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Acute Leukemias

A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia

Abstract

Allogeneic stem cell transplantation (SCT) provides the best mechanism of preventing relapse in acute myeloid leukaemia (AML). However non-relapse mortality (NRM) negates this benefit in older patients. Reduced intensity conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure is uncertain. In the MRC AML15 Trial, patients in remission without favourable risk disease could receive SCT from a matched sibling or unrelated donor (MUD). If aged >45 years, a RIC was recommended and in patients aged 35–44 years, either RIC or myeloablative conditioning was permitted. The aim was to determine which approach improved survival and within which prespecified cytogenetic groups. RIC transplants significantly reduced relapse (adjusted hazard ratio (HR) 0.66 (0.50–0.85), P=0.002) compared to chemotherapy The 5-year overall survival from a sibling RIC (61%) was superior to a MUD RIC (37%; adjusted HR 1.50 (1.01–2.21), P=0.04) due to lower NRM (34 vs 14%, P=0.002) In adjusted analyses, there was a survival benefit for sibling RIC over chemotherapy (59 vs 49%, HR 0.75 (0.57–0.97), P=0.03), with consistent results in intermediate and adverse-risk patients. In patients aged 35–44 years, best outcomes were seen with a sibling RIC transplant, although a comparison with chemotherapy and myeloablative transplant was not significant in adjusted analyses (P=0.3).

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Acknowledgements

The research costs of the AML15 trial were supported by the UK Medical Research Council. Research Funding for this trial was provided by the Medical Research Council of Great Britain.

Author Contributions

AKB, NHR and RKH were responsible for the conception and design of the study. AKB, NHR, LK, AP, CC, REC and JAY provided the study materials or patients. AKB, NHR, RKH, LK, AP, CC, REC and JAY were responsible for the collection and assembly of the data. AKB, NHR, RKH, AH were responsible for data analysis and interpretation. All the authors contributed to the writing and final approval of the manuscript.

UK NCRI Adult AML Working Party

The following centres performed transplants analysed in this study: Aberdeen Royal Infirmary; Addenbrooke's Hospital; Auckland City Hospital; Beatson West of Scotland Cancer Centre; Belfast City Hospital; Birmingham Heartlands Hospital; Bristol BMT Unit; Christchurch Hospital; Christie Hospital; Derriford Hospital; Glasgow Royal Infirmary; Guy's Hospital; Hammersmith Hospital; John Radcliffe Hospital; King's College Hospital; Leeds General Infirmary; Leicester Royal Infirmary; Manchester Royal Infirmary; Nottingham City Hospital; Queen Elizabeth Hospital Birmingham; Rigshospitalet; Royal Free Hospital; Royal Hallamshire Hospital Sheffield; Royal Liverpool University Hospital; Royal Marsden Hospital; Royal Victoria Infirmary; Southampton General Hospital; St Bartholomew's Hospital; St George's Hospital; St James University Hospital; University College Hospital; University Hospital of Wales; Wellington Hospital; Western General Hospital.

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Correspondence to N H Russell.

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Russell, N., Kjeldsen, L., Craddock, C. et al. A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia. Leukemia 29, 1478–1484 (2015). https://doi.org/10.1038/leu.2014.319

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