The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the Medical Research Council UKALLR1 study

We have examined the toxicity and overall outcome of the Medical Research C ouncil UKALL R1 protocol for 256 patients with relapsed childhood acute lym phoblastic leukaemia (ALL). Second remission was achieved in over 95% of pa tients. Two patients died during induction and seven patients died of resis tant disease. The overall actuarial event-free survival (EFS) at 5 years fo r all patients experiencing a first relapse was 46% (95% CI 40-52). Duratio n of first remission, site of relapse, age at diagnosis and sex emerged as factors of prognostic significance. Five-year EFS was only 7% for children relapsing in the bone marrow within 2 years of diagnosis, but was 77% for t hose relapsing without bone marrow involvement > 2.5 years from diagnosis. All analyses in this report are by treatment received. For those receiving chemotherapy alone, the 5-year EFS was 48%; for autologous bone marrow tran splantation (BMT), the 5-year EFS was 47%; for unrelated donor BMT, it was 52%; and for related donor BMT, the 5-year EFS was 45%. The groups, however , were not comparable with respect to risk factor profile, and therefore di rect comparison of EFS is misleading. Adjustment for time to transplant and prognostic factors was used to reduce the effects of biases between treatm ent groups, but did not suggest benefit for any particular treatment. There was failure of our planned randomization scheme in this trial with only 9% of those eligible being randomized, which highlights the difficulties in r unning randomized trials especially in patients who have relapsed from a pr evious trial. The optimal treatment for relapsed ALL therefore remains unce rtain. Alternative approaches are clearly needed for those with early bone marrow relapse if outcome is to improve.