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Blood. 2016 Mar 24;127(12):1551-8. doi: 10.1182/blood-2015-07-657403. Epub 2016 Jan 11.

Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups.

Author information

1
Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA;
2
Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Biostatistics Center, Dana-Farber Cancer Institute, Boston, MA;
3
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL;
4
Human Oncology and Pathogenesis Program, and Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY;
5
Department of Pathology, University of Rochester, Rochester, NY;
6
Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN;
7
Seidman Cancer Center, Case Western Reserve University, Cleveland, OH;
8
Department of Hematology, Mayo Clinic, Rochester, MN;
9
Department of Oncology, Montefiore Medical Center, Bronx, NY; and.
10
Human Oncology and Pathogenesis Program, and.
11
Rambam Medical Center, Haifa, Israel.
12
Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY;

Abstract

The initial report of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group trial E1900 (#NCT00049517) showed that induction therapy with high-dose (HD) daunorubicin (90 mg/m(2)) improved overall survival in adults <60 years old with acute myeloid leukemia (AML); however, at initial analysis, the benefit was restricted to younger patients (<50 years) and patients without unfavorable cytogenetics or aFLT3-ITD mutation. Here, we update the results of E1900 after longer follow-up (median, 80.1 months among survivors), focusing on the benefit of HD daunorubicin on common genetic subgroups. Compared with standard-dose daunorubicin (45 mg/m(2)), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P= .001). Younger patients (<50 years) benefited from HD daunorubicin (HR, 0.66;P= .002), as did patients with favorable and intermediate cytogenetics (HR, 0.51;P= .03 and HR, 0.68;P= .01, respectively). Patients with unfavorable cytogenetics were shown to benefit from HD daunorubicin on multivariable analysis (adjusted HR, 0.66;P= .04). Patients with FLT3-ITD (24%),DNMT3A(24%), and NPM1(26%) mutant AML all benefited from HD daunorubicin (HR, 0.61,P= .009; HR, 0.62,P= .02; and HR, 0.50,P= .002; respectively). HD benefit was seen in the subgroup of older patients (50-60 years) with the FLT3-ITD or NPM1 mutation. Additionally, the presence of an NPM1 mutation confers a favorable prognosis only for patients receiving anthracycline dose intensification during induction.

PMID:
26755712
PMCID:
PMC4807422
DOI:
10.1182/blood-2015-07-657403
[Indexed for MEDLINE]
Free PMC Article

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