Imatinib mesylate as treatment for blastic transformation of Philadelphia chromosome positive chronic myelogenous leukemia

Clinical Hematology Division, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. asureda@hsp.santpau.es

BACKGROUND AND OBJECTIVES: Imatinib mesylate (STI571) is a selective inhibitor of the bcr/abl tyrosine kinase with therapeutic potential in the blast crisis (BC) of chronic myelogenous leukemia (CML). DESIGN AND METHODS: We report the characteristics and clinical outcome of 30 patients [16 males and 14 females, median age 50 (range, 18 to 72) years] with CML in BC included in a phase II international multicenter extended trial of treatment with imatinib. The initially administered dose of imatinib was 600 mg orally once daily. RESULTS: Eighteen patients (60%) achieved a sustained hematologic remission (SHR) at a median time of 4 weeks (range, 2-14) after starting therapy. The median duration of SHR was 5 months (range, 4-13). Four patients (13%) achieved a cytogenetic remission at a median time of 8 weeks (range, 6-10) after beginning imatinib therapy. The rates of event-free survival (EFS) and overall survival (OS) at 1 year were 29%+/-8% and 36%+/-13%, respectively. In univariate analysis, the achievement of a SHR was more frequent in patients without a complex karyotype and in those receiving imatinib without having had previous chemotherapy. A long interval between the diagnosis of BC and imatinib therapy (> or = 9.5 weeks) (p=0.0011), the presence of additional cytogenetic abnormalities (p=0.015), and extramedullary involvement (p=0.02) were associated with significantly shorter EFS. In contrast, longer OS was observed in patients treated with imatinib shortly after the diagnosis of BC (p=0.0003) and in those without additional cytogenetic abnormalities (p=0.0043). Multivariate analyses indicated that the time interval between the diagnosis of BC and the beginning of imatinib therapy was the only significant prognostic factor for both EFS and OS. INTERPRETATION AND CONCLUSIONS: STI571 therapy produces a high percentage of SHR in patients with CML in BC; a minority of the patients also obtain some degree of cytogenetic response. Nevertheless, these responses are transient and additional therapy should be offered.

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