PROLONGED SURVIVAL IN CHRONIC MYELOGENOUS LEUKEMIA AFTER CYTOGENETIC RESPONSE TO INTERFERON-ALPHA THERAPY

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 10(6) U/m(2) 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 less than or equal to 0.01) and of survival outcomes (P less than or equal to 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.