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Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial

Burnett, Alan Kenneth, Hills, Robert Kerrin, Milligan, Donald W., Goldstone, Anthony H., Prentice, Archibald G., McMullin, Mary-Frances, Duncombe, Andrew, Gibson, Brenda and Wheatley, Keith 2010. Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial. Journal of Clinical Oncology 28 (4) , pp. 586-595. 10.1200/JCO.2009.22.9088

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Abstract

Purpose. To optimize treatment for younger patients with acute myeloid leukemia and high-risk myelodysplastic syndrome by comparing induction options and the number of consolidation courses and whether consolidation should include transplantation. Patients and Methods. We randomly assigned 1,658 patients younger than age 60 years to receive mitoxantrone/cytarabine/etoposide versus cytarabine/daunorubicin/etoposide and subsequently 1,193 patients to daunorubicin/cytarabine/thioguanine (DAT) where the cytarabine dose was standard (S-DAT) versus double the standard dose (H-DAT). Patients in this randomization were randomly assigned to all-trans-retinoic acid or not. In consolidation, 992 patients were randomly assigned between a total of four courses versus five courses, and 324 patients who were not good risk were randomly assigned to transplantation or chemotherapy as the final course. Results. Complete remission (CR) was achieved in 74% of patients and CR without recovery was achieved in an additional 11%; overall survival (OS) at 8 years was 38%. No differences in CR, relapse-free survival, relapse, or OS were seen between any of the induction randomizations except for a reduction in relapse risk (RR) on the mitoxantrone arm, which was offset by increased myelosuppression and deaths in CR. The addition of a fifth course did not improve OS and may be detrimental in older patients. Although transplantation reduced RR, it did not improve OS for the intermediate-risk group but was probably of benefit in high-risk patients. Conclusion. Several chemotherapy schedules achieved similar remission rates and OS. Four courses of chemotherapy are adequate, but the addition of transplantation as a final course does not improve OS. New agents are required to enhance conventional chemotherapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Publisher: American Society of Clinical Oncology
ISSN: 0732-183X
Last Modified: 25 Jun 2017 03:28
URI: http://orca-mwe.cf.ac.uk/id/eprint/29236

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