Clinical outcomes of <scp>HLA</scp>‐<scp>DPB</scp>1 mismatches in 10/10 <scp>HLA</scp>‐matched unrelated donor‐recipient pairs undergoing allogeneic stem cell transplant

Moyer, Ann M.; Hashmi, Shahrukh K.; Kroning, Cynthia M.; Kremers, Walter K.; Goey, Steven R. De; Patnaik, Mrinal M.; Litzow, Mark R.; Gastineau, Dennis A.; Jacob, Eapen K.; Kreuter, Justin D.; Wakefield, Laurie L.; Gandhi, Manish J.

doi:10.1111/ejh.12916

Cited by 12 publications

(11 citation statements)

References 34 publications

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“…Retrospective genotyping of HLA-DPB1 locus in patients and their respective donors confirmed the high prevalence of HLA-DPB1 mismatches in both, 10/10 and 9/10 HLA-matched transplantations already reported elsewhere ( 7 , 25 , 26 ). Specifically, in the subgroup of 10/10 HLA-matched transplantations only 21.3% (n=521) were HLA-DP identical, while in the subgroup of 9/10 HLA-matched this fraction was 18.5% (n=198).…”

Section: Resultssupporting

confidence: 82%

The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis

et al. 2021

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T-cell epitope matching according to the TCE3 algorithm classifies HLA-DPB1 mismatches in permissive and non-permissive. This classification has been shown to be predictive for mortality and acute GvHD (aGvHD) events in large international cohorts. We retrospectively genotyped HLA-DPB1 in 3523 patients transplanted in Germany between 2000 and 2014 and in their unrelated donors using an Illumina amplicon-NGS based assay. Aim of the study was to evaluate DP-compatibility beyond the established TCE3 algorithm by assessing the combined effect of several DP-mismatch parameters on post-transplant outcome. We implemented an extended DP-mismatch assessment model where TCE3, DP allotype expression with respect to rs9277534, mismatch vector and number of mismatches were conjointly taken into consideration. In this model, non-permissive HLA-DPB1 mismatches showed significantly increased aGvHD risk if they were accompanied by two HLA-DPB1 mismatches in GvH direction (HR: 1.46) or one mismatched highly expressed patient allotype (HR: 1.53). As previously reported, non-permissive HLA-DPB1 mismatches associated with a significantly higher risk of aGvHD and non-relapse mortality (HR 1.36 and 1.21, respectively), which in turn translated into worse GvHD and relapse free survival (HR 1.13). Effects on GvL and GvHD appeared strongest in GvH-directed non-permissive mismatches. Our study results support the consideration of additional HLA-DPB1 mismatch parameters along with the established TCE3 matching algorithm for refinement of future donor selection. In particular, our findings suggest that DP non-permissiveness associated with two HLA-DPB1 mismatches or at least on highly expressed mismatched patient allotype should be avoided.

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Section: Resultssupporting

confidence: 82%

The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis

et al. 2021

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“…Previous studies have shown that rejected graft-specific CD4 + and CD8 + T cells derived from the "winner" UCB can recognize leukemic cells in dUCBT studies [7,8,12,23]. In addition, mismatch of HLA-DPB1 between the "winner" UCB and the recipient likely would reduce the risk of relapse in different patterns of HSCT [22,31,32]. The mechanism and effector cell population(s) remain unclear, however, requiring further laboratory research.…”

Section: Discussionmentioning

confidence: 99%

Cord Haploidentical Non-In Vitro T Cell Depletion Allogeneic Hematopoietic Stem Cell Transplantation Reduces Relapse of Refractory Acute Leukemia

Wang

Wei

et al. 2019

Biology of Blood and Marrow Transplantation

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Whether a graft-versus-graft (GVG) response in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) is associated with an enhanced graft-versus-leukemia (GVL) effect remains highly controversial. Furthermore, it is unknown if the GVG response overwhelms the impact of refractory acute leukemia. We aimed to compare the characteristics and therapeutic outcomes between patients undergoing a modified haploidentical cord blood (cord-haplo) HSCT protocol (n = 97) and those undergoing haploidentical HSCT (n = 42) for refractory acute leukemia. A reliable and stable predominant haploidentical donor chimerism was established. The 2-year relapse rate was more favorable in patients undergoing cord-haplo HSCT than in those undergoing haploidentical HSCT (25.9% versus 53.2%; P = .007), as was progression-free survival (PFS; 35.5% versus 17.9%; P = .049). Meanwhile, nonrelapse mortality at 2years was not significantly different (38.0% versus 24.6%; P = .367). We also found that a higher number of mutual haploidentical donor-mismatched antigens, a concept similar to HLA mismatching, was associated with better disease control. Multivariate analysis identified cord-haplo HSCT as an independent significant predictor of reduced relapse (hazard ratio [HR], .44; P = .028) and improved PFS (HR, .58; P = .033), as was chronic graft-versus-host disease (GVHD) (relapse: HR, .42; P = .013; PFS: HR, .63: P = .052). However, the incidences of neutrophil and platelet engraftment, GVHD, and virus reactivation were comparable in the 2 groups. This study demonstrates that cord-haplo HSCT significantly enhances the GVL effect and improves PFS, providing a reliable and efficient therapeutic platform for patients with refractory acute leukemia.

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“…Legend: GvHD = graft versus host disease (a=acute; c=chronic); HLA = human leukocyte antigen; MM = mismatch; No =Number; Non-p = non-permissive; NRM = non-relapse mortality; OS = overall survival; TRM = transplant relate mortality; / = not investigated in the study [18] 1342 HLA-DPB1 MMno effect HLA-DPB1 MMincreased GvHD HLA-DPB1 MMno effect Non-p HLA-DPB1 MMincreased relapse Moyer AM et al 2017, [19] 153 HLA-DPB1 MMno effect HLA-DPB1 MMincreased cGvHD; Non-p HLA-DPB1 MMincreased aGVHD HLA-DPB1 MMno effect HLA-DPB1 MMno effect…”

Section: Conflict Of Interestmentioning

confidence: 99%

“…Retrospective studies analysing HLA-DPB1-matching status between matched unrelated donors (MUDs) and recipients at the allelic level, or classified as permissive/non-permissive mismatches were performed [5,6,[8][9][10][11][12][13][14][15][16][17][18][19]. The given results are heterogeneous and an overview of results from literature is summarized in Table 1.…”

Section: Introductionmentioning

confidence: 99%

HLA-DPB1 matching in unrelated hematopoietic stem cell transplantation program contributes to a higher incidence of disease relapse

et al. 2017

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Clinical outcomes of HLA‐DPB1 mismatches in 10/10 HLA‐matched unrelated donor‐recipient pairs undergoing allogeneic stem cell transplant

Abstract: In this single-center study, HLA-DPB1 matching influenced outcomes of patients undergoing ASCT for hematologic malignancy.

Cited by 12 publications

References 34 publications

The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis

The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis

Cord Haploidentical Non-In Vitro T Cell Depletion Allogeneic Hematopoietic Stem Cell Transplantation Reduces Relapse of Refractory Acute Leukemia

HLA-DPB1 matching in unrelated hematopoietic stem cell transplantation program contributes to a higher incidence of disease relapse

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