Mismatched unrelated donor transplantation

Petersdorf, Effie W.

doi:10.1053/j.seminhematol.2016.07.003

Cited by 9 publications

(6 citation statements)

References 25 publications

(34 reference statements)

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“…Human leukocyte antigen (HLA) matching between recipients and donors is a prerequisite for successful allogeneic hematopoietic stem cell transplantation (HSCT), notably to avoid graft versus host disease (GVHD) as main posttransplant complication. Although new protocols for selecting donors are increasingly sought, even across the histocompatibility barrier [1][2][3], the gold standard is to look first for an HLA identical sibling. If such a genotypically identical sibling cannot be found, the preferred alternative is to search for a 10/10 or 12/12 phenotypically matched unrelated donor (MUD) [4,5].…”

Section: Introductionmentioning

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: Introductionmentioning

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 genes are inherited within parental haplotypes that represent groups of physically linked alleles with possible conserved association because of positive "linkage disequilibrium" [32]. By definition, "HLA haploidentical transplant" means the familiar donor and recipient share only 1 inherited HLA haplotype, whereas the second is different and randomly derived.…”

Section: Introductionmentioning

confidence: 99%

“…Conversely, from the patient's perspective the presence of donor disparity not shared by the recipient provokes the HVG alloresponse that increases the risk of graft failure. Thus, in the case of homozygosis of some HLA loci, reduced HLA disparity may involve only 1 vector of the allo-immune response; this may affect GVH allo-response in the case of homozygosis of the recipient or HVG allo-response in the case of homozygosis of the donor [32].…”

Section: Introductionmentioning

confidence: 99%

Impact of HLA Disparity in Haploidentical Bone Marrow Transplantation Followed by High-Dose Cyclophosphamide

Raiola

Risitano

Sacchi

et al. 2018

Biology of Blood and Marrow Transplantation

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We studied the impact of HLA mismatching on the outcome of 318 consecutive patients who received an unmanipulated haploidentical bone marrow transplant, followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched antigens was tested for its impact on overall survival (OS) and nonrelapse mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction were tested for prediction of graft-versus-host disease (GVHD and relapse. Finally, we studied whether graft rejection correlated with the number of HLA mismatched antigens in host-versus-graft (HVG) direction. Two hundred thirty-one donor-recipient pairs (72%) had 4/8 mismatches at the -A, -B, -C, -DRB1 HLA loci. HLA mismatches did not predict the 2-year OS (hazard ratio, .83; P = .58) and NRM (subhazard ratio, 1.08; P = .93). The cumulative incidence of acute GVHD (P = .13), 1-year chronic GVHD (P = .84), and relapse rate (P = .26) did not correlate with univectorial GVH mismatches. Similarly, no correlation was observed between the amount of HLA mismatch in the HVG direction and graft rejection. In multivariate analysis advanced disease at transplant was the strongest predictor of survival, NRM, relapse, and graft rejection. In conclusion, the degree of HLA mismatching should not be used as a criterion to select family haploidentical donors when using bone marrow as stem cell source and PTCy for GVHD prophylaxis.

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“…23,[27][28][29][30] There is currently a consensus that a single HLA MM at the HLA-A, -B, -C, and -DRB1 loci is clinically relevant; however, which of these loci is the most important one has not been agreed upon. 20,31,32 Different studies reported various results, for example, Petersdorf et al reported that mortality and GvHD increase with increasing numbers of HLA MMs as well as that a single HLA-B MM increased grade III-IV aGvHD incidence. 33 Ayuk et al reported that an increasing HLA disparity was associated with a lower OS and DFS for patients with a 9/10 and ≤8/10 MUD compared with the patients with a 10/10 MUD.…”

Section: Discussionmentioning

confidence: 99%

An intermediate‐sized donor registry experience: HLA barriers in matching procedures

Grubic,

Maskalan,

Stingl Jankovic

et al. 2024

HLA

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The data enabling the estimation of the possibility of finding a matched unrelated donor (MUD) within a relatively short time is important for the success of hematopoietic stem cell transplantation (HSCT). In the present study, 738 unrelated Croatian patients in the program of unrelated HSCT were retrospectively analyzed for gender matching, donor origin (national or international), the distribution of HLA alleles and haplotypes, as well as for the probability of finding a 9‐10/10 MUD. Almost 70% of the patients in our study group had a 10/10 MUD, while among the patients with a 9/10 MUD, a 1st field resolution level mismatched donor was selected for 55.0% of patients. The majority of pairs were HLA‐A mismatched (33.8%). A comparison of HLA allele frequencies between two subgroups of patients revealed significant differences for 13 alleles. However, after p value correction, the difference in frequency remained significant only for four alleles; three HLA alleles (B*08:01, C*07:01, and DRB1*03:01) demonstrated a significantly higher frequency among patients with a 10/10 MUD (Pcorr < 0.0001, Pcorr = 0.0096, and Pcorr < 0.0001, respectively), while the B*35:08 allele was significantly more present among patients with a 9/10 MUD (Pcorr = 0.0328). The comparison of the distribution of HLA haplotypes between patients with a 10/10 MUD and patients with a 9/10 MUD showed significant differences for a number of two‐locus and three‐locus haplotypes, as well as for one five‐locus haplotype (HLA‐A*01:01~B*08:01~C*07:01~DRB1*03:01~DQB1*02:01), which was significantly more present in the group of patients with a 10/10 MUD. At least one HLA haplotype from the group of non‐frequent HLA haplotypes (positions >1000) was carried by patients with a 9/10 MUD. The data obtained by the present study will contribute to a better estimation of the probability of finding a suitable 9‐10/10 MUD for Croatian patients in need of HSCT.

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Mismatched unrelated donor transplantation

Cited by 9 publications

References 25 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

Impact of HLA Disparity in Haploidentical Bone Marrow Transplantation Followed by High-Dose Cyclophosphamide

An intermediate‐sized donor registry experience: HLA barriers in matching procedures

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