Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation. Blood 2010 Mar 18;115(11):2311-8
Date
01/14/2010Pubmed ID
20068218Pubmed Central ID
PMC2844018DOI
10.1182/blood-2009-08-237768Scopus ID
2-s2.0-77950427009 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
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.
Author List
McDermott DH, Conway SE, Wang T, Ricklefs SM, Agovi MA, Porcella SF, Tran HT, Milford E, Spellman S, Abdi RAuthor
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Bone Marrow Transplantation
Child
Child, Preschool
Disease-Free Survival
Female
Haplotypes
Humans
Infant
Male
Middle Aged
Multivariate Analysis
Receptors, CCR5
Tissue Donors
Transplantation Conditioning
Young Adult
