Impact of Donor Characteristics and HLA Matching on Survival of Chinese Patients with Hematologic Malignancies Undergoing Unrelated Hematopoietic Stem Cell Transplantation

Abstract

We retrospectively analyzed the impact of donor characteristics and HLA matching on outcomes in Chinese patients undergoing unrelated hematopoietic stem cell transplantation (HSCT). A total of 693 patients with hematologic malignancies who underwent HSCT between 2005 and 2010 had available survival data at 100 days or 1 year posttransplantation in the Buddhist Tzu-Chi Stem Cell Center database. The overall survival rates at 100 days and 1 year were 83.3% and 65.2%, respectively. Mismatches of HLA-A, -B, and -DRB1 at the antigen or allele level, along with inadequate cell dose, were associated with a significant risk of mortality (hazard ratio [HR] = 2.36, P < .001; HR = 1.44, P = .005; and HR = 2.20, P = .009, respectively). In 107 donors with matched HLA-A, -B and -DRB1 and known HLA-C match status, 22.4% had an HLA-C antigen mismatch, resulting in an HR of 2.87 for mortality relative to complete 8/8 matches (P = .005). Recipients with unknown HLA-C match status also had a significantly worse outcome (HR = 1.73; P = .039). Multivariate analysis revealed that cell dose and HLA-A, -B, -C, and -DRB1 antigen match status significantly affected the final outcome of survival (P = .012 and <.001, respectively). Our data indicate that HLA-C match status should be confirmed before HSCT from an unrelated donor. Inadequate cell dose remains an important determinant of poor transplantation survival. Further studies to elucidate the importance of matching of specific HLA loci are needed to better understand the risk of HSCT and improve patient outcomes.

Allogeneic hematopoietic stem cell transplantation in children and adults with acute lymphoblastic leukemia

“…Sufficient HLA-incompatibility between the donor and recipient, both for major and minor antigens, is also known the exert a negative effect on the results of allo-HSCT, by association of severe immunological complications which enhance mortality of patients [8,20]. It was also confirmed by our results obtained in the groups with different types of HSC donors.…”

Clinical implications of HLA locus mismatching in unrelated donor hematopoietic cell transplantation: a meta-analysis

“…The search strategy was showed in Supplementary Table 1. A total of 36 studies were included [16–51], of which, 15 studies analyzed 6 HLA loci [17, 18, 23, 24, 26, 28, 30, 31, 35, 42, 44–47, 50], 8 researches mentioned 5 HLA loci [16, 19–22, 27, 29, 38], and 14 studies investigated 4 HLA loci [25, 32–34, 37, 39–41, 43, 44, 48, 49, 51] (Table 1). Study characteristics were showed in Supplementary Table 2, all of the included studies were at low risk of bias.…”

High-allelic variability in HLA-C mRNA expression: association with HLA-extended haplotypes

“…Among such 9/10 matched donors, HLA-C incompatibilities account for a large fraction of the HLA class I/II disparities, [4][5][6][7] and their clinical relevance has been documented in several studies. 2,3,[6][7][8][9] The impact of HLA-C disparities on T-cell alloreactivity could be influenced by the expression level of HLA-C antigens at the cell surface. Low-expression HLA-C alleles could thus possibly represent good candidates for more permissive mismatches.…”