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

Roelof Willemze, Stefan Suciu, Giovanna Meloni, Boris Labar, Jean Pierre Marie, Constantijn J M Halkes, Petra Muus, Martin Mistrik, Sergio Amadori, Giorgina Specchia, Francesco Fabbiano, Francesco Nobile, Marco Sborgia, Andrea Camera, Dominik L D Selleslag, Francois Lefrer̀e, Domenico Magro, Simona Sica, Nicola Cantore, Meral BeksacZwi Berneman, Xavier Thomas, Lorella Melillo, Jose E. Guimaraes, Pietro Leoni, Mario Luppi, Maria E. Mitra, Dominique Bron, Georges Fillet, Erik W A Marijt, Adriano Venditti, Anne Hagemeijer, Marco Mancini, Joop Jansen, Daniela Cilloni, Liv Meert, Paola Fazi, Marco Vignetti, Silvia M. Trisolini, Franco Mandelli, Theo De Witte

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)219-228
Number of pages10
JournalJournal of Clinical Oncology
Issue number3
Publication statusPublished - Jan 20 2014

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)


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