HLA-A, -B and -DR antigen frequencies of the London Cord Blood Bank units differ from those found in established bone marrow donor registries

Brown, Juliette; Poles, Anthony; Brown, Colin J.; Contreras, Marcela; Navarrete, Cristina

doi:10.1038/sj.bmt.1702197

Cited by 30 publications

(29 citation statements)

References 20 publications

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“…For instance, the Swiss Cord Blood Bank (CBB, not included in this survey) puts a special emphasis on the recruitment of ethnic minorities living in Switzerland in order to improve the probability of donor-recipient matching, and this registry differs from the Volunteer Unrelated Donors (VUD) dataset [45]. Also, ethnic minorities are extensively represented in the London Cord Blood Bank while they make up only 2% of the VUD in the British Bone Marrow registry [49]. In such situations where the data are very heterogeneous on purpose, analyses focusing on scientific questions related to anthropology and human peopling history might not be recommended.…”

Section: Discussionmentioning

confidence: 99%

The Heterogeneous HLA Genetic Makeup of the Swiss Population

et al. 2012

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This study aims at investigating the HLA molecular variation across Switzerland in order to determine possible regional differences, which would be highly relevant to several purposes: optimizing donor recruitment strategies in hematopoietic stem cell transplantation (HSCT), providing reliable reference data in HLA and disease association studies, and understanding the population genetic background(s) of this culturally heterogeneous country. HLA molecular data of more than 20,000 HSCT donors from 9–13 recruitment centers of the whole country were analyzed. Allele and haplotype frequencies were estimated by using new computer tools adapted to the heterogeneity and ambiguity of the data. Non-parametric and resampling statistical tests were performed to assess Hardy-Weinberg equilibrium, selective neutrality and linkage disequilibrium among different loci, both in each recruitment center and in the whole national registry. Genetic variation was explored through genetic distance and hierarchical analysis of variance taking into account both geographic and linguistic subdivisions in Switzerland. The results indicate a heterogeneous genetic makeup of the Swiss population: first, allele frequencies estimated on the whole national registry strongly deviate from Hardy-Weinberg equilibrium, by contrast with the results obtained for individual centers; second, a pronounced differentiation is observed for Ticino, Graubünden, and, to a lesser extent, Wallis, suggesting that the Alps represent(ed) a barrier to gene flow; finally, although cultural (linguistic) boundaries do not represent a main genetic differentiation factor in Switzerland, the genetic relatedness between population from south-eastern Switzerland and Italy agrees with historical and linguistic data. Overall, this study justifies the maintenance of a decentralized donor recruitment structure in Switzerland allowing increasing the genetic diversity of the national—and hence global—donor registry. It also indicates that HLA data of local donor recruitment centers can be used as reference data in both epidemiological and population genetic studies focusing on the genetic history of present European populations.

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Section: Discussionmentioning

confidence: 99%

The Heterogeneous HLA Genetic Makeup of the Swiss Population

et al. 2012

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“…Brown et al 15 showed that UCB units of the London Cord Blood Bank are more likely to be derived from ethnic minorities, although they represented only 2% of the VUD in the British Bone Marrow registry. Furthermore, their UCB units show an HLA profile that differs from that of their VUD.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13][14] The national organization Swiss Blood stem cells (SBsc) registers UCB from two Swiss cord blood banks in two hospitals with distinct recruitment areas and different sociocultural background and also VUD recruited by the country-wide blood banks. Presently there is little information 15,16 about whether cord blood banks recruit donors with HLA-alleles and haplotypes different from adult donor registries within the same geographical area.…”

Section: Introductionmentioning

confidence: 99%

Cord blood banks collect units with different HLA alleles and haplotypes to volunteer donor banks: a comparative report from Swiss Blood stem cells

Meyer-Monard

Passweg

Troeger

et al. 2008

Bone Marrow Transplant

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Allogeneic haematopoietic SCT is a standard therapy for many patients with haematological diseases. A major aim of public umbilical cord blood (UCB) banking is to establish an inventory with a large HLA diversity. Few studies have compared HLA diversity between UCB banks and volunteer unrelated donor (VUD) registries and examined whether UCB banks indeed collect more units with rare alleles and haplotypes. This study compares HLA-A/B/DRB1 allele frequencies and inferred A/B/DRB1-haplotypes in 1602 UCB units and 3093 VUD from two centres in distinct recruitment areas in Switzerland. The results show that the frequencies of HLA-DRB1 alleles as well as of the HLA-A/B/DRB1 haplotypes differ between UCB and VUD. Ten DRB1 alleles occurred at a 2-to 12-fold higher relative frequency in UCB than in VUD and 27 rare alleles were identified in UCB. Out of these 27 alleles, 15 were absent in the entire VUD data set of the national registry. This difference in allele frequencies was found only by intermediate/highresolution typing. Targeted recruitment of UCB units from non-Caucasian donors could further increase HLA allele and haplotype diversity of available donors. Intermediate or high-resolution DNA typing is essential to identify rare alleles or allele groups.

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“…16 Selective recruitment of CB donors among ethnic minorities has been shown to be successful. 17 It is unknown at this time if selective recruitment among ethnic minorities will substantially increase the chances of identifying a CB donor among patients of similar ethnicity, and the impact of HLAmismatched transplant in this population. The medianinfused nucleated cell dose was 4.3 Â 10 7 /kg in CB patients.…”

Section: Discussionmentioning

confidence: 99%

Results of an unrelated transplant search strategy using partially HLA-mismatched cord blood as an immediate alternative to HLA-matched bone marrow

Dalle

Duval

Moghrabi

et al. 2004

Bone Marrow Transplant

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Summary:Cord blood (CB) is an alternative to other sources of stem cells for transplantation. However, the impact of including CB in the initial strategy of unrelated graft search in a cohort of patients has been the object of limited analysis. Here, we report the results of such a strategy in 91 consecutive children. Absence of mismatch was required for adult donors, and up to two mismatches were allowed for CB grafts, with a nucleated cell dose over 2.5 Â 10 7 cells/kg. A graft was found for 84 of the 85 children who remained available for a 3-month search. In all, 64 patients were transplanted, 36 with CB and 28 with bone marrow (BM). Primary graft failure, acute grade II-IV and extensive chronic graft-versus-host disease occurred in five, five and zero CB, and in three, one and two BM patients, respectively. The 3-year survival was 59% in CB and 57% in BM patients. Accepting CB as a source of stem cells offers a graft to almost every child in need of an unrelated transplantation, with a probability of survival similar to that of unrelated BM transplantation. Advantages of unrelated cord blood (CB) over unrelated bone marrow (BM) include less stringent requirements for HLA compatibility between the donor and recipient, resulting from a lower risk of graft-versus-host disease (GVHD). 1,2 CB viral contamination rate is very low, which may be especially important in pediatric patients who are often cytomegalovirus (CMV) and Epstein-Barr virus (EBV) negative. Further, CB units from banks are more rapidly available than BM volunteer donors from international registries. 3 Accepting CB transplant as a first-line alternative to BM transplant for patients in need for an unrelated transplantation is expected to increase the probability of finding a suitable graft. However, the results of such a search strategy have not been reported to date. It carries two major risks. First, the increase in the pool of donors may be marginal. Second, if CB transplantation outcome is worse, waiting for an unrelated BM donor may be preferable to early CB transplantation. Also, in the absence of an identified HLA-compatible BM donor, other therapeutic options are also available, such as haplo-identical grafts.To randomize patients in a study comparing unrelated CB and BM transplantation, each patient would need a CB and a BM donor available. Conducting such a study has so far not been possible. One has thus to rely on registries or single-institution studies. Clinical reports comparing outcomes for patients undergoing unrelated CB and BM transplantation recipients point to delayed time to hematopoietic recovery, and sometimes to a higher treatmentrelated mortality. [4][5][6][7][8][9] One pediatric registry survey demonstrated a slightly better outcome after unrelated BM transplantation when compared with CB. 8 In this survey, the mean number of CB transplantations for each center was 2.6. A single-institution pediatric study, analyzing 63 CB transplantations, reported a similar outcome after unrelated CB and BM transplantation. 9 In a l...

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HLA-A, -B and -DR antigen frequencies of the London Cord Blood Bank units differ from those found in established bone marrow donor registries

Cited by 30 publications

References 20 publications

The Heterogeneous HLA Genetic Makeup of the Swiss Population

The Heterogeneous HLA Genetic Makeup of the Swiss Population

Cord blood banks collect units with different HLA alleles and haplotypes to volunteer donor banks: a comparative report from Swiss Blood stem cells

Results of an unrelated transplant search strategy using partially HLA-mismatched cord blood as an immediate alternative to HLA-matched bone marrow

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