Identification of a 10/10 matched donor for patients with an uncommon haplotype is unlikely

Olson, Janelle A.; Gibbens, Ying; Tram, Kevin V.; Kempenich, Jane; Novakovich, Jennifer; Buck, Kelly; Dehn, Jason

doi:10.1111/tan.12946

Cited by 10 publications

(9 citation statements)

References 22 publications

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“…In the unrelated setting, the probability of finding a 10/10 matched donor is largely determined by haplotype frequencies, our analyses thus agree with previous publications [13,[27][28][29][37][38][39]. Accurate prediction allows to define the optimal strategy to find the best suitable donor, whether a matched unrelated, mismatched unrelated or a haploidentical donor [40,41].…”

Section: Discussionsupporting

confidence: 87%

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: Discussionsupporting

confidence: 87%

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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“…identifying matched donors 1,7,[12][13][14][15][16] which led to the development of various software programs computing the likelihoods to identify donors with suitable matching criteria. [17][18][19][20] With the increasing diversity of HLA haplotypes across Europe, 3,4,21 the need for continuing growth of small/intermediate size registries has become more obvious. 22 However, with few exceptions 9,23,24 no detailed analysis has been performed on the selected donors with respect to HLA and non-HLA characteristics.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have demonstrated the direct link between haplotype frequencies in different HSC registries and the probabilities of identifying matched donors which led to the development of various software programs computing the likelihoods to identify donors with suitable matching criteria . With the increasing diversity of HLA haplotypes across Europe, the need for continuing growth of small/intermediate size registries has become more obvious .…”

Section: Discussionmentioning

confidence: 99%

A study of selected hematopoietic stem cell donors provided by an intermediate size registry

Nicoloso

Kürsteiner

Bussmann

et al. 2019

European J of Haematology

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Objective Planning new hematopoietic stem cell (HSC) donor recruitment strategies requires a sound understanding of the factors underlying donor selection, especially considering HLA‐matching criteria. Method A total of 182 consecutive workups of Swiss donors performed from 2014 to 2017 were analyzed for HLA match level, locus disparities, number of potentially 10/10 matched donors in the international database, donor ranking on the lists, donor date of registration, age, ABO, CMV, gender matching, patient genotype frequency, and country performing the search. Results Matching status of the selected donors was 10/10 for 38.5%, 10‐12/12 for 35.1%, and 8‐9/10 for 26.4% donors, without differences in average donor age in the three categories. HLA‐A and ‐C mismatches were most frequent and ‐DRB1 very rare. 8.2% patients were matched for HLA‐DPB1 (12/12). ABO matching was 46.3%, and CMV matching was 59.1%. Based on “HaploStat”‐derived genotype frequencies, 50.3% patients belonged to the “good,” 38.5% to the “fair,” and 11.2% to the “poor” search prognosis categories. 37.9% of transplants were gender‐mismatched, and 42.3% of donors were female. Conclusion HLA typing quality (high resolution, all loci typed), great diversity of haplotypes and donor age are main factors impacting the selection of Swiss donors, while gender and ABO matching seem to be of secondary importance.

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“…This delay can adversely affect transplant outcomes and has special relevance for patients of non-European or mixed ancestries. Such patients due to diverse HLA haplotypes, lesser registry representation, and lower rates of donor availability are far less likely to identify donors who are HLA-matched 11-13 . It can also adversely affect the care of patients in need of urgent transplantation as disease status at the time of transplant is an important determinant of survival in patients with hematologic malignancies (reviewed in Lown et al 14 and references 15-17 ).…”

Section: Introductionmentioning

confidence: 99%

Validation of an Algorithm to Predict the Likelihood of an 8/8 HLA-Matched Unrelated Donor at Search Initiation

Davis

Devlin

Cooper

et al. 2018

Biology of Blood and Marrow Transplantation

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A strategy to rapidly determine if a matched unrelated donor (URD) can be secured for allograft recipients is needed. We sought to validate the accuracy of (1) HapLogic match predictions and (2) a resultant novel Search Prognosis (SP) patient categorization that could predict 8/8 HLA-matched URD(s) likelihood at search initiation. Patient prognosis categories at search initiation were correlated with URD confirmatory typing results. HapLogic-based SP categorizations accurately predicted the likelihood of an 8/8 HLA-match in 830 patients (1530 donors tested). Sixty percent of patients had 8/8 URD(s) identified. Patient SP categories (217 very good, 104 good, 178 fair, 33 poor, 153 very poor, 145 futile) were associated with a marked progressive decrease in 8/8 URD identification and transplantation. Very good to good categories were highly predictive of identifying and receiving an 8/8 URD regardless of ancestry. Europeans in fair/poor categories were more likely to identify and receive an 8/8 URD compared with non-Europeans. In all ancestries very poor and futile categories predicted no 8/8 URDs. HapLogic permits URD search results to be predicted once patient HLA typing and ancestry is obtained, dramatically improving search efficiency. Poor, very poor, andfutile searches can be immediately recognized, thereby facilitating prompt pursuit of alternative donors.

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Identification of a 10/10 matched donor for patients with an uncommon haplotype is unlikely

Cited by 10 publications

References 22 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

A study of selected hematopoietic stem cell donors provided by an intermediate size registry

Validation of an Algorithm to Predict the Likelihood of an 8/8 HLA-Matched Unrelated Donor at Search Initiation

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