The first 2 authors contributed equally.
Imatinib combined with mitoxantrone/etoposide and cytarabine is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis
Version of Record online: 5 MAR 2007
Copyright © 2007 American Cancer Society
Volume 109, Issue 8, pages 1543–1549, 15 April 2007
How to Cite
Fruehauf, S., Topaly, J., Buss, E. C., Fischer, T., Ottmann, O. G., Emmerich, B., Müller, M. C., Schuld, P., Balleisen, L., Hehlmann, R., Ho, A. D. and Hochhaus, A. (2007), Imatinib combined with mitoxantrone/etoposide and cytarabine is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis. Cancer, 109: 1543–1549. doi: 10.1002/cncr.22535
- Issue online: 4 APR 2007
- Version of Record online: 5 MAR 2007
- Manuscript Accepted: 18 DEC 2006
- Manuscript Revised: 13 DEC 2006
- Manuscript Received: 6 NOV 2006
- Suddeutsche Hamoblastosegesellschaft (SHG)
- Competence Network ‘Acute and chronic leukemais,’ sponsored by the German Bundesministerium fur Bildung und Forschung (Projekttrager Gesundheitsforschung: DLR e.V.-01 GI9980/6)
- European LeukemiaNet within the 6th Framework program of the European Commission
- myeloid blast crisis;
- allogeneic transplantation
Despite 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.
A 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/m2/day and etoposide 100 mg/m2/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/m2/day in addition to imatinib as maintenance treatment.
A 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).
The 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. Cancer 2007. © 2007 American Cancer Society.