Prolonged Survival in Chronic Myelogenous Leukemia after Cytogenetic Response to Interferon-α Therapy
- Hagop M. Kantarjian, MD;
- Terry L. Smith, MS;
- Susan O'Brien, MD;
- Miloslav Beran, MD, PhD;
- Sherry Pierce, RN;
- Moshe Talpaz, MD; and
- The Leukemia Service*
- From the M.D. Anderson Cancer Center, Houston, Texas. For members of the Leukemia Service, see Appendix. Requests for Reprints: Hagop Kantarjian, MD, Department of Hematology, Box 61, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Grant Support: In part by National Cancer Institute grant CA19639. Dr. Kantarjian is a Scholar of the Leukemia Society of America.
Abstract
Objective: To determine whether a cytogenetic response after interferon-α therapy in patients with chronic myelogenous leukemia is independently associated with improved survival.
Design: Retrospective analysis.
Patients: 274 patients with a diagnosis of Philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase who were treated with interferon-α-based programs between 1982 and 1990.
Intervention: Therapy with daily subcutaneous interferon-α given at 5 × 106 U/m2 body surface area (highest dose schedule allowed on studies) or the maximally tolerated lower-dose schedule.
Results: Overall, 219 (80%) patients achieved a complete hematologic response and 104 (38%) achieved a major cytogenetic response (<35% Philadelphia chromosome-positive cells). Estimated median survival was 89 months. Several pretreatment factors were associated with failure to achieve a major cytogenetic response and with worse survival. The existing prognostic models were generally predictive of which patients were likely to achieve a major cytogenetic response (P ≤ 0.01) and of survival outcomes (P ≤ 0.01). Multivariate analysis identified bone marrow basophilia (P < 0.01) and splenomegaly (P < 0.01) as independent poor prognostic factors for survival. Achievement of a major cytogenetic response, entered as a time-dependent variable while accounting for the other independent factors, was associated with improved survival (P < 0.001). Comparison of survival (dated from 12 months into therapy) with cytogenetic response at 12 months showed that a cytogenetic response was associated with longer survival (P < 0.001).
Conclusion: Achieving a cytogenetic response with interferon-α therapy in patients with chronic myelogenous leukemia was independently associated with improved survival when tested as a time-dependent variable in a multivariate analysis, and this association was confirmed by landmark analysis at 12 months.
*For members of the Leukemia Service, see Appendix.
- Copyright ©2004 by the American College of Physicians
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