HLA-inferred extended haplotype disparity level is more relevant than the level of HLA mismatch alone for the patients survival and GvHD in T cell-replate hematopoietic stem cell transplantation from unrelated donor

Nowak, Jacek; Nestorowicz, Klaudia; Graczyk‐Pol, Elżbieta; Mika‐Witkowska, Renata; Rogatko-Koroś, Marta; Jaskuła, Emilia; Kościńska, Katarzyna; Madej, Sylwia; Tomaszewska, Agnieszka; Nasiłowska-Adamska, Barbara; Szczepiński, Andrzej; Hałaburda, Kazimierz; Dybko, Jarosław; Kuliczkowski, Kazimierz; Czerw, Tomasz; Giebel, Sebastian; Hołowiecki, Jerzy; Barańska, Małgorzata; Pieczonka, Anna; Wachowiak, Jacek; Czyż, Anna; Gil, Lidia; Łojko‐Dankowska, Anna; Komarnicki, Mieczysław; Bieniaszewska, Maria; Kucharska, Agnieszka; Hellmann, Andrzej; Gronkowska, Anna; Jędrzejczak, Wiesław Wiktor; Markiewicz, Mirosław; Koclęga, Anna; Kyrcz‐Krzemień, Sławomira; Mielcarek, M.; Kałwak, Krzysztof; Styczyński, Jan; Wysocki, Mariusz; Drabko, Katarzyna; Wójcik, Beata; Kowalczyk, Jerzy; Goździk, Jolanta; Pawliczak, Daria; Gwozdowicz, Slawomir; Dziopa, Joanna; Szlendak, Urszula; Witkowska, Agnieszka; Zubala, Marta; Gawron, Agnieszka; Warzocha, Krzysztof; Lange, Andrzej

doi:10.1016/j.humimm.2018.03.011

Cited by 10 publications

(11 citation statements)

References 34 publications

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“…Indeed, the impact of non-HLA genes (e.g. cytokines, cytokine receptors) and polymorphisms such as microsatellites and SNPs has been reported to influence clinical outcome in unrelated HSCT [6,8,9,11,12,46]. Although SNPs can directly affect the sequences of immunogenic peptides leading to mHA disparities, they may also modify genes encoding proteins involved in the pathophysiology of GVHD, such as TNF alpha, complement, TAP1/2, LMP1/7.…”

Section: Discussionmentioning

confidence: 99%

High-resolution HLA phased haplotype frequencies to predict the success of unrelated donor searches and clinical outcome following hematopoietic stem cell transplantation

Bühler

Baldomero

Ferrari‐Lacraz

et al. 2019

Bone Marrow Transplant

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HLA matching is a critical factor for successful allogeneic hematopoietic stem cell transplantation. For unrelated donor searches, matching is usually based on high-resolution typing at five HLA loci, looking for a 10/10 match. Some studies have proposed that further matching at the haplotype level could be beneficial for clinical outcome. In this study, we determined the phased haplotypes of 291 patients using family members and segregation analysis. The sum of ranks of the haplotypes carried by patients was used as a surrogate predictor of a successful unrelated donor search. The putative impact of haplotypes was then analyzed in a cohort of 211 recipients transplanted with 10/10 matched unrelated donors. A logistic regression analysis showed a highly significant effect of the haplotypes in the outcome of a search, but we did not find any significant effect on overall survival, graft versus host disease or relapse/progression following HSCT. This study provides useful data for the optimization of unrelated bone marrow donor searches, but does not confirm previous reports that matching at the haplotype level has a clinical impact following HSCT. Due to the extreme polymorphism of HLA genes, further studies are warranted to better understand the many factors at play.

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Section: Discussionmentioning

confidence: 99%

High-resolution HLA phased haplotype frequencies to predict the success of unrelated donor searches and clinical outcome following hematopoietic stem cell transplantation

Bühler

Baldomero

Ferrari‐Lacraz

et al. 2019

Bone Marrow Transplant

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“…Matching the entire HLA haplotypes has been reported to significantly decrease the risk of GVHD and increase the overall survival in allogenic HSCT. Conversely, the incompatibility of extended MHC haplotypes significantly impairs GVHD and overall survival, emphasizing the importance of matching the entire MHC region [35,38,[60][61][62].…”

Section: Discussionmentioning

confidence: 99%

“…The specific MHC constitution of the Finnish population would favor a Finnish donor for a Finnish patient to minimize the risk of GVHD. Also, because nonclassic HLA and haplotype matches are reported to reduce the risk of HSCT complications [35,36,39,[60][61][62], genetic and clinical data were combined to evaluate the effects of C4 and haplotype mismatching on GVHD, relapse, and survival. However, we did not find any statistically significant association between C4 compatibility and HSCT outcome, which is consistent with recent reports [75,76], although controversial results have also been reported [77].…”

Section: Discussionmentioning

confidence: 99%

Increased MHC Matching by C4 Gene Compatibility in Unrelated Donor Hematopoietic Stem Cell Transplantation

Clancy

Ritari

Lobier

et al. 2019

Biology of Blood and Marrow Transplantation

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HLA matching is a prerequisite for successful allogeneic hematopoietic stem cell transplantation (HSCT) because it lowers the occurrence and severity of graft-versus-host disease (GVHD). However, matching a few alleles of the classic HLA genes only may not ensure matching of the entire MHC region. HLA haplotype matching has been reported to be beneficial in HSCT because of the variation relevant to GVHD risk in the non-HLA region. Because polymorphism in the MHC is highly population specific, we hypothesized that donors from the Finnish registry are more likely to be matched at a higher level for the Finnish patients than donors from other registries. In the present study we determined 25 single nucleotide polymorphisms (SNPs) of the complement component 4 (C4) gene in the g-block segment of MHC from 115 Finnish HSCT patients and their Finnish (n = 201) and non-Finnish (n = 280) donor candidates. Full matching of HLA alleles and C4 SNPs, independently or additively, occurred more likely in the FinnishÀFinnish group as compared with the FinnishÀnon-Finnish group (P < .003). This was most striking in cases with HLA haplotypes typical of the Finnish population. Patients with ancestral HLA haplotypes (AH) were more likely to find a full HLA and C4 matched donor, regardless of donor origin, as compared with patients without AH (P < .0001). Despite the clear differences at the population level, we could not find a statistical association between C4 matching and clinical outcome. The results suggest that screening C4 SNPs can be advantageous when an extended MHC matching or HLA haplotype matching in HSCT is required. This study also supports the need for small population-specific stem cell registries.

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“…A similar approach was conducted by Nowak et al (116), who hypothesized that the increased risk of post-transplant complications might be dependent on disparity in nonroutinely-tested polymorphisms in the MHC region, being organized in combinations of two extended MHC haplotypes. They tested the hypothesis that clinical outcome in unrelated HSCT with a certain level of HLA-mismatch is affected by the level of HLA-inferred extended MHC haplotype disparity.…”

Section: Matching Non-hla Mhc-linked Variationmentioning

confidence: 99%

Review of Genetic Variation as a Predictive Biomarker for Chronic Graft-Versus-Host-Disease After Allogeneic Stem Cell Transplantation

et al. 2020

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HLA-inferred extended haplotype disparity level is more relevant than the level of HLA mismatch alone for the patients survival and GvHD in T cell-replate hematopoietic stem cell transplantation from unrelated donor

Cited by 10 publications

References 34 publications

High-resolution HLA phased haplotype frequencies to predict the success of unrelated donor searches and clinical outcome following hematopoietic stem cell transplantation

High-resolution HLA phased haplotype frequencies to predict the success of unrelated donor searches and clinical outcome following hematopoietic stem cell transplantation

Increased MHC Matching by C4 Gene Compatibility in Unrelated Donor Hematopoietic Stem Cell Transplantation

Review of Genetic Variation as a Predictive Biomarker for Chronic Graft-Versus-Host-Disease After Allogeneic Stem Cell Transplantation

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