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 chemokin...

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Bibliographic Details
Published in:Blood 2010-03, Vol.115 (11), p.2311-2318
Main Authors: McDermott, David H., Conway, Susan E., Wang, Tao, Ricklefs, Stacy M., Agovi, Manza A., Porcella, Stephen F., Tran, Huong Thi Bich, Milford, Edgar, Spellman, Stephen, Abdi, Reza
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Biological and medical sciences
Bone Marrow Transplantation - mortality
Child
Child, Preschool
Disease-Free Survival
Female
Haplotypes - genetics
Hematologic and hematopoietic diseases
Humans
Infant
Male
Medical sciences
Middle Aged
Multivariate Analysis
Receptors, CCR5 - genetics
Tissue Donors
Transplantation
Transplantation Conditioning
Young Adult
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2009-08-237768