Different outcome in older children with acute lymphoblastic leukemia with different treatment protocols in the Netherlands

Background: From 1991 until 2004 children with acute lymphoblastic leukemia (ALL) in the Netherlands were treated according to protocols ALL-8 and ALL-9 which were based on different principles. An earlier study showed that the outcome of adolescents highly differed on these protocols. Procedure: In this retrospective study, we analyzed whether the outcome of older children 10-15 years of age at diagnosis differed between the Berlin-Frankfurt-Münster (BFM)-based ALL-8 regimen and the ALL-9 regimen. Two hundred fifty-four older children who were treated according to protocol ALL-8 (n=82) or ALL-9 (n=172) were included in the analysis. Results: A higher 5-year event-free survival (EFS) rate was found for patients treated according to ALL-8 compared to ALL-9 (79±5% vs. 65±4%, P=0.02). Patient characteristics did not differ except for a slightly higher age in ALL-8. Therefore, additional analyses were done including only patients who were 12-15 years of age. In this age group there was also a difference in the 5-year EFS (82±5% vs. 61±5%, P=0.00) as well as in the 5-year overall survival rate; 89±4% compared to 68±5%, respectively (P=0.01). Major difference between protocols was the use of a consolidation and reinduction/intensification course and higher cumulative doses of asparaginase, methotrexate, and anthracyclines in ALL-8. Conclusions: Children 10-15 years of age have been undertreated with the ALL-9 regimen and benefit by intensive treatment components as used in ALL-8. We recommend using BFM-based protocols for these older children with ALL.