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The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: A phase-III intergroup study

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Summary

One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4–33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS.

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Authors and Affiliations

  1. Tufts New England medical Center Hospital, Boston, MA

    K. B. Miller

  2. Dana-Farber Cancer Institute, Boston, MA

    K. Kyungmann

  3. University of Mississippi Medical Center, Jackson, MS

    F. S. Morrison

  4. Northwestern University Medical Center, Chicago, IL

    J. N. Winter

  5. University of Rochester Cancer Center, Rochester, NY

    J. M. Bennett

  6. Indiana University Medical Center, Indianapolis, IN

    R. S. Neiman

  7. St. Jude's Childrens Research Hospital, Memphis, TN

    D. R. Head

  8. University of Pennsylvania Cancer Center, Philadelphia, PA

    P. A. Cassileth

  9. Mayo Clinic, Rochester, MN, USA

    M. J. O'Connell

Authors
  1. K. B. Miller
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  2. K. Kyungmann
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  3. F. S. Morrison
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  4. J. N. Winter
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  5. J. M. Bennett
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  6. R. S. Neiman
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  7. D. R. Head
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  8. P. A. Cassileth
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  9. M. J. O'Connell
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Additional information

This study was conducted by the Eastern Cooperative Oncology Group (Douglas C. Tormey, M.D., Ph.D., Chairman, CA 21115) and supported by Public Health Service grants from the NCI, National Institutes of Health, and the Department of Health and Human Services. Institutions from the Southwestern Oncology Group also participated

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Miller, K.B., Kyungmann, K., Morrison, F.S. et al. The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: A phase-III intergroup study. Ann Hematol 65, 162–168 (1992). https://doi.org/10.1007/BF01703109

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  • DOI: https://doi.org/10.1007/BF01703109

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