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Idarubicin dose escalation during consolidation therapy for adult acute myeloid leukemia


Bradstock, KF and Link, E and Iulio, JD and Szer, J and Marlton, P and Wei, AH and Enno, A and Schwarer, A and Lewis, ID and Da Rozario, J and Coyle, L and Cull, G and Campbell, P and Leahy, MF and Hahn, U and Cannell, P and Tiley, C and Lowenthal, RM and Moore, J and Cartwright, K and Cunningham, I and Taper, J and Grigg, A and Roberts, AW and Benson, W and Hertzberg, M and Deveridge, S and Rowlings, P and Mills, AK and Gill, D and Bardy, P and Campbell, L and Seymour, JF, on behalf of the Australasian Leukaemia & Lymphoma Group, Idarubicin dose escalation during consolidation therapy for adult acute myeloid leukemia, Journal of Clinical Oncology, 35, (15) pp. 1678-1685. ISSN 0732-183X (2017) [Refereed Article]

Copyright Statement

Copyright 2017 American Society of Clinical Oncology

DOI: doi:10.1200/JCO.2016.70.6374


Purpose: Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy.

Patients and Methods: Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m2 daily for 5 days, etoposide 75 mg/m2 daily for 5 days, and idarubicin 9 mg/m2 daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS).

Results: Two hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3-internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation (P < .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm (P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3-internal tandem duplication and NPM1 gene mutation subgroups.

Conclusion: An increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in improved LFS, without increased nonhematologic toxicity.

Item Details

Item Type:Refereed Article
Keywords:acute mylenoid leukemia, AML, idarubicin, consolidation therapy, induction therapy, daunorubicin
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Oncology and carcinogenesis not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Lowenthal, RM (Professor Ray Lowenthal)
ID Code:124617
Year Published:2017
Web of Science® Times Cited:11
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-03-01
Last Modified:2018-07-20

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