HLA haplotype effects in allogeneic hematopoietic stem cell transplantation

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461455
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: University of the Ryukyus (2016); Fujita Health University (2014-2015)
• Principal Investigator: MORISHIMA Satoko 琉球大学, 医学(系)研究科(研究院), 准教授 (40463195)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 同種造血幹細胞移植 / HLA / HLAハプロタイプ / 急性GVHD

Outline of Final Research Achievements

We demonstrated the structure of Japanese common HLA haplotypes using multi-SNP data in HLA region of 1500 patient-donor unrelated bone marrow transplantation (UR-BMT) pairs.
We also identified high-risk HLA alleles and haplotypes for severe acute graft-versus-host disease (aGVHD) using database of 6967 UR-BMT pairs from the Japan Marrow Donor Program. The patient and/or donor HLA-B*51:01 and patient HLA-C*14:02 were significantly associated with an increased risk of severe aGVHD. Furthermore, patient mismatched HLA-C*14:02 showed the highest risk of severe aGVHD and overall mortality among all patient mismatched HLA-C alleles. KIR2DL-ligand mismatch has been considered as high-risk HLA-C mismatch in Japanese UR-BMT, however our data demonstrated that the effect of KIR2DL-ligand mismatch was attributable to patient HLA-C*14:02 and donor HLA-C*15:02 mismatch combination. Patient mismatched HLA-C*14:02 should be considered a non-permissive HLA-C mismatch in donor selection for UR-BMT.

Free Research Field

血液内科学