• Stefan Fruehauf, Julian Topaly, Eike C Buss, Thomas Fischer, Oliver G Ottmann, Bertold Emmerich, Martin C Müller, Peter Schuld, Leopold Balleisen, Rüdiger Hehlmann, Anthony D Ho, and Andreas Hochhaus.
• Internal Medicine V, University of Heidelberg, Heidelberg, Germany. prof.stefan.fruehauf@pk-mx.de
• Cancer. 2007 Apr 15; 109 (8): 1543-9.

BackgroundDespite advances in drug therapy and allogeneic stem cell transplantation (allo-SCT), the prognosis of patients with chronic myeloid leukemia (CML) in blast crisis remains poor. Imatinib has demonstrated synergistic effects in vitro with mitoxantrone, etoposide, and cytarabine.MethodsA Phase I/II trial was performed in patients with CML myeloid blast crisis. Patients were treated with imatinib + mitoxantrone/etoposide in four cohorts: mitoxantrone 10 mg/m(2)/day and etoposide 100 mg/m(2)/day for 2 or 3 consecutive days and imatinib 600 mg/day from Day 15 (cohorts 1 and 2) or from Day 1 (cohorts 3 and 4). After hematologic reconstitution after the cytopenic phase, cytarabine was given at a dose of 10 mg/m(2)/day in addition to imatinib as maintenance treatment.ResultsA total of 16 patients were available for analysis, median age 59 years (range, 37-74). All patients who received more intensive induction treatment (cohorts 3 and 4, n = 7) achieved a hematologic response (HR). In contrast, HR was achieved in only 6 of 9 patients treated in cohorts 1 and 2. The induction treatment was well tolerated. Six patients who achieved HR received an allo-SCT with myeloablative conditioning. The median survival in the transplant group was 16.2 months vs 4.7 months in the group with conventional treatment only (P = .067).ConclusionsThe combination of mitoxantrone/etoposide and imatinib is well tolerated, with mild nonhematologic toxicity even in older patients. Eligible patients benefit from allo-SCT after response to the induction treatment.

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