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

   

Authors:	Luskin, M. R.; Lee, J. W.; Fernandez, H. F.; Abdel-Wahab, O.; Bennett, J. M.; Ketterling, R. P.; Lazarus, H. M.; Levine, R. L.; Litzow, M. R.; Paietta, E. M.; Patel, J. P.; Racevskis, J.; Rowe, J. M.; Tallman, M. S.; Sun, Z.; Luger, S. M.
Article Title:	Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups
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/m2) 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 a FLT3-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/m2), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P 5 .001). Younger patients (<50 years) benefited from HD daunorubicin (HR, 0.66; P 5 .002), as did patients with favorable and intermediate cytogenetics (HR, 0.51; P 5 .03 andHR, 0.68;P5.01, respectively). Patients with unfavorable cytogenetics wereshownto benefit from HD daunorubicin on multivariable analysis (adjusted HR, 0.66; P 5 .04). Patients with FLT3-ITD (24%), DNMT3A (24%), and NPM1 (26%) mutant AML all benefited from HDdaunorubicin (HR, 0.61, P5.009; HR, 0.62, P5.02; and HR, 0.50, P5.002; 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. © 2016 by The American Society of Hematology.
Journal Title:	Blood
Volume:	127
Issue:	12
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	2016-03-24
Start Page:	1551
End Page:	1558
Language:	English
DOI:	10.1182/blood-2015-07-657403
PROVIDER:	scopus
PMCID:	PMC4807422
PUBMED:	26755712
DOI/URL:	https://www.scopus.com/inward/record.url?eid=2-s2.0-84962304176&partnerID=40&md5=02ba748c26c02cc85c1e7af0e31f6bf2
Notes:	Article -- Export Date: 2 May 2016 -- Source: Scopus

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