Outcome of haematopoietic stem cell transplantation in patients transplanted with matched unrelated donors vs allele‐mismatched donors: a single centre study

Abstract

We studied the importance of human leucocyte antigen (HLA)-A, -B and -DRB1 high-resolution matching on the outcome of haematopoietic stem cell transplantation (HSCT) with matched unrelated donors (MUDs) vs single allele-mismatched unrelated donors. Fifty consecutive HSCT patients receiving an HLA-A, -B or -DR allele-level-mismatched unrelated graft (mmUD) were compared with a matched cohort of 100 patients with an HLA-A, -B and -DR-MUD. Rejection occurred in seven patients (14%) in the mmUD group and in four patients (4%) in the MUD group (P = 0.04), but this was mainly an effect of HLA-C mismatch. The cumulative incidence of acute graft vs host disease (GVHD) grades II-IV were 61%, 26% and 33% in the class I mmUD, class II mmUD and MUD groups, respectively. In multivariate analysis, HLA class I mismatch was associated with an increased risk of acute GVHD grades II-IV (2.09, P = 0.007) and transplant-related mortality (TRM) (1.99, P = 0.06). The 5-year overall survival was 81% in patients with a class II allele-mismatched donor compared with 52% (P = 0.025) and 50% (P = 0.017) in patients with a class I mismatch and a MUD. In multivariate analysis, HLA class II allele mismatch was associated with improved survival (3.38, P = 0.019). Relapse-free survival were 53%, 37% and 42% in patients with a class II mmUD, class I mmUD and a MUD, respectively (not significant). An HLA-C or -DQ mismatch had no significant impact on survival, TRM and relapse. In conclusion, compared with MUD, HLA class I allele mmUD had an increased risk of acute GVHD and TRM.

Shedding a new light on the HLA matching

“…Park et al retrospectively analyzed a large group of patients (N=142, including 109 patients with hematologic malignancies and 33 patients with non-malignant diseases; all the patients belonged to the pediatric age group [≤18 years old]) who had undergone URD HSCT, and all HSC donors and patients were fully typed for HLA-A, HLA-B, HLA-C, and HLA-DR by using high-resolution molecular typing (4-digit level). Park et al suggested that increased numbers of HLA Mms were associated with reduced overall survival, increased risk of grade III-IV aGVHD, and greater TRM risk, thus confirming the results of many other studies [5-7]. Other important observations included that a single locus Mm at HLA-B or HLA-C was associated with significantly lower survival compared to the survival of patients with 8/8 allele match or a single Mm at HLA-A or DR; these results vary in American and Japanese reports.…”

“…An HSCT donor is referred to as a "10/10 allele match" or "perfect match" when both HLA alleles are identical at each of the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci. While searching for an unrelated donor, high-resolution (4-digit) genetic typing of both the patient and the donor is necessary [4, 5]. …”

“…Many retrospective studies have been done to analyze the effects of HLA mismatches (Mms) in adult patients who had undergone URD HSCT in different countries [5-8]. Crocchiolo et al [6] reported that Mms patients with 9/10 allele match showed a significantly higher risk of mortality, graft failure, and acute GVHD (aGVHD) than patients with 10/10 allele match.…”

“…Crocchiolo et al [6] reported that Mms patients with 9/10 allele match showed a significantly higher risk of mortality, graft failure, and acute GVHD (aGVHD) than patients with 10/10 allele match. Hauzenberger et al [5] showed that patients with HLA class I allele Mms had high risk of aGVHD and transplant-related mortality (TRM), but HLA class II allele Mms were associated with improved survival. Weisdorf et al [7] observed significantly worse survival rates in URD HSCT patients at any matching level, and did not observe augmented graft-versus-leukemia (GVL) effects in Mm URD HSCT patients.…”

Stem cell transplantation during cancer

“…For the remaining two thirds of the patients a donor may be available through the international donor registries. A full HLA match (10/10) is desirable when searching for a donor but some HLA-mismatches may be accepted for certain patients on an individual basis (14,15). Other important factors usually kept in mind included cytomegalovirus (CMV) status, gender, age of donor and recipient and sometimes ABO-blood group.…”