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Moore, Joseph Odell

Overview:

· Clinical research in the diagnosis and treatment of acute myeloid and lymphoid leukemias
· Malignant lymphoma
· Chronic myeloid and lymphoid leukemias
· Patient care and support programs and protocols
· Drug development and evaluation
· Soft tissue sarcoma
· Neuroendocrine tumors, carcinoid
· Delivery of continuing medical education
· Telemedicine
Research Program in Malignant Lymphoma and the Lymphocytic Leukemias (Acute and Chronic).

Duke has a long history of contribution to basic research and to clinical research programs which advance the understanding and treatment of the malignant lymphomas and the lymphocytic leukemias.
Currently, I am Duke principal investigator on a protocol for the investigation of Acute Lymphocytic Leukemia (CLL) designed to effect the first major change in induction therapy of this disease in the last twenty years. This is in cooperation with the overall PI at Memorial Sloan-Kettering Cancer Center. Additionally, we currently participate in a CALGB protocol for the primary treatment of Acute Lymphocytic Leukemia.

Chronic Lymphocytic Leukemia (CLL) represents a group of usually low-grade lymphoproliferative disorders. Duke's study of these disorders began with Dr. R. Wayne Rundles in the 1950s and 1960s, and proceeded on to current studies of both local initiative and participation and cooperative group protocols. Cancer and leukemic group B (CALGB) protocols currently investigate the use of rituximab and Fludarabine in CLL, and explore treatment with the investigative agent flavopiridol. Several other programs are currently being written in this cooperative group and will be participating in all of these. Additionally, we are currently extending the basic research and pharmacologic studies begun by Dr. Robert Silber (deceased) with The Clinical Pharmacology Section under the direction of Dr. Michael Colvin and his colleagues

Dr. Brice Weinberg has a long track record of innovative basic research in leukemias. He currently has initiated studies with several chemicals which inhibit nitric oxide (NO), a critical chemical transmitter in CLL and other cells. Initial pilot studies have demonstrated CLL cells are almost completely destroyed by inhibition of this enzyme. This work has the potential for bringing to the clinic an entirely new class
of chemical medications for the treatment of CLL.

In concert with the Duke Bone Marrow Transplant Program (DBMT), we are beginning to extend transplantation for Chronic Lymphocytic Leukemia to patients in all age groups, employing both standard allogeneic transplants, unrelated cord blood (UCBT) transplantation, and "mini-allo" transplants employing related donors. These studies are ongoing at this time and initial results are quite encouraging.

The Malignant Lymphomas represent an extremely varied group of diseases occurring in all age groups. These studies also encompass all of the cooperative efforts described above for CLL. We are currently participating in CALGB studies treating all levels of malignant lymphoma, and I am currently principal investigator (PI) on a program which is exploring the use of erythropoietin alpha (a growth factor stimulating the growth of red blood cells) in patients with malignant lymphomas and Hodgkin's disease. Likewise, I am principal investigator (PI) of another study using a white cell growth factor (SD-
to maintain white blood cell function in patients being treated with the aggressive program ESHAP, as a prelude to treatment with high dose chemotherapy and transplantation.

Dr. Jon P. Gockerman of our group is principal investigator employing the use of BEXXAR, a monoclonal antibody targeting CD20 and employed as a carrier for local radiation with I-131. These studies will facilitate the transfer of this particular very encouraging drug from the laboratory to general use in the clinic

Currently, Dr. Nelson Chao and his colleagues have developed, with our clinical help, a very comprehensive program for the transplantation of appropriate patients with malignant lymphoma, and with the malignant non-Hodgkin's lymphomas, and with Hodgkin's disease. Innovative programs are underway for treatment of mantle zone lymphoma and we are currently participating in a National Cancer Institute-generated study to treat intermediate grade malignant lymphoma with both chemotherapy and a unique immune treatment with anti-idiotypic antibody uniquely generated for each individual patient. Duke will be one of only three sites in the country responsible for this trial, but will also extend eligibility to other Duke cooperative sites under the Duke Oncology Consortium, of which I am the Medical Director.

In addition to the above transplantation studies, we are currently activating transplantation protocols employing allogeneic (sibling) donors, unrelated cord blood (UCB) donors, and matched unrelated donors (MUD).

Positions:

Professor of Medicine

Medicine, Hematological Malignancies
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1970

M.D. — Johns Hopkins University

Grants:

Ariad AP24534-14-2003 Pronatinib Dose Range Study

Administered By
Duke Cancer Institute
AwardedBy
Ariad Pharmaceuticals
Role
Principal Investigator
Start Date
December 17, 2015
End Date
December 16, 2020

Stopping Tyrosine Kinase Inhibitors in CML Patients (Stop-TKIs)

Administered By
Medicine, Hematological Malignancies
AwardedBy
Medical College of Wisconsin
Role
Principal Investigator
Start Date
September 19, 2014
End Date
August 31, 2017

Informal Caregiver Training in Cancer Symptom Management

Administered By
School of Nursing
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
March 01, 2006
End Date
August 31, 2009

Cancer And Leukemia Group B

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
April 06, 1993
End Date
March 31, 1998

Nimh Clinical Training

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 1987
End Date
June 30, 1989
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Publications:

Hodgkin lymphoma, version 2.2015.

Hodgkin lymphoma (HL) is an uncommon malignancy involving lymph nodes and the lymphatic system. Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma are the 2 main types of HL. CHL accounts for most HL diagnosed in the Western countries. Chemotherapy or combined modality therapy, followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale), is the standard initial treatment for patients with newly diagnosed CHL. Brentuximab vedotin, a CD30-directed antibody-drug conjugate, has produced encouraging results in the treatment of relapsed or refractory disease. The potential long-term effects of treatment remain an important consideration, and long-term follow-up is essential after completion of treatment.

Authors
Hoppe, RT; Advani, RH; Ai, WZ; Ambinder, RF; Aoun, P; Bello, CM; Benitez, CM; Bierman, PJ; Blum, KA; Chen, R; Dabaja, B; Forero, A; Gordon, LI; Hernandez-Ilizaliturri, FJ; Hochberg, EP; Huang, J; Johnston, PB; Khan, N; Maloney, DG; Mauch, PM; Metzger, M; Moore, JO; Morgan, D; Moskowitz, CH; Mulroney, C; Poppe, M; Rabinovitch, R; Seropian, S; Tsien, C; Winter, JN; Yahalom, J; Burns, JL; Sundar, H
MLA Citation
Hoppe, RT, Advani, RH, Ai, WZ, Ambinder, RF, Aoun, P, Bello, CM, Benitez, CM, Bierman, PJ, Blum, KA, Chen, R, Dabaja, B, Forero, A, Gordon, LI, Hernandez-Ilizaliturri, FJ, Hochberg, EP, Huang, J, Johnston, PB, Khan, N, Maloney, DG, Mauch, PM, Metzger, M, Moore, JO, Morgan, D, Moskowitz, CH, Mulroney, C, Poppe, M, Rabinovitch, R, Seropian, S, Tsien, C, Winter, JN, Yahalom, J, Burns, JL, and Sundar, H. "Hodgkin lymphoma, version 2.2015." Journal of the National Comprehensive Cancer Network : JNCCN 13.5 (May 2015): 554-586.
PMID
25964641
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
13
Issue
5
Publish Date
2015
Start Page
554
End Page
586

Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia.

DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (⩾60 years) adults with primary, cytogenetically normal acute myeloid leukemia (CN-AML). Patients were dichotomized into high versus low expressers using median cut. Outcomes were assessed in the context of known CN-AML prognosticators. Gene and microRNA expression, and DNA methylation profiles were analyzed using microarrays and MethylCap-sequencing, respectively. High DNMT3B expressers had fewer complete remissions (CR; P=0.002) and shorter disease-free (DFS; P=0.02) and overall (OS; P<0.001) survival. In multivariable analyses, high DNMT3B expression remained an independent predictor of lower CR rates (P=0.04) and shorter DFS (P=0.04) and OS (P=0.001). High DNMT3B expression associated with a gene expression profile comprising 363 genes involved in differentiation, proliferation and survival pathways, but with only four differentially expressed microRNAs (miR-133b, miR-148a, miR-122, miR-409-3p) and no differential DNA methylation regions. We conclude that high DNMT3B expression independently associates with adverse outcome in older CN-AML patients. Gene expression analyses suggest that DNMT3B is involved in the modulation of several genes, although the regulatory mechanisms remain to be investigated to devise therapeutic approaches specific for these patients.

Authors
Niederwieser, C; Kohlschmidt, J; Volinia, S; Whitman, SP; Metzeler, KH; Eisfeld, A-K; Maharry, K; Yan, P; Frankhouser, D; Becker, H; Schwind, S; Carroll, AJ; Nicolet, D; Mendler, JH; Curfman, JP; Wu, Y-Z; Baer, MR; Powell, BL; Kolitz, JE; Moore, JO; Carter, TH; Bundschuh, R; Larson, RA; Stone, RM; Mrózek, K; Marcucci, G; Bloomfield, CD
MLA Citation
Niederwieser, C, Kohlschmidt, J, Volinia, S, Whitman, SP, Metzeler, KH, Eisfeld, A-K, Maharry, K, Yan, P, Frankhouser, D, Becker, H, Schwind, S, Carroll, AJ, Nicolet, D, Mendler, JH, Curfman, JP, Wu, Y-Z, Baer, MR, Powell, BL, Kolitz, JE, Moore, JO, Carter, TH, Bundschuh, R, Larson, RA, Stone, RM, Mrózek, K, Marcucci, G, and Bloomfield, CD. "Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia." Leukemia 29.3 (March 2015): 567-575.
PMID
25204569
Source
epmc
Published In
Leukemia
Volume
29
Issue
3
Publish Date
2015
Start Page
567
End Page
575
DOI
10.1038/leu.2014.267

Blast phase in chronic myelogenous leukemia is skewed toward unusual blast types in patients treated with tyrosine kinase inhibitors: a comparative study of 67 cases.

OBJECTIVES: To compare the features of the blast phase of chronic myelogenous leukemia (CML) in patients treated with tyrosine kinase inhibitors (TKIs) with those in the pre-TKI era. METHODS: Sixty-seven patients with blast phase CML were identified in the Duke Pathology database from 1991 to 2011. The morphology and immunophenotype of blasts were evaluated, along with cytogenetic studies and associated findings in the peripheral blood and bone marrow. RESULTS: In the TKI era, the blasts were more frequently of a type other than the usual myeloid or lymphoid types when compared with the pre-TKI era. Blast phase in TKI-treated patients was associated with a higher peripheral WBC count and a lower blast percentage in the bone marrow. Of the 23 patients with cytogenetic studies during blast phase, additional cytogenetic changes more frequently occurred in patients with an unusual blast type, and some patients showed these changes months before the onset of blast phase. CONCLUSIONS: Blast phase CML in TKI- and non-TKI-treated patients differs in the morphology and immunophenotype of blasts, cytogenetic findings, and associated findings in the peripheral blood and bone marrow.

Authors
Shi, Y; Rand, AJ; Crow, JH; Moore, JO; Lagoo, AS
MLA Citation
Shi, Y, Rand, AJ, Crow, JH, Moore, JO, and Lagoo, AS. "Blast phase in chronic myelogenous leukemia is skewed toward unusual blast types in patients treated with tyrosine kinase inhibitors: a comparative study of 67 cases." American journal of clinical pathology 143.1 (January 2015): 105-119.
PMID
25511149
Source
epmc
Published In
American Journal of Clinical Pathology
Volume
143
Issue
1
Publish Date
2015
Start Page
105
End Page
119
DOI
10.1309/ajcpwex5yy4phscn

Expression and prognostic impact of lncRNAs in acute myeloid leukemia.

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged ≥60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive lncRNA profiles were found associated with selected mutations, such as internal tandem duplications in the FLT3 gene (FLT3-ITD) and mutations in the NPM1, CEBPA, IDH2, ASXL1, and RUNX1 genes. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older patients with CN-AML, we derived a lncRNA score composed of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P < 0.001, odds ratio = 0.14, 54% vs. 89%], shorter disease-free survival (DFS) [P < 0.001, hazard ratio (HR) = 2.88] and overall survival (OS) (P < 0.001, HR = 2.95). The validation set analyses confirmed these results (CR, P = 0.03; DFS, P = 0.009; OS, P = 0.009). Multivariable analyses for CR, DFS, and OS identified the lncRNA score as an independent marker for outcome. In conclusion, lncRNA expression in AML is closely associated with recurrent mutations. A small subset of lncRNAs is correlated strongly with treatment response and survival.

Authors
Garzon, R; Volinia, S; Papaioannou, D; Nicolet, D; Kohlschmidt, J; Yan, PS; Mrózek, K; Bucci, D; Carroll, AJ; Baer, MR; Wetzler, M; Carter, TH; Powell, BL; Kolitz, JE; Moore, JO; Eisfeld, A-K; Blachly, JS; Blum, W; Caligiuri, MA; Stone, RM; Marcucci, G; Croce, CM; Byrd, JC; Bloomfield, CD
MLA Citation
Garzon, R, Volinia, S, Papaioannou, D, Nicolet, D, Kohlschmidt, J, Yan, PS, Mrózek, K, Bucci, D, Carroll, AJ, Baer, MR, Wetzler, M, Carter, TH, Powell, BL, Kolitz, JE, Moore, JO, Eisfeld, A-K, Blachly, JS, Blum, W, Caligiuri, MA, Stone, RM, Marcucci, G, Croce, CM, Byrd, JC, and Bloomfield, CD. "Expression and prognostic impact of lncRNAs in acute myeloid leukemia." Proceedings of the National Academy of Sciences of the United States of America 111.52 (December 15, 2014): 18679-18684.
PMID
25512507
Source
epmc
Published In
Proceedings of the National Academy of Sciences of USA
Volume
111
Issue
52
Publish Date
2014
Start Page
18679
End Page
18684
DOI
10.1073/pnas.1422050112

Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies.

Abstract Because of the importance of the phosphoinositide 3-kinase (PI3K)/AKT pathway in chronic lymphocytic leukemia (CLL), we evaluated in vitro cytotoxicity induced by perifosine, an AKT inhibitor, in CLL lymphocytes and found that the mean 50% effective dose (ED50) was 313 nM. We then performed a phase II trial of perifosine in patients with relapsed/refractory CLL to assess response, outcomes, toxicity and ex vivo correlative measures. After 3 months of treatment, six of eight patients showed stable disease, one achieved a partial response and one had progressive disease. Median event-free survival and overall survival in all patients treated were 3.9 and 9.7 months. Adverse events included hematologic, infectious/fever, pain, gastrointestinal and constitutional toxicities. Unexpectedly, AKT phosphorylation in CLL lymphocytes from treated patients was not correlated with response. Additionally, perifosine did not inhibit AKT phosphorylation in cultured CLL lymphocytes. Perifosine is cytotoxic to CLL cells in vitro, and largely induces stabilized disease in vivo, with an AKT-independent mechanism.

Authors
Friedman, DR; Lanasa, MC; Davis, PH; Allgood, SD; Matta, KM; Brander, DM; Chen, Y; Davis, ED; Volkheimer, AD; Moore, JO; Gockerman, JP; Sportelli, P; Weinberg, JB
MLA Citation
Friedman, DR, Lanasa, MC, Davis, PH, Allgood, SD, Matta, KM, Brander, DM, Chen, Y, Davis, ED, Volkheimer, AD, Moore, JO, Gockerman, JP, Sportelli, P, and Weinberg, JB. "Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies." Leuk Lymphoma 55.5 (May 2014): 1067-1075.
PMID
23863122
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
55
Issue
5
Publish Date
2014
Start Page
1067
End Page
1075
DOI
10.3109/10428194.2013.824080

Chronic myelogenous leukemia, version 1.2015

Copyright © 2014 by the National Comprehensive Cancer Network. All rights reserved.Chronic myelogenous leukemia (CML) is usually diagnosed in the chronic phase. Untreated chronic phase CML will eventually progress to advanced phase (accelerated or blast phase) CML. Tyrosine kinase inhibitors (TKIs) have been shown to induce favorable response rates in patients with accelerated and blast phase CML. The addition of TKIs to chemotherapy has also been associated with improved outcomes in patients with blast phase CML. Allogeneic hematopoietic stem cell transplant remains a potentially curative option for patients with advanced phase CML, although treatment with a course of TKIs will be beneficial as a bridge to transplant. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with advanced phase CML.

Authors
O'Brien, S; Radich, JP; Abboud, CN; Akhtari, M; Altman, JK; Berman, E; Curtin, P; DeAngelo, DJ; Deininger, M; Devine, S; Fathi, AT; Gotlib, J; Jagasia, M; Kropf, P; Moore, JO; Pallera, A; Reddy, VVB; Shah, NP; Smith, BD; Snyder, DS; Wetzler, M; Gregory, K; Sundar, H
MLA Citation
O'Brien, S, Radich, JP, Abboud, CN, Akhtari, M, Altman, JK, Berman, E, Curtin, P, DeAngelo, DJ, Deininger, M, Devine, S, Fathi, AT, Gotlib, J, Jagasia, M, Kropf, P, Moore, JO, Pallera, A, Reddy, VVB, Shah, NP, Smith, BD, Snyder, DS, Wetzler, M, Gregory, K, and Sundar, H. "Chronic myelogenous leukemia, version 1.2015." JNCCN Journal of the National Comprehensive Cancer Network 12.11 (January 1, 2014): 1590-1610.
Source
scopus
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
12
Issue
11
Publish Date
2014
Start Page
1590
End Page
1610

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

Chronic Myelogenous Leukemia, Version 1.2014.

The 2014 NCCN Clinical Practice Guidelines in Oncology for Chronic Myelogenous Leukemia recommend quantitative reverse-transcription polymerase chain reaction (QPCR) standardized to International Scale (IS) as the preferred method for monitoring molecular response to tyrosine kinase inhibitor (TKI) therapy. A BCR-ABL1 transcript level of 10% or less (IS) is now included as the response milestone at 3 and 6 months. Change of therapy to an alternate TKI is recommended for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with imatinib. Continuing the same dose of TKI or switching to an alternate TKI are options for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with dasatinib or nilotinib. The guidelines recommend 6-month evaluation with QPCR (IS) for patients with BCR-ABL1 transcript levels greater than 10% at 3 months. Monitoring with QPCR (IS) every 3 months is recommended for all patients, including those who meet response milestones at 3, 6, 12, and 18 months (BCR-ABL1 transcript level ≤10% [IS] at 3 and 6 months, complete cytogenetic response at 12 and 18 months).

Authors
O'Brien, S; Radich, JP; Abboud, CN; Akhtari, M; Altman, JK; Berman, E; DeAngelo, DJ; Deininger, M; Devine, S; Fathi, AT; Gotlib, J; Jagasia, M; Kropf, P; Moore, JO; Pallera, A; Pinilla-Ibarz, J; Reddy, VV; Shah, NP; Smith, BD; Snyder, DS; Wetzler, M; Gregory, K; Sundar, H
MLA Citation
O'Brien, S, Radich, JP, Abboud, CN, Akhtari, M, Altman, JK, Berman, E, DeAngelo, DJ, Deininger, M, Devine, S, Fathi, AT, Gotlib, J, Jagasia, M, Kropf, P, Moore, JO, Pallera, A, Pinilla-Ibarz, J, Reddy, VV, Shah, NP, Smith, BD, Snyder, DS, Wetzler, M, Gregory, K, and Sundar, H. "Chronic Myelogenous Leukemia, Version 1.2014." Journal of the National Comprehensive Cancer Network : JNCCN 11.11 (November 2013): 1327-1340.
PMID
24225967
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
11
Issue
11
Publish Date
2013
Start Page
1327
End Page
1340

Acute Myeloid Leukemia, Version 2.2013 Featured Updates to the NCCN Guidelines

Authors
O'Donnell, MR; Tallman, MS; Abboud, CN; Altman, JK; Appelbaum, FR; Arber, DA; Attar, E; Borate, U; Coutre, SE; Damon, LE; Lancet, J; Maness, LJ; Marcucci, G; Martin, MG; Millenson, MM; Moore, JO; Ravandi, F; Shami, PJ; Smith, BD; Stone, RM; Strickland, SA; Wang, ES; Gregory, KM; Naganuma, M
MLA Citation
O'Donnell, MR, Tallman, MS, Abboud, CN, Altman, JK, Appelbaum, FR, Arber, DA, Attar, E, Borate, U, Coutre, SE, Damon, LE, Lancet, J, Maness, LJ, Marcucci, G, Martin, MG, Millenson, MM, Moore, JO, Ravandi, F, Shami, PJ, Smith, BD, Stone, RM, Strickland, SA, Wang, ES, Gregory, KM, and Naganuma, M. "Acute Myeloid Leukemia, Version 2.2013 Featured Updates to the NCCN Guidelines." JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK 11.9 (September 2013): 1047-1055.
PMID
24029121
Source
wos-lite
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
11
Issue
9
Publish Date
2013
Start Page
1047
End Page
1055

In rare acute myeloid leukemia patients harboring both RUNX1 and NPM1 mutations, RUNX1 mutations are unusual in structure and present in the germline.

Authors
Mendler, JH; Maharry, K; Becker, H; Eisfeld, AK; Senter, L; Mrózek, K; Kohlschmidt, J; Metzeler, KH; Schwind, S; Whitman, SP; Khalife, J; Caligiuri, MA; Klisovic, RB; Moore, JO; Carter, TH; Marcucci, G; Bloomfield, CD
MLA Citation
Mendler, JH, Maharry, K, Becker, H, Eisfeld, AK, Senter, L, Mrózek, K, Kohlschmidt, J, Metzeler, KH, Schwind, S, Whitman, SP, Khalife, J, Caligiuri, MA, Klisovic, RB, Moore, JO, Carter, TH, Marcucci, G, and Bloomfield, CD. "In rare acute myeloid leukemia patients harboring both RUNX1 and NPM1 mutations, RUNX1 mutations are unusual in structure and present in the germline." Haematologica 98.8 (August 1, 2013). (Letter)
Source
scopus
Published In
Haematologica
Volume
98
Issue
8
Publish Date
2013

Treatment of adults with acute lymphoblastic leukemia: Do the specifics of the regimen matter? Results From a Prospective Randomized Trial

Authors
Lamanna, N; Heffner, LT; Kalaycio, M; Schiller, G; Coutre, S; Moore, J; Seiter, K; Maslak, P; Panageas, K; Golde, D; Weiss, MA
MLA Citation
Lamanna, N, Heffner, LT, Kalaycio, M, Schiller, G, Coutre, S, Moore, J, Seiter, K, Maslak, P, Panageas, K, Golde, D, and Weiss, MA. "Treatment of adults with acute lymphoblastic leukemia: Do the specifics of the regimen matter? Results From a Prospective Randomized Trial." CANCER 119.6 (March 15, 2013): 1186-1194.
PMID
23280086
Source
wos-lite
Published In
Cancer
Volume
119
Issue
6
Publish Date
2013
Start Page
1186
End Page
1194
DOI
10.1002/cncr.27901

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

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

Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function.

Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin (IL)-10 (B10 cells). To identify functional links between CLL cells and regulatory B10 cells, the phenotypes and abilities of leukemia cells from 93 patients with overt CLL to express IL-10 were assessed. CD5(+) CLL cells purified from 90% of the patients were IL-10-competent and secreted IL-10 following appropriate ex vivo stimulation. Serum IL-10 levels were also significantly elevated in CLL patients. IL-10-competent cell frequencies were higher among CLLs with IgV(H) mutations, and correlated positively with TCL1 expression. In the TCL1-transgenic (TCL1-Tg) mouse model of CLL, IL-10-competent B cells with the cell surface phenotype of B10 cells expanded significantly with age, preceding the development of overt, CLL-like leukemia. Malignant CLL cells in TCL1-Tg mice also shared immunoregulatory functions with mouse and human B10 cells. Serum IL-10 levels varied in TCL1-Tg mice, but in vivo low-dose lipopolysaccharide treatment induced IL-10 expression in CLL cells and high levels of serum IL-10. Thus, malignant IL-10-competent CLL cells exhibit regulatory functions comparable to normal B10 cells that may contribute to the immunosuppression observed in patients and TCL1-Tg mice.

Authors
DiLillo, DJ; Weinberg, JB; Yoshizaki, A; Horikawa, M; Bryant, JM; Iwata, Y; Matsushita, T; Matta, KM; Chen, Y; Venturi, GM; Russo, G; Gockerman, JP; Moore, JO; Diehl, LF; Volkheimer, AD; Friedman, DR; Lanasa, MC; Hall, RP; Tedder, TF
MLA Citation
DiLillo, DJ, Weinberg, JB, Yoshizaki, A, Horikawa, M, Bryant, JM, Iwata, Y, Matsushita, T, Matta, KM, Chen, Y, Venturi, GM, Russo, G, Gockerman, JP, Moore, JO, Diehl, LF, Volkheimer, AD, Friedman, DR, Lanasa, MC, Hall, RP, and Tedder, TF. "Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function." Leukemia 27.1 (January 2013): 170-182.
PMID
22713648
Source
pubmed
Published In
Leukemia
Volume
27
Issue
1
Publish Date
2013
Start Page
170
End Page
182
DOI
10.1038/leu.2012.165

Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function

Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin (IL)-10 (B10 cells). To identify functional links between CLL cells and regulatory B10 cells, the phenotypes and abilities of leukemia cells from 93 patients with overt CLL to express IL-10 were assessed. CD5 + CLL cells purified from 90% of the patients were IL-10-competent and secreted IL-10 following appropriate ex vivo stimulation. Serum IL-10 levels were also significantly elevated in CLL patients. IL-10-competent cell frequencies were higher among CLLs with IgV H mutations, and correlated positively with TCL1 expression. In the TCL1-transgenic (TCL1-Tg) mouse model of CLL, IL-10-competent B cells with the cell surface phenotype of B10 cells expanded significantly with age, preceding the development of overt, CLL-like leukemia. Malignant CLL cells in TCL1-Tg mice also shared immunoregulatory functions with mouse and human B10 cells. Serum IL-10 levels varied in TCL1-Tg mice, but in vivo low-dose lipopolysaccharide treatment induced IL-10 expression in CLL cells and high levels of serum IL-10. Thus, malignant IL-10-competent CLL cells exhibit regulatory functions comparable to normal B10 cells that may contribute to the immunosuppression observed in patients and TCL1-Tg mice. © 2013 Macmillan Publishers Limited All rights reserved.

Authors
Dilillo, DJ; Weinberg, JB; Yoshizaki, A; Horikawa, M; Bryant, JM; Iwata, Y; Matsushita, T; Matta, KM; Chen, Y; Venturi, GM; Russo, G; Gockerman, JP; Moore, JO; Diehl, LF; Volkheimer, AD; Friedman, DR; Lanasa, MC; Hall, RP; Tedder, TF
MLA Citation
Dilillo, DJ, Weinberg, JB, Yoshizaki, A, Horikawa, M, Bryant, JM, Iwata, Y, Matsushita, T, Matta, KM, Chen, Y, Venturi, GM, Russo, G, Gockerman, JP, Moore, JO, Diehl, LF, Volkheimer, AD, Friedman, DR, Lanasa, MC, Hall, RP, and Tedder, TF. "Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function." Leukemia 27.1 (2013): 170-182.
Source
scival
Published In
Leukemia
Volume
27
Issue
1
Publish Date
2013
Start Page
170
End Page
182
DOI
10.1038/leu.2012.165

In rare acute myeloid leukemia patients harboring both RUNX1 and NPM1 mutations, RUNX1 mutations are unusual in structure and present in the germline

Authors
Mendler, JH; Maharry, K; Becker, H; Eisfeld, A-K; Senter, L; Mrózek, K; Kohlschmidt, J; Metzeler, KH; Schwind, S; Whitman, SP; Khalife, J; Caligiuri, MA; Klisovic, RB; Moore, JO; Carter, TH; Marcucci, G; Bloomfield, CD
MLA Citation
Mendler, JH, Maharry, K, Becker, H, Eisfeld, A-K, Senter, L, Mrózek, K, Kohlschmidt, J, Metzeler, KH, Schwind, S, Whitman, SP, Khalife, J, Caligiuri, MA, Klisovic, RB, Moore, JO, Carter, TH, Marcucci, G, and Bloomfield, CD. "In rare acute myeloid leukemia patients harboring both RUNX1 and NPM1 mutations, RUNX1 mutations are unusual in structure and present in the germline." Haematologica 98.8 (2013): 98.e92-98.e94.
PMID
23753029
Source
scival
Published In
Haematologica
Volume
98
Issue
8
Publish Date
2013
Start Page
98.e92
End Page
98.e94
DOI
10.3324/haematol.2013.089904

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

Chronic myelogenous leukemia.

Authors
O'Brien, S; Abboud, CN; Akhtari, M; Altman, J; Berman, E; DeAngelo, DJ; Devine, S; Fathi, AT; Gotlib, J; Jagasia, M; Moore, JO; Pinilla-Ibarz, J; Radich, JP; Reddy, VVB; Shah, NP; Shami, PJ; Smith, BD; Snyder, DS; Wetzler, M; Yunus, F; National Comprehensive Cancer Network,
MLA Citation
O'Brien, S, Abboud, CN, Akhtari, M, Altman, J, Berman, E, DeAngelo, DJ, Devine, S, Fathi, AT, Gotlib, J, Jagasia, M, Moore, JO, Pinilla-Ibarz, J, Radich, JP, Reddy, VVB, Shah, NP, Shami, PJ, Smith, BD, Snyder, DS, Wetzler, M, Yunus, F, and National Comprehensive Cancer Network, . "Chronic myelogenous leukemia." J Natl Compr Canc Netw 10.1 (January 2012): 64-110.
PMID
22223870
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
1
Publish Date
2012
Start Page
64
End Page
110

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

RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and microRNA expression signatures

Purpose: To determine the association of RUNX1 mutations with therapeutic outcome in younger and older patients with primary cytogenetically normal acute myeloid leukemia (CN-AML) and with gene/ microRNA expression signatures. Patients and Methods: Younger (< 60 years; n = 175) and older (≥ 60 years; n = 225) patients with CN-AML treated with intensive cytarabine/anthracycline- based first-line therapy on Cancer and Leukemia Group B protocols were centrally analyzed for RUNX1 mutations by polymerase chain reaction and direct sequencing and for established prognostic gene mutations. Gene/microRNA expression profiles were derived using microarrays. Results: RUNX1 mutations were found in 8% and 16% of younger and older patients, respectively (P = .02). They were associated with ASXL1 mutations (P < .001) and inversely associated with NPM1 (P < .001) and CEBPA (P = .06) mutations. RUNX1-mutated patients had lower complete remission rates (P = .005 in younger; P = .006 in older) and shorter disease-free survival (P = .058 in younger; P < .001 in older), overall survival (P = .003 in younger; P < .001 in older), and event-free survival (P < .001 for younger and older) than RUNX1 wild-type patients. Because RUNX1 mutations were more common in older patients and almost never coexisted with NPM1 mutations, RUNX1 mutation-associated expression signatures were derived in older, NPM1 wild-type patients and featured upregulation of genes normally expressed in primitive hematopoietic cells and B-cell progenitors, including DNTT, BAALC, BLNK, CD109, RBPMS, and FLT3, and downregulation of promoters of myelopoiesis, including CEBPA and miR-223. Conclusion: RUNX1 mutations are twice as common in older than younger patients with CN-AML and negatively impact outcome in both age groups. RUNX1-mutated blasts have molecular features of primitive hematopoietic and lymphoid progenitors, potentially leading to novel therapeutic approaches. © 2012 by American Society of Clinical Oncology.

Authors
Mendler, JH; Maharry, K; Radmacher, MD; Mrózek, K; Becker, H; Metzeler, KH; Schwind, S; Whitman, SP; Khalife, J; Kohlschmidt, J; Nicolet, D; Powell, BL; Carter, TH; Wetzler, M; Moore, JO; Kolitz, JE; Baer, MR; Carroll, AJ; Larson, RA; Caligiuri, MA; Marcucci, G; Bloomfield, CD
MLA Citation
Mendler, JH, Maharry, K, Radmacher, MD, Mrózek, K, Becker, H, Metzeler, KH, Schwind, S, Whitman, SP, Khalife, J, Kohlschmidt, J, Nicolet, D, Powell, BL, Carter, TH, Wetzler, M, Moore, JO, Kolitz, JE, Baer, MR, Carroll, AJ, Larson, RA, Caligiuri, MA, Marcucci, G, and Bloomfield, CD. "RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and microRNA expression signatures." Journal of Clinical Oncology 30.25 (2012): 3109-3118.
PMID
22753902
Source
scival
Published In
Journal of Clinical Oncology
Volume
30
Issue
25
Publish Date
2012
Start Page
3109
End Page
3118
DOI
10.1200/JCO.2011.40.6652

Acute myeloid leukemia

Acute myeloid leukemia (AML) remains the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML provide recommendations on the diagnostic evaluation and workup for AML, risk assessment based on cytogenetic and molecular features, treatment options for induction and consolidation therapies for younger and older (age ≥ 65 years) adult patients, and key supportive care considerations. © JNCCN - Journal of the National Comprehensive Cancer Network.

Authors
O'Donnell, MR; Abboud, CN; Altman, J; Appelbaum, FR; Arber, DA; Attar, E; Borate, U; Coutre, SE; Damon, LE; Goorha, S; Lancet, J; Maness, LJ; Marcucci, G; Millenson, MM; Moore, JO; Ravandi, F; Shami, PJ; Smith, BD; Stone, RM; Strickland, SA; Tallman, MS; Wang, ES; Naganuma, M; Gregory, KM
MLA Citation
O'Donnell, MR, Abboud, CN, Altman, J, Appelbaum, FR, Arber, DA, Attar, E, Borate, U, Coutre, SE, Damon, LE, Goorha, S, Lancet, J, Maness, LJ, Marcucci, G, Millenson, MM, Moore, JO, Ravandi, F, Shami, PJ, Smith, BD, Stone, RM, Strickland, SA, Tallman, MS, Wang, ES, Naganuma, M, and Gregory, KM. "Acute myeloid leukemia." JNCCN Journal of the National Comprehensive Cancer Network 10.8 (2012): 984-1021.
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
8
Publish Date
2012
Start Page
984
End Page
1021

miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia

High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40 , were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications. © 2012 by The American Society of Hematology.

Authors
Eisfeld, A-K; Marcucci, G; Maharry, K; Schwind, S; Radmacher, MD; Nicolet, D; Becker, H; Mrózek, K; Whitman, SP; Metzeler, KH; Mendler, JH; Wu, Y-Z; Liyanarachchi, S; Patel, R; Baer, MR; Powell, BL; Carter, TH; Moore, JO; Kolitz, JE; Wetzler, M; Caligiuri, MA; Larson, RA; Tanner, SM; Chapelle, ADL; Bloomfield, CD
MLA Citation
Eisfeld, A-K, Marcucci, G, Maharry, K, Schwind, S, Radmacher, MD, Nicolet, D, Becker, H, Mrózek, K, Whitman, SP, Metzeler, KH, Mendler, JH, Wu, Y-Z, Liyanarachchi, S, Patel, R, Baer, MR, Powell, BL, Carter, TH, Moore, JO, Kolitz, JE, Wetzler, M, Caligiuri, MA, Larson, RA, Tanner, SM, Chapelle, ADL, and Bloomfield, CD. "miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia." Blood 120.2 (2012): 249-258.
PMID
22529287
Source
scival
Published In
Blood
Volume
120
Issue
2
Publish Date
2012
Start Page
249
End Page
258
DOI
10.1182/blood-2012-02-408492

Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia

Purpose: To determine the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene- and microRNA-expression signatures in primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods: Four hundred fifteen previously untreated adults were analyzed for DNMT3A mutations and established prognostic gene mutations and expression markers. Gene- and microRNA-expression profiles were derived using microarrays. Results: Younger (< 60 years; n = 181) and older (≥ 60 years; n = 234) patients had similar frequencies of DNMT3A mutations (35.3% v 33.3%). Missense mutations affecting arginine codon 882 (R882-DNMT3A) were more common (n = 92; 62%) than those affecting other codons (non-R882-DNMT3A). DNMT3A-mutated patients did not differ regarding complete remission rate, but had shorter disease-free survival (DFS; P = .03) and, by trend, overall survival (OS; P = .07) than DNMT3A-wild-type patients. In multivariable analyses, DNMT3A mutations remained associated with shorter DFS (P = .01), but not with shorter OS. When analyzed separately, the two DNMT3A mutation types had different significance by age group. Younger patients with non-R882-DNMT3A mutations had shorter DFS (P = .002) and OS (P = .02), whereas older patients with R882-DNMT3A mutations had shorter DFS (P = .005) and OS (P =.002) after adjustment for other clinical and molecular prognosticators. Gene- and microRNA-expression signatures did not accurately predict DNMT3A mutational status. Conclusion: DNMT3A mutations are frequent in CN-AML, and their clinical significance seems to be age dependent. DNMT3A-R882 mutations are associated with adverse prognosis in older patients, and non-R882-DNMT3A mutations are associated with adverse prognosis in younger patients. Low accuracy of gene- and microRNA-expression signatures in predicting DNMT3A mutation status suggested that the role of these mutations in AML remains to be elucidated. © 2012 by American Society of Clinical Oncology.

Authors
Marcucci, G; Metzeler, KH; Schwind, S; Becker, H; Maharry, K; Mroźek, K; Radmacher, MD; Kohlschmidt, J; Nicolet, D; Whitman, SP; Wu, Y-Z; Powell, BL; Carter, TH; Kolitz, JE; Wetzler, M; Carroll, AJ; Baer, MR; Moore, JO; Caligiuri, MA; Larson, RA; Bloomfield, CD
MLA Citation
Marcucci, G, Metzeler, KH, Schwind, S, Becker, H, Maharry, K, Mroźek, K, Radmacher, MD, Kohlschmidt, J, Nicolet, D, Whitman, SP, Wu, Y-Z, Powell, BL, Carter, TH, Kolitz, JE, Wetzler, M, Carroll, AJ, Baer, MR, Moore, JO, Caligiuri, MA, Larson, RA, and Bloomfield, CD. "Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia." Journal of Clinical Oncology 30.7 (2012): 742-750.
PMID
22291079
Source
scival
Published In
Journal of Clinical Oncology
Volume
30
Issue
7
Publish Date
2012
Start Page
742
End Page
750
DOI
10.1200/JCO.2011.39.2092

Hodgkin lymphoma, version 2.2012: Featured updates to the NCCN guidelines

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin Lymphoma (HL) include the clinical management of classical HL and lymphocyte-predominant HL (LPHL). Major changes have been incorporated into these guidelines since their inception. In the 2012 NCCN Guidelines for HL, PET scans are not recommended for interim restaging of patients with stage I to II favorable disease. After reevaluating the available evidence on the use of interim PET imaging, the panel recommends the use of diagnostic CT scan of involved sites for interim restaging after completion of chemotherapy for this group of patients. Maintenance rituximab for 2 years is included as an option for patients with stage IB to IIB or stage III to IV LPHL treated with rituximab alone in the first-line setting. Brentuximab vedotin is included as an option for patients with progressive disease or relapsed disease after second-line chemotherapy or high-dose therapy with autologous stem cell rescue. © JNCCN-Journal of the National Comprehensive Cancer Network.

Authors
Hoppe, RT; Advani, RH; Ai, WZ; Ambinder, RF; Aoun, P; Bello, CM; Bierman, PJ; Blum, KA; Chen, R; Dabaja, B; Duron, Y; Forero, A; Gordon, LI; Hernandez-Ilizaliturri, FJ; Hochberg, EP; Maloney, DG; Mansur, D; Mauch, PM; Metzger, M; Moore, JO; Morgan, D; Moskowitz, CH; Poppe, M; Pro, B; Winter, JN; Yahalom, J; Sundar, H
MLA Citation
Hoppe, RT, Advani, RH, Ai, WZ, Ambinder, RF, Aoun, P, Bello, CM, Bierman, PJ, Blum, KA, Chen, R, Dabaja, B, Duron, Y, Forero, A, Gordon, LI, Hernandez-Ilizaliturri, FJ, Hochberg, EP, Maloney, DG, Mansur, D, Mauch, PM, Metzger, M, Moore, JO, Morgan, D, Moskowitz, CH, Poppe, M, Pro, B, Winter, JN, Yahalom, J, and Sundar, H. "Hodgkin lymphoma, version 2.2012: Featured updates to the NCCN guidelines." JNCCN Journal of the National Comprehensive Cancer Network 10.5 (2012): 589-597.
PMID
22570290
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
5
Publish Date
2012
Start Page
589
End Page
597

Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia

Purpose: To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML). Patients and Methods: We analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), and overall survival (OS) among patients classified into the four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse) separately for 818 younger (age < 60 years) and 732 older (age ≥ 60 years) patients. Results: The percentages of younger versus older patients in the favorable (41% v 20%; P < .001), intermediate-II (19% v 30%; P < .001), and adverse (22% v 31%; P < .001) genetic groups differed. The favorable group had the best and the adverse group the worst CR rates, DFS, and OS in both age groups. Both intermediate groups had significantly worse outcomes than the favorable but better than the adverse group. Intermediate-I and intermediate-II groups in older patients had similar outcomes, whereas the intermediate-II group in younger patients had better OS but not better CR rates or DFS than the intermediate-I group. The prognostic significance of ELN classification was confirmed by multivariable analyses. For each ELN group, older patients had worse outcomes than younger patients. Conclusion: The ELN classification clearly separates the genetic groups by outcome, supporting its use for risk stratification in clinical trials. Because they have different proportions of genetic alterations and outcomes, younger and older patients should be reported separately when using the ELN classification. © 2012 by American Society of Clinical Oncology.

Authors
Mroźek, K; Marcucci, G; Nicolet, D; Maharry, KS; Becker, H; Whitman, SP; Metzeler, KH; Schwind, S; Wu, Y-Z; Kohlschmidt, J; Pettenati, MJ; Heerema, NA; Block, AW; Patil, SR; Baer, MR; Kolitz, JE; Moore, JO; Carroll, AJ; Stone, RM; Larson, RA; Bloomfield, CD
MLA Citation
Mroźek, K, Marcucci, G, Nicolet, D, Maharry, KS, Becker, H, Whitman, SP, Metzeler, KH, Schwind, S, Wu, Y-Z, Kohlschmidt, J, Pettenati, MJ, Heerema, NA, Block, AW, Patil, SR, Baer, MR, Kolitz, JE, Moore, JO, Carroll, AJ, Stone, RM, Larson, RA, and Bloomfield, CD. "Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia." Journal of Clinical Oncology 30.36 (2012): 4515-4523.
PMID
22987078
Source
scival
Published In
Journal of Clinical Oncology
Volume
30
Issue
36
Publish Date
2012
Start Page
4515
End Page
4523
DOI
10.1200/JCO.2012.43.4738

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

SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target.

B-cell chronic lymphocytic leukemia (CLL), an incurable leukemia, is characterized by defective apoptosis. We found that the SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A) tumor suppressor, is overexpressed in primary CLL cells and B-cell non-Hodgkin lymphoma (NHL) cell line cells. In CLL, increased levels of SET correlated significantly with disease severity (shorter time to treatment and overall survival). We developed SET antagonist peptides that bound SET, increased cellular PP2A activity, decreased Mcl-1 expression, and displayed selective cytotoxicity for CLL and NHL cells in vitro. In addition, shRNA for SET was cytotoxic for NHL cells in vitro. The SET antagonist peptide COG449 inhibited growth of NHL tumor xenografts in mice. These data demonstrate that SET is a new treatment target in B-cell malignancies and that SET antagonists represent novel agents for treatment of CLL and NHL.

Authors
Christensen, DJ; Chen, Y; Oddo, J; Matta, KM; Neil, J; Davis, ED; Volkheimer, AD; Lanasa, MC; Friedman, DR; Goodman, BK; Gockerman, JP; Diehl, LF; de Castro, CM; Moore, JO; Vitek, MP; Weinberg, JB
MLA Citation
Christensen, DJ, Chen, Y, Oddo, J, Matta, KM, Neil, J, Davis, ED, Volkheimer, AD, Lanasa, MC, Friedman, DR, Goodman, BK, Gockerman, JP, Diehl, LF, de Castro, CM, Moore, JO, Vitek, MP, and Weinberg, JB. "SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target." Blood 118.15 (October 13, 2011): 4150-4158.
PMID
21844565
Source
pubmed
Published In
Blood
Volume
118
Issue
15
Publish Date
2011
Start Page
4150
End Page
4158
DOI
10.1182/blood-2011-04-351072

Escalation of daunorubicin and addition of etoposide in the ADE regimen in acute myeloid leukemia patients aged 60 years and older: Cancer and Leukemia Group B Study 9720.

Untreated de novo (n=421) and secondary (n=189) acute myeloid leukemia (AML) patients ≥60 years received intensified chemotherapy, including daunorubicin 60 mg/m(2) and etoposide 100 mg/m(2) during days 1, 2, 3 with cytarabine 100 mg/m(2) during days 1-7, with a second induction if needed and one consolidation course with these drugs and doses for 2, 2 and 5 days, respectively. In all, 287 (47%) achieved complete remission (CR), 136 (22%) died and 187 (31%) were non-responders. CR rates were 27, 44 and 52% for complex karyotypes, rare aberrations and neither (P<0.001), 52 and 37% for de novo and secondary AML (P=0.003), and 53 and 42% for age 60-69 and ≥70 years (P=0.015). In multivariable analysis, CR predictors included non-complex/non-rare karyotypes (P<0.001), de novo AML (P<0.001), better performance status (PS) (P<0.001) and younger age (P=0.001). Disease-free (DFS) and overall (OS) survival medians were 6.8 (95% CI: 6.2, 7.8) and 7.2 (95% CI: 6.4, 8.6) months. In multivariable analysis, DFS was shorter for complex karyotypes (P<0.001) and increasing white blood count (WBC) (P<0.001) and age (P=0.038), and OS for complex karyotypes (P<0.001), increasing WBC (P=0.001) and age (P<0.001), poorer PS (P<0.001) and secondary AML (P=0.010). Outcomes and prognostic factors were similar to those in previous Cancer and Leukemia Group B studies.

Authors
Baer, MR; George, SL; Sanford, BL; Mrózek, K; Kolitz, JE; Moore, JO; Stone, RM; Powell, BL; Caligiuri, MA; Bloomfield, CD; Larson, RA; Cancer and Leukemia Group B,
MLA Citation
Baer, MR, George, SL, Sanford, BL, Mrózek, K, Kolitz, JE, Moore, JO, Stone, RM, Powell, BL, Caligiuri, MA, Bloomfield, CD, Larson, RA, and Cancer and Leukemia Group B, . "Escalation of daunorubicin and addition of etoposide in the ADE regimen in acute myeloid leukemia patients aged 60 years and older: Cancer and Leukemia Group B Study 9720." Leukemia 25.5 (May 2011): 800-807.
PMID
21321569
Source
pubmed
Published In
Leukemia
Volume
25
Issue
5
Publish Date
2011
Start Page
800
End Page
807
DOI
10.1038/leu.2011.9

Sequential development of histiocytic sarcoma and diffuse large b-cell lymphoma in a patient with a remote history of follicular lymphoma with genotypic evidence of a clonal relationship: a divergent (bilineal) neoplastic transformation of an indolent B-cell lymphoma in a single individual.

Follicular lymphoma (FL) often transforms to diffuse large B-cell lymphoma (DLBCL) during its protracted clinical course. Rarely, histiocytic sarcoma (HS) occurs secondary to or concurrent with FL, although the biological relationship between these 2 morphologically and immunophenotypically distinct entities in the same individual has not been well characterized. We report a unique case showing the sequential occurrence of first, HS and then DLBCL in a patient with a remote history of FL. In this case, HS developed 17 years after the diagnosis of FL and was shown to partly retain the immunophenotypic features characteristic of FL, while showing the morphologic and immunophenotypic profiles diagnostic of HS. DLBCL occurred 18.5 years after FL. Both HS and DLBCL harbored the IGH/BCL2 fusion gene, a hallmark of FL, per interphase fluorescence in situ hybridization analysis. Immunoglobulin gene rearrangement studies showed a clonal rearrangement of the IGH gene in both HS and DLBCL with identical amplicons, suggesting a shared origin of the neoplastic clones. These data support the hypothesis of transdifferentiation or transevolution in a mature B-cell neoplasm, and, in addition, suggest the possibility of a divergent (bilineal) neoplastic transformation of FL in a single individual.

Authors
Wang, E; Papalas, J; Hutchinson, CB; Kulbacki, E; Huang, Q; Sebastian, S; Rehder, C; Silbermins, D; Moore, J; Datto, M
MLA Citation
Wang, E, Papalas, J, Hutchinson, CB, Kulbacki, E, Huang, Q, Sebastian, S, Rehder, C, Silbermins, D, Moore, J, and Datto, M. "Sequential development of histiocytic sarcoma and diffuse large b-cell lymphoma in a patient with a remote history of follicular lymphoma with genotypic evidence of a clonal relationship: a divergent (bilineal) neoplastic transformation of an indolent B-cell lymphoma in a single individual." Am J Surg Pathol 35.3 (March 2011): 457-463.
PMID
21317718
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
35
Issue
3
Publish Date
2011
Start Page
457
End Page
463
DOI
10.1097/PAS.0b013e3182098799

NCCN Task Force report: tyrosine kinase inhibitor therapy selection in the management of patients with chronic myelogenous leukemia.

The advent of imatinib has dramatically improved outcomes in patients with chronic myelogenous leukemia (CML). It has become the standard of care for all patients with newly diagnosed chronic-phase CML based on its successful induction of durable responses in most patients. However, its use is complicated by the development of resistance in some patients. Dose escalation might overcome this resistance if detected early. The second-generation tyrosine kinase inhibitors (TKIs) dasatinib and nilotinib provide effective therapeutic options for managing patients resistant or intolerant to imatinib. Recent studies have shown that dasatinib and nilotinib provide quicker and potentially better responses than standard-dose imatinib when used as a first-line treatment. The goal of therapy for patients with CML is the achievement of a complete cytogenetic response, and eventually a major molecular response, to prevent disease progression to accelerated or blast phase. Selecting the appropriate TKI depends on many factors, including disease phase, primary or secondary resistance to TKI, the agent's side effect profile and its relative effectiveness against BCR-ABL mutations, and the patient's tolerance to therapy. In October 2010, NCCN organized a task force consisting of a panel of experts from NCCN Member Institutions with expertise in the management of patients with CML to discuss these issues. This report provides recommendations regarding the selection of TKI therapy for the management of patients with CML based on the evaluation of available published clinical data and expert opinion among the task force members.

Authors
O'Brien, S; Berman, E; Moore, JO; Pinilla-Ibarz, J; Radich, JP; Shami, PJ; Smith, BD; Snyder, DS; Sundar, HM; Talpaz, M; Wetzler, M
MLA Citation
O'Brien, S, Berman, E, Moore, JO, Pinilla-Ibarz, J, Radich, JP, Shami, PJ, Smith, BD, Snyder, DS, Sundar, HM, Talpaz, M, and Wetzler, M. "NCCN Task Force report: tyrosine kinase inhibitor therapy selection in the management of patients with chronic myelogenous leukemia." J Natl Compr Canc Netw 9 Suppl 2 (February 2011): S1-25.
PMID
21335443
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9 Suppl 2
Publish Date
2011
Start Page
S1
End Page
25

ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category

The associations of mutations in the enhancer of trithorax and polycomb family gene ASXL1 with pretreatment patient characteristics, outcomes, and gene-/microRNA-expression profiles in primary cytogenetically normal acute myeloid leukemia (CN-AML) are unknown. We analyzed 423 adult patients for ASXL1 mutations, other prognostic gene mutations, and gene-/microRNA-expression profiles. ASXL1 mutations were 5 times more common in older (≥60 years) patients (16.2%) than those younger than 60 years (3.2%; P < .001). Among older patients, ASXL1 mutations associated with wild-type NPM1 (P < .001), absence of FLT3-internal tandem duplications (P = .002), mutated CEBPA (P = .01), and with inferior complete remission (CR) rate (P = .04), disease-free survival (DFS; P = .03), overall survival (OS; P = .006), and event-free survival (EFS; P = .002). Within the European LeukemiaNet (ELN) genetic categories of older CN-AML, ASXL1 mutations associated with inferior CR rate (P = .02), OS (P < .001), and EFS (P < .001) among ELN Favorable, but not among ELN Intermediate-I patients. Multivariable analyses confirmed associations of ASXL1 mutations with unfavorable CR rate (P = .03), DFS (P < .001), OS (P < .001), and EFS (P < .001) among ELN Favorable patients. We identified an ASXL1 mutation-associated gene-expression signature, but no microRNA-expression signature. This first study of ASXL1 mutations in primary CN-AML demonstrates that ASXL1-mutated older patients, particularly within the ELN Favorable group, have unfavorable outcomes and may be candidates for experimental treatment approaches. © 2011 by The American Society of Hematology.

Authors
Metzeler, KH; Becker, H; Maharry, K; Radmacher, MD; Kohlschmidt, J; Mrózek, K; Nicolet, D; Whitman, SP; Wu, Y-Z; Schwind, S; Powell, BL; Carter, TH; Wetzler, M; Moore, JO; Kolitz, JE; Baer, MR; Carroll, AJ; Larson, RA; Caligiuri, MA; Marcucci, G; Bloomfield, CD
MLA Citation
Metzeler, KH, Becker, H, Maharry, K, Radmacher, MD, Kohlschmidt, J, Mrózek, K, Nicolet, D, Whitman, SP, Wu, Y-Z, Schwind, S, Powell, BL, Carter, TH, Wetzler, M, Moore, JO, Kolitz, JE, Baer, MR, Carroll, AJ, Larson, RA, Caligiuri, MA, Marcucci, G, and Bloomfield, CD. "ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category." Blood 118.26 (2011): 6920-6929.
PMID
22031865
Source
scival
Published In
Blood
Volume
118
Issue
26
Publish Date
2011
Start Page
6920
End Page
6929
DOI
10.1182/blood-2011-08-368225

Clinical outcome and gene- and microRNA-expression profiling according to the wilms tumor 1 (WT1) single nucleotide polymorphism rs16754 in adult de novo cytogenetically normal acute myeloid leukemia: A cancer and leukemia group B study

Background The alleles of the Wilms tumor 1 (WT1) polymorphism rs16754 harbor adenine (A) or guanine (G). Recently, rs16754 has been reported to affect the outcome of patients with cytogenetically normal acute myeloid leukemia. To validate this finding, we investigated pretreatment features and outcome associated with rs16754 in a large cohort of patients with cytogenetically normal acute myeloid leukemia. Design and Methods Four-hundred and thirty-three intensively treated and molecularly characterized cytogenetically normal patients with de novo acute myeloid leukemia (18-83 years old) were analyzed for rs16754. To gain biological insights, we studied the gene- and microRNA-expression profiles for associations with rs16754. Results Three-hundred and nine (71%) patients were homozygous for A (WT1 AA), 112 (26%) were heterozygous (WT1 AG) and 12 (3%) were homozygous for G (WT1 GG). For comparison with previous studies, we grouped WT1 AG and WT1 GG patients and compared them with WT1 AA patients divided into younger (<60 years) and older (≥60 years) adults. We found no independent prognostic impact of WT1 AA. However, WT1 GG patients, who were less often Caucasian than WT1 AG (P=0.001) or WT1 AA (P=0.008) patients, and had TET2 mutations more often than WT1 AG (P=0.02) patients, had, among patients with FLT3-internal tandem duplication and/or NPM1 wild-type, better disease-free (P=0.02) and overall survival (P=0.04) than WT1 AA and WT1 AG patients combined. Unsupervised and supervised analyses of the gene- and microRNA-expression profiles suggested that there were no distinct expression patterns associated with any rs16754 genotype. Conclusions We did not observe the previously reported adverse impact of WT1 AA but found favorable outcomes associated with the homozygous WT1 GG. Considering its low frequency, confirmatory studies are necessary. The biological significance of rs16754 remains questionable as no distinct expression profiles were associated with the genotypes. © 2011 Ferrata Storti Foundation.

Authors
Becker, H; Maharry, K; Radmacher, MD; Mrózek, K; Metzeler, KH; Whitman, SP; Schwind, S; Kohlschmidt, J; Wu, Y-Z; Powell, BL; Carter, TH; Kolitz, JE; Wetzler, M; Carroll, AJ; Baer, MR; Moore, JO; Caligiuri, MA; Larson, RA; Marcucci, G; Bloomfield, CD
MLA Citation
Becker, H, Maharry, K, Radmacher, MD, Mrózek, K, Metzeler, KH, Whitman, SP, Schwind, S, Kohlschmidt, J, Wu, Y-Z, Powell, BL, Carter, TH, Kolitz, JE, Wetzler, M, Carroll, AJ, Baer, MR, Moore, JO, Caligiuri, MA, Larson, RA, Marcucci, G, and Bloomfield, CD. "Clinical outcome and gene- and microRNA-expression profiling according to the wilms tumor 1 (WT1) single nucleotide polymorphism rs16754 in adult de novo cytogenetically normal acute myeloid leukemia: A cancer and leukemia group B study." Haematologica 96.10 (2011): 1488-1495.
PMID
21659357
Source
scival
Published In
Haematologica
Volume
96
Issue
10
Publish Date
2011
Start Page
1488
End Page
1495
DOI
10.3324/haematol.2011.041905

Hodgkin lymphoma: Clinical practice guidelines in oncology

Authors
Hoppe, RT; Advani, RH; Ai, WZ; Ambinder, RF; Bello, CM; Bierman, PJ; Blum, KA; Dabaja, B; Duron, Y; Forero, A; Gordon, LI; Hernandez-Ilizaliturri, FJ; Hochberg, EP; Maloney, DG; Mansur, D; Mauch, PM; Metzger, M; Moore, JO; Morgan, D; Moskowitz, CH; Poppe, M; Pro, B; Weiss, L; Winter, JN; Yahalom, J
MLA Citation
Hoppe, RT, Advani, RH, Ai, WZ, Ambinder, RF, Bello, CM, Bierman, PJ, Blum, KA, Dabaja, B, Duron, Y, Forero, A, Gordon, LI, Hernandez-Ilizaliturri, FJ, Hochberg, EP, Maloney, DG, Mansur, D, Mauch, PM, Metzger, M, Moore, JO, Morgan, D, Moskowitz, CH, Poppe, M, Pro, B, Weiss, L, Winter, JN, and Yahalom, J. "Hodgkin lymphoma: Clinical practice guidelines in oncology." JNCCN Journal of the National Comprehensive Cancer Network 9.9 (2011): 1020-1058.
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
9
Publish Date
2011
Start Page
1020
End Page
1058

TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: A cancer and leukemia group B study

Purpose: To determine the frequency of TET2 mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene-and microRNA-expression signatures in patients with primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods: Four-hundred twenty-seven patients with CN-AML were analyzed for TET2 mutations by polymerase chain reaction and direct sequencing and for established prognostic gene mutations. Geneand microRNA-expression profiles were derived using microarrays Results: TET2 mutations, found in 23% of patients, were associated with older age (P <.001) and higher pretreatment WBC (P =.04) compared with wild-type TET2 (TET2-wt). In the European LeukemiaNet (ELN) favorable-risk group (patients with CN-AML who have mutated CEBPA and/or mutated NPM1 without FLT3 internal tandem duplication [FLT3-ITD]), TET2-mutated patients had shorter event-free survival (EFS; P <.001) because of a lower complete remission (CR) rate (P =.007), and shorter disease-free survival (DFS; P =.003), and also had shorter overall survival (P =.001) compared with TET2-wt patients. TET2 mutations were not associated with outcomes in the ELN intermediate-I-risk group (CN-AML with wild-type CEBPA and wild-type NPM1 and/or FLT3-ITD). In multivariable models, TET2 mutations were associated with shorter EFS (P =.004), lower CR rate (P = 03), and shorter DFS (P =.05) only among favorable-risk CN-AML patients. We identified a TET2 mutation-associated gene-expression signature in favorable-risk but not in intermediate-I-risk patients and found distinct mutation-associated microRNA signatures in both ELN groups. Conclusion: TET2 mutations improve the ELN molecular-risk classification in primary CN-AML because of their adverse prognostic impact in an otherwise favorable-risk patient subset. Our data suggest that these patients may be candidates for alternative therapies © 2011 by American Society of Clinical Oncology.

Authors
Metzeler, KH; Maharry, K; Radmacher, MD; Mrózek, K; Margeson, D; Becker, H; Curfman, J; Holland, KB; Schwind, S; Whitman, SP; Wu, Y-Z; Blum, W; Powell, BL; Carter, TH; Wetzler, M; Moore, JO; Kolitz, JE; Baer, MR; Carroll, AJ; Larson, RA; Caligiuri, MA; Marcucci, G; Bloomfield, CD
MLA Citation
Metzeler, KH, Maharry, K, Radmacher, MD, Mrózek, K, Margeson, D, Becker, H, Curfman, J, Holland, KB, Schwind, S, Whitman, SP, Wu, Y-Z, Blum, W, Powell, BL, Carter, TH, Wetzler, M, Moore, JO, Kolitz, JE, Baer, MR, Carroll, AJ, Larson, RA, Caligiuri, MA, Marcucci, G, and Bloomfield, CD. "TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: A cancer and leukemia group B study." Journal of Clinical Oncology 29.10 (2011): 1373-1381.
PMID
21343549
Source
scival
Published In
Journal of Clinical Oncology
Volume
29
Issue
10
Publish Date
2011
Start Page
1373
End Page
1381
DOI
10.1200/JCO.2010.32.7742

Acute myeloid leukemia: Clinical practice guidelines in oncology

Authors
O'Donnell, MR; Abboud, CN; Altman, J; Appelbaum, FR; Coutre, SE; Damon, LE; Foran, JM; Goorha, S; Maness, LJ; Marcucci, G; Maslak, P; Millenson, MM; Moore, JO; Ravandi, F; Shami, PJ; Smith, BD; Stone, RM; Strickland, SA; Tallman, MS; Wang, ES; Gregory, K; Kumar, R
MLA Citation
O'Donnell, MR, Abboud, CN, Altman, J, Appelbaum, FR, Coutre, SE, Damon, LE, Foran, JM, Goorha, S, Maness, LJ, Marcucci, G, Maslak, P, Millenson, MM, Moore, JO, Ravandi, F, Shami, PJ, Smith, BD, Stone, RM, Strickland, SA, Tallman, MS, Wang, ES, Gregory, K, and Kumar, R. "Acute myeloid leukemia: Clinical practice guidelines in oncology." JNCCN Journal of the National Comprehensive Cancer Network 9.3 (2011): 280-317.
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
3
Publish Date
2011
Start Page
280
End Page
317

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

LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells.

B-cell chronic lymphocytic leukemia (CLL) is characterized by slow accumulation of malignant cells, which are supported in the microenvironment by cell-cell interactions and soluble cytokines such as tumor necrosis factor (TNF). We evaluated the effect of the small molecule TNF inhibitor LMP-420 on primary CLL cells. The mean concentration of LMP-420 required to induce 50% cytotoxicity (ED50) at 72 h was 245 n. LMP-420-induced time- and dose-dependent apoptosis, as shown by annexin V staining, caspase activation and DNA fragmentation. These changes were associated with decreased expression of anti-apoptotic proteins Mcl-1, Bcl-xL and Bcl-2. CLL cells from patients with poor prognostic indicators showed LMP-420 sensitivity equal to that for cells from patients with favorable characteristics. In addition, LMP-420 potentiated the cytotoxic effect of fludarabine and inhibited in vitro proliferation of stimulated CLL cells. Gene expression profiling indicated that the mechanism of action of LMP-420 may involve suppression of nuclear factor-kappaB and immune response pathways in CLL cells. LMP-420 had minimal effects on normal peripheral blood mononuclear cell, B- and T-cell function, and hematopoietic colony formation. Our data suggest that LMP-420 may be a useful treatment for CLL with negligible hematologic toxicities.

Authors
Mowery, YM; Weinberg, JB; Kennedy, MN; Bond, KM; Moore, JO; Lanasa, MC; Gockerman, JP; Diehl, LF; Pizzo, SV; Cianciolo, GJ; Friedman, DR
MLA Citation
Mowery, YM, Weinberg, JB, Kennedy, MN, Bond, KM, Moore, JO, Lanasa, MC, Gockerman, JP, Diehl, LF, Pizzo, SV, Cianciolo, GJ, and Friedman, DR. "LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells." Leukemia 24.9 (September 2010): 1580-1587.
PMID
20613784
Source
pubmed
Published In
Leukemia
Volume
24
Issue
9
Publish Date
2010
Start Page
1580
End Page
1587
DOI
10.1038/leu.2010.150

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

Histiocytic sarcoma arising in indolent small B-cell lymphoma: report of two cases with molecular/genetic evidence suggestive of a 'transdifferentiation' during the clonal evolution.

The biologic relationship between small B-cell lymphoma and histiocytic sarcoma (HS) when occurring in the same patient remains unclear, though recent data suggest a possible 'transdifferentiation' from follicular lymphoma (FL) to HS. We investigated the clonal relationship in two cases of small B-cell lymphoma with subsequent HS. Case 1: A 62-year-old female with splenic marginal zone lymphoma (SMZL) developed HS in a groin lymph node 1 year after the primary diagnosis. PCR/sequence analysis of the IGH gene showed a monoclonal rearrangement carrying an identical nucleotide sequence of PCR products from the spleen with SMZL and the lymph node with HS. Case 2: A 61-year-old female with a remote history of FL developed supraclavicular lymphadenopathy, which was confirmed to be HS. PCR analysis of the HS detected a monoclonal rearrangement of the IGH gene and FISH analysis revealed IGH/BCL2 fusion, a genetic hallmark for FL. The transformed HSs showed partial retention of their prior B-cell lymphomas' signatures, including expression of OCT2 in both cases and expression of BCL6 and enhanced expression of BCL2 in case 2. Both HSs demonstrated hypermutated IGH variable regions, arguing against a common progenitor mechanism of the transformation process. The data suggest a common clonal origin of B-cell lymphoma and subsequent HS occurring in the same patient, indicating that 'transdifferentiation' occurs in other small B-cell lymphomas, in addition to the previously reported FL or B-cell lymphoma with IGH/BCL2.

Authors
Wang, E; Hutchinson, CB; Huang, Q; Sebastian, S; Rehder, C; Kanaly, A; Moore, J; Datto, M
MLA Citation
Wang, E, Hutchinson, CB, Huang, Q, Sebastian, S, Rehder, C, Kanaly, A, Moore, J, and Datto, M. "Histiocytic sarcoma arising in indolent small B-cell lymphoma: report of two cases with molecular/genetic evidence suggestive of a 'transdifferentiation' during the clonal evolution." Leuk Lymphoma 51.5 (May 2010): 802-812.
PMID
20331331
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
51
Issue
5
Publish Date
2010
Start Page
802
End Page
812
DOI
10.3109/10428191003699845

Management of acutemyeloid leukemia in older adults

© Cambridge University Press 2010.Introduction It is estimated that acute myeloid leukemia (AML) accounts for 70 percent of newly diagnosed acute leukemias. In the United States, approximately 13,000 individuals were diagnosed with AML in 2008, and nearly 9,000 died of the disease. Notably, 35 percent of patients with newly diagnosed AML are 75 years of age or older, and the median age at diagnosis is 67 years. The incidence of AML will likely increase over time, as the number of individuals over 65 years of age in the United States – estimated to be 37.3 million in 2006 – is expected to double by year 2030 and represent 20 percent of the population. Elderly patients, defined in the AML literature as those aged 60 years or older, historically have lower complete remission (CR) and relapse-free survival (RFS) rates when compared to their younger counterparts. In elderly patients with AML, CR rates vary between 30 and 50 percent, with the lowest value reported for patients aged 70–75 years (CR rate about 38%) and for those over 75 years (CR rate about 22%). In contrast, in patients aged up to 50–55 years, CR rates vary between 70 and 80 percent. More important, most studies have shown that median RFS in AML patients older than 60 years is significantly lower, that is, less than 12 months, as opposed to younger adults (i.e., up to 50 years of age), who tend to have longer RFS of almost 24 months.

Authors
Rao, AV; Moore, JO
MLA Citation
Rao, AV, and Moore, JO. "Management of acutemyeloid leukemia in older adults." Practical Geriatric Oncology. January 1, 2010. 245-259.
Source
scopus
Publish Date
2010
Start Page
245
End Page
259
DOI
10.1017/CBO9780511763182.017

Single-cell analysis reveals oligoclonality among 'low-count' monoclonal B-cell lymphocytosis.

Monoclonal B-cell lymphocytosis (MBL) is a preclinical hematologic syndrome characterized by small accumulations of CD5(+) B lymphocytes. Most MBL share phenotypic characteristics with chronic lymphocytic leukemia (CLL). Although some MBL progress to CLL, most MBL have apparently limited potential for progression to CLL, particularly those MBL with normal absolute B-cell counts ('low-count' MBL). Most CLL are monoclonal and it is not known whether MBL are monoclonal or oligoclonal; this is important because it is unclear whether MBL represent indolent CLL or represent a distinct premalignant precursor before the development of CLL. We used flow cytometry analysis and sorting to determine immunophenotypic characteristics, clonality and molecular features of MBL from familial CLL kindreds. Single-cell analysis indicated four of six low-count MBL consisted of two or more unrelated clones; the other two MBL were monoclonal. 87% of low-count MBL clones had mutated immunoglobulin genes, and no immunoglobulin heavy-chain rearrangements of V(H) family 1 were observed. Some MBL were diversified, clonally related populations with evidence of antigen drive. We conclude that although low-count MBL share many phenotypic characteristics with CLL, many MBL are oligoclonal. This supports a model for step-wise development of MBL into CLL.

Authors
Lanasa, MC; Allgood, SD; Volkheimer, AD; Gockerman, JP; Whitesides, JF; Goodman, BK; Moore, JO; Weinberg, JB; Levesque, MC
MLA Citation
Lanasa, MC, Allgood, SD, Volkheimer, AD, Gockerman, JP, Whitesides, JF, Goodman, BK, Moore, JO, Weinberg, JB, and Levesque, MC. "Single-cell analysis reveals oligoclonality among 'low-count' monoclonal B-cell lymphocytosis." Leukemia 24.1 (January 2010): 133-140.
PMID
19946263
Source
pubmed
Published In
Leukemia
Volume
24
Issue
1
Publish Date
2010
Start Page
133
End Page
140
DOI
10.1038/leu.2009.192

"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

FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: A cancer and leukemia group B study

The clinical impact of FLT3-internal tandem duplications (ITDs), an adverse prognostic marker in adults aged < 60 years with primary cytogenetically normal acute myeloid leukemia (CN-AML), requires further investigation in older patients. In CN-AML patients aged ≥ 60 years treated on Cancer and Leukemia Group B frontline trials, we found that FLT3-ITD remained associated with shorter disease-free survival (P < .001; hazard ratio = 2.10) and overall survival (P < .001; hazard ratio = 1.97) in multivariable analyses. This impact on shorter disease-free survival and overall survival was in patients aged 60-69 (P < .001, each) rather than in those aged ≥ 70 years. An FLT3-ITD-associated gene-expression signature revealed overexpression of FLT3, homeobox genes (MEIS1, PBX3, HOXB3), and immunotherapeutic targets (WT1, CD33) and underexpression of leukemia-associated (MLLT3, TAL1) and erythropoiesis-associated (GATA3, EPOR, ANK1, HEMGN) genes. An FLT3-ITD-associated microRNA-expression signature included overexpressed miR-155 and underexpressed miR-144 and miR-451. FLT3-ITD identifies older CN-AML patients with molecular high risk and is associated with gene- and microRNA-expression signatures that provide biologic insights for novel therapeutic approaches. © 2010 by The American Society of Hematology.

Authors
Whitman, SP; Maharry, K; Radmacher, MD; Becker, H; Mrózek, K; Margeson, D; Holland, KB; Wu, Y-Z; Schwind, S; Metzeler, KH; Wen, J; Baer, MR; Powell, BL; Carter, TH; Kolitz, JE; Wetzler, M; Moore, JO; Stone, RM; Carroll, AJ; Larson, RA; Caligiuri, MA; Marcucci, G; Bloomfield, CD
MLA Citation
Whitman, SP, Maharry, K, Radmacher, MD, Becker, H, Mrózek, K, Margeson, D, Holland, KB, Wu, Y-Z, Schwind, S, Metzeler, KH, Wen, J, Baer, MR, Powell, BL, Carter, TH, Kolitz, JE, Wetzler, M, Moore, JO, Stone, RM, Carroll, AJ, Larson, RA, Caligiuri, MA, Marcucci, G, and Bloomfield, CD. "FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: A cancer and leukemia group B study." Blood 116.18 (2010): 3622-3626.
PMID
20656931
Source
scival
Published In
Blood
Volume
116
Issue
18
Publish Date
2010
Start Page
3622
End Page
3626
DOI
10.1182/blood-2010-05-283648

BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: A cancer and leukemia group B study

BAALC and ERG expression levels are prognostic markers in younger (< 60 years) cytogenetically normal acute myeloid leukemia (CN-AML) adults; their prognostic impact in older (≥ 60 years) patients requires further investigation. We evaluated pretreatment expression of BAALC and ERG in 158 de novo patients treated on cytarabine/daunorubicin-based protocols. The patients were also characterized for other established molecular prognosticators. Low BAALC and ERG expression levels were associated with better outcome in univariable and multivariable analyses. Expression levels of both BAALC and ERG were the only factors significantly associated with overall survival upon multivariable analysis. To gain biological insights, we derived gene expression signatures associated with BAALC and ERG expression in older CN-AML patients. Furthermore, we derived the first microRNA expression signatures associated with the expression of these 2 genes. In low BAALC expressers, genes associated with undifferentiated hematopoietic precursors and unfavorable outcome predictors were down-regulated, whereas HOX genes and HOX-gene-embedded microRNAs were up-regulated. Low ERG expressers presented with down-regulation of genes involved in the DNA-methylation machinery, and upregulation of miR-148a, which targets DNMT3B. We conclude that in older CN-AML patients, low BAALC and ERG expression associates with better outcome and distinct gene and microRNA expression signatures that could aid in identifying new targets and novel therapeutic strategies for older patients. © 2010 by The American Society of Hematology.

Authors
Schwind, S; Marcucci, G; Maharry, K; Radmacher, MD; Mrózek, K; Holland, KB; Margeson, D; Becker, H; Whitman, SP; Wu, Y-Z; Metzeler, KH; Powell, BL; Kolitz, JE; Carter, TH; Moore, JO; Baer, MR; Carroll, AJ; Caligiuri, MA; Larson, RA; Bloomfield, CD
MLA Citation
Schwind, S, Marcucci, G, Maharry, K, Radmacher, MD, Mrózek, K, Holland, KB, Margeson, D, Becker, H, Whitman, SP, Wu, Y-Z, Metzeler, KH, Powell, BL, Kolitz, JE, Carter, TH, Moore, JO, Baer, MR, Carroll, AJ, Caligiuri, MA, Larson, RA, and Bloomfield, CD. "BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: A cancer and leukemia group B study." Blood 116.25 (2010): 5660-5669.
PMID
20841507
Source
scival
Published In
Blood
Volume
116
Issue
25
Publish Date
2010
Start Page
5660
End Page
5669
DOI
10.1182/blood-2010-06-290536

Control of plasma uric acid in adults at risk for tumor lysis syndrome: Efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone - Results of a multicenter phase III study

Purpose: Rasburicase is effective in controlling plasma uric acid in pediatric patients with hematologic malignancies. This study in adults evaluated safety of and compared efficacy of rasburicase alone with rasburicase followed by oral allopurinol and with allopurinol alone in controlling plasma uric acid. Patients and Methods: Adults with hematologic malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS) were randomly assigned to rasburicase (0.20 mg/kg/d intravenously days 1-5), rasburicase plus allopurinol (rasburicase 0.20 mg/kg/d days 1 to 3 followed by oral allopurinol 300 mg/d days 3 to 5), or allopurinol (300 mg/d orally days 1 to 5). Primary efficacy variable was plasma uric acid response rate defined as percentage of patients achieving or maintaining plasma uric acid ≤ 7.5 mg/dL during days 3 to 7. Results: Ninety-two patients received rasburicase, 92 rasburicase plus allopurinol, and 91 allopurinol. Plasma uric acid response rate was 87% with rasburicase, 78% with rasburicase plus allopurinol, and 66% with allopurinol. It was significantly greater for rasburicase than for allopurinol (P = .001) in the overall study population, in patients at high risk for TLS (89% v 68%; P = .012), and in those with baseline hyperuricemia (90% v 53%; P = .015). Time to plasma uric acid control in hyperuricemic patients was 4 hours for rasburicase, 4 hours for rasburicase plus allopurinol, and 27 hours for allopurinol. Conclusion: In adults with hyperuricemia or at high risk for TLS, rasburicase provided control of plasma uric acid more rapidly than allopurinol. Rasburicase was well tolerated as a single agent and in sequential combination with allopurinol. © 2010 by American Society of Clinical Oncology.

Authors
Cortes, J; Moore, JO; Maziarz, RT; Wetzler, M; Craig, M; Matous, J; Luger, S; Dey, BR; Schiller, GJ; Pham, D; Abboud, CN; Krishnamurthy, M; Jr, AB; Laadem, A; Seiter, K
MLA Citation
Cortes, J, Moore, JO, Maziarz, RT, Wetzler, M, Craig, M, Matous, J, Luger, S, Dey, BR, Schiller, GJ, Pham, D, Abboud, CN, Krishnamurthy, M, Jr, AB, Laadem, A, and Seiter, K. "Control of plasma uric acid in adults at risk for tumor lysis syndrome: Efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone - Results of a multicenter phase III study." Journal of Clinical Oncology 28.27 (2010): 4207-4213.
PMID
20713865
Source
scival
Published In
Journal of Clinical Oncology
Volume
28
Issue
27
Publish Date
2010
Start Page
4207
End Page
4213
DOI
10.1200/JCO.2009.26.8896

Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: A Cancer and leukemia group B study

We previously reported the adverse prognostic impact of Wilms tumor 1 gene (WT1) mutations in younger adult cytogenetically normal acute myeloid leukemia (CN-AML). Here, we investigated 243 older (≥ 60 years) primary CN-AML patients. WT1 mutated (WT1mut) patients (7%) had FLT3-ITD more frequently (P < .001), lower hemoglobin (P = .01), higher white blood cell count (P = .03) and percentage blood blasts (P = .03), and a shorter overall survival (P = .08) than WT1 wild-type (WT1wt) patients. Comparing older and younger WT1mut patients, they had similar pretreatment characteristics and outcome. By contrast, among WT1wt CN-AML, younger patients had a significantly better outcome.AWT1 mutation-associated gene-expression signature, reported here for the first time, included CD96, a leukemia stem cell-specific marker, and genes involved in gene regulation (eg, MLL, PML, and SNRPN) and in proliferative and metabolic processes (eg, INSR, IRS2, and PRKAA1), supporting the role of mutatedWT1in deregulating multiple homeostatic processes. Our results indicate thatWT1mut CN-AML represents a distinct entity with poor treatment response across age groups. This study has been registered at www.clinicaltrials. gov as #NCT00900224. © 2010 by The American Society of Hematology.

Authors
Becker, H; Marcucci, G; Maharry, K; Radmacher, MD; Mrózek, K; Margeson, D; Whitman, SP; Paschka, P; Holland, KB; Schwind, S; Wu, Y-Z; Powell, BL; Carter, TH; Kolitz, JE; Wetzler, M; Carroll, AJ; Baer, MR; Moore, JO; Caligiuri, MA; Larson, RA; Bloomfield, CD
MLA Citation
Becker, H, Marcucci, G, Maharry, K, Radmacher, MD, Mrózek, K, Margeson, D, Whitman, SP, Paschka, P, Holland, KB, Schwind, S, Wu, Y-Z, Powell, BL, Carter, TH, Kolitz, JE, Wetzler, M, Carroll, AJ, Baer, MR, Moore, JO, Caligiuri, MA, Larson, RA, and Bloomfield, CD. "Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: A Cancer and leukemia group B study." Blood 116.5 (2010): 788-792.
PMID
20442368
Source
scival
Published In
Blood
Volume
116
Issue
5
Publish Date
2010
Start Page
788
End Page
792
DOI
10.1182/blood-2010-01-262543

A genomic approach to improve prognosis and predict therapeutic response in chronic lymphocytic leukemia.

PURPOSE: Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized by a variable clinical course. Several parameters have prognostic capabilities but are associated with altered response to therapy in only a small subset of patients. EXPERIMENTAL DESIGN: We used gene expression profiling methods to generate predictors of therapy response and prognosis. Genomic signatures that reflect progressive disease and responses to chemotherapy or chemoimmunotherapy were created using cancer cell lines and patient leukemia cell samples. We validated and applied these three signatures to independent clinical data from four cohorts, representing a total of 301 CLL patients. RESULTS: A genomic signature of prognosis created from patient leukemic cell gene expression data coupled with clinical parameters significantly differentiated patients with stable disease from those with progressive disease in the training data set. The progression signature was validated in two independent data sets, showing a capacity to accurately identify patients at risk for progressive disease. In addition, genomic signatures that predict response to chlorambucil or pentostatin, cyclophosphamide, and rituximab were generated and could accurately distinguish responding and nonresponding CLL patients. CONCLUSIONS: Thus, microarray analysis of CLL lymphocytes can be used to refine prognosis and predict response to different therapies. These results have implications for standard and investigational therapeutics in CLL patients.

Authors
Friedman, DR; Weinberg, JB; Barry, WT; Goodman, BK; Volkheimer, AD; Bond, KM; Chen, Y; Jiang, N; Moore, JO; Gockerman, JP; Diehl, LF; Decastro, CM; Potti, A; Nevins, JR
MLA Citation
Friedman, DR, Weinberg, JB, Barry, WT, Goodman, BK, Volkheimer, AD, Bond, KM, Chen, Y, Jiang, N, Moore, JO, Gockerman, JP, Diehl, LF, Decastro, CM, Potti, A, and Nevins, JR. "A genomic approach to improve prognosis and predict therapeutic response in chronic lymphocytic leukemia." Clin Cancer Res 15.22 (November 15, 2009): 6947-6955.
PMID
19861443
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
15
Issue
22
Publish Date
2009
Start Page
6947
End Page
6955
DOI
10.1158/1078-0432.CCR-09-1132

5-year survival in patients with relapsed or refractory chronic lymphocytic leukemia in a randomized, phase III trial of fludarabine plus cyclophosphamide with or without oblimersen.

PURPOSE: A randomized trial of oblimersen plus fludarabine/cyclophosphamide (OBL-FC; n = 120) versus FC (n = 121) was conducted in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). The primary end point was met: the complete response (CR) rate, defined as complete or nodular partial response, was significantly greater with OBL-FC than with FC (17% v 7%; P = .025). Among patients with CR, response duration was significantly longer with OBL-FC than with FC (median not reached; > 36 months v 22 months; P = .03). Maximum benefit with OBL-FC, including a four-fold increase in CR rate and a survival benefit with 3 years of follow-up (hazard ratio, 0.53; P = .05), was observed in patients with fludarabine-sensitive disease. We evaluated long-term survival and poststudy CLL therapy among all randomly assigned patients. METHODS: Poststudy CLL treatment information was collected. Patients were observed for survival for up to 5 years from the date of random assignment. RESULTS: Poststudy CLL treatment was balanced between arms. Intent-to-treat analysis of 5-year survival showed no significant between-treatment difference (hazard ratio, 0.87; P = .34). Among the greater than 40% of patients with complete or partial remission, a significant 5-year survival benefit was observed with OBL-FC (hazard ratio, 0.60; P = .038). Among patients with fludarabine-sensitive disease who had previously demonstrated maximum benefit with OBL-FC, the previously observed survival benefit improved: a 50% reduction in the risk of death was observed (P = .004). CONCLUSION: In relapsed/refractory CLL, OBL combined with FC offers patients who achieve complete or partial remission, as well as those who have fludarabine-sensitive disease, a significant survival benefit.

Authors
O'Brien, S; Moore, JO; Boyd, TE; Larratt, LM; Skotnicki, AB; Koziner, B; Chanan-Khan, AA; Seymour, JF; Gribben, J; Itri, LM; Rai, KR
MLA Citation
O'Brien, S, Moore, JO, Boyd, TE, Larratt, LM, Skotnicki, AB, Koziner, B, Chanan-Khan, AA, Seymour, JF, Gribben, J, Itri, LM, and Rai, KR. "5-year survival in patients with relapsed or refractory chronic lymphocytic leukemia in a randomized, phase III trial of fludarabine plus cyclophosphamide with or without oblimersen." J Clin Oncol 27.31 (November 1, 2009): 5208-5212.
PMID
19738118
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
27
Issue
31
Publish Date
2009
Start Page
5208
End Page
5212
DOI
10.1200/JCO.2009.22.5748

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

Giant thoracic liposarcoma treated with induction chemotherapy followed by surgical resection.

Authors
Berry, MF; Sporn, TA; Moore, JO; D'Amico, TA
MLA Citation
Berry, MF, Sporn, TA, Moore, JO, and D'Amico, TA. "Giant thoracic liposarcoma treated with induction chemotherapy followed by surgical resection." J Thorac Oncol 4.6 (June 2009): 768-769.
PMID
19461403
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
4
Issue
6
Publish Date
2009
Start Page
768
End Page
769
DOI
10.1097/JTO.0b013e31819e77ff

A pilot study on the influence of an individualized and experiential training on cancer caregiver's self-efficacy in home care and symptom management.

The aim of this pilot study was to investigate if an individualized and experiential training can promote family caregiver's confidence (self-efficacy) in home care and symptom management. The study was conducted in a hematology/oncology unit in a southeastern regional medical center. Twenty informal cancer caregivers participated in the study. The individualized and experiential training was conducted at the bedside prior to patient's hospital discharge. Self-efficacy in home care and cancer symptom management was measured using the Cancer Caregiver Self-Efficacy Measure before and after training, and at 1 week after hospital discharge of cancer patients. Results of the study showed mean Cancer Caregiver Self-Efficacy Measure increased by 41.1 points immediately after the training (z = 4.49, p < 0.001) and was 31.7 points higher at 1-week follow-up (z = 3.22, p < 0.01). The findings of this study suggest that individualized and experiential training may be another avenue for nurses, including home care nurses, to support family home caregiving. By helping family members in home care, favorable patient outcomes may be achieved, enabling older patients with cancer to stay longer in the comfort of their homes.

Authors
Hendrix, CC; Abernethy, A; Sloane, R; Misuraca, J; Moore, J
MLA Citation
Hendrix, CC, Abernethy, A, Sloane, R, Misuraca, J, and Moore, J. "A pilot study on the influence of an individualized and experiential training on cancer caregiver's self-efficacy in home care and symptom management." Home Healthc Nurse 27.5 (May 2009): 271-278.
PMID
19448494
Source
pubmed
Published In
Home Healthcare Nurse
Volume
27
Issue
5
Publish Date
2009
Start Page
271
End Page
278

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

Chronic myelogenous leukemia

CML is a hematopoietic stem cell disease characterized by the presence of Ph chromosome resulting from the translocation between chromosomes 9 and 22 [t(9;22)]. © Journal of the National Comprehensive Cancer Network.

Authors
O'Brien, S; Berman, E; Borghaei, H; DeAngelo, DJ; Devetten, MP; Devine, S; Erba, HP; Gotlib, J; Jagasia, M; Moore, JO; Mughal, T; Pinilla-Ibarz, J; Radich, JP; Shah, NP; Shami, PJ; Smith, BD; Snyder, DS; Tallman, MS; Talpaz, M; Wetzler, M
MLA Citation
O'Brien, S, Berman, E, Borghaei, H, DeAngelo, DJ, Devetten, MP, Devine, S, Erba, HP, Gotlib, J, Jagasia, M, Moore, JO, Mughal, T, Pinilla-Ibarz, J, Radich, JP, Shah, NP, Shami, PJ, Smith, BD, Snyder, DS, Tallman, MS, Talpaz, M, and Wetzler, M. "Chronic myelogenous leukemia." JNCCN Journal of the National Comprehensive Cancer Network 7.9 (2009): 984-1023.
PMID
19878641
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
7
Issue
9
Publish Date
2009
Start Page
984
End Page
1023

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

Low-dose interleukin-2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B Study 9720.

PURPOSE: Cancer and Leukemia Group B (CALGB) 9720 evaluated subcutaneous low-dose recombinant interleukin-2 (rIL-2) maintenance immunotherapy as a strategy for prolonging remission in older patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: AML patients age 60 years and older in first complete remission after induction and consolidation chemotherapy were randomly assigned to no further therapy or a 90-day regimen of 14-day cycles of low-dose rIL-2, aimed at expanding natural killer (NK) cells, followed by 3-day higher doses aimed at activating cytotoxicity of expanded NK cells to lyse residual AML cells. All randomly assigned patients were included in an intention-to-treat analysis. RESULTS: A total of 163 (64%) of 254 patients who completed induction and consolidation chemotherapy on CALGB 9720 were randomly assigned to rIL-2 (n = 81) or no further therapy (n = 82); the most common reasons for lack of random assignment were patient refusal and relapse. Fifteen patients randomly assigned to rIL-2 never initiated it because of refusal, intercurrent medical problems, or relapse, and 24 patients initiated rIL-2 but stopped early because of toxicity or relapse. Grade 4 toxicities during rIL-2 therapy included thrombocytopenia (65%) and neutropenia (64%), and grade 3 toxicities included anemia (33%), infection (24%) and malaise/fatigue (14%). Forty-two patients (52%) randomly assigned to rIL-2 completed the full 90-day course. Patients in both arms had similar distributions of both disease-free (combined median = 6.1 months; P = .47) and overall survival (combined median = 14.7 months; P = .61) after random assignment. Moreover, the 42 patients who completed all planned therapy did not show prolongation of disease-free or overall survival. CONCLUSION: Low-dose rIL-2 maintenance immunotherapy is not a successful strategy in older AML patients.

Authors
Baer, MR; George, SL; Caligiuri, MA; Sanford, BL; Bothun, SM; Mrózek, K; Kolitz, JE; Powell, BL; Moore, JO; Stone, RM; Anastasi, J; Bloomfield, CD; Larson, RA
MLA Citation
Baer, MR, George, SL, Caligiuri, MA, Sanford, BL, Bothun, SM, Mrózek, K, Kolitz, JE, Powell, BL, Moore, JO, Stone, RM, Anastasi, J, Bloomfield, CD, and Larson, RA. "Low-dose interleukin-2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B Study 9720." J Clin Oncol 26.30 (October 20, 2008): 4934-4939.
PMID
18591543
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
30
Publish Date
2008
Start Page
4934
End Page
4939
DOI
10.1200/JCO.2008.17.0472

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

CLL cell apoptosis induced by nitric oxide synthase inhibitors: correlation with lipid solubility and NOS1 dissociation constant.

Nitric oxide synthase (NOS) inhibitors induce chronic lymphocytic leukemia (CLL) cell apoptosis and have potential as CLL therapeutics. We determined the half-maximal concentration (ED(50)) of 22 NOS inhibitors that induced CLL cell death in vitro. There was a direct correlation of the NOS1 (but not NOS2) dissociation constant (K(d)) and the hydrophobicity partitioning coefficient of each NOS inhibitor and its ED(50). NOS inhibitors that bound tightly to CLL cell NOS1 and were hydrophobic potently induced CLL cell death. CLL cell RNA and protein analyses confirmed CLL cell NOS1 expression. Our studies permit the rational selection of NOS inhibitors for testing as CLL therapeutics.

Authors
Levesque, MC; Ghosh, DK; Beasley, BE; Chen, Y; Volkheimer, AD; O'Loughlin, CW; Gockerman, JP; Moore, JO; Weinberg, JB
MLA Citation
Levesque, MC, Ghosh, DK, Beasley, BE, Chen, Y, Volkheimer, AD, O'Loughlin, CW, Gockerman, JP, Moore, JO, and Weinberg, JB. "CLL cell apoptosis induced by nitric oxide synthase inhibitors: correlation with lipid solubility and NOS1 dissociation constant." Leuk Res 32.7 (July 2008): 1061-1070.
PMID
18180035
Source
pubmed
Published In
Leukemia Research
Volume
32
Issue
7
Publish Date
2008
Start Page
1061
End Page
1070
DOI
10.1016/j.leukres.2007.11.026

Acute myeloid leukemia

Authors
O'Donnell, MR; Appelbaum, FR; Coutre, SE; Damon, LE; Erba, HP; Foran, J; Lancet, J; Maness, LJ; Marcucci, G; Maslak, PG; Millenson, M; Moore, JO; Ravandi, F; Schuening, F; Shami, P; Smith, BD; Stone, RM; Tallman, MS; Wang, E; White, FL
MLA Citation
O'Donnell, MR, Appelbaum, FR, Coutre, SE, Damon, LE, Erba, HP, Foran, J, Lancet, J, Maness, LJ, Marcucci, G, Maslak, PG, Millenson, M, Moore, JO, Ravandi, F, Schuening, F, Shami, P, Smith, BD, Stone, RM, Tallman, MS, Wang, E, and White, FL. "Acute myeloid leukemia." JNCCN Journal of the National Comprehensive Cancer Network 6.10 (2008): 962-992.
PMID
19176196
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
6
Issue
10
Publish Date
2008
Start Page
962
End Page
992

Hodgkin disease/lymphoma

The management of HL continues to evolve. Major changes have been incorporated into these guidelines since inception. Current management of HL involves initial treatment with chemotherapy or combined modality therapy, followed by restaging to assess treatment response. PET scans are recommended to evaluate initial staging and assess treatment response at restaging. However, they are not recommended for routine surveillance. Combined modality therapy (brief course of chemotherapy and limited irradiation) is the preferred treatment for early-stage favorable CHL (stage IA-IIA nonbulky) and early-stage unfavorable CHL (stage I-II bulky). Chemotherapy alone or combined modality therapy is recommended for advanced-stage CHL (stage IB-IIB nonbulky and stage III-IV). Combined modality therapy or radiation alone is the option for early-stage LPHL. Patients with advanced-stage LPHL may be treated with more aggressive therapy. The role of chemotherapy or antibody-based therapy is being explored in ongoing clinical trials for early-and advanced-stage LPHL. HDT/ASCR is the best treatment option for patients with relapsed or refractory HL, although it does not improve overall survival. Consistent with NCCN philosophy, participation in clinical trials is always encouraged. HL is now curable in most patients because more effective, less toxic regimens have been introduced. However, survivors may experience late treatment-related side effects. For this reason, long-term follow-up by an oncologist is essential after completion of treatment. Counseling about survivorship issues and careful monitoring for late treatment-related side effects should be integral follow-up for these patients. © Journal of the National Comprehensive Cancer Network.

Authors
Hoppe, RT; Advani, RH; Ambinder, RF; Bierman, PJ; Bloomfield, CD; Blum, K; Dabaja, B; Djulbegovic, B; Forero, A; Gordon, LI; Hernandez-Ilizaliturri, FJ; Hudson, MM; Kaminski, MS; Love, G; Maloney, DG; Mansur, D; Mauch, PM; Moore, JO; Schilder, RJ; Weiss, LM; Winter, JN; Yahalom, J; Zelenetz, AD
MLA Citation
Hoppe, RT, Advani, RH, Ambinder, RF, Bierman, PJ, Bloomfield, CD, Blum, K, Dabaja, B, Djulbegovic, B, Forero, A, Gordon, LI, Hernandez-Ilizaliturri, FJ, Hudson, MM, Kaminski, MS, Love, G, Maloney, DG, Mansur, D, Mauch, PM, Moore, JO, Schilder, RJ, Weiss, LM, Winter, JN, Yahalom, J, and Zelenetz, AD. "Hodgkin disease/lymphoma." JNCCN Journal of the National Comprehensive Cancer Network 6.6 (2008): 594-622.
PMID
18597713
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
6
Issue
6
Publish Date
2008
Start Page
594
End Page
622

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

A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, follicular lymphoma.

BACKGROUND: Galiximab is a monoclonal antibody that targets CD80, a costimulatory molecule constitutively expressed on follicular and other lymphomas. Modest single-agent clinical activity and tolerability were demonstrated in a phase I study in relapsed or refractory, follicular non-Hodgkin's lymphoma (NHL). A phase I/II study was conducted to evaluate galiximab in combination with a standard course of rituximab. Safety, pharmacokinetics, and efficacy were evaluated. PATIENTS AND METHODS: Patients with follicular NHL who had relapsed or failed primary therapy were enrolled. Rituximab-refractory patients (no response or a response with time to progression <6 months) were excluded. Patients received 4 weekly i.v. infusions of galiximab (125, 250, 375, or 500 mg/m(2)) and rituximab (375 mg/m(2)). International Workshop Response Criteria (IWRC) were used to evaluate response. RESULTS: Seventy-three patients received treatment. All had received at least one prior lymphoma therapy; 40% were rituximab naive. Infusions were delivered in an outpatient setting and were well tolerated. The most common study-related adverse events (AE) were lymphopenia, leukopenia, neutropenia, fatigue, and chills. The overall response rate at the recommended phase II dose of galiximab (500 mg/m(2)) was 66%: 19% complete response, 14% unconfirmed complete response, and 33% partial response. The median progression free survival was 12.1 months. Combination therapy did not appear to alter pharmacokinetics. CONCLUSION: These results indicate that galiximab can be safely combined with a standard course of rituximab. This doublet biologic approach offers the potential to avoid or delay chemotherapy or to integrate with other lymphoma therapies. A phase III, randomized study evaluating clinical benefit of rituximab versus the combination has been initiated.

Authors
Leonard, JP; Friedberg, JW; Younes, A; Fisher, D; Gordon, LI; Moore, J; Czuczman, M; Miller, T; Stiff, P; Cheson, BD; Forero-Torres, A; Chieffo, N; McKinney, B; Finucane, D; Molina, A
MLA Citation
Leonard, JP, Friedberg, JW, Younes, A, Fisher, D, Gordon, LI, Moore, J, Czuczman, M, Miller, T, Stiff, P, Cheson, BD, Forero-Torres, A, Chieffo, N, McKinney, B, Finucane, D, and Molina, A. "A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, follicular lymphoma." Ann Oncol 18.7 (July 2007): 1216-1223.
PMID
17470451
Source
pubmed
Published In
Annals of Oncology
Volume
18
Issue
7
Publish Date
2007
Start Page
1216
End Page
1223
DOI
10.1093/annonc/mdm114

Chronic myelogenous leukemia.

Authors
O'Brien, S; Berman, E; Bhalla, K; Copelan, EA; Devetten, MP; Emanuel, PD; Erba, HP; Greenberg, PL; Moore, JO; Przepiorka, D; Radich, JP; Schilder, RJ; Shami, P; Smith, BD; Snyder, DS; Soiffer, RJ; Tallman, MS; Talpaz, M; Wetzler, M; National Comprehensive Cancer Network,
MLA Citation
O'Brien, S, Berman, E, Bhalla, K, Copelan, EA, Devetten, MP, Emanuel, PD, Erba, HP, Greenberg, PL, Moore, JO, Przepiorka, D, Radich, JP, Schilder, RJ, Shami, P, Smith, BD, Snyder, DS, Soiffer, RJ, Tallman, MS, Talpaz, M, Wetzler, M, and National Comprehensive Cancer Network, . "Chronic myelogenous leukemia." J Natl Compr Canc Netw 5.5 (May 2007): 474-496.
PMID
17509252
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
5
Issue
5
Publish Date
2007
Start Page
474
End Page
496

Randomized phase III trial of fludarabine plus cyclophosphamide with or without oblimersen sodium (Bcl-2 antisense) in patients with relapsed or refractory chronic lymphocytic leukemia.

PURPOSE: Expression of Bcl-2 protein is associated with chemotherapy resistance and decreased survival in chronic lymphocytic leukemia (CLL). We evaluated whether oblimersen would improve response to chemotherapy in patients with relapsed or refractory CLL. PATIENTS AND METHODS: Patients had received at least one prior fludarabine-containing regimen and were stratified on the basis of prior fludarabine response, number of prior regimens, and duration of response to last prior therapy. Patients were randomly assigned to 28-day cycles of fludarabine 25 mg/m2/d plus cyclophosphamide 250 mg/m2/d administered intravenously for 3 days with or without oblimersen 3 mg/kg/d as a 7-day continuous intravenous infusion (beginning 4 days before chemotherapy) for up to six cycles. The primary end point was the proportion of patients who achieved complete response (CR) or nodular partial response (nPR). RESULTS: Of 241 patients randomly assigned, CR/nPR was achieved in 20 (17%) of 120 patients in the oblimersen group and eight (7%) of 121 patients in the chemotherapy-only group (P = .025). Achievement of CR/nPR was correlated with both an extended time to progression and survival (P < .0001). In patients who remained sensitive to fludarabine, oblimersen was associated with a four-fold increase in the CR/nPR rate and a significant survival benefit (P = .05). Oblimersen was frequently associated with thrombocytopenia and, rarely, tumor lysis syndrome and cytokine release reactions; the incidence of opportunistic infections and second malignancies was similar in both groups. CONCLUSION: The addition of oblimersen to fludarabine plus cyclophosphamide significantly increases the CR/nPR rate in patients with relapsed or refractory CLL (particularly fludarabine-sensitive patients), as well as response duration among patients who achieve CR/nPR.

Authors
O'Brien, S; Moore, JO; Boyd, TE; Larratt, LM; Skotnicki, A; Koziner, B; Chanan-Khan, AA; Seymour, JF; Bociek, RG; Pavletic, S; Rai, KR
MLA Citation
O'Brien, S, Moore, JO, Boyd, TE, Larratt, LM, Skotnicki, A, Koziner, B, Chanan-Khan, AA, Seymour, JF, Bociek, RG, Pavletic, S, and Rai, KR. "Randomized phase III trial of fludarabine plus cyclophosphamide with or without oblimersen sodium (Bcl-2 antisense) in patients with relapsed or refractory chronic lymphocytic leukemia." J Clin Oncol 25.9 (March 20, 2007): 1114-1120.
PMID
17296974
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
9
Publish Date
2007
Start Page
1114
End Page
1120
DOI
10.1200/JCO.2006.07.1191

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

Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification.

Somatic mutations of immunoglobulin genes characterize mature memory B cells, and intraclonal B-cell diversification is typically associated with expansion of B-cell clones with greater affinity for antigen (antigen drive). Evidence for a role of antigen in progression of intraclonal chronic lymphocytic leukemia (CLL) cell diversification in patients with mutated immunoglobulin genes has not been previously presented. We performed a single-cell analysis of immunoglobulin heavy and light chains in 6 patients with somatically mutated CLL-cell immunoglobulin genes and identified 2 patients with multiple related (oligoclonal) subgroups of CLL cells. We constructed genealogic trees of these oligoclonal CLL-cell subgroups and assessed the effects of immunoglobulin somatic mutations on the ratios of replacement and silent amino acid changes in the framework and antigen-binding regions (CDRs) of the immunoglobulin heavy and light chains from each oligoclonal CLL-cell population. In one subject, the amino acid changes were consistent with an antigen-driven progression of clonally related CLL-cell populations. In the other subject, intraclonal diversification was associated with immunoglobulin amino acid changes that would have likely lessened antigen affinity. Taken together, these studies support the hypothesis that in some CLL cases intraclonal diversification is dependent on antigen interactions with immunoglobulin receptors.

Authors
Volkheimer, AD; Weinberg, JB; Beasley, BE; Whitesides, JF; Gockerman, JP; Moore, JO; Kelsoe, G; Goodman, BK; Levesque, MC
MLA Citation
Volkheimer, AD, Weinberg, JB, Beasley, BE, Whitesides, JF, Gockerman, JP, Moore, JO, Kelsoe, G, Goodman, BK, and Levesque, MC. "Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification." Blood 109.4 (February 15, 2007): 1559-1567.
PMID
17082314
Source
pubmed
Published In
Blood
Volume
109
Issue
4
Publish Date
2007
Start Page
1559
End Page
1567
DOI
10.1182/blood-2006-05-020644

A Phase II study of Bcl-2 antisense (oblimersen sodium) combined with gemtuzumab ozogamicin in older patients with acute myeloid leukemia in first relapse.

Oblimersen selectively targets Bcl-2 mRNA and has been shown to enhance the apoptotic activity of various antileukemic agents, including gemtuzumab ozogamicin (GO), in preclinical studies. We evaluated the efficacy and safety of oblimersen combined with GO in patients > or =60 years of age in first relapse with CD33+ acute myeloid leukemia. Oblimersen 7 mg/kg/day was given as a continuous intravenous infusion on days 1-7 and 15-21. GO 9 mg/m2 was given intravenously on days 4 and 18. Twelve of 48 patients (25%) achieved a major response (five, complete response and seven, complete response without platelet recovery). Ten of the 12 patients who achieved a major response survived >6 months compared with six of 36 non-responders. Serious adverse events for the oblimersen/GO combination were qualitatively similar to those reported for GO alone. Oblimersen can be safely combined with GO. Assessment of incremental benefit will require a randomized trial.

Authors
Moore, J; Seiter, K; Kolitz, J; Stock, W; Giles, F; Kalaycio, M; Zenk, D; Marcucci, G
MLA Citation
Moore, J, Seiter, K, Kolitz, J, Stock, W, Giles, F, Kalaycio, M, Zenk, D, and Marcucci, G. "A Phase II study of Bcl-2 antisense (oblimersen sodium) combined with gemtuzumab ozogamicin in older patients with acute myeloid leukemia in first relapse." Leuk Res 30.7 (July 2006): 777-783.
PMID
16730060
Source
pubmed
Published In
Leukemia Research
Volume
30
Issue
7
Publish Date
2006
Start Page
777
End Page
783
DOI
10.1016/j.leukres.2005.10.025

Combined-modality therapy versus radiotherapy alone for treatment of early-stage Hodgkin's disease: cure balanced against complications.

PURPOSE: The treatment of early-stage Hodgkin's disease (HD) has evolved from radiotherapy alone (RT) to combined-modality therapy (CMT) because of concerns about late adverse effects from high-dose subtotal nodal irradiation (STNI). However, there is little information regarding the long-term results of CMT programs that substantially reduce the dose and extent of radiation. In addition, lowering the total radiation dose may reduce the complication rate without compromising cure. This retrospective study compares the long-term results of STNI with CMT using modestly reduced RT dose in the treatment of early-stage HD. PATIENTS AND METHODS: Between 1982 and 2002, 111 patients with stage IA and IIA HD were treated definitively with RT (mean dose, 37.9 Gy); 70 patients were treated with CMT with low-dose involved-field radiotherapy (LDIFRT; mean dose, 25.5 Gy). Median follow-up was 11.7 years for RT patients and 8.1 years for the CMT group. RESULTS: There was a trend toward improved 20-year overall survival with CMT (83% v 70%; P = .405). No second cancers were observed in the CMT group; in the RT group the actuarial frequency of a second cancer was 16% at 20 years. There was no difference in the frequency of cardiac complications (9% v 6%, RT v CMT). CONCLUSION: In this retrospective review, CMT with LDIFRT was effective in curing early-stage HD and was not associated with an increase in second malignancies. For RT alone, a moderate dose seemed to reduce cardiac complications but did not lessen second malignancies compared with higher doses used historically.

Authors
Koontz, BF; Kirkpatrick, JP; Clough, RW; Prosnitz, RG; Gockerman, JP; Moore, JO; Prosnitz, LR
MLA Citation
Koontz, BF, Kirkpatrick, JP, Clough, RW, Prosnitz, RG, Gockerman, JP, Moore, JO, and Prosnitz, LR. "Combined-modality therapy versus radiotherapy alone for treatment of early-stage Hodgkin's disease: cure balanced against complications." J Clin Oncol 24.4 (February 1, 2006): 605-611.
PMID
16446333
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
4
Publish Date
2006
Start Page
605
End Page
611
DOI
10.1200/JCO.2005.02.9850

Chronic lymphocytic leukemia cell CD38 expression and inducible nitric oxide synthase expression are associated with serum IL-4 levels.

B cell chronic lymphocytic leukemia (CLL) CD38 expression is variable and may predict outcome. Inducible nitric oxide synthase (NOS2) expression regulates CLL cell apoptosis. IL-4 and IFN-gamma regulate B cell CD38 expression and NOS2 expression. We compared IL-4 and IFN-gamma serum levels between CLL patients and normal individuals, and determined whether serum IL-4 and IFN-gamma levels correlated with CLL cell CD38 expression and NOS enzyme activity. IL-4 levels, but not IFN-gamma levels, differed between normal individuals and CLL patients. Furthermore, there was an association of IL-4 levels, but not IFN-gamma levels, with CD38 and NOS2 expression in CLL patients.

Authors
Levesque, MC; Chen, Y; Beasley, BE; O'Loughlin, CW; Gockerman, JP; Moore, JO; Weinberg, JB
MLA Citation
Levesque, MC, Chen, Y, Beasley, BE, O'Loughlin, CW, Gockerman, JP, Moore, JO, and Weinberg, JB. "Chronic lymphocytic leukemia cell CD38 expression and inducible nitric oxide synthase expression are associated with serum IL-4 levels." Leuk Res 30.1 (January 2006): 24-28.
PMID
16039714
Source
pubmed
Published In
Leukemia Research
Volume
30
Issue
1
Publish Date
2006
Start Page
24
End Page
28
DOI
10.1016/j.leukres.2005.05.022

Hodgkin disease/lymphoma: Clinical practice guidelines in oncology™

The management of HD continues to evolve, and the NCCN guidelines have undergone major changes since their inception. Current management programs are based on comprehensive clinical staging followed by combined modality therapy for patients with favorable and intermediate prognosis, or chemotherapy alone for patients with advanced disease. Relapse is uncommon, but secondary management with peripheral stem cell transplantation may be effective. The excellent prognosis for these patients mandates careful long-term follow-up to detect late treatment effects. © Journal of the National Comprehensive Cancer Network.

Authors
Hoppe, RT; Advani, RH; Bierman, PJ; Bloomfield, CD; Buadi, F; Djulgegovic, B; Forero, A; Gordon, LI; Hernandez-Ilizaliturri, FJ; Kaminski, MS; Love, G; Maloney, DG; Mauch, PM; Moore, JO; Schilder, RJ; Weiss, L; Winter, JN; Yahalom, J; Zelenetz, AD
MLA Citation
Hoppe, RT, Advani, RH, Bierman, PJ, Bloomfield, CD, Buadi, F, Djulgegovic, B, Forero, A, Gordon, LI, Hernandez-Ilizaliturri, FJ, Kaminski, MS, Love, G, Maloney, DG, Mauch, PM, Moore, JO, Schilder, RJ, Weiss, L, Winter, JN, Yahalom, J, and Zelenetz, AD. "Hodgkin disease/lymphoma: Clinical practice guidelines in oncology™." JNCCN Journal of the National Comprehensive Cancer Network 4.3 (2006): 210-230.
PMID
16507269
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
4
Issue
3
Publish Date
2006
Start Page
210
End Page
230

Acute myeloid leukemia: Clinical Practice Guidelines in Oncology

Approximately 11,960 people will be diagnosed with acute myeloid leukemia (AML) in 2005, and 9,000 patients will die of the disease. As the population ages, the incidence of AML, along with myelodysplasia, appears to be rising. Equally disturbing is the increasing incidence of treatment-related myelodysplasia and leukemia in survivors of tumors of childhood and young adulthood such as Hodgkin's disease, sarcomas, breast and testicular cancers, and lymphomas. Recent large clinical trials have highlighted the need for new, innovative strategies because outcomes for AML patients, particularly older patients, have not substantially changed in the past 3 decades. © Journal of the National Comprehensive Cancer Network.

Authors
O'Donnell, MR; Appelbaum, FR; Baer, MR; Byrd, JC; Coutre, SE; Damon, LE; Erba, HP; Estey, E; Foran, J; Lancet, J; Maness, LJ; Maslak, PG; Millenson, M; Moore, JO; Przepiorka, D; Shami, P; Smith, BD; Stone, RM; Tallman, MS
MLA Citation
O'Donnell, MR, Appelbaum, FR, Baer, MR, Byrd, JC, Coutre, SE, Damon, LE, Erba, HP, Estey, E, Foran, J, Lancet, J, Maness, LJ, Maslak, PG, Millenson, M, Moore, JO, Przepiorka, D, Shami, P, Smith, BD, Stone, RM, and Tallman, MS. "Acute myeloid leukemia: Clinical Practice Guidelines in Oncology." JNCCN Journal of the National Comprehensive Cancer Network 4.1 (2006): 16-36.
PMID
16403402
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
4
Issue
1
Publish Date
2006
Start Page
16
End Page
36

Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222.

The Cancer and Leukemia Group B (CALGB) study 9222 tested the hypothesis that treatment intensification of acute myeloid leukemia (AML) in first remission with multiple chemotherapy agents is superior to high-dose cytarabine (HiDAC) alone. We enrolled 474 patients younger than 60 years old with untreated de novo AML. Daunorubicin and cytarabine resulted in complete remission (CR) in 342 patients (72%), and 309 of these patients were randomized to receive one of 2 different intensification regimens. The first regimen consisted of 3 courses of HiDAC. The second regimen consisted of one course of HiDAC, a second course with etoposide and cyclophosphamide, and a third course with diaziquone and mitoxantrone. After a median follow-up time of 8.3 years, the median survival for all randomized patients was 2.8 years (95% CI, 1.9-6.8 years). There was no difference in disease-free survival (DFS) between the 2 regimens (P = .66). The median DFS was 1.1 years (95% CI, 0.9-1.7 years) for patients receiving HiDAC and 1.0 year (95% CI, 0.9-1.3 years) for those receiving multiagent chemotherapy. Cytogenetics was the only pretreatment characteristic prognostic for DFS, but there was no evidence of a differential treatment effect within cytogenetic risk groups. Toxicity was greater with multiagent chemotherapy. These 2 postremission regimens produced similar outcomes.

Authors
Moore, JO; George, SL; Dodge, RK; Amrein, PC; Powell, BL; Kolitz, JE; Baer, MR; Davey, FR; Bloomfield, CD; Larson, RA; Schiffer, CA
MLA Citation
Moore, JO, George, SL, Dodge, RK, Amrein, PC, Powell, BL, Kolitz, JE, Baer, MR, Davey, FR, Bloomfield, CD, Larson, RA, and Schiffer, CA. "Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222." Blood 105.9 (May 1, 2005): 3420-3427.
PMID
15572587
Source
pubmed
Published In
Blood
Volume
105
Issue
9
Publish Date
2005
Start Page
3420
End Page
3427
DOI
10.1182/blood-2004-08-2977

Molecular and cytogenetic characterization of a novel rearrangement involving chromosomes 9, 12, and 17 resulting in ETV6 (TEL) and ABL fusion.

We performed chromosome analysis on the bone marrow of a patient with BCR/ABL negative chronic myelogenous leukemia (CML). By interphase fluorescence in situ hybridization (FISH), an extra ABL signal was present in interphase nuclei and appeared to be located at 17p in the metaphase cells. Chromosome analysis showed a subtle abnormality at 17p13 and 12p13 but no visible rearrangement at 9q34 (ABL). Additional FISH experiments disclosed a rearrangement between the short arms of chromosomes 12 and 17 at approximately bands 12p13 and 17p13, respectively. In addition, subtelomeric FISH analysis confirmed the presence of terminal 12p at 17p13 and showed terminal 9q34 to be intact on each chromosome 9. Taken together, these results indicated a rearrangement involving chromosomes 9, 12, and 17 that suggested the possibility of juxtaposition of part of the ETV6 (also known as TEL) locus (12p13) with a portion of ABL (9q34) together at 17p13. The ETV6/ABL fusion was confirmed by RT-PCR, which showed that the first 5 exons of ETV6 were fused in frame with ABL at exon 2. Wild-type ETV6 and ABL were also expressed, in accordance with the FISH results that showed no loss of the second ETV6 or ABL allele.

Authors
Tirado, CA; Sebastian, S; Moore, JO; Gong, JZ; Goodman, BK
MLA Citation
Tirado, CA, Sebastian, S, Moore, JO, Gong, JZ, and Goodman, BK. "Molecular and cytogenetic characterization of a novel rearrangement involving chromosomes 9, 12, and 17 resulting in ETV6 (TEL) and ABL fusion." Cancer Genet Cytogenet 157.1 (February 2005): 74-77.
PMID
15676152
Source
pubmed
Published In
Cancer Genetics and Cytogenetics
Volume
157
Issue
1
Publish Date
2005
Start Page
74
End Page
77
DOI
10.1016/j.cancergencyto.2004.06.001

Chronic myelogenous leukemia: Clinical practice guidelines in oncology

Chronic myelogenous leukemia (CML) accounts for 15% of adult leukemias. In 2005, an estimated 4,600 cases will be diagnosed, and 850 patients will die of the disease. The median age of disease onset is 53 years; however, CML occurs in all age groups, with an increasing proportion of younger patients in more recent series. ML progresses from a chronic phase to a rapidly fatal blastic phase, generally over 3 to 5 years. The blast phase is often preceded by a transition period, called the accelerated phase, which is marked by the acquisition of new cytogenetic abnormalities in 50% to 80% of patients. Several definitions of the accelerated phase of the disease are summarized. © Journal of the National Comprehensive Cancer Network.

Authors
O'Brien, S; Berman, E; Bhalla, K; Copelan, EA; Devetten, MP; Emanuel, PD; Erba, HP; Greenberg, PL; Moore, JO; Przepiorka, D; Radich, JP; Schilder, RJ; Shami, P; Smith, BD; Snyder, DS; Soiffer, RJ; Tallman, MS; Talpaz, M; Wetzler, M
MLA Citation
O'Brien, S, Berman, E, Bhalla, K, Copelan, EA, Devetten, MP, Emanuel, PD, Erba, HP, Greenberg, PL, Moore, JO, Przepiorka, D, Radich, JP, Schilder, RJ, Shami, P, Smith, BD, Snyder, DS, Soiffer, RJ, Tallman, MS, Talpaz, M, and Wetzler, M. "Chronic myelogenous leukemia: Clinical practice guidelines in oncology." JNCCN Journal of the National Comprehensive Cancer Network 3.6 (2005): 732-755.
PMID
16316611
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
3
Issue
6
Publish Date
2005
Start Page
732
End Page
755

Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: A Cancer and Leukemia Group B study

Purpose: To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML). Patients and Methods: Pretreatment blood samples from 84 cytogenetically normal AML patients aged less than 60 years, who were characterized for BAALC expression, FLT3 internal tandem duplication (ITD), and MLL partial tandem duplication (PTD) and uniformly treated on Cancer and Leukemia Group B 9621 protocol, were analyzed for ERG expression by real-time reverse transcriptase polymerase chain reaction. Patients were divided into quartiles according to ERG levels and were compared for clinical outcome. High-density oligonucleotide arrays were used to identify genes differentially expressed between high and low ERG expressers. Results: With a median follow-up of 5.7 years, patients with the upper 25% of ERG expression values had a worse cumulative incidence of relapse (CIR; P < .001) and overall survival (OS; P = .011) than the remaining patients. In a multivariable analysis, high ERG expression (P < .001) and the presence of MLL PTD (P = .027) predicted worse CIR. With regard to OS, an interaction was observed between expression of ERG and BAALC (P = .013), with ERG overexpression predicting shorter survival only in low BAALC expressers (P = .002). ERG overexpression was an independent prognostic factor even when the unfavorable group of FLT3 ITD patients lacking an FLT3 wild-type allele was included. High ERG expression was associated with upregulation of 112 expressed-sequenced tags and named genes, many of which are involved in cell proliferation, differentiation, and apoptosis. Conclusion: ERG overexpression in AML patients with normal cytogenetics predicts an adverse clinical outcome and seems to be associated with a specific molecular signature. © 2005 by American Society of Clinical Oncology.

Authors
Marcucci, G; Baldus, CD; Ruppert, AS; Radmacher, MD; Mrózek, K; Whitman, SP; Kolitz, JE; Edwards, CG; Vardiman, JW; Powell, BL; Baer, MR; Moore, JO; Perrotti, D; Caligiuri, MA; Carroll, AJ; Larson, RA; Chapelle, ADL; Bloomfield, CD
MLA Citation
Marcucci, G, Baldus, CD, Ruppert, AS, Radmacher, MD, Mrózek, K, Whitman, SP, Kolitz, JE, Edwards, CG, Vardiman, JW, Powell, BL, Baer, MR, Moore, JO, Perrotti, D, Caligiuri, MA, Carroll, AJ, Larson, RA, Chapelle, ADL, and Bloomfield, CD. "Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: A Cancer and Leukemia Group B study." Journal of Clinical Oncology 23.36 (2005): 9234-9242.
PMID
16275934
Source
scival
Published In
Journal of Clinical Oncology
Volume
23
Issue
36
Publish Date
2005
Start Page
9234
End Page
9242
DOI
10.1200/JCO.2005.03.6137

Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): A Cancer and Leukemia Group B study

Purpose: Because both t(8;21) and inv(16) disrupt core binding factor (CBF) in acute myeloid leukemia (AML) and confer relatively favorable prognoses, these cytogenetic groups are often treated similarly. Recent studies, however, have shown different gene profiling for the two groups, underscoring potential biologic differences. Therefore, we sought to determine whether these two cytogenetic groups should also be considered separate entities from a clinical standpoint. Patients and Methods: We analyzed 144 consecutive adults with t(8;21) and 168 with inv(16) treated on Cancer and Leukemia Group B front-line studies. We compared pretreatment features, probability of achieving complete remission (CR), overall survival (OS) and cumulative incidence of relapse (CIR) between the two groups. Results: With a median follow-up of 6.4 years, for CBF AML as a whole, the CR rate was 88%, 5-year OS was 50% and CIR was 53%. After adjusting for covariates, patients with t(8;21) had shorter OS (hazard ratio [HR] = 1.5; P = .045) and survival after first relapse (HR = 1.7; P = .009) than patients with inv(16). Unexpectedly, race was an important predictor for t(8;21) AML, in that nonwhites failed induction more often (odds ratio = 5.7; P = .006) and had shorter OS than whites when certain secondary cytogenetic abnormalities were present. In patients with t(8;21) younger than 60 years, type of induction also correlated with relapse risk. For inv(16) AML, secondary cytogenetic abnormalities (especially +22) and male sex predicted better outcome. Conclusion: When the prognostic impact of race, secondary cytogenetic abnormalities, sex, and response to salvage treatment is considered, t(8;21) and inv(16) AMLs seem to be distinct clinical entities and should be stratified and reported separately. © 2005 by American Society of Clinical Oncology.

Authors
Marcucci, G; Mrózek, K; Ruppert, AS; Maharry, K; Kolitz, JE; Moore, JO; Mayer, RJ; Pettenati, MJ; Powell, BL; Edwards, CG; Sterling, LJ; Vardiman, JW; Schiffer, CA; Carroll, AJ; Larson, RA; Bloomfield, CD
MLA Citation
Marcucci, G, Mrózek, K, Ruppert, AS, Maharry, K, Kolitz, JE, Moore, JO, Mayer, RJ, Pettenati, MJ, Powell, BL, Edwards, CG, Sterling, LJ, Vardiman, JW, Schiffer, CA, Carroll, AJ, Larson, RA, and Bloomfield, CD. "Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): A Cancer and Leukemia Group B study." Journal of Clinical Oncology 23.24 (2005): 5705-5717.
PMID
16110030
Source
scival
Published In
Journal of Clinical Oncology
Volume
23
Issue
24
Publish Date
2005
Start Page
5705
End Page
5717
DOI
10.1200/JCO.2005.15.610

Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia

Purpose: Lintuzumab (HuM195) is an unconjugated humanized murine monoclonal antibody directed against the cell surface myelomonocytic differentiation antigen CD33. In this study, the efficacy of lintuzumab in combination with induction chemotherapy was compared with chemotherapy alone in adults with first relapsed or primary refractory acute myeloid leukemia (AML). Patients and Methods: Patients with relapsed or primary resistant AML (duration of first response, zero to 12 months) were randomly assigned to receive either mitoxantrone 8 mg/m2, etoposide 80 mg/m2, and cytarabine 1 g/m2 daily for 6 days (MEC) in combination with lintuzumab 12 mg/m2, or MEC alone. Overall response, defined as the rate of complete remission (CR) and CR with incomplete platelet recovery (CRp), was the primary end point of the study, with additional analyses of survival time and toxicity. Results: A total of 191 patients were randomly assigned from November 1999 to April 2001. The percent CR plus CRp with MEC plus lintuzumab was 36% v 28% in patients treated with MEC alone (P = .28). The overall median survival was 156 days and was not different in the two arms of the study. Apart from mild antibody infusion-related toxicities (fever, chills, and hypotension), no differences in chemotherapy-related adverse effects, including hepatic and cardiac dysfunction, were observed with the addition of lintuzumab to induction chemotherapy. Conclusion: The addition of lintuzumab to salvage induction chemotherapy was safe, but did not result in a statistically significant improvement in response rate or survival in patients with refractory/relapsed AML. © 2005 by American Society of Clinical Oncology.

Authors
Feldman, EJ; Brandwein, J; Stone, R; Kalaycio, M; Moore, J; O'Connor, NWJ; Roboz, GJ; Miller, C; Chopra, R; Jurcic, JC; Brown, R; Ehmann, WC; Schulman, P; Frankel, SR; Angela, DD; Scheinberg, D
MLA Citation
Feldman, EJ, Brandwein, J, Stone, R, Kalaycio, M, Moore, J, O'Connor, NWJ, Roboz, GJ, Miller, C, Chopra, R, Jurcic, JC, Brown, R, Ehmann, WC, Schulman, P, Frankel, SR, Angela, DD, and Scheinberg, D. "Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia." Journal of Clinical Oncology 23.18 (2005): 4110-4116.
PMID
15961759
Source
scival
Published In
Journal of Clinical Oncology
Volume
23
Issue
18
Publish Date
2005
Start Page
4110
End Page
4116
DOI
10.1200/JCO.2005.09.133

Phase I/II study of galiximab, an anti-CD80 antibody, for relapsed or refractory follicular lymphoma

Purpose: This multicenter, dose-escalation study evaluates the safety, pharmacokinetics, and efficacy of galiximab (anti-CD80 monoclonal antibody) in patients with relapsed or refractory follicular lymphoma. Patients and Methods: Patients had follicular lymphoma that had relapsed or failed to respond to primary therapy; the majority (90%) presented with stage III or IV disease. Four weekly intravenous infusions of galiximab were administered at doses of 125, 250, 375, or 500 mg/m2. Results: Thirty-seven patients received galiximab treatment and were evaluated for safety; 35 were assessable for response. Antibody infusions were safe and well tolerated with no dose-limiting toxicities. A total of 22 (60%) of 37 patients experienced adverse events related to galiximab. All but one of the events were grade 1 or 2; the most common were fatigue, nausea, and headache. Cytopenias were rare; only one patient experienced anemia and febrile neutropenia, which were unrelated to galiximab and resolved after treatment. No patient developed antigaliximab antibody formation. The mean serum half-life ranged from 13 to 24 days. The overall response rate was 11% (two complete responses and two partial responses). Time to best response was delayed (months 3, 6, 9, and 12). Twelve patients (34%) maintained stable disease. Nearly half of all patients (49%) had a decrease in indicator lesions. Two responders remain on study without progression (22 and 24.4 months). Conclusion: The favorable safety profile of galiximab and evidence of single-agent biologic activity and dose-dependent pharmacokinetics support further evaluation of galiximab as a treatment for follicular lymphoma, possibly in combination with other lymphoma therapies. © 2005 by American Society of Clinical Oncology.

Authors
Czuczman, MS; Thall, A; Witzig, TE; Vose, JM; Younes, A; Emmanouilides, C; Miller, TP; Moore, JO; Leonard, JP; Gordon, LI; Sweetenham, J; Alkuzweny, B; Finucane, DM; Leigh, BR
MLA Citation
Czuczman, MS, Thall, A, Witzig, TE, Vose, JM, Younes, A, Emmanouilides, C, Miller, TP, Moore, JO, Leonard, JP, Gordon, LI, Sweetenham, J, Alkuzweny, B, Finucane, DM, and Leigh, BR. "Phase I/II study of galiximab, an anti-CD80 antibody, for relapsed or refractory follicular lymphoma." Journal of Clinical Oncology 23.19 (2005): 4390-4398.
PMID
15994148
Source
scival
Published In
Journal of Clinical Oncology
Volume
23
Issue
19
Publish Date
2005
Start Page
4390
End Page
4398
DOI
10.1200/JCO.2005.09.018

Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype: A cancer and leukemia group B study

Purpose: Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML). Patients and Methods: In 490 patients, induction included cytarabine and daunorubicin (AD) or cytarabine and escalated doses of daunorubicin and etoposide ± PSC-833 (ADE/ADEP). Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV). Results: Of 350 patients receiving AD, 73% achieved complete remission (CR), compared with 82% of 140 receiving ADE/ADEP (P = .04). Splenomegaly was associated with a lower CR rate (P < .001), and ADE/ADEP, with a higher CR rate in younger patients (P = .005). The 5-year disease-free survival (DFS) rate was 28% each for intensification groups I and II, compared with 41% and 45% for groups III and IV, respectively (P = .02). The 5-year cumulative incidence of relapse (CIR) was 62% and 67% for groups I and II, respectively, compared with 54% and 44% for groups III and IV, respectively (P = .049). The type of postremission intensification remained significant for DFS and CIR in multivariable analysis. Conclusion: In younger adults with normal cytogenetics AML, splenomegaly predicts a lower CR rate, and the postremission strategies of either four cycles of I/HDAC or one cycle of HDAC/etoposide followed by ASCT are associated with improved DFS and reduced relapse compared with therapies that include fewer cycles of cytarabine or no transplantation. © 2005 by American Society of Clinical Oncology.

Authors
Farag, SS; Ruppert, AS; Mrózek, K; Mayer, RJ; Stone, RM; Carroll, AJ; Powell, BL; Moore, JO; Pettenati, MJ; Koduru, PRK; Stamberg, J; Baer, MR; Block, AW; Vardiman, JW; Kolitz, JE; Schiffer, CA; Larson, RA; Bloomfield, CD
MLA Citation
Farag, SS, Ruppert, AS, Mrózek, K, Mayer, RJ, Stone, RM, Carroll, AJ, Powell, BL, Moore, JO, Pettenati, MJ, Koduru, PRK, Stamberg, J, Baer, MR, Block, AW, Vardiman, JW, Kolitz, JE, Schiffer, CA, Larson, RA, and Bloomfield, CD. "Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype: A cancer and leukemia group B study." Journal of Clinical Oncology 23.3 (2005): 482-493.
PMID
15534356
Source
scival
Published In
Journal of Clinical Oncology
Volume
23
Issue
3
Publish Date
2005
Start Page
482
End Page
493
DOI
10.1200/JCO.2005.06.090

Dose escalation studies of cytarabine, daunorubicin, and etoposide with and without multidrug resistance modulation with PSC-833 in untreated adults with acute myeloid leukemia younger than 60 years: final induction results of Cancer and Leukemia Group B Study 9621.

PURPOSE: P-glycoprotein (Pgp) is strongly inhibited by PSC-833. A chemotherapy dose-escalation study was performed with PSC-833 in patients younger than 60 years with untreated acute myeloid leukemia. Clinical rather than pharmacokinetic end points were used to develop two induction therapies containing drugs susceptible to Pgp-mediated efflux and associated with comparable toxicities at the maximum-tolerated doses. PATIENTS AND METHODS: A total of 410 patients were enrolled. Fifteen induction regimens containing variable doses of daunorubicin (DNR) and etoposide (ETOP) and fixed doses of cytarabine were evaluated with (ADEP) or without (ADE) a fixed dose of PSC-833. RESULTS: Doses selected for phase III testing were DNR 90 mg/m(2) and ETOP 100 mg/m(2) in ADE, and DNR and ETOP each 40 mg/m(2) in ADEP. Intolerable mucosal toxicity occurred at higher doses of ADEP. Although the design of this study precludes direct comparisons, there was an apparent advantage for receiving ADEP with respect to disease-free and overall survival in patients < or = 45 years old, despite the significantly lower doses of DNR and ETOP given in ADEP compared with ADE. CONCLUSION: A large clinical data set was used to develop induction regimens containing two drugs susceptible to Pgp-mediated efflux, with and without an inhibitor of Pgp function. The chosen doses have comparable antileukemia activity and toxicity, making them suitable for use in a phase III comparative study of induction chemotherapy for patients with acute myeloid leukemia younger than 60 years. That trial will also clarify whether patients < or = 45 years old are especially likely to benefit from Pgp inhibition during induction therapy.

Authors
Kolitz, JE; George, SL; Dodge, RK; Hurd, DD; Powell, BL; Allen, SL; Velez-Garcia, E; Moore, JO; Shea, TC; Hoke, E; Caligiuri, MA; Vardiman, JW; Bloomfield, CD; Larson, RA; Cancer and Leukemia Group B,
MLA Citation
Kolitz, JE, George, SL, Dodge, RK, Hurd, DD, Powell, BL, Allen, SL, Velez-Garcia, E, Moore, JO, Shea, TC, Hoke, E, Caligiuri, MA, Vardiman, JW, Bloomfield, CD, Larson, RA, and Cancer and Leukemia Group B, . "Dose escalation studies of cytarabine, daunorubicin, and etoposide with and without multidrug resistance modulation with PSC-833 in untreated adults with acute myeloid leukemia younger than 60 years: final induction results of Cancer and Leukemia Group B Study 9621." J Clin Oncol 22.21 (November 1, 2004): 4290-4301.
PMID
15514371
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
21
Publish Date
2004
Start Page
4290
End Page
4301
DOI
10.1200/JCO.2004.11.106

Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients.

BACKGROUND: Iodine-131 metaiodobenzylguanidine (131I-MIBG) is useful for imaging carcinoid tumors and recently has been applied to the palliative treatment of metastatic carcinoid in small studies. The authors now report their results on the therapeutic utility of high-dose 131I-MIBG treatment in a large group of patients with metastatic carcinoid tumors. METHODS: The authors performed a retrospective review of 98 patients with metastatic carcinoid who were treated at their institution with 131I-MIBG over a 15-year period. Endpoints examined included the World Health Organization criteria for treatment response: symptoms, hormone (5-hydroxyindoleacetic acid [5-HIAA]) production, and clinical tumor response. RESULTS: Patients received a median dose of 401 +/- 202 millicuries (mCi) 131I-MIBG. The median survival after treatment was 2.3 years. Patients who experienced a symptomatic response had improved survival (5.76 years vs. 2.09 years; P < 0.01). For the 56 patients who had 5-HIAA levels monitored, the mean urine 5-HIAA levels decreased significantly after 131I-MIBG treatment (126 +/- 122 ng/mL vs. 91 +/- 125 ng/mL; P < 0.01); however, the patients with reduced 5-HIAA levels did not experience improved survival (4.11 years vs. 3.42 years; P = 0.2). Patients who received an initial 131I-MIBG dose > 400 mCi lived longer than patients who received < 400 mCi (4.69 years vs. 1.86 years; P = 0.05). Radiographic tumor response did not predict survival. Toxicity included pancytopenia, thrombocytopenia, nausea, and emesis. CONCLUSIONS: The current data support 131I-MIBG treatment in select patients with metastatic carcinoid who progress despite optimal medical management. Improved survival was predicted best by symptomatic response to 131I-MIBG treatment, but not by hormone or radiographic response.

Authors
Safford, SD; Coleman, RE; Gockerman, JP; Moore, J; Feldman, J; Onaitis, MW; Tyler, DS; Olson, JA
MLA Citation
Safford, SD, Coleman, RE, Gockerman, JP, Moore, J, Feldman, J, Onaitis, MW, Tyler, DS, and Olson, JA. "Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients." Cancer 101.9 (November 1, 2004): 1987-1993.
PMID
15455358
Source
pubmed
Published In
Cancer
Volume
101
Issue
9
Publish Date
2004
Start Page
1987
End Page
1993
DOI
10.1002/cncr.20592

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

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

Differences in prognostic factors and outcomes in African Americans and whites with acute myeloid leukemia

Whites have a more favorable prognosis than African Americans for a number of cancers. The relationship between race and outcome is less clear in acute myeloid leukemia (AML). Using data from 7 Cancer and Leukemia Group B studies initiated from 1985 to 1997, we conducted a retrospective cross-sectional analysis of 2570 patients (270 African American and 2300 white) with de novo AML who received induction chemotherapy. African Americans were younger than whites (48 versus 54 years, P < .001). African Americans also had different cytogenetic risk group distributions than whites (P < .001): they were more commonly classified in the favorable (23% versus 14%) and unfavorable (31% versus 23%) groups, and less commonly classified in the intermediate group (47% versus 63%). African American men had a lower complete remission (CR) rate (54%, compared with 64% for white men, 65% for white women, and 70% for African American women, P = .001) and a worse overall survival compared with all other patients (P= .004), when known risk factors are taken into account. African Americans and whites with AML differ with respect to important prognostic factors. African American men have worse CR rates and overall survival than whites and African American women, and should be considered a poor-risk group. © 2004 by The American Society of Hematology.

Authors
Sekeres, MA; Peterson, B; Dodge, RK; Mayer, RJ; Moore, JO; Lee, EJ; Kolitz, J; Baer, MR; Schiffer, CA; Carroll, AJ; Vardiman, JW; Davey, FR; Bloomfield, CD; Larson, RA; Stone, RM
MLA Citation
Sekeres, MA, Peterson, B, Dodge, RK, Mayer, RJ, Moore, JO, Lee, EJ, Kolitz, J, Baer, MR, Schiffer, CA, Carroll, AJ, Vardiman, JW, Davey, FR, Bloomfield, CD, Larson, RA, and Stone, RM. "Differences in prognostic factors and outcomes in African Americans and whites with acute myeloid leukemia." Blood 103.11 (2004): 4036-4042.
PMID
14976037
Source
scival
Published In
Blood
Volume
103
Issue
11
Publish Date
2004
Start Page
4036
End Page
4042
DOI
10.1182/blood-2003-09-3118

Retrospective analysis of capecitabine and radiation therapy in the treatment of pancreatic cancer

Purpose: To report our clinical experience with 25 patients receiving concurrent capecitabine and irradiation in the treatment of locally advanced or resected pancreatic cancer. Methods and Materials: We reviewed the medical records of patients with pancreatic cancer who received treatment with capecitabine and irradiation for pancreatic cancer and received capecitabine 1200 to 1600 mg/m2 orally twice daily Monday through Friday with concurrent radiation (5040-5400 cGy, 180 cGy, 5 days/week), followed by a 4-week rest, then 6 to 8 cycles of capecitabine alone 2000 to 2500 mg/m2 twice daily for 14 days every 3 weeks (surgically resected), and capecitabine 2000 to 2500 mg/m2 BID for 14 days every 3 weeks until progressive disease (unresected). Results: The population consisted of 14 females and 11 males, with a median age of 64 years (range 37-80 years). Histology was adenocarcinoma in 23 patients and neuroendocrine tumor in 2 patients. One patient had resected tumor, 3 patients were resected with positive margins, 1 patient was resectable with poor performance status prohibiting resection, and 20 patients had unresected locally advanced disease. Median dose of capecitabine concurrent with radiation was 1500 mg/m2/day (600-1600 mg/m 2/day) given orally in two divided doses, 5 days per week on days of treatment with radiation therapy. Patients received a median total radiation dose of 5040 cGy (4500-5040 cGy) over 6 weeks. Eleven patients were continued on capecitabine cycles after treatment with concurrent capecitabine and irradiation. The median number of cycles completed was 3, with one patient completing 8 cycles. Median survival was 14 months, with 18 patients surviving through the end of the study period. Median overall primary tumor response over the study period was-2% (-100%-100%). Five patients were taken to laparotorny after treatment based on radiographic response and two patients were successfully resected. By the end of the study period, there were 4 complete remissions, 2 partial remissions, 6 stable disease, and 13 progressive disease. Grade 3 or 4 toxicity was observed mainly with gastrointestinal symptoms including nausea, vomiting, diarrhea, and anorexia. Three patients had G3 hand-foot syndrome, 1 patient had G3 peripheral neuropathy, 1 patient had G4 gastrointestinal bleed, and 1 patient had G3 radiation enteritis. There was one death directly related to treatment secondary to uncontrolled GI bleeding. Conclusion: In patients with locally advanced pancreatic cancer, concurrent capecitabine and radiation had good survival response in patients and good tumor response. Toxicity of oral capecitabine was well tolerated.

Authors
Saif, MW; Joseph, M; Tang, S; Vickers, S; Plants, B; Russo, S
MLA Citation
Saif, MW, Joseph, M, Tang, S, Vickers, S, Plants, B, and Russo, S. "Retrospective analysis of capecitabine and radiation therapy in the treatment of pancreatic cancer." Journal of Applied Research 4.4 (2004): 635-646.
Source
scival
Published In
The journal of applied research
Volume
4
Issue
4
Publish Date
2004
Start Page
635
End Page
646

Core binding factor acute myeloid leukemia. Cancer and Leukemia Group B (CALGB) Study 8461.

Authors
Bloomfield, CD; Ruppert, AS; Mrózek, K; Kolitz, JE; Moore, JO; Mayer, RJ; Edwards, CG; Sterling, LJ; Vardiman, JW; Carroll, AJ; Pettenati, MJ; Stamberg, J; Byrd, JC; Marcucci, G; Larson, RA
MLA Citation
Bloomfield, CD, Ruppert, AS, Mrózek, K, Kolitz, JE, Moore, JO, Mayer, RJ, Edwards, CG, Sterling, LJ, Vardiman, JW, Carroll, AJ, Pettenati, MJ, Stamberg, J, Byrd, JC, Marcucci, G, and Larson, RA. "Core binding factor acute myeloid leukemia. Cancer and Leukemia Group B (CALGB) Study 8461." Annals of hematology 83 Suppl 1 (2004): S84-S85.
PMID
15124687
Source
scival
Published In
Annals of hematology
Volume
83 Suppl 1
Publish Date
2004
Start Page
S84
End Page
S85

Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): Results from CALGB 8461

Purpose: To study the impact of repetitive (three to four courses) versus a single course of high-dose cytarabine (HDAC) consolidation therapy on outcome of patients with acute myeloid leukemia (AML) and inv(16)(p13q22) or t(16;16)(p13;q22). Patients and Methods: We examined the cumulative incidence of relapse (CIR). relapse-free survival (RFS), and overall survival (OS) for 48 adults younger than 60 years with inv(16)/t(16;16) who had attained a complete remission on one of four consecutive clinical trials and were assigned to receive HDAC consolidation therapy. Twenty-eight patients were assigned to either three or four courses of HDAC, and 20 patients were assigned to one course of HDAC followed by alternative intensive consolidation therapy. Results: Pretreatment features were similar for the two groups. The CIR was significantly decreased in patients assigned to receive three to four cycles of HDAC compared with patients assigned to one course (P = .03; 5-year CIR, 43% v 70%, respectively). The difference in RFS also approached statistical significance (P = .06). In a multivariable analysis that adjusted for potential confounding covariates, only treatment assignment (three to four cycles of HDAC) predicted for superior RFS (P = .02). The OS of both groups was similar (P = .93; 5-year OS, 75% for the three to four cycles of HDAC group v 70% for the one cycle of HDAC group), reflecting a high success rate with stem-cell transplantation salvage treatment administered among patients in both treatment groups. Conclusion: We conclude that, in AML patients with inv(16)/t(16;16), repetitive HDAC therapy decreases the likelihood of relapse compared with consolidation regimens including less HDAC.

Authors
Byrd, JC; Ruppert, AS; Mrózek, K; Carroll, AJ; Edwards, CG; Arthur, DC; Pettenati, MJ; Stamberg, J; Koduru, PRK; Moore, JO; Mayer, RJ; Davey, FR; Larson, RA; Bloomfield, CD
MLA Citation
Byrd, JC, Ruppert, AS, Mrózek, K, Carroll, AJ, Edwards, CG, Arthur, DC, Pettenati, MJ, Stamberg, J, Koduru, PRK, Moore, JO, Mayer, RJ, Davey, FR, Larson, RA, and Bloomfield, CD. "Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): Results from CALGB 8461." Journal of Clinical Oncology 22.6 (2004): 1087-1094.
PMID
15020610
Source
scival
Published In
Journal of Clinical Oncology
Volume
22
Issue
6
Publish Date
2004
Start Page
1087
End Page
1094
DOI
10.1200/JCO.2004.07.012

Iodine -131 metaiodobenzylguanidine is an effective treatment for malignant pheochromocytoma and paraganglioma.

INTRODUCTION: Iodine 131-meta-iodobenzylguanidine ((131)I-MIBG) has been applied to the palliative treatment of metastatic pheochromocytoma in small studies. We report our institutional experience for the treatment of metastatic pheochromocytoma and paraganglioma. METHODS: We performed a retrospective review of 33 patients with metastatic pheochromocytoma (n=22) and paraganglioma (n=11) treated at our institution with (131)I-MIBG over a 10-year period. RESULTS: Patients received a mean dose of 388+/-131 mCi (131)I-MIBG. Median survival after treatment was 4.7 years. Most patients experienced a symptomatic response leading to an improved survival (4.7 years vs 1.8 years, P<.01). Patients with a measurable hormone response demonstrated an increased survival in comparison to those with no response (4.7 years vs 2.6 years, P=.01). Patients who received a high dose (>500 mCi) as their initial therapy also had improved survival (3.8 years vs 2.8 years, P=.02). CONCLUSION: These data support (131)I-MIBG treatment for select patients with metastatic pheochromocytoma. In our experience, prolonged survival was best predicted by symptomatic and hormone response to (131)I-MIBG treatment. An initial dose of 500 mCi may be optimal. The benefit of (131)I-MIBG treatment for metastatic pheochromocytoma must also be weighed against its side effects.

Authors
Safford, SD; Coleman, RE; Gockerman, JP; Moore, J; Feldman, JM; Leight, GS; Tyler, DS; Olson, JA
MLA Citation
Safford, SD, Coleman, RE, Gockerman, JP, Moore, J, Feldman, JM, Leight, GS, Tyler, DS, and Olson, JA. "Iodine -131 metaiodobenzylguanidine is an effective treatment for malignant pheochromocytoma and paraganglioma." Surgery 134.6 (December 2003): 956-962.
PMID
14668728
Source
pubmed
Published In
Surgery
Volume
134
Issue
6
Publish Date
2003
Start Page
956
End Page
962
DOI
10.1016/S0039

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

Cytogenetic and molecular analysis of an unusual case of acute promyelocytic leukemia with a t(15;17;17)(q22;q23;q21).

We present a 52-year-old female with a clinical history of acute myelocytic leukemia, probable acute promyelocytic leukemia (APL). Flow cytometry results were somewhat unusual. Specifically, the promyelocytic population showed partial positivity for antigens not usually expressed in APL (HLA-DR and CD117). The interpretation of these results was that the abnormal population contained a proportion of very early promyeolocytes that had not completely lost all their "precursor" antigens. Cytogenetic analysis of a bone marrow aspirate showed a t(15:17;17)(q22;q23;q21) in all cells analyzed. Fluorescence in situ hybridization (FISH) analysis using the PML-RARA DNA probe showed a positive signal pattern (fusion) in 100% of 200 total interphase and metaphase cells examined, confirming the presence of the PML-RARA rearrangement. Multicolor FISH, which produces 24 colors to differentiate all chromosomes in a single hybridization, was applied. This study confirmed the cytogenetic interpretation of the rearrangement. No material from any other chromosome was detected on the second smaller derivative chromosome 17. Additional studies using the RARA(17q21) break-apart DNA FISH probe showed that 17q21 (RARA) was not rearranged on the derivative chromosome 17 that received the q22-->qter segment from chromosome 15. The RARA locus on the smaller derivative 17 was the allele involved in the fusion in this three-way rearrangement. The signal pattern was consistent in 100% of interphase and metaphase cells scored. This unusual t(15;17;17) prompted us to investigate further using reverse-transcription polymerase chain reaction with primers from the 3' and 5' regions of both the RARA and PML loci. These studies showed that the PML-RARA fusion was present, but the complementary fusion RARA-PML, which is usually detectable, was absent. The patient is responding well to standard treatment protocols.

Authors
Tirado, CA; Golembiewski-Ruiz, V; Horvatinovich, J; Moore, JO; Buckley, PJ; Stenzel, TT; Goodman, BK
MLA Citation
Tirado, CA, Golembiewski-Ruiz, V, Horvatinovich, J, Moore, JO, Buckley, PJ, Stenzel, TT, and Goodman, BK. "Cytogenetic and molecular analysis of an unusual case of acute promyelocytic leukemia with a t(15;17;17)(q22;q23;q21)." Cancer Genet Cytogenet 145.1 (August 2003): 31-37.
PMID
12885460
Source
pubmed
Published In
Cancer Genetics and Cytogenetics
Volume
145
Issue
1
Publish Date
2003
Start Page
31
End Page
37

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

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

BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: A Cancer and Leukemia Group B study

Cytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). Of adults with de novo AML, 45% lack cytogenetic abnormalities, and identification of predictive molecular markers might improve therapy. We studied the prognostic impact of BAALC (Brain And Acute Leukemia, Cytoplasmic), a novel gene involved in leukemia, in 86 de novo AML patients with normal cytogenetics who were uniformly treated on Cancer and Leukemia Group B 9621. BAALC expression was determined by comparative real-time reverse transcriptase-polymerase chain reaction in pretreatment blood samples, and patients were dichotomized at BAALC's median expression into low and high expressers. Low expressers had higher white counts (P = .03) and more frequent French-American-British M5 morphology (P = .007). Compared to low expressers, high BAALC expressers showed significantly inferior overall survival (OS; median, 1.7 vs 5.8 years, P = .02), event-free survival (EFS; median, 0.8 vs 4. 9 years, P = .03), and disease-free survival (DFS; median, 1.4 vs 7.3 years, P = .03). Multivariable analysis confirmed high BAALC expression as an independent risk factor. For high BAALC expressers the hazard ratio of an event for OS, EFS, and DFS was respectively 2.7, 2.6, and 2.2. We conclude that high BAALC expression predicts an adverse prognosis and may define an important risk factor in AML with normal cytogenetics. © 2003 by The American Society of Hematology.

Authors
Baldus, CD; Tanner, SM; Ruppert, AS; Whitman, SP; Archer, KJ; Marcucci, G; Caligiuri, MA; Carroll, AJ; Vardiman, JW; Powell, BL; Allen, SL; Moore, JO; Larson, RA; Kolitz, JE; Chapelle, ADL; Bloomfield, CD
MLA Citation
Baldus, CD, Tanner, SM, Ruppert, AS, Whitman, SP, Archer, KJ, Marcucci, G, Caligiuri, MA, Carroll, AJ, Vardiman, JW, Powell, BL, Allen, SL, Moore, JO, Larson, RA, Kolitz, JE, Chapelle, ADL, and Bloomfield, CD. "BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: A Cancer and Leukemia Group B study." Blood 102.5 (2003): 1613-1618.
PMID
12750167
Source
scival
Published In
Blood
Volume
102
Issue
5
Publish Date
2003
Start Page
1613
End Page
1618
DOI
10.1182/blood-2003-02-0359

Randomized, multicenter, open-label study of pegfilgrastim compared with daily filgrastim after chemotherapy for lymphoma

Purpose: The primary objective was to assess the duration of grade 4 neutropenia (neutrophil count < 0.5 × 109/L) after one cycle of chemotherapy with etoposide, methyl-prednisolone, cisplatin, and cytarabine in patients randomly assigned to receive one dose of pegfilgrastim or daily filgrastim after chemotherapy. Febrile neutropenia, neutrophil profiles, time to neutrophil recovery, pharmacokinetics, and safety were also assessed. Patients and Methods: An open-label, randomized, phase II study was designed to compare the effects of a single subcutaneous injection of pegfilgrastim (sustained-duration filgrastim) 100 μg/kg per chemotherapy cycle (n = 33) with daily subcutaneous injections of filgrastim 5 μg/kg (n = 33) in patients receiving salvage chemotherapy for relapsed or refractory Hodgkin's or non-Hodgkin's lymphoma. Results: The incidence of grade 4 neutropenia in the pegfilgrastim and filgrastim groups was 69% and 68%, respectively. In addition, the mean duration of grade 4 neutropenia was similar in both groups (2.8 and 2.4 days, respectively). The results for the two groups were also not significantly different for febrile neutropenia, neutrophil profile, time to neutrophil recovery, or toxicity profile. A single subcutaneous injection of pegfilgrastim 100 μg/kg produced a sustained serum concentration relative to daily subcutaneous injections of filgrastim. Filgrastim-treated patients received a median of 11 injections per cycle. Conclusion: Pegfilgrastim was safe and well tolerated in this patient population. A single injection of pegfilgrastim per chemotherapy cycle provided neutrophil support with safety and efficacy similar to that provided by daily injections of filgrastim. Once-per-cycle administration of pegfilgrastim simplifies the management of neutropenia and may have important clinical benefits for patients and healthcare providers. © 2003 by American Society of Clinical Oncology.

Authors
Vose, JM; Crump, M; Lazarus, H; Emmanouilides, C; Schenkein, D; Moore, J; Frankel, S; Flinn, I; Lovelace, W; Hackett, J; Liang, BC
MLA Citation
Vose, JM, Crump, M, Lazarus, H, Emmanouilides, C, Schenkein, D, Moore, J, Frankel, S, Flinn, I, Lovelace, W, Hackett, J, and Liang, BC. "Randomized, multicenter, open-label study of pegfilgrastim compared with daily filgrastim after chemotherapy for lymphoma." Journal of Clinical Oncology 21.3 (2003): 514-519.
PMID
12560443
Source
scival
Published In
Journal of Clinical Oncology
Volume
21
Issue
3
Publish Date
2003
Start Page
514
End Page
519
DOI
10.1200/JCO.2003.03.040

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

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

Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: Results from cancer and leukemia group B (CALGB 8461)

We analyzed prospectively 1213 adults with de novo acute myeloid leukemia (AML) to ascertain the prognostic impact of cytogenetic abnormalities on complete remission (CR) rate, 5-year cumulative incidence of relapse (CIR), and 5-year overall survival (OS). All patients received similar induction therapy. Median follow-up for surviving patients was 8.3 years. Nonprioritized cytogenetics distinguished t(8;21) and inv(16)/t(16;16) as conferring a significantly better prognosis than normal karyotype. Prognostic impact of many abnormalities could not be determined independently because of their association with complex karyo type. Neither complex karyotype nor secondary aberrations affected outcome of patients with t(8;21), inv(16)/t(16;16), or t(9;11). Among other patients, those with complex karyotypes had significantly worse outcomes than cytogenetically normal patients. Based on outcome for specific cytogenetic abnormalities and karyotype complexity, patients were divided into 3 risk groups: favorable (CR 88%, CIR 54%, OS 55%), intermediate (CR 67%, CIR 67%, OS 24%), and adverse (CR 32%, CIR 92%, OS 5%). Multivariate analyses confirmed the major contribution of cytogenetics to the probability of attaining CR, CIR, and OS. For the adverse-risk group, the probability of achieving CR was 4.0 and 11.9 times lower, the probability of relapse 3.0 and 4.4 times higher, and the risk of death 2.1 and 4.3 times higher than those for the intermediate and favorable groups, respectively. We conclude that although the prognostic impact of many recurring abnormalities has not been ascertained independently of complex karyotype, cytogenetics is among the most useful factors predicting attainment of CR, CIR, and long-term survival in adult AML. © 2002 by The American Society of Hematology.

Authors
Byrd, JC; Mrózek, K; Dodge, RK; Carroll, AJ; Edwards, CG; Arthur, DC; Pettenati, MJ; Patil, SR; Rao, KW; Watson, MS; Koduru, PRK; Moore, JO; Stone, RM; Mayer, RJ; Feldman, EJ; Davey, FR; Schiffer, CA; Larson, RA; Bloomfield, CD
MLA Citation
Byrd, JC, Mrózek, K, Dodge, RK, Carroll, AJ, Edwards, CG, Arthur, DC, Pettenati, MJ, Patil, SR, Rao, KW, Watson, MS, Koduru, PRK, Moore, JO, Stone, RM, Mayer, RJ, Feldman, EJ, Davey, FR, Schiffer, CA, Larson, RA, and Bloomfield, CD. "Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: Results from cancer and leukemia group B (CALGB 8461)." Blood 100.13 (2002): 4325-4336.
PMID
12393746
Source
scival
Published In
Blood
Volume
100
Issue
13
Publish Date
2002
Start Page
4325
End Page
4336
DOI
10.1182/blood-2002-03-0772

Isolated trisomy of chromosomes 8, 11, 13 and 21 is an adverse prognostic factor in adults with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B 8461.

Isolated trisomy is a relatively common cytogenetic abnormality in acute myeloid leukemia (AML), but with uncertain prognostic significance. We studied a large cohort of newly diagnosed de novo AML patients karyotyped on CALGB 8461 from 1984-1999, where trisomy was the sole abnormality. The common isolated trisomies (IT(C)), +8, +11, +13 and +21, comprised 90% of all sole trisomies. The outcome of 101 IT(C) patients was compared to that of 976 with normal and "poor risk" cytogenetics. The overall survival (OS) for IT(C) patients was unsatisfactory with 10% [95% confidence interval (CI), 3-17%] alive at 5 years. Repeated cycles of I/HDAC intensification did not improve outcome. However, SCT significantly improved relapse-free survival (RFS). Among IT(C) patients <60 years in first remission, only 1 of 7 receiving SCT relapsed, compared to 16 of 19 patients treated with chemotherapy only. The prognosis of IT(C) was dependent on SCT. For non-transplanted patients, the 5-year OS for IT(C) was 5% (95% CI, 0-11%), compared to 20% (95% CI, 16-23%) for 640 normal cytogenetics patients. IT(C) was an independent adverse prognostic factor for OS in non-transplanted patients. In those receiving SCT, however, the 5-year OS for IT(C) patients (69%, 95% CI, 32-100%) was not different to that of transplanted normal cytogenetics patients (60%, 95% CI, 38-81%). We conclude that in de novo adult AML patients not receiving SCT, IT(C) appears to independently predict a poor outcome that may be improved with SCT in first remission. Prospective studies are required to confirm this hypothesis.

Authors
Farag, SS; Archer, KJ; Mrózek, K; Vardiman, JW; Carroll, AJ; Pettenati, MJ; Moore, JO; Kolitz, JE; Mayer, RJ; Stone, RM; Larson, RA; Bloomfield, CD
MLA Citation
Farag, SS, Archer, KJ, Mrózek, K, Vardiman, JW, Carroll, AJ, Pettenati, MJ, Moore, JO, Kolitz, JE, Mayer, RJ, Stone, RM, Larson, RA, and Bloomfield, CD. "Isolated trisomy of chromosomes 8, 11, 13 and 21 is an adverse prognostic factor in adults with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B 8461." International journal of oncology 21.5 (2002): 1041-1051.
PMID
12370753
Source
scival
Published In
International journal of oncology
Volume
21
Issue
5
Publish Date
2002
Start Page
1041
End Page
1051

Nitric oxide enhancement of fludarabine cytotoxicity for B-CLL lymphocytes.

Fludarabine is active but not curative in the treatment of chronic lymphocytic leukemia (B-CLL). Nitric oxide (NO) supplied from exogenous, NO-donating pro-drugs can also induce apoptosis and death of acute leukemia cells. This study investigated combinations of fludarabine with NO-donating pro-drugs for their cytotoxicity against freshly isolated B-CLL lymphocytes following a 72 h exposure in vitro. The median IC(50)for fludarabine was 2.2 microM (n = 85). The nitric oxide donors DETA-NO, PAPA-NO, and MAHMA-NO were also cytotoxic, and their effects were inversely related to rates of NO release. Neither DETA-NO depleted of NO nor DETA itself was effective, indicating that NO was required for cytotoxicity. Drug interactions were evaluated by a modified combination index method. Synergy was observed in combinations of fludarabine or nelarabine (506U78) with DETA-NO in 52% and 88% of samples, respectively. Interestingly, the combination of fludarabine and DETA-NO was more cytotoxic in B-CLL cells less sensitive to fludarabine. DETA-NO did not enhance the activity of other DNA anti-metabolites, topoisomerase I and II inhibitors, or alkylating agents. Finally, the anti-leukemic activity of fludarabine alone or in combination with DETA-NO was found to correlate with inhibition of cellular RNA synthesis. These results indicate that NO donors could enhance fludarabine therapy for B-CLL.

Authors
Adams, DJ; Levesque, MC; Weinberg, JB; Smith, KL; Flowers, JL; Moore, J; Colvin, OM; Silber, R
MLA Citation
Adams, DJ, Levesque, MC, Weinberg, JB, Smith, KL, Flowers, JL, Moore, J, Colvin, OM, and Silber, R. "Nitric oxide enhancement of fludarabine cytotoxicity for B-CLL lymphocytes." Leukemia 15.12 (December 2001): 1852-1859.
PMID
11753605
Source
pubmed
Published In
Leukemia
Volume
15
Issue
12
Publish Date
2001
Start Page
1852
End Page
1859

Adjuvant chemotherapy for osteosarcoma may not increase survival after neoadjuvant chemotherapy and surgical resection.

BACKGROUND AND OBJECTIVES: Osteosarcoma is a primary malignancy of bone. Current therapy includes neoadjuvant chemotherapy, surgery, and postoperative (adjuvant) chemotherapy. Prolonged treatment with chemotherapeutic agents may place patients at increased risk for complications including secondary malignancy. The authors have had promising results with neoadjuvant therapy and surgery alone in the treatment of osteosarcoma. This study retrospectively examines neoadjuvant therapy and surgery alone for the treatment of primary osteosarcoma of bone with no evidence of distant metastases. METHODS: Fifty-four patients, with localized osteosarcoma of bone received neoadjuvant therapy followed by definitive surgical resection. Thirty-five patients received chemotherapy after surgery (adjuvant group) and nineteen patients were followed without postoperative chemotherapy (no adjuvant group). RESULTS: Tumor necrosis was predictive of survival. Kaplan-Meier analysis revealed the use of postoperative chemotherapy was not a predictor of improved outcome. Four patients in the adjuvant therapy group died of secondary malignancy compared with none of the no adjuvant therapy group. Patient age, sex, race, and tumor location were not predictive of survival. CONCLUSIONS: The use of adjuvant chemotherapy in the treatment of localized osteosarcoma of bone did not increase survival after neoadjuvant therapy and definitive surgical therapy. Instead, there was an increased incidence of secondary malignancy after its use.

Authors
Berend, KR; Pietrobon, R; Moore, JO; Dibernardo, L; Harrelson, JM; Scully, SP
MLA Citation
Berend, KR, Pietrobon, R, Moore, JO, Dibernardo, L, Harrelson, JM, and Scully, SP. "Adjuvant chemotherapy for osteosarcoma may not increase survival after neoadjuvant chemotherapy and surgical resection." J Surg Oncol 78.3 (November 2001): 162-170.
PMID
11745799
Source
pubmed
Published In
Journal of Surgical Oncology
Volume
78
Issue
3
Publish Date
2001
Start Page
162
End Page
170

Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine.

The treatment of older patients with acute myeloid leukemia (AML) remains unsatisfactory, with complete remission (CR) achieved in only approximately 50% and long-term disease-free survival in 10% to 20%. Three hundred eighty-eight patients (60 years of age and older) with newly diagnosed de novo AML were randomly assigned to receive placebo (P) or granulocyte-macrophage colony-stimulating factor (GM-CSF) or GM in a double-blind manner, beginning 1 day after the completion of 3 days of daunorubicin and 7 days of cytarabine therapy. No differences were found in the rates of leukemic regrowth, CR, or infectious complications in either arm. Of 205 patients who achieved CR, 169 were medically well and were randomized to receive cytarabine alone or a combination of cytarabine and mitoxantrone. With a median follow-up of 7.7 years, the median disease-free survival times were 11 months and 10 months for those randomized to cytarabine or cytarabine/mitoxantrone, respectively. Rates of relapse, excluding deaths in CR, were 77% for cytarabine and 82% for cytarabine/mitoxantrone. Induction randomization had no effect on leukemic relapse rate or remission duration in either postremission arm. Because cytarabine/mitoxantrone was more toxic and no more effective than cytarabine, it was concluded that this higher-dose therapy had no benefit in the postremission management of older patients with de novo AML. These results suggest the need to develop novel therapeutic strategies for these patients. (Blood. 2001;98:548-553)

Authors
Stone, RM; Berg, DT; George, SL; Dodge, RK; Paciucci, PA; Schulman, PP; Lee, EJ; Moore, JO; Powell, BL; Baer, MR; Bloomfield, CD; Schiffer, CA
MLA Citation
Stone, RM, Berg, DT, George, SL, Dodge, RK, Paciucci, PA, Schulman, PP, Lee, EJ, Moore, JO, Powell, BL, Baer, MR, Bloomfield, CD, and Schiffer, CA. "Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine." Blood 98.3 (August 1, 2001): 548-553.
PMID
11468148
Source
pubmed
Published In
Blood
Volume
98
Issue
3
Publish Date
2001
Start Page
548
End Page
553

High frequency of immunophenotype changes in acute myeloid leukemia at relapse: Implications for residual disease detection (Cancer and Leukemia Group B Study 8361)

Multiparameter flow cytometry (MFC) has the potential to allow for sensitive and specific monitoring of residual disease (RD) in acute myeloid leukemia (AML). The use of MFC for RD monitoring assumes that AML cells identified by their immunophenotype at diagnosis can be detected during remission and at relapse. AML cells from 136 patients were immunophenotyped by MFC at diagnosis and at first relapse using 9 panels of 3 monoclonal antibodies. Immunophenotype changes occurred in 124 patients (91%); they consisted of gains or losses of discrete leukemia cell populations resolved by MFC (42 patients) and gains or losses of antigens on leukemia cell populations present at both time points (108 patients). Antigen expression defining unusual phenotypes changed frequently: CD13, CD33, and CD34, absent at diagnosis in 3, 33, and 47 cases, respectively, were gained at relapse in 2 (67%), 15 (45%), and 17 (36%); CD56, CD19, and CD14, present at diagnosis in 5, 16, and 20 cases, were lost at relapse in 2 (40%), 6 (38%), and 8 (40%). Leukemia cell gates created in pretreatment samples using each 3-antibody panel allowed identification of relapse AML cells in only 68% to 91% of cases, but use of 8 3-antibody panels, which included antibodies to a total of 16 antigens, allowed identification of relapse AML cells in all cases. Thus, the immunophenotype of AML cells is markedly unstable; nevertheless, despite this instability, MFC has the potential to identify RD in AML if multiple antibody panels are used at all time points. © 2001 by The American Society of Hematology.

Authors
Baer, MR; Stewart, CC; Dodgé, RK; Leget, G; Suie, N; Mrózek, K; Schiffer, CA; Powell, BL; Kolitz, JE; Moore, JO; Stone, RM; Davey, FR; Carroll, AJ; Larson, RA; Bloomfield, CD
MLA Citation
Baer, MR, Stewart, CC, Dodgé, RK, Leget, G, Suie, N, Mrózek, K, Schiffer, CA, Powell, BL, Kolitz, JE, Moore, JO, Stone, RM, Davey, FR, Carroll, AJ, Larson, RA, and Bloomfield, CD. "High frequency of immunophenotype changes in acute myeloid leukemia at relapse: Implications for residual disease detection (Cancer and Leukemia Group B Study 8361)." Blood 97.11 (2001): 3574-3580.
PMID
11369653
Source
scival
Published In
Blood
Volume
97
Issue
11
Publish Date
2001
Start Page
3574
End Page
3580
DOI
10.1182/blood.V97.11.3574

Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia

Purpose: To determine the maximum-tolerated dose, pharmacokinetic interaction, and activity of PSC 833 compared with daunorubicin (DNR) and cytarabine in patients with poor-risk acute myeloid leukemia. Patients and Methods: Patients received ara-C 3 g/m2/d on 5 consecutive days, followed by an IV loading dose of PSC 833 (1.5 mg/kg) and an 84-hour continuous infusion escalating from 6, 9, or 10 mg/kg/d. Daunorubicin was administered as a 72-hour continuous infusion at 34 or 45 mg/kg/d. Responding patients received consolidation chemotherapy with DNR pharmacokinetics performed without PSC-833 on day 1, and with PSC-833 on day 4. Response was correlated with expression of P-glycoprotein and lung resistance protein (LRP), and in vitro sensitization of leukemia progenitors to DNR cytotoxicity by PSC 833. Results: All 43 patients are assessable for toxicity and response. Grade 3 or greater hyperbilirubinemia (70%) was the only dose-dependent toxicity. Four patients (9%) succumbed to treatment-related complications. Twentyone patients (49%) achieved a complete remission or restored chronic phase, including 10 of 20 patients treated at the maximum-tolerated dose of 10 mg/kg/d of PSC-833 and 45 mg/m2 of DNR. The 95% confidence interval for complete response was 33.9% to 63.7%. Administration of PSC 833 did not alter the mean area under the curve for DNR, although clearance decreased approximately two-fold (P = .04). Daunorubicinol clearance decreased 3.3-fold (P = .016). Remission rates were not effected by mdr-1 expression, but LRP overexpression was associated with chemotherapy resistance. Conclusion: Combined treatment with infused PSC 833 and DNR is well tolerated and has activity in patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays elimination of daunorubicinol, but yields variable changes in DNR systemic exposure. © 2001 by American Society of Clinical Oncology.

Authors
Dorr, R; Karanes, C; Spier, C; Grogan, T; Greer, J; Moore, J; Weinberger, B; Schiller, G; Pearce, T; Litchman, M; Dalton, W; Roe, D; List, AF
MLA Citation
Dorr, R, Karanes, C, Spier, C, Grogan, T, Greer, J, Moore, J, Weinberger, B, Schiller, G, Pearce, T, Litchman, M, Dalton, W, Roe, D, and List, AF. "Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia." Journal of Clinical Oncology 19.6 (2001): 1589-1599.
PMID
11250987
Source
scival
Published In
Journal of Clinical Oncology
Volume
19
Issue
6
Publish Date
2001
Start Page
1589
End Page
1599

Post transplant CD8+ gammadelta T-cell lymphoma associated with human herpes virus-6 infection.

Gammadelta T-cell lymphoma is a rare T-cell lymphoproliferative disorder that has been reported in both immunocompetent and immunocompromised persons. This report describes a forty eight year old patient who developed gammadelta T-cell lymphoma four years after undergoing living-related kidney transplantation. The lymphoma expressed CD2, CD3, CD7, CD8 and CD56, and the gammadelta T-cell receptor and did not express CD5, CD4 and the alphabeta T-cell receptor. In addition, HHV-6 was cultured from the patient's bone marrow, marking the first time that this virus has been associated with gammadelta T-cell lymphoma. Since all patients with gammadelta T-cell lymphoma described to date have responded poorly to standard combination chemotherapies, the patient was treated with the purine analogue 2-chlorodeoxyadenosine. While he responded transiently to treatment, long term remission was not achieved indicating that additional therapeutic approches still need to be developed, for the management of this disorder.

Authors
Lin, WC; Moore, JO; Mann, KP; Traweek, ST; Smith, C
MLA Citation
Lin, WC, Moore, JO, Mann, KP, Traweek, ST, and Smith, C. "Post transplant CD8+ gammadelta T-cell lymphoma associated with human herpes virus-6 infection." Leuk Lymphoma 33.3-4 (April 1999): 377-384. (Review)
PMID
10221519
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
33
Issue
3-4
Publish Date
1999
Start Page
377
End Page
384
DOI
10.3109/10428199909058439

Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered

Purpose: To examine the effect of single compared with repetitive (at least three) cycles of high-dose cytarabine after induction therapy for patients with acute myeloid leukemia (AML) who have the t(8;21)(q22;q22) karyotype. Patients and Methods: Patients entered onto the study had AML and t(8;21) and attained a complete remission on four successive Cancer and Leukemia Group B studies. In these studies, either ≥ three cycles of high- dose cytarabine or one cycle of high-dose cytarabine was administered, followed by sequential cyclophosphamide/etoposide and mitoxantrone/diaziquone with or without filgrastim support. Outcomes of these two groups of t(8;21) patients were compared. Results: A total of 50 patients with centrally reviewed AML and t(8;21) were assigned to receive one (n = 29) or ≥ three cycles (n = 21) of high-dose cytarabine as postinduction therapy. The clinical features of these two groups of patients were similar. Initial remission duration for t(8;21) patients assigned to one cycle of high-dose cytarabine was significantly inferior (P = .03), with 62% of patients experiencing relapse with a median failure-free survival of 10.5 months, compared with the group of patients who received ≥ three cycles, in which only 19% experienced relapse and failure-free survival is estimated to be greater than 35 months. Furthermore, overall survival was also significantly compromised (P = .04) in patients assigned to one cycle of high-dose cytarabine, with 59% having died as a consequence of AML, compared with 24% of those who received ≥ three cycles of high-dose cytarabine. Conclusion: These data demonstrate that failure-free survival and overall survival of patients with t(8; 21)(q22;q22) may be compromised by treatment approaches that do not include sequential high-dose cytarabine therapy.

Authors
Byrd, JC; Dodge, RK; Carroll, A; Baer, MR; Edwards, C; Stamberg, J; Qumsiyeh, M; Moore, JO; Mayer, RJ; Davey, F; Schiffer, CA; Bloomfield, CD
MLA Citation
Byrd, JC, Dodge, RK, Carroll, A, Baer, MR, Edwards, C, Stamberg, J, Qumsiyeh, M, Moore, JO, Mayer, RJ, Davey, F, Schiffer, CA, and Bloomfield, CD. "Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered." Journal of Clinical Oncology 17.12 (1999): 3767-3775.
PMID
10577848
Source
scival
Published In
Journal of Clinical Oncology
Volume
17
Issue
12
Publish Date
1999
Start Page
3767
End Page
3775

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

Follicular mucinosis as a presenting sign of acute myeloblastic leukemia

Follicular mucinosis is often associated with mycosis fungoides and has been rarely observed to occur with other neoplastic and inflammatory conditions. We describe a 60-year-old patient with follicular mucinosis who later developed acute myelogenous leukemia. This is the first reported case of follicular mucinosis as a presenting sign of acute myeloblastic leukemia in the absence of mycosis fungoides or leukemia cutis.

Authors
Sumner, WT; Grichnik, JM; Shea, CR; Moore, JO; Miller, WS; Burton, CS
MLA Citation
Sumner, WT, Grichnik, JM, Shea, CR, Moore, JO, Miller, WS, and Burton, CS. "Follicular mucinosis as a presenting sign of acute myeloblastic leukemia." Journal of the American Academy of Dermatology 38.5 II (1998): 803-805.
Source
scival
Published In
Journal of The American Academy of Dermatology
Volume
38
Issue
5 II
Publish Date
1998
Start Page
803
End Page
805

Neural cell adhesion molecule (CD56)-positive acute myelogenous leukemia and myelodysplastic and myeloproliferative syndromes.

The CD56 antigen is normally expressed on natural-killer cells but has additionally been shown to be present on a variety of hematologic malignancies, including a subset of acute myelogenous leukemia (AML). There is disagreement, however, about its prognostic significance and its association with specific cytogenetic abnormalities. All clinical samples from June 1994, through September 1995, with increased myeloblasts were analyzed by multiparameter flow cytometry for anomalous expression of CD56. Patients with CD56+ blast cells were selected, and morphologic review was performed. Clinical information was obtained, and cytogenetic data were reviewed. Southern blot analysis to detect rearrangement of the mixed lineage leukemia (MLL) gene was performed when possible. The samples from 23 of 114 patients studied demonstrated anomalous expression of CD56 on myeloblasts, including patients with AML, myelodysplastic syndromes (MDS), and chronic myelogenous leukemia in blast crisis. The samples from 10 of 15 patients with CD56+ AML demonstrated at least partial monocytic differentiation. Dysplastic features were displayed in the samples of 12 patients. Correlation with specific cytogenetic abnormalities was not found. The MLL gene was rearranged in five of 18 patients. Seventeen patients have died, with a median survival of 4.6 months for patients with AML. Three have sustained a complete remission. One has findings of high-grade myelodysplastic syndrome. Two were unavailable for follow-up. Expression of CD56 was found in 20% of patients with increased myeloblasts, including patients with high-grade MDS, chronic myelogenous leukemia in blast crisis, and AML. This phenotype was associated with dysplasia, monocytic differentiation, and rearrangement of the MLL gene.

Authors
Mann, KP; DeCastro, CM; Liu, J; Moore, JO; Bigner, SH; Traweek, ST
MLA Citation
Mann, KP, DeCastro, CM, Liu, J, Moore, JO, Bigner, SH, and Traweek, ST. "Neural cell adhesion molecule (CD56)-positive acute myelogenous leukemia and myelodysplastic and myeloproliferative syndromes." Am J Clin Pathol 107.6 (June 1997): 653-660.
PMID
9169661
Source
pubmed
Published In
American Journal of Clinical Pathology
Volume
107
Issue
6
Publish Date
1997
Start Page
653
End Page
660

Granulocyte-colony stimulating factor (filgrastim) accelerates granulocyte recovery after intensive postremission chemotherapy for acute myeloid leukemia with aziridinyl benzoquinone and mitoxantrone: Cancer and Leukemia Group B study 9022.

This study evaluated the effect of filgrastim (granulocyte colony-stimulating factor [G-CSF]) on the duration of granulocytopenia and thrombocytopenia after intensive consolidation therapy with diaziquone (AZO) and mitroxantrone for patients less than 60 years of age with acute myeloid leukemia (AML) in complete remission. Patients less than 60 years of age with AML who achieved complete remission (CR) with daunorubicin and cytarabine induction therapy, were scheduled to receive three sequential courses of high-dose cytarabine, cyclophosphamide/etoposide, AZQ, and mitroxantrone in a pilot study to determine their tolerance of these three sequential consolidation regimens. The initial patients treated with AZQ and mitroxantrone experienced prolonged bone marrow suppression and, therefore, subsequent cohorts were treated with G-CSF, 5 micrograms/kg, beginning the day after completion of the third cycle of chemotherapy. There was a marked decrease in the duration of granulocytopenia less than 500/microL in two groups of patients receiving two different dose levels of AZQ and the same dose of mitoxantrone compared with patients not receiving the G-CSF. There was also a decrease in the need for hospitalization, as well as the duration of hospitalization. There was a trend towards shortening of the duration of thromobocytopenia, as well. The duration of complete remission and overall survival was similar in patients who received or did not receive G-CSF. G-CSF markedly shortened the duration of granulocytopenia in patients with AML receiving intensive postremission consolidation with AZQ and mitoxantrone. There was no adverse effect on CR duration or survival.

Authors
Moore, JO; Dodge, RK; Amrein, PC; Kolitz, J; Lee, EJ; Powell, B; Godfrey, S; Robert, F; Schiffer, CA
MLA Citation
Moore, JO, Dodge, RK, Amrein, PC, Kolitz, J, Lee, EJ, Powell, B, Godfrey, S, Robert, F, and Schiffer, CA. "Granulocyte-colony stimulating factor (filgrastim) accelerates granulocyte recovery after intensive postremission chemotherapy for acute myeloid leukemia with aziridinyl benzoquinone and mitoxantrone: Cancer and Leukemia Group B study 9022." Blood 89.3 (February 1, 1997): 780-788.
PMID
9028308
Source
pubmed
Published In
Blood
Volume
89
Issue
3
Publish Date
1997
Start Page
780
End Page
788

Craniocerebral plasmacytoma: MR features.

We report the MR imaging findings in two patients with solitary craniocerebral plasmacytoma, a benign plasma cell tumor that can arise from the skull, the dura, or, rarely, the brain. In both patients, the lesion was extraaxial and nearly isointense with gray matter on T2-weighted MR images, and diffusely enhanced after administration of contrast material, bearing some similarities to meningioma. A diagnosis of solitary craniocerebral plasmacytoma should be considered when a mass with these imaging features is seen, because total excision may not be necessary for this radiosensitive tumor.

Authors
Provenzale, JM; Schaefer, P; Traweek, ST; Ferry, J; Moore, JO; Friedman, AH; McLendon, RE
MLA Citation
Provenzale, JM, Schaefer, P, Traweek, ST, Ferry, J, Moore, JO, Friedman, AH, and McLendon, RE. "Craniocerebral plasmacytoma: MR features." AJNR Am J Neuroradiol 18.2 (February 1997): 389-392.
PMID
9111682
Source
pubmed
Published In
American Journal of Neuroradiology
Volume
18
Issue
2
Publish Date
1997
Start Page
389
End Page
392

Arthritis syndromes associated with human T cell lymphotropic virus type I infection.

Arthritis syndromes occur associated with HTLV-I infection both in the presence and in the absence of clinical ATL, and polyarthritis may be the presenting manifestation of HTLV-I-associated ATL. In both clinical settings, HTLV-I-infected T cells home to affected joints, and tax-transgenic mouse studies have suggested a pathogenic role for the HTLV-I tax gene in inducing synovial cell proliferation in HAA. Understanding the pathogenesis of rheumatoid arthritis-like arthritis syndromes that occur in the setting of HTLV-I infection should also provide insights into understanding of cellular and molecular mechanisms of synovial cell proliferation in HTLV-I-negative rheumatoid arthritis.

Authors
McCallum, RM; Patel, DD; Moore, JO; Haynes, BF
MLA Citation
McCallum, RM, Patel, DD, Moore, JO, and Haynes, BF. "Arthritis syndromes associated with human T cell lymphotropic virus type I infection." Med Clin North Am 81.1 (January 1997): 261-276. (Review)
PMID
9012764
Source
pubmed
Published In
Medical Clinics of North America
Volume
81
Issue
1
Publish Date
1997
Start Page
261
End Page
276

Adult patients with de novo acute myeloid leukemia and t(9;11)(p22;q23) have a superior outcome to patients with other translocations involving band 11q23: A Cancer and Leukemia Group B Study

Following reports of childhood acute myeloid leukemia (AML) showing that patients with t(9;11)(p22;q23) have a better prognosis than those with translocations between 11q23 and other chromosomes, we compared response to therapy and survival of 24 adult de novo AML patients with t(9; 11) with those of 23 patients with other 11q23 translocations [t(11q23)]. Apart from a higher proportion of French-American-British (FAB) M5 subtype in the t(9;11) group (83% v 43%, P = .006), the patients with t(9;11) did not differ significantly from patients with t(11q23) in terms of their presenting clinical or hematologic features. Patients with t(9;11) more frequently had an extra chromosome(s) 8 or 8q as secondary abnormalities (46% v 9%, P = .008). All patients received standard cytarabine and daunorubicin induction therapy, and most of them also received cytarabine-based intensification treatment. Two patients, both with t(9;11), underwent bone marrow transplantation (BMT) in first complete remission (CR). Nineteen patients (79%) with t(9;11) and 13 (57%) with t(11q23) achieved a CR (P = .13). The clinical outcome of patients with t(9;11) was significantly better: the median CR duration was 10.7 versus 8.9 months (P = .02), median event-free survival was 6.2 versus 2.2 months (P = .009), and median survival was 13.2 versus 7.7 months (P = .009). All patients with t(11q23) have died, whereas seven (29%) patients with t(9;11) remain alive in first CR. Seven of eight patients with t(9;11) who received postremission regimens with cytarabine at a dose of 100 (four patients) or 400 mg/m2 (2 patients) or who did not receive postremission therapy (2 patients) have relapsed. In contrast, 7 (64%) of 11 patients who received intensive postremission chemotherapy with high-dose cytarabine (at a dose 3 g/m2) (5 patients), or underwent BMT (2 patients) remain in continuous CR. We conclude that the outcome of adults with de novo AML and t(9;11) is more favorable than that of adults with other 11q23 translocations; this is especially true for t(9;11) patients who receive intensive postremission therapy.

Authors
Mrózek, K; Heinonen, K; Lawrence, D; Carroll, AJ; Koduru, PRK; Rao, KW; Strout, MP; Hutchison, RE; Moore, JO; Mayer, RJ; Schiffer, CA; Bloomfield, CD
MLA Citation
Mrózek, K, Heinonen, K, Lawrence, D, Carroll, AJ, Koduru, PRK, Rao, KW, Strout, MP, Hutchison, RE, Moore, JO, Mayer, RJ, Schiffer, CA, and Bloomfield, CD. "Adult patients with de novo acute myeloid leukemia and t(9;11)(p22;q23) have a superior outcome to patients with other translocations involving band 11q23: A Cancer and Leukemia Group B Study." Blood 90.11 (1997): 4532-4538.
PMID
9373264
Source
scival
Published In
Blood
Volume
90
Issue
11
Publish Date
1997
Start Page
4532
End Page
4538

Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): Results from Cancer and Leukemia Group B 8461

Purpose: To examine the prognostic significance of extramedullary leukemia (EML) at presentation in patients with t(8;21)(q22;q22) karyotype. Patients and Methods: Consecutive patients with t(8;21) treated on Cancer and Leukemia Group B de nova acute myeloid leukemia (AML) treatment studies were examined for the presence of EML (granulocytic sarcoma, subcutaneous nodules, leukemia cutis, or meningeal leukemia) at initial presentation. Clinical features and outcome of t(8;21) patients with and without EML were compared. Results: Of 84 patients with t(8;21), eight (9.5%) had EML manifesting as granulocytic sarcoma (five paraspinal, one breast, and one subcutaneous) or symptomatic meningeal leukemia (n = 1). The pretreatment prognostic variables of t(8;21) patients with and without EML were similar. The hematologic complete remission (CR) rate for t(8;21) patients with EML was 50% versus 92% for those without EML (P = .006). The median CR duration for EML patients was 14.7 months. Patients with EML had a shorter survival (P = 0.002, median 5.4 months versus 59.5 months). This poor outcome may relate to inadequate local (radiation or intrathecal) therapy for patients with spinal or meningeal EML, resulting in residual/recurrent EML following induction chemotherapy (n = 2) or at relapse (n = 1) and permanent neurologic deficits (n = 4). Only one of the EML patients received high-dose cytarabine (HDAC) intensification; this is the only EML patient remaining alive in CR. Conclusion: Patients with t(8;21) and EML have a low CR rate and overall survival. An aggressive local and systemic induction therapy should be considered for this patient subset. The effectiveness of HDAC intensification in t(8;21) patients with EML is uncertain and warrants further study.

Authors
Byrd, JC; Weiss, RB; Arthur, DC; Lawrence, D; Baer, MR; Davey, F; Trikha, ES; Carroll, AJ; Tantravahi, R; Qumsiyeh, M; Patil, SR; Moore, JO; Mayer, RJ; Schiffer, CA; Bloomfield, CD
MLA Citation
Byrd, JC, Weiss, RB, Arthur, DC, Lawrence, D, Baer, MR, Davey, F, Trikha, ES, Carroll, AJ, Tantravahi, R, Qumsiyeh, M, Patil, SR, Moore, JO, Mayer, RJ, Schiffer, CA, and Bloomfield, CD. "Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): Results from Cancer and Leukemia Group B 8461." Journal of Clinical Oncology 15.2 (1997): 466-475.
PMID
9053467
Source
scival
Published In
Journal of Clinical Oncology
Volume
15
Issue
2
Publish Date
1997
Start Page
466
End Page
475

A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy

Thrombocytopenia is a complication of cancer treatment that can limit dose intensity. Interleukin-11 (IL-11) is a growth factor that increases platelet production. We conducted a multicenter, randomized, placebo-controlled trial of recombinant human IL-11 (rhIL-11) in 93 patients with cancer who had already been transfused platelets for severe thrombocytopenia resulting from chemotherapy. The patients had received platelet transfusions for nadir platelet counts of ≤20,000/μL during the chemotherapy cycle immediately preceding study entry. Chemotherapy was continued during the study without dose reduction. Patients were randomized to receive placebo or rhIL-11 at 50 or 25 μg/kg subcutaneously once daily for 14 to 21 days beginning 1 day after chemotherapy. Eight of 27 (30%) evaluable patients treated with rhIL- 11 at a dose of 50 μg/kg did not require platelet transfusions versus 1 of 27 (4%) patients who received placebo (P < .05). Five of 28 (18%) patients treated with rhIL-11 at 25 μg/kg avoided platelet transfusions (P = .23). Side effects were fatigue and cardiovascular symptoms, including a low incidence of atrial arrhythmias and syncope. There were no differences among treatment groups in the incidence of neutropenic fever, days of hospitalization, or number of red blood cell transfusions. This study shows that rhIL-11 treatment at a dose of 50 μg/kg significantly increases the likelihood that patients who have already been transfused platelets for severe chemotherapy-induced thrombocytopenia will not require platelet transfusions during a subsequent chemotherapy cycle.

Authors
Tepler, I; Elias, L; II, JWS; Hussein, M; Rosen, G; Chang, AY-C; Moore, JO; Gordon, MS; Kuca, B; Beach, KJ; Loewy, JW; Garnick, MB; Kaye, JA
MLA Citation
Tepler, I, Elias, L, II, JWS, Hussein, M, Rosen, G, Chang, AY-C, Moore, JO, Gordon, MS, Kuca, B, Beach, KJ, Loewy, JW, Garnick, MB, and Kaye, JA. "A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy." Blood 87.9 (1996): 3607-3614.
PMID
8611684
Source
scival
Published In
Blood
Volume
87
Issue
9
Publish Date
1996
Start Page
3607
End Page
3614

Nitric oxide modulation of the growth and differentiation of freshly isolated acute non-lymphocytic leukemia cells.

Freshly isolated acute non-lymphocytic leukemia (ANLL) cells were treated with the nitric oxide (NO)-liberating compounds sodium nitroprusside or S-nitrosoacetyl penicillamine and analyzed for viability, growth, and differentiation at 3-5 days. NO decreased the viability and the growth of freshly isolated ANLL cells in vitro. NO treatment significantly increased expression of CD14 in blast cells from patients with M5 ANLL, and increased at least one differentiation parameter in M4 or M5 cells. It had little or no effect on parameters of differentiation in other ANLL cells. We conclude that in vitro culture with NO decreases the growth and viability of most freshly isolated ANLL cells. NO also induces the differentiation of ANLL cells with a monocytic phenotype.

Authors
Shami, PJ; Moore, JO; Gockerman, JP; Hathorn, JW; Misukonis, MA; Weinberg, JB
MLA Citation
Shami, PJ, Moore, JO, Gockerman, JP, Hathorn, JW, Misukonis, MA, and Weinberg, JB. "Nitric oxide modulation of the growth and differentiation of freshly isolated acute non-lymphocytic leukemia cells." Leuk Res 19.8 (August 1995): 527-533.
PMID
7658698
Source
pubmed
Published In
Leukemia Research
Volume
19
Issue
8
Publish Date
1995
Start Page
527
End Page
533

Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B.

BACKGROUND: Elderly patients with primary acute myelogenous leukemia (AML) are less likely to enter remission than younger adults, in part because of a higher mortality rate related to severe myelosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to shorten the duration of neutropenia and decrease infectious complications when administered after chemotherapy to patients with lymphomas and solid tumors. METHODS: We randomly assigned 388 patients 60 years of age or older who had newly diagnosed primary AML to receive placebo or GM-CSF (5 micrograms per kilogram of body weight per day intravenously over a period of six hours) in a double-blind manner, beginning the day after the completion of three days of daunorubicin (45 mg per square meter of body-surface area per day) and seven days of cytarabine (200 mg per square meter per day by continuous intravenous infusion). If leukemia cells persisted in the marrow three weeks after the initiation of chemotherapy, further daunorubicin (two days) and cytarabine (five days) were administered. GM-CSF or placebo was given daily until the neutrophil count was at least 1000 per cubic millimeter, there was evidence of the regrowth of leukemia, or severe toxic effects attributable to the study infusion occurred. Patients who had a complete remission were then randomly assigned to receive one of two intensification regimens. RESULTS: Of 388 patients (median age, 69 years), 193 were randomly assigned to receive GM-CSF and 195 to placebo. The rate of complete remission was 51 percent (95 percent confidence interval, 44 to 59 percent) among those assigned to GM-CSF and 54 percent (95 percent confidence interval, 47 to 61 percent) among those assigned to receive placebo (P = 0.61). The reasons for failure (early death, death during marrow hypoplasia, and persistent leukemia), the incidence of severe or lethal infection, and the incidence of the regrowth of leukemia (2 percent overall) were similar in the two groups. The median duration of neutropenia was slightly shorter (P = 0.02) in the patients who received GM-CSF (15 days) than in those who received placebo (17 days), but the clinical importance of this result was minimal because the growth factor failed to lower the treatment-related mortality rate or improve the rate of complete remission. CONCLUSIONS: GM-CSF, in the dose and schedule we used, does not stimulate the regrowth of leukemia, but it also does not decrease the severe myelosuppressive consequences of initial chemotherapy or improve the response rate in patients 60 years of age or older with primary AML. It should not be recommended for use in such patients.

Authors
Stone, RM; Berg, DT; George, SL; Dodge, RK; Paciucci, PA; Schulman, P; Lee, EJ; Moore, JO; Powell, BL; Schiffer, CA
MLA Citation
Stone, RM, Berg, DT, George, SL, Dodge, RK, Paciucci, PA, Schulman, P, Lee, EJ, Moore, JO, Powell, BL, and Schiffer, CA. "Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B." N Engl J Med 332.25 (June 22, 1995): 1671-1677.
PMID
7760868
Source
pubmed
Published In
The New England journal of medicine
Volume
332
Issue
25
Publish Date
1995
Start Page
1671
End Page
1677
DOI
10.1056/NEJM199506223322503

Predictors of outcome of tricuspid valve replacement in carcinoid heart disease.

The cardiac valvular surgical experience of patients in the Duke Carcinoid Database was reviewed to assess operative outcome. Of the 604 patients in the database, 19 patients with carcinoid heart disease were identified by cardiac catheterization or echocardiography, or both. Eight of these underwent tricuspid valve replacement surgery with bioprostheses (2 also had open pulmonic valvuloplasty). Compared with patients medically managed, surgically treated patients were similar with the exception that they had higher right atrial mean (17 +/- 6 vs 9 +/- 4 mm Hg, p = 0.03) and v-wave (27 +/- 6 vs 17 +/- 7 mm Hg, p = 0.04) pressures. Of the 8 surgical patients, 5 (63%) died within 30 days. Causes of death included tricuspid valve thrombosis, cerebral vascular accident, coagulopathy, renal failure, and intractable right heart failure. High comorbidity was present in all 8 patients. There was a weak trend (p = 0.17) toward lower Charlson comorbidity indexes in survivors (6.7 +/- 0.6) compared with nonsurvivors (7.6 +/- 0.9). Age was significantly lower (p = 0.036) in survivors (46 +/- 13 years) compared with nonsurvivors (69 +/- 4 years). Extended follow-up revealed 2 patients who survived beyond a decade. Review of 47 carcinoid valve replacement cases (Duke Carcinoid Database and 39 published cases) revealed a 30-day mortality of 56% for patients > 60 years of age, and 0% for those < or = 60 years of age (p < 0.0001). Although valve replacement surgery can afford prolonged palliation from carcinoid heart disease, it is associated with a significant mortality risk. Careful preoperative risk stratification by age and comorbidity may provide a means for optimal selection of surgical candidates.

Authors
Robiolio, PA; Rigolin, VH; Harrison, JK; Lowe, JE; Moore, JO; Bashore, TM; Feldman, JM
MLA Citation
Robiolio, PA, Rigolin, VH, Harrison, JK, Lowe, JE, Moore, JO, Bashore, TM, and Feldman, JM. "Predictors of outcome of tricuspid valve replacement in carcinoid heart disease." Am J Cardiol 75.7 (March 1, 1995): 485-488.
PMID
7863994
Source
pubmed
Published In
The American Journal of Cardiology
Volume
75
Issue
7
Publish Date
1995
Start Page
485
End Page
488

Long-term follow-up of a randomized post-induction therapy trial in acute myeloeenous leukemia (A Southeastern Cancer Study Group Trial)

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 200 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.

Authors
Vogler, WR; Weiner, RS; Moore, JO; Omura, GA; Bartolucci, AA; Stagg, M
MLA Citation
Vogler, WR, Weiner, RS, Moore, JO, Omura, GA, Bartolucci, AA, and Stagg, M. "Long-term follow-up of a randomized post-induction therapy trial in acute myeloeenous leukemia (A Southeastern Cancer Study Group Trial)." Leukemia 9.9 (1995): 1456-1460.
PMID
7544851
Source
scival
Published In
Leukemia
Volume
9
Issue
9
Publish Date
1995
Start Page
1456
End Page
1460

A pilot study of etoposide, vinblastine, and doxorubicin plus involved field irradiation in advanced, previously untreated Hodgkin's disease.

BACKGROUND: Advanced stage Hodgkin's disease (HD) usually is treated with combination chemotherapy with or without supplemental irradiation. The risk of significant acute and long term toxicity when the chemotherapy regimen contains alkylating agents has provided the impetus for the development of systemic combinations that do not include alkylating agents. This trial was designed to assess the toxicity and efficacy of a regimen of etoposide, vinblastine, and doxorubicin (EVA) as part of a combined modality approach in patients with moderate to high risk HD. METHODS: This was a prospective pilot study that included 26 previously untreated patients. They received 6 cycles of EVA, and complete responders received low dose (1500-2500 cGy) involved field radiation. RESULTS: Four patients were hospitalized for sepsis during chemotherapy. Complete response was achieved in 54% of patients, and 46% patients experienced induction failures. Two year failure-free survival is 44%, while 2 year overall survival is 86%. Median follow-up is 27 months. CONCLUSIONS: The EVA regimen is no more efficacious than other programs already in use and may be less so. It also is potentially leukemogenic because of the presence of etoposide. New combinations that do not contain etoposide should be explored in therapy programs for advanced HD in the hopes of discovering an efficacious treatment program that has minimal long term side effects.

Authors
Brizel, DM; Gockerman, JP; Crawford, J; Hathorn, JW; Moore, JO; Osborne, B; Prosnitz, LR
MLA Citation
Brizel, DM, Gockerman, JP, Crawford, J, Hathorn, JW, Moore, JO, Osborne, B, and Prosnitz, LR. "A pilot study of etoposide, vinblastine, and doxorubicin plus involved field irradiation in advanced, previously untreated Hodgkin's disease." Cancer 74.1 (July 1, 1994): 159-163.
PMID
8004571
Source
pubmed
Published In
Cancer
Volume
74
Issue
1
Publish Date
1994
Start Page
159
End Page
163

Hepatosplenic T-cell lymphoma: an unusual case of a gamma delta T-cell lymphoma with a blast-like terminal transformation.

We describe a case of a middle-aged women who presented with anemia and mild hepatosplenomegaly and who was found to have an unusual peripheral T-cell lymphoma with only subtle morphologically abnormal but mature-appearing cells noted in the blood and bone marrow. Less than 2 years after diagnosis the patient presented with an increasing white blood cell count to 26 x 10(9)/L, and numerous blasts were noted in the periphery. Flow cytometry studies showed cells with an unusual T-cell phenotype expressing the gamma delta T-cell receptor and restricted expression of the V delta 1 but not the V delta 2 protein, indicating the clonal nature of the proliferation. A clonal T-cell receptor gene rearrangement was seen with a V delta 1 probe. The patient died and was found at autopsy to have extensive hepatic sinusoidal infiltration by abnormal cells. The histopathologic, immunophenotypic, and molecular findings are those of "hepatosplenic T-cell lymphoma." In spite of the striking morphologic change during the course of the patient's disease the same phenotype and clonal rearrangement were found both at initial diagnosis and during terminal phase, indicating that this change represented a blast-like transformation of the patient's original lymphoproliferative disorder.

Authors
Mastovich, S; Ratech, H; Ware, RE; Moore, JO; Borowitz, MJ
MLA Citation
Mastovich, S, Ratech, H, Ware, RE, Moore, JO, and Borowitz, MJ. "Hepatosplenic T-cell lymphoma: an unusual case of a gamma delta T-cell lymphoma with a blast-like terminal transformation." Hum Pathol 25.1 (January 1994): 102-108.
PMID
8314255
Source
pubmed
Published In
Human Pathology
Volume
25
Issue
1
Publish Date
1994
Start Page
102
End Page
108

A phase III trial of high-dose cytosine arabinoside with or without etoposide in relapsed and refractory acute myelogenous leukemia. A Southeastern Cancer Study Group trial

A phase lll clinical trial was developed to test whether the addition of etoposide to a high-dose cytosine arabinoside regimen would improve the remission rate, duration of remission, and survival in relapsed and refractory patients with acute myelogenous leukemia. One hundred and thirty-one patients stratified by age, performance status, percentage of marrow blasts, platelet count, bilirubin and presence or absence of clinical infection, refractory or relapsed ( ± 9 months) were randomized to receive high-dose cytosine arabinoside, 3 g/m2 every 12 h for 6 days with or without three doses of etoposide, 100 mg/m2 days 7-9. Of 67 patients randomized to cytosine arabinoside alone, 31% obtained a complete remission with a median remission duration of 11.9 months. Of 66 patients randomized to the combination regimen, 38% obtained a complete remission with a median duration of 25 months. None of these differences were statistically significant. Significantly (p= 0.036) longer survival was seen in patients on the combination regimen under the age of 50. There was no difference in overall survival. Six and 8%, respectively, of patients were free of disease at 5 years. The addition of etoposide to a highdose cytosine arabinoside regimen had at best a marginal effect at the expense of some increase in toxicity.

Authors
Vogler, WR; McCarley, DL; Stagg, M; Bartolucci, AA; Moore, J; Martelo, O; Omura, GA
MLA Citation
Vogler, WR, McCarley, DL, Stagg, M, Bartolucci, AA, Moore, J, Martelo, O, and Omura, GA. "A phase III trial of high-dose cytosine arabinoside with or without etoposide in relapsed and refractory acute myelogenous leukemia. A Southeastern Cancer Study Group trial." Leukemia 8.11 (1994): 1847-1853.
PMID
7967730
Source
scival
Published In
Leukemia
Volume
8
Issue
11
Publish Date
1994
Start Page
1847
End Page
1853

Intensive postremission chemotherapy in adults with acute myeloid leukemia

Background. About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions. Methods. We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3- hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment. Results. Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). In contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups. Conclusions. These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.

Authors
Mayer, RJ; Davis, RB; Schiffer, CA; Berg, DT; Powell, BL; Schulman, P; Omura, GA; Moore, JO; McIntyre, OR; III, EF
MLA Citation
Mayer, RJ, Davis, RB, Schiffer, CA, Berg, DT, Powell, BL, Schulman, P, Omura, GA, Moore, JO, McIntyre, OR, and III, EF. "Intensive postremission chemotherapy in adults with acute myeloid leukemia." New England Journal of Medicine 331.14 (1994): 896-903.
PMID
8078551
Source
scival
Published In
The New England journal of medicine
Volume
331
Issue
14
Publish Date
1994
Start Page
896
End Page
903
DOI
10.1056/NEJM199410063311402

The syndrome of 5-fluorouracil cardiotoxicity. An elusive cardiopathy.

BACKGROUND: A case of reversible cardiogenic shock linked to 5-fluorouracil (5-FU) was observed. Recognizing the increasing use of 5-FU, the authors tried to map this syndrome. METHODS: They reviewed 134 additional case reports, retrieved information from literature searches, focused on clinical features, and discussed possible pathophysiologic findings and prevention of this syndrome. RESULTS: Although angina and electrocardiographic changes were common and reproducible (approximately 90% each), coronary artery disease was found in a few patients. A total of 33 patients had severe left ventricular dysfunction, 28 without evidence of myocardial infarction. The symptoms were responsive to conservative management (90%). CONCLUSIONS: Cardiac toxicity is a little known complication of 5-FU therapy, with an unknown but significant incidence. It is highly treatable.

Authors
Robben, NC; Pippas, AW; Moore, JO
MLA Citation
Robben, NC, Pippas, AW, and Moore, JO. "The syndrome of 5-fluorouracil cardiotoxicity. An elusive cardiopathy." Cancer 71.2 (January 15, 1993): 493-509. (Review)
PMID
8422644
Source
pubmed
Published In
Cancer
Volume
71
Issue
2
Publish Date
1993
Start Page
493
End Page
509

Cigarette smoking and risk of acute leukemia: Associations with morphology and cytogenetic abnormalities in bone marrow

Background: Cigarette smoking may be a risk factor for leukemia. No detailed biological mechanism has been proposed, but a causal link is made plausible by evidence of systemic effects of cigarette smoke and the presence in cigarette smoke of chemicals that have been associated with leukemia risk. Purpose: Our purpose was to investigate the leukemia risk associated with cigarette smoking in a multicenter case-control study of acute leukemias in adults. Methods: Adults aged 18-79 with newly diagnosed leukemia were contacted to participate in this epidemiologic study when they entered a clinical trial to be treated under protocols sponsored by Cancer and Leukemia Group B. Smoking histories for 610 patients with acute leukemia and 618 population control subjects were obtained by telephone interviews. We examined bone marrow samples and classified patients by morphology of leukocyte precursor cells according to the French-American-British (FAB) classification system and, for 378 patients, by the presence or absence of specific clonal chromosome abnormalities. We calculated odds ratios (ORs) for risk of leukemia associated with smoking cigarettes. ORs were adjusted for age, race, and sex. Results: Smoking was associated with only a modest increase in risk for leukemia overall (adjusted OR = 1.13; 95% confidence interval [CI] = 0.89-1.44). However, among participants aged 60 and older, smoking was associated with a twofold increase in risk for acute myeloid leukemia (AML) (OR = 1.96; 95% CI = 1.17-3.28) and a threefold increase in risk for acute lymphocytic leukemia (ALL) (OR = 3.40; 95% CI = 0.97-11.9). Among older persons, risks increased with amount and duration of smoking. Smoking was associated with increased risk for AML classified as FAB type M2 at all ages, with ORs of 1.70 (95% CI = 1.00-2.90) for those younger than 60 and 3.50 (95% CI = 1.53-8.03) for those aged 60 and older. Smoking was also associated with ALL type L2 at all ages, with ORs of 1.72 (95% CI = 0.90- 3.27) for those younger than 60 and 5.34 (95% CI = 1.03-27.6) for those who were older. Smoking was more common among patients with specific chromosome abnormalities in AML [-7 or 7q-, -Y, +13] and in ALL [t(9;22)(q34;q11)]. Conclusions: Cigarette smoking is associated with increased risk for leukemia and may lead to leukemias of specific morphologic and chromosomal types. The association varies with age. Implication: Examining discrete subtypes of disease may permit more accurate assessment of risk. As standardized morphologic classification and cytogenetic and molecular evaluation of leukemia patients becomes more common, epidemiologic studies that take advantage of these advances will begin to contribute to the identification of additional risk factors and mechanisms in acute leukemia.

Authors
Sandler, DP; Shore, DL; Anderson, JR; Davey, FR; Arthur, D; Mayer, RJ; Silver, RT; Weiss, RB; Moore, JO; Schiffer, CA; Wurster-Hill, DH; McIntyre, OR; Bloomfield, CD
MLA Citation
Sandler, DP, Shore, DL, Anderson, JR, Davey, FR, Arthur, D, Mayer, RJ, Silver, RT, Weiss, RB, Moore, JO, Schiffer, CA, Wurster-Hill, DH, McIntyre, OR, and Bloomfield, CD. "Cigarette smoking and risk of acute leukemia: Associations with morphology and cytogenetic abnormalities in bone marrow." Journal of the National Cancer Institute 85.24 (1993): 1994-2003.
PMID
8246285
Source
scival
Published In
Journal of the National Cancer Institute
Volume
85
Issue
24
Publish Date
1993
Start Page
1994
End Page
2003

CALGB Studies with Hematopoietic Growth Factors in Patients with AML

Authors
Schiffer, CA; Stone, RM; Peterson, BA; Moore, J
MLA Citation
Schiffer, CA, Stone, RM, Peterson, BA, and Moore, J. "CALGB Studies with Hematopoietic Growth Factors in Patients with AML." Leukemia & Lymphoma 7.sup2 (January 1992): 65-65.
Source
crossref
Published In
Leukemia & Lymphoma (Informa)
Volume
7
Issue
sup2
Publish Date
1992
Start Page
65
End Page
65
DOI
10.3109/10428199209058664

CALGB studies with hematopoietic growth factors in patients with AML

Authors
Schiffer, CA; Stone, RM; Peterson, BA; Moore, J
MLA Citation
Schiffer, CA, Stone, RM, Peterson, BA, and Moore, J. "CALGB studies with hematopoietic growth factors in patients with AML." Leukemia and Lymphoma 7.SUPPL. 2 (1992): 65--.
Source
scival
Published In
Leukemia and Lymphoma
Volume
7
Issue
SUPPL. 2
Publish Date
1992
Start Page
65-

The erythrocytes in paroxysmal nocturnal haemoglobinuria of intermediate sensitivity to complement lysis.

The sensitivity to lysis by complement of the erythrocytes of 56 patients with paroxysmal nocturnal haemoglobinuria (PNH) was compared to the membrane expression of decay accelerating factor (DAF, CD55), membrane inhibitor of reactive lysis (MIRL, CD59) and acetylcholinesterase (AChE). Most patients (36/50 72% in whom the analysis could be made) appeared to have erythrocytes of intermediate sensitivity to complement in the blood. These cells appeared as a discrete population of cells (PNH II cells), as a 'tail' of cells slightly less sensitive than the predominant PNH III cells (previously called PNH IIIb cells), or as a continuous spectrum of cells sensitive to complement. The PNH III cells totally lacked all three proteins (DAF, MIRL, AChE) by flow cytometric analysis whereas PNH I cells appeared to have normal or nearly normal amounts of each. The cells of intermediate sensitivity (PNH II) had coordinately decreased expression of all three proteins; the level of expression of DAF and MIRL paralleled the sensitivity of the cells to the haemolytic action of complement.

Authors
Rosse, WF; Hoffman, S; Campbell, M; Borowitz, M; Moore, JO; Parker, CJ
MLA Citation
Rosse, WF, Hoffman, S, Campbell, M, Borowitz, M, Moore, JO, and Parker, CJ. "The erythrocytes in paroxysmal nocturnal haemoglobinuria of intermediate sensitivity to complement lysis." Br J Haematol 79.1 (September 1991): 99-107.
PMID
1716964
Source
pubmed
Published In
British Journal of Haematology
Volume
79
Issue
1
Publish Date
1991
Start Page
99
End Page
107

Improved survival in advanced Hodgkin's disease with the use of combined modality therapy.

To compare the effectiveness of combined modality therapy and chemotherapy alone for the treatment of advanced Hodgkin's disease (Stages IIB-IV), records of 154 patients who achieved a complete or partial response to induction combination chemotherapy were analyzed. Sixty-seven patients received consolidation radiotherapy and 87 patients received no further treatment. Thirty of 154 patients participated in a prospective randomized trial of the Southeastern Cancer Study Group (SEG). Ten-year actuarial survival (Hodgkin's disease deaths only) was 93% for the combined modality therapy patients compared with 59% for the chemotherapy alone patients (p less than 0.0005). Combined modality therapy patients had an 87% 10-year actuarial freedom from relapse as opposed to 56% for the chemotherapy alone patients (p less than 0.0005). Relapse occurred in 33 of the chemotherapy alone patients, 28 (85%) being in sites involved at initial diagnosis. Seven combined modality therapy patients recurred with only two true in-field failures. Multi-variate analysis demonstrated treatment (combined modality) as the only variable affecting outcome. Patients prospectively treated with combined modality therapy in the Southeastern Cancer Study Group trial also showed a statistically significant improvement in both survival and freedom from relapse compared with patients receiving chemotherapy only. There was no apparent increase in toxicity from using combined modality therapy compared with chemotherapy. Three chemotherapy patients and one combined modality therapy patients developed acute leukemia.

Authors
Brizel, DM; Winer, EP; Prosnitz, LR; Scott, J; Crawford, J; Moore, JO; Gockerman, JP
MLA Citation
Brizel, DM, Winer, EP, Prosnitz, LR, Scott, J, Crawford, J, Moore, JO, and Gockerman, JP. "Improved survival in advanced Hodgkin's disease with the use of combined modality therapy." Int J Radiat Oncol Biol Phys 19.3 (September 1990): 535-542.
PMID
2211201
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
19
Issue
3
Publish Date
1990
Start Page
535
End Page
542

The Duke AFM Program. Intensive induction chemotherapy for metastatic breast cancer.

Forty-five patients have completed treatment with AFM, an intensive induction chemotherapy regimen composed of Adriamycin (doxorubicin, Adria Laboratories, Columbus, Ohio), 5-fluorouracil, and methotrexate with folinic acid rescue. This regimen was designed to produce rapid and extensive tumor shrinkage prior to high-dose alkylating agent chemotherapy with autologous marrow support. The overall response rate was 91%, and 38% of patients achieved complete clinical responses after a mean of 70 days on treatment. Hematologic and mucosal toxicity were extensive, but no toxic deaths were noted. AFM is a potent remission induction regimen for metastatic breast cancer, but its considerable toxicity suggests caution in its use for routine breast cancer treatment.

Authors
Jones, RB; Shpall, EJ; Shogan, J; Affronti, ML; Coniglio, D; Hart, L; Halperin, E; Iglehart, JD; Moore, J; Gockerman, J
MLA Citation
Jones, RB, Shpall, EJ, Shogan, J, Affronti, ML, Coniglio, D, Hart, L, Halperin, E, Iglehart, JD, Moore, J, and Gockerman, J. "The Duke AFM Program. Intensive induction chemotherapy for metastatic breast cancer." Cancer 66.3 (August 1, 1990): 431-436.
PMID
2364358
Source
pubmed
Published In
Cancer
Volume
66
Issue
3
Publish Date
1990
Start Page
431
End Page
436

Treatment of patients with recurrent gliomas with cyclophosphamide and vincristine.

Seventeen patients with recurrent gliomas were treated with the combination of cyclophosphamide and vincristine. All but one had previously received and failed chemotherapy. Cyclophosphamide was administered at doses ranging from 250 to 1000 mg/sq m by intravenous infusion on Days 1 and 2, and vincristine was given at a dose of 1.0 mg/sq m (2 mg maximal dose) intravenously on Day 1; cycles were repeated every 4 weeks. Clinical and radiographic improvement was observed in eight of 16 evaluable patients, and four other patients had stabilization of previously progressive disease. Four patients are alive and off treatment without evidence of recurrence for a median period of 37 months; these included an adult with a cerebral anaplastic astrocytoma now more than 51 months after therapy. Toxicity included moderately severe myelosuppression that required hospitalization in seven patients. These results indicate that the combination of cyclophosphamide and vincristine has activity in the treatment of recurrent gliomas, and warrant the use of these drugs in larger controlled studies, particularly if they can be used in conjunction with hematopoietic growth factors.

Authors
Longee, DC; Friedman, HS; Albright, RE; Burger, PC; Oakes, WJ; Moore, JO; Schold, SC
MLA Citation
Longee, DC, Friedman, HS, Albright, RE, Burger, PC, Oakes, WJ, Moore, JO, and Schold, SC. "Treatment of patients with recurrent gliomas with cyclophosphamide and vincristine." J Neurosurg 72.4 (April 1990): 583-588.
PMID
2319317
Source
pubmed
Published In
Journal of neurosurgery
Volume
72
Issue
4
Publish Date
1990
Start Page
583
End Page
588
DOI
10.3171/jns.1990.72.4.0583

Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL)

This phase III, randomized trial in previously untreated adults with ANLL compared mitoxantrone plus cytosine arabinoside with the CALGB "7 + 3" daunorubicin-based regimen. Two hundred evaluable patients (98 treated with the mitoxantrone-based regimen and 102 with the daunorubicin-based regimen) were included in the analysis of efficacy. The median age of the patients was 60 years. The induction regimen comprised cytosine arabinoside 100 mg/m2 by infusion daily for 7 days and mitoxantrone 12 mg/m2 or daunorubicin 45 mg/m2 daily for days 1-3. If needed, a second induction course was administered: cytosine arabinoside for 5 days and mitoxantrone or daunorubicln for 2 days. Postremission therapy consisted of two consolidation courses, identical to the second induction course. Sixty-three percent (62 of 98) of patients treated with mitoxantrone achieved complete remission (CR), compared to 53% (54 of 102) treated with daunorubicin. The median time to CR was 35 days in patients treated with mitoxantrone and 43 days for those treated with daunorubicin. Eighty-nine percent (55 of 62) of patients treated with mitoxantrone who entered complete remission achieved CR following one induction course, compared to 68% (37 of 54) of patients treated with daunorubicin who entered CR. The median duration of CR was 240 days in patients treated with mitoxantrone and 198 days in those treated with daunorubicin; the median length of survival was 328 days in patients who received mitoxantrone and 247 days in those who received daunorubucin. The toxicity profiles in patients treated with either of the two regimens were comparable in incidence and in severity. Patients treated with mitoxantrone required fewer median platelet units and were treated with fewer median days of intravenous antibiotics, compared to those who received daunorubicin. Mitoxantrone in combination with cytosine arabinoside is effective in previously untreated ANLL. Complete remissions occur more frequently after a single induction course of the mitoxantrone-based regimen, compared to the standard Cancer and Acute Leukemia Group B regimen. This should be explored in further trials.

Authors
Arlin, Z; Jr, DCC; Moore, J; Wiernik, P; Feldman, E; Saletan, S; Desai, P; Sia, L; Cartwright, K; Abramson, N; Weintraub, L; Rubin, A; Weaver, Z; Bickers, J; Gabriel, D; Hicks, W; Schade, S; Silver, R; Tranum, B; Dosik, H; Stein, R; Groppe, C; Villa, L; Dara, P; Doty, G; Dresdner, D; Wheeler, R; Karp, D; Kloss, R; Robinson, W
MLA Citation
Arlin, Z, Jr, DCC, Moore, J, Wiernik, P, Feldman, E, Saletan, S, Desai, P, Sia, L, Cartwright, K, Abramson, N, Weintraub, L, Rubin, A, Weaver, Z, Bickers, J, Gabriel, D, Hicks, W, Schade, S, Silver, R, Tranum, B, Dosik, H, Stein, R, Groppe, C, Villa, L, Dara, P, Doty, G, Dresdner, D, Wheeler, R, Karp, D, Kloss, R, and Robinson, W. "Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL)." Leukemia 4.3 (1990): 177-183.
PMID
2179638
Source
scival
Published In
Leukemia
Volume
4
Issue
3
Publish Date
1990
Start Page
177
End Page
183

Surgical management of pancreatic lymphoma.

The clinical and pathologic records of 12 patients with pancreatic lymphoma were reviewed retrospectively to determine distinguishing clinical features. Radiologically, all patients had large abdominal masses in the region of the pancreas. Preoperative percutaneous cytologic biopsy specimens failed to make the diagnosis, and two specimens were interpreted incorrectly as poorly differentiated adenocarcinoma. The diagnosis was difficult to make in two cases, even at laparotomy. Four patients underwent a biliary bypass, and two underwent a concomitant gastric or duodenal bypass. Two patients died postoperatively. Four patients responded well to chemotherapy and/or radiation therapy, and two did not have any recurrences at 3 and 7 years postoperatively. Although rare, lymphoma should be considered in patients with undiagnosed pancreatic masses. The diagnosis may only be made with appropriate preoperative or intraoperative suspicion, and treatment may be rewarding, particularly in comparison with pancreatic adenocarcinoma.

Authors
Mansour, GM; Cucchiaro, G; Niotis, MT; Fetter, BF; Moore, J; Rice, RR; Branum, GD; Meyers, WC
MLA Citation
Mansour, GM, Cucchiaro, G, Niotis, MT, Fetter, BF, Moore, J, Rice, RR, Branum, GD, and Meyers, WC. "Surgical management of pancreatic lymphoma." Arch Surg 124.11 (November 1989): 1287-1289.
PMID
2818182
Source
pubmed
Published In
Archives of Surgery
Volume
124
Issue
11
Publish Date
1989
Start Page
1287
End Page
1289

Monocytoid differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells induced by the glutamine antagonist acivicin.

Previously we showed that starvation of HL-60 promyelocytic leukemia cells for a single essential amino acid induced irreversible differentiation into more mature monocyte-like cells. Although not an essential amino acid, glutamine is important in the growth of normal and neoplastic cells. The glutamine analogue, alpha S,5S-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) inhibits several glutamine-utilizing enzymes and therefore depletes cells of certain metabolic end products. The current study was designed to examine in vitro the effects of acivicin on growth and differentiation of several established human myeloid leukemia cell lines, including the HL-60 cell line, and of freshly isolated cells from patients with acute nonlymphocytic leukemia (ANLL). Four-day culture of HL-60 cells with acivicin at concentrations of 0.1 to 10.0 micrograms/mL (0.56 to 56 nmol/L) decreased cell growth by 33% to 88% as compared with untreated control cells. Viability of cells was greater than 92% for untreated cells and 93% to 41% for acivicin-treated cells. Cells treated with acivicin differentiated along a monocytic pathway as shown by increased H2O2 production and alpha-naphthyl butyrate esterase (NSE) content. Differentiation was time and dose dependent, and was irreversible. Changes in H2O2 production and NSE content were partially abrogated by co-culture with 10 mmol/L exogenous cytidine and guanosine but not by co-culture with other nucleosides or glutamine. At these concentrations of acivicin, differentiation was associated with expression of the N-formyl-methyl-leucyl-phenylalanine-receptor (FMLP-R) on 8% to 29% of cells as compared with 8% for control cells. Acivicin potentiated the differentiating effects of interferon-gamma, tumor necrosis factor, dihydroxyvitamin D3, dimethylsulfoxide, and retinoic acid. Culture of cells from the U937 (monoblastic), K562 (erythroleukemia), and KG-1 (myeloblastic) cell lines resulted in decreased growth and viability, but not consistently in differentiation. Acivicin decreased survival of freshly isolated ANLL cells and increased their H2O2 production and NSE content. These results suggest that the glutamine analogue acivicin may be useful as a differentiating agent with antileukemia activity in patients with ANLL.

Authors
Nichols, KE; Chitneni, SR; Moore, JO; Weinberg, JB
MLA Citation
Nichols, KE, Chitneni, SR, Moore, JO, and Weinberg, JB. "Monocytoid differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells induced by the glutamine antagonist acivicin." Blood 74.5 (October 1989): 1728-1737.
PMID
2790198
Source
pubmed
Published In
Blood
Volume
74
Issue
5
Publish Date
1989
Start Page
1728
End Page
1737

Carcinoid tumors: iodine-131 MIBG scintigraphy.

Eighty-two patients with pathologically proved carcinoid tumors were examined with iodine-131 metaio-dobenzylguanidine (MIBG) scintigraphy. Localization scores of I-131 MIBG accumulation in the primary tumor or metastatic site ranged from 0 to 3+ on the basis of comparison with normal liver. I-131 MIBG uptake varied greatly in different patients with carcinoid tumors. The localization scores in known tumor sites were related to the location of the primary tumor in the stomach (1-3+ in two of five patients), pancreas (1-3+ in four of five patients), cecum (3+ in two of two patients), appendix (0 in one of one patient), jejunum (0 in one of one patient), Meckel diverticulum (3+ in one of one patient), terminal ileum (2-3+ in 19 of 28 patients), bronchus (3+ in one of nine patients), thymus (1+ in one of two patients), and unknown (2-3+ in 18 of 28 patients). Tumors of midgut origin concentrated I-131 MIBG more frequently than those of foregut origin. Uptake of I-131 MIBG was more likely if neurohumor levels, particularly serum serotonin, were elevated. There was no relationship of I-131 MIBG uptake to carcinoid syndrome. I-131 MIBG is useful in the determination of the location and extent of some carcinoid tumors, particularly those of midgut origin.

Authors
Hanson, MW; Feldman, JM; Blinder, RA; Moore, JO; Coleman, RE
MLA Citation
Hanson, MW, Feldman, JM, Blinder, RA, Moore, JO, and Coleman, RE. "Carcinoid tumors: iodine-131 MIBG scintigraphy." Radiology 172.3 (September 1989): 699-703.
PMID
2772175
Source
pubmed
Published In
Radiology
Volume
172
Issue
3
Publish Date
1989
Start Page
699
End Page
703
DOI
10.1148/radiology.172.3.2772175

Familial aggregation of multiple myeloma and central nervous system diseases.

Degenerative central nervous system diseases such as Alzheimer's disease and lymphoreticular malignancies such as multiple myeloma occur with increased frequency with advancing age. Relatives of early-onset Alzheimer's disease patients may have an increased risk of lymphoreticular malignancies. This led us to evaluate the family history of central nervous system diseases in a case-control study of multiple myeloma. Thirteen of 439 multiple myeloma cases had one or more first-degree relatives with degenerative or demyelinating central nervous system disease. In comparison, there were nine "positive" family histories in 1,317 matched hospital controls (relative risk = 4.4, 95% confidence interval = 1.9-10.3). Relative risks for the component categories of Parkinson's disease, multiple sclerosis, and miscellaneous degenerative central nervous system diseases were 3.0, 4.0 and 11.9, respectively. Our findings suggest that the degenerative and demyelinating central nervous system diseases and the lymphoreticular malignancies may comprise an etiologically related group of "protean diseases." These diseases may have a shared genetic susceptibility, possibly an immunologic abnormality. The varied disease manifestation in family members suggests a second necessary etiologic step of a variable and possibly environmental nature.

Authors
Grufferman, S; Cohen, HJ; Delzell, ES; Morrison, MC; Schold, SC; Moore, JO
MLA Citation
Grufferman, S, Cohen, HJ, Delzell, ES, Morrison, MC, Schold, SC, and Moore, JO. "Familial aggregation of multiple myeloma and central nervous system diseases." J Am Geriatr Soc 37.4 (April 1989): 303-309.
PMID
2921451
Source
pubmed
Published In
Journal of American Geriatrics Society
Volume
37
Issue
4
Publish Date
1989
Start Page
303
End Page
309

Clinicopathologic and cytogenic features of CD34 (My 10)-positive acute nonlymphocytic leukemia.

The authors performed membrane antigen phenotyping on 75 patients with acute nonlymphocytic leukemia with a panel of myeloid-associated monoclonal antibodies. The 34 patients (45%) with CD34-positive leukemia were not significantly different from the 41 with CD34-negative leukemia with respect to age, hemoglobin, white blood cell count, or platelet count at presentation, but their blasts were more likely to lack the CD15 or CD33 antigens and to have FAB M1 or M2 morphologic characteristics. CD34-positive leukemia was more likely to arise after chemotherapy. Patients with CD34-positive leukemia were less likely to enter a complete remission even when analysis was limited to those patients receiving a high-dose induction-type chemotherapy regimen. Giemsa-banding karyotyping studies were obtained in 55 of the cases. In 30 of these cases (56%) clonal karyotypic abnormalities were demonstrated. Although the karyotypic abnormalities and phenotypes were varied, there was a high degree of association between the karyotypic abnormalities monosomy 7/del (7q) and the CD34-positive phenotype; this antigen was expressed on blasts from eight of the nine patients displaying this abnormality. Monoclonal antibody phenotyping of myeloid leukemia with reagents such as anti-CD34 may help to define biologically interesting subsets of ANLL with distinct clinicopathologic expression.

Authors
Borowitz, MJ; Gockerman, JP; Moore, JO; Civin, CI; Page, SO; Robertson, J; Bigner, SH
MLA Citation
Borowitz, MJ, Gockerman, JP, Moore, JO, Civin, CI, Page, SO, Robertson, J, and Bigner, SH. "Clinicopathologic and cytogenic features of CD34 (My 10)-positive acute nonlymphocytic leukemia." Am J Clin Pathol 91.3 (March 1989): 265-270.
PMID
2646903
Source
pubmed
Published In
American Journal of Clinical Pathology
Volume
91
Issue
3
Publish Date
1989
Start Page
265
End Page
270

CD7+, CD4-, CD8- acute leukemia: a syndrome of malignant pluripotent lymphohematopoietic cells.

Following our initial observation of in vivo conversion of CD7+, CD4-, CD8- acute lymphoblastic leukemia (ALL) cells from lymphoid to myeloid lineages (Proc Natl Acad Sci (USA) 81:253, 1984) we have studied eight additional cases of ALL with this leukemic cell phenotype. The CD7+, CD4-, CD8- phenotype was associated with a distinct clinical entity with those affected predominantly male (either less than 35 years or greater than 65 years of age), with frequent mediastinal and/or thymic masses, skin and CNS disease, high peripheral WBC counts, and bone marrow blasts that were morphologically L1 or not ascribable to a specific lineage. These patients did not respond to conventional chemotherapeutic regimens for either acute lymphoid or myeloid leukemias. No common karyotype or T-cell gene rearrangement pattern could be defined. Importantly, seven of eight patient's leukemic cells studied were capable of multilineage (myeloid, erythroid, monocytoid, megakaryocytoid, and lymphoid) differentiation in vitro. Data is presented suggesting that CD7+, CD4-, CD8- leukemias, in many instances, are leukemias of immature hematopoietic cells. The development of novel therapeutic approaches to this form of leukemia will be necessary to alter its poor prognosis.

Authors
Kurtzberg, J; Waldmann, TA; Davey, MP; Bigner, SH; Moore, JO; Hershfield, MS; Haynes, BF
MLA Citation
Kurtzberg, J, Waldmann, TA, Davey, MP, Bigner, SH, Moore, JO, Hershfield, MS, and Haynes, BF. "CD7+, CD4-, CD8- acute leukemia: a syndrome of malignant pluripotent lymphohematopoietic cells." Blood 73.2 (February 1989): 381-390.
PMID
2783859
Source
pubmed
Published In
Blood
Volume
73
Issue
2
Publish Date
1989
Start Page
381
End Page
390

A phase I/II study of combined cisplatin and hyperthermia treatment for refractory malignancy.

Research in animal and human cell cultures has shown that some chemotherapeutic agents, cisplatin in particular, have cytotoxicity that is significantly potentiated at elevated temperatures. Concurrent administration of systemic cisplatin and local hyperthermia in human patients has not been previously reported. A phase I/II study was undertaken to assess the systemic and local toxicities and activity of concurrently administered local hyperthermia and systemic cisplatin in human tumours. Nine patients with histologically proven malignant tumours have been treated from March 1985 to July 1987. Their histologies were: breast, four; SCC of head and neck, two; SCC of skin, one; malignant melanoma, one; synovial cell sarcoma, one. Once-weekly hyperthermia was administered for 60 min by external microwave devices in an attempt to achieve minimum intratumoral temperatures of 42 degrees C. Plastic catheters were placed intratumorally under CT guidance for thermometry purposes. Cisplatin 40-60 mg/m2 was given over 60 min when steady-state heating was achieved. A total of 44 treatments are available for analysis. All nine patients had minimum intratumoral temperatures below the desired goal of 42 degrees C, and only two patients achieved average intratumoral temperatures of 42 degrees C or greater. Two of the responding patients sustained significant thermal injury consisting of blistering and necrosis. Three patients required transfusion and delay of weekly treatment because of anaemia and leukopenia. Four patients had partial response (PR) and one patient had minor response (MR) within the heated treatment volume. Three of these five patients experienced significant subjective palliation. This combination of treatment modalities can be delivered safely.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Green, DM; Burton, GV; Cox, EB; Hanson, D; Moore, J; Oleson, JR
MLA Citation
Green, DM, Burton, GV, Cox, EB, Hanson, D, Moore, J, and Oleson, JR. "A phase I/II study of combined cisplatin and hyperthermia treatment for refractory malignancy." Int J Hyperthermia 5.1 (January 1989): 13-21.
PMID
2646381
Source
pubmed
Published In
International Journal of Hyperthermia (Informa)
Volume
5
Issue
1
Publish Date
1989
Start Page
13
End Page
21

Biogenic amines in carcinoid tumors

We determined the content of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (E) in the tumors and urine of 12 patients with carcinoid tumors of midgut origin and 14 patients with carcinoid tumors of foregut origin. All of the midgut carcinoid tumors had a higher DA content than the foregut carcinoid tumors. Three of the patients with carcinoid tumors of midgut origin had increased excretion of DA or homovanillic acid (HVA) in their urine; all of the patients with carcinoid tumors of foregut origin had normal excretion of DA or HVA. We conclude that midgut carcinoid tumors usually contain more DA than foregut carcinoid tumors.

Authors
Feldman, JM; Moore, JO
MLA Citation
Feldman, JM, and Moore, JO. "Biogenic amines in carcinoid tumors." Biogenic Amines 6.3 (1989): 247-252.
Source
scival
Published In
Biogenic Amines
Volume
6
Issue
3
Publish Date
1989
Start Page
247
End Page
252

Hodgkin's disease presenting as myelofibrosis

Four patients with Hodgkin's disease and bone marrow fibrosis are presented in whom the clinical presentation was dominated by cytopenias; this was associated with a delayed diagnosis for an average of 20 months. Despite marrow involvement, chemotherapy resulted in complete remissions and two patients appear to have been cured. Marrow fibrosis resolved at least partially after chemotherapy. The medical literature relevant to bone marrow involvement by Hodgkin's disease is reviewed. Hodgkin's disease should be considered in the differential diagnosis of idiopathic myelofibrosis.

Authors
Meadows, LM; Rosse, WR; Moore, JO; Crawford, J; Laszlo, J; Kaufman, RE
MLA Citation
Meadows, LM, Rosse, WR, Moore, JO, Crawford, J, Laszlo, J, and Kaufman, RE. "Hodgkin's disease presenting as myelofibrosis." Cancer 64.8 (1989): 1720-1726.
PMID
2790685
Source
scival
Published In
Cancer
Volume
64
Issue
8
Publish Date
1989
Start Page
1720
End Page
1726

High-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. A clinical and pharmacologic study.

A total of 23 patients were treated at five dose escalations with high-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. The maximum tolerated doses of cyclophosphamide, cisplatin, and melphalan were 5,625, 180, and 80 mg/m2, respectively. The dose-limiting toxicity was cardiac toxicity. Objective tumor regression occurred in 14 of 18 evaluable cases, with a median duration of 3.5 months. Pharmacokinetic evaluation of melphalan in 20 patients revealed a dose-related increase in maximum plasma concentration (Cmax) and area under the curve (AUC). Perturbation of the melphalan plasma half-life and AUC, associated with severe toxicity, resulted when renal insufficiency occurred. The results suggest that high-dose combination cyclophosphamide, cisplatin, and melphalan produces frequent, rapid responses in breast cancer, melanoma, and sarcoma, although with significant extramedullary toxicity. The pharmacokinetics suggest that modification of the treatment schedule may result in a reduction of treatment-related toxicity.

Authors
Peters, WP; Stuart, A; Klotman, M; Gilbert, C; Jones, RB; Shpall, EJ; Gockerman, J; Bast, RC; Moore, JO
MLA Citation
Peters, WP, Stuart, A, Klotman, M, Gilbert, C, Jones, RB, Shpall, EJ, Gockerman, J, Bast, RC, and Moore, JO. "High-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. A clinical and pharmacologic study." Cancer Chemother Pharmacol 23.6 (1989): 377-383.
PMID
2653660
Source
pubmed
Published In
Cancer Chemotherapy and Pharmacology
Volume
23
Issue
6
Publish Date
1989
Start Page
377
End Page
383

Deforaxime treatment as a risk factor for zygomycete infection

Authors
Sane, A; Manzi, S; Perfect, J; Herzberg, AJ; Moore, JO
MLA Citation
Sane, A, Manzi, S, Perfect, J, Herzberg, AJ, and Moore, JO. "Deforaxime treatment as a risk factor for zygomycete infection." Journal of Infectious Diseases 159.1 (1989): 151-152.
Source
scival
Published In
Journal of Infectious Diseases
Volume
159
Issue
1
Publish Date
1989
Start Page
151
End Page
152

Demonstration of phenotypic abnormalities of thymic epithelium in thymoma including two cases with abundant Langerhans cells.

A panel of monoclonal antibodies that phenotypically define stages of normal human thymic epithelial (TE) cell maturation was used to compare thymic epithelium of nine thymomas with hyperplastic thymic epithelium in myasthenia gravis (MG) and thymic epithelium of normal thymuses. It has been shown previously that normal thymic epithelial cells express antigens of early TE cell maturation (A2B5, TE-4) throughout thymic ontogeny and acquire antigens 12/1-2, TE8, and TE-15 at 14 to 16 weeks of fetal gestation. Hyperplastic MG thymic epithelial cells expressed TE antigens in phenotypic patterns similar to that seen in normal postnatal thymus, ie, TE in subcapsular cortex and medulla was TE4+, A2B5+, and 12/1 - 2+ and Hassall's bodies were reactive with antibodies TE8 and TE15. In contrast, thymic epithelium in primary mediastinal thymomas was TE4+, A2B5+, TE8-, and greater than 75% of thymoma epithelium was 12/1 - 2-, a thymic epithelial phenotype similar to that seen on normal fetal thymic epithelium at 14 to 16 weeks fetal gestation. In one subject with a mature epithelial histologic pattern, thymoma epithelium was found to be strongly TE8+, a phenotype suggestive of a later stage of TE maturation. Lymphocytes in five of seven thymomas with immature thymic epithelial cells predominantly expressed immature thymocyte phenotype while two thymomas with immature epithelial phenotype showed a predominance of Langerhans cells and surrounding lymphocytes expressing a mature phenotype. Lymphocytes in the thymoma with differentiated epithelial cells expressed a mature thymocyte phenotype. Thus, in thymomas of varying histologic types, phenotypic abnormalities of thymic epithelium are present; these phenotypic abnormalities may reflect abnormal thymic epithelial maturation.

Authors
Kraus, VB; Harden, EA; Wittels, B; Moore, JO; Haynes, BF
MLA Citation
Kraus, VB, Harden, EA, Wittels, B, Moore, JO, and Haynes, BF. "Demonstration of phenotypic abnormalities of thymic epithelium in thymoma including two cases with abundant Langerhans cells." Am J Pathol 132.3 (September 1988): 552-562.
PMID
3261946
Source
pubmed
Published In
The American journal of pathology
Volume
132
Issue
3
Publish Date
1988
Start Page
552
End Page
562

Computed tomography of primary retroperitoneal malignancies.

The CT examinations and medical records of 33 patients with primary retroperitoneal malignancies were reviewed. Computed tomography findings were then compared with those from scans performed on 122 patients with non-Hodgkin lymphoma who presented during the same time interval. Primary retroperitoneal neoplasms had three distinct CT appearances. Twenty-one patients (64%) had large soft tissue masses. Seven patients (21%) had masses with fatty density components, and five patients (15%) had tumors that were primarily of water attenuation. With the exception of those liposarcomas that contained recognizable fat, CT could not distinguish among the different cell types. Seventeen patients with non-Hodgkin lymphoma had large dominant retroperitoneal soft tissue masses that resembled primary retroperitoneal malignancies. In most cases, however, CT was able to differentiate these tumor masses from primary retroperitoneal tumors. Although 19 of 20 sarcomas of soft tissue attenuation were heterogeneous, only six of the 17 lymphomas presenting as dominant masses had such an appearance. Computed tomography is extremely helpful in initially evaluating patients with primary retroperitoneal tumors and in assisting the surgeon in planning his or her approach by accurately defining tumor extent.

Authors
Cohan, RH; Baker, ME; Cooper, C; Moore, JO; Saeed, M; Dunnick, NR
MLA Citation
Cohan, RH, Baker, ME, Cooper, C, Moore, JO, Saeed, M, and Dunnick, NR. "Computed tomography of primary retroperitoneal malignancies." J Comput Assist Tomogr 12.5 (September 1988): 804-810.
PMID
3170843
Source
pubmed
Published In
Journal of Computer Assisted Tomography
Volume
12
Issue
5
Publish Date
1988
Start Page
804
End Page
810

High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer.

To evaluate the effect of high-dose chemotherapy in the treatment of metastatic breast cancer, we performed a phase II trial of a single treatment with high-dose cyclophosphamide (5,625 mg/m2), cisplatin (165 mg/m2), and carmustine (600 mg/m2), or melphalan (40 mg/m2) and bone marrow support as the initial chemotherapy for metastatic breast cancer. Twenty-two premenopausal patients with estrogen receptor negative, measurable metastatic disease were treated. Twelve of 22 patients (54%) obtained a complete response at a median 18 days. The overall response rate is 73% (complete and partial response). Median duration of response in the patients achieving complete response was 9.0 months with a median duration of survival for complete responders that is currently undefined. Relapse occurred predominantly at sites of pretreatment bulk disease or within areas of previous radiation therapy. Toxicity was frequent and five patients died of therapy-related complications. The results indicate that a single treatment with intensive combination alkylating agents with bone marrow support can produce more rapid and frequent complete responses than conventional chemotherapy when used as initial chemotherapy for metastatic breast cancer, although median disease-free and overall survival is not improved. Three patients (14%) remain in unmaintained remission beyond 16 months.

Authors
Peters, WP; Shpall, EJ; Jones, RB; Olsen, GA; Bast, RC; Gockerman, JP; Moore, JO
MLA Citation
Peters, WP, Shpall, EJ, Jones, RB, Olsen, GA, Bast, RC, Gockerman, JP, and Moore, JO. "High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer." J Clin Oncol 6.9 (September 1988): 1368-1376.
PMID
3047332
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
6
Issue
9
Publish Date
1988
Start Page
1368
End Page
1376
DOI
10.1200/JCO.1988.6.9.1368

Pleural amyloidosis.

Pleural amyloidosis has been reported rarely, and the diagnosis of this disease by Cope needle biopsy has, to our knowledge, been reported only once previously. We report two patients in whom the diagnosis of pleural amyloidosis was made by biopsy specimens obtained in the examination of large, unilateral pleural effusions. In one patient, the diagnosis was made by Cope needle biopsy. The clinical and diagnostic significance of these cases are discussed.

Authors
Knapp, MJ; Roggli, VL; Kim, J; Moore, JO; Shelburne, JD
MLA Citation
Knapp, MJ, Roggli, VL, Kim, J, Moore, JO, and Shelburne, JD. "Pleural amyloidosis." Arch Pathol Lab Med 112.1 (January 1988): 57-60.
PMID
3337619
Source
pubmed
Published In
Archives of Pathology and Laboratory Medicine
Volume
112
Issue
1
Publish Date
1988
Start Page
57
End Page
60

Clinical and pharmacologic effects of high dose single agent busulfan with autologous bone marrow support in the treatment of solid tumors.

A Phase I-II clinical trial of high dose single agent busulfan (16-20 mg/kg) administered over a 4-day period was undertaken. Pharmacokinetic measurements reveal that steady state total plasma busulfan levels between 2 and 10 microM were achieved by the second day and maintained through the remaining treatment period. Urinary excretion of mutagenic activity monitored by the Salmonella mutagenesis assay persisted for up to 48 h following the last dose of busulfan. The treatment showed specificity for myelocytic precursors as evidenced by selective depression of granulocytes with relative sparing of lymphocytic elements, and by differences in DNA damage as measured by a nucleoid sedimentation assay. Dose limiting toxicity was mucositis, anorexia, and hepatic toxicity. Transient autoimmune disorders were observed in three of the six patients. Partial responses were seen in two of five patients with melanoma, but these lasted for only 2 and 3 months. High dose busulfan represents an alkylating agent with marked myelocytic selectivity and may be useful for inclusion in intensive combination regimens.

Authors
Peters, WP; Henner, WD; Grochow, LB; Olsen, G; Edwards, S; Stanbuck, H; Stuart, A; Gockerman, J; Moore, J; Bast, RC
MLA Citation
Peters, WP, Henner, WD, Grochow, LB, Olsen, G, Edwards, S, Stanbuck, H, Stuart, A, Gockerman, J, Moore, J, and Bast, RC. "Clinical and pharmacologic effects of high dose single agent busulfan with autologous bone marrow support in the treatment of solid tumors." Cancer Res 47.23 (December 1, 1987): 6402-6406.
PMID
2824032
Source
pubmed
Published In
Cancer Research
Volume
47
Issue
23
Publish Date
1987
Start Page
6402
End Page
6406

Sarcomas in the elderly.

Though rare, osteosarcomas and soft tissue sarcomas do occur in the geriatric population. When possible, surgical excision is the treatment of choice, with radiation therapy and chemotherapy having largely an adjuvant role. Classic Kaposi's sarcoma is a chronically progressive and ultimately fatal disease of the elderly which can be managed effectively with both radiation therapy and chemotherapy.

Authors
Hertler, AA; Moore, JO
MLA Citation
Hertler, AA, and Moore, JO. "Sarcomas in the elderly." Clin Geriatr Med 3.4 (November 1987): 781-801. (Review)
PMID
3315168
Source
pubmed
Published In
Clinics in Geriatric Medicine
Volume
3
Issue
4
Publish Date
1987
Start Page
781
End Page
801

Comparison of the efficacy of a two-day and a five-day schedule for infusing intravenous gamma globulin in the treatment of immune thrombocytopenic purpura in adults

The standard schedule for treating immune thrombocytopenia purpura in adults with intravenous immunoglobulin G infusion (IVIG), 400 mg/kg per day for five days, was compared with a shorter schedule using 1,000 mg/kg per day for two days. Both schedules were found to be effective in correcting thrombocytopenia. Eleven of the 17 patients treated with the five-day regimen and nine of 10 patients treated with the two-day regimen had significant responses. Patients with an initial platelet count of less than 20,000 platelets/mm3 or with an estimated in vivo platelet survival in excess of 90 hours were less likely to have a response than were other patients. There were no serious side effects in either group, but thrombophlebitis was observed in some patients receiving the five-day regimen when a single intravenous catheter was used for more than three days. Headaches and, less commonly low-grade fever were noted in some patients receiving the two-day regimen when infusions were given at flow rates in excess of 0.04 ml/kg/minute. Since the two-day regimen requires shorter hospitalization and corrects thrombocytopenia slightly faster than the five-day course, it may be particularly useful in correcting thrombocytopenia in hospitalized patients requiring splenectomy or other surgery.

Authors
Kurlander, R; Coleman, RE; Moore, J; Gockerman, J; Rosse, W; Siegal, R
MLA Citation
Kurlander, R, Coleman, RE, Moore, J, Gockerman, J, Rosse, W, and Siegal, R. "Comparison of the efficacy of a two-day and a five-day schedule for infusing intravenous gamma globulin in the treatment of immune thrombocytopenic purpura in adults." American Journal of Medicine 83.4 A (1987): 17-24.
Source
scival
Published In
American Journal of Medicine
Volume
83
Issue
4 A
Publish Date
1987
Start Page
17
End Page
24

Intraluminal thrombus and bowel obstruction in acute leukemia due to bleeding Meckel's diverticulum.

Gastrointestinal bleeding from Meckel's diverticulum resulted in small bowel obstruction by thrombus in two patients with acute myelogenous leukemia during bone marrow aplasia and recovery from induction chemotherapy. Although gastrointestinal symptoms and complications are common in acute leukemia, these two cases are unique and describe a new syndrome that requires prompt recognition and surgical intervention. The complication of localized bowel obstruction by intraluminal thrombus is heretofore unreported.

Authors
Neuss, MN; Garbutt, JT; Leight, GS; Moore, JO
MLA Citation
Neuss, MN, Garbutt, JT, Leight, GS, and Moore, JO. "Intraluminal thrombus and bowel obstruction in acute leukemia due to bleeding Meckel's diverticulum." Am J Med 80.6 (June 1986): 1194-1196.
PMID
3487978
Source
pubmed
Published In
The American Journal of Medicine
Volume
80
Issue
6
Publish Date
1986
Start Page
1194
End Page
1196

PHASE-II TRIAL OF DIAZIQUONE IN ANTHRACYCLINE-RESISTANT ADULT SOFT-TISSUE AND BONE SARCOMA PATIENTS - A SOUTHEASTERN-CANCER-STUDY-GROUP TRIAL

Authors
CHAN, C; BARTOLUCCI, A; BRENNER, D; PRESANT, C; DAVILA, E; CARPENTER, J; GRECO, FA; CLAMON, G; MOORE, J
MLA Citation
CHAN, C, BARTOLUCCI, A, BRENNER, D, PRESANT, C, DAVILA, E, CARPENTER, J, GRECO, FA, CLAMON, G, and MOORE, J. "PHASE-II TRIAL OF DIAZIQUONE IN ANTHRACYCLINE-RESISTANT ADULT SOFT-TISSUE AND BONE SARCOMA PATIENTS - A SOUTHEASTERN-CANCER-STUDY-GROUP TRIAL." CANCER TREATMENT REPORTS 70.3 (March 1986): 427-428.
PMID
3456834
Source
wos-lite
Published In
Cancer Treatment Reports
Volume
70
Issue
3
Publish Date
1986
Start Page
427
End Page
428

Primary intraaortic malignancy-A case report

Malignant peripheral arterial emboli are extremely unusual. Most reported cases of malignant arterial emboli are secondary to invasion of the systemic circulation by pulmonary malignancies via the pulmonary veins. We report a rare case of a primary sarcoma of the aortic arch that presented as malignant emboli. When confronted by a patient with malignant emboli, a normal chest radiograph, and no evidence of a right-to-left shunt, a primary malignancy of the aorta should be suspected and angiography should be performed. © 1986 Springer-Verlag New York Inc.

Authors
Moeser, P; Perlmutt, LM; Moore, J; Rinker, GE
MLA Citation
Moeser, P, Perlmutt, LM, Moore, J, and Rinker, GE. "Primary intraaortic malignancy-A case report." Cardiovascular and Interventional Radiology 9.4 (1986): 182-183.
PMID
3094948
Source
scival
Published In
CardioVascular and Interventional Radiology
Volume
9
Issue
4
Publish Date
1986
Start Page
182
End Page
183
DOI
10.1007/BF02577936

Prevention of amphotericin B-induced rigors by dantrolene

Three patients had severe amphotericin B-induced rigors refractory to conventional prophylactic measures. Rigors improved or disappeared when dantrolene sodium was given prophylactically or during an episode. These observations suggest that dantrolene is useful as an alternative or adjuvant agent for severe rigors associated with amphotericin B infusion.

Authors
Gross, MH; Fulkerson, WJ; Moore, JO
MLA Citation
Gross, MH, Fulkerson, WJ, and Moore, JO. "Prevention of amphotericin B-induced rigors by dantrolene." Archives of Internal Medicine 146.8 (1986): 1587-1588.
PMID
3729640
Source
scival
Published In
Archives of Internal Medicine
Volume
146
Issue
8
Publish Date
1986
Start Page
1587
End Page
1588

Lipid cerebral embolization following lymphogram

Lipid emboli to the brain following lymphangiogram has been reported (1-6). This unusual complication following Ethiodol injection is rare, and its mechanism of occurrence is poorly understood. We present an additional case with documentation by computed tomography (CT) and suggest possible routes of embolism to the cerebrum.

Authors
Sane, DC; Massey, EW; Moore, J
MLA Citation
Sane, DC, Massey, EW, and Moore, J. "Lipid cerebral embolization following lymphogram." Clinical Neuropharmacology 8.2 (1985): 184-188.
PMID
2988771
Source
scival
Published In
Clinical Neuropharmacology
Volume
8
Issue
2
Publish Date
1985
Start Page
184
End Page
188

PHASE-I-II TRIAL OF MITOXANTRONE IN ACUTE-LEUKEMIA - AN INTERIM-REPORT

Authors
ARLIN, ZA; DUKART, G; SCHOCH, I; REISMAN, A; MOORE, J; SILVER, RA; CASSILETH, P; BERTINO, J; GAMS, R
MLA Citation
ARLIN, ZA, DUKART, G, SCHOCH, I, REISMAN, A, MOORE, J, SILVER, RA, CASSILETH, P, BERTINO, J, and GAMS, R. "PHASE-I-II TRIAL OF MITOXANTRONE IN ACUTE-LEUKEMIA - AN INTERIM-REPORT." INVESTIGATIONAL NEW DRUGS 3.2 (1985): 213-217.
PMID
3860491
Source
wos-lite
Published In
Investigational New Drugs
Volume
3
Issue
2
Publish Date
1985
Start Page
213
End Page
217

Leukemia-associated arthritis: identification of leukemic cells in synovial fluid using monoclonal and polyclonal antibodies.

Authors
Harden, EA; Moore, JO; Haynes, BF
MLA Citation
Harden, EA, Moore, JO, and Haynes, BF. "Leukemia-associated arthritis: identification of leukemic cells in synovial fluid using monoclonal and polyclonal antibodies." Arthritis Rheum 27.11 (November 1984): 1306-1308.
PMID
6497923
Source
pubmed
Published In
Arthritis and Rheumatism
Volume
27
Issue
11
Publish Date
1984
Start Page
1306
End Page
1308

Specific receptors for phorbol diesters on freshly isolated human myeloid and lymphoid leukemia cells: comparable binding characteristics despite different cellular responses.

Freshly isolated human leukemia cells have been shown in the past to display varying in vitro responses to phorbol diesters, depending on their cell type. Specific receptors for the phorbol diesters have been demonstrated on numerous different cells. This study was designed to characterize the receptors for phorbol diesters on leukemia cells freshly isolated from patients with different kinds of leukemia and to determine if differences in binding characteristics for tritium-labeled phorbol 12,13-dibutyrate (3H-PDBu) accounted for the different cellular responses elicited in vitro by phorbol diesters. Cells from 26 patients with different kinds of leukemia were studied. PDBu or phorbol 12-myristate 13-acetate (PMA) caused cells from patients with acute myeloblastic leukemia (AML), acute promyelocytic (APML), acute myelomonocytic (AMML), acute monocytic (AMoL), acute erythroleukemia (AEL), chronic myelocytic leukemia (CML) in blast crisis (myeloid), acute undifferentiated leukemia (AUL), and hairy cell leukemia (HCL) (n = 15) to adhere to plastic and spread. However, they caused no adherence or spreading and only slight aggregation of cells from patients with acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or CML-blast crisis (lymphoid) (n = 11). All leukemia cells studied, irrespective of cellular type, displayed specific receptors for 3H-PDBu. The time courses for binding by all leukemia types were similar, with peak binding at 5-10 min at 37 degrees C and 120 min at 4 degrees C. The binding affinities were similar for patients with ALL (96 +/- 32 nM, n = 4), CLL (126 +/- 32 nM, n = 6), and acute nonlymphoid leukemia (73 +/- 14 nM, n = 11). Likewise, the numbers of specific binding sites/cell were comparable for the patients with ALL (6.2 +/- 1.3 X 10(5) sites/cell, n = 4), CLL (5.0 +/- 2.0 X 10(5) sites/cell, n = 6), and acute nonlymphoid leukemia (4.4 +/- 1.9 X 10(5) sites/cell, n = 11). Thus, the differing responses to phorbol diesters of various types of freshly isolated leukemia cells appear to be due to differences other than initial ligand-receptor binding.

Authors
Goodwin, BJ; Moore, JO; Weinberg, JB
MLA Citation
Goodwin, BJ, Moore, JO, and Weinberg, JB. "Specific receptors for phorbol diesters on freshly isolated human myeloid and lymphoid leukemia cells: comparable binding characteristics despite different cellular responses." Blood 63.2 (February 1984): 298-304.
PMID
6318866
Source
pubmed
Published In
Blood
Volume
63
Issue
2
Publish Date
1984
Start Page
298
End Page
304

Mitoxantrone in the treatment of relapsed and refractory acute leukemia

Eleven academic institutions were selected to study mitoxantrone administered on a schedule of 10 mg/ m2/d for five days initially and later at 12 mg/m2/d for five days, each given as a 30 minute intravenous (IV) infusion each day. Patients with acute or chronic leukemia were stratified by leukemic type and clinical status and included one group of patients considered to be in relapse after complete remission from previous chemotherapy and another group of patients considered refractory to standard induction and/or salvage chemotherapy. During the initial treatment schedule, complete remissions were obtained in two of seven patients with acute nonlymphoblastic leukemia, in one of three patients with acute lymphoblastic leukemia, but in none of the patients with chronic granulocytic leukemia in blast crisis. The durations of remission for these three patients were 22, 57, and 78 days, respectively. An increase in mitoxantrone dose to 12 mg/m2/d produced complete remissions in 8 of 19 evaluable patients with acute nonlymphoblastic leukemia, in one of ten patients with refractory acute nonlymphoblastic leukemia, and in one of four patients with chronic granulocytic leukemia in blast crisis. Each of these patients required only a single course of mitoxantrone to achieve remission; the median time to remission was 37 days (range 18 to 64 days). Remission duration ranged from 35 days (chronic granulocytic leukemia) to 186 days, with the median duration for those patients with acute nonlymphoblastic leukemia achieving remission being 135 days. Of the six patients with acute lymphoblastic leukemia, none achieved remission at the higher dose level. Drugrelated gastrointestinal toxicity included mucositis (25%), diarrhea (21%), and nausea and vomiting (61%). Systemic infection (nonfatal) was experienced by 21% of patients and alopecia by 17%. Other side effects that occurred occasionally were hepatic dysfunction, decreased renal function, confusion, lethargy, anxiety, and fever. Possible drug-related phlebitis developed in one patient, and a single episode of minor epistaxis was reported in another. Cardiovascular toxicity was low. At a mitoxantrone dose of 10 mg/m2/d for five days, one patient developed hypotension, and one episode of congestive heart failure was reported in another. At the higher dose of 12 mg/m2/d, no drug-related hypotension, congestive heart failure, tachycardia, or chest pain were reported. These data indicate that mitoxantrone is a promising single drug for the treatment of acute nonlymphoblastic leukemia and possibly for acute lymphoblastic leukemia. © 1984.

Authors
Moore, JO; Olsen, GA
MLA Citation
Moore, JO, and Olsen, GA. "Mitoxantrone in the treatment of relapsed and refractory acute leukemia." Seminars in Oncology 11.3 SUPPL. 1 (1984): 41-46.
Source
scival
Published In
Seminars in Oncology
Volume
11
Issue
3 SUPPL. 1
Publish Date
1984
Start Page
41
End Page
46

Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2'-deoxycoformycin

Selective failure of lymphoid development occurs in genetic deficiency of adenosine deaminase (ADA). We examined the in vivo effects of a potent inhibitor of ADA, 2'-deoxycoformycin, which was used to treat a patient with refractory acute leukemia. Unexpectedly, within 7 days of starting treatment, the leukemic phenotype underwent complete conversion from T lymphoblastic to promyelocytic, with kinetics that suggested a precursor-product relationship between the two cell populations. Pretreatment of T lymphoblasts and posttreatment of promyelocytes had the same abnormal karyotype. Upon culture in vitro, the former transformed spontaneously over several weeks into mature myeloid cells. We conclude that the leukemia arose from a multipotent stem cell capable of both lymphoid and myeloid differentiation. Effects of ADA inhibition on leukemia cells during treatment included expansion of the deoxyadenosine nucleotide pool and accumulation of S-adenosylhomocysteine, a potent inhibitor of S-adenosylmethionine-dependent methylation. The influence of these changes on the leukemic phenotype is discussed in terms of (i) selective cytotoxicity to T lymphoblasts, which accumulated deoxyadenosine nucleotides more efficiently than did the patient's promyelocytes during in vitro incubation with deoxycoformycin plus deoxyadenosine, and (ii) induction of an altered program of differentiation.

Authors
Hershfield, MS; Kurtzberg, J; Harden, E; Moore, JO; Whang-Peng, J; Haynes, BF
MLA Citation
Hershfield, MS, Kurtzberg, J, Harden, E, Moore, JO, Whang-Peng, J, and Haynes, BF. "Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2'-deoxycoformycin." Proceedings of the National Academy of Sciences of the United States of America 81.1 I (1984): 253-257.
Source
scival
Published In
Proceedings of the National Academy of Sciences of USA
Volume
81
Issue
1 I
Publish Date
1984
Start Page
253
End Page
257

Septic arthritis due to Mycoplasma hominis.

Authors
McDonald, MI; Moore, JO; Harrelson, JM; Browning, CP; Gallis, HA
MLA Citation
McDonald, MI, Moore, JO, Harrelson, JM, Browning, CP, and Gallis, HA. "Septic arthritis due to Mycoplasma hominis." Arthritis Rheum 26.8 (August 1983): 1044-1047.
PMID
6882481
Source
pubmed
Published In
Arthritis and Rheumatism
Volume
26
Issue
8
Publish Date
1983
Start Page
1044
End Page
1047

Phase II trial of lymphoblastoid interferon in metastatic colon carcinoma

Nineteen patients with advanced metastatic colon carcinoma were treated with human lymphoblastoid interferon at a dose of 3.0 x 106 units/m2 im three times/week for 6 weeks. Patients who did not progress at the 6-week interval were randomized to receive maintenance treatment with either interferon (3.0 x 106 units/m2 once/week) or no further treatment. All patients had evaluable metastatic lung, liver, or abdominal disease as measured by radiographs or computerized tomographic scans. Complete remission or partial remission of > 50% decrease in tumor measurements was not demonstrated with interferon treatment. Among 18 evaluable patients, seven had stabilization of measurable disease at 6 weeks, but 11 showed progressive disease. Of the seven patients followed during maintenance, only one (placebo maintenance) remained with no objective progression. No serious organ toxic effects were attributed to interferon, but one patient demonstrated liver enzyme elevation that persisted after cessation of interferon therapy. All patients had significant constitutional symptoms of fever, muscle aches, and malaise. Using interferon at the dose schedule outlined, this study failed to demonstrate significant regressions in metastatic colon carcinoma.

Authors
Chaplinski, T; Laszlo, J; Moore, J; Silverman, P
MLA Citation
Chaplinski, T, Laszlo, J, Moore, J, and Silverman, P. "Phase II trial of lymphoblastoid interferon in metastatic colon carcinoma." Cancer Treatment Reports 67.11 (1983): 1009-1012.
PMID
6640552
Source
scival
Published In
Cancer Treatment Reports
Volume
67
Issue
11
Publish Date
1983
Start Page
1009
End Page
1012

Identification of human T cell leukemia virus in a Japanese patient with adult T cell leukemia and cutaneous lymphomatous vasculitis

We have identified a Japanese patient with adult T-cell leukemia (ATL) whose T cells in vitro produced the human T-cell leukemia virus (HTLV). This patient presented with lymphomatous arthritis and leukemia and subsequently developed skin lesions. Skin invasion by malignant T-cells was angiocentric and produced vessel wall destruction, resulting in necrotic cutaneous tumor nodules. Malignant T cells in peripheral blood, skin, and joint prior to culture in vitro did not express p19 HTLV-associated antigen. However, by electron microscopy, intracellular type C viral particles were seen in skin-infiltrating T cells. Peripheral blood malignant cells after 7 days in culture with T-cell growth factor-supplemented media expressed p19 antigen, and type C virus particles were seen by electron microscopy to be budding from malignant T lymphocytes. Mitomycin-C-treated peripheral-blood T cells induced the transformation of cord blood T cells into HTLV-infected p19+ T cells. The demonstration of HTLV in malignant T cells from our patient confirms the association of HTLV with Japanese adult T-cell leukemia. Moreover, HTLV may be associated with a vasculitis-arthritis syndrome.

Authors
Haynes, BF; Miller, SE; Palker, TJ; Moore, JO; Dunn, PH; Bolognesi, DP; Metzgar, RS
MLA Citation
Haynes, BF, Miller, SE, Palker, TJ, Moore, JO, Dunn, PH, Bolognesi, DP, and Metzgar, RS. "Identification of human T cell leukemia virus in a Japanese patient with adult T cell leukemia and cutaneous lymphomatous vasculitis." Proceedings of the National Academy of Sciences of the United States of America 80.7 I (1983): 2054-2058.
Source
scival
Published In
Proceedings of the National Academy of Sciences of USA
Volume
80
Issue
7 I
Publish Date
1983
Start Page
2054
End Page
2058

Mental neuropathy from systemic cancer

19 patients with mental neuropathy secondary to systemic cancer are described. In nine patients, the numb chin was the presenting symptom of a neoplasm. Nine patients had lymphoreticular malignancies, and the others had a variety of solid tumors. Radiograms of the mandible were abnormal in 5 of 12 patients. The cerebrospinal fluid contained malignant cells in two. Resolution, complete or partial, occurred in 16 of 19 patients receiving radiation or chemotherapy, including 8 who received chemotherapy alone. 16 of the 19 patients died within 17 months of the onset of the neuropathy. A nontraumatic mental neuropathy should initiate a search for cancer.

Authors
Massey, EW; Moore, J; Jr, SCS
MLA Citation
Massey, EW, Moore, J, and Jr, SCS. "Mental neuropathy from systemic cancer." Neurology 31.10 (1981): 1277-1281.
PMID
6287347
Source
scival
Published In
Neurology
Volume
31
Issue
10
Publish Date
1981
Start Page
1277
End Page
1281

MEDUSA CELLS - CYTOSTRUCTURE AND CYTO-CHEMISTRY OF AMEBOID EOSINOPHILS WITH PSEUDOPOD-LIKE PROCESSES

Authors
HANKER, JS; CHANDROSS, RJ; SOLIC, JJ; WEATHERLY, NF; LASZLO, J; MOORE, JO; OTTOLENGHI, A
MLA Citation
HANKER, JS, CHANDROSS, RJ, SOLIC, JJ, WEATHERLY, NF, LASZLO, J, MOORE, JO, and OTTOLENGHI, A. "MEDUSA CELLS - CYTOSTRUCTURE AND CYTO-CHEMISTRY OF AMEBOID EOSINOPHILS WITH PSEUDOPOD-LIKE PROCESSES." HISTOCHEMICAL JOURNAL 13.6 (1981): 905-&.
PMID
7338480
Source
wos-lite
Published In
The Histochemical journal
Volume
13
Issue
6
Publish Date
1981
Start Page
905
End Page
&
DOI
10.1007/BF01002631

Medusa cells: the morphology and cytochemistry of common amoeboid variants of eosinophils.

Authors
Hanker, JS; Chandross, RJ; Weatherly, NF; Laszlo, J; Moore, JO; Buckley, RH; Ottolenghi, A
MLA Citation
Hanker, JS, Chandross, RJ, Weatherly, NF, Laszlo, J, Moore, JO, Buckley, RH, and Ottolenghi, A. "Medusa cells: the morphology and cytochemistry of common amoeboid variants of eosinophils." Histochem J 12.6 (November 1980): 701-715.
PMID
6449493
Source
pubmed
Published In
The Histochemical journal
Volume
12
Issue
6
Publish Date
1980
Start Page
701
End Page
715

Detection and partial characterization of human thymus-leukemia antigens.

Two monkey antisera against human thymocytes after absorption with human erythrocytes and peripheral blood leukocytes were shown to detect human thymus-leukemia (HTL)-like antigens. These sera were cytotoxic for thymocytes (> 90% lysis at a 1:10 dilution) but were nonreactive with enriched peripheral blood T- and B-lymphocytes or with cells from myeloid or B-cell lymphoid leukemias. Most (16/17) sheep erythrocyte rosette-forming acute lymphoblastic leukemia (ALL) cells reacted with these sera. Cells from patients with T-cell chronic lymphocytic leukemia, lymphoblastic lymphoma (LBL), and thymoma were also positive. Three of 4 T-cell lymphoblastoid lines derived from ALL patients reacted with these sera. Absorption of the sera with MOLT-4F cells, thymocytes, or LBL cells removed the reactivity against all types of cells tested. However, sera absorbed with the T-cell line HSB remained cytotoxic for thymocytes, MOLT-4F, and most (6/9) T-cell cancers tested. The peripheral blood cell-absorbed sera precipitated a molecule with an apparent molecular weight of 48,000 from lactoperoxidase-labeled thymocytes but not from similarly labeled peripheral blood lymphocytes. The ability of the sera to precipitate this antigen was decreased by absorption with thymocytes, MOLT-4, or LBL cells but not by absorption with HSB, SB, or non-T, non-B ALL cells. Sequential precipitation studies suggested that the HTL antigen was not associated with beta 2 microglobulin.

Authors
Dowell, BL; Falletta, JM; Moore, JO; Metzgar, RS
MLA Citation
Dowell, BL, Falletta, JM, Moore, JO, and Metzgar, RS. "Detection and partial characterization of human thymus-leukemia antigens." J Natl Cancer Inst 65.4 (October 1980): 691-701.
PMID
6968369
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
65
Issue
4
Publish Date
1980
Start Page
691
End Page
701

Pulmonary metastasis from ameloblastoma of the mandible: report of case and review of the literature

Ameloblastoma is an uncommon tumor of the jaw that accounts for approximately 1% of all tumors and cysts of the jaw. It is thought to arise from odontogenic epithelium such as that found lining dentigerous cysts or from remnants of dental lamina or enamel organs. The tumor generally appears benign histologically and rarely metastasizes, although it has a high incidence of local recurrence after surgical resection. Mestastatic lesions to the lung from ameloblastomas are rare; only 16 histologically proven cases of lung metastasis have been reported in the English literature. The following report documents another such case, emphasizing the radiologic findings and the importance of adequate treatment of the primary lesion in the prevention of metastasis.

Authors
Buff, SJ; Chen, JTT; Ravin, CC; Moore, JO
MLA Citation
Buff, SJ, Chen, JTT, Ravin, CC, and Moore, JO. "Pulmonary metastasis from ameloblastoma of the mandible: report of case and review of the literature." Journal of Oral Surgery 38.5 (1980): 374-376.
PMID
6928939
Source
scival
Published In
Journal of Oral Surgery
Volume
38
Issue
5
Publish Date
1980
Start Page
374
End Page
376

Malignant effusions in recurrent breast cancer. Steroid hormone receptor analysis of effusion fluid derived cells

Estrogen and progesterone receptor determination in breast cancer is of significance in determining a patient's potential response to hormonal manipulation. One practical limitation to this procedure has been availability of material for receptor assay. We describe 12 patients in whom quantitative estrogen and/or progesterone receptor analysis was accomplished utilizing tumor cells obtained from malignant effusions. The ability to obtain quantitative steroid receptor data on material derived from malignant effusions provides an effective source for this biochemical parameter in patients in whom no other tumor tissue is available for study.

Authors
Jr, KSM; Wortman, J; Moore, JO; Rundles, RW
MLA Citation
Jr, KSM, Wortman, J, Moore, JO, and Rundles, RW. "Malignant effusions in recurrent breast cancer. Steroid hormone receptor analysis of effusion fluid derived cells." Cancer 45.7 (1980): 1609-1614.
PMID
6989478
Source
scival
Published In
Cancer
Volume
45
Issue
7
Publish Date
1980
Start Page
1609
End Page
1614

Facilitated light microscopic cytochemical diagnosis of acute myelogenous leukemia.

Hydroperoxidase-positive Phi bodies and rods are much more prominent and prevalent than rods visualized with a Romanovsky-type stain (Auer rods) in immature leukocytes of patients with active acute myelogenous leukemia (AML). They are readily observed with the light microscope in peripheral blood or marrow films of AML patients stained to show their peroxidatic activity. In many of these patients, Auer rods, which apparently constitute only a small subpopulation of the hydroperoxidase-positive Phi bodies and rods, were detected with difficulty, if at all. The hydroperoxidase-positive Phi bodies and rods were observed in 92% of 36 patients with active disease. They were never observed in leukocytes of patients with other hematopoietic disorders or of normal individuals. Thus, they facilitated the distinction of AML from acute lymphocytic leukemia and chronic granulocytic leukemia in blast crisis. They were absent in full clinical remission after chemotherapy and were greatly diminished in partial remission. They were present in disease relapse and reappeared in five patients who had been in full remission. These results suggest that these hydroperoxidase-positive enlarged particles are pathognomonic of AML and that monitoring them with the light microscope may aid in guiding its clinical management.

Authors
Hanker, JS; Ambrose, WW; James, CJ; Mandelkorn, J; Yates, PE; Gall, SA; Bossen, EH; Fay, JW; Laszlo, J; Moore, JO
MLA Citation
Hanker, JS, Ambrose, WW, James, CJ, Mandelkorn, J, Yates, PE, Gall, SA, Bossen, EH, Fay, JW, Laszlo, J, and Moore, JO. "Facilitated light microscopic cytochemical diagnosis of acute myelogenous leukemia." Cancer Res 39.5 (May 1979): 1635-1639.
PMID
85486
Source
pubmed
Published In
Cancer Research
Volume
39
Issue
5
Publish Date
1979
Start Page
1635
End Page
1639

Acute lymphoblastic leukemia: classification and characterization with antisera to human T-cell and Ia antigens.

Authors
Anderson, JK; Moore, JO; Falletta, JM; Terry, WF; Metzgar, RS
MLA Citation
Anderson, JK, Moore, JO, Falletta, JM, Terry, WF, and Metzgar, RS. "Acute lymphoblastic leukemia: classification and characterization with antisera to human T-cell and Ia antigens." J Natl Cancer Inst 62.2 (February 1979): 293-298.
PMID
310908
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
62
Issue
2
Publish Date
1979
Start Page
293
End Page
298

Autologous marrow transplantation for patients with acute myelogenous leukemia--a preliminary report.

Twelve consecutive adult patients with acute myelogenous leukemia have been entered on a treatment protocol which examines the role of "remission-intensification" during maintenance using high-dose chemoradiotherapy and autologous remission marrow transplantation. Nine patients have achieved complete remission: 5/9 patients have had remission marrow stored followed by high-dose chemoradiotherapy and autologous marrow transfusion; two patients were removed from study because of excessive toxicity during remission-induction precluding high-dose therapy; two patients are currently ready for marrow storage; and two patients are receiving remission-induction therapy. Of the five transplanted patients, four experienced excellent return of blood counts and one patient has had prolonged pancytopenia and continues to require red cell and platelet transfusions. There have been no serious infectious or hemorrhagic problems associated with post-transplant period in any of the patients. Autologous remission bone marrow transplantation following lethal high-dose chemoradiotherapy results in effective restoration of normal hemopoiesis, is associated with acceptable toxicity and may be an effective means of increasing the numbers of acute leukemia patients having long-term complete remission.

Authors
Fay, JW; Silberman, HR; Moore, JO; Noell, KT; Huang, AT
MLA Citation
Fay, JW, Silberman, HR, Moore, JO, Noell, KT, and Huang, AT. "Autologous marrow transplantation for patients with acute myelogenous leukemia--a preliminary report." Experimental Hematology 7 Suppl 5 (1979): 302-308.
PMID
400693
Source
scival
Published In
Experimental Hematology
Volume
7 Suppl 5
Publish Date
1979
Start Page
302
End Page
308

Leukopheresis therapy of leukemic reticuloendotheliosis (hairy cell leukemia)

Intensive leukopheresis has been valuable in the short-term palliation of chronic lymphocytic and granulocytic leukemias. A 47-yr-old man with refractory leukemic reticuloendotheliosis (hairy cell leukemia) manifested by anemia, thrombocytopenia, elevated peripheral leukemia cell counts, generalized lymph node enlargement, and leukemic infiltrative skin disease was treated with serial leukophresis. Removal of approximately 7 x 1011 peripheral leukemia cells resulted in marked clinical and hematologic improvement with resolution of enlarged lymph nodes and clearing of skin infiltrates. At the time of this reporting, more than 100 wk since the last leukopheresis, the patient continues to do well. The improvement in all blood counts, reduction in lymph node size, and clearing of skin lesions paralleled the reduction of peripheral leukemia cell load by leukopheresis, suggesting mobilization of leukemia cells from marrow, lymph nodes, and skin. Removal of large numbers of leukemia cells in hairy cell leukemia has the potential of achieving sustained clinical improvement and may be a useful alternative therapy for these patients.

Authors
Fay, JW; Moore, JO; Logue, GL; Huang, AT
MLA Citation
Fay, JW, Moore, JO, Logue, GL, and Huang, AT. "Leukopheresis therapy of leukemic reticuloendotheliosis (hairy cell leukemia)." Blood 54.3 (1979): 747-749.
PMID
465739
Source
scival
Published In
Blood
Volume
54
Issue
3
Publish Date
1979
Start Page
747
End Page
749

Detection of both T-cell and Ia-like antigens on cells from patients with acute myelomonocytic leukemia and chronic myelogenous leukemia in blast crisis

Appropriately absorbed antisera to the lymphoblastoid cell lines HSB and SB detect a human T-lymphocyte-associated antigen (TLAA) and the human Ia-like antigens, respectively. Cells from some patients with acute myelomonocytic leukemia (AMML) and chronic myelogenous leukemia in blast crisis expressed both TLAA and Ia antigens when tested in a complement-dependent microcytotoxicity assay (>90% lysis with both antisera). When patients were in remission, expression of TLAA and Ia antigens returned to normal values. Quantitative absorption of anti-TLAA serum with increasing numbers of AMML cells showed that these cells could remove reactivity of the serum for both HSB and human thymocytes. Similarly, absorption of anti-Ia serum with AMML cells removed all serological reactivity when this serum was tested on chronic lymphocytic leukemia cells or normal B-cells. These serological findings were confirmed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis studies using radiolabeled antigens. Cells from an AMML patient were labeled with 125I using lactoperoxidase; both the TLAA and Ia antigens were precipitated from the resulting solubilized membrane preparation. Leukemic cells from one AMML patient and one patient with chronic myelogenous leukemia in blast crisis were studied for Ia and TLAA antigens with a double fluorescence technique. Over 80% of the cells showed dual fluorescence.

Authors
Anderson, JK; Moore, JO; Metzgar, RS
MLA Citation
Anderson, JK, Moore, JO, and Metzgar, RS. "Detection of both T-cell and Ia-like antigens on cells from patients with acute myelomonocytic leukemia and chronic myelogenous leukemia in blast crisis." Cancer Research 39.12 (1979): 4810-4815.
PMID
91428
Source
scival
Published In
Cancer Research
Volume
39
Issue
12
Publish Date
1979
Start Page
4810
End Page
4815

Estrogen receptor determination in percutaneous bone marrow biopsies of patients with metastatic breast cancer

Because material for biopsy among breast cancer patients is often scarce, a new procedure using material obtained from percutaneous bone marrow biopsy was developed and is presented. Bone marrow biopsy was the source of neoplastic material in 42 patients and was used to determine whether percutaneous bone marrow biopsy specimens could provide the necessary neoplastic tissue for estrogen receptor (ER) determination. Of the 42 patients, specimens from 11 (26%) were found to have insufficient tumor material for further evaluation; of the remaining 31 patients, 12 (39%) contained quantitatively ( 7 fmol) or qualitatively significant estrogen binding. All 12 patients were treated with endocrine therapy alone. Of the 12 patients, 8 (67%) responded to hormonal manipulation. The majority of patients evaluated were without other measureable signs of recurrent disease. All data obtained served to corroborate the usefulness of routine percutaneous bone marrow specimen for receptor analysis. This use of bone marrow represents an important application of improved technology to clinical practice.

Authors
Wortman, JE; Rundles, RW; Moore, JO; Sr, KSM; Jr, KSM
MLA Citation
Wortman, JE, Rundles, RW, Moore, JO, Sr, KSM, and Jr, KSM. "Estrogen receptor determination in percutaneous bone marrow biopsies of patients with metastatic breast cancer." Medical and Pediatric Oncology 7.3 (1979): 277-283.
PMID
542192
Source
scival
Published In
Pediatric Blood and Cancer
Volume
7
Issue
3
Publish Date
1979
Start Page
277
End Page
283

The light microscopic demonstration of hydroperoxidase-positive Phi bodies and rods in leukocytes in acute myeloid leukemia

Unique fusiform or spindle-shaped particles (Phi bodies) and rods with hydroperoxidase (catalase and/or peroxidase) activity are present in human granulocyte precursors only in acute myelogenous leukemia (AML). These newly recognized particles are much more numerous and prominent than Auer rods. They may be rapidly and readily identified using the microscope in marrow or peripheral blood films when the procedures recommended in this paper for fixation, incubation for hydroperoxidase demonstration in 3,3′-diaminobenzidine (DAB)/H2O2 medium, copper salt treatment and counterstaining (optional) with the Papanicolaou method are employed. Films prepared in the same manner but treated with benzidine/H2O2 medium for myeloperoxidase did not reveal these particles. We believe that Phi bodies are pathognomonic of AML since they are almost invariably present in AML patients with active disease. Their presence serves to distinguish AML from acute lymphocytic leukemia and from chronic granulocytic leukemia in blast crisis. Since the particles disappear in disease remission and reappear upon relapse, the recommended procedure is not only useful in diagnosis but in guiding therapy. When a very rapid diagnosis is needed, it is not necessary to counterstain the preparations, but the nuclei, cytoplasm and plasmalemma can readily be observed in the granulocyte precursors when they are counterstained by the Papanicolaou method. This treatment does not diminish the clarity of the Phi bodies and rods which stain by virtue of their peroxidatic activity. This cytochemical diagnostic procedure should be considered for adoption by hematology laboratories. © 1978 Springer-Verlag.

Authors
Hanker, JS; Laszlo, J; Moore, JO
MLA Citation
Hanker, JS, Laszlo, J, and Moore, JO. "The light microscopic demonstration of hydroperoxidase-positive Phi bodies and rods in leukocytes in acute myeloid leukemia." Histochemistry 58.4 (1978): 241-252.
PMID
216654
Source
scival
Published In
Histochemistry
Volume
58
Issue
4
Publish Date
1978
Start Page
241
End Page
252
DOI
10.1007/BF00495380

Preparation and characterization of lymphocyte-activating factor (LAF) from acute monocytic and myelomonocytic leukemia cells

Leukemia cells from acute monocytic and myelomonocytic patients undergoing leukophoresis have been used to prepare large quantities of lymphocyte-activating factor (LAF). The chemical properties of normal leukocyte LAF and leukemia cell LAF from a single donor for industrial-scale purification. The human histiocytic lymphoma cell line U937 was also evaluated as a possible source of LAF. Although exhibiting several monocyte-specific properties, the U937 cell line failed to release LAF. © 1978 Academic Press, Inc. All rights reserved.

Authors
Lachman, LB; Moore, JO; Metzgar, RS
MLA Citation
Lachman, LB, Moore, JO, and Metzgar, RS. "Preparation and characterization of lymphocyte-activating factor (LAF) from acute monocytic and myelomonocytic leukemia cells." Cellular Immunology 41.1 (1978): 199-206.
PMID
281262
Source
scival
Published In
Cellular Immunology
Volume
41
Issue
1
Publish Date
1978
Start Page
199
End Page
206

I and i antigens on normal and leukemic leukocytes

Human leukocytes I and i antigens were quantitated using 125I labelled purified antibodies. Binding of these antibodies to leukocytes was dependent on reduced temperature. No significant difference in antigen content was observed between normal and leukemic myeloid leukocytes. B lymphocytes bound much greater amounts of both I and i antibodies than did T lymphocytes. Neoplastic lymphoid cells bound widely divergent amounts of both antibodies with chronic lymphocytic leukemia and lymphosarcoma cell leukemia cells binding much decreased amounts compared to normal lymphocytes. Cells from patients with hairy cell leukemia bound very large quantities of these antibodies in a cold dependent fashion. These elevated levels of binding were not due to nonspecific binding of IgM.

Authors
Moore, JO; Logue, GL
MLA Citation
Moore, JO, and Logue, GL. "I and i antigens on normal and leukemic leukocytes." Cancer 42.1 (1978): 140-148.
PMID
276411
Source
scival
Published In
Cancer
Volume
42
Issue
1
Publish Date
1978
Start Page
140
End Page
148

Chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the commonest type of leukemia seen in Western countries. It affects an older group of individuals than most other varieties of leukemia, and men more often than women, in a ratio of 2:1. The incidence of CLL is significantly increased in some families. In most instances, CLL is due to the overgrowth or accumulation of immunoglobulin producing B lymphocytes. Hypogammaglobulinemia is a common feature, and anomalous immunoglobulin components occur in 3 to 5% of patients. The early symptoms and signs of CLL include fatigue, reduced exercise tolerance, enlarged lymph nodes, and splenomegaly. Fever, weight loss, and impairment of bone marrow function, with anemia, bleeding and susceptibility to infection are characteristic of severe or advanced disease. In the great majority of patients, the disease can be controlled for 6 to 10 or more years with simple regimens using chlorambucil or cyclophosphamide, often in combination with prednisone. Radiotherapy and splenectomy are useful in some instances. The terminal phase of the disease is characterized by exacerbation or increasing severity of the leukemia and the development of opportunistic infections associated with immunodeficiency.

Authors
Rundles, RW; Moore, JO
MLA Citation
Rundles, RW, and Moore, JO. "Chronic lymphocytic leukemia." Cancer 42.2 ,SUPPL. (1978): 941-945.
Source
scival
Published In
Cancer
Volume
42
Issue
2 ,SUPPL.
Publish Date
1978
Start Page
941
End Page
945

Disseminated aspergillosis in a renal transplant patient: diagnostic difficulties re emphasized

An asymptomatic and radiographically occult lung abscess was the primary focus of infection in this case of fatal disseminated aspergillosis in a renal transplant recipient. Extensive neurological evaluation in response to a change in personality failed to reveal a brain abscess, which was the cause of death. This case illustrates the variability in presentations of aspergillosis and the continuing difficulties in diagnosing this infection in immunosuppressed patients.

Authors
Murray, HW; Moore, JO; Luff, RD
MLA Citation
Murray, HW, Moore, JO, and Luff, RD. "Disseminated aspergillosis in a renal transplant patient: diagnostic difficulties re emphasized." Johns Hopkins Medical Journal 137.5 (1975): 235-237.
PMID
1102746
Source
scival
Published In
Johns Hopkins Medical Journal
Volume
137
Issue
5
Publish Date
1975
Start Page
235
End Page
237

Bowel transit-times in two populations experiencing similar colon-cancer risks.

Authors
Glober, GA; Klein, KL; Moore, JO; Abba, BC
MLA Citation
Glober, GA, Klein, KL, Moore, JO, and Abba, BC. "Bowel transit-times in two populations experiencing similar colon-cancer risks." Lancet 2.7872 (1974): 80-81.
Source
scival
Published In
Lancet
Volume
2
Issue
7872
Publish Date
1974
Start Page
80
End Page
81

Population studies of pepsinogen polymorphism.

Authors
Samloff, IM; Liebman, WM; Glober, GA; Moore, JO; Indra, D
MLA Citation
Samloff, IM, Liebman, WM, Glober, GA, Moore, JO, and Indra, D. "Population studies of pepsinogen polymorphism." American Journal of Human Genetics 25.2 (1973): 178-180.
PMID
4689038
Source
scival
Published In
American Journal of Human Genetics
Volume
25
Issue
2
Publish Date
1973
Start Page
178
End Page
180

Nutritional cirrhosis in rhesus monkeys: Electron microscopy and histochemistry

A choline-deficient low protein diet was fed to twelve Rhesus monkeys for two years. Eight of the animals died, most of them during the latter part of the first year. Mortality among males was higher than in females. Three of the four surviving animals developed fatty metamorphosis followed by cirrhosis. Eight sequential liver biopsies from each of these animals were studied. Control specimens showed paracrystalline mitochondrial inclusions in the hepatocytes and cytoplasmic crystalloids in the endothelial cells of the hepatic sinusoids and portal vessels. The significance of both structures remains unknown. Striking cytoplasmic vacuoles, possibly produced by anoxia during surgical liver biopsy, were observed in some specimens. The hepatocytes of the animals on the experimental diet, in addition to fatty change, showed mitochondria with bizarre shapes, circular cristae or increased electron opacity. Focal cytoplasmic degradation and Golgi dilatation were prominent. Microvilli developed along the intercellular spaces and became more prominent in the space of Disse. Basement membranes which were rarely continuous could be seen between hepatocytes and sinusoidal lining cells. In Disse spaces and intercellular spaces microfibrils and increased collagen fibers developed. In the later biopsies septa were formed which contained a higher proportion of typical collagen to microfibrils than the fibrillar material in the Disse spaces. The hepatocytes in the cirrhotic nodules stained more strongly for glycogen and were more active in nearly all histochemical enzyme reactions than the hepatocytes in non-nodular areas. This suggests that the nodules differed metabolically from the rest of the parenchyma. © 1969.

Authors
Ruebner, BH; Moore, J; Rutherford, RB; Seligman, AM; Zuidema, GD
MLA Citation
Ruebner, BH, Moore, J, Rutherford, RB, Seligman, AM, and Zuidema, GD. "Nutritional cirrhosis in rhesus monkeys: Electron microscopy and histochemistry." Experimental and Molecular Pathology 11.1 (1969): 53-70.
PMID
4980689
Source
scival
Published In
Experimental and Molecular Pathology
Volume
11
Issue
1
Publish Date
1969
Start Page
53
End Page
70
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