Interferon Alfa Versus Chemotherapy for Chronic Myeloid Leukemia: A Meta-analysis of Seven Randomized Trials

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Abstract
Background: Several randomized clinical trials in chronic myeloid leukemia (CML) have reported better patient survival with interferon alfa (IFN α) than with standard chemotherapeutic agents, such as busulfan or hydroxyurea. However, the size and persistence of this survival benefit is uncertain. Our aim was to assess these reliably, both overall and in particular patient subgroups. Methods: We collaborated in a worldwide overview of all clinical trials in which patients with CML were randomly assigned to receive either IFN α as the main drug or standard chemotherapy. Trials were identified by electronic and hand searching of the medical literature and databases and by personal contact. Individual patient data were available for each of 1554 patients who had been randomly assigned to treatment in seven trials (German, Italian, British, French, Japanese, and “Benelux”). Intentionto- treat stratified logrank survival analyses were performed, reporting two-sided P values. Results: Almost all of the patients in these trials had disease with the Philadelphia chromosome abnormality. Among those who did, the regimens that involved IFN α produced a statistically significantly better survival than those involving either hydroxyurea ( P = .001) or busulfan ( P = .00007) alone. The 5-year survival rates were 57% with IFN α and 42% with chemotherapy, with an absolute difference of 15% (standard deviation = 3%; P <.00001). There were no trials or subgroups of patients in which the treatment difference was statistically significantly different from the average. Conclusion: For patients with Philadelphia chromosome-positive chronic myeloid leukemia, the inclusion of IFN α in the therapeutic regimen produced substantially better 5-year survival than standard chemotherapy alone.