Indiscernible benefit of high-resolution HLA typing in improving long-term clinical outcome of unrelated umbilical cord blood transplant

Abstract

The success of allogeneic hematopoietic stem cell transplantation depends in part on the accuracy of human leukocyte antigen (HLA) matching between the donorrecipient pair. The higher the number of matching HLA alleles, the smaller the chance that the transplant recipient will develop complications. Umbilical cord blood (UCB) transplantation was noted to result in a remarkably low frequency and severity of graft-versus-host disease (GvHD) and graft rejection compared to that in unrelated bone marrow transplant recipients. At present most banks match UCB donors for respective recipients by HLA-A, -B low-resolution typing and -DRB1 high-resolution typing. We retrospectively conducted high-resolution sequence-based HLA typing on DNA samples available from 65 Chinese UCB-recipient pairs typed previously by using low-resolution sequence-specific oligonucleotide probes and sequence-specific primers, and evaluated the clinical outcome. High-resolution typing revealed imperceptible HLA alleles that were hardly identified in lowresolution typing. Univariate analyses demonstrated no significant correlation between the extents of highresolution HLA disparity with engraftment, graft failure, acute GvHD, transplant-related mortality and long-term 6-year overall survival. Data from the study suggest that high-resolution typing for HLA-A, -B and -DRB1 contributed no substantial improvement to UCB transplant outcome. Low-resolution typing appears to be amenable to matching UCB-recipient pairs without compromising the quality of transplant.

The impact of HLA genotyping on survival following unrelated donor haematopoietic stem cell transplantation

“…Prospective clinical trial data comparing the outcome of UCB and PBSC/bone marrow from adult UD is lacking. The impact of HLA matching in cord blood transplantation has been studied Rocha & Gluckman, 2009;Smith & Wagner, 2009), however very few studies (with small numbers) have analysed the impact of matching at high resolution (Kogler et al, 2005;Liao et al, 2007). Practice may change as more results become available, but extending patient searches to include adult UD and cord blood simultaneously may streamline donor selection.…”

Inference of high resolution HLA types using genome-wide RNA or DNA sequencing reads

“…HLA-A*02:01). For example, resolving HLAs at high resolution substantially improves the clinical outcome in unrelated cord blood transplantation and in cancer vaccination trials [15, 19]. In addition, amino acid variations may lead to diverse functional perturbations.…”

Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts

“…Although the importance of the TNC and CD34 ϩ cell dose, and from 4/6 to 6/6 HLA-A, HLA-B antigen, HLA-DRB1 allele matching in determining single-unit CB engraftment is well documented, 9-15 the effect of the same variables on the kinetics of engraftment after double-unit CBT has not been adequately demonstrated. [4][5][6]8,16 In addition, because donor-recipient matching at 6 HLA loci (HLA-A, HLA-B antigen, and HLA-DRB1 allele) is the current standard for CB unit selection, relatively little is known about the influence on engraftment of matching at 10 HLA alleles (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQ), with no 13,17 or minimal 18 influence detected after single-unit CBT, and limited investigation reported in double-unit CBT to date. Moreover, the requirement for HLA-matching between the 2 units of a double-unit graft is based on empiric considerations.…”