High-Dose Cytarabine in Induction Treatment Improves the Outcome of Adult Patients Younger Than Age 46 Years With Acute Myeloid Leukemia: Results of the EORTC-GIMEMA AML-12 Trial
[en] Purpose : Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m2 for remission induction. Consensus has not been reached on the benefit of higher dosages of cytarabine.
Patients and Methods : The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m2 per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m2 every 12 hours by 3-hour infusion on days 1, 3, 5, and 7). Patients in complete remission (CR) received a single consolidation cycle containing daunorubicin and intermediate-dose cytarabine (500 mg/m2 every 12 hours for 6 days).
Subsequently, a stem-cell transplantation was planned. The primary end point was survival.
Results : At a median follow-up of 6 years, overall survival was 38.7% for patients randomly assigned to SD cytarabine and 42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06; multivariable analysis P = .009). For patients younger than age 46 years, survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P = .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%, respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P = .001) and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and 68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal tandem duplication) mutation, or with secondary AML benefitted from HD cytarabine.
Conclusion : HD cytarabine produces higher remission and survival rates than SD cytarabine, especially in patients younger than age 46 years.
Disciplines :
Hematology
Author, co-author :
Willemze, Roelof
Suciu, Stefan
Meloni, Giovanna
Labar, Boris
Marie, Jean-Pierre
Halkes, Constantijn
Muus, Petra
Mistrik, Martin
Amadori, Sergio
Specchia, Giorgina
Fabbiano, Francesco
Nobile, Francesco
Sborgia, Marco
Camera, Andrea
Selleslag, Dominik
Lefrère, François
Magro, Domenico
Sica, Simona
Cantore, Nicola
Beksac, Meral
Berneman, Zwi
Thomas, Xavier
Melillo, Lorella
Guimaraes, Jose
Leoni, Pietro
Luppi, Mario
Mitra, Maria
Bron, Dominique
Fillet, Georges ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
High-Dose Cytarabine in Induction Treatment Improves the Outcome of Adult Patients Younger Than Age 46 Years With Acute Myeloid Leukemia: Results of the EORTC-GIMEMA AML-12 Trial
Publication date :
2014
Journal title :
Journal of Clinical Oncology
ISSN :
0732-183X
eISSN :
1527-7755
Publisher :
American Society of Clinical Oncology, Alexandria, United States - Virginia
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