A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia.
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).
Department of Haematology, Centre for Clinical Haematology, Nottingham University Hospital, Nottingham, UK.
N H
NH
Russell
Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
L
L
Kjeldsen
Department of Haematology, Queen Elizabeth Hospital, Birmingham, UK.
C
C
Craddock
Department of Haematology, Kings College Hospital, London, UK.
A
A
Pagliuca
Department of Haematology, Manchester Royal Infirmary, Manchester, UK.
J A
JA
Yin
Department of Haematology, Royal Liverpool Hospital, Liverpool, UK.
R E
RE
Clark
School of Cancer Studies, University of Birmingham, Birmingham, UK.
A
A
Howman
Department of Haematology, Cardiff University School of Medicine, Cardiff, UK.
R K
RK
Hills
Department of Haematology, Cardiff University School of Medicine, Cardiff, UK.
A K
AK
Burnett
D000328:Adult; D064591:Allografts; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D035781:Siblings; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D061349:Unrelated Donors