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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, The Leukemia Service*
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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.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;122(4):254-261. doi:10.7326/0003-4819-122-4-199502150-00003
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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.


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Figure 1.
Survival of 274 patients with Philadelphia chromosome-positive, early chronic-phase chronic myelogenous leukemia who were treated with interferon-α between 1982 and 1990.

Data are censored for patients having allogeneic bone marrow transplantation in the chronic phase.

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Figure 2.
Survival of patients in different prognostic groups according to the three models derived from our institution and the Sokal model.top lefttop right[14][15][16]PPP

The overall ( ) and clinical ( ) prognostic models have been previously described , as have the synthesis model (bottom left ), and the Sokal model (bottom right ). The four models show a good discrimination of patients treated with interferon-α into good-, intermediate-, and poor-risk groups ( = 0.01 for the overall model, < 0.01 for the clinical and synthesis models, and = 0.10 for the Sokal model).

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Figure 3.
Landmark analysis of survival dated from 12 months into therapy by the cytogenetic response at 12 months. P

< 0.001 for survival of patients with a cytogenetic response compared with those without a response. CR = complete response; IFN-α = interferon-α; PR = partial response.

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