Impact of the source of hematopoietic stem cell in unrelated transplants: Comparison between 10/10, 9/10‐HLAmatched donors and cord blood

Abstract

In absence of available matched-related or unrelated donor (MUD), mismatched unrelated donors (MMUD) and unrelated cord blood (UCB) are both considered to be suitable donors, with similar post-transplant overall survival. In most of these retrospective comparisons, HLA typing of adult donors was performed at eight loci. The aim of this study was to compare the outcome of patients transplanted from UCB (N 5 64) with those transplanted from 9/10-HLA MMUD (N 5 84) or 10/10-HLA MUD (N 5 196). In multivariate analysis, UCB was associated with less Grade II-IV acute GVHD in comparison with MUD (aHR 1.97, 95% CI 1.19-3.27, P 5 0.009) and MMUD transplants (aHR 1.79, 95% CI 1.02-3.15, P 5 0.042), while the cumulative incidence of chronic GVHD was not significantly different between the three groups. Overall survival (OS), non-relapse mortality, and relapse were not different between MMUD and UCB transplantation, whereas OS was impaired after UCB in comparison with MUD (aHR 0.65, 95% CI 0.43-0.99, P 5 0.043). Factors also impacting OS were the donor/recipient CMV serostatus (Donor2/Recipient1 aHR 1.76, 95% CI 1.23-2.52, P 5 0.002 compared with D2/R2), the donor/recipient gender combination (Female/Male versus other combinations aHR 1.57, 95% CI 1.11-2.22, P 5 0.012) and disease risk (aHR 1.58, 95% CI 1.05-2.38, P 5 0.027 for high vs. low risk disease). Our data confirm that UCB and 9/10-HLA MMUD are both relevant alternative options when no 10/10-HLA donor is available. Donor/recipient gender combination and CMV serostatus had a significant impact on survival and may be taken into account, along with donor type, in the setting of MMUD and UCB transplants.

Risk Factors for Graft-Versus-Host Disease After Transplantation of Hematopoietic Stem Cells from Unrelated Donors in the China Marrow Donor Program

“…Similarly, with the exception of DR sites other than a full match or the DRB1 12: 02-12: 01 mismatch, HLA loci matching was not associated with OS in the present study. This is in agreement with previous studies that showed similar survival rates for patients undergoing matched related and unrelated, single-antigen mismatched unrelated, double cord blood [ 49 , 50 ], and haploidentical relative procedures [ 51 ]. Given the association of the natural killer cell immunoglobulin-like receptors with HLA class I ligands and patient survival and relapse [ 52 ], further studies will examine these haplotypes with GVHD occurrence in patients undergoing HSCT.…”

Pitfalls of haplotype phasing from amplicon-based long-read sequencing

“…Accurately determining genotype phase is important in many aspects of genetics. For example, in pharmacogenetics 1 , transplant HLA typing 2 and disease association mapping 3 . Until recently, haplotype phasing has generally relied on parental genotypes or statistical phasing based on allele frequency patterns within the population.…”

Hematopoietic cell transplantation in pediatric patients with acute leukemias or myelodysplastic syndrome using unrelated adult or umbilical cord blood donors in Brazil

“…Many studies have observed higher NRM in CMV seropositive compared to seronegative recipients of UCB transplants. [22][23][24] In Brazil, the prevalence of CMV seropositivity is high. 25 We speculate that CMV could have contributed to the high mortality in these patients, since 80% of them were CMV seropositive.…”