HLA-DP in unrelated hematopoietic cell transplantation revisited: challenges and opportunities

Fleischhauer, Katharina; Shaw, Bronwen E.

doi:10.1182/blood-2017-03-742346

Cited by 69 publications

(63 citation statements)

References 79 publications

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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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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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“…Our study has several limitations. First, we only analyzed HLA‐A, ‐B, ‐C, and DRB1 loci and did not examine other class II HLA loci such as HLA‐DPB1 and HLA‐DQB1, although they have also been suggested to influence transplantation outcomes in recent studies . Second, some patient populations were too small for a detailed analysis, such as a precise calculation of the distribution or combinations of mismatched HLA loci in each pair.…”

Section: Discussionmentioning

confidence: 99%

Wide availability of HLA‐matched or a few loci‐mismatched donors in the graft‐vs‐host direction among nonsibling first‐degree relatives

Watanabe

Kanda

Kojima³

et al. 2020

HLA

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Although outcomes of hematopoietic stem cell transplantation from alternative donors have been improved, it has not yet challenged the precedence of HLA-matched or a few loci-mismatched donors. Because the availabilities of these donors among nonsibling relatives have been scarcely discussed, we analyzed them using a large Japanese dataset of HLA typing. Data set included HLA data from 2838 patients and their relatives, distributed in all parts of Japan. Antigen mismatches at the HLA-A, -B, -DR loci and allele mismatches at the HLA-A, -B, -C, -DRB1 loci were examined. The availabilities of 0 to 1/6 antigen-mismatched donors among one parent-candidate and one siblingcandidate were 24.3% and 33.9%, and those of 0 to 2/8 allele-mismatched donors were 18.6% and 32.1%, respectively. Additional HLA-C antigen mismatches (18.1% vs 0.0%) along with the possession of 1 to 3/8 allele mismatches (31.3% vs 3.0%) were more frequently observed in parent-candidates than in sibling-candidate. Most multiple allele-mismatched pairs had HLA-B allele mismatches. In conclusion, expanding donor searches to include nonsibling relatives could widen the availability of conventional relative donors with 0 to 1/6 antigen mismatches or 0 to 2/8 allele mismatch to 20% to 30%.High-resolution typing including HLA-C locus examination should be performed, because additional mismatches at HLA-C loci along with multiple allele mismatches were often observed, especially among nonsibling pairs. K E Y W O R D Sallele-mismatched donors, antigen-mismatched donors, HLA, relative donors

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“…There are several encouraging new ways to prevent and to treat GVHD including modification of the gut microbiome [30,49,82]; it is now time to select donors according to their immune repertoire and their genetic background for T cell activation. Possibly this can be combined with an anti-leukemic effect based on anti-microbial activity [50,62] and HLA class II DP histocompatibility [83]. The immune repertoire may be primed by prior infections as they may be primed by prior transfusions and pregnancies, but activation may be decisive that is induced by the actual microbiome and determined genetically by the donor and the host.…”

Section: Discussionmentioning

confidence: 99%

Infection and GVHD

Kolb¹,

Weber²,

Simões³

et al. 2018

CTT

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HLA-DP in unrelated hematopoietic cell transplantation revisited: challenges and opportunities

Cited by 69 publications

References 79 publications

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

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

Wide availability of HLA‐matched or a few loci‐mismatched donors in the graft‐vs‐host direction among nonsibling first‐degree relatives

Infection and GVHD

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