUCED INTENSITY HAPLOIDENTICAL PERIPHERAL BLOOD STEM CELL TRANSPLANTS

Authors
Chen, D-F; Prasad, VK; Broadwater, G; Clark, A; Rizzieri, DA; Chao, NJ; Reinsmoen, NL
MLA Citation
Chen, D-F, Prasad, VK, Broadwater, G, Clark, A, Rizzieri, DA, Chao, NJ, and Reinsmoen, NL. "RELEVANCE OF INHIBITORY AND ACTIVATING KIR AND HLA LIGAND ON OUTCOMES IN REDUCED INTENSITY HAPLOIDENTICAL PERIPHERAL BLOOD STEM CELL TRANSPLANTS." 2008.
Source
wos-lite
Published In
Human Immunology
Volume
69
Publish Date
2008
Start Page
S8
End Page
S8
DOI
10.1016/j.humimm.2008.08.018

Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia.

Several parameters may predict disease severity and overall survival in chronic lymphocytic leukemia (CLL). The purpose of our study of 190 CLL patients was to compare immunoglobulin heavy chain variable region (IgV(H)) mutation status, cytogenetic abnormalities, and leukemia cell CD38 and Zap-70 to older, traditional parameters. We also wanted to construct a simple, inexpensive prognosis score that would significantly predict TTT and survival in patients at the time of diagnosis and help practicing clinicians. In univariate analyses, patients with higher clinical stage, higher leukocyte count at diagnosis, shorter leukocyte doubling time, elevated serum lactate dehydrogenase (LDH), unmutated immunoglobulin heavy chain variable region (IgV(H)) genes, and higher CD38 had a shorter overall survival and time-to-treatment (TTT). CLL cell Zap-70 expression was higher in patients with unmutated IgV(H), and those with higher Zap-70 tended to have shorter survival. IgV(H)4-34 or IgV(H)1-69 was the most common IgV(H) genes used (16 and 12%, respectively). Of those with IgV(H)1-69, 86% had unmutated IgV(H) and had a significantly shorter TTT. A cytogenetic abnormality was noted in 71% of the patients tested. Patients with 11q22 del and 17p13 del or complex abnormalities were significantly more likely to have unmutated IgV(H). We found that a prognostic score constructed using modified Rai stage, cellular CD38, and serum LDH (parameters easily obtained clinically) significantly predicted TTT and survival in patients at the time of diagnosis and performed as well or better than models using the newer markers.

Authors
Weinberg, JB; Volkheimer, AD; Chen, Y; Beasley, BE; Jiang, N; Lanasa, MC; Friedman, D; Vaccaro, G; Rehder, CW; Decastro, CM; Rizzieri, DA; Diehl, LF; Gockerman, JP; Moore, JO; Goodman, BK; Levesque, MC
MLA Citation
Weinberg, JB, Volkheimer, AD, Chen, Y, Beasley, BE, Jiang, N, Lanasa, MC, Friedman, D, Vaccaro, G, Rehder, CW, Decastro, CM, Rizzieri, DA, Diehl, LF, Gockerman, JP, Moore, JO, Goodman, BK, and Levesque, MC. "Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia." Am J Hematol 82.12 (December 2007): 1063-1070.
PMID
17654680
Source
pubmed
Published In
American Journal of Hematology
Volume
82
Issue
12
Publish Date
2007
Start Page
1063
End Page
1070
DOI
10.1002/ajh.20987

Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics.

End-organ damage is common in patients with sickle cell disease (SCD) thereby limiting the use of allogeneic stem cell transplantation (SCT). We report the outcome of 2 adult SCD patients, 1 with end-stage renal disease (ESRD), who underwent fludarabine-based nonmyeloablative SCT from HLA-identical matched siblings. To prevent fludarabine toxicity, the patient with ESRD underwent aggressive dialysis following adjusted fludarabine dosing. Pharmacokinetics of the fludarabine metabolite F-Ara-A was studied on the patient with ESRD and 2 additional patients with normal renal function. Both patients with SCD achieved full donor erythroid chimerism, have normal blood counts, and are on no immunosuppressive medications. With a 20% dose reduction followed by daily dialysis, we achieved fludarabine drug exposure that is nearly identical to that achieved in patients with normal renal function. We conclude that fludarabine-based nonmyeloablative allogeneic SCT for adult patients with SCD is feasible, even in the setting of ESRD.

Authors
Horwitz, ME; Spasojevic, I; Morris, A; Telen, M; Essell, J; Gasparetto, C; Sullivan, K; Long, G; Chute, J; Chao, N; Rizzieri, D
MLA Citation
Horwitz, ME, Spasojevic, I, Morris, A, Telen, M, Essell, J, Gasparetto, C, Sullivan, K, Long, G, Chute, J, Chao, N, and Rizzieri, D. "Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics." Biol Blood Marrow Transplant 13.12 (December 2007): 1422-1426.
PMID
18022571
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
12
Publish Date
2007
Start Page
1422
End Page
1426
DOI
10.1016/j.bbmt.2007.08.050

Cytotoxicity of the type 4 phosphodiesterase inhibitor CD160130 for freshly isolated human CLL cells in vitro

Authors
Weinberg, JB; Jiang, N; Volkheimer, AD; Chen, Y; Bond, KM; Moore, JO; Gockerman, JP; Diehl, LF; de Castro, CM; Rizzieri, DA; Levesque, MC; Mugridge, K; DeAngelo, J
MLA Citation
Weinberg, JB, Jiang, N, Volkheimer, AD, Chen, Y, Bond, KM, Moore, JO, Gockerman, JP, Diehl, LF, de Castro, CM, Rizzieri, DA, Levesque, MC, Mugridge, K, and DeAngelo, J. "Cytotoxicity of the type 4 phosphodiesterase inhibitor CD160130 for freshly isolated human CLL cells in vitro." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
920A
End Page
921A

Apolipoprotein E (APOE) genotype as a determinant of survival in women with chronic lymphocytic leukemia

Authors
Weinberg, JB; Volkheimer, AD; Mihovilovic, M; Jiang, N; Chen, Y; Moore, JO; Gockerman, JP; Diehl, LF; de Castro, CM; Rizzieri, DA; Levesque, MC; DeKroon, R; Strittmatter, WJ
MLA Citation
Weinberg, JB, Volkheimer, AD, Mihovilovic, M, Jiang, N, Chen, Y, Moore, JO, Gockerman, JP, Diehl, LF, de Castro, CM, Rizzieri, DA, Levesque, MC, DeKroon, R, and Strittmatter, WJ. "Apolipoprotein E (APOE) genotype as a determinant of survival in women with chronic lymphocytic leukemia." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
906A
End Page
906A

Phase I study demonstrates activity and tolerability of diphtheria toxin interleukin-3 fusion protein in patients with AML and MDS

Authors
Frankel, AE; Smith, ER; George, TA; Liu, JS; Lee, J; Park, SK; Rizzieri, DA; Hogge, DE
MLA Citation
Frankel, AE, Smith, ER, George, TA, Liu, JS, Lee, J, Park, SK, Rizzieri, DA, and Hogge, DE. "Phase I study demonstrates activity and tolerability of diphtheria toxin interleukin-3 fusion protein in patients with AML and MDS." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
273A
End Page
273A

Allogeneic hematopoietic stem cell transplant using mismatched/haploidentical donors.

Haploidentical hematopoietic stem cell transplantation (HSCT) provides an opportunity for nearly all patients to benefit from HSCT when a human leukocyte antigen (HLA) genotypically matched sibling is not available. Initial results with the use of mismatched allografts led to limited enthusiasm because of graft-versus-host disease (GVHD) and infectious complications, resulting in an unacceptable treatment-related morbidity and mortality. Recent advances with effective T cell depletion, the use of a "megadose" of stem cells, earlier detection of severe infections, combined with better antimicrobial therapy and reduced-intensity conditioning (RIC) has significantly decreased the early transplant-related mortality and GVHD, whereas enabling prompt engraftment, hence advancing the therapeutic benefit of haploidentical transplantation. However, the cardinal problems related to delayed immune reconstitution allowing posttransplant infectious complications and relapse remain, limiting the efficacy of haploidentical HSCT. Preliminary data has demonstrated the potential for use of adoptive cellular immunity and selective allodepletion in rapidly reconstituting immunity without GVHD. The encouraging reports from haploidentical transplant using noninherited maternal antigen (NIMA)-mismatched or natural killer (NK) alloreactive donors may greatly increase the donor availability and open the way to more appropriate donor selection in HLA-haploidentical HSCT. Future challenges remain in determining the safest approach for haploidentical transplant to be performed with minimal risk of GVHD, whereas preserving effective graft-versus-leukemia activity and promoting prompt immune reconstitution.

Authors
Koh, L-P; Rizzieri, DA; Chao, NJ
MLA Citation
Koh, L-P, Rizzieri, DA, and Chao, NJ. "Allogeneic hematopoietic stem cell transplant using mismatched/haploidentical donors." Biol Blood Marrow Transplant 13.11 (November 2007): 1249-1267. (Review)
PMID
17950913
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
11
Publish Date
2007
Start Page
1249
End Page
1267
DOI
10.1016/j.bbmt.2007.08.003

Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution.

PURPOSE: Allogeneic transplantation is typically limited to younger patients having a matched donor. To allow a donor to be found for nearly all patients, we have used a nonmyeloablative conditioning regimen in conjunction with stem cells from a related donor with one fully mismatched HLA haplotype. PATIENTS AND METHODS: Fludarabine, cyclophosphamide, and alemtuzumab were used as the preparatory regimen. Additional graft-versus-host disease (GVHD) prophylaxis included mycophenolate with or without cyclosporine. Patients with persistence of disease had a donor lymphocyte boost planned. Toxicities, engraftment, response, survival, and immune recovery are reported. RESULTS: Forty-nine patients with hematologic malignancies or marrow failure and no other available donors were enrolled. Ninety-four percent of patients had successful engraftment, and 8% had secondary graft failure. The treatment-related mortality rate was 10.2%, and 8% of patients had severe GVHD. Encouraging evidence of quantitative lymphocyte recovery through expansion of transplanted T cells was noted by 3 to 6 months. Seventy-five percent of patients attained a complete remission, and 1-year survival rate was 31% (95% CI, 18% to 44%). A standard-risk group of 19 patients with aplasia or in remission at transplantation demonstrated a 63% 1-year survival rate (95% CI, 38% to 80%) and 2.9-year median overall survival time (95% CI, 6.2 to 48 months). CONCLUSION: Nonmyeloablative therapy using haploidentical family member donors is feasible because the main obstacles of GVHD and graft rejection are manageable, allowing readily available stem-cell donors to be found for nearly all patients. Further qualitative and quantitative improvement in immune recovery is needed to address the high rate of relapse and risk of severe infections.

Authors
Rizzieri, DA; Koh, LP; Long, GD; Gasparetto, C; Sullivan, KM; Horwitz, M; Chute, J; Smith, C; Gong, JZ; Lagoo, A; Niedzwiecki, D; Dowell, JM; Waters-Pick, B; Liu, C; Marshall, D; Vredenburgh, JJ; Gockerman, J; Decastro, C; Moore, J; Chao, NJ
MLA Citation
Rizzieri, DA, Koh, LP, Long, GD, Gasparetto, C, Sullivan, KM, Horwitz, M, Chute, J, Smith, C, Gong, JZ, Lagoo, A, Niedzwiecki, D, Dowell, JM, Waters-Pick, B, Liu, C, Marshall, D, Vredenburgh, JJ, Gockerman, J, Decastro, C, Moore, J, and Chao, NJ. "Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution." J Clin Oncol 25.6 (February 20, 2007): 690-697.
PMID
17228020
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
6
Publish Date
2007
Start Page
690
End Page
697
DOI
10.1200/JCO.2006.07.0953

Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia.

PURPOSE: Cloretazine (VNP40101M) is a sulfonylhydrazine alkylating agent with significant antileukemia activity. A multicenter phase II study of cloretazine was conducted in patients 60 years of age or older with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). PATIENTS AND METHODS: Cloretazine 600 mg/m2 was administered as a single intravenous infusion. Patients were stratified by age, performance score, cytogenetic risk category, type of AML, and comorbidity. RESULTS: One hundred four patients, median age 72 years (range, 60 to 84 years), were treated on study. Performance status was 2 in 31 patients (30%) and no patient had a favorable karyotype. Forty-seven patients (45%) had cardiac disease, 25 patients (24%) had hepatic disease, and 19 patients (18%) had pulmonary disease, defined as per the Hematopoietic Cell Transplantation-Specific Comorbidity Index, at study entry. The overall response rate was 32%, with 29 patients (28%) achieving complete response (CR) and four patients (4%) achieving CR with incomplete platelet recovery. Response rates in 44 de novo AML patients, 45 secondary AML patients, and 15 high-risk MDS patients were 50%, 11%, and 40%, respectively. Response by cytogenetic risk category was 39% in 56 patients with intermediate cytogenetic risk and 24% in 46 patients with unfavorable cytogenetic risk. Nineteen (18%) patients died within 30 days of receiving cloretazine therapy. Median overall survival was 94 days, with a 1-year survival of 14%; the median duration of survival was 147 days, with a 1-year survival of 28% for those who achieved CR. CONCLUSION: Cloretazine has significant activity and modest extramedullary toxicity in elderly patients with AML or high-risk MDS. Response rates remain consistent despite increasing age and comorbidity.

Authors
Giles, F; Rizzieri, D; Karp, J; Vey, N; Ravandi, F; Faderl, S; Khan, KD; Verhoef, G; Wijermans, P; Advani, A; Roboz, G; Kantarjian, H; Bilgrami, SFA; Ferrant, A; Daenen, SMGJ; Karsten, V; Cahill, A; Albitar, M; Mufti, G; O'Brien, S
MLA Citation
Giles, F, Rizzieri, D, Karp, J, Vey, N, Ravandi, F, Faderl, S, Khan, KD, Verhoef, G, Wijermans, P, Advani, A, Roboz, G, Kantarjian, H, Bilgrami, SFA, Ferrant, A, Daenen, SMGJ, Karsten, V, Cahill, A, Albitar, M, Mufti, G, and O'Brien, S. "Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia." J Clin Oncol 25.1 (January 1, 2007): 25-31.
PMID
17146105
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
1
Publish Date
2007
Start Page
25
End Page
31
DOI
10.1200/JCO.2006.07.0961

MK-0457, a novel multikinase inhibitor, has activity in refractory AML, including transformed JAK2 positive myeloproliferative disease (MPD), and in Philadelphia-positive ALL.

Authors
Giles, F; Freedman, SJ; Xiao, A; Borthakur, G; Garcia-Manero, G; Wierda, W; Kornblau, SM; O'Brien, S; Bergstrom, DA; Rizzieri, DA
MLA Citation
Giles, F, Freedman, SJ, Xiao, A, Borthakur, G, Garcia-Manero, G, Wierda, W, Kornblau, SM, O'Brien, S, Bergstrom, DA, and Rizzieri, DA. "MK-0457, a novel multikinase inhibitor, has activity in refractory AML, including transformed JAK2 positive myeloproliferative disease (MPD), and in Philadelphia-positive ALL." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
556A
End Page
557A

MK-0457, a novel multikinase inhibitor, has activity in refractory AML, including transformed JAK2 positive myeloproliferative disease (MPD), and in Philadelphia-positive ALL.

Authors
Giles, F; Freedman, SJ; Xiao, A; Borthakur, G; Garcia-Manero, G; Wierda, W; Kornblau, SM; O'Brien, S; Bergstrom, DA; Rizzieri, DA
MLA Citation
Giles, F, Freedman, SJ, Xiao, A, Borthakur, G, Garcia-Manero, G, Wierda, W, Kornblau, SM, O'Brien, S, Bergstrom, DA, and Rizzieri, DA. "MK-0457, a novel multikinase inhibitor, has activity in refractory AML, including transformed JAK2 positive myeloproliferative disease (MPD), and in Philadelphia-positive ALL." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
556A
End Page
556A

A phase I study of cloretazine (R) and temozolomide in patients with hematologic malignancies.

Authors
Rizzieri, DA; Tse, W; Khan, KD; Advani, A; Donze, J; Karsten, V; Geller, RB; Gerson, SL
MLA Citation
Rizzieri, DA, Tse, W, Khan, KD, Advani, A, Donze, J, Karsten, V, Geller, RB, and Gerson, SL. "A phase I study of cloretazine (R) and temozolomide in patients with hematologic malignancies." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
557A
End Page
558A

Antiproliferative activity of ELACYT (TM) (CP-4055) in combination with cloretazine (VNP40101M), idarubicin or gemcitabine in HL-60 human myeloid leukemia cells.

Authors
Adams, DJ; Sandvold, ML; Myhren, F; Jacobsen, TF; Rizzieri, DA
MLA Citation
Adams, DJ, Sandvold, ML, Myhren, F, Jacobsen, TF, and Rizzieri, DA. "Antiproliferative activity of ELACYT (TM) (CP-4055) in combination with cloretazine (VNP40101M), idarubicin or gemcitabine in HL-60 human myeloid leukemia cells." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
563A
End Page
564A

Morphologic examination of sequential bone marrow biopsies after nonmyeloablative stem cell transplantation complements molecular studies of donor engraftment.

CONTEXT: Nonmyeloablative stem cell transplantation (NMSCT) is a mode of immunotherapy increasingly employed in treating hematologic, lymphoid, and solid tumors. Patients are monitored principally by molecular analysis of donor engraftment. OBJECTIVE: To determine the role of morphologic examination of bone marrow after NMSCT. DESIGN: Seventy-three patients undergoing NMSCT under the Campath 1H (humanized anti-CD52 antibody) protocol were studied. Pretransplant and sequential posttransplant bone marrow specimens were evaluated and the findings were correlated with corresponding engraftment data. RESULTS: Pretransplant bone marrow specimens from 43% of the patients were involved by disease, and these marrow specimens were significantly more cellular than those that were free of disease. Morphologically detectable disease was still present in day 14 posttransplant marrow specimens in more than one half of these patients, but there was no difference in engraftment in those with or without marrow disease. Early posttransplant marrow in nearly one half of the patients showed myeloid hyperplasia and atypical localization of immature myeloid precursors. Marrow cellularity for the first 2 months after NMSCT was significantly lower in those patients receiving stem cells mismatched at 1 to 3 loci as compared with those who received fully matched grafts (mean cellularity, 38.1% vs 54.1% at day 14). Marrow failure without recurrent disease at 3 to 6 months after transplant was detected by engraftment study in only approximately 15% of cases. Similarly, early recurrence of disease was detected first by morphologic examination in 4 of 13 cases before a decline in donor engraftment occurred. CONCLUSION: Morphologic examination of bone marrow provides additional information that is complementary to donor engraftment analysis for optimal management after NMSCT.

Authors
Lagoo, AS; Gong, JZ; Stenzel, TT; Goodman, BK; Buckley, PJ; Chao, NJ; Gasparetto, C; Long, GD; Rizzieri, DA
MLA Citation
Lagoo, AS, Gong, JZ, Stenzel, TT, Goodman, BK, Buckley, PJ, Chao, NJ, Gasparetto, C, Long, GD, and Rizzieri, DA. "Morphologic examination of sequential bone marrow biopsies after nonmyeloablative stem cell transplantation complements molecular studies of donor engraftment." Arch Pathol Lab Med 130.10 (October 2006): 1479-1488.
PMID
17090189
Source
pubmed
Published In
Archives of Pathology and Laboratory Medicine
Volume
130
Issue
10
Publish Date
2006
Start Page
1479
End Page
1488
DOI
10.1043/1543-2165(2006)130[1479:MEOSBM]2.0.CO;2

Diptheria toxin-interleukin 3 fusion protein therapy of patients with elderly or relapsed/refractory acute myeloid leukemia (AML).

Authors
Frankel, AE; Weir, MA; Hall, PD; Hogge, DE; Rizzieri, DA
MLA Citation
Frankel, AE, Weir, MA, Hall, PD, Hogge, DE, and Rizzieri, DA. "Diptheria toxin-interleukin 3 fusion protein therapy of patients with elderly or relapsed/refractory acute myeloid leukemia (AML)." June 20, 2006.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
24
Issue
18
Publish Date
2006
Start Page
354S
End Page
354S

Consolidation with high-dose combination alkylating agents with bone marrow transplantation significantly improves disease-free survival in hormone-insensitive metastatic breast cancer in complete remission compared with intensive standard-dose chemotherapy alone.

We conducted this study to determine event-free and overall survival among women with hormone-insensitive or hormone-resistant metastatic breast cancer receiving consolidation with high-dose chemotherapy (HDC) and hematopoietic support versus no further chemotherapy after intensive induction chemotherapy. Eligible patients received induction doxorubicin, 5-fluorouracil, and methotrexate (AFM) for 2 to 4 cycles. Women in complete remission were randomized to immediate HDC with cyclophosphamide, cisplatin, and carmustine followed by autologous hematopoietic support or to no further therapy. Patients on the observation arm of therapy were offered salvage HDC at the time of relapse. Partial responders to AFM were offered immediate HDC. A total of 425 patients were enrolled onto the study. The median event-free survival for women randomized to induction therapy alone was 3.8 months, compared with 9.7 months for women who completed HDC (P < .006). Of the patients randomized to observation, 5 (10%) of 51 remain event free, compared with 13 (26%) of 49 patients who underwent immediate HDC (P = .03). Of women converted to a complete response by salvage HDC after a partial response to AFM, overall survival was similar to that in women randomized to immediate HDC. Follow-up is now in excess of 5 years. The 5-year event-free survival is 15% (95% confidence interval, 12%-18%), and the 5-year overall survival is 20% (95% confidence interval, 17%-25%). Immediate HDC after a complete response to AFM produced some durable long-term responses in hormone-insensitive/-resistant metastatic breast cancer. Salvage HDC converted 30% of partial responders to complete responders with similar survivals. The addition of novel targeted therapies to intensive-dose chemotherapy regimens may further improve survival in metastatic breast cancer.

Authors
Vredenburgh, JJ; Coniglio, D; Broadwater, G; Jones, RB; Ross, M; Shpall, EJ; Hussein, A; Rizzieri, D; Marks, LB; Gilbert, C; Affronti, ML; Moore, S; McDonald, C; Petros, WP; Peters, WP
MLA Citation
Vredenburgh, JJ, Coniglio, D, Broadwater, G, Jones, RB, Ross, M, Shpall, EJ, Hussein, A, Rizzieri, D, Marks, LB, Gilbert, C, Affronti, ML, Moore, S, McDonald, C, Petros, WP, and Peters, WP. "Consolidation with high-dose combination alkylating agents with bone marrow transplantation significantly improves disease-free survival in hormone-insensitive metastatic breast cancer in complete remission compared with intensive standard-dose chemotherapy alone." Biol Blood Marrow Transplant 12.2 (February 2006): 195-203.
PMID
16443517
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
195
End Page
203
DOI
10.1016/j.bbmt.2005.10.009

Impact of donor KIR genotype and recipient hla ligand incompatibility on relapse related mortality and acute graft versus host disease in high-risk patients undergoing haploidentical non-myeloablative peripheral blood stem cell transplants: Differences between lymphoid and myeloid malignancies

Authors
Prasad, VK; Chen, DF; Reinsmoen, NL; Broadwater, G; Chao, NJ; Rizzieri, DA
MLA Citation
Prasad, VK, Chen, DF, Reinsmoen, NL, Broadwater, G, Chao, NJ, and Rizzieri, DA. "Impact of donor KIR genotype and recipient hla ligand incompatibility on relapse related mortality and acute graft versus host disease in high-risk patients undergoing haploidentical non-myeloablative peripheral blood stem cell transplants: Differences between lymphoid and myeloid malignancies." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
15
End Page
15
DOI
10.1016/j.bbmt.2005.11.050

Phase II multicenter study of arsenic trioxide in patients with myelodysplastic syndromes

Purpose: To evaluate the efficacy and safety of arsenic trioxide monotherapy in patients with myelodysplastic syndromes (MDS). Patients and Methods: Patients received arsenic trioxide (0.25 mg/kg/d) on 5 consecutive days per week for 2 weeks, followed by 2 weeks' rest (one cycle). Two patient cohorts were established according to International Prognostic Scoring System risk category: lower-risk (low or intermediate-1) or higher-risk MDS (intermediate-2 or high). For lower-risk MDS, hematologic improvement (HI) was the primary response end point. For higher-risk MDS, additional end points included complete or partial remission. Based on the expected time to response, patients receiving two or more cycles were prospectively evaluated. Results: Hematologic adverse events included neutropenia, thrombocytopenia, and febrile neutropenia. Two patients died during the study due to treatment-related toxicities. Most common grade 3/4 nonhematologic events were pneumonia, fatigue, hemorrhage, pain, and dyspnea. Among patients who received one or more doses (n = 70) or completed two or more cycles (n = 51), the HI rates were 34% and 39% in lower-risk patients, and 6% and 9% in higher-risk patients, respectively; the overall major HI rates were 20% and 22%. One higher-risk patient achieved a complete remission (3%). Major HIs were observed in all hematologic lineages; erythroid responses were the most common. Transfusion independence or reduction by ≥ 50% occurred in 33% of patients dependent on RBC transfusions. The overall median duration of HI was 6.8 months (range, 2 to 40 months). Conclusion: Arsenic trioxide monotherapy has moderate activity against MDS, with a manageable adverse effect profile. The further study of arsenic trioxide in MDS, particularly in combination with other agents, is warranted. © 2006 by American Society of Clinical Oncology.

Authors
Schiller, GJ; Slack, J; Hainsworth, JD; Mason, J; Saleh, M; Rizzieri, D; Douer, D; List, AF
MLA Citation
Schiller, GJ, Slack, J, Hainsworth, JD, Mason, J, Saleh, M, Rizzieri, D, Douer, D, and List, AF. "Phase II multicenter study of arsenic trioxide in patients with myelodysplastic syndromes." Journal of Clinical Oncology 24.16 (2006): 2456-2464.
PMID
16651647
Source
scival
Published In
Journal of Clinical Oncology
Volume
24
Issue
16
Publish Date
2006
Start Page
2456
End Page
2464
DOI
10.1200/JCO.2005.03.7903

Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells.

In this study, we investigated whether elimination of CD4+/CD25+ Tregs using the recombinant IL-2 diphtheria toxin conjugate DAB(389)IL-2 (also known as denileukin diftitox and ONTAK) is capable of enhancing the immunostimulatory efficacy of tumor RNA-transfected DC vaccines. We show that DAB(389)IL-2 is capable of selectively eliminating CD25-expressing Tregs from the PBMCs of cancer patients without inducing toxicity on other cellular subsets with intermediate or low expression of CD25. DAB(389)IL-2-mediated Treg depletion resulted in enhanced stimulation of proliferative and cytotoxic T cell responses in vitro but only when DAB(389)IL-2 was omitted during T cell priming. DAB(389)IL-2 significantly reduced the number of Tregs present in the peripheral blood of metastatic renal cell carcinoma (RCC) patients and abrogated Treg-mediated immunosuppressive activity in vivo. Moreover, DAB(389)IL-2-mediated elimination of Tregs followed by vaccination with RNA-transfected DCs significantly improved the stimulation of tumor-specific T cell responses in RCC patients when compared with vaccination alone. Our findings may have implications in the design of immune-based strategies that may incorporate the Treg depletion strategy to achieve potent antitumor immunity with therapeutic impact.

Authors
Dannull, J; Su, Z; Rizzieri, D; Yang, BK; Coleman, D; Yancey, D; Zhang, A; Dahm, P; Chao, N; Gilboa, E; Vieweg, J
MLA Citation
Dannull, J, Su, Z, Rizzieri, D, Yang, BK, Coleman, D, Yancey, D, Zhang, A, Dahm, P, Chao, N, Gilboa, E, and Vieweg, J. "Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells." J Clin Invest 115.12 (December 2005): 3623-3633.
PMID
16308572
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
115
Issue
12
Publish Date
2005
Start Page
3623
End Page
3633
DOI
10.1172/JCI25947

A phase 2 clinical trial of AP23573, an mTOR inhibitor, In patients with relapsed or refractory hematologic malignancies

Authors
Rizzieri, DA; Feldman, E; Moore, JO; Roboz, GJ; DiPersio, JF; Gabrail, N; Stock, W; Rivera, VM; Albitar, M; Bedrosian, CL; Giles, F
MLA Citation
Rizzieri, DA, Feldman, E, Moore, JO, Roboz, GJ, DiPersio, JF, Gabrail, N, Stock, W, Rivera, VM, Albitar, M, Bedrosian, CL, and Giles, F. "A phase 2 clinical trial of AP23573, an mTOR inhibitor, In patients with relapsed or refractory hematologic malignancies." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
835A
End Page
836A

Phase I study of gemcitabine, fludarabine and mitoxantrone for relapsed or refractory leukemia.

Authors
Misra, D; Moore, JO; Gockerman, JP; Diehl, L; de Castro, C; Yang, YP; Gasparetto, C; Abernathy, A; Horwitz, M; Long, GD; Chute, J; Peterson, B; Chao, NJ; Rizzieri, DA
MLA Citation
Misra, D, Moore, JO, Gockerman, JP, Diehl, L, de Castro, C, Yang, YP, Gasparetto, C, Abernathy, A, Horwitz, M, Long, GD, Chute, J, Peterson, B, Chao, NJ, and Rizzieri, DA. "Phase I study of gemcitabine, fludarabine and mitoxantrone for relapsed or refractory leukemia." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
235B
End Page
235B

Partially HLA matched, non-myeloablative allogeneic transplantation

Authors
Rizzieri, DA; Koh, LP; Long, GD; Gasparetto, C; Sullivan, KM; Horwitz, M; Chute, J; Gong, JZ; Lagoo, AS; Niedzwiecki, D; Lu, CX; Marshall, D; Dowell, JM; Chao, NJ
MLA Citation
Rizzieri, DA, Koh, LP, Long, GD, Gasparetto, C, Sullivan, KM, Horwitz, M, Chute, J, Gong, JZ, Lagoo, AS, Niedzwiecki, D, Lu, CX, Marshall, D, Dowell, JM, and Chao, NJ. "Partially HLA matched, non-myeloablative allogeneic transplantation." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
812A
End Page
812A

Outcome and immune reconstitution following T cell depleted nonmyeloablative allogeneic transplantation using matched donors

Authors
Rizzieri, DA; Koh, LP; Long, GD; Gasparetto, C; Gong, JZ; Lagoo, AS; Niedzwiecki, D; Sullivan, KM; Chute, J; Horwitz, M; Ashley, M; Chao, NJ
MLA Citation
Rizzieri, DA, Koh, LP, Long, GD, Gasparetto, C, Gong, JZ, Lagoo, AS, Niedzwiecki, D, Sullivan, KM, Chute, J, Horwitz, M, Ashley, M, and Chao, NJ. "Outcome and immune reconstitution following T cell depleted nonmyeloablative allogeneic transplantation using matched donors." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
576A
End Page
576A

A prospective study of bortezomib in combination with melphalan and prednisone for patients with previously untreated multiple myeloma.

Authors
Gasparetto, C; Keogh, GP; Gockerman, JP; Horwitz, M; Moore, JO; DeCastro, C; Diehl, L; Davis, P; Chao, N; Rizzieri, DA
MLA Citation
Gasparetto, C, Keogh, GP, Gockerman, JP, Horwitz, M, Moore, JO, DeCastro, C, Diehl, L, Davis, P, Chao, N, and Rizzieri, DA. "A prospective study of bortezomib in combination with melphalan and prednisone for patients with previously untreated multiple myeloma." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
379B
End Page
379B

Efficacy of performing a second non-myeloablative allogenic stem cell transplant.

Authors
Byrne, BJ; Antin, JH; Alyea, EP; Choa, NJ; Rizzieri, DA
MLA Citation
Byrne, BJ, Antin, JH, Alyea, EP, Choa, NJ, and Rizzieri, DA. "Efficacy of performing a second non-myeloablative allogenic stem cell transplant." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
1020A
End Page
1020A

Multimodal dose dense therapy for mantle cell lymphoma.

Authors
Wanko, SO; Gockerman, JP; Moore, JO; de Castro, C; Diehl, L; Pronitz, R; Gasparetto, C; Chute, J; Horwitz, M; Morris, A; Ali-Osman, F; Rao, A; Niedzweicki, D; Long, GD; Chao, NJ; Rizzieri, DA
MLA Citation
Wanko, SO, Gockerman, JP, Moore, JO, de Castro, C, Diehl, L, Pronitz, R, Gasparetto, C, Chute, J, Horwitz, M, Morris, A, Ali-Osman, F, Rao, A, Niedzweicki, D, Long, GD, Chao, NJ, and Rizzieri, DA. "Multimodal dose dense therapy for mantle cell lymphoma." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
463B
End Page
463B

An unusual 4-way translocation resulting in a rare BCR-ABL fusion transcript (e13a3) and cytogenetic evolution in chronic myeloid leukemia (CML).

Authors
Sebastian, S; Rehder, CW; Lagoo, AS; Gong, JZ; Buckley, PJ; Rizzieri, DA; Goodman, BK
MLA Citation
Sebastian, S, Rehder, CW, Lagoo, AS, Gong, JZ, Buckley, PJ, Rizzieri, DA, and Goodman, BK. "An unusual 4-way translocation resulting in a rare BCR-ABL fusion transcript (e13a3) and cytogenetic evolution in chronic myeloid leukemia (CML)." November 2005.
Source
wos-lite
Published In
The Journal of molecular diagnostics : JMD
Volume
7
Issue
5
Publish Date
2005
Start Page
661
End Page
661

Impact of donor KIR genotype and recipient HLA ligand incompatibility on relapse-related mortality in high-risk patients undergoing haploidentical non-myeloablative peripheral blood stem cell transplants: Differences between lymphoid and myelloid malignanc

Authors
Chen, DF; Prasad, VK; Broadwater, G; Rizzieri, DA; Chao, NJ; Reinsmoen, NL
MLA Citation
Chen, DF, Prasad, VK, Broadwater, G, Rizzieri, DA, Chao, NJ, and Reinsmoen, NL. "Impact of donor KIR genotype and recipient HLA ligand incompatibility on relapse-related mortality in high-risk patients undergoing haploidentical non-myeloablative peripheral blood stem cell transplants: Differences between lymphoid and myelloid malignanc." November 2005.
Source
wos-lite
Published In
Tissue Antigens
Volume
66
Issue
5
Publish Date
2005
Start Page
376
End Page
376

Tenascin and microvessel stromal changes in patients with non-Hodgkin's lymphoma are isolated to the sites of disease and vary in correlation to disease activity.

This study investigated stromal changes in expression of tenascin and vasculogenesis in lymphoma. Documenting the dynamic nature of the stromal changes in lymphoma in relation to response to therapy is helpful in planning new therapies directed at these targets. Two hundred and sixty one samples from 111 patients with varying types of non-Hodgkin's lymphoma were reviewed and examined using immunohistochemistry techniques. Samples were stained for factor VIII - related antigen for microvessel density (MVD) analysis and anti-tenascin antibody for qualitative assessment of the stromal expression. Multiple samples from the same patient were taken at the same point in time to assess whether stromal changes were limited to sites of disease. Multiple samples were examined over the course of a patient's illness to assess whether the stromal changes were modulated according to disease activity. There was a significant increase in tenascin expression and MVD in the sites of disease compared with uninvolved sites (p = 0.01 and p < 0.0001, respectively). In patients who responded to therapy, there was a decrease in the expression of tenascin (p = 0.0049) and MVD (p < 0.0001), and in those with disease progression there was an increase in the tenascin expression (p = 0.0050) and MVD (p < 0.0001). Our results suggest stromal changes are isolated to the sites of disease within patients, allowing targeted therapies to be developed. Further, stromal changes correlate with disease response over the course of the patient's disease. This new finding may have implications for the timing of anti-stromally directed therapies.

Authors
Rizzieri, DA; Wadleigh, M; Wikstrand, CJ; Mann, KP; Sen, F; Peterson, BL; Niedzwiecki, D; Proia, AD; Bigner, DD
MLA Citation
Rizzieri, DA, Wadleigh, M, Wikstrand, CJ, Mann, KP, Sen, F, Peterson, BL, Niedzwiecki, D, Proia, AD, and Bigner, DD. "Tenascin and microvessel stromal changes in patients with non-Hodgkin's lymphoma are isolated to the sites of disease and vary in correlation to disease activity." Leuk Lymphoma 46.10 (October 2005): 1455-1462.
PMID
16194891
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
46
Issue
10
Publish Date
2005
Start Page
1455
End Page
1462
DOI
10.1080/10428190500158060

Radioimmunotherapy for Non-Hodgkin's Lymphoma.

Non-Hodgkin's lymphoma (NHL) is the most common hematological malignancy in the United States with a rapidly increasing incidence. Most follicular NHL is indolent but incurable, whereas the more aggressive varieties do respond to therapy. Most patients with follicular NHL who transform to an aggressive NHL are very difficult to treat successfully. Treatment options have included chemotherapy, radiation, immunotherapy with monoclonal antibodies, alone or in combination, and hematopoietic stem cell transplantation. The efficacy of monoclonal antibodies is augmented when they are combined with a radioisotope like iodine-131 or yttrium-90. There have been a number of studies done in recent years studying the efficacy of this form of therapy, i.e., radioimmunotherapy (RIT) in patients with NHL. This review attempts to integrate the information from the various clinical trials done using RIT in patients with relapsed/refractory or newly diagnosed NHL and in hematopoietic stem cell transplantation. It also includes updates on the use of RIT in elderly patients and in patients with significant bone marrow involvement among other recent advances made in this field.

Authors
Rao, AV; Akabani, G; Rizzieri, DA
MLA Citation
Rao, AV, Akabani, G, and Rizzieri, DA. "Radioimmunotherapy for Non-Hodgkin's Lymphoma." Clin Med Res 3.3 (August 2005): 157-165. (Review)
PMID
16160070
Source
pubmed
Published In
Clinical medicine & research
Volume
3
Issue
3
Publish Date
2005
Start Page
157
End Page
165

Preclinical evaluation of gemcitabine combination regimens for application in acute myeloid leukemia.

The DNA antimetabolite gemcitabine is an anticancer agent with shown preclinical and clinical utility and a low toxicity profile. In this study, we sought to identify and optimize drug partners for binary and tertiary combinations with gemcitabine for use in the treatment of acute myelogenous leukemia (AML). Drug interaction was assessed by growth inhibition assay with metabolic end points. The combination index method was used to evaluate combinations of gemcitabine with fludarabine, paclitaxel, chlorambucil, doxorubicin, mitoxantrone, and SN-38 in U937 human AML cells. A three-dimensional method was used to determine the effect of dose ratio and schedule on drug interaction. Mechanisms underlying interactions related to cell cycle effects and apoptosis were assessed by flow cytometric and caspase-3 and -7 assays, respectively. The most synergistic binary combination was gemcitabine + fludarabine. The most synergistic tertiary combination was gemcitabine + fludarabine + paclitaxel, where the interaction was sequence dependent with paclitaxel given before gemcitabine + fludarabine, producing a 2-fold increase in synergy. Cell cycle analysis did not reveal a significant G(2)-M arrest, suggesting that the synergistic effect of paclitaxel in this combination, which produced the greatest caspase activation, might be independent of microtubule stabilization. In contrast, the gemcitabine + fludarabine + mitoxantrone combination was synergistic and schedule independent. Moreover, few ratios of gemcitabine + fludarabine to mitoxantrone were antagonistic, which could be important for clinical translation. In conclusion, synergistic interactions with gemcitabine occurred with several drugs, the most promising being gemcitabine + fludarabine, gemcitabine + fludarabine + paclitaxel, and gemcitabine + fludarabine + mitoxantrone. These findings provided a rationale for clinical trials of gemcitabine + fludarabine and gemcitabine + mitoxantrone where responses were observed in heavily pretreated AML patients.

Authors
Shanks, RH; Rizzieri, DA; Flowers, JL; Colvin, OM; Adams, DJ
MLA Citation
Shanks, RH, Rizzieri, DA, Flowers, JL, Colvin, OM, and Adams, DJ. "Preclinical evaluation of gemcitabine combination regimens for application in acute myeloid leukemia." Clin Cancer Res 11.11 (June 1, 2005): 4225-4233.
PMID
15930361
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
11
Publish Date
2005
Start Page
4225
End Page
4233
DOI
10.1158/1078-0432.CCR-04-2106

Multimodal dose dense therapy for mantle cell lymphoma.

Authors
Wanko, SO; Gocherman, JP; Moore, JO; Decastro, C; Prosnitz, R; Gasparetto, C; Chute, J; Horowitz, M; Ashley, M; Emily, E; Patty, D; Nelson, CJ; Rizzieri, DA
MLA Citation
Wanko, SO, Gocherman, JP, Moore, JO, Decastro, C, Prosnitz, R, Gasparetto, C, Chute, J, Horowitz, M, Ashley, M, Emily, E, Patty, D, Nelson, CJ, and Rizzieri, DA. "Multimodal dose dense therapy for mantle cell lymphoma." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
329A
End Page
330A

The use of DT388-IL3 fusion protein in patients with refractory acute myeloid leukemia(AML)

Authors
Misra, D; Frankel, A; Hall, P; Liu, TF; Black, J; Moore, JO; de Castro, C; Gockerman, JP; Gasparetto, C; Horwitz, M; Davis, PH; Chao, NJ; Rizzieri, DA
MLA Citation
Misra, D, Frankel, A, Hall, P, Liu, TF, Black, J, Moore, JO, de Castro, C, Gockerman, JP, Gasparetto, C, Horwitz, M, Davis, PH, Chao, NJ, and Rizzieri, DA. "The use of DT388-IL3 fusion protein in patients with refractory acute myeloid leukemia(AML)." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
212B
End Page
212B

Dose dense, high intensity induction therapy followed by early high dose chemotherapy (HDT) and autologous hematopoietic stem cell transplantation (AHSCT) for mantle cell lymphoma (MCL).

Authors
Koh, LP; Gockerman, JP; Moore, JO; DeCastro, C; Long, GD; Gasparetto, C; Niedzwiecki, D; Edwards, J; Prosnitz, L; Horwitz, M; Chute, J; Morris, A; Lassiter, M; Loftis, J; Davis, P; Chao, NJ; Rizzieri, DA
MLA Citation
Koh, LP, Gockerman, JP, Moore, JO, DeCastro, C, Long, GD, Gasparetto, C, Niedzwiecki, D, Edwards, J, Prosnitz, L, Horwitz, M, Chute, J, Morris, A, Lassiter, M, Loftis, J, Davis, P, Chao, NJ, and Rizzieri, DA. "Dose dense, high intensity induction therapy followed by early high dose chemotherapy (HDT) and autologous hematopoietic stem cell transplantation (AHSCT) for mantle cell lymphoma (MCL)." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
261A
End Page
261A

Phase II study of thalidomide in escalating doses for follicular (F-NHL) and small lymphocytic lymphoma (Sll): CALGB study 50002

Authors
Grinblatt, DL; Johnson, J; Niedzwicki, D; Rizzieri, DA; Bartlett, N; Cheson, BD
MLA Citation
Grinblatt, DL, Johnson, J, Niedzwicki, D, Rizzieri, DA, Bartlett, N, and Cheson, BD. "Phase II study of thalidomide in escalating doses for follicular (F-NHL) and small lymphocytic lymphoma (Sll): CALGB study 50002." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
897A
End Page
898A

Dose dense, high intensity therapy in newly diagnosed elderly patients with acute myeloid leukemia using gemtuzumab ozogamicin (Mylotarg (TM)) and high dose cytarabine (HiDAC).

Authors
Rao, AV; Rizzieri, DA; Moore, JO; Decastro, C; Abernethy, AP; Jordan, M; Davis, P; Edmonds, E; Gockerman, JP
MLA Citation
Rao, AV, Rizzieri, DA, Moore, JO, Decastro, C, Abernethy, AP, Jordan, M, Davis, P, Edmonds, E, and Gockerman, JP. "Dose dense, high intensity therapy in newly diagnosed elderly patients with acute myeloid leukemia using gemtuzumab ozogamicin (Mylotarg (TM)) and high dose cytarabine (HiDAC)." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
212B
End Page
213B

Phase II feasibility and pharmacokinetic study of concurrent administration of trastuzumab and high-dose chemotherapy in advanced HER2+ breast cancer.

PURPOSE: To evaluate the safety of concurrent treatment with trastuzumab and high-dose chemotherapy (HDC), using cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), with autologous hematopoietic progenitor cells support, in patients with HER2+ advanced breast cancer. EXPERIMENTAL DESIGN: Patients with HER2-overexpressing high-risk primary breast cancer (HRPBC; defined as > or =4 involved nodes or inflammatory disease), or metastatic breast cancer (MBC) were eligible. Treatment consisted of a loading dose of trastuzumab at 4 mg/kg (day -5), HDC (days -5 to -2), autologous hematopoietic progenitor cells infusion on day 0, and weekly maintenance trastuzumab (2 mg/kg) from day +1 (minimum of 9 doses). Cardiac monitoring included serial left ventricular ejection fraction measurements before treatment and on days +20 and +65. RESULTS: Thirty-three patients were prospectively enrolled (13 HRPBC, 20 MBC). Toxicity seemed similar to that expected with this HDC regimen alone. Neutrophils and platelets engrafted promptly. There were no cases of grade 4 or 5 toxicity. One patient experienced symptomatic grade 3 acute cardiac failure on day -4, responsive to treatment. Trastuzumab did not alter the pharmacokinetics of HDC. Eleven of twelve MBC patients with measurable disease (nine of them refractory to previous chemotherapy) experienced an objective response (9 complete and 2 partial responses). At median follow-up of 34 (13-58) months, all HRPBC patients remain alive and free of disease; the MBC group has event-free survival and overall survival rates of 45 and 70%, respectively. CONCLUSIONS: Incorporation of trastuzumab into HDC (cyclophosphamide, cisplatin, and BCNU) is feasible, with no apparent increased toxicity or pharmacokinetic interactions.

Authors
Nieto, Y; Vredenburgh, JJ; Shpall, EJ; Bearman, SI; McSweeney, PA; Chao, N; Rizzieri, D; Gasparetto, C; Matthes, S; Barón, AE; Jones, RB
MLA Citation
Nieto, Y, Vredenburgh, JJ, Shpall, EJ, Bearman, SI, McSweeney, PA, Chao, N, Rizzieri, D, Gasparetto, C, Matthes, S, Barón, AE, and Jones, RB. "Phase II feasibility and pharmacokinetic study of concurrent administration of trastuzumab and high-dose chemotherapy in advanced HER2+ breast cancer." Clin Cancer Res 10.21 (November 1, 2004): 7136-7143.
PMID
15534084
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
10
Issue
21
Publish Date
2004
Start Page
7136
End Page
7143
DOI
10.1158/1078-0432.CCR-04-0891

Detection of genomic losses and gains in myelodysplastic syndrome and acute myeloid leukemia by array comparative genomic hybridization

Authors
Gong, JZ; Trembath, DY; Goodman, BK; Quigley, D; Sebastian, S; Rizzieri, DA; Gockerman, JP; Lagoo, AS; Buckley, PJ
MLA Citation
Gong, JZ, Trembath, DY, Goodman, BK, Quigley, D, Sebastian, S, Rizzieri, DA, Gockerman, JP, Lagoo, AS, and Buckley, PJ. "Detection of genomic losses and gains in myelodysplastic syndrome and acute myeloid leukemia by array comparative genomic hybridization." November 2004.
Source
wos-lite
Published In
The Journal of molecular diagnostics : JMD
Volume
6
Issue
4
Publish Date
2004
Start Page
420
End Page
420

Dose-intense cyclophosphamide and etoposide for patients with refractory or high-risk non-Hodgkin's lymphoma.

A retrospective review was performed on the toxicity and response to one cycle of dose-intense cyclophosphamide/etoposide, followed by consolidation in patients with refractory or previously untreated, high-risk non-Hodgkin's lymphoma (NHL). Fifty-five patients with refractory NHL and 13 with untreated, high-risk NHL were administered one cycle of daily cyclophosphamide 1.5 g/m2 intravenously on days 1-4 and etoposide 300 mg/m2 intravenously every 12 hours on days 1-3. Responders then received other consolidated regimens. Twenty-seven percent of patients with refractory disease had moderate or severe stomatitis, and 44% had moderate or severe infections with 6 (11%) dying of this complication. Similar complication rates were noted in the previously untreated, high-risk group, but there was no treatment-related mortality. The overall response rate to this one cycle of therapy was 31% in the refractory group, with 18% complete response and 13% partial response. The overall response rate in the previously untreated, high-risk group was 69%, with 54% complete and 15% partial responses. In responders, the 2-year event-free survival was 27% in the refractory group and 56% in high-risk group. Dose-intense cyclophosphamide/etoposide has promising efficacy; however, nonhematologic toxicity can be considerable. The better tolerance, high response rate, and encouraging 2-year survival of this regimen in combination with further dose-dense consolidation in patients with high-risk NHL are encouraging.

Authors
Talbot, J; Ibom, VK; Rizzieri, DA; Barrier, R; Niedzwieki, D; DeCastro, CM; Moore, JO; Buckley, P; Laney, R; Stevenson, D; Rumbaugh, H; Gockerman, JP
MLA Citation
Talbot, J, Ibom, VK, Rizzieri, DA, Barrier, R, Niedzwieki, D, DeCastro, CM, Moore, JO, Buckley, P, Laney, R, Stevenson, D, Rumbaugh, H, and Gockerman, JP. "Dose-intense cyclophosphamide and etoposide for patients with refractory or high-risk non-Hodgkin's lymphoma." Clin Lymphoma 5.2 (September 2004): 116-122.
PMID
15453927
Source
pubmed
Published In
Clinical lymphoma
Volume
5
Issue
2
Publish Date
2004
Start Page
116
End Page
122

Phase 1 trial study of 131I-labeled chimeric 81C6 monoclonal antibody for the treatment of patients with non-Hodgkin lymphoma.

We report a phase 1 study of pharmacokinetics, dosimetry, toxicity, and response of (131)I anti-tenascin chimeric 81C6 for the treatment of lymphoma. Nine patients received a dosimetric dose of 370 MBq (10 mCi). Three patients received an administered activity of 1480 MBq (40 mCi), and 2 developed hematologic toxicity that required stem cell infusion. Six patients received an administered activity of 1110 MBq (30 mCi), and 2 developed toxicity that required stem cell infusion. The clearance of whole-body activity was monoexponential with a mean effective half-life of 110 hours (range, 90-136 hours) and a mean effective whole-body residence time of 159 hours (range, 130-196 hours). There was rapid uptake within the viscera; however, tumor uptake was slower. Activity in normal viscera decreased proportional to the whole body; however, tumor sites presented a slow clearance (T(1/2), 86-191 hours). The mean absorbed dose to whole-body was 67 cGy (range, 51-89 hours), whereas the dose to tumor sites was 963 cGy (range, 363-1517 cGy). Despite lack of a "blocking" antibody, 1 of 9 patients attained a complete remission and 1 a partial remission. These data demonstrate this radiopharmaceutical to be an encouraging agent for the treatment of lymphoma particularly if methods to protect the normal viscera are developed.

Authors
Rizzieri, DA; Akabani, G; Zalutsky, MR; Coleman, RE; Metzler, SD; Bowsher, JE; Toaso, B; Anderson, E; Lagoo, A; Clayton, S; Pegram, CN; Moore, JO; Gockerman, JP; DeCastro, C; Gasparetto, C; Chao, NJ; Bigner, DD
MLA Citation
Rizzieri, DA, Akabani, G, Zalutsky, MR, Coleman, RE, Metzler, SD, Bowsher, JE, Toaso, B, Anderson, E, Lagoo, A, Clayton, S, Pegram, CN, Moore, JO, Gockerman, JP, DeCastro, C, Gasparetto, C, Chao, NJ, and Bigner, DD. "Phase 1 trial study of 131I-labeled chimeric 81C6 monoclonal antibody for the treatment of patients with non-Hodgkin lymphoma." Blood 104.3 (August 1, 2004): 642-648.
PMID
15100153
Source
pubmed
Published In
Blood
Volume
104
Issue
3
Publish Date
2004
Start Page
642
End Page
648
DOI
10.1182/blood-2003-12-4264

Adult recipients of umbilical cord blood transplants after nonmyeloablative preparative regimens.

We report the outcome of 13 patients with advanced malignancies who underwent nonmyeloablative conditioning therapy followed by infusion of partially matched unrelated cord blood cells. The median age of these patients was 49 years, and their median weight was 65.7 kg. The median nucleated cell dose infused was 2.07 x 10(7)/kg. Eight of the 13 patients demonstrated donor chimerism between 4 weeks and 6 months, and subsequent conversion to full donor chimerism was achieved in 5 patients. Three patients were alive and free of disease at 158 to 1054 days, with a median survival of 288 days after transplantation. The 100-day event-free survival is 69%, and overall survival is 77%. At 1 year, the event-free and overall survival was 43%. Treatment-related mortality observed within the first 100 days after transplantation was low: 1 previously extensively pretreated patient died of multiorgan failure. This result provides a basis for further exploring this potentially curative approach to selected patients who lack matched related or unrelated hematopoietic stem cell donors.

Authors
Chao, NJ; Koh, L-P; Long, GD; Gasparetto, C; Horwitz, M; Morris, A; Lassiter, M; Sullivan, KM; Rizzieri, DA
MLA Citation
Chao, NJ, Koh, L-P, Long, GD, Gasparetto, C, Horwitz, M, Morris, A, Lassiter, M, Sullivan, KM, and Rizzieri, DA. "Adult recipients of umbilical cord blood transplants after nonmyeloablative preparative regimens." Biol Blood Marrow Transplant 10.8 (August 2004): 569-575.
PMID
15282535
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Issue
8
Publish Date
2004
Start Page
569
End Page
575
DOI
10.1016/j.bbmt.2004.05.001

Pulmonary sarcoidosis following stem cell transplantation: is it more than a chance occurrence?

Noninfectious pulmonary complications are one of the major side effects of hematopoetic stem cell transplant (HSCT); however, the development of pulmonary sarcoidosis post-HSCT is uncommon, with only three cases previously reported. In each of those cases, sarcoidosis was also diagnosed in the stem cell donor. We now report four cases of de novo pulmonary sarcoidosis occurring post-HSCT (3 autologous HSCT and 1 allogeneic HSCT). We suggest that pulmonary sarcoidosis may develop following either autologous or allogeneic HSCT, and the prevalence may be 10-fold higher than that of the normal population.

Authors
Bhagat, R; Rizzieri, DA; Vredenburgh, JJ; Chao, NJ; Folz, RJ
MLA Citation
Bhagat, R, Rizzieri, DA, Vredenburgh, JJ, Chao, NJ, and Folz, RJ. "Pulmonary sarcoidosis following stem cell transplantation: is it more than a chance occurrence?." Chest 126.2 (August 2004): 642-644.
PMID
15302757
Source
pubmed
Published In
Chest
Volume
126
Issue
2
Publish Date
2004
Start Page
642
End Page
644
DOI
10.1378/chest.126.2.642

Phase I trial study of [131]I-labeled chimeric 81C6 mAb for the treatment of patients with non-Hodgkin's lymphoma

Authors
Akabani, G; Rizzieri, DA; Zalutsky, MR; Coleman, RE; Metzler, SD; Bowsher, JE; Toaso, B; Lagoo, A; Moore, JO; Gockerman, JP; DeCastro, C; Gasparetto, C; Chao, NJ; Bigner, DD
MLA Citation
Akabani, G, Rizzieri, DA, Zalutsky, MR, Coleman, RE, Metzler, SD, Bowsher, JE, Toaso, B, Lagoo, A, Moore, JO, Gockerman, JP, DeCastro, C, Gasparetto, C, Chao, NJ, and Bigner, DD. "Phase I trial study of [131]I-labeled chimeric 81C6 mAb for the treatment of patients with non-Hodgkin's lymphoma." August 2004.
Source
wos-lite
Published In
European Journal of Nuclear Medicine and Molecular Imaging
Volume
31
Publish Date
2004
Start Page
S222
End Page
S222

Low-dose weekly paclitaxel for recurrent or refractory aggressive non-Hodgkin lymphoma.

BACKGROUND: Many patients with recurrent, intermediate or high-grade non-Hodgkin lymphoma (NHL) may not respond to or are not candidates for aggressive salvage chemotherapy. Effective, less toxic regimens are needed. Although high-dose taxanes have not been reported to be very effective for the treatment of lymphoma, different delivery rates may allow for different mechanisms of action to be manifest and result in a different toxicity profile and response rate. The current study tested this hypothesis by using low-dose, weekly paclitaxel in patients with recurrent or refractory NHL. METHODS: Adults age > 18 years with refractory or recurrent, aggressive NHL who were not considered curable with standard high-dose therapy received paclitaxel at a dose of 80 mg/m2 weekly for 5 weeks for 2 cycles. RESULTS: Thirty-four patients with refractory NHL and 4 patients with recurrent disease were treated. Approximately 45% of the patients had achieved a prior disease remission. The median number of prior regimens received was 3, 74% of the patients had an International Prognostic Index of > or = 3 at the time of study entry, and 29% had failed high-dose therapy with autologous hematopoietic support. Only one patient encountered severe toxicity (sepsis). Myelosuppression was reported to occur in approximately 20% of patients. A total of 10 patients (26%) achieved a complete disease response and 4 patients (11%) achieved a partial response. CONCLUSIONS: In the current study, low-dose, weekly paclitaxel therapy was found to provide a well tolerated and less toxic approach to the treatment of refractory NHL, with encouraging responses noted in heavily pretreated patients. However, evaluation in patients with an earlier stage of disease is warranted.

Authors
Rizzieri, DA; Sand, GJ; McGaughey, D; Moore, JO; DeCastro, C; Chao, NJ; Vredenburgh, JJ; Gasparetto, C; Long, GD; Anderson, E; Foster, T; Toaso, B; Adams, D; Niedzwiecki, D; Gockerman, JP
MLA Citation
Rizzieri, DA, Sand, GJ, McGaughey, D, Moore, JO, DeCastro, C, Chao, NJ, Vredenburgh, JJ, Gasparetto, C, Long, GD, Anderson, E, Foster, T, Toaso, B, Adams, D, Niedzwiecki, D, and Gockerman, JP. "Low-dose weekly paclitaxel for recurrent or refractory aggressive non-Hodgkin lymphoma." Cancer 100.11 (June 1, 2004): 2408-2414.
PMID
15160345
Source
pubmed
Published In
Cancer
Volume
100
Issue
11
Publish Date
2004
Start Page
2408
End Page
2414
DOI
10.1002/cncr.20245

Posttransplant lymphoproliferative disorder following nonmyeloablative allogeneic stem cell transplantation.

Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication of conventional bone marrow/stem cell and solid organ transplantation. However, not much is known about PTLD following the more recently introduced nonmyeloablative allogeneic stem cell transplantation (NMST). This study reports the findings from two cases of PTLD following NMST and compares them to the one previously reported case. The donor origin of the PTLD was determined using short tandem repeat analysis, and B- and T-cell clonalities were evaluated by polymerase chain reaction. Two cases of PTLD evolved in a total of 70 patients who have undergone NMST at our institution from 1999 to 2003. Both patients received conditioning with Fludarabine/Cytoxan/Campath 1H (alemtuzumab, anti-CD52 antibody) and T-cell-depleted donor cells with Campath-1H. Both PTLDs were EBV positive (by immunohistochemistry and in situ hybridization) with diffuse large B-cell lymphoma morphology. Our findings indicate the incidence of PTLD following NMST is 3% (2 of 70 patients from our institution and 1 of 30 from the previously reported case). All three PTLDs arose 6 to 7 months after NMST and were rapidly fatal. The pathology of the PTLD in all cases was donor origin, EBV positive, diffuse large B-cell lymphoma.

Authors
Snyder, MJ; Stenzel, TT; Buckley, PJ; Lagoo, AS; Rizzieri, DA; Gasparetto, C; Vredenburgh, JJ; Chao, NJ; Gong, JZ
MLA Citation
Snyder, MJ, Stenzel, TT, Buckley, PJ, Lagoo, AS, Rizzieri, DA, Gasparetto, C, Vredenburgh, JJ, Chao, NJ, and Gong, JZ. "Posttransplant lymphoproliferative disorder following nonmyeloablative allogeneic stem cell transplantation." Am J Surg Pathol 28.6 (June 2004): 794-800.
PMID
15166672
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
28
Issue
6
Publish Date
2004
Start Page
794
End Page
800

Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251.

BACKGROUND: The objective of the current study was to evaluate the efficacy of intensive chemotherapy with and without cranial radiation for central nervous system (CNS) prophylaxis in adults with Burkitt leukemia or lymphoma. METHODS: Patients received 18 weeks of therapy. Prophylactic cranial radiation (2400 centigrays) and 12 doses of triple intrathecal chemotherapy were administered to the first cohort of patients. A subsequent cohort received the same therapy, with the exceptions that intrathecal therapy was reduced to six doses and radiotherapy was administered only to high-risk individuals. RESULTS: The median follow-up durations were 6.8 years in Cohort 1 and 4.1 years in Cohort 2. Three occurrences of transverse myelitis, 2 severe neuropathies, 3 cases of aphasia, and 1 case of blindness were documented in the first cohort of 52 patients (Cohort 1). In the subsequent cohort of 40 patients (Cohort 2), none of these occurrences were observed, and patients experienced less neurologic toxicity overall (61% vs. 26%; P=0.001). Responses were similar, and the 3-year event-free survival rate was 0.52 (95% confidence interval, 0.38-0.65) for Cohort 1 and 0.45 (0.29-0.60) for Cohort 2. CONCLUSIONS: Intensive, short-duration chemotherapy with less intensive CNS prophylaxis led to control at this sanctuary site with little neurotoxicity and may be curative for adults with Burkitt leukemia or lymphoma.

Authors
Rizzieri, DA; Johnson, JL; Niedzwiecki, D; Lee, EJ; Vardiman, JW; Powell, BL; Barcos, M; Bloomfield, CD; Schiffer, CA; Peterson, BA; Canellos, GP; Larson, RA
MLA Citation
Rizzieri, DA, Johnson, JL, Niedzwiecki, D, Lee, EJ, Vardiman, JW, Powell, BL, Barcos, M, Bloomfield, CD, Schiffer, CA, Peterson, BA, Canellos, GP, and Larson, RA. "Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251." Cancer 100.7 (April 1, 2004): 1438-1448.
PMID
15042678
Source
pubmed
Published In
Cancer
Volume
100
Issue
7
Publish Date
2004
Start Page
1438
End Page
1448
DOI
10.1002/cncr.20143

Identification of compounds that enhance the anti-lymphoma activity of rituximab using flow cytometric high-content screening

In this report, we describe a new flow cytometry technique termed flow cytometric high-content screening (FC-HCS) which involves semi-automated processing and analysis of multiparameter flow cytometry samples. As a first test of the FC-HCS technique, we used it to screen a 2000-compound library, called the National Cancer Institute (NCI) Diversity Set, to identify agents that would enhance the anti-lymphoma activity of the therapeutic monoclonal antibody rituximab. FC-HCS identified 15 compounds from the Diversity Set that significantly enhanced the ability of rituximab to inhibit cell cycle progression and induce apoptosis in lymphoma cells. The validity of the screening results was confirmed for several compounds using additional assays of cell proliferation, apoptosis and cell growth. The FC-HCS technique was relatively simple and reliable and could process up to 1000 samples/day on a single flow cytometer. The FC-HCS technique may be useful for a variety of applications including drug discovery, immunologic monitoring of patients, functional genomics studies and tissue engineering efforts. © 2004 Elsevier B.V. All rights reserved.

Authors
Gasparetto, M; Gentry, T; Sebti, S; O'Bryan, E; Nimmanapalli, R; Blaskovich, MA; Bhalla, K; Rizzieri, D; Haaland, P; Dunne, J; Smith, C
MLA Citation
Gasparetto, M, Gentry, T, Sebti, S, O'Bryan, E, Nimmanapalli, R, Blaskovich, MA, Bhalla, K, Rizzieri, D, Haaland, P, Dunne, J, and Smith, C. "Identification of compounds that enhance the anti-lymphoma activity of rituximab using flow cytometric high-content screening." Journal of Immunological Methods 292.1-2 (2004): 59-71.
PMID
15350512
Source
scival
Published In
Journal of Immunological Methods
Volume
292
Issue
1-2
Publish Date
2004
Start Page
59
End Page
71
DOI
10.1016/j.jim.2004.06.003

Nonmyeloablative Allogeneic Stem Cell Transplantation Using Alternative Donors

Background: The reduced intensity of nonmyeloablative stem cell transplant (NMSCT) has enabled older patients to benefit from allogeneic therapy. Identification of suitable donors remains an obstacle. The use of alternative donors for stem cell therapy is essential to ensure broad applicability of allogeneic therapy. Methods: Clinical results using alternative hematopoietic stem cell donors are reviewed, including matched unrelated donors, partially matched family member donors, and unrelated partially matched umbilical cord blood. Results: The successful use of NMSCT in the treatment of hematologic and nonhematologic diseases has increased the number of patients capable of receiving allogeneic therapy. However, the stem cell donor pool remains limited due to the infrequent number of patients with matched siblings. Conclusions: The use of alternative donor stem cell sources can expand the number of patients able to receive allogeneic therapy.

Authors
Goggins, TF; Rizzieri, DA
MLA Citation
Goggins, TF, and Rizzieri, DA. "Nonmyeloablative Allogeneic Stem Cell Transplantation Using Alternative Donors." Cancer Control 11.2 (2004): 86-96.
PMID
15024345
Source
scival
Published In
Cancer Control
Volume
11
Issue
2
Publish Date
2004
Start Page
86
End Page
96

An EBV-positive lymphoproliferative disorder after therapy with alemtuzumab

Authors
Rizzieri, DA; Weitman, S; Vaughn, DM
MLA Citation
Rizzieri, DA, Weitman, S, and Vaughn, DM. "An EBV-positive lymphoproliferative disorder after therapy with alemtuzumab." NEW ENGLAND JOURNAL OF MEDICINE 349.26 (December 25, 2003): 2571-2572.
Source
wos-lite
Published In
The New England journal of medicine
Volume
349
Issue
26
Publish Date
2003
Start Page
2571
End Page
2572

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

Phase I trial with pharmocokinetics, dosimetry, toxicity and response of anti-stromal therapy using I-131 labeled chimeric anti-tenascin therapy for lymphoma.

Authors
Rizzieri, DA; Akabani, G; Zalutsky, M; Coleman, RE; Toaso, B; Anderson, E; Lagoo, A; Clayton, S; Niedzwiecki, D; Moore, JO; Gockerman, JP; DeCastro, C; Chao, NJ; Gasparetto, C; Bigner, DD
MLA Citation
Rizzieri, DA, Akabani, G, Zalutsky, M, Coleman, RE, Toaso, B, Anderson, E, Lagoo, A, Clayton, S, Niedzwiecki, D, Moore, JO, Gockerman, JP, DeCastro, C, Chao, NJ, Gasparetto, C, and Bigner, DD. "Phase I trial with pharmocokinetics, dosimetry, toxicity and response of anti-stromal therapy using I-131 labeled chimeric anti-tenascin therapy for lymphoma." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
635A
End Page
636A

Dose-intense cyclophosphamide and etoposide for patients with refractory or high risk non-Hogdkin's lymphoma.

Authors
Talbot, JT; Ibom, VK; Barrier, R; Niedzwieki, D; Castro, CM; Moore, JO; Buckley, PJ; Laney, R; Stevenson, D; Brumbaugh, H; Rizzieri, DA; Gockerman, JP
MLA Citation
Talbot, JT, Ibom, VK, Barrier, R, Niedzwieki, D, Castro, CM, Moore, JO, Buckley, PJ, Laney, R, Stevenson, D, Brumbaugh, H, Rizzieri, DA, and Gockerman, JP. "Dose-intense cyclophosphamide and etoposide for patients with refractory or high risk non-Hogdkin's lymphoma." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
287B
End Page
287B

Clinical outcome and immune reconstitution following alemtuzumab T cell depleted nonmyeloablative allogeneic immunotherapy from HLA matched siblings.

Authors
Rizzieri, DA; Koh, LP; Long, GD; Lagoo, AS; Gasparatto, C; Vredenburgh, JJ; Buckley, PJ; Gong, G; Loftis, J; Rowe, K; Rooney, B; Niedzweicki, D; Waters-Pick, B; Eren, P; Vujevich, D; Catlin, C; Folz, RJ; Sullivan, K; Horwitz, ME; Morris, A; Chao, NJ
MLA Citation
Rizzieri, DA, Koh, LP, Long, GD, Lagoo, AS, Gasparatto, C, Vredenburgh, JJ, Buckley, PJ, Gong, G, Loftis, J, Rowe, K, Rooney, B, Niedzweicki, D, Waters-Pick, B, Eren, P, Vujevich, D, Catlin, C, Folz, RJ, Sullivan, K, Horwitz, ME, Morris, A, and Chao, NJ. "Clinical outcome and immune reconstitution following alemtuzumab T cell depleted nonmyeloablative allogeneic immunotherapy from HLA matched siblings." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
238A
End Page
239A

Clinical outcome and immune reconstitution following alemtuzumab T cell depleted nonmyeloablative allogeneic immunotherapy using HLA mis-matched (3-5/6) related hematopoietic stem cells.

Authors
Rizzieri, DA; Koh, LP; Long, GD; Gasparetto, C; Vredenburgh, JJ; Buckley, PJ; Gong, G; Lagoo, A; Davis, P; Lassiter, M; Rooney, B; Niedzwiecki, D; Waters-Pick, B; Burleson, J; Thompson, M; Johns, A; Folz, RJ; Horwtiz, ME; Sullivan, K; Morris, A; Chao, NJ
MLA Citation
Rizzieri, DA, Koh, LP, Long, GD, Gasparetto, C, Vredenburgh, JJ, Buckley, PJ, Gong, G, Lagoo, A, Davis, P, Lassiter, M, Rooney, B, Niedzwiecki, D, Waters-Pick, B, Burleson, J, Thompson, M, Johns, A, Folz, RJ, Horwtiz, ME, Sullivan, K, Morris, A, and Chao, NJ. "Clinical outcome and immune reconstitution following alemtuzumab T cell depleted nonmyeloablative allogeneic immunotherapy using HLA mis-matched (3-5/6) related hematopoietic stem cells." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
482A
End Page
482A

Phase one evaluation of gemcitabine, fludarabine, and mitoxantrone for relapsed or refractory leukemia.

Authors
Sand, GJ; Moore, JO; DeCastro, C; Gockerman, JP; Peterson, B; Buckley, PJ; Toaso, B; Adams, D; Rizzieri, DA
MLA Citation
Sand, GJ, Moore, JO, DeCastro, C, Gockerman, JP, Peterson, B, Buckley, PJ, Toaso, B, Adams, D, and Rizzieri, DA. "Phase one evaluation of gemcitabine, fludarabine, and mitoxantrone for relapsed or refractory leukemia." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
250B
End Page
250B

One day preparative regimen for allogeneic non-myeloablative stem cell transplantation (NMSCT) using 3-5/6 HLA matched related donors.

Authors
Goggins, TF; Rizzieri, DA; Prosnitz, R; Gasparetto, C; Long, G; Horwitz, ME; Sullivan, K; Morris, A; Thompson, M; Lassiter, M; Rowe, K; Chao, NJ
MLA Citation
Goggins, TF, Rizzieri, DA, Prosnitz, R, Gasparetto, C, Long, G, Horwitz, ME, Sullivan, K, Morris, A, Thompson, M, Lassiter, M, Rowe, K, and Chao, NJ. "One day preparative regimen for allogeneic non-myeloablative stem cell transplantation (NMSCT) using 3-5/6 HLA matched related donors." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
476B
End Page
477B

Low-dose weekly paclitaxel for relapsed or refractory aggressive non-Hodgkins lymphoma.

Authors
Rizzieri, DA; Sand, GJ; McGaughey, D; Moore, J; DeCastro, C; Chao, N; Vredenburgh, J; Gasparetto, C; Anderson, L; Foster, T; Niedzwiecki, D; Gockerman, J
MLA Citation
Rizzieri, DA, Sand, GJ, McGaughey, D, Moore, J, DeCastro, C, Chao, N, Vredenburgh, J, Gasparetto, C, Anderson, L, Foster, T, Niedzwiecki, D, and Gockerman, J. "Low-dose weekly paclitaxel for relapsed or refractory aggressive non-Hodgkins lymphoma." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
641A
End Page
641A

Pharmacokinetics of subcutaneous alemtuzumab in a patient with myeloma.

Authors
Gasparetto, C; Chao, NJ; Horwitz, ME; Moore, JO; DeCastro, C; Gockerman, J; Sullivan, K; Rooney, B; Houser, L; Anderson, E; Hale, G; Toaso, B; Rizzieri, DA
MLA Citation
Gasparetto, C, Chao, NJ, Horwitz, ME, Moore, JO, DeCastro, C, Gockerman, J, Sullivan, K, Rooney, B, Houser, L, Anderson, E, Hale, G, Toaso, B, and Rizzieri, DA. "Pharmacokinetics of subcutaneous alemtuzumab in a patient with myeloma." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
385B
End Page
385B

Successful treatment of pure red cell aplasia (PRCA) with alemtuzumab (CAMPATH-1H).

Authors
de Castro, CM; Uronis, H; Moore, JO; Gockerman, JP; Rizzieri, DA; Chao, NJ
MLA Citation
de Castro, CM, Uronis, H, Moore, JO, Gockerman, JP, Rizzieri, DA, and Chao, NJ. "Successful treatment of pure red cell aplasia (PRCA) with alemtuzumab (CAMPATH-1H)." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
19B
End Page
19B

Rituximab in lymphocyte predominance Hodgkin's disease: a case series.

Rituximab in combination with chlorambucil or radiation therapy may be an effective and less-toxic therapeutic alternative for patients with lymphocyte predominance Hodgkin's disease (LPHD). We treated 6 patients with LPHD with weekly rituximab at 375 mg/m2 for 4 weeks, followed by either radiation therapy or chlorambucil. Four patients had previously untreated disease and 2 had relapsed LPHD. All patients had no evidence of disease progression at a median follow-up time of 12.5 months after receiving rituximab therapy (range, 6-39 months) and a median follow-up time of 6.5 months after completion of chlorambucil or radiation therapy (range, 3-25 months). Further follow-up is warranted to evaluate response duration and late toxicity of this novel treatment strategy

Authors
Ibom, VK; Prosnitz, RG; Gong, JZ; Moore, JO; DeCastro, CM; Prosnitz, LR; Rizzieri, DA; Gockerman, JP
MLA Citation
Ibom, VK, Prosnitz, RG, Gong, JZ, Moore, JO, DeCastro, CM, Prosnitz, LR, Rizzieri, DA, and Gockerman, JP. "Rituximab in lymphocyte predominance Hodgkin's disease: a case series." Clin Lymphoma 4.2 (September 2003): 115-118.
PMID
14556684
Source
pubmed
Published In
Clinical lymphoma
Volume
4
Issue
2
Publish Date
2003
Start Page
115
End Page
118

High-dose cyclophosphamide and etoposide for patients with refractory acute myeloid leukemia: a case series.

Authors
Talbot, J; Rizzieri, DA; DeCastro, CM; Moore, JO; Buckley, P; Laney, R; Stevenson, D; Brumbaugh, H; Gockerman, JP
MLA Citation
Talbot, J, Rizzieri, DA, DeCastro, CM, Moore, JO, Buckley, P, Laney, R, Stevenson, D, Brumbaugh, H, and Gockerman, JP. "High-dose cyclophosphamide and etoposide for patients with refractory acute myeloid leukemia: a case series." Am J Hematol 73.4 (August 2003): 295-296. (Letter)
PMID
12879438
Source
pubmed
Published In
American Journal of Hematology
Volume
73
Issue
4
Publish Date
2003
Start Page
295
End Page
296
DOI
10.1002/ajh.10362

Burkitt lymphoma arising in organ transplant recipients: a clinicopathologic study of five cases.

We report five cases of Burkitt lymphoma arising in organ transplant recipients. There were four men and one woman with a mean age of 35 years. All were solid organ recipients with three renal, one liver, and one double lung transplantation. The time interval between organ transplantation and lymphoma averaged 4.5 years. Patients typically presented with high-stage disease with generalized lymphadenopathy and bone marrow involvement. Histology showed classic Burkitt lymphoma or atypical variant/Burkitt-like morphology. C-MYC rearrangement, including three cases with immunoglobulin heavy chain and two cases with lambda light chain, and Epstein-Barr virus were detected in all the cases. Additional chromosomal abnormalities were present in two of three cases and p53 mutation was found in one of three cases. Aberrant genotype and phenotype were frequently encountered, including minor monoclonal or oligoclonal T-cell populations and undetectable surface immunoglobulin light chain expression. Four patients received antilymphoma regimens, with combination chemotherapy (three patients) and/or Rituximab (three patients), in addition to reduction of immunosuppression. All four patients achieved complete remission. We conclude that posttransplant Burkitt lymphoma represents a characteristic clinicopathologic entity and occurs later after transplantation. Genotypic and phenotypic aberrations are often present. Rituximab may be an effective alternative to conventional combination chemotherapy in the treatment of a posttransplant Burkitt lymphoma.

Authors
Gong, JZ; Stenzel, TT; Bennett, ER; Lagoo, AS; Dunphy, CH; Moore, JO; Rizzieri, DA; Tepperberg, JH; Papenhausen, P; Buckley, PJ
MLA Citation
Gong, JZ, Stenzel, TT, Bennett, ER, Lagoo, AS, Dunphy, CH, Moore, JO, Rizzieri, DA, Tepperberg, JH, Papenhausen, P, and Buckley, PJ. "Burkitt lymphoma arising in organ transplant recipients: a clinicopathologic study of five cases." Am J Surg Pathol 27.6 (June 2003): 818-827.
PMID
12766587
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
27
Issue
6
Publish Date
2003
Start Page
818
End Page
827

4-hydroperoxycyclophosphamide--purged peripheral blood stem cells for autologous transplantation in patients with acute myeloid leukemia.

We have performed a phase I dose escalation of 4-Hydroperoxycyclophosphamide (4HC) purging of autologous peripheral blood progenitor cells (PBPCs) to improve the outcome of autologous transplantation for patients with myeloid leukemia. Peripheral blood stem cells were mobilized after cytosine arabinoside of 2 g/m(2) every 12 hours x 8 doses with etoposide of 40 mg/kg total dose infused over 4 days, followed by growth factor support. The preparative regimen included Busulfan of 1 mg/kg orally every 6 hours x 16 doses, followed by etoposide of 60 mg/kg x 1 day (the patient with chronic myeloid leukemia received cyclophosphamide of 60 mg/kg/d x 2 days in lieu of etoposide). PBPCs purged with 4HC were infused following this induction. Toxicities included grade 3 or 4 skin rashes, stomatitis/mucositis, and delay in time to hematopoietic recovery. The maximum tolerated dose of 4HC used to purge PBPCs in this trial was 20 microg/mL, which resulted in an average of 18 days for white blood cells and 28 days for platelet recovery. With a median follow-up of 2.25 years in surviving patients, the 3-year disease free survival rate is 44% and the overall survival rate is 89%. These data suggest that autologous PBPCs are more sensitive than marrow purged with 4HC, tolerating less intense purging, although a survival advantage may still be seen and should be assessed in larger studies. Approaches to minimize stomatitis and protect normal stem cells from the toxicity of 4HC may improve the tolerance and efficacy of this approach.

Authors
Rizzieri, DA; Talbot, JT; Long, GD; Vredenburgh, JJ; Gasparetto, C; Smith, CS; Colvin, MO; Adams, D; Morris, A; Dodge, R; Loftis, J; Waters-Pick, B; Reese, M; Carawan, H; Koh, LP; Chao, NJ
MLA Citation
Rizzieri, DA, Talbot, JT, Long, GD, Vredenburgh, JJ, Gasparetto, C, Smith, CS, Colvin, MO, Adams, D, Morris, A, Dodge, R, Loftis, J, Waters-Pick, B, Reese, M, Carawan, H, Koh, LP, and Chao, NJ. "4-hydroperoxycyclophosphamide--purged peripheral blood stem cells for autologous transplantation in patients with acute myeloid leukemia." Biol Blood Marrow Transplant 9.3 (March 2003): 183-188.
PMID
12652469
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
9
Issue
3
Publish Date
2003
Start Page
183
End Page
188
DOI
10.1053/bbmt.2003.50011

Phase I evaluation of prolonged-infusion gemcitabine with fludarabine for relapsed or refractory acute myelogenous leukemia.

PURPOSE: The purpose of this study was to determine the maximum tolerated duration of infusion of gemcitabine at 10 mg/m(2)/min in combination with fludarabine at 25 mg/m(2) daily for 5 days in the treatment of relapsed or refractory acute myelogenous leukemia. EXPERIMENTAL DESIGN: Eighteen patients with relapsed or refractory acute myelogenous leukemia were enrolled. The median age was 54.5 years (range, 21-80 years). Patients received a 30-min infusion of fludarabine at 25 mg/m(2) daily for 5 days. i.v. gemcitabine was given as a single infusion at 10 mg/m(2)/min with the duration adjusted following a modified continuous reassessment method. RESULTS: After 18 patients, the maximum recommended duration of infusion of gemcitabine in combination with fludarabine was selected as a 15-h infusion given at 10 mg/m(2)/min (9,000 mg/m(2)). Severe stomatitis or esophagitis was the most common nonhematological dose-limiting toxicity. Myelosuppression was universal. Febrile neutropenia was common, and 3 of 18 (17%) patients developed bacteremia. Occasional nausea, vomiting, or diarrhea was also reported. There were three complete responses and two partial responses for an overall response rate of 28%. CONCLUSIONS: Prolonged-infusion gemcitabine at a fixed dose rate of 10 mg/m(2)/min for 15 h with 25 mg/m(2)/day fludarabine for 5 days is a tolerable induction regimen for relapsed or refractory leukemia. Stomatitis, esophagitis, febrile neutropenia, and myelosuppression should be anticipated; however, this regimen may be beneficial in patients with relapsed or refractory leukemia.

Authors
Rizzieri, DA; Ibom, VK; Moore, JO; DeCastro, CM; Rosner, GL; Adams, DJ; Foster, T; Payne, N; Thompson, M; Vredenburgh, JJ; Gasparetto, C; Long, GD; Chao, NJ; Gockerman, JP
MLA Citation
Rizzieri, DA, Ibom, VK, Moore, JO, DeCastro, CM, Rosner, GL, Adams, DJ, Foster, T, Payne, N, Thompson, M, Vredenburgh, JJ, Gasparetto, C, Long, GD, Chao, NJ, and Gockerman, JP. "Phase I evaluation of prolonged-infusion gemcitabine with fludarabine for relapsed or refractory acute myelogenous leukemia." Clin Cancer Res 9.2 (February 2003): 663-668.
PMID
12576433
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
9
Issue
2
Publish Date
2003
Start Page
663
End Page
668

Post-transplant lymphoproliferative disorder following non-myeloablative allogeneic stem cell transplantation

Authors
Snyder, MJ; Stenzel, TT; Lagoo, AS; Rizzieri, DA; Chao, N; Buckley, PJ; Gong, JZ
MLA Citation
Snyder, MJ, Stenzel, TT, Lagoo, AS, Rizzieri, DA, Chao, N, Buckley, PJ, and Gong, JZ. "Post-transplant lymphoproliferative disorder following non-myeloablative allogeneic stem cell transplantation." January 2003.
Source
wos-lite
Published In
Laboratory Investigation
Volume
83
Issue
1
Publish Date
2003
Start Page
253A
End Page
253A

Post-transplant lymphoproliferative disorder following non-myeloablative allogeneic stem cell transplantation

Authors
Snyder, MJ; Stenzel, TT; Lagoo, AS; Rizzieri, DA; Chao, N; Buckley, PJ; Gong, JZ
MLA Citation
Snyder, MJ, Stenzel, TT, Lagoo, AS, Rizzieri, DA, Chao, N, Buckley, PJ, and Gong, JZ. "Post-transplant lymphoproliferative disorder following non-myeloablative allogeneic stem cell transplantation." January 2003.
Source
wos-lite
Published In
Modern Pathology
Volume
16
Issue
1
Publish Date
2003
Start Page
253A
End Page
253A

An EBV-Positive Lymphoproliferative Disorder after Therapy with Alemtuzumab [6] (multiple letters)

Authors
Ghobrial, IM; Otteman, LA; White, WL; Rizzieri, DA; Weitman, S; Vaughn, DM
MLA Citation
Ghobrial, IM, Otteman, LA, White, WL, Rizzieri, DA, Weitman, S, and Vaughn, DM. "An EBV-Positive Lymphoproliferative Disorder after Therapy with Alemtuzumab [6] (multiple letters)." New England Journal of Medicine 349.26 (2003): 2570-2572.
PMID
14695424
Source
scival
Published In
New England Journal of Medicine
Volume
349
Issue
26
Publish Date
2003
Start Page
2570
End Page
2572
DOI
10.1056/NEJM200312253492621

Donor chimerism after T-Cell depleted (TCD)-Non-Myeloablative allogeneic SCT (NST) in hemoglobinopathies.

Authors
Isola, LM; Chao, JN; Weinberg, S; Fruchtman, SM; Atweh, G; McCune, S; Telen, MJ; DeCastro, LM; Long, GD; Vredenburgh, JJ; Gasparetto, C; Liesveld, J; Rowley, S; Rizzieri, DA
MLA Citation
Isola, LM, Chao, JN, Weinberg, S, Fruchtman, SM, Atweh, G, McCune, S, Telen, MJ, DeCastro, LM, Long, GD, Vredenburgh, JJ, Gasparetto, C, Liesveld, J, Rowley, S, and Rizzieri, DA. "Donor chimerism after T-Cell depleted (TCD)-Non-Myeloablative allogeneic SCT (NST) in hemoglobinopathies." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
401B
End Page
402B

GLAT (Copaxone) for treatment of steroid-refractory acute graft versus host disease.

Authors
Johnston, LJ; Shizuru, JS; Stockerl-Goldstein, KE; Stuart, MJ; Gasparetto, C; Long, GD; Rizzieri, DA; Vredenburgh, JJ; Blume, KG; Negrin, RS; Chao, NJ
MLA Citation
Johnston, LJ, Shizuru, JS, Stockerl-Goldstein, KE, Stuart, MJ, Gasparetto, C, Long, GD, Rizzieri, DA, Vredenburgh, JJ, Blume, KG, Negrin, RS, and Chao, NJ. "GLAT (Copaxone) for treatment of steroid-refractory acute graft versus host disease." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
421A
End Page
421A

Three methods of T-cell depletion of HPCT products: Analysis of CD34+ cell and lymphocyte purity and recovery.

Authors
Lonial, S; Rizzieri, DA; Koh, LP; Jones, M; Langston, AA; Redei, I; Long, GD; Gasparetto, C; Vredenburgh, JJ; Waller, EK; Chao, N
MLA Citation
Lonial, S, Rizzieri, DA, Koh, LP, Jones, M, Langston, AA, Redei, I, Long, GD, Gasparetto, C, Vredenburgh, JJ, Waller, EK, and Chao, N. "Three methods of T-cell depletion of HPCT products: Analysis of CD34+ cell and lymphocyte purity and recovery." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
835A
End Page
836A

Donor-specific tolerance after hematopoietic reconstitution with Campath-1H treated mobilized peripheral blood cells in a sublethal preconditioning regimen.

Authors
Gandy, KL; Chao, NJ; Long, GD; Sartain, V; Seigler, HF; Rizzieri, DA
MLA Citation
Gandy, KL, Chao, NJ, Long, GD, Sartain, V, Seigler, HF, and Rizzieri, DA. "Donor-specific tolerance after hematopoietic reconstitution with Campath-1H treated mobilized peripheral blood cells in a sublethal preconditioning regimen." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
410A
End Page
410A

Campath-1H, T cell depleted nonmyeloablative peripheral blood stem cell transplantation from 3-6/6 HLA matched family members.

Authors
Koh, LP; Rizzieri, DA; Long, GD; Vredenburgh, JJ; Gaparetto, C; Morris, A; Water-Picks, B; Stenzel, T; Lagoo, A; Gong, J; Buckley, P; Chao, NJ
MLA Citation
Koh, LP, Rizzieri, DA, Long, GD, Vredenburgh, JJ, Gaparetto, C, Morris, A, Water-Picks, B, Stenzel, T, Lagoo, A, Gong, J, Buckley, P, and Chao, NJ. "Campath-1H, T cell depleted nonmyeloablative peripheral blood stem cell transplantation from 3-6/6 HLA matched family members." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
638A
End Page
638A

A phase II, open-label study of CLOPAREX(TM) in adult patients with refractory or relapsed acute myelogenous leukemia

Authors
Foran, J; Wetzler, M; Karitarjian, HM; Faderl, S; Abramson, N; Rizzieri, DA; Craig, A; Weiss, J; Douer, D
MLA Citation
Foran, J, Wetzler, M, Karitarjian, HM, Faderl, S, Abramson, N, Rizzieri, DA, Craig, A, Weiss, J, and Douer, D. "A phase II, open-label study of CLOPAREX(TM) in adult patients with refractory or relapsed acute myelogenous leukemia." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
271B
End Page
271B

Patients with refractory B-CLL and T-PLL treated with alemtuzumab (Campath (R)) on a compassionate basis. A report on efficacy and safety of CAM 511 trial.

Authors
Rai, KR; Keating, MJ; Coutre, S; Rizzieri, DA; Grp, CS
MLA Citation
Rai, KR, Keating, MJ, Coutre, S, Rizzieri, DA, and Grp, CS. "Patients with refractory B-CLL and T-PLL treated with alemtuzumab (Campath (R)) on a compassionate basis. A report on efficacy and safety of CAM 511 trial." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
802A
End Page
802A

Dendritic cell recovery following nonmyeloablative allogeneic stem cell transplants.

Nonmyeloablative allogeneic stem cell transplantation (NMSCT) may destroy some malignancies through a graft-versus-tumor (GVT) effect, but tumor relapse and viral reactivation remain challenges for which immunizations may be helpful. Dendritic cells (DC), particularly DC1 and ex vivo-cultured DC, induce antigen-specific immune responses following viral infections and anti-tumor immunizations. DC2 may be tolerogenic. We hypothesize that successful immunizations following NMSCT will require adequate numbers of functional DC1 or ex vivo-generated DC. We determined the number, phenotype, and function of blood DC1 and DC2 and ex vivo-generated DC obtained from donor-recipient pairs before and up to 90 days after NMSCT. Although the percentage and number of recipient blood Lin(-) HLA-DR(+) CD11c(+) DC1 following NMSCT (median 0.46%, IQR 0.33-0.52%) was lower than donor DC1 (median 0.94%, IQR 0.40-2.2%) this was not significant. In contrast, the percentage and absolute number of blood Lin(-) HLA-DR(+) CD11c(-) CD123(+) DC2 was significantly decreased following the transplant (median 0.01% IQR 0.01-0.01% at day 60 compared with median 0.14%, IQR 0.10-0.38% for the donor before transplantation, p < 0.05). The yield (median 6.0%, IQR 5.5-8.5%) and allostimulatory function of ex vivo-generated DC did not differ significantly at any time point. The donor chimerism of blood and cultured DC reflected that of the overall white blood cells. Ex vivo-generated, donor DC loaded with cytomegalovirus (CMV) antigens were capable of stimulating a CMV-specific immune response in vitro within peripheral blood mononuclear cells of a patient following NMSCT. We conclude that blood DC numbers may be diminished following NMSCT transplant, but that DC1 recovery exceeds DC2 and functional DC may be generated from peripheral blood progenitors at all time points suggesting a possible use in immunization strategies.

Authors
Morse, MA; Rizzieri, D; Stenzel, TT; Hobeika, AC; Vredenburgh, JJ; Chao, NJ; Clay, TM; Mosca, PJ; Lyerly, HK
MLA Citation
Morse, MA, Rizzieri, D, Stenzel, TT, Hobeika, AC, Vredenburgh, JJ, Chao, NJ, Clay, TM, Mosca, PJ, and Lyerly, HK. "Dendritic cell recovery following nonmyeloablative allogeneic stem cell transplants." J Hematother Stem Cell Res 11.4 (August 2002): 659-668.
PMID
12201954
Source
pubmed
Published In
Journal of hematotherapy & stem cell research
Volume
11
Issue
4
Publish Date
2002
Start Page
659
End Page
668
DOI
10.1089/15258160260194802

Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma.

PURPOSE: To estimate the maximum-tolerated duration of infusion of gemcitabine at 10 mg/m(2)/min in combination with irinotecan at 40 mg/m(2) daily for 3 days in the treatment of relapsed or refractory acute leukemia or lymphoma. PATIENTS AND METHODS: Patients with leukemia or lymphoma were escalated in separate strata. Stratum I consisted of 11 patients, median age of 47 years (range, 18 to 68 years), with relapsed or refractory leukemia. Stratum II contained nine patients, median age of 48 years (range, 39 to 68 years), who had refractory non-Hodgkin's lymphoma. Patients received irinotecan at 40 mg/m(2) daily for 3 days, beginning just before the first dose of gemcitabine. Gemcitabine was given at 10 mg/m(2)/min, with the total duration adjusted following a modified continuous reassessment model. RESULTS: Severe myelosuppression and stomatitis/esophagitis were the most serious hematologic and nonhematologic toxicities. Several patients developed febrile neutropenia, nausea, or vomiting. In both strata, the maximum recommended duration of infusion of gemcitabine was 12 hours delivered at 10 mg/m(2)/min (7,200 mg/m(2)). The overall response rate for one cycle of this therapy in this phase I trial for patients with leukemia was 18% (95% confidence interval, 8% to 45%), and for those with lymphoma, 33% (95% confidence interval, 17% to 66%). CONCLUSION: A prolonged infusion of gemcitabine at 10 mg/m(2)/min for 12 hours with 3 days of irinotecan at 40 mg/m(2)/d is a tolerable induction regimen for patients with acute leukemia or lymphoma. Stomatitis/esophagitis should be anticipated; however, this regimen may induce responses in patients with difficult-to-treat hematologic malignancies.

Authors
Bass, AJ; Gockerman, JP; Hammett, E; DeCastro, CM; Adams, DJ; Rosner, GL; Payne, N; Davis, P; Foster, T; Moore, JO; Rizzieri, DA
MLA Citation
Bass, AJ, Gockerman, JP, Hammett, E, DeCastro, CM, Adams, DJ, Rosner, GL, Payne, N, Davis, P, Foster, T, Moore, JO, and Rizzieri, DA. "Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma." J Clin Oncol 20.13 (July 1, 2002): 2995-3000.
PMID
12089230
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
13
Publish Date
2002
Start Page
2995
End Page
3000
DOI
10.1200/JCO.2002.08.166

Alemtuzumab in relapsed or refractory chronic lymphocytic leukemia and prolymphocytic leukemia.

Twenty-three adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL) were treated for up to 12 weeks with the anti-CD52 monoclonal antibody alemtuzumab. Patients were a median of six years from diagnosis and had been treated with a median of four chemotherapy regimens (median of 24 total cycles) prior to enrollment. Fourteen patients (61%) had received prior monoclonal antibody therapy with rituximab. Adverse symptoms were primarily mild to moderate fever, rigor/chills, nausea/vomiting, or fatigue/malaise in up to 86% of patients. Patients with low blood counts at the initiation of alemtuzumab tolerated therapy well. A total of 17 patients were evaluable for disease response. Nine patients (53%) responded with complete remissions in the peripheral blood. Of these nine, five were evaluated by bone marrow biopsy with four complete responses (CR) and one partial response. Six of the nine presented with nodal disease at the start of alemtuzumab therapy with three CRs and three partial responses. Alemtuzumab is a monoclonal antibody that offers effective treatment for chemotherapy refractory CLL and PLL and is generally well tolerated in the outpatient setting.

Authors
McCune, SL; Gockerman, JP; Moore, JO; Decastro, CM; Bass, AJ; Chao, NJ; Long, GD; Vredenburgh, JJ; Gasparetto, C; Adams, D; Payne, N; Rizzieri, DA
MLA Citation
McCune, SL, Gockerman, JP, Moore, JO, Decastro, CM, Bass, AJ, Chao, NJ, Long, GD, Vredenburgh, JJ, Gasparetto, C, Adams, D, Payne, N, and Rizzieri, DA. "Alemtuzumab in relapsed or refractory chronic lymphocytic leukemia and prolymphocytic leukemia." Leuk Lymphoma 43.5 (May 2002): 1007-1011.
PMID
12148879
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
43
Issue
5
Publish Date
2002
Start Page
1007
End Page
1011
DOI
10.1080/10428190290021597

Mobilization of dendritic cells from patients with breast cancer into peripheral blood stem cell leukapheresis samples using Flt-3-Ligand and G-CSF or GM-CSF.

Treatment with myeloablative chemotherapy and autologous peripheral blood stem cell (PBSC) transplantation followed by vaccination with autologous dendritic cells (DCs) treated with tumor antigens is a promising therapeutic strategy for several types of cancer. Obtaining sufficient numbers of both PBSCs and DCs is central to this approach. Previously, it has been shown that administration of Flt-3-Ligand (FL) combined with either G-CSF or GM-CSF mobilizes large numbers of PBSCs in patients with cancer. In the current study, we sought to determine whether these same cytokines could simultaneously mobilize DCs into the PBSC leukapheresis collection. DCs were analysed in PBSC leukapheresis samples obtained from five patients with high-risk breast cancer who received G-CSF alone as priming prior to leukapheresis, four patients who received FL+G-CSF and five patients who received FL+GM-CSF. DCs were defined as cells with a lin(dim/-) HLA-DR+ CD11c+ phenotype. The proportions of DCs in the FL+G-CSF and FL+GM-CSF samples were significantly higher than in pre-mobilization peripheral blood and G-CSF leukapheresis samples. The mean yield of DCs/kg in the FL+GM-CSF samples was also significantly higher than the mean yield of DCs in the G-CSF samples. The FL+G-CSF and FL+GM-CSF mobilized DCs were immature by morphologic and phenotypic criteria but stimulated allogeneic T-cells at levels similar to DCs generated in culture from PBMCs. Overnight culture?of the immature DCs obtained from patients receiving either FL+G-CSF or FL+GM-CSF in TNF-alpha?resulted in the generation of mature DCs. In summary, administration of FL in combination with GM-CSF and G-CSF to patients with breast cancer can mobilize large numbers of immature DCs into PBSC leukapheresis collections.

Authors
Gasparetto, C; Gasparetto, M; Morse, M; Rooney, B; Vredenburgh, JJ; Long, GD; Rizzieri, DA; Loftis, J; Chao, NJ; Smith, C
MLA Citation
Gasparetto, C, Gasparetto, M, Morse, M, Rooney, B, Vredenburgh, JJ, Long, GD, Rizzieri, DA, Loftis, J, Chao, NJ, and Smith, C. "Mobilization of dendritic cells from patients with breast cancer into peripheral blood stem cell leukapheresis samples using Flt-3-Ligand and G-CSF or GM-CSF." Cytokine 18.1 (April 7, 2002): 8-19.
PMID
12090755
Source
pubmed
Published In
Cytokine
Volume
18
Issue
1
Publish Date
2002
Start Page
8
End Page
19

Allogeneic engraftment of mismatched unrelated cord blood following a non-myeloablative preparative regimen

Authors
Chao, NJ; Rizzieri, DA; Long, GD; Vredenburgh, JJ; Gasparetto, C; Morris, A; Davis, P
MLA Citation
Chao, NJ, Rizzieri, DA, Long, GD, Vredenburgh, JJ, Gasparetto, C, Morris, A, and Davis, P. "Allogeneic engraftment of mismatched unrelated cord blood following a non-myeloablative preparative regimen." LEUKEMIA 16.3 (March 2002): 407-407.
Source
wos-lite
Published In
Leukemia
Volume
16
Issue
3
Publish Date
2002
Start Page
407
End Page
407

Phase I evaluation of prolonged-infusion gemcitabine with mitoxantrone for relapsed or refractory acute leukemia.

PURPOSE: To ascertain the maximum tolerated duration of infusion of gemcitabine at 10 mg/m(2)/min in combination with mitoxantrone at 12 mg/m(2) daily for 3 days in the treatment of acute leukemia. PATIENTS AND METHODS: Thirty-four patients were enrolled. Stratum I consisted of 26 patients, median age 50 years (range, 25 to 71 years), with relapsed or refractory leukemia. Stratum II contained eight patients, median age 62.5 years (range, 38 to 83 years), who had received fewer than three cycles of myelotoxic therapy for chronic myeloid leukemia or myelodysplasia that had evolved into leukemia. Patients received mitoxantrone at 12 mg/m(2) daily for 3 days. After the first mitoxantrone dose, gemcitabine was provided intravenously at 10 mg/m(2)/min with the duration adjusted by following a continuous reassessment model. RESULTS: Severe myelosuppression, and stomatitis or esophagitis were the most common hematologic and nonhematologic dose-limiting toxicities. Several patients developed febrile neutropenia, nausea, or vomiting. In both strata, the maximum recommended duration of infusion of gemcitabine was 12 hours (7,200 mg/m(2)). The mean steady-state concentration of gemcitabine was 24.72 micromol/L and varied over a fivefold range among patients. Overall response rates in this phase I trial for strata I and II were 42% and 63%, respectively. CONCLUSION: Prolonged-infusion gemcitabine at a fixed dose rate of 10 mg/m(2)/min for 12 hours with 12 mg/m(2)/d mitoxantrone for 3 days is a tolerable induction regimen and achieves plasma concentrations sufficient for maximal intracellular activation. Stomatitis or esophagitis should be anticipated; however, this regimen may induce significant responses in patients with difficult-to-treat leukemias.

Authors
Rizzieri, DA; Bass, AJ; Rosner, GL; Gockerman, JP; DeCastro, CM; Petros, WP; Adams, DJ; Laughlin, MJ; Davis, P; Foster, T; Jacobson, R; Hurwitz, H; Moore, JO
MLA Citation
Rizzieri, DA, Bass, AJ, Rosner, GL, Gockerman, JP, DeCastro, CM, Petros, WP, Adams, DJ, Laughlin, MJ, Davis, P, Foster, T, Jacobson, R, Hurwitz, H, and Moore, JO. "Phase I evaluation of prolonged-infusion gemcitabine with mitoxantrone for relapsed or refractory acute leukemia." J Clin Oncol 20.3 (February 1, 2002): 674-679.
PMID
11821447
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
3
Publish Date
2002
Start Page
674
End Page
679
DOI
10.1200/JCO.2002.20.3.674

CD52 expression in mantle cell lymphoma.

Mantle cell lymphoma is one of the most difficult to treat of all the non-Hodgkin's lymphomas. CAMPATH-1H, a humanized monoclonal antibody against the CD52 antigen, has been used with some success in other lymphoproliferative diseases, especially chronic lymphocytic leukemia. This report demonstrates that tumor samples from patients with mantle cell lymphoma express the CD52 antigen and suggests that CAMPATH-1H should be studied in patients with mantle cell lymphoma.

Authors
Bass, AJ; Gong, J; Nelson, R; Rizzieri, DA
MLA Citation
Bass, AJ, Gong, J, Nelson, R, and Rizzieri, DA. "CD52 expression in mantle cell lymphoma." Leuk Lymphoma 43.2 (February 2002): 339-342.
PMID
11999566
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
43
Issue
2
Publish Date
2002
Start Page
339
End Page
342
DOI
10.1080/10428190290006125

Nonmyeloablative regimen preserves "niches" allowing for peripheral expansion of donor T-cells.

T-cell recovery following myeloablative preparatory regimens and cord blood transplantation in adult patients gen erally occurs between 1 and 3 years following allogeneic bone marrow transplantation. T-cell reconstitution may involve thymic education of donor-derived precursors or peripheral expansion of mature T-cells transferred in the graft. We measured quantitative and qualitative immunologic reconstitution, T-cell receptor spectratyping, and T-cell receptor excision circle (TREC) levels in adult recipients of umbilical cord blood transplants following a novel nonmyeloablative regimen. These results were compared to previously published results of similar patients receiving a myeloablative regimen and cord blood stem cells. With small numbers of patients treated so far, T-cells (CD3+) reached normal levels in adults 6 to 12 months following nonmyeloablative transplantation compared with 24 months in adults receiving a myeloablative regimen. At 12 months after transplantation, the numbers of phenotypically naive (CD45RA) T-cells were higher in those receiving the nonmyeloablative regimen. The T-cell repertoire in cord blood recipients treated with a nonmyeloablative regimen was markedly more diverse and robust compared with the repertoire in those receiving the myeloablative regimen at similar time points. TRECs (which are generated within the thymus and identify new thymic emigrants and those that have not divided) were detected 12 months after transplantation in the nonmyeloablative recipients, whereas TRECs were not detected in adults until 18 to 24 months in those receiving myeloablative regimens. Thus, in adults receiving a nonmyeloablative preparatory regimen, the quantitative and qualitative recovery of T-cells occurs through rapid peripheral expansion. The ability of patients receiving a nonmyeloablative regimen to recover within a few months suggests that the peripheral niches in which T-cells can proliferate are preserved in these patients compared to those receiving ablative regimens. Moreover, the presence of TREC-positive cells within 1 year suggests that thymic recovery is likewise accelerated in non myeloablative compared to myeloablative regimens.

Authors
Chao, NJ; Liu, CX; Rooney, B; Chen, BJ; Long, GD; Vredenburgh, JJ; Morris, A; Gasparetto, C; Rizzieri, DA
MLA Citation
Chao, NJ, Liu, CX, Rooney, B, Chen, BJ, Long, GD, Vredenburgh, JJ, Morris, A, Gasparetto, C, and Rizzieri, DA. "Nonmyeloablative regimen preserves "niches" allowing for peripheral expansion of donor T-cells." Biol Blood Marrow Transplant 8.5 (2002): 249-256.
PMID
12064361
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
8
Issue
5
Publish Date
2002
Start Page
249
End Page
256

High-dose chemotherapy and hematopoietic support for patients with high-risk primary breast cancer and involvement of 4 to 9 lymph nodes

Despite modern chemotherapy, advanced breast cancer remains a significant cause of cancer morbidity and mortality in women. Patients with disease involvement of multiple lymph nodes represent a subgroup with a high risk of relapse. In particular, 50% of patients with 4 to 9 axillary lymph nodes involved will relapse after standard chemotherapy. In an effort to improve the survival of patients with 4 to 9 involved nodes, we performed a phase II study in which 61 patients with surgically diagnosed stage II or III breast cancer and 4 to 9 positive lymph nodes received 3 cycles of doxorubicin and 5-fluorouracil followed by high-dose chemotherapy consisting of cisplatin, cyclophosphamide, and carmustine and infusion of autologous hematopoietic progenitor cells. All patients received posttransplantation localized radiotherapy unless contraindicated, and all patients with hormone receptor-positive disease received tamoxifen. After a median patient follow-up of 6.7 years (range, 4.6-8.6 years), the 5-year overall survival rate was 79% (95% CI, 69%-90%), with relapse-free survival of 73% (95% CI, 62%-85%). Treatment-related mortality was 3%. Interstitial pneumonitis occurred in 69% of patients but did not contribute to mortality. Our study presents long-term favorable results regarding the use of consolidative HDC with autologous hematopoietic support in previously untreated patients with high-risk primary breast cancer.

Authors
Stuart, MJ; Peters, WP; Broadwater, G; Hussein, A; Ross, M; Marks, LB; Folz, RJ; Long, GD; Rizzieri, D; Chao, NJ; Vredenburgh, JJ
MLA Citation
Stuart, MJ, Peters, WP, Broadwater, G, Hussein, A, Ross, M, Marks, LB, Folz, RJ, Long, GD, Rizzieri, D, Chao, NJ, and Vredenburgh, JJ. "High-dose chemotherapy and hematopoietic support for patients with high-risk primary breast cancer and involvement of 4 to 9 lymph nodes." Biology of Blood and Marrow Transplantation 8.12 (2002): 666-673.
PMID
12523579
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
8
Issue
12
Publish Date
2002
Start Page
666
End Page
673
DOI
10.1053/bbmt.2002.v8.abbmt080666

Successful allogeneic engraftment of mismatched unrelated cord blood following a nonmyeloablative preparative regimen.

Reduction in the toxicity of allogeneic transplantation with nonmyeloablative induction regimens has expanded the scope of practice to older and more debilitated patients. However, the limited availability of matched sibling donors requires that alternative donor sources be investigated. Reported here are 2 cases of patients with advanced hematologic malignancies without matched siblings, partially matched family members, or matched unrelated donors who successfully underwent nonmyeloablative conditioning therapy followed by infusion of partially matched, unrelated-donor cord blood cells. The patients are in remission and remain 100% donor as assessed by short tandem repeat analysis of the marrow 6 and 12 months following transplantation.

Authors
Rizzieri, DA; Long, GD; Vredenburgh, JJ; Gasparetto, C; Morris, A; Stenzel, TT; Davis, P; Chao, NJ
MLA Citation
Rizzieri, DA, Long, GD, Vredenburgh, JJ, Gasparetto, C, Morris, A, Stenzel, TT, Davis, P, and Chao, NJ. "Successful allogeneic engraftment of mismatched unrelated cord blood following a nonmyeloablative preparative regimen." Blood 98.12 (December 1, 2001): 3486-3488.
PMID
11719394
Source
pubmed
Published In
Blood
Volume
98
Issue
12
Publish Date
2001
Start Page
3486
End Page
3488

Radiolabeled anti-tenascin antibody for refractory non-Hodgkins lymphoma (NHL).

Authors
Rizzieri, DA; Akabani, G; Coleman, RE; Zalutsky, MR; Niedzwiecki, D; Payne, N; Wikstrand, C; Bigner, DD
MLA Citation
Rizzieri, DA, Akabani, G, Coleman, RE, Zalutsky, MR, Niedzwiecki, D, Payne, N, Wikstrand, C, and Bigner, DD. "Radiolabeled anti-tenascin antibody for refractory non-Hodgkins lymphoma (NHL)." BLOOD 98.11 (November 16, 2001): 247B-247B.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
247B
End Page
247B

Molecular evidence of engraftment in bone marrow after nonmyeloablative allogeneic stem cell transplant (NMASCT) is an unreliable indicator of residual/recurrent disease in the marrow.

Authors
Lagoo, AS; Gong, JZ; Rizzieri, DA; Stenzel, TT; Chao, NJ; Buckley, PJ
MLA Citation
Lagoo, AS, Gong, JZ, Rizzieri, DA, Stenzel, TT, Chao, NJ, and Buckley, PJ. "Molecular evidence of engraftment in bone marrow after nonmyeloablative allogeneic stem cell transplant (NMASCT) is an unreliable indicator of residual/recurrent disease in the marrow." BLOOD 98.11 (November 16, 2001): 185A-185A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
185A
End Page
185A

Durable engraftment of mismatched unrelated cord blood following a non-myeloablative preparative regimen for adults.

Authors
Rizzieri, DA; Long, GD; Vredenburgh, JJ; Gasparetto, C; Morris, A; Niedzwiecki, D; Lassiter, M; Loftis, J; Davis, P; McDonald, C; Stenzel, T; Waters-Pick, B; Kurtzberg, J; Chao, NJ
MLA Citation
Rizzieri, DA, Long, GD, Vredenburgh, JJ, Gasparetto, C, Morris, A, Niedzwiecki, D, Lassiter, M, Loftis, J, Davis, P, McDonald, C, Stenzel, T, Waters-Pick, B, Kurtzberg, J, and Chao, NJ. "Durable engraftment of mismatched unrelated cord blood following a non-myeloablative preparative regimen for adults." BLOOD 98.11 (November 16, 2001): 185A-185A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
185A
End Page
185A

Prolonged infusion gemcitabine in combination with CPT-11 for relapsed or refractory hematologic malignancies.

Authors
Bass, A; Moore, JO; DeCastro, C; Gockerman, JP; Rosner, G; Payne, N; Foster, T; Hammett, E; Adams, D; Long, G; Gasparetto, C; Vredenburgh, JJ; Chao, NJ; Rizzieri, DA
MLA Citation
Bass, A, Moore, JO, DeCastro, C, Gockerman, JP, Rosner, G, Payne, N, Foster, T, Hammett, E, Adams, D, Long, G, Gasparetto, C, Vredenburgh, JJ, Chao, NJ, and Rizzieri, DA. "Prolonged infusion gemcitabine in combination with CPT-11 for relapsed or refractory hematologic malignancies." BLOOD 98.11 (November 16, 2001): 209B-209B.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
209B
End Page
209B

Non-myeloablative allogeneic transplantation using T depleted matched sibling peripheral blood stem cells.

Authors
Rizzieri, DA; Long, GD; Vredenburgh, JJ; Gasparetto, C; Morris, A; Lassiter, M; Loftis, J; Davis, P; McDonald, C; Stenzel, T; Niedzwiecki, D; Chao, NJ
MLA Citation
Rizzieri, DA, Long, GD, Vredenburgh, JJ, Gasparetto, C, Morris, A, Lassiter, M, Loftis, J, Davis, P, McDonald, C, Stenzel, T, Niedzwiecki, D, and Chao, NJ. "Non-myeloablative allogeneic transplantation using T depleted matched sibling peripheral blood stem cells." BLOOD 98.11 (November 16, 2001): 420A-421A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
420A
End Page
421A

Dose dense, high intensity therapy for mantle cell lymphoma.

Authors
Rizzieri, DA; Gockerman, JP; Moore, JO; DeCastro, C; Long, GD; Vredenburgh, JJ; Niedzwiecki, D; Edwards, J; Prosnitz, L; Gasparetto, C; Morris, A; Lassiter, M; Davis, P; Chao, NJ
MLA Citation
Rizzieri, DA, Gockerman, JP, Moore, JO, DeCastro, C, Long, GD, Vredenburgh, JJ, Niedzwiecki, D, Edwards, J, Prosnitz, L, Gasparetto, C, Morris, A, Lassiter, M, Davis, P, and Chao, NJ. "Dose dense, high intensity therapy for mantle cell lymphoma." BLOOD 98.11 (November 16, 2001): 681A-682A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
681A
End Page
682A

Low dose, weekly, paclitaxel as salvage therapy for non-Hodgkins lymphoma (NHL).

Authors
Rizzieri, DA; DeCastro, C; Gockerman, JP; Niedzwiecki, D; Vredenburgh, JJ; Gasparetto, C; Long, G; Payne, N; Ibom, V; Chao, NJ; Moore, JO
MLA Citation
Rizzieri, DA, DeCastro, C, Gockerman, JP, Niedzwiecki, D, Vredenburgh, JJ, Gasparetto, C, Long, G, Payne, N, Ibom, V, Chao, NJ, and Moore, JO. "Low dose, weekly, paclitaxel as salvage therapy for non-Hodgkins lymphoma (NHL)." BLOOD 98.11 (November 16, 2001): 246B-246B.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
246B
End Page
246B

Alemtuzumab (Campath) in relapsed or refractory CLL or PLL.

Authors
McCune, SL; Gockerman, JP; Moore, JO; deCastro, CM; Bass, AJ; Chao, NJ; Long, GD; Vredenburgh, JJ; Gasparetto, C; Adams, DB; Payne, NP; Rizzieri, DA
MLA Citation
McCune, SL, Gockerman, JP, Moore, JO, deCastro, CM, Bass, AJ, Chao, NJ, Long, GD, Vredenburgh, JJ, Gasparetto, C, Adams, DB, Payne, NP, and Rizzieri, DA. "Alemtuzumab (Campath) in relapsed or refractory CLL or PLL." BLOOD 98.11 (November 16, 2001): 290B-291B.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
290B
End Page
291B

Non-myeloablative transplantation using CAMPATH 1H for T depletion of mismatched, related donor peripheral blood stem cells.

Authors
Rizzieri, DA; Long, GD; Vredenburgh, JJ; Gasparetto, C; Morris, A; Lassiter, M; Loftis, J; Davis, P; McDonald, C; Stenzel, T; Niedzwiecki, D; Chao, NJ
MLA Citation
Rizzieri, DA, Long, GD, Vredenburgh, JJ, Gasparetto, C, Morris, A, Lassiter, M, Loftis, J, Davis, P, McDonald, C, Stenzel, T, Niedzwiecki, D, and Chao, NJ. "Non-myeloablative transplantation using CAMPATH 1H for T depletion of mismatched, related donor peripheral blood stem cells." BLOOD 98.11 (November 16, 2001): 669A-669A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
669A
End Page
669A

Translocations of the MLL gene can be detected in an increased proportion of mononuclear cells collected after etoposide priming in patients subsequently developing secondary acute leukemia.

Authors
Klein, AK; Qumsiyeh, MB; Hayes, N; Long, GD; Vredenburgh, JJ; Rizzieri, DA; Gasparetto, C; Chao, NJ
MLA Citation
Klein, AK, Qumsiyeh, MB, Hayes, N, Long, GD, Vredenburgh, JJ, Rizzieri, DA, Gasparetto, C, and Chao, NJ. "Translocations of the MLL gene can be detected in an increased proportion of mononuclear cells collected after etoposide priming in patients subsequently developing secondary acute leukemia." BLOOD 98.11 (November 16, 2001): 401A-402A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
401A
End Page
402A

PRA reduction after sublethal preconditioning and hematopoietic reconstitution with Campath-1-treated mobilized peripheral blood.

Authors
Gandy, KL; Chao, NJ; Gasparetto, C; Long, GD; Reinsmoen, NL; Rizzieri, DA
MLA Citation
Gandy, KL, Chao, NJ, Gasparetto, C, Long, GD, Reinsmoen, NL, and Rizzieri, DA. "PRA reduction after sublethal preconditioning and hematopoietic reconstitution with Campath-1-treated mobilized peripheral blood." BLOOD 98.11 (November 16, 2001): 315B-315B.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
315B
End Page
315B

Increased microvessel density in non-Hodgkin's lymphoma (NHL) is localized to the site of disease changes in accordance with disease response.

Authors
Wadleigh, M; Niedzwiecki, D; Davis, P; Payne, N; Sen, F; Mann, KP; Proia, A; Hollis, D; Rizzieri, DA
MLA Citation
Wadleigh, M, Niedzwiecki, D, Davis, P, Payne, N, Sen, F, Mann, KP, Proia, A, Hollis, D, and Rizzieri, DA. "Increased microvessel density in non-Hodgkin's lymphoma (NHL) is localized to the site of disease changes in accordance with disease response." BLOOD 98.11 (November 16, 2001): 236B-236B.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
236B
End Page
236B

Unique molecular characteristics of primitive human AML cells permit apoptosis to be specifically induced in leukemic but not normal stem cells.

Authors
Guzman, ML; Neering, SJ; Swiderski, C; Grimes, B; Howard, DS; Rizzieri, DA; Jordan, CT
MLA Citation
Guzman, ML, Neering, SJ, Swiderski, C, Grimes, B, Howard, DS, Rizzieri, DA, and Jordan, CT. "Unique molecular characteristics of primitive human AML cells permit apoptosis to be specifically induced in leukemic but not normal stem cells." BLOOD 98.11 (November 16, 2001): 93A-93A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
93A
End Page
93A

Phase I trial of prolonged infusion gemcitabine with fludarabine for relapsed/refractory acute leukemia.

Authors
Rizzieri, DA; Ibom, V; DeCastro, C; Moore, JO; Payne, N; Adams, D; Adams, DJ; Rosner, G; Vredenburgh, JJ; Gasparetto, C; Long, G; Chao, NJ; Gockerman, JP
MLA Citation
Rizzieri, DA, Ibom, V, DeCastro, C, Moore, JO, Payne, N, Adams, D, Adams, DJ, Rosner, G, Vredenburgh, JJ, Gasparetto, C, Long, G, Chao, NJ, and Gockerman, JP. "Phase I trial of prolonged infusion gemcitabine with fludarabine for relapsed/refractory acute leukemia." BLOOD 98.11 (November 16, 2001): 220B-221B.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
220B
End Page
221B

Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells.

Human acute myelogenous leukemia (AML) is thought to arise from a rare population of malignant stem cells. Cells of this nature, herein referred to as leukemic stem cells (LSCs), have been documented for nearly all AML subtypes and appear to fulfill the criteria for stem cells in that they are self-renewing and give rise to the cells found in many leukemic populations. Because these cells are likely to be critical for the genesis and perpetuation of leukemic disease, the present studies sought to characterize unique molecular properties of the LSC population, with particular emphasis on the transcription factor, nuclear factor-kappaB (NF-kappaB). Previous experiments have shown that unstimulated human CD34(+) progenitor cells do not express NF-kappaB. In contrast, primary AML CD34(+) cells display readily detectable NF-kappaB activity as assessed by electrophoretic mobility shift assay and gene expression studies. Furthermore, detailed analyses of enriched AML stem cells (CD34(+)/CD38(-)/CD123(+)) indicate that NF-kappaB is also active in the LSC population. Given the expression of NF-kappaB in leukemic, but not normal primitive cells, the hypothesis that inhibition of NF-kappaB might induce leukemia-specific apoptosis was tested by treating primary cells with the proteasome inhibitor MG-132, a well-known inhibitor of NF-kappaB. Leukemic CD34(+)/CD38(-) cells displayed a rapid induction of cell death in response to MG-132, whereas normal CD34(+)/CD38(-) cells showed little if any effect. Taken together, these data indicate that primitive AML cells aberrantly express NF-kappaB and that the presence of this factor may provide unique opportunities to preferentially ablate LSCs.

Authors
Guzman, ML; Neering, SJ; Upchurch, D; Grimes, B; Howard, DS; Rizzieri, DA; Luger, SM; Jordan, CT
MLA Citation
Guzman, ML, Neering, SJ, Upchurch, D, Grimes, B, Howard, DS, Rizzieri, DA, Luger, SM, and Jordan, CT. "Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells." Blood 98.8 (October 15, 2001): 2301-2307.
PMID
11588023
Source
pubmed
Published In
Blood
Volume
98
Issue
8
Publish Date
2001
Start Page
2301
End Page
2307

Monoclonal antibody therapy in the treatment of non-Hodgkin lymphoma.

Authors
McCune, SL; Gockerman, JP; Rizzieri, DA
MLA Citation
McCune, SL, Gockerman, JP, and Rizzieri, DA. "Monoclonal antibody therapy in the treatment of non-Hodgkin lymphoma." JAMA 286.10 (September 12, 2001): 1149-1152. (Review)
PMID
11559240
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
286
Issue
10
Publish Date
2001
Start Page
1149
End Page
1152

Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors.

BACKGROUND: Umbilical-cord blood from unrelated donors who are not HLA-identical with the recipients can restore hematopoiesis after myeloablative therapy in children. We studied the use of transplantation of umbilical-cord blood to restore hematopoiesis in adults. METHODS: Sixty-eight adults with life-threatening hematologic disorders received intensive chemotherapy or total-body irradiation and then transplants of HLA-mismatched umbilical-cord blood. We evaluated the outcomes in terms of hematologic reconstitution, the occurrence of acute and chronic graft-versus-host disease (GVHD), relapses, and event-free survival. RESULTS: Of the 68 patients, 48 (71 percent) received grafts of umbilical-cord blood that were mismatched for two or more HLA antigens. Of the 60 patients who survived 28 days or more after transplantation, 55 had neutrophil engraftment at a median of 27 days (range, 13 to 59). The estimated probability of neutrophil recovery in the 68 patients was 0.90 (95 percent confidence interval, 0.85 to 1.0). The presence of a relatively high number of nucleated cells in the umbilical-cord blood before it was frozen was associated with faster recovery of neutrophils. Severe acute GVHD (of grade III or IV) occurred in 11 of 55 patients who could be evaluated within the first 100 days after transplantation. Chronic GVHD developed in 12 of 33 patients who survived for more than 100 days after transplantation. The median follow-up for survivors was 22 months (range, 11 to 51). Of the 68 patients, 19 were alive and 18 of these (26 percent) were disease-free 40 months after transplantation. The presence of a high number of CD34+ cells in the graft was associated with improved event-free survival (P=0.05). CONCLUSIONS: Umbilical-cord blood from unrelated donors can restore hematopoiesis in adults who receive myeloablative therapy and is associated with acceptable rates of severe acute and chronic GVHD.

Authors
Laughlin, MJ; Barker, J; Bambach, B; Koc, ON; Rizzieri, DA; Wagner, JE; Gerson, SL; Lazarus, HM; Cairo, M; Stevens, CE; Rubinstein, P; Kurtzberg, J
MLA Citation
Laughlin, MJ, Barker, J, Bambach, B, Koc, ON, Rizzieri, DA, Wagner, JE, Gerson, SL, Lazarus, HM, Cairo, M, Stevens, CE, Rubinstein, P, and Kurtzberg, J. "Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors." N Engl J Med 344.24 (June 14, 2001): 1815-1822.
PMID
11407342
Source
pubmed
Published In
The New England journal of medicine
Volume
344
Issue
24
Publish Date
2001
Start Page
1815
End Page
1822
DOI
10.1056/NEJM200106143442402

Expression of tumor-suppressor genes interferon regulatory factor 1 and death-associated protein kinase in primitive acute myelogenous leukemia cells.

Previous studies indicate that human acute myelogenous leukemia (AML) arises from a rare population of leukemic stem cells. Cells of this nature can initiate and maintain leukemic cell growth in both long-term cultures and nonobese diabetic/severe combined immune-deficient mice. To characterize the biology of primitive AML cells, gene expression screens were performed with 7 primary AML and 3 normal specimens. For each sample, stem cell populations (CD34(+)/CD38(-)) were isolated and used to synthesize radiolabeled complementary DNA (cDNA). AML vs normal probes were then hybridized to cDNA arrays containing genes related to cancer and apoptosis. Of approximately 1400 genes analyzed, 2 tumor-suppressor genes were identified that were overexpressed in all 7 of the AML CD34(+)/CD38(-) cell populations: death-associated protein kinase and interferon regulatory factor 1. Expression of each gene was confirmed by reverse-transcription polymerase chain reaction and immunoblot analysis. It is proposed that tumor-suppressor proteins play a role in the biology of primitive AML cells. (Blood. 2001;97:2177-2179)

Authors
Guzman, ML; Upchurch, D; Grimes, B; Howard, DS; Rizzieri, DA; Luger, SM; Phillips, GL; Jordan, CT
MLA Citation
Guzman, ML, Upchurch, D, Grimes, B, Howard, DS, Rizzieri, DA, Luger, SM, Phillips, GL, and Jordan, CT. "Expression of tumor-suppressor genes interferon regulatory factor 1 and death-associated protein kinase in primitive acute myelogenous leukemia cells." Blood 97.7 (April 1, 2001): 2177-2179.
PMID
11264190
Source
pubmed
Published In
Blood
Volume
97
Issue
7
Publish Date
2001
Start Page
2177
End Page
2179

Serial morphologic changes in the bone arrow after non-myeloablative allogenic "mini-allogenic" stem cell transplant (NMASCT): correlation with engraftment.

Authors
Gong, JZ; Lagoo, AS; Rizzieri, DA; Stenzel, TT; Chao, NJ; Buckley, PJ
MLA Citation
Gong, JZ, Lagoo, AS, Rizzieri, DA, Stenzel, TT, Chao, NJ, and Buckley, PJ. "Serial morphologic changes in the bone arrow after non-myeloablative allogenic "mini-allogenic" stem cell transplant (NMASCT): correlation with engraftment." LABORATORY INVESTIGATION 81.1 (January 2001): 164A-164A.
Source
wos-lite
Published In
Laboratory Investigation
Volume
81
Issue
1
Publish Date
2001
Start Page
164A
End Page
164A

Serial morphologic changes in the bone marrow after nonmyeloablative allogenic "mini-allogenic" stem cell transplant (NMASCT): correlation with engraftment.

Authors
Gong, JZ; Lagoo, AS; Rizzieri, DA; Stenzel, TT; Chao, NJ; Buckley, PJ
MLA Citation
Gong, JZ, Lagoo, AS, Rizzieri, DA, Stenzel, TT, Chao, NJ, and Buckley, PJ. "Serial morphologic changes in the bone marrow after nonmyeloablative allogenic "mini-allogenic" stem cell transplant (NMASCT): correlation with engraftment." MODERN PATHOLOGY 14.1 (January 2001): 164A-164A.
Source
wos-lite
Published In
Modern Pathology
Volume
14
Issue
1
Publish Date
2001
Start Page
164A
End Page
164A

Inhaled steroids as prophylaxis for delayed pulmonary toxicity syndrome in breast cancer patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

PURPOSE: To evaluate the efficacy of inhaled fluticasone propionate (Flovent) as prophylaxis against delayed pulmonary toxicity syndrome (DPTS) and decline in pulmonary function in breast cancer patients undergoing high-dose chemotherapy with the conditioning regimen of cyclophosphamide, cisplatin, and carmustine (CPB) followed by autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: Sixty-three consecutive patients with multinode-positive or metastatic breast cancer undergoing high-dose chemotherapy with CPB and ASCT who were treated at the Duke University Adult Bone Marrow Transplant Program. All patients were started on inhaled fluticasone propionate, 880 microg every 12 hours, for 12 weeks from the start date of their CPB conditioning regimen. Pulmonary function tests (PFTs) with a single-breath diffusing capacity of carbon monoxide (DLCO) were performed pre-ASCT as well as approximately 6 and 12 weeks post-ASCT. DPTS was defined as follows: (1) development of a nonproductive cough and dyspnea with or without fever, plus a fall in DLCO to less than 60% predicted; or (2) decline in DLCO to less than 50% predicted with or without symptoms. RESULTS: Pulmonary function tests were done on all patients pre-ASCT, on 56 of the 63 patients at a median of 44 days (range, 25 to 73 days) post-ASCT, and on 51 of the 63 patients at a median of 96 days (range, 50 to 190 days) post-ASCT. The PFTs showed an average of an 8% (+/-26%) and 21% (+/-22%) decline in DLCO. These declines compare favorably with our historical control group of 45 consecutive breast cancer patients undergoing ASCT with CPB as a conditioning regimen, who experienced average declines in DLCO of 29% (+/-18%) (P < .001) and 33% (+/-18%) (P < .001) at comparable time periods post-ASCT. Delayed pulmonary toxicity syndrome occurred in 35% of treated patients compared to 73% of the historical controls (P = .0003). No patients died of DPTS or pulmonary problems, and there were no fungal pneumonias. CONCLUSION: Inhaled fluticasone propionate may decrease the incidence of DPTS in patients treated with CPB as a conditioning regimen for ASCT, as well as help to preserve pulmonary function as measured by DLCO. These results are worthy of further study in a randomized clinical trial.

Authors
McGaughey, DS; Nikcevich, DA; Long, GD; Vredenburgh, JJ; Rizzieri, D; Smith, CA; Broadwater, G; Loftis, JS; McDonald, C; Morris, AK; Folz, RF; Chao, NF
MLA Citation
McGaughey, DS, Nikcevich, DA, Long, GD, Vredenburgh, JJ, Rizzieri, D, Smith, CA, Broadwater, G, Loftis, JS, McDonald, C, Morris, AK, Folz, RF, and Chao, NF. "Inhaled steroids as prophylaxis for delayed pulmonary toxicity syndrome in breast cancer patients undergoing high-dose chemotherapy and autologous stem cell transplantation." Biol Blood Marrow Transplant 7.5 (2001): 274-278.
PMID
11400949
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
7
Issue
5
Publish Date
2001
Start Page
274
End Page
278

Phase i trial of continuously infused gemcitabine with cpt-11 for refractory hematologic malignancies

In vitro modeling suggests additive efficacy of the nucleoside analogue gemcitabine with the topoisomerease inhibitor CPT-11. We are performing a phase I trial for patients with refractory leukemia or lymphoma using 1 cycle of variable durations of infusion of gemcitabine delivered at a rate of 10 mg/sq m/min in combination with CPT-11 40 mg/sq m infused over 90 minutes daily for 3 days, followed by growth factor support. Duration of gemcitabine infusion is varied according to a modified continuous reassessment model with the MTD being the duration at which we estimate 1/3 of patients will experience a DLT. In the NHL strata, a DLT is neutropenia for > 10 days, non-heme grade 4 toxicity for >1 day or grade 3 for > 4 days. In the leukemia strata, a DLT is neutropenia for > 4 weeks (not due to disease), non-heme grade 4 toxicity for >2 days or grade 3 for > 6 days. 12 patients aged 19-69 yo have been treated to date. 3-6 days of myelosuppression is anticipated in the NHL group and 2-4 weeks in the leukemia cohort. Average # 9 hours gem/ 12 hours gem/ 15 hours gem/ Responses prior regimens toxicity toxicity toxicity NHL 4(2-8) 0 3; 1 with grade 2; 1 DLT stomatitis 1PR;3SD;1NR 3 stomatitis x 2d Leukemia 3 (2-6) 2; no DLT 4; 1 with grade 1; no DLT 1PR;2SD 5 tumor lysis, 1 fungal pn Patients in the NHL cohort had low grade or transformed disease. Two had a significant PR, 3 have SD lasting for 1 -2 months after therapy. In the Leukemia cohort, 3/6 évaluable cleared all blasts from the marrow at nadir and at recovery 1 had a PR and 2 had SD. These data suggest the combination is feasible with toxicities similar to other aggressive regimens. The few preliminary responses noted in this refractory group encourage continued investigation with this regimen.

Authors
Rizzieri, DA; Gockerman, JP; Decastro, CM; Lilly, S; Foster, T
MLA Citation
Rizzieri, DA, Gockerman, JP, Decastro, CM, Lilly, S, and Foster, T. "Phase i trial of continuously infused gemcitabine with cpt-11 for refractory hematologic malignancies." Blood 96.11 PART II (2001): 216b-.
Source
scival
Published In
Blood
Volume
96
Issue
11 PART II
Publish Date
2001
Start Page
216b

Chimerism mediated immunotherapy using Campath T cell depleted peripheral blood progenitor cells (PBPC) with nonablative therapy provides reliable, durable allogeneic engraftment.

Authors
Rizzieri, DA; Long, GD; Vredenburgh, JJ; Gasparetto, C; Smith, CS; Morris, AK; Petros, WP; Davis, PH; Lassiter, ME; Waters-Pick, BA; Chao, NJ
MLA Citation
Rizzieri, DA, Long, GD, Vredenburgh, JJ, Gasparetto, C, Smith, CS, Morris, AK, Petros, WP, Davis, PH, Lassiter, ME, Waters-Pick, BA, and Chao, NJ. "Chimerism mediated immunotherapy using Campath T cell depleted peripheral blood progenitor cells (PBPC) with nonablative therapy provides reliable, durable allogeneic engraftment." BLOOD 96.11 (November 16, 2000): 521A-521A.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
521A
End Page
521A

Phase I trial of continuously infused gemcitabine with CPT-11 for refractory hematologic malignancies.

Authors
Rizzieri, DA; Gockerman, JP; Decastro, CM; Lilly, S; Foster, T; Adams, D; Moore, JO
MLA Citation
Rizzieri, DA, Gockerman, JP, Decastro, CM, Lilly, S, Foster, T, Adams, D, and Moore, JO. "Phase I trial of continuously infused gemcitabine with CPT-11 for refractory hematologic malignancies." BLOOD 96.11 (November 16, 2000): 216B-216B.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
216B
End Page
216B

Hematopoietic engraftment and survival after unrelated donor umbilical cord blood (UCB) transplantation in adult recipients.

Authors
Laughlin, MJ; Barker, J; Bambach, B; Koc, ON; Rizzieri, DA; Wagner, JE; Gerson, SL; Lazarus, HM; Cairo, M; Stevens, CE; Rubinstein, P; Kurtzberg, J
MLA Citation
Laughlin, MJ, Barker, J, Bambach, B, Koc, ON, Rizzieri, DA, Wagner, JE, Gerson, SL, Lazarus, HM, Cairo, M, Stevens, CE, Rubinstein, P, and Kurtzberg, J. "Hematopoietic engraftment and survival after unrelated donor umbilical cord blood (UCB) transplantation in adult recipients." BLOOD 96.11 (November 16, 2000): 587A-+.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
587A
End Page
+

Expression of tumor suppressor genes IRF-1 and DAP-kinase in primitive AML cells.

Authors
Guzman, ML; Upchurch, D; Grimes, B; Howard, DS; Phillips, GL; Rizzieri, DA; Luger, SM; Jordan, CT
MLA Citation
Guzman, ML, Upchurch, D, Grimes, B, Howard, DS, Phillips, GL, Rizzieri, DA, Luger, SM, and Jordan, CT. "Expression of tumor suppressor genes IRF-1 and DAP-kinase in primitive AML cells." BLOOD 96.11 (November 16, 2000): 696A-696A.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
696A
End Page
696A

Induction of apoptosis in primitive human AML cells using the proteasome inhibitor MG-132 and/or sodium salicylate.

Authors
Guzman, HL; Upchurch, D; Grimes, B; Howard, DS; Phillips, GL; Rizzieri, DA; Luger, SM; Jordan, CT
MLA Citation
Guzman, HL, Upchurch, D, Grimes, B, Howard, DS, Phillips, GL, Rizzieri, DA, Luger, SM, and Jordan, CT. "Induction of apoptosis in primitive human AML cells using the proteasome inhibitor MG-132 and/or sodium salicylate." BLOOD 96.11 (November 16, 2000): 80A-80A.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
80A
End Page
80A

Phase I trial of continuously infused gemcitabine with mitoxantrone for high risk or relapsed acute leukemia.

Authors
Rizzieri, DA; Gockerman, JP; DeCastro, CM; Petros, WP; Lilly, S; Davis, PH; Foster, T; Jarrell, E; Laughlin, MJ; Adams, DJ; Moore, JO
MLA Citation
Rizzieri, DA, Gockerman, JP, DeCastro, CM, Petros, WP, Lilly, S, Davis, PH, Foster, T, Jarrell, E, Laughlin, MJ, Adams, DJ, and Moore, JO. "Phase I trial of continuously infused gemcitabine with mitoxantrone for high risk or relapsed acute leukemia." BLOOD 96.11 (November 16, 2000): 326A-326A.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
326A
End Page
326A

Phase I trial of escalting doses of 4-hydroxycyclophosphamide (4HC) purged autologous peripheral blood progenitor cells (PBPC) for leukemia.

Authors
Rizzieri, DA; Long, GD; Gasparetto, C; Smith, CS; Vredenburgh, JJ; Morris, AK; Petros, WP; Loftis, J; McDonald, CS; Waters-Pick, B; Adams, DJ; Chao, NJ
MLA Citation
Rizzieri, DA, Long, GD, Gasparetto, C, Smith, CS, Vredenburgh, JJ, Morris, AK, Petros, WP, Loftis, J, McDonald, CS, Waters-Pick, B, Adams, DJ, and Chao, NJ. "Phase I trial of escalting doses of 4-hydroxycyclophosphamide (4HC) purged autologous peripheral blood progenitor cells (PBPC) for leukemia." BLOOD 96.11 (November 16, 2000): 385A-385A.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
385A
End Page
385A

Radiation dose selection in Hodgkin's disease patients with large mediastinal adenopathy treated with combined modality therapy.

PURPOSE: To determine the effective dose of consolidation radiation in Hodgkin's disease (HD) patients with large mediastinal adenopathy (LMA) treated with combined modality therapy (CMT). METHODS AND MATERIALS: Eighty-three HD patients with LMA receiving CMT between 1983 and 1997 at Duke University and Yale University were identified. Patients underwent complete clinical staging. The staging breakdown was: IA, 4 patients; IB, 1 patient; IIA, 25 patients; IIB, 33 patients; IIIA, 3 patients; IIIB-6 patients; IVA, 2 patients; and IVB, 9 patients. All patients received induction chemotherapy (CT) as follows: MOPP/ABV(D), 31 patients; BCVPP, 15 patients; ABVD, 24 patients; MOPP, 3 patients; and other regimens, 10 patients. Following 6 cycles of CT, patients were restaged and classified as having either complete response (CR) or induction failure (IF). Post-CT gallium scans were obtained in 52 patients. Patients with residual radiographic abnormalities were classified as having CR if they were gallium-negative and clinically well otherwise. Following induction CT, 78 patients had a CR. There were 5 IFs. Consolidation irradiation was administered to all sites of initial involvement in patients who had achieved CR. RT dose varied. Patients were grouped into the following dose ranges: < or = 20 Gy, 12 patients; 20-25 Gy, 24 patients; 25-30 Gy, 30 patients; > or = 30 Gy, 12 patients. RESULTS: Overall survival and failure-free survival were both 76% at 10 years. Of the 78 CR patients, 15 failed. Patterns of failure were in-field alone, 8 patients; out of field alone, 2 patients; and combined, 5 patients. Failure patterns by RT dose were: < or = 20 Gy, 0/12; 20-25 Gy, 7/24; 25-30 Gy, 5/30; > or = 30 Gy, 3/11. There was no apparent correlation between RT dose and subsequent failure. Post chemotherapy gallium scans were helpful in predicting for failure. Of 48 patients in whom the gallium was negative after chemotherapy, there were 6 failures, compared with 9 failures among 30 patients in whom gallium was not done after chemotherapy (p = 0.066). Additionally, patients receiving adriamycin-based chemotherapy regimens had improved outcomes compared to those not receiving adriamycin (p = 0.03.) CONCLUSIONS: These retrospective data suggest that low-dose radiotherapy following CR achieved with induction chemotherapy (particularly when documented with gallium scanning) may be as effective as higher doses for bulky HD at presentation. Phase III trials are necessary for confirmation of this hypothesis.

Authors
Elconin, JH; Roberts, KB; Rizzieri, DA; Vermont, C; Clough, RW; Kim, C; Dodge, RK; Prosnitz, LR
MLA Citation
Elconin, JH, Roberts, KB, Rizzieri, DA, Vermont, C, Clough, RW, Kim, C, Dodge, RK, and Prosnitz, LR. "Radiation dose selection in Hodgkin's disease patients with large mediastinal adenopathy treated with combined modality therapy." Int J Radiat Oncol Biol Phys 48.4 (November 1, 2000): 1097-1105.
PMID
11072168
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
48
Issue
4
Publish Date
2000
Start Page
1097
End Page
1105

The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells.

Recent studies suggest that the population of malignant cells found in human acute myelogenous leukemia (AML) arises from a rare population of leukemic stem cells (LSCs). LSCs have been documented for nearly all AML subtypes and have been phenotypically described as CD34+/CD38- or CD34+/HLA-DR-. Given the potentially critical role of these primitive cells in perpetuating leukemic disease, we sought to further investigate their molecular and cellular characteristics. Flow cytometric studies using primary AML tissue showed that the interleukin-3 receptor alpha chain (IL-3Ralpha or CD123) was strongly expressed in CD34+/CD38- cells (98 +/- 2% positive) from 16 of 18 primary specimens. Conversely, normal bone marrow derived CD34+/CD38- cells showed virtually no detectable expression of the CD123 antigen. To assess the functional role of IL-3Ralpha positive cells, purified CD34+/CD123+ leukemia cells were transplanted into immune deficient NOD/SCID mice. These experiments showed that CD123+ cells were competent to establish and maintain leukemic populations in vivo. To begin to elucidate a biological role for CD123 in leukemia, primary AML samples were analyzed with respect to signal transduction activity in the MAPK, Akt, and Stat5 pathways. Phosphorylation was not detected in response to IL-3 stimulation, thereby suggesting CD123 is not active in conventional IL-3-mediated signaling. Collectively, these data indicate that CD123 represents a unique marker for primitive leukemic stem cells. Given the strong expression of this receptor on LSCs, we propose that targeting of CD123 may be a promising strategy for the preferential ablation of AML cells.

Authors
Jordan, CT; Upchurch, D; Szilvassy, SJ; Guzman, ML; Howard, DS; Pettigrew, AL; Meyerrose, T; Rossi, R; Grimes, B; Rizzieri, DA; Luger, SM; Phillips, GL
MLA Citation
Jordan, CT, Upchurch, D, Szilvassy, SJ, Guzman, ML, Howard, DS, Pettigrew, AL, Meyerrose, T, Rossi, R, Grimes, B, Rizzieri, DA, Luger, SM, and Phillips, GL. "The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells." Leukemia 14.10 (October 2000): 1777-1784.
PMID
11021753
Source
pubmed
Published In
Leukemia
Volume
14
Issue
10
Publish Date
2000
Start Page
1777
End Page
1784

Dendritic cell (DC) reconstitution after nonmyeloablative allogeneic stem cell transplants

Non-myeloablative allogeneic peripheral blood stem cell transplants {mini-allo PBSCT) are being evaluated as a lower toxicity alternative to conventional allogeneic transplantation for harnessing graft versus tumor effects. Induction of anti-tumor immunity post-transplant requires donor derived DC be available to process and present antigen to the donor lymphocytes. Because the kinetics of DC reconstitution after mini-allo PBSCT are unknown, we have initiated a study to evaluate DC number and function in 8 donor/recipient pairs prior to the preparative regimen and at various times after PBSC reinfusion. Peripheral blood mononuclear cells (PBMC) were separated over Ficoll and stained for FACS with antibodies to CD lie, HLA DR, and CD 14 to detect myeloid DC1, or lineage markers, CD123, HLA-DR, and CD1 le to detect lymphoid DC2. To determine the number of DC that can be generated from PBMC, we cultured the plastic adherent PBMC in serum free medium containing GM-CSF (800U/ml) and IL-4 (500U/ml) for 7 days and determined the percentage of large HLA DR+ cells by FACS. Diagnoses were AML 1, NHL 4, MDS 1, ET 1, and thalassemia 1. The preparative regimen was cyclophosphamide, fludarabine, and CAMPATH-1. Donor-derived G-CSF mobilized leukaphereses were depleted of T cells with CAMPATH-1 and reinfused. Five patients have reached day 14 following reinfusion. One failed to engraft, and the remainder achieved 43-99% donor chimerism in the bone marrow by RFLP analysis. Two patients died of disease progression. The median number of CD1 lc+CD14-HLA-DR+DC was 2.3% of the recipient PBMC prior to the preparative regimen, 1.5% of the donor leukapheresis PBMC, and 0.9% of the recipient peripheral blood at day 14 (P=NS). In two recipients who had CD1 lc-CD123bright DC2 measured after transplant, they were 0% and 0.7% of the PBMC compared to 0.13% and 0.26% in the donor leukapheresis. The median yield of DC generated from PBMC was 14% in the donor leukaphereses and 17% in the recipient peripheral blood at day 14 (P=NS). Three recipients had DC yields of < 1 % prior to the preparative regimen. This preliminary data suggests that myeloid DC 1 and DC precursors are present in the peripheral blood at the time of myeloid re-engraftment two weeks after mini-allo PBSCT. We are currently evaluating a) whether these DC are of donor or recipient origin, b) whether DC numbers stabilize at subsequent time points, c) whether DC function following transplant is diminished from pre-transplant levels. These results will guide studies of anti-tumor immunization following transplantation.

Authors
Morse, MA; Rizzieri, D; Hobeika, AC; Chao, N; Lyerly, HK
MLA Citation
Morse, MA, Rizzieri, D, Hobeika, AC, Chao, N, and Lyerly, HK. "Dendritic cell (DC) reconstitution after nonmyeloablative allogeneic stem cell transplants." 2000.
Source
scival
Published In
Blood
Volume
96
Issue
11 PART II
Publish Date
2000
Start Page
305b

Cell cycle analyses and apoptosis in primitive leukemic and normal cells.

Authors
Jordan, CT; Phillips, GL; Rizzieri, DA; Luger, SM; Grimes, B; Upchurch, D
MLA Citation
Jordan, CT, Phillips, GL, Rizzieri, DA, Luger, SM, Grimes, B, and Upchurch, D. "Cell cycle analyses and apoptosis in primitive leukemic and normal cells." BLOOD 94.10 (November 15, 1999): 687A-687A.
Source
wos-lite
Published In
Blood
Volume
94
Issue
10
Publish Date
1999
Start Page
687A
End Page
687A

The interleukin-3 receptor alpha chain is highly expressed on primitive acute myelogenous leukemia cells.

Authors
Jordan, CT; Rizzieri, DA; Upchurch, D; Grimes, B; Phillips, GL
MLA Citation
Jordan, CT, Rizzieri, DA, Upchurch, D, Grimes, B, and Phillips, GL. "The interleukin-3 receptor alpha chain is highly expressed on primitive acute myelogenous leukemia cells." BLOOD 94.10 (November 15, 1999): 67A-67A.
Source
wos-lite
Published In
Blood
Volume
94
Issue
10
Publish Date
1999
Start Page
67A
End Page
67A

Prognostic and predictive factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high-dose chemotherapy with autologous stem-cell support.

PURPOSE: We performed a retrospective review to determine predictive and prognostic factors in patients with metastatic breast cancer who received induction therapy, and, if they responded to treatment, high-dose chemotherapy. PATIENTS AND METHODS: Patients with metastatic breast cancer received induction therapy with doxorubicin, fluorouracil, and methotrexate (AFM). Partial responders then received immediate high-dose chemotherapy, whereas those who achieved complete remission were randomized to immediate or delayed high-dose chemotherapy with hematopoietic stem-cell support. We performed a retrospective review of data from these patients and used Cox proportional hazards regression models for analyses. RESULTS: The overall response rate for the 425 patients enrolled was 74% (95% confidence interval, 70% to 78%). Multivariate analysis of data from all 425 patients revealed that positive estrogen receptor status (P =.0041), smaller metastatic foci ( 2 cm) (P =. 0165), a longer disease-free interval from initial diagnosis to diagnosis of metastases ( 2 years) (P =.0051), and prior treatment with tamoxifen (P =.0152) were good prognostic signs for overall survival. Patients who had received prior adjuvant therapy (P =.0001) and those who developed liver metastases (P =.0001) had decreased long-term survival. In the subgroup of responders to AFM induction, multivariate analysis showed that those with visceral metastases did less well (P =.0006), as did patients who had received prior adjuvant therapy (P =.0023). However, those who had received tamoxifen therapy in the adjuvant setting did better (P =. 0143). CONCLUSION: The chance for long-term remission with induction therapy with AFM and high-dose chemotherapy is increased for hormone receptor positive-patients with nonvisceral metastases who have not received prior adjuvant chemotherapy and have long disease-free intervals.

Authors
Rizzieri, DA; Vredenburgh, JJ; Jones, R; Ross, M; Shpall, EJ; Hussein, A; Broadwater, G; Berry, D; Petros, WP; Gilbert, C; Affronti, ML; Coniglio, D; Rubin, P; Elkordy, M; Long, GD; Chao, NJ; Peters, WP
MLA Citation
Rizzieri, DA, Vredenburgh, JJ, Jones, R, Ross, M, Shpall, EJ, Hussein, A, Broadwater, G, Berry, D, Petros, WP, Gilbert, C, Affronti, ML, Coniglio, D, Rubin, P, Elkordy, M, Long, GD, Chao, NJ, and Peters, WP. "Prognostic and predictive factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high-dose chemotherapy with autologous stem-cell support." J Clin Oncol 17.10 (October 1999): 3064-3074.
PMID
10506601
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
17
Issue
10
Publish Date
1999
Start Page
3064
End Page
3074
DOI
10.1200/JCO.1999.17.10.3064

Genetic manipulation of primitive leukemic and normal hematopoietic cells using a novel method of adenovirus-mediated gene transfer

Authors
Howard, DS; Rizzieri, DA; Grimes, B; Upchurch, D; Phillips, GL; Stewart, AK; Yannelli, JR; Jordan, CT
MLA Citation
Howard, DS, Rizzieri, DA, Grimes, B, Upchurch, D, Phillips, GL, Stewart, AK, Yannelli, JR, and Jordan, CT. "Genetic manipulation of primitive leukemic and normal hematopoietic cells using a novel method of adenovirus-mediated gene transfer." LEUKEMIA 13.10 (October 1999): 1608-1616.
PMID
10516763
Source
wos-lite
Published In
Leukemia
Volume
13
Issue
10
Publish Date
1999
Start Page
1608
End Page
1616

Long term disease free survival for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high dose therapy with hematopoietic support.

Authors
Rizzieri, DA; Vredenburgh, JJ; Chao, NJ; Broadwater, G; Berry, D; Peters, WP
MLA Citation
Rizzieri, DA, Vredenburgh, JJ, Chao, NJ, Broadwater, G, Berry, D, and Peters, WP. "Long term disease free survival for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high dose therapy with hematopoietic support." BLOOD 92.10 (November 15, 1998): 323A-323A.
Source
wos-lite
Published In
Blood
Volume
92
Issue
10
Publish Date
1998
Start Page
323A
End Page
323A

Prognostic factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high dose therapy with hematopoietic support.

Authors
Rizzieri, DA; Vredenburgh, JJ; Chao, NJ; Broadwater, G; Berry, D; Peters, WP
MLA Citation
Rizzieri, DA, Vredenburgh, JJ, Chao, NJ, Broadwater, G, Berry, D, and Peters, WP. "Prognostic factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high dose therapy with hematopoietic support." BLOOD 92.10 (November 15, 1998): 462A-463A.
Source
wos-lite
Published In
Blood
Volume
92
Issue
10
Publish Date
1998
Start Page
462A
End Page
463A

Secondary myelodysplasia and acute leukemia in breast cancer patients after autologous bone marrow transplant.

PURPOSE: To determine the incidence of myelodysplasia (MDS) and/or acute leukemia (AL) in breast cancer patients after high-dose chemotherapy (HDC) with a single conditioning regimen and autologous bone marrow transplant (ABMT), and analyze the cytogenetic abnormalities that arise after HDC. PATIENTS AND METHODS: We retrospectively reviewed the records of 864 breast cancer patients who underwent ABMT at Duke University Medical Center, Durham, NC, from 1985 through 1996 who received the same preparative regimen of cyclophosphamide 1,875 mg/m2 for 3 days, cisplatin 55 mg/m2 for 3 days, and BCNU 600 mg/m2 for 1 day (CPB). Pretransplant cytogenetics were analyzed in all patients and posttransplant cytogenetics were evaluated in four of five patients who developed MDS/AL. RESULTS: Five of 864 patients developed MDS/AL after HDC with CPB and ABMT. The crude cumulative incidence of MDS/AL was 0.58%. The Kaplan-Meier curve shows a 4-year probability of developing MDS/AL of 1.6%. Pretransplant cytogenetics performed on these five patients were all normal. Posttransplant cytogenetics were performed on four of five patients and they were abnormal in all four, although only one patient had the most common cytogenetic abnormality associated with secondary MDS/AL (chromosome 5 and/or 7 abnormality). CONCLUSION: Whereas MDS/AL is a potential complication of HDC with CPB and ABMT, the incidence in this series of patients with breast cancer was relatively low compared with that reported in patients with non-Hodgkin's lymphoma who underwent ABMT. The cytogenetic abnormalities reported in this group of breast cancer patients were not typical of those seen in prior reports of secondary MDS/AL and appear to have occurred after HDC.

Authors
Laughlin, MJ; McGaughey, DS; Crews, JR; Chao, NJ; Rizzieri, D; Ross, M; Gockerman, J; Cirrincione, C; Berry, D; Mills, L; Defusco, P; LeGrand, S; Peters, WP; Vredenburgh, JJ
MLA Citation
Laughlin, MJ, McGaughey, DS, Crews, JR, Chao, NJ, Rizzieri, D, Ross, M, Gockerman, J, Cirrincione, C, Berry, D, Mills, L, Defusco, P, LeGrand, S, Peters, WP, and Vredenburgh, JJ. "Secondary myelodysplasia and acute leukemia in breast cancer patients after autologous bone marrow transplant." J Clin Oncol 16.3 (March 1998): 1008-1012.
PMID
9508184
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
16
Issue
3
Publish Date
1998
Start Page
1008
End Page
1012
DOI
10.1200/JCO.1998.16.3.1008

Hematologic engraftment and reconstitution of immune function post unrelated placental cord blood transplant in an adult with acute lymphocytic leukemia.

Authors
Laughlin, MJ; Rizzieri, DA; Smith, CA; Moore, JO; Lilly, S; McGaughey, D; Martin, P; Carrier, C; Stevens, CE; Rubinstein, P; Buckley, R; Kurtzberg, J
MLA Citation
Laughlin, MJ, Rizzieri, DA, Smith, CA, Moore, JO, Lilly, S, McGaughey, D, Martin, P, Carrier, C, Stevens, CE, Rubinstein, P, Buckley, R, and Kurtzberg, J. "Hematologic engraftment and reconstitution of immune function post unrelated placental cord blood transplant in an adult with acute lymphocytic leukemia." Leuk Res 22.3 (March 1998): 215-219.
PMID
9619913
Source
pubmed
Published In
Leukemia Research
Volume
22
Issue
3
Publish Date
1998
Start Page
215
End Page
219

Hematopoietic recovery in adult recipients following unrelated umbilical cord blood (UCB) transplantation.

Authors
Kurtzberg, J; Laughlin, MJ; Smith, CA; Rizzieri, DA; Vredenburgh, JJ; Lassiter, ME; Affronti, ML; Coniglio, DM; Carrier, C; Stevens, CE; Rubinstein, P; Chao, NJ
MLA Citation
Kurtzberg, J, Laughlin, MJ, Smith, CA, Rizzieri, DA, Vredenburgh, JJ, Lassiter, ME, Affronti, ML, Coniglio, DM, Carrier, C, Stevens, CE, Rubinstein, P, and Chao, NJ. "Hematopoietic recovery in adult recipients following unrelated umbilical cord blood (UCB) transplantation." BLOOD 90.10 (November 15, 1997): 480-480.
Source
wos-lite
Published In
Blood
Volume
90
Issue
10
Publish Date
1997
Start Page
480
End Page
480

Treatment of non-Hodgkin's lymphoma with high-dose therapy and hematopoietic stem cell support.

Standard therapies for advanced low-grade lymphomas are not likely to provide a cure, prompting the use of more aggressive approaches. Patients with low-grade lymphoma who receive high-dose therapy with stem cell support appear to have a prolonged disease-free survival, although the benefit to overall survival remains unproven. Patients with chemotherapy-sensitive intermediate- or high-grade relapsed disease have improved survival with high-dose therapy, and those with high-risk disease may benefit from early consolidation while in first remission. Significant questions remain in terms of the proper timing of high-dose therapy, appropriate stratification by risk factors, the value of purging, the role of radiotherapy after transplantation, and the most appropriate source of stem cells for transplantation.

Authors
Rizzieri, DA; Chao, NJ
MLA Citation
Rizzieri, DA, and Chao, NJ. "Treatment of non-Hodgkin's lymphoma with high-dose therapy and hematopoietic stem cell support." Curr Opin Oncol 9.5 (September 1997): 420-427. (Review)
PMID
9327219
Source
pubmed
Published In
Current Opinion in Oncology
Volume
9
Issue
5
Publish Date
1997
Start Page
420
End Page
427

Thrombocytosis associated with low-molecular-weight heparin - Response

Authors
Rizzieri, DA; Gockerman, JP
MLA Citation
Rizzieri, DA, and Gockerman, JP. "Thrombocytosis associated with low-molecular-weight heparin - Response." ANNALS OF INTERNAL MEDICINE 126.9 (May 1, 1997): 742-743.
Source
wos-lite
Published In
Annals of internal medicine
Volume
126
Issue
9
Publish Date
1997
Start Page
742
End Page
743

Kaposi's-sarcoma-associated herpesvirus is detected in peripheral blood mononuclear cells of HIV-infected homosexuals more often than in heterosexuals.

PURPOSE: The Kaposi's-sarcoma-associated herpesvirus is thought likely to play an important part in the pathogenesis of Kaposi's sarcoma, which is the most common tumor in AIDS patients. To determine whether peripheral blood is also infected by the virus, we prospectively tested mononuclear cells from HIV-infected individuals, both with and without Kaposi's sarcoma. PATIENTS AND METHODS: Thirty-three patients with AIDS were studied. Twenty-three were homosexuals, and 10 of these patients had Kaposi's sarcoma. All 10 nonhomosexual patients were free of Kaposi's sarcoma. PCR amplification of peripheral blood mononuclear cells was performed for a 233-base-pair segment of Kaposi's-sarcoma-associated herpesvirus on all patients. Fisher's exact test was used to compare the patient groups. RESULTS: Kaposi's-sarcoma-associated herpesvirus sequences were detected in the peripheral blood mononuclear cells of homosexual men both with (7/10) and without (5/13) Kaposi's sarcoma. However, none of the nonhomosexual patients (0/10) had detectable virus. Therefore, those with Kaposi's sarcoma are at greater risk for Kaposi's-sarcoma-associated herpesvirus infection than patients without Kaposi's sarcoma, and among HIV-positive patients without Kaposi's sarcoma, homosexuals are more likely to have detectable Kaposi's-sarcoma-associated herpesvirus than are nonhomosexuals. In the homosexual patients, the presence of virus was unrelated to total CD4+ cell counts. A comparative dilutional analysis showed that the nonhomosexual patients had a low viral load in their peripheral blood mononuclear cells relative to most homosexuals with Kaposi's sarcoma. Sequential studies on two patients revealed clearing of the virus while on therapy; one patient was treated for HIV with the protease inhibitor indinavir, and the other patient was treated for Kaposi's sarcoma with liposomal doxorubicin. CONCLUSIONS: These results indicate that Kaposi's-sarcoma-associated herpesvirus is harbored in peripheral blood mononuclear cells of HIV-infected patients, and that the rates of infection are significantly higher in homosexual men compared with their nonhomosexual counterparts. The significance of viral clearing in response to therapy is unknown but warrants further study, as prophylactic treatment for this virus might alter the occurrence of Kaposi's sarcoma in this susceptible patient population.

Authors
Rizzieri, DA; Liu, J; Miralles, D; Traweek, ST
MLA Citation
Rizzieri, DA, Liu, J, Miralles, D, and Traweek, ST. "Kaposi's-sarcoma-associated herpesvirus is detected in peripheral blood mononuclear cells of HIV-infected homosexuals more often than in heterosexuals." Cancer J Sci Am 3.3 (May 1997): 153-156.
PMID
9161780
Source
pubmed
Published In
The cancer journal from Scientific American
Volume
3
Issue
3
Publish Date
1997
Start Page
153
End Page
156

Clearance of HHV-8 from peripheral blood mononuclear cells with a protease inhibitor.

Authors
Rizzieri, DA; Liu, J; Traweek, ST; Miralles, GD
MLA Citation
Rizzieri, DA, Liu, J, Traweek, ST, and Miralles, GD. "Clearance of HHV-8 from peripheral blood mononuclear cells with a protease inhibitor." Lancet 349.9054 (March 15, 1997): 775-776. (Letter)
PMID
9074582
Source
pubmed
Published In
The Lancet
Volume
349
Issue
9054
Publish Date
1997
Start Page
775
End Page
776
DOI
10.1016/S0140-6736(05)60200-0

Thrombocytosis associated with low-molecular-weight heparin [6] (multiple letters)

Authors
Williams, E; Rizzieri, DA; Gockerman, JP
MLA Citation
Williams, E, Rizzieri, DA, and Gockerman, JP. "Thrombocytosis associated with low-molecular-weight heparin [6] (multiple letters)." Annals of Internal Medicine 126.9 (1997): 742-743.
PMID
9139569
Source
scival
Published In
Annals of internal medicine
Volume
126
Issue
9
Publish Date
1997
Start Page
742
End Page
743

Increased prevalence of Kaposi's sarcoma-associated herpesvirus in peripheral blood mononuclear cells of HIV-infected homosexuals.

Authors
Rizzieri, DA; Liu, J; Miralles, D; Traweek, ST
MLA Citation
Rizzieri, DA, Liu, J, Miralles, D, and Traweek, ST. "Increased prevalence of Kaposi's sarcoma-associated herpesvirus in peripheral blood mononuclear cells of HIV-infected homosexuals." BLOOD 88.10 (November 15, 1996): 1992-1992.
Source
wos-lite
Published In
Blood
Volume
88
Issue
10
Publish Date
1996
Start Page
1992
End Page
1992

Thrombocytosis associated with low-molecular-weight heparin.

Authors
Rizzieri, DA; Wong, WM; Gockerman, JP
MLA Citation
Rizzieri, DA, Wong, WM, and Gockerman, JP. "Thrombocytosis associated with low-molecular-weight heparin." Ann Intern Med 125.2 (July 15, 1996): 157-. (Letter)
PMID
8678382
Source
pubmed
Published In
Annals of internal medicine
Volume
125
Issue
2
Publish Date
1996
Start Page
157

CAUSES OF RHABDOMYOLYSIS - RESPONSE

Authors
RIZZIERI, DA
MLA Citation
RIZZIERI, DA. "CAUSES OF RHABDOMYOLYSIS - RESPONSE." MAYO CLINIC PROCEEDINGS 70.12 (December 1995): 1225-1225.
Source
wos-lite
Published In
Mayo Clinic Proceedings
Volume
70
Issue
12
Publish Date
1995
Start Page
1225
End Page
1225

T cell lymphoblastic leukemia with mediastinal mass and c-kit expression.

Authors
Rizzieri, DA; DeCastro, CM; Mann, KP; Moore, JO
MLA Citation
Rizzieri, DA, DeCastro, CM, Mann, KP, and Moore, JO. "T cell lymphoblastic leukemia with mediastinal mass and c-kit expression." BLOOD 86.10 (November 15, 1995): 3095-3095.
Source
wos-lite
Published In
Blood
Volume
86
Issue
10
Publish Date
1995
Start Page
3095
End Page
3095

Rhabdomyolysis after correction of hyponatremia due to psychogenic polydipsia.

Severe neurologic complications resulting from correction of hyponatremia are common, but reports of nonneurologic sequelae are scarce. This article describes a patient in whom rhabdomyolysis developed during correction of severe hyponatremia attributable to psychogenic polydipsia. Relevant material about volume regulation in the cell is presented, and a potential mechanism of cell damage is proposed. This case report emphasizes the importance of monitoring for nonneurologic complications during correction of hyponatremia.

Authors
Rizzieri, DA
MLA Citation
Rizzieri, DA. "Rhabdomyolysis after correction of hyponatremia due to psychogenic polydipsia." Mayo Clin Proc 70.5 (May 1995): 473-476.
PMID
7731258
Source
pubmed
Published In
Mayo Clinic Proceedings
Volume
70
Issue
5
Publish Date
1995
Start Page
473
End Page
476
DOI
10.1016/S0025-6196(11)63886-X
Show More