Meng-Ju Li1,2, Hsi-Che Liu3, Hsiu-Ju Yen4, Tang-Her Jaing5, Dong-Tsamn Lin1, Chao-Ping Yang5, Kai-Hsin Lin1, Iou-Jih Hung5, Shiann-Tarng Jou1, Meng-Yao Lu1, Chih-Cheng Hsiao6, Ching-Tien Peng7,8, Tai-Tsung Chang9, Shih-Chung Wang10, Ming-Tsan Lin10, Jiann-Shiuh Chen11, Te-Kau Chang12, Giun-Yi Hung4, Kang-Hsi Wu7, Yung-Li Yang13, Hsiu-Hao Chang1, Shih-Hsiang Chen5, Ting-Chi Yeh3, Chao-Neng Cheng11, Pei-Chin Lin14, Shyh-Shin Chiou14, Jiunn-Ming Sheen6, Shin-Nan Cheng15, Shu-Huey Chen16, Yu-Hsiang Chang17, Wan-Ling Ho1,18,19, Yu-Hua Chao20, Rong-Long Chen21, Bow-Wen Chen21, Jinn-Li Wang22, Yuh-Lin Hsieh23, Yu-Mei Liao14, Shang-Hsien Yang24, Wan-Hui Chang25, Yu-Mei Y Chao25, Der-Cherng Liang3. 1. Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. 2. Department of Pediatrics, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan. 3. Department of Pediatrics, Mackay Memorial Hospital, Mackay Medical College, Taipei, Taiwan. 4. Department of Pediatrics, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan. 5. Department of Hematology-Oncology, Chang Gung Children's Hospital-Linkou, Taoyuan, Taiwan. 6. Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 7. Division of Pediatric Hematology & Oncology, China Medical University Children's Hospital, Taichung, Taiwan. 8. Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan. 9. Department of Pediatrics, E-Da Hospital, Kaohsiung, Taiwan. 10. Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan. 11. Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan. 12. Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan. 13. Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. 14. Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 15. Department of Pediatrics, Tungs' Taichung Metro Harbor Hospital, Taichung, Taiwan. 16. Department of Pediatrics, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan. 17. Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. 18. Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. 19. School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. 20. Department of Pediatrics, Chung Shan Medical University Hospital, School of Medicine, Chung Shan Medical University, Taichung, Taiwan. 21. Division of Pediatric Hematology and Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan. 22. Department of Pediatrics, Wanfang Hospital Taipei Medical University, Taipei, Taiwan. 23. Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan. 24. Department of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan. 25. Childhood Cancer Foundation, Taipei, Taiwan.
Abstract
BACKGROUND:Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or "low-risk" in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol. SR patients were randomized to receive single or double reinduction courses. The patients enrolled before 2009 received CrRT, while those enrolled later did not. The Kaplan-Meier method was used to estimate survival rates and the difference between two groups was compared by the two-sided log-rank test. RESULTS: In 1,366 eligible patients, the 5-year overall survival (OS) was 81.6 ± 1.1% (standard error) and 5-year event-free survival (EFS) was 74.3 ± 1.2%. In SR patients, the 5-year OS for one and two reinduction courses was 91.6 ± 2.1% and 93.7 ± 1.8%, respectively, and the 5-year EFS was 85.2 ± 2.7% and 89.8 ± 2.3%, respectively. There were no significant differences in survival between these two groups. Patients with MLL or BCR-ABL1 had the worst outcomes: 5-year EFS was 23.4 and 31.8% and 5-year OS was 28.6 and 44.7%, respectively. There was no significant difference in CNS relapse or survival between the era with or without CrRT. CONCLUSIONS: For SR patients, one-course reinduction was adequate. Triple intrathecal therapy alone successfully prevented CNS relapse.
RCT Entities:
BACKGROUND: Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or "low-risk" in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol. SR patients were randomized to receive single or double reinduction courses. The patients enrolled before 2009 received CrRT, while those enrolled later did not. The Kaplan-Meier method was used to estimate survival rates and the difference between two groups was compared by the two-sided log-rank test. RESULTS: In 1,366 eligible patients, the 5-year overall survival (OS) was 81.6 ± 1.1% (standard error) and 5-year event-free survival (EFS) was 74.3 ± 1.2%. In SR patients, the 5-year OS for one and two reinduction courses was 91.6 ± 2.1% and 93.7 ± 1.8%, respectively, and the 5-year EFS was 85.2 ± 2.7% and 89.8 ± 2.3%, respectively. There were no significant differences in survival between these two groups. Patients with MLL or BCR-ABL1 had the worst outcomes: 5-year EFS was 23.4 and 31.8% and 5-year OS was 28.6 and 44.7%, respectively. There was no significant difference in CNS relapse or survival between the era with or without CrRT. CONCLUSIONS: For SR patients, one-course reinduction was adequate. Triple intrathecal therapy alone successfully prevented CNS relapse.