Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Abstract

Increasing donor-recipient HLA disparity is associated with negative outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), but its comparative relevance amid non-HLA donor characteristics is not well established. We addressed this question in 3215 HSCTs performed between 2005 and 2013 in Germany for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donors were HLA-matched related (MRD; n = 872) or unrelated (10/10 MUD, n = 1553) or HLA-mismatched unrelated (<10/10 MMUD, n = 790). Overall survival (OS) was similar after MRD compared with 10/10 MUD HSCT, reflecting opposing hazards of relapse (hazard ratio [HR], 1.32; P < .002) and nonrelapse mortality (HR, .63; P < .001). After UD HSCT, increasing HLA disparity was associated with inferior OS (HR, 1.21 [P < .02] and HR, 1.57 [P < .001] for 9/10 and ≤8/10 MMUD, respectively, compared with 10/10 MUD). Among non-HLA donor characteristics, age, sex mismatching (male recipient-female donor), and cytomegalovirus (CMV) mismatching (positive recipient-negative donor) impacted OS. Multivariate subgroup analysis showed that OS was similar after HSCT from the youngest 9/10 MMUD (<30 years) compared with the oldest 10/10 MUD (>40 years) (HR, 1.18; P = .25) and also in male patients transplanted from female 10/10 MUD compared with male 9/10 MMUD (HR, .89; P = .46). In contrast, OS of CMV-positive patients tended to be better with CMV-negative 10/10 MUDs compared with CMV-positive 9/10 MMUDs (HR, 1.31; P = .04). Because of low patient numbers in subgroups, definite conclusions and establishment of a hierarchy among HLA matching and non-HLA donor characteristics could not be made. Our data suggest that the impact of donor age and sex mismatch but not CMV mismatch on outcome of allogeneic HSCT may be comparable with that of single HLA disparity.

Evaluation of the AllType kit for HLA typing using the Ion Torrent S5 XL platform

“…The key roles of HLA genes in solid organ and hematopoietic stem cell transplantation (HSCT) are well established. HLA typing and matching between donors and recipients are fundamental for improving graft outcomes . Recently, next‐generation sequencing (NGS) methods have revolutionized HLA typing.…”

“…are fundamental for improving graft outcomes. [1][2][3][4][5] Recently, next-generation sequencing (NGS) methods have revolutionized HLA typing. These methods are now widespread and allow rapid and inexpensive sequencing of full-length loci from the 5 0 UTR to 3 0 UTR regions.…”

Allogeneic Bone Marrow Transplantation versus Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies in Children: A Systematic Review and Meta-Analysis

“…Adverse events after hematopoietic cell transplantation include the immune reaction called graft-versus-host disease (GVHD); bacterial, viral, and fungal infections; and hepatic sinusoidal obstruction syndrome [1]. Risk factors for treatment-related mortality include HLA mismatch, age, myeloablative conditioning regimen, and comorbidities [2][3][4][5]. Bone marrow was initially used as a source of hematopoietic stem cells; however, peripheral blood stem cells, mobilized by granulocyte colony-stimulating factor, was introduced as an alternative stem cell source in the early 2000s [6].…”

HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 allele and haplotype frequencies: An analysis of umbilical cord blood units at the Barcelona Cord Blood Bank

“…HLA genes are highly polymorphic and as such are involved in allogeneic immune responses following hematopoietic stem cell transplantation (HSCT), where they play an important role in graft‐vs‐host disease (GVHD) . Studies have shown that donor‐recipient HLA mismatch is significantly associated with worse survival outcomes …”

“…3 Studies have shown that donor-recipient HLA mismatch is significantly associated with worse survival outcomes. [4][5][6][7] Around 35 000 units of umbilical cord blood (CB) have been transplanted worldwide since the first successful transplant in 1988. 8 CB is now a well-established source of hematopoietic stem cells (HSCs) for patients with malignant and non-malignant hematologic diseases 9 and it requires a lower degree of donor-recipient HLA compatibility than adult tissue types.…”