Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980-1997

Results of three consecutive completed UK trials (1980-1997) for childhood lymphoblastic leukaemia are presented. National accrual has progressively i ncreased so that over 90% of all the country's ALL cases were treated on th e latest trial reported, UKALLXI. From 1980 to 1990, event-free and overall survival progressively improved, following adoption of an American therapy template and use of two post-remission intensification modules. Since 1990 despite demonstration of the benefit of a third intensification module ove rall event-free survival (EFS) has not improved further. Survival remains h igh due to a good retrieval rate especially for those relapsing off treatme nt after receipt of two intensification pulses. Possible reasons for the pl ateau in event-free survival (including type and dose of induction steroid, dropping of induction anthracycline, type and dose of asparaginase, gaps e arly in therapy following intensification, and overall lack of compliance i n maintenance) are being explored in the latest protocol ALL '97. Cranial i rradiation had been successfully replaced by a long course of intrathecal m ethotrexate injections for the majority of patients. Age (<1 year >10 years ) sex (mate) and white count >50 x 10(9)/I plus slow initial bone marrow cl earance were consistently the most important independent prognostic indicat ors during this time period. Rome/NCI criteria accurately predict standard and highrisk groups for B cell lineage, but not consistently for T cell dis ease. This international collaborative Venture might help us to define thos e truly at highest risk, and how we can optimise therapy for specific subgr oups including T-ALL and those with unfavourable cytogenetics.