Fasslrinner F, et al. - Whether reduced-intensity conditioning before allogeneic haemopoietic cell transplantation (HCT) increases the risk of late relapse compared with myeloablative conditioning in patients with acute myeloid leukaemia in first complete remission, was investigated in this retrospective 10-year follow-up of an open-label, randomised phase 3 trial. No evidence demonstrated that reduced-intensity conditioning increases the risk of late relapse compared with myeloablative conditioning. For patients with acute myeloid leukaemia who are younger than 60 years and transplanted in first complete remission, the preferred conditioning strategy could be reduced-intensity conditioning with moderately reduced total-body irradiation doses because it has been reported in the original trial that the reduced-intensity conditioning group was associated with lower early morbidity and toxicity.

• Participants included in the original randomised phase 3 trial were of 18–60 years of age, with intermediate-risk or high-risk acute myeloid leukaemia, an adequate organ function, and an available HLA-matched sibling donor or an unrelated donor with at least nine out of ten HLA alleles matched.
• Random allocation of patients (1:1) to 120 mg/m² fludarabine combined with four 2 Gy doses of total-body irradiation (reduced-intensity conditioning) or six 2 Gy doses of total-body irradiation and 120 mg/kg cyclophosphamide (myeloablative conditioning) was done.
• The primary and secondary efficacy endpoints of this trial have been published previously.
• Researchers gathered data from medical reports from individual participating study centres, and from physician and patient interviews, to perform this retrospective, long-term follow-up analysis.
• The following endpoints were included in this analysis: cumulative relapse incidence, overall survival, disease-free survival, and non-relapse mortality in the original study population and in patients alive and relapse-free at 12 months after HCT (landmark analysis).
• Calculation of 10-year time to event rates was done in the intention-to-treat population, followed by comparison with the Gray test.

• Data showed random assignment of a total of 195 patients to receive reduced-intensity conditioning (n=99) or myeloablative conditioning (n=96) in the original trial.
• This retrospective analysis was performed by collecting data with a nearly complete follow-up (completeness index 99%).
• For surviving patients, median follow-up time was 9·9 years (IQR 8·5–11·4).
• During that time, the cumulative incidence of relapse in the complete study population was identical in both groups (30% [95% CI 20–39] in the reduced-intensity conditioning group vs 30% [21–40] in the myeloablative conditioning group; Gray test p=0·99).
• Researchers noted the occurrence of relapse at a median of 5·0 months (IQR 3·0–8·8) in the reduced-intensity conditioning group vs 9·5 months (4·5–20·5) in the myeloablative conditioning group.
• Ten-year disease-free survival of 55% (95% CI 45–66) and 43% (34–55) was reported in the reduced-intensity conditioning group and in the myeloablative conditioning group, respectively (hazard ratio [HR] 0·76 [0·51–1·14]; p=0·19).
• Findings demonstrated that 10-year non-relapse mortality was 16% (95% CI 8–24) in the reduced-intensity conditioning group and 26% (17–36) in the myeloablative conditioning group (subdistribution HR 0·60 [95% CI 0·32–1·11]; Gray test p=0·10).
• A comparable incidence of long-term toxicities associated with total-body irradiation was noted; occurrence of secondary malignancies was reported in six (6%) of 94 patients in the reduced-intensity conditioning group and five (6%) of 90 in the myeloablative conditioning group (p=1·00).