Overcoming Donor-Specific Anti-Human Leukocyte Antigen Antibodies With Desensitization in Adult Ex-Vivo T-Cell Depleted Haploidentical Hematopoietic Stem Cell Transplantation: A Real-World Analysis.

The presence of anti-human leukocyte antigen (HLA) antibodies directed against donor HLA (HLA-DSA) in HLA-mismatched hematopoietic stem cell transplantation (HCT) can affect engraftment and transplant outcomes. Desensitization treatment to eliminate the effect of HLA-DSA is now routine practice, but questions as to the optimal regimen and the true effect of these antibodies on transplant outcomes remain. This is the first analysis specifically assessing the effect of HLA-DSA desensitization in the setting of adult patients undergoing ex-vivo partial T-cell (T-cell receptor-αβ and CD45RA+) depleted haploidentical-HCT (pTCD-haplo). The aim was to assess effectiveness of desensitization treatment on reduction of HLA-DSA mean fluorescence intensity (MFI) and subsequently its impact on engraftment and overall survival in the setting of adult patients undergoing pTCD-haplo. This was a real-world retrospective analysis carried out between 2017 and 2025 at the 2 largest tertiary transplant centers in Singapore. Consecutive patients with HLA-DSA MFI greater than 2000 undergoing pTCD-haplo were identified. HLA-DSA MFI before and after desensitization treatment was analyzed. Engraftment outcomes and overall survival were also assessed against a control group of patients without HLA-DSA, who underwent pTCD-haplo over the same period. Between 2017 and 2025, 13 consecutive patients undergoing pTCD-haplo received desensitization treatment with plasma exchange, intravenous immunoglobulin and rituximab. Median reduction of HLA-DSA MFI was 46.8%. A statistically significant median reduction of HLA antibodies was observed in both groups stratified by a baseline MFI greater or less than 5000 (39.7% and 73.2% respectively). In patients undergoing desensitization, median time to neutrophil and platelet engraftment was 11 and 12 d, respectively, with all patients achieving neutrophil engraftment. A comparison cohort without HLA-DSA (n = 106) who underwent pTCD-haplo over the same period was used to assess the impact of HLA-DSA on engraftment and overall survival, in which no significant difference was identified. For neutrophils, median time to engraftment was 11 (interquartile range 10 to 18) d for the desensitized group compared to 12 (IQR 11 to 14) d in those without HLA-DSA in the comparison cohort (p = .722). Time to platelet engraftment was also similar in both groups at 12 (IQR 10 to 14) d and 10 (IQR 10 to 12) d in the HLA-DSA-desensitization and comparison cohort, respectively (p = .285). Median overall survival was 70 months in the DSA group and not reached in the control group, with a hazard ratio 0.754 (CI 0.263 to 2.17). This analysis reaffirms that the standard desensitization method with plasma exchange, rituximab and IVIg, used to abrogate the effect of HLA-DSA in mismatched HCT is also effective in haploidentical HCT with partial T-cell depleted graft, with respect to its impact on engraftment and overall survival.