title: The impact of donor factors on primary non-engraftment in recipients of reduced intensity conditioned transplants from unrelated donors.
abstract: OBJECTIVE
  Primary graft failure is a serious complication following hematopoietic cell transplants, particularly when using unrelated donors. We analyzed factors affecting primary graft failure in recipients of hematopoietic cell transplants from unrelated donors, which were performed using reduced intensity conditioning.
  
  
  METHODS
  This was a retrospective analysis of 144 patients whose transplants took place between March 1998 and October 2004. The data were analyzed in January 2005.
  
  
  RESULTS
  The median age of the patients was 51 years. The diagnoses were varied. Conditioning regimens were fludarabine, melphalan, campath (n=80), fludarabine, busulphan, campath (n=38), fludarabine, BEAM, campath (n=9) and other (n=17). The donor was 10/10 allele matched in 95/144 (66%) cases; 94 donated bone marrow and 50 peripheral blood stem cells. The 3-year probability of overall survival was 43%. The median follow-up was 724 days (range: 91-1651 days). Of evaluable patients, 7/140 (5%) failed to achieve myeloid engraftment. Primary graft failure was significantly associated with the use of a mismatched donor (6/47,13% versus 1/93, 1%, p=0.006), as well as: bone marrow as the source of stem cells (p=0.046), chronic myeloid leukemia compared to other diagnoses (p=0.022), and a female rather than a male donor (p=0.019). In multivariate analysis chronic myeloid leukemia, HLA mismatched and/or female donors remained significantly associated with primary graft failure. Single HLA mismatches were tolerated, however in multiply mismatched grafts, overall survival was worse (p=0.005); transplanted-related mortality (p=0.005) and chronic graft-versus-host disease (p=0.025) were increased.
  
  
  CONCLUSIONS
  These data have implications for the choice of donor and stem cell source in transplants performed using reduced intensity conditioning regimens, suggesting that the use of bone marrow, female donors and HLA-mismatched grafts increase the risk of primary graft failure, and should be avoided in certain situations.
authors.affiliation: Nottingham City Hospital, United Kingdom. bshaw@doctors.org.uk
authors.forename: Bronwen E
authors.initials: BE
authors.lastname: Shaw
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Russell
authors.forename: Steve
authors.initials: S
authors.lastname: Devereux
authors.forename: Emma
authors.initials: E
authors.lastname: Das-Gupta
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
authors.forename: Josè Alejandro
authors.initials: JA
authors.lastname: Madrigal
authors.forename: Anthony
authors.initials: A
authors.lastname: Pagliuca
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Byrne
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D006085:Graft Survival / Q000502:physiology*; D006086:Graft vs Host Disease / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000401:mortality