Originally published as JCO Early Release 10.1200/JCO.2008.18.7948 on July 20 2009

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Risk-Stratified Therapy and the Intensive Use of Cytarabine Improves the Outcome in Childhood Acute Myeloid Leukemia: The AML99 Trial From the Japanese Childhood AML Cooperative Study Group

From the Department of Pediatrics, Toho University School of Medicine, Tokyo; Department of Pediatrics, Osaka National Hospital, Osaka; Clinical Research Center, Nagoya Hospital Organization Nagoya Medical Center; Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya; Division of Hematology, Kanagawa Children's Medical Center, Yokohama; Department of Pediatrics, Ibaraki Children's Hospital, Mito; Specialized Clinical Science, Pediatrics, Tokai University School of Medicine, Kanagawa; Department of Pediatrics, Hamanomachi Hospital, Fukuoka; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo; Department of Pediatrics, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima; Department of Hematology and Oncology, Miyagi Children's Hospital, Sendai; Department of Pediatrics, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto; Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Miyagi; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.

Corresponding author: Akio Tawa, MD, PhD, Department of Pediatrics, National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka 540-0006, Japan; e-mail: tawa{at}onh.go.jp.

Purpose To improve the prognosis in children with newly diagnosed acute myeloid leukemia (AML) by introducing a dose-dense intensive chemotherapy regimen and an appropriate risk stratification system.

Patients and Methods Two hundred forty children with de novo AML were treated with continuous cytarabine-based induction therapy and stratified to three risk groups based on the initial treatment response, age, and WBC at diagnosis and cytogenetics. All of the patients were treated with intensive consolidation chemotherapy including three or four courses of high-dose cytarabine. Allogeneic hematopoietic stem-cell transplantation (HSCT) was indicated for only the intermediate-risk patients with matched related donors and for all the high-risk subsets.

Results Two hundred twenty-seven children (94.6%) achieved a complete remission (CR). Four children demonstrated induction death. The median follow-up of the live patients was 55 months (range, 37 to 73 months). The 5-year overall survival of all 240 children was 75.6% (95% CI, 70.3% to 81.4%) and event-free survival was 61.6% (95% CI, 55.8% to 68.1%). The 5-year disease-free survival in each risk group were 71.3% (95% CI, 63.4% to 80.2%) in the low-risk group (n = 112), 59.8% (95% CI, 50.6% to 70.7%) in the intermediate-risk group (n = 92), and 56.5% (95% CI, 39.5% to 80.9%) in the high-risk group (n = 23). Eight children died during the first CR, including four after HSCT.

Conclusion A high survival rate, 75.6% at 5 years, was achieved for childhood with de novo AML in the AML99 trial. The treatment strategy was well tolerated with only 1.7% induction death rate and 3.5% remission death rate. Low-risk children were successfully treated with chemotherapy alone.

Supported by a grant-in aid for cancer research and a grant for clinical cancer research from the Ministry of Health, Labor and Welfare, Japan.

Presented in part in the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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