Jeffrey J. Molldrem, MD; Eric Leifer, PhD; Erkut Bahceci, MD; Yogen Saunthararajah, MD; Mary Rivera, RN; Cynthia Dunbar, MD; Johnson Liu, MD; Riotoro Nakamura, MD; Neal S. Young, MD; A. John Barrett, MD
Grant Support: Dr. Molldrem is supported, in part, by a grant from the National Institutes of Health (CA85843).
Requests for Single Reprints: Jeffrey J. Molldrem, MD, University of Texas M.D. Anderson Cancer Center, Transplantation Immunology Section, Department of Blood and Marrow Transplantation, 1515 Holcombe Boulevard, Box 448, Houston, TX 77030; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Molldrem: University of Texas M.D. Anderson Cancer Center, Transplantation Immunology Section, Department of Blood and Marrow Transplantation, 1515 Holcombe Boulevard, Box 448, Houston TX 77030.
Drs. Leifer, Bahceci, Saunthararajah, Dunbar, Liu, Nakamura, Young, and Barrett and Ms. Rivera: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10, Room 7C-103, 9000 Rockville Pike, Bethesda, MD 70892.
Author Contributions: Conception and design: J. Molldrem, A.J. Barrett.
Analysis and interpretation of the data: J. Molldrem, E. Leifer, E. Bahceci, Y. Saunthararajah, C. Dunbar, J. Liu, N.S. Young, A.J. Barrett.
Drafting of the article: J. Molldrem, E. Leifer, E. Bahceci, A.J. Barrett.
Critical revision of the article for important intellectual content: J. Molldrem, E. Leifer.
Final approval of the article: J. Molldrem, J. Liu, A.J. Barrett.
Provision of study materials or patients: J. Molldrem, Y. Saunthararajah, C. Dunbar, N.S. Young, R. Nakamura.
Statistical expertise: E. Leifer, E. Bahceci.
Administrative, technical, or logistic support: R. Nakamura.
Collection and assembly of data: J. Molldrem, Y. Saunthararajah, M. Rivera, A.J. Barrett.
Almost half of the deaths that result from myelodysplastic syndromes are due to cytopenia associated with bone marrow failure. Treatment is mostly supportive care.
To determine whether treatment with antithymocyte globulin improves cytopenia and reverses dependence on red blood cell transfusions in patients with myelodysplastic syndromes.
Single-treatment, prospective study.
Tertiary referral center.
61 patients with myelodysplastic syndromes.
Antithymocyte globulin, 40 mg/kg of body weight, given daily for 4 days.
Evaluation of bone marrow, blood counts, transfusions, progression, and survival for a median of 30 months (range, 1 to 88 months).
Within 8 months of treatment, 21 of 61 patients (34%) no longer required red blood cell transfusions. This independence from transfusions was maintained in 17 responders (81%) for a median of 36 months (range, 3 to 72 months). Ten of 21 patients (47.5%) with severe thrombocytopenia had sustained platelet count increases, and 6 of 11 patients (55%) with severe neutropenia had sustained neutrophil counts of greater than 1 × 109 cells/L. Characteristics favorable for response were younger patient age (P = 0.005) and lower platelet counts (P = 0.038). One of the 21 responders (5%) and 22 of the 40 nonresponders (55%) died before the end of the study (P = 0.008). One of the 21 responders (5%) and 13 of the 40 nonresponders (33%) had disease progression (P = 0.086).
Although this study was a nonrandomized, single-treatment study, 34% of patients treated with antithymocyte globulin became transfusion independent. Response was associated with a statistically significant longer survival and an almost significant decreased time to disease progression. Treatment with antithymocyte globulin did not seem to be detrimental because historical overall median survival times were similar to those of nonresponders.
Myelodysplastic syndromes are bone marrow disorders that are characterized by ineffective hematopoiesis and leukemic transformation.
Almost half of the deaths caused by these syndromes are from cytopenia.
Standard supportive care (red blood cell and platelet transfusions and hematopoietic growth factors) often fails.
This prospective case series found that one third of 61 patients with red blood cell transfusion-dependent myelodysplastic syndrome became transfusion independent within 8 months of a 4-day course of intravenous antithymocyte globulin.
Before instituting treatment changes on the basis of these exciting preliminary findings, physicians should watch for controlled studies that compare transfusion and survival outcomes in patients treated with antithymocyte globulin and patients given usual care (or other therapies).
Table 1. Patient Characteristics, Diagnoses, and Treatment
Table 2. Outcome after Treatment with Antithymocyte Globulin
Table 3. Univariate and Multivariate Logistic Regression Analyses for Predicting Response
Overall survival of the 61 patients enrolled in the study.Top.Bottom.
Table 4. Univariate and Multivariate Cox Regression Analyses for Mortality
Overall time to progression (to refractory anemia with excess blast cells in transformation or to acute myelogenous leukemia) for the 61 patients enrolled in the study.Top.Bottom.
Table 5. Univariate and Multivariate Cox Regression Analyses for Leukemic Progression
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Molldrem JJ, Leifer E, Bahceci E, Saunthararajah Y, Rivera M, Dunbar C, et al. Antithymocyte Globulin for Treatment of the Bone Marrow Failure Associated with Myelodysplastic Syndromes. Ann Intern Med. 2002;137:156–163. doi: 10.7326/0003-4819-137-3-200208060-00007
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Published: Ann Intern Med. 2002;137(3):156-163.
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