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ARTICLE

Prolonged Survival in Chronic Myelogenous Leukemia after Cytogenetic Response to Interferon-{alpha} Therapy

right arrow Hagop M. Kantarjian; Terry L. Smith; Susan O'Brien; Miloslav Beran; Sherry Pierce; Moshe Talpaz, The Leukemia Service*

15 February 1995 | Volume 122 Issue 4 | Pages 254-261

Objective: To determine whether a cytogenetic response after interferon-{alpha} 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-{alpha}-based programs between 1982 and 1990.

Intervention: Therapy with daily subcutaneous interferon-{alpha} given at 5 x 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-{alpha} 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.

Author and Article Information
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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.




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