Philadelphiachromosomepositive Disease

Patients with Ph-chromosome-positive ALL (Ph+ ALL) have a poor prognosis even with modern treatment regimens. Thus, it is generally recommended that these patients undergo allogeneic transplantation in first CR, as this strategy is curative in a minority of patients.44,45 The development of imatinib, a tyrosine kinase inhibitor with relative specificity for bcr-abl, has dramatically altered the natural history and treatment of patients with CML.46 Imatinib also has some activity in Ph+ ALL, although less so than in patients with CML, with only 29% of relapsed or refractory patients achieving a CR.47 In addition, the median time to progression for responding patients is only 2.2 months, illustrating the development of resistance to imatinib in this patient group.4849 A recent study investigated prognostic factors for response to imatinib mesylatetherapy in patients with ALL.50 Prior CR <6 months, WBC count >10 X 109/L, circulating peripheral blood blasts at diagnosis, additional Ph chromosomes, and at least 2 bcr-abl fusion signals were all associated with a significantly inferior frequency of response and response duration to imatinib mesylate. Given the disappointing responses seen in patients with Ph+ ALL compared with patients with CML treated with imatinib mesylate, many investigators are evaluating the role of imatinib mesylate combination chemotherapy in both the initial treatment setting51 as well as in the relapsed setting.52

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