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 Hematological Malignancies

Abstract

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.

Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA‐matched haematopoietic cell transplant for sickle cell disease

“…In our secondary analysis, HLA alloimmunization was associated with acute GVHD, a finding that others have reported in unrelated donor HCT settings (Ansari et al , ; Pan et al , ). A question raised by this secondary analysis is why pre‐HCT HLA class I antibodies are associated with acute GVHD in our patients undergoing solely HLA‐matched HCT.…”

Risk factors associated with the development of moderate to severe chronic graft-versus-host disease after non-myeloablative conditioning allogeneic stem cell transplantation in patients with AML or MDS

“…Our results on the correlation of HLA antibodies with the severity of cGVHD are in accordance with a previously reported study [19]. Pan et al described a correlation between the presence in patients' serum of antibodies against HLA before or in the 1st month after transplantation and cGVHD.…”

“…They studied a cohort of patients diagnosed with hematological malignancies who received a BM/PBSCT with myeloablative conditioning. They found a higher rate of extensive cGVHD in the group with HLA antibodies in comparison to the group of patients without HLA antibodies prior to transplantation [19]. In our study, the HLA antibody status before transplantation was associated with the development of moderate to severe cGVHD.…”

Impact of HLA-DPB1 Matching in Unrelated Allogeneic Stem Cell Transplantation: Results of Two Centers From Turkey

“…Similarly, the results of Pan et al showed that 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 GVHD, higher treatment-related mortality, and reduced OS and disease-free survival. 27 There was no significant difference in grades II-IV aGVHD, OS and disease free survival in patients receiving grafts from either HLA-DPB1 matched donors or HLA-DPB1 mismatched donors in this study. As we retrospectively examined our study group, we were not able to demonstrate the status of anti-HLA antibodies in our study group.…”

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] For instance, in the study by Loiseau et al reported increased frequency of severe aGVHD and poorer survival in two HLA-DP incompatibilities in a group of unrelated ASCT patients. 10 In this study they were not able show a significant relationship between HLA-DP mismatches and disease relapse.…”