Keizo Horibe1, Keiko Yumura-Yagi, Tooru Kudoh, Shinichiro Nishimura, Megumi Oda, Makoto Yoshida, Yoshihiro Komada, Junichi Hara, Akio Tawa, Ikuya Usami, Akihiko Tanizawa, Koji Kato, Ryoji Kobayashi, Keitaro Matsuo, Hiroki Hori. 1. *Clinical Research Center, National Hospital Organization Nagoya Medical Center ∥∥Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital ##Division of Molecular Medicine, Aichi Cancer Center, Nagoya †Department of Pediatrics, Osaka General Medical Center **Department of Pediatric, Osaka City General Hospital ††Department of Pediatric Hematolgy/Oncology, National Hospital Organization Osaka Medical Center, Osaka ‡Department of Pediatrics, Hokkaido Medical Center for Child Health and Rehabilitation ¶¶Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo §Hiroshima University Hospital, Hiroshima ∥Department of Pediatrics, Okayama University Hospital, Okayama ¶Department of Pediatrics, Asahikawa Medical College Hospital, Asahikawa #Department of Pediatrics, Mie University Hospital, Tsu ‡‡Department of Pediatrics, Kobe City Medical Center General Hospital, Kobe §§Department of Pediatrics, University of Fukui, Fukui, Japan.
Abstract
PURPOSE: This study was conducted as the first clinical trial by Japan Association of Childhood Leukemia Study to improve the outcome of B-cell acute lymphoblastic leukemia and explore a less toxic reinduction block. PATIENTS AND METHODS: From 1997 to 2002, 563 patients with B-cell acute lymphoblastic leukemia aged 1 to 15 years were enrolled. The patients were assigned into 4 risk groups (standard, intermediate, high, or extremely high risk) and treated with regimens intensified according to the risk. Two randomized trials were conducted to compare 2 regimens with and without a 3-week reinduction therapy in the standard-risk group, and to compare the efficacy of pirarubicin with daunorubicin in the intermediate-risk and high-risk groups. Prophylactic cranial irradiation was restricted in patients with high or extremely high risk. RESULTS: The event-free survival (EFS) rate at 10 years for all patients was 77.0%. Those in the standard-risk to extremely high-risk groups were 79.3%, 72.5%, 71.7%, and 66.3%, respectively. The 15-week induction/consolidation not followed by reinduction produced 76.4% of the EFS at 10 years comparable with the regimen with reinduction therapy. Pirarubicin at 25 mg/m administered 11 times throughout the treatment produced the EFS comparable with daunorubicin at 30 mg/m. CONCLUSION: The trial produced high survival rates in NCI-HR patients, although the outcomes in NCI-SR patients were not satisfactory possibly due to less intensive central nervous system-directed therapy.
RCT Entities:
PURPOSE: This study was conducted as the first clinical trial by Japan Association of Childhood Leukemia Study to improve the outcome of B-cell acute lymphoblastic leukemia and explore a less toxic reinduction block. PATIENTS AND METHODS: From 1997 to 2002, 563 patients with B-cell acute lymphoblastic leukemia aged 1 to 15 years were enrolled. The patients were assigned into 4 risk groups (standard, intermediate, high, or extremely high risk) and treated with regimens intensified according to the risk. Two randomized trials were conducted to compare 2 regimens with and without a 3-week reinduction therapy in the standard-risk group, and to compare the efficacy of pirarubicin with daunorubicin in the intermediate-risk and high-risk groups. Prophylactic cranial irradiation was restricted in patients with high or extremely high risk. RESULTS: The event-free survival (EFS) rate at 10 years for all patients was 77.0%. Those in the standard-risk to extremely high-risk groups were 79.3%, 72.5%, 71.7%, and 66.3%, respectively. The 15-week induction/consolidation not followed by reinduction produced 76.4% of the EFS at 10 years comparable with the regimen with reinduction therapy. Pirarubicin at 25 mg/m administered 11 times throughout the treatment produced the EFS comparable with daunorubicin at 30 mg/m. CONCLUSION: The trial produced high survival rates in NCI-HRpatients, although the outcomes in NCI-SR patients were not satisfactory possibly due to less intensive central nervous system-directed therapy.