Treatment for childhood acute lymphoblastic leukemia in Taiwan: Taiwan Pediatric Oncology Group ALL-2002 study emphasizing optimal reinduction therapy and central nervous system preventive therapy without cranial radiation

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 TaiwanPediatricOncology 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 SRpatients, the 5-yearOSfor 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.