JCCG ALL-B12: Evaluation of Intensified Therapies With Vincristine/Dexamethasone Pulses and Asparaginase and Augmented High-Dose Methotrexate for Pediatric B-ALL
Abstract
PURPOSE The JCCG ALL-B12 clinical trial aimed to evaluate the effectiveness of unvalidated treatment phases for pediatric ALL and develop a safety-focused treatment framework. PATIENTS AND METHODS Patients age 1-19 years with newly diagnosed B-ALL were enrolled in this study. These patients were stratified into standard-risk (SR), intermediate-risk (IR), and high-risk (HR) groups. Randomized comparisons assessed the effectiveness of vincristine (VCR)/dexamethasone pulses in the SR group, evaluated the effects of L-asparaginase (ASP) intensification in the IR group, and compared standard consolidation including block-type treatment with experimental consolidation with high-dose methotrexate (HD-MTX) intensified with VCR and ASP in the HR group. RESULTS Of 1,936 patients enrolled, 1,804 were eligible for the experimental treatment. The overall 5-year event-free survival and overall survival rates were 85.2% (95% CI, 83.5 to 86.8) and 94.3% (95% CI, 93.1 to 95.3), respectively. The cumulative incidence of relapse and postremission nonrelapse mortality was 13.2% (95% CI, 11.6 to 14.8) and 0.6% (95% CI, 0.3 to 1.0), respectively. Random assignment in the SR group showed no significant benefit from pulse therapy. In the IR group, ASP intensification had limited effects. In the HR group, standard block therapy and HD-MTX yielded equivalent outcomes. CONCLUSION The ALL-B12 trial achieved favorable outcomes in a nationwide cohort by stratifying treatment on the basis of risk and balancing treatment intensity. This study not only demonstrated that existing standard of care can be further refined but also indicated that improvement in outcomes with intensified chemotherapy has reached a plateau.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (27)
Motohiro Kato
6Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Yasuhiro Okamoto
Toshihiko Imamura
Akiko Kada
5NHO Nagoya Medical Center, Nagoya, Japan
Akiko M. Saito
National Hospital Organization Nagoya Medical Center, Aichi, Japan
Yuka Iijima-Yamashita
5NHO Nagoya Medical Center, Nagoya, Japan
Takao Deguchi
22Division of Cancer Immunodiagnostics, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
Kentaro Ohki
14Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan
Takashi Fukushima
Kenichi Anami
Department of Medical Oncology, Hematology, and Infectious Diseases, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
Masashi Sanada
5NHO Nagoya Medical Center, Nagoya, Japan
Tomohiko Taki
8Kyorin University Faculty of Health Sciences, Mitaka, Japan
Yoshiko Hashii
9Osaka University, Suita, Japan
Takeshi Inukai
Nobutaka Kiyokawa
14Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan
Yoshiyuki Kosaka
Department of Hematology and Oncology, Kobe Children's Hospital, Kobe, Japan
Nao Yoshida
Yuki Yuza
10Tokyo Metropolitan Children's Medical Center, Department of Hematology and Oncology, Tokyo, Japan
Masakatsu Yanagimachi
7Kanagawa Children's Medical Center, Yokohama, Japan
Kenichiro Watanabe
8Shizuoka Children's Hospital, Shizuoka, Japan
Atsushi Sato
Chihaya Imai
Takashi Taga
8Shiga University of Medical Science, Department of Pediatrics, Shiga, Japan
Souichi Adachi
9Kyoto University Graduate School of Medicine, Department of Human Health Sciences, Kyoto, Japan
Keizo Horibe
14NHO Nagoya Medical Center, Clinical Research Center, Nagoya, Japan
Atsushi Manabe
9Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Katsuyoshi Koh
23Japan Children’s Cancer Group ALL Committee, Nagoya, Japan