Outcomes of Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia

Abstract

Acute myeloid leukaemia is a disease of people in their late sixties and seventies, and transplantation is the only reliably curative option. Reduced-intensity conditioning was developed to make that option available to them. The registry data suggest chronological age is the wrong thing to be selecting on. Objectives: To review the published evidence on reduced-intensity conditioning allogeneic transplantation in older adults with acute myeloid leukaemia: how outcomes compare with chemotherapy and with myeloablative conditioning, whether age itself predicts outcome once intensity is reduced, and what should be selected on instead. Material and Methods: Narrative review of randomised trials, registry analyses, comparative cohorts and consensus documents indexed in PubMed and the major haematology and transplantation journals. Studies were eligible if they reported outcomes after reduced-intensity conditioning transplantation in a defined acute myeloid leukaemia population, compared conditioning intensities, or examined the effect of age or comorbidity on transplant outcome. No new patient data were generated and no patients were recruited; every estimate quoted is one published by the original investigators. Results: Comparing 94 patients aged 60 to 70 transplanted in first remission against 96 treated with chemotherapy on cooperative group protocols, transplantation reduced three-year relapse from 81 to 32 per cent (p < 0.001) and improved leukaemia-free survival from 15 to 32 per cent (p = 0.001), at the cost of raising non-relapse mortality from 4 to 36 per cent (p < 0.001); overall survival favoured transplantation at 37 against 25 per cent but did not reach significance (p = 0.08). In the randomised comparison of conditioning intensity, four-year survival was 65 per cent with myeloablative and 49 per cent with reduced-intensity conditioning (HR 1.54, 95% CI 1.07-2.20), but the median age was 55. Among 757 patients receiving reduced-intensity conditioning, three-year survival was 47.8, 45.2, 37.9 and 36.6 per cent across age bands from 50 to 65 and above, with no significant difference (p = 0.24), and non-relapse mortality was similarly flat. Conclusion: Once conditioning intensity is reduced, chronological age adds little to outcome prediction across the range from 50 to over 65. The randomised evidence favouring myeloablative conditioning comes from a population whose median age was 55 and does not settle the question for older patients.
Abbreviations: AML – Acute Myeloid Leukaemia, MDS – Myelodysplastic Syndrome, allo-HCT – Allogeneic Haematopoietic Cell Transplantation, RIC –  Reduced-Intensity Conditioning, MAC – Myeloablative Conditioning, NMA – Non-Myeloablative, NRM – Non-Relapse Mortality, TRM – Treatment-Related Mortality, LFS – Leukaemia-Free Survival, GVHD – Graft-Versus-Host Disease, HCT-CI – HCT Comorbidity Index, CR1 – First Complete Remission, PBSC – Peripheral Blood Stem Cells