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.

Kim, Dong Hwan; Lee, Nan Young; Sohn, Sang Kyun; Baek, Jin Ho; Kim, Jong Gwang; Lee, Jung Lim; Suh, Jang Soo; Lee, Kun Soo; Lee, Kyu Bo

doi:10.1182/blood.V104.11.422.422

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.