RANDOMIZED COMPARISON OF ADDITION OF AUTOLOGOUS BONE-MARROW TRANSPLANTATION TO INTENSIVE CHEMOTHERAPY FOR ACUTE MYELOID-LEUKEMIA IN FIRST REMISSION - RESULTS OF MRC AML-10 TRIAL

Background Three strategies are used to prevent relapse in patients wi th acute myeloid leukaemia in first remission. Most of those with suit able donors are offered allogeneic haemopoietic-stem-cell transplant. Other patients may receive intensive chemotherapy or autologous transp lantation; we undertook this randomised prospective trial to assess wh ich is the better option. Methods After three courses of intensive che motherapy, bone marrow was harvested from patients (<56 years of age) in remission who lacked an HLA-matched sibling donor. These patients w ere then randomised to receive, after one more course of chemotherapy, no further treatment (n=191) or an autologous bone-marrow transplant (BMT) after preparation with cyclophosphamide and total-body irradiati on (n=190). Outcome comparisons were by intention to treat with adjust ment for the most important risk factors for relapse. Findings 381 pat ients were randomised (38% of those eligible). Of the 190 patients all ocated autologous BMT. 126 received it. On intention-to-treat analysis the number of relapses was substantially lower in the autologous BMT group than in the group assigned no further treatment (64/190 [37%] vs 101/191 [58%], p=0.0007), resulting in superior disease-free survival at 7 years (53 vs 40%; p=0.04). These benefits were observed in all r isk groups and age-groups. There were more deaths in remission in the autologous BMT group than in the no further treatment group (22 [12%] vs 7 [4%], p=0.008). In children (<15 years) and patients with good-ri sk disease, survival from relapse in the no further treatment group wa s 35% and 38% at 2 years. There was an overall survival advantage in t he autologous BMT group at 7 years (57 vs 45%, p=0.2). Interpretation The addition of autologous BMT to four courses of intensive chemothera py substantially reduces the risk of relapse in ail risk groups, leadi ng to improvement in long-term survival. The good chance of salvage fo r children or patients with good-risk disease who relapse from chemoth erapy, and the mortality, morbidity, late effects, and expense of auto logous BMT, suggest that delay of autograft until second remission in these two groups may be appropriate.