Beneficial effect of the CXCL12-3'A variant for patients undergoing hematopoietic stem cell transplantation from unrelated donors

Cytokine. 2015 Dec;76(2):182-186. doi: 10.1016/j.cyto.2015.05.001. Epub 2015 May 14.

Abstract

The present study aimed to assess the impact of the CXCL12 gene polymorphism (rs1801157) on clinical outcome of hematopoietic stem cell transplantation from unrelated donors. Toxic complications were less frequent among patients transplanted from donors carrying the CXCL12-3'-A allele (42/79 vs. 105/151, p=0.014 and 24/79 vs. 73/151, p=0.009, for grade II-IV and III-IV, respectively). Logistic regression analyses confirmed a role of donor A allele (OR=0.509, p=0.022 and OR=0.473, p=0.013 for grade II-IV and III-IV toxicity). In addition, age of recipients (OR=0.980, p=0.036 and OR=0.981, p=0.040, respectively) was independently protective while female to male transplantation and HLA compatibility were not significant. The incidence of aGvHD (grades I-IV) was lower in patients having A allele (52/119 vs. 113/204, p=0.043) and AA homozygous genotype (6/25 vs. 159/298, p=0.005). Independent associations of both genetic markers with a decreased risk of aGvHD were also seen in multivariate analyses (A allele: OR=0.591, p=0.030; AA homozygosity: OR=0.257, p=0.006) in which HLA compatibility seemed to play less protective role (p<0.1) while recipient age and donor-recipient gender relation were not significant. Moreover, CXCL12-3'-A-positive patients were less prone to early HHV-6 reactivation (2/34 vs. 19/69, p=0.026). The presence of the CXCL12-3'-A variant was found to facilitate outcome of unrelated HSCT.

Keywords: CXCL12 polymorphism; Graft-versus-host disease; Hematopoietic stem cell transplantation from alternative donors; Toxicity; Viral reactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Alleles
  • Chemokine CXCL12 / genetics*
  • Child
  • Child, Preschool
  • Female
  • Genotype
  • Graft vs Host Disease / genetics
  • Hematopoietic Stem Cell Transplantation*
  • Herpesvirus 6, Human / physiology
  • Histocompatibility Testing
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Sex Factors
  • Transplantation, Homologous
  • Unrelated Donors*
  • Virus Activation
  • Young Adult

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12