Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: Results of MRC AML 10 trial

Background: Three strategies are used to prevent relapse in patients with acute myeloid leukaemia in first remission. Most of those with suitable donors are offered allogeneic haemopoietic-stem-cell transplant. Other patients may receive intensive chemotherapy or autologous transplantation; we undertook this randomised prospective trial to assess which is the better option. Methods: After three courses of intensive chemotherapy, bone marrow was harvested from patients (< 56 years of age) in remission who lacked an HLA-matched sibling donor. These patients were 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 irradiation (n = 190). Outcome comparisons were by intention to treat with adjustment for the most important risk factors for relapse. Findings: 381 patients were randomised (38% of those eligible). Of the 190 patients allocated 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 risk 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-risk disease, survival from relapse in the no further treatment group was 35% and 38% at 2 years. There was an overall survival advantage in the autologous BMT group at 7 years (57 vs 45%, p = 0.2). Interpretation: The addition of autologous BMT to four courses of intensive chemotherapy substantially reduces the risk of relapse in all risk groups, leading to improvement in long-term survival. The good chance of salvage for children or patients with good-risk disease who relapse from chemotherapy, and the mortality, morbidity, late effects, and expense of autologous BMT, suggest that delay of autograft until second remission in these two groups may be appropriate.