HLA-DPB1 matching in unrelated hematopoietic stem cell transplantation program contributes to a higher incidence of disease relapse

The impact of patient/donor matching for HLA-A, -B, -C, -DRB1 and -DQB1 genes in hematopoietic stem cell transplantation (HSCT) is well-recognized, but typing for additional genes, such as HLA-DPB1, is still controversial. Based on defined T-cell epitope (TCE) groups, all HLA-DPB1 mismatches can be classified as permissive or non-permissive. In this retrospective study we analysed 82 patient-matched unrelated donor (MUD) pairs who underwent HSCT, and explored the impact of HLA-DPB1 matches, permissive and non-permissive mismatches on transplantation outcomes. Patient-MUD pairs matched for HLA-DPB1 alleles in univariate analysis were associated with a significantly higher incidence of disease relapse compared to pairs who were permissive/non-permissive HLA-DPB1 mismatched according to the TCE3 and TCE4 algorithms (P=0.025 and P=0.026, respectively), although the significance was lost in multivariate analysis. The analysis did not reveal any significant influence of HLA-DPB1 alleles on overall survival (OS), non-relapse mortality (NRM) or graft-versus-host disease (GvHD) incidence. In conclusion, our study presents evidence that HLA-DPB1 matching influenced the relapse rate in patients after HSCT so the HLA-DPB1 alleles should be implemented in the MUD search algorithm as a transplantation determinant

HLA allele and haplotype diversity in Croatia and its impact on donor selection in hematopoietic stem cell transplantation

Istraživanja raspodjele alela i haplotipova glavnog sustava tkivne snošljivosti (engl. Human Leukocyte Antigen, HLA) provode se u svrhu populacijskih istraživanja kao i u programu transplantacije krvotvornih matičnih stanica (TKMS) od HLA podudarnog nesrodnog davatelja. Ovim radom obuhvaćena je skupina od 10 000 zdravih nesrodnih dobrovoljnih davatelja iz Hrvatskog registra dobrovoljnih davatelja krvotvornih matičnih stanica (HRDDKMS) te skupina od 261 nesrodnog bolesnika u programu nesrodne TKMS. Svim ispitanicima analizirani su geni HLA-A, -B, -C i -DRB1 jednom od molekularnih metoda. Obradom podataka o učestalosti alela i haplotipova HLA dobivene su vrijedne informacije o raznolikosti alela HLA te čestim, rijetkim i vrlo rijetkim alelima i haplotipovima HLA u Hrvatskoj. Rezultati rada ističu važnost održavanja manjih i srednjih registara dobrovoljnih davatelja KMS čime se doprinosi prepoznavanju raznolikosti alela i haplotipova HLA. Također, ističu ulogu HLA kao ograničavajućeg čimbenika u pronalaženju fenotipski HLA podudarnog nesrodnog davatelja te služe unaprjeđenju postupka pronalaska najboljeg mogućeg davatelja za pojedinog bolesnika.Investigation of allele and haplotype distribution of genes pertaining to Human Leukocyte Antigen complex (HLA) is relevant for population studies but also in hematopoietic stem cell transplantation (HSCT) from HLA matched unrelated donor. This study encompassed 10 000 healthy unrelated volunteer donors from Croatian Bone Marrow Donor Registry (CBMDR) and 261 patients who underwent unrelated HSCT. All subjects were analyzed for HLA-A, -B, -C and -DRB1 genes by one of DNA analysis based methods. HLA allele and haplotype frequency analysis provided valuable information about HLA allelic polymorphism as well as data about common, rare and very rare HLA alleles and haplotypes in Croatia. Obtained results emphasize importance of maintaining small and medium size registries of HSC donors due to their contribution to HLA allele and haplotype diversity identification. Results also highlight the role of HLA as a limitation factor in identification of HLA phenotypically matched unrelated donor. Finally, data provided by this study will serve to improve the procedure of finding the best donor for a given patient

HLA allele and haplotype diversity in Croatia and its impact on donor selection in hematopoietic stem cell transplantation

Istraživanja raspodjele alela i haplotipova glavnog sustava tkivne snošljivosti (engl. Human Leukocyte Antigen, HLA) provode se u svrhu populacijskih istraživanja kao i u programu transplantacije krvotvornih matičnih stanica (TKMS) od HLA podudarnog nesrodnog davatelja. Ovim radom obuhvaćena je skupina od 10 000 zdravih nesrodnih dobrovoljnih davatelja iz Hrvatskog registra dobrovoljnih davatelja krvotvornih matičnih stanica (HRDDKMS) te skupina od 261 nesrodnog bolesnika u programu nesrodne TKMS. Svim ispitanicima analizirani su geni HLA-A, -B, -C i -DRB1 jednom od molekularnih metoda. Obradom podataka o učestalosti alela i haplotipova HLA dobivene su vrijedne informacije o raznolikosti alela HLA te čestim, rijetkim i vrlo rijetkim alelima i haplotipovima HLA u Hrvatskoj. Rezultati rada ističu važnost održavanja manjih i srednjih registara dobrovoljnih davatelja KMS čime se doprinosi prepoznavanju raznolikosti alela i haplotipova HLA. Također, ističu ulogu HLA kao ograničavajućeg čimbenika u pronalaženju fenotipski HLA podudarnog nesrodnog davatelja te služe unaprjeđenju postupka pronalaska najboljeg mogućeg davatelja za pojedinog bolesnika.Investigation of allele and haplotype distribution of genes pertaining to Human Leukocyte Antigen complex (HLA) is relevant for population studies but also in hematopoietic stem cell transplantation (HSCT) from HLA matched unrelated donor. This study encompassed 10 000 healthy unrelated volunteer donors from Croatian Bone Marrow Donor Registry (CBMDR) and 261 patients who underwent unrelated HSCT. All subjects were analyzed for HLA-A, -B, -C and -DRB1 genes by one of DNA analysis based methods. HLA allele and haplotype frequency analysis provided valuable information about HLA allelic polymorphism as well as data about common, rare and very rare HLA alleles and haplotypes in Croatia. Obtained results emphasize importance of maintaining small and medium size registries of HSC donors due to their contribution to HLA allele and haplotype diversity identification. Results also highlight the role of HLA as a limitation factor in identification of HLA phenotypically matched unrelated donor. Finally, data provided by this study will serve to improve the procedure of finding the best donor for a given patient

HLA allele and haplotype diversity in Croatia and its impact on donor selection in hematopoietic stem cell transplantation

Istraživanja raspodjele alela i haplotipova glavnog sustava tkivne snošljivosti (engl. Human Leukocyte Antigen, HLA) provode se u svrhu populacijskih istraživanja kao i u programu transplantacije krvotvornih matičnih stanica (TKMS) od HLA podudarnog nesrodnog davatelja. Ovim radom obuhvaćena je skupina od 10 000 zdravih nesrodnih dobrovoljnih davatelja iz Hrvatskog registra dobrovoljnih davatelja krvotvornih matičnih stanica (HRDDKMS) te skupina od 261 nesrodnog bolesnika u programu nesrodne TKMS. Svim ispitanicima analizirani su geni HLA-A, -B, -C i -DRB1 jednom od molekularnih metoda. Obradom podataka o učestalosti alela i haplotipova HLA dobivene su vrijedne informacije o raznolikosti alela HLA te čestim, rijetkim i vrlo rijetkim alelima i haplotipovima HLA u Hrvatskoj. Rezultati rada ističu važnost održavanja manjih i srednjih registara dobrovoljnih davatelja KMS čime se doprinosi prepoznavanju raznolikosti alela i haplotipova HLA. Također, ističu ulogu HLA kao ograničavajućeg čimbenika u pronalaženju fenotipski HLA podudarnog nesrodnog davatelja te služe unaprjeđenju postupka pronalaska najboljeg mogućeg davatelja za pojedinog bolesnika.Investigation of allele and haplotype distribution of genes pertaining to Human Leukocyte Antigen complex (HLA) is relevant for population studies but also in hematopoietic stem cell transplantation (HSCT) from HLA matched unrelated donor. This study encompassed 10 000 healthy unrelated volunteer donors from Croatian Bone Marrow Donor Registry (CBMDR) and 261 patients who underwent unrelated HSCT. All subjects were analyzed for HLA-A, -B, -C and -DRB1 genes by one of DNA analysis based methods. HLA allele and haplotype frequency analysis provided valuable information about HLA allelic polymorphism as well as data about common, rare and very rare HLA alleles and haplotypes in Croatia. Obtained results emphasize importance of maintaining small and medium size registries of HSC donors due to their contribution to HLA allele and haplotype diversity identification. Results also highlight the role of HLA as a limitation factor in identification of HLA phenotypically matched unrelated donor. Finally, data provided by this study will serve to improve the procedure of finding the best donor for a given patient

Mapping the Human Leukocyte Antigen Diversity among Croatian Regions: Implication in Transplantation

In the present study, HLA allele and haplotype frequencies were studied using the HLA data of 9277 Croatian unrelated individuals, typed using high-resolution methods for the HLA-A, -B, -C, and -DRB1 loci. The total numbers of observed alleles were 47 for HLA-A, 88 for HLA-B, 34 for HLA-C, and 53 for HLA-DRB1. HLA-A∗02:01 (29.5%), B∗51:01 (10.5%), C∗04:01 (15.8%), and DRB1∗16:01 (10.4%) were the most frequent alleles in the Croatian general population. The three most frequent haplotypes were HLA-A∗01:01~C∗07:01~B∗08:01~DRB1∗03:01 (4.7%), HLA-A∗03:01~C∗07:02~B∗07:02~DRB1∗15:01 (1.7%), and HLA-A∗02:01~C∗07:01~B∗18:01~DRB1∗11:04 (1.5%). Allele and haplotype frequencies were compared between national and regional data, and differences were observed, particularly in the North Croatia region. The data has potential use in refining donor recruitment strategies for national registries of volunteer hematopoietic stem cell donors, solid organ allocation schemes, and the design of future disease and anthropological studies