IL-10 Promoter Gene Polymorphism Associated with the Occurrence of Chronic GVHD and Its Clinical Course during Systemic Immunosuppressive Treatment for Chronic GVHD after Allogeneic Peripheral Blood Stem Cell Transplantation.

Abstract

Introduction: The current study attempted to evaluate the association between the IL-10 promoter gene polymorphism and transplant outcomes, including the occurrence of chronic GVHD and its clinical course during systemic immunosuppressive treatment (IST) after allogeneic peripheral blood stem cell transplantation (PBSCT).Methods: Three single-nucleotide polymorphisms in the proximal region of the IL-10 promoter gene (−1082/−819/−592) were analyzed in 60 recipients of cytokine-mobilized PBSCs from HLA-matched sibling donors, and the transplant outcomes compared in terms of the occurrence of chronic GVHD and its clinical course.Results: The current study only found two haplotypes (1082*A/819*T/592*A [ATA] and 1082*A/819*C/592*C [ACC]). An increased occurrence of chronic GVHD was noted dependent on the IL-10 haplotype (43% vs 68% vs 96% in ACC/ACC vs ATA/ACC vs ATA/ATA haplotype, p=0.003). In a logistic regression based on a multinomial model, the ATA/ATA homozygote presented a 7-fold increased risk of the development of chronic GVHD compared with the ACC/ACC homozygote. The cumulative incidence of chronic GVHD at 1 year post-transplant was 46±20%, 64±10%, and 82±5% in the ACC/ACC, ATA/ACC, and ATA/ATA groups, respectively (p=0.0266). The recipients without the ACC haplotype had a more frequent history of acute exacerbation of chronic GVHD (p=0.031, odds ratio 6.750), while 72% of the recipients with the ACC haloptype did not experience any history of acute exacerbation after the initiation of systemic IST for chronic GVHD compared to 38% of those without the ACC haplotype (p=0.014, odds ratio 4.375). Plus, the duration of systemic IST was significantly shorter in the recipients without the ATA-haplotype compared to those with the ATA haplotype (339 days versus 1,146 days, p=0.0091). In terms of GVHD-specific survival, the recipients without the ATA haplotype showed a 100% survival compared to 70.5% for the ATA haplotype group (p=0.2825).Conclusion: The IL-10 promoter gene polymorphism was found to be apparently associated with the occurrence of chronic GVHD and its clinical course during systemic IST for chronic GVHD in an allogeneic PBSCT setting. [Display omitted] [Display omitted]