Dynamic Detection of Anti–Human Leukocyte Antigen (HLA) Antibodies but not HLA-DP Loci Mismatches Can Predict Acute Graft-versus-Host Disease and Overall Survival in HLA 12/12–Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for

1.Dynamic detection of anti-HLA antibodies can predict graft-versus-host disease and overall survival in HLA 12/12–matched unrelated donor hematopoietic stem cell transplantation for hematological malignancies, especially for acute myeloid leukemia/myelodysplastic syndromes2.Routine monitoring for anti-HLA antibody dynamics should be conducted before and after hematopoietic stem cell transplantation3.Anti-HLA antibodies independently predicted for negative outcome of hematopoietic stem cell transplantation independent of HLA-DP loci mismatches. HLA-DP loci mismatches were associated with poor prognosis in the anti-HLA Abs-negative group4.For the first time, we reported the impact of anti-HLA antibodies and HLA-DP loci mismatches on hematopoietic stem cell transplantation outcomes in HLA 12/12–matched unrelated donor hematopoietic stem cell transplantation

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.