The effect of inter-unit HLA matching in double umbilical cord blood transplantation for acute leukemia

Abstract

The effects of inter-unit HLA-match on early outcomes with regards to double cord blood transplantation have not been established. Therefore, we studied the effect of inter-unit HLA-mismatching on the outcomes of 449 patients with acute leukemia after double cord blood transplantation. Patients were divided into two groups: one group that included transplantations with inter-unit mismatch at 2 or less HLA-loci (n=381) and the other group with inter-unit mismatch at 3 or 4 HLA-loci (n=68). HLA-match considered low resolution matching at HLA-A and -B loci and allele-level at HLA-DRB1, the accepted standard for selecting units for double cord blood transplants. Patients’, disease, and transplant characteristics were similar in the two groups. We observed no effect of the degree of inter-unit HLA-mismatch on neutrophil (Hazard Ratio 1.27, P=0.11) or platelet (Hazard Ratio 0.1.13, P=0.42) recovery, acute graft-versus-host disease (Hazard Ratio 1.17, P=0.36), treatment-related mortality (Hazard Ratio 0.92, P=0.75), relapse (Hazard Ratio 1.18, P=0.49), treatment failure (Hazard Ratio 0.99, P=0.98), or overall survival (Hazard Ratio 0.98, P=0.91). There were no differences in the proportion of transplants with engraftment of both units by three months (5% after transplantation of units with inter-unit mismatch at ≤2 HLA-loci and 4% after transplantation of units with inter-unit mismatch at 3 or 4 HLA-loci). Our observations support the elimination of inter-unit HLA-mismatch criterion when selecting cord blood units in favor of optimizing selection based on individual unit characteristics.

Cord Haploidentical Non-In Vitro T Cell Depletion Allogeneic Hematopoietic Stem Cell Transplantation Reduces Relapse of Refractory Acute Leukemia

“…Consistent with that study, cord-haplo HSCT in our patients with refractory acute leukemias manifested a GVG response, resulting in significantly reduced relapse rates. Notably, previous analyses seldom focused on HLA matching between the "loser" unit and the recipient [30]. Overall, the MHMA algorithm should be helpful in predicting whether higher-degree HLA mismatching improves outcomes in terms of relapse and NRM rates [18,20].…”

Selection of unrelated donors and cord blood units for hematopoietic cell transplantation: guidelines from the NMDP/CIBMTR

“…111 There are no data that support consideration of interunit HLA matching in double-unit graft selection. 101,112,113 Taken together, guidelines have been developed by the ASBMT CB Special Interest Group (summarized in Table 2). Overall, the current data support selecting units using the following unit principles: (1) adequate unit quality, (2) minimum required TNC and CD34 1 cell doses, and (3) optimal HLA high-resolution matched unit considering HLA-A, HLA-B, HLA-C, and HLA-DRB1.…”

Optimizing selection of double cord blood units for transplantation of adult patients with malignant diseases

“…The median time to neutrophil recovery was 27 days (95% CI, [26][27][28], whereas day 128 and day 142 neutrophil recovery cumulative incidences were 56% (95% CI, 53-58) and 82% (95% CI, 80-85), respectively. The median time to platelet recovery was 48 days (95% CI, 47%-50%).…”