MRC trials in childhood acute myeloid leukaemia

The modern approach to therapy for acute myeloid leukaemia (AML) in children began in the late 80's and in the MRC series led to a 30% improvement in survival, up to levels of about 50%. Since 1995 the most recent trial AML 12 has taken those figures to two thirds event free survival and similar overall survival. Resistant disease rates remain at 4% overall but the death rate in complete remission has fallen from 11% to 6% despite increasing intensity of therapy, and due to advances in supportive care including nutrition and antibiotics/antifungals. However, although relapse rates have continued to fall, the biggest challenge is to reduce the currently one third relapse rate. We are much better at predicting who is likely to relapse, based mainly on primary resistance to therapy and karyotype. Analysis of 629 out of the last 808 cases in whom cytogenetic testing was successful (78%) has shown very clearly that t(8;21), t(15;17), inv(16) are independent good risk features. Additionally, loss of a sex chromosome in the 8;21 group defines a group which does exceptionally well, with 93% EFS at 5 years. Chromosome 7 abnormalities also remain of independent prognostic significance when age, WHO classification and white cell count are taken into account, with monosomy 7 doing even worse than 7q abnormalities. The current trial MRC AML 15 investigates the role of fludarabine--idarubicin combination therapy in the induction courses and the role of high dose cytarabine during consolidation; the aim being to increase efficacy and reduce toxicity, particularly that involving the heart. New approaches such as targeted antibody therapy will be explored when toxicity data for children permits.