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2006 CTLA-4 Polymorphisms and Haplotype Correlate with Survival and aGVHD after Allogeneic Stem Cell Transplantation from Related HLA-Haplotype-Mismatched Donor

Clinical Allogeneic Transplantation: Results
Program: Oral and Poster Abstracts
Session: 732. Clinical Allogeneic Transplantation: Results: Poster I
Saturday, December 5, 2015, 5:30 PM-7:30 PM
Hall A, Level 2 (Orange County Convention Center)

Xiao-Ying Qin1,2,3*, Yu Wang1,2,3*, Guo-Xuan Li1,2,3*, Yazhen Qin1,3,4*, Lan-Ping Xu1,2,3*, Fengrong Wang1,2,3*, Huan Chen1,2,3*, Wei Han1,2,3*, Jing-Zhi Wang1,2,3*, Xiao-Hui Zhang1,2,3*, Ying-Jun Chang1,2,3*, Kaiyan Liu2,3,5, Zheng-Fan Jiang6* and Xiao-jun Huang1,2,3

1Peking University Institute of Hematology, Peking University People’s Hospital, Beijing, China
2Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
3Peking-Tsinghua Center for Life Sciences, Beijing, China
4Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
5Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
6State Key Laboratory of Protein and Plant Gene Research, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China; Peking University-Tsinghua University Joint Center, Beijing, China

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure.T cell homeostasis is critical to determine the potency of the GVT effect. Cytotoxic T lymphocyte antigen-4 (CTLA-4 or CD152) is a T cell activation negative regulator. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT.

Patients and Methods:In this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 154 acute leukemia patients after related HLA-haplotype-mismatched transplantation. The four SNP genotypes (-1661, -318, CT60 and +49) were determined by TaqMan SNP genotyping assays.

Results:Recipients of donors with +49 GG showed significantly lower OS (69.1% vs. 85.6%, P=0.024) and higher incidence of III–IV aGVHD (10.0% vs. 2.1%, P=0.032) than those with GA + AA(Fig.1,Fig.2). Multivariate analyses showed that +49GG was an independent risk factor for OS (HR:0.457,95%CI=0.227–0.920,P=0.028). Patients receiving mDLI showed significantly lower OS with +49 GG donor than those with AG+AA (P=0.011).The haplotype analysis revealed only three haplotypes in the donor population -1661/-318/CT60/+49 i.e.,ACGG,ACAA and GTGA,the frequencies were 64.3%, 19.5%, and 16.2%, respectively.Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcome as those with +49 GG and +49 AG+AA.

Conclusion:The CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival and increased the aGVHD after allo-HSCT from the related HLA-haplotype-mismatched donor,knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Disclosures: No relevant conflicts of interest to declare.

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