Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 22, Issue 1, Pages 86-95Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2015.08.015
Keywords
Anti-HLA antibodies; HLA-DP; Acute graft-versus-host disease (aGVHD); Unrelated donor; Hematopoietic stem cell transplantation (HSCT); Outcomes
Categories
Funding
- National Natural Science Foundation of China [81273266, 81072435]
- Outstanding Medical Academic Leader Program of Jiangsu Province [LJ 201138]
- science and technology key project on clinical medicine of Jiangsu Province [BL2014038, SBL201320030]
- Program Development of Jiangsu Higher Education Institutions (PAPD)
- Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
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The National Marrow Donor Program and Center for International Blood and Marrow Transplant Research provided guidelines for the use of anti-HLA antibodies and HLA-DP mismatched loci in unrelated donor hematopoietic stem cell transplantation (HSCT). However, a deeper understanding of other potentially useful biomarkers for predicting clinical outcomes in HLA-A, -B, -C, -DRB1, -DQB1, and -DQA1 (12/12)-matched unrelated donor HSCT is needed to further improve clinical outcomes. We tested HLA genotyping for 123 pairs of patients and donors. Anti-HLA antibodies using the Luminex method was applied to 123, 117, and 106 serum samples collected before and 1 month and 3 months after transplantation. The presences of anti-HLA antibodies at the 3 time points were 37.4% (46 of 123), 40.2% (47 of 117), and 22.6% (24 of 106). Mismatch of HLA-DPB1 and/or DPA1 allele between patient-donor pairs was 83.6% (92 of 110). Patients with anti-HLA antibodies had delayed platelet recovery. The presence of anti-HLA antibodies and their dynamic changes after transplantation were associated with increased occurrence of grades II to IV acute and chronic graft-versus-host disease (GVHD), higher treatment-related mortality, and reduced overall survival (OS) and disease-free survival, especially in acute myeloid leukemia and myelodysplastic syndrome patients. Multivariate analysis showed that presence of anti-HLA antibodies before transplantation was a risk factor for GVHD and OS. Furthermore, HLA-DP loci matched subgroup showed a trend towards a lower rate of acute GVHD and a higher OS in the anti-HLA Abs-negative group. Our results suggest that dynamic changes of anti-HLA antibodies independently predict for a negative outcome of HSCT, independent of HLA-DP loci mismatches. Routine monitoring for anti-HLA antibody dynamics should be conducted before and after HSCT. (C) 2016 American Society for Blood and Marrow Transplantation.
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