Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation.
Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen-matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P = .005) and overall survival (P = .021). When the same genotype of both the donor and recipient were considered in the models, a highly significant association with DFS and overall survival was noted (P < .001 and P = .007, respectively) with absolute differences in survival of up to 20% seen between the groups at 3 years after transplantation (50% DFS for pairs with recipient CCR5 H1/H1 vs 30% for pairs with donor CCR5 H1/H1). This finding suggests that donor and/or recipient CCR5 genotypes may be associated with HSCT outcome and suggests new diagnostic and therapeutic strategies for optimizing therapy.
McDermott
David H
DH
Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Conway
Susan E
SE
Wang
Tao
T
Ricklefs
Stacy M
SM
Agovi
Manza A
MA
Porcella
Stephen F
SF
Tran
Huong Thi Bich
HT
Milford
Edgar
E
Spellman
Stephen
S
Abdi
Reza
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019713:Receptors, CCR5 / Q000235:genetics*; D014019:Tissue Donors; D019172:Transplantation Conditioning; D055815:Young Adult
D019713:Receptors, CCR5