Long-term results in children with standard risk acute lymphoblastic leukaemia treated with 5.0 g/m2 versus 3.0 g/m2 methotrexate i.v. according to the modified ALL-BFM 90 protocol. The report of Polish paediatric Leukemia/lymphoma study group
PURPOSE: A non objective randomised, retrospective study was performed to assess and compare the efficacy of two different high doses of methotrexate (HD-MTX) in combination with intrathecal therapy in children with standard risk (SR) ALL as central nervous system (CNS) preventive therapy in a place of cranial radiation. PATIENTS AND METHODS: Between July 1993 and April 2002, in 650 children standard risk (SR) ALL were diagnosed and treated in Poland according to the modified ALL-BFM 90 protocol. Methotrexate was used in the dose of either 3.0 g/m2 (group A) or 5.0 g/m2 (group B) four times in two week intervals during consolidation (protocol M). RESULTS: Probability for 10-year event-free survival (pEFS) and relapse-free survival (pRFS) for all evaluated patients (n = 611) was 0.77 ± 0.02 and 0.82 ± 0.02, respectively. EFS probability for group A (n = 411) was 0.73 ± 0.03 and for group B (n = 200) – 0.85 ± 0.04, whilst RFS probability for group A was 0.79 ± 0.04 and for group B – 0.89 ± 0.03, and these differences proved statistically significant (P = 0.0050 and P = 0.0012). In multivariate analysis, T-cell immunophenotype (P = 0.0046) and age older than 10 years (P = 0.0250) had a significantly adverse impact on the outcome. CONCLUSIONS: HD-MTX used in dose 5.0 g/m2 has been found to be more effective in the treatment of SR ALL in children than HD-MTX in dose 3.0 g/m2.