Patients with Hematologic Malignancies Can Benefit More from Allele-Level HLA Matching Than Antigen-Level after Single Unit Umbilical Cord Blood transplantation: a Retrospective Single Center Clinical Analysis

Introduction:The increasing number of unrelated umbilical cord blood (UCB) has been used as an alternative graft because greater degrees of donor-recipient HLA mismatch are tolerated. Generally, lower resolution

HLA typing (antigen-level) for HLA-A and -B and at the allele level for HLA-DRB1 is used to select UCB units; HLA-C and -DQB1 are not typically considered. A few studies have suggested that HLA-matching based upon allelic typing for 8 HLA loci(HLA-A, -B, -C and -DRB1 )should be taken into account when searching UCB units; and the NMDP also encourages extended high-resolution typing of umbilical cord blood units to facilitate further study of the impact of HLA. Nevertheless, few studies have taken into consideration that if HLA-matching based upon allelic typing for 10 loci (HLA-A, -B, -C,-DRB1 and -DQB1) can benefit more patients than traditional HLA typing method (antigen-level for HLA-A,-B and allele-level for HLA-DRB1). In this study, we aim to compare the clinical outcomes between patients using allele-level HLA typing and those using traditional HLA typing method, such as engraftment, relapse and survival after unrelated cord blood transplantation (UCBT).

Patients and methods: 309 patients with hematologic malignancies who underwent UCBT in Anhui Provincial Hospital from May 2008 to December 2015 were analyzed. All patients received a single UCB unit after intensified myeloablative conditioning regimens and a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) was given for graft-versus-host disease (GVHD) prophylaxis. Of 309 patients at enrollment, 95 patients used traditional HLA typing method (antigen level for HLA-A,-B and allele level for HLA-DRB1, at least 4/6 HLA loci matching must be met) and 214 patients used allele-level HLA typing method (allele-level for HLA-A,-B,-C,-DRB1 and -DQB1, at least 5/10 HLA loci matching must be met). The follow-up assessment was conducted before May, 31, 2016.

Results: Patients using allele-level HLA typing method had a statistically significant higher cumulative incidence of platelet engraftment (P=0.039), and the risk of grades 2-4 acute GVHD was statistically significant lower than patients using traditional HLA typing method (P=0.01). The risk of transplant-related mortality (TRM) by 1 year was also lower than patients using traditional HLA typing method (P=0.043), while there was no increase in the risk of relapse (P=0.338). Conclusion: Using allele-level HLA typing method when searching UCB units (at least 5/10 HLA loci matching must be met) can improve the engraftment of platelet, reduce the risk of grades 2-4 acute GVHD and TRM, which can take the place of traditional HLA typing method to search UCB units.