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Race, ethnicity, and ancestry are terms that are often misinterpreted and/or used interchangeably. There is lack of consensus in the scientific literature on the definition of these terms and insufficient guidelines on the proper classification, collection, and application of this data in the scientific community. However, defining groups for human populations is crucial for multiple healthcare applications and clinical research. Some examples impacted by population classification include HLA matching for stem-cell or solid organ transplant, identifying disease associations and/or adverse drug reactions, defining social determinants of health, understanding diverse representation in research studies, and identifying potential biases. This article describes aspects of race, ethnicity and ancestry information that impact the stem-cell or solid organ transplantation field with particular focus on HLA data collected from donors and recipients by donor registries or transplant centers.
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Allogeneic hematopoietic stem cell (HSC) transplantation is a curative therapy for many severe blood diseases. As many patients have no suitable family donor, large unrelated donor registries and donor centers have been established in many countries, along with an international system for the provision of unrelated donor HSC products. As an essential part of this system, DKMS operates donor centers in 7 countries with a total of 12.2 million donors and over 114,000 donations so far, and a multinational donor registry. In 2022, DKMS donors contributed 57.5% of all cross-border donations worldwide. In this review, we describe the international system for the provision of unrelated donor HSC products as well as tasks and responsibilities of donor registries and donor centers. We also discuss relevant aspects of DKMS donor centers, namely donor file composition, matching and donation probabilities and actual donations, and the unique multinational approach of the DKMS Registry.
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Transplante de Células-Tronco Hematopoéticas , Doadores não Relacionados , Humanos , Doadores de Tecidos , Sistema de Registros , Células-Tronco HematopoéticasRESUMO
Young adults from underserved racial/ethnic groups are critically needed as unrelated hematopoietic stem cell (HSC) donors, yet they are more likely than other groups to opt out of donation after having matched a patient. Understanding which factors are most strongly associated with opting out among young underserved racial/ ethnic registered donors compared with their White counterparts will provide the basis for specific interventions to improve donor retention. We sought to determine the key, modifiable psychosocial, registry-related, and donation-related characteristics that are uniquely associated with opting out across 5 key racial/ethnic groups of young HSC donor registry members who had been contacted as a potential match for a patient. This study examines data from a large cross-sectional survey of young (age 18 to 30) registry members shortly after they preliminarily matched a patient (CT-stage) and continued toward or opted out of donation (CT-C and CT-NI), stratified by racial/ethnic group and sex. We assessed psychosocial, registry-related, and donation-related characteristics for all participants. We used chi-squared and F tests to assess differences between racial/ethnic groups. A separate logistic regression analysis for each racial/ethnic group was conducted to quantify adjusted associations between each variable and opting out. Then, we compared these associations across the racial/ethnic groups by evaluating the interaction effect between each variable and racial/ethnic group, with the same outcome (CT-C versus CT-NI) in question. Nine hundred thirty-five participants were surveyed, including 284 White, 165 Hispanic, 191 Black, 192 Asian/Pacific Islander, and 103 Multiracial/multiethnic participants. There were significant differences across racial/ethnic groups in values/goals, religious objections to donation, HSC-related medical mistrust, and parental involvement in donation decisions. Adjusted logistic regression subgroup analyses indicated that ambivalence was strongly associated with opting out across all racial/ethnic groups. Greater focus on intrinsic life goals (e.g., raising a family, becoming a community leader, influencing social values) was associated with opting out in the Multiracial/multiethnic, Hispanic, and Asian/Pacific Islander groups. Healthcare mistrust and insufficient registry contact was a significant factor for Hispanic participants. Protective factors against opting out included remembering joining the registry (Black participants), and parental support for donation decision (Asian/Pacific Islander participants). The performance of each logistic regression model was strong, with area-under-the curve ≥.88, CT-stage outcome classification accuracy ≥89%, and good fit between expected and observed opt-out probabilities. In the analysis across different racial/ethnic groups, the only significant interaction was race/ethnicity by whether more contact with the registry would have changed the decision at CT-stage; this variable was significant only for the Hispanic group. In the within-group analysis for Hispanic participants, the "more registry contact" variable was strongly associated with opting out (odds ratio 5.8, P = .03). Consistent with a growing body of HSC donor research, ambivalence was a key factor associated with opting-out for all racial/ethnic groups. Other key variables were differentially associated with opting-out depending on racial/ethnic group. Our study highlights key variables that registries should focus on as they develop targeted and tailored strategies to enhance commitment and reduce attrition of potential donors.
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Transplante de Células-Tronco Hematopoéticas , Sistema de Registros , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Estudos Transversais , Etnicidade/estatística & dados numéricos , Etnicidade/psicologia , Transplante de Células-Tronco Hematopoéticas/psicologia , Células-Tronco Hematopoéticas , Grupos Raciais/estatística & dados numéricos , Grupos Raciais/psicologia , Estados Unidos , Doadores não Relacionados , Brancos , Hispânico ou Latino , Negro ou Afro-Americano , Nativo Asiático-Americano do Havaí e das Ilhas do PacíficoRESUMO
Currently, approximately 19 million people with a migration background live in Germany. The majority of those descend from regions where the population has a genetically different distribution of HLA antigens when compared to the HLA frequencies usually found in North Western Europe. In case of severe haematological disorders of these individuals, allogeneic stem cell transplantation may be the treatment of choice. However, finding appropriate histocompatible hematopoietic stem cell donors continues to be a major challenge. If no matching sibling donors are available, there are only few suitable donors with a similar genetic background available in international blood stem cell donor registries. The "BluStar.NRW" project aimed to recruit new blood and hematopoietic stem cell donors with a migration background and to noticeably increase the number of suitable donors for patients within this group. Since December 2017, a total number of 9100 blood and stem cell donors with a migration background were recruited and typed for this project. HLA typing for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 was performed by Next Generation Sequencing. We assessed the proportion of rare alleles according to HLA frequency tables, as defined by a frequency of <1:1000. The rare HLA allele frequencies according to HLA frequency tables of the BluStar.NRW cohort were compared with a matched control donor cohort: Rare HLA-A, -B, -C, -DRB1 and -DQB1 alleles occurred three times more frequent than in the control group, but rare HLA-DPB1 alleles occurred more frequently in the control cohort. This difference was highly significant for all HLA alleles (p < 0.0001 for HLA-A, -B, -C, -DRB1, -DPB1; p = 0.0002 for HLA-DQB1). In addition, the distribution of rare alleles differed between the two groups. To date, 29 work-ups were initiated, 12 PBSC, one BM and three DLI were collected so far out of the BluStar.NRW cohort. The apheresis probability is twofold higher (0.18% vs. 0.07%) compared to the control group which clearly shows a serious medical need. However, 13 work-ups were cancelled in the BluStar.NRW donor cohort which represents an almost twice as higher cancellation rate (45% vs. 25%). This single registry analysis with a large sample cohort clearly indicates that hematopoietic stem cell donors with a migration background represent an adequate donor pool to serve patients of comparable ethnicity.
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Transplante de Células-Tronco Hematopoéticas , Refugiados , Migrantes , Humanos , Etnicidade/genética , Doadores de Tecidos , Antígenos de Histocompatibilidade Classe I/genética , Células-Tronco Hematopoéticas , Frequência do Gene , Antígenos HLA-A/genética , Alelos , Teste de Histocompatibilidade , HaplótiposRESUMO
Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed worldwide to treat blood cancer and other life-threatening blood disorders. As successful transplantation requires an HLA-compatible donor, unrelated donor centers and registries have been established worldwide to identify donors for patients without a family match. Ethnic minorities are underrepresented in large donor registries. Matching probabilities are higher when donors and patients share the same ethnic background, making it desirable to increase the diversity of the global donor pool by recruiting donors in new regions. Here, we report the establishment and the first 5 years of operation of the first unrelated stem cell donor center in Chile, a high-income country in South America with a population of over 19 million. Methods: We used online and in-person donor recruitment practices through patient appeals and donor drives in companies, universities, the armed forces, and public services. After confirmatory typing donors were subjected to medical work-up and cleared for donation. Results: We recruited almost 170,000 donors in 5 years. There were 1,488 requests received for confirmatory typing and donor availability checks, of which 333 resulted in medical work-up, leading to 194 stem cell collections. Products were shipped to Chile (48.5%) and abroad. Even when the COVID-19 pandemic challenged our activities, the number of donors recruited and shipped stem cell products remained steady. In Chile there was an almost 8-fold increase in unrelated donor transplantation activity from 16 procedures in 2016-2018 to 124 procedures in 2019-2021, mainly for pediatric patients following the center's establishment. We estimate that 49.6% of Chilean patients would find at least one matched unrelated donor in the global DKMS donor pool. Discussion: Establishing a DKMS donor center in Chile has significantly increased donor availability for Chilean patients and contributed to an increase of unrelated donor stem cell transplant activity.
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Patients in need of hematopoietic stem cell transplantation often rely on unrelated stem cell donors matched in certain human leukocyte antigen (HLA) genes. Donor search is complicated by the extensive allelic variability of the HLA system. Therefore, large registries of potential donors are maintained in many countries worldwide. Population-specific HLA characteristics determine the registry benefits for patients and also the need for further regional donor recruitment. In this work, we analyzed HLA allele and haplotype frequencies of donors of DKMS Chile, the first Chilean donor registry, with self-assessed "non-Indigenous" (n=92,788) and "Mapuche" (n=1,993) ancestry. We identified HLA alleles that were distinctly more abundant in the Chilean subpopulations than in worldwide reference populations, four of them particularly characteristic for the Mapuche subpopulation, namely B*39:09g, B*35:09, DRB1*04:07g, and DRB1*16:02g. Both population subsamples carried haplotypes of both Native American and European origin at high frequencies, reflecting Chile's complex history of admixture and immigration. Matching probability analysis revealed limited benefits for Chilean patients (both non-Indigenous and Mapuche) from donor registries of non-Chilean donors, thus indicating a need for ongoing significant donor recruitment efforts in Chile.
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Transplante de Células-Tronco Hematopoéticas , Humanos , Chile , Alelos , HaplótiposRESUMO
The guidelines for the implementation and reporting of HLA nomenclature for the World Marrow Donor Association have served as a reliable standard for communication of HLA data in the hematopoietic cell transplantation process. Wider use of next-generation sequencing made a special provision of the guidelines increasingly pertinent: how to communicate novel HLA alleles. Novel alleles need to be recognized by the WHO Nomenclature Committee for Factors of the HLA system to obtain official allele designations. Until then they have to be handled according to the specific rules. Leaving the actual rules basically unchanged we give some advice on how to communicate novel alleles to best facilitate the search process for cases where novel alleles are identified on donor or patient side.
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Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Humanos , Alelos , Antígenos HLA/genética , Teste de Histocompatibilidade , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Background: The Coronavirus Disease 2019 (COVID-19) pandemic in early 2020 has resulted in an unprecedented level of uncertainty and challenge for the stem cell donor registries. To address these challenges, rapid strategies were implemented by the National Marrow Donor Registry (NMDP) and its network partners. Herein, we aim to report the impact of the COVID-19 pandemic on the collection, utilization of grafts, and short-term outcomes of patients who received stem cell products from COVID-19-positive donors. Methods: NMDP data during the early phase (1 March 2020 through 1 May 2020) of the pandemic were compared to the later phase (1 March 2021 through 1 May 2021). Odds ratios were calculated to determine the impact of the pandemic on graft sources requested by transplant centers (TCs). The Kruskal-Wallis test was used to test the effect of the pandemic on the disease indication, volume of searches, and number of products not infused. Results: Although there was an initial decline in overall donor searches during the early phase of the pandemic, these numbers increased reaching pre-pandemic levels during the later phase. Urgent malignant diseases remained the most common indication for transplant in 2021. The pandemic necessitated cryopreservation of stem cell products due to transportation restrictions as well as clinical uncertainties in managing the virus. Cryopreserved grafts remained the most common requested grafts throughout the pandemic. In the later phase of the pandemic, the total numbers of requests for fresh grafts increased, mostly due to the increase in requests for fresh bone marrow (BM) grafts. As the pandemic continued, TCs became more accepting of cryopreservation, resulting in a reduction in the number of products not infused. Lastly, no short-term deleterious outcomes were noted among the patients who had stem cell products infused from a SARS-CoV-2-positive donor. Conclusion: Throughout the pandemic, the NMDP and TCs worked tirelessly to ensure that patients would receive lifesaving grafts when needed. The data reported here, although limited by small numbers, illustrate that transplantation from donors with COVID-19 is feasible and safe.
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COVID-19 , Transplante de Células-Tronco Hematopoéticas , Medula Óssea , Criopreservação/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Pandemias/prevenção & controle , SARS-CoV-2RESUMO
Many stem cell donor registries determine the cytomegalovirus (CMV) IgG serostatus at donor recruitment as it is an important marker for donor selection in the context of hematopoietic stem cell transplantation. To make sample collection less uncomfortable for the donor, we have developed a method that allows CMV status determination from buccal swab samples, thus avoiding blood drawing. However, the determination fails in some cases which leads to new donors being listed for donor search without CMV status, thus hindering donor searches. In this work, we evaluated the success rate of repeating CMV status analysis from a new swab. Our results show that about 90% of the samples could be successfully determined. Due to the great importance of the CMV status in donor search, we consider the retesting approach to be highly recommended for stem cell donor registries.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Doadores de Tecidos , Sistema de Registros , Anticorpos Antivirais , Imunoglobulina GRESUMO
Background: The frequency of ABO, Rh and Kell blood group antigens differs among populations of different ethnic ancestry. There are low-frequency antigens (<1%) and high-frequency antigens (>90%). A rare blood group is defined as the absence of a high-frequency antigen in the general population, as well as absence of multiple frequent antigens within a single or multiple blood group systems. Aim: To perform red blood cell typing and to calculate the antigen and phenotype frequencies, in order to identify rare blood group donors within the clinically most important ÐÐÐ, Rh and Kell systems. Material and Methods: ÐÐÐ, Rh (D, C, E, c, e) and Kell (K) antigen typing was performed using specific monoclonal sera and microplate technique, while Cellano (k) typing was performed with a monoclonal anti-k, antihuman globulin and column agglutination technique. Weak ABO subgroups were determined using the absorption elution method or molecular genotyping (PCR-SSP). Results: ABO antigen frequency is: A (40.89%), O (34.22%), B (16.97%), AB (7.92%) and weak ABO subgroups (0, 009 %). The established genotypes were AxO1 (0, 0026%) and AxB (0, 001%). Rh antigen frequency is: D (85.79%), C (71.7%), c (76.0%), E (26.0%) and е (97.95%). The most common Rh pheno-type is the DCcee (32.7%) while the rarest phenotype is the DCCEE phenotype (0. 003%). The prevalence of K and k antigen is 7.5% and 99.94%, respectively. The frequency of the rare phenotype K+k- is 0.06%. Conclusion: Large scale phenotyping of blood group antigens enables the identification of blood donors with rare blood groups for patients with rare phenotypes or with antibodies to high-frequency antigens and to frequent antigens within one or more blood group systems.
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Antígenos de Grupos Sanguíneos , Doadores de Sangue , Antígenos de Grupos Sanguíneos/genética , Humanos , Sistema do Grupo Sanguíneo de Kell/genética , Fenótipo , PrevalênciaRESUMO
Allogeneic stem cell transplantation (SCT) offers a potential cure for some hematological malignancies. For those patients without a family donor, unrelated donor (MUD) registries serve for identifying the best donor. In the present study, we aimed to give a cross-sectional report of our registry's activity and experience as the first established national MUD registry in the country. The study is retrospective and covers the period of 2016 to 2019. A total of 1855 donor searches were performed, and 642 were included in the study. All data were electronically obtained from the institutional database system. All SCTs were either 10/10 or 9/10 HLA matched and originated from an international registry. The most preferred stem cell source was peripheral blood (70.2%). A quarter of transplants were performed using bone marrow, and cord blood was used with a rate of 1.4%. The pandemic-related problems were similar for the other two national registries. During the pandemic, 71 of 432 patients who were searched for donors underwent stem cell transplant(SCT). The low number was related mostly with postponing of SCTs and/also difficulties in continuing of volunteering and in achievement of stem cells from international registry. During the Covid19 pandemic, the SCT activity of centers decreased according to the national, and international guidelines. The study revealed an organized, and multidirectional capacity of the registry and also the adaptation to unpredicted conditions such as pandemic. On the other hand, there is a need for more effective strategies for donor recruitment and retention programme.
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Medula Óssea , COVID-19 , COVID-19/epidemiologia , Estudos Transversais , Documentação , Docentes de Medicina , Humanos , Sistema de Registros , Estudos Retrospectivos , Doadores de Tecidos , TurquiaRESUMO
INTRODUCTION: The aim of this study was to investigate the allele and genotype frequencies of 8 human platelet antigen (HPA) systems among blood donors from the Blood Transfusion Institute of Serbia and to compare them with published studies. These data would be useful to establish the basis for a platelet apheresis donor registry. MATERIAL AND METHODS: Seventy-two unrelated male platelet apheresis/blood donors from Serbia were typed for 8 HPA systems (HPA-1 to HPA-6, HPA-9, and HPA-15) via the FluoGene method, based on polymerase chain reaction-sequence-specific amplification (PCR-SSP; PCR using sequence-specific primers) with fluorometric signal detection. Allele and genotype frequencies were estimated by direct counting and compared to the expected genotype frequencies according to the Hardy-Weinberg principle. The transfusion mismatch probability was calculated for every HPA specificity. RESULTS: The allele frequencies were: HPA-1a, 0.868; HPA-1b, 0.132; HPA-2a, 0.917; HPA-2b, 0.083; HPA-3a, 0.611; HPA-3b, 0.389; HPA-5a, 0.903; HPA-5b, 0.097; HPA-9a, 0.993; HPA-9b, 0.007; HPA-15a, 0.472; and HPA-15b, 0.528. For HPA-4 and HPA-6 only allele a was detected. DISCUSSION: The HPA allele frequencies of European populations showed no significant differences in comparison with our results. Statistically significant differences were revealed in comparison with some populations of non-European origin. In the tested donors no HPA-2 bb genotype was detected, but we found 1 donor with the rare HPA-9b allele. The biggest transfusion mismatch probability in the Serbian population is for systems HPA-15 (37.4%) and HPA-3 (36.2%), which means that more than a third of random transfusions could cause mismatch in these systems. This study was enabled by the introduction of molecular HPA typing, and it provides initial results of the HPA allele and genotype frequencies in the population of blood donors in Serbia. They will be used to provide a compatible blood supply on demand for treating patients with alloimmune thrombocytopenic disorders. The successful implementation of PCR-SSP with fluorometric signal detection could be further complemented in the future by the introduction of high-throughput methods, which will largely depend on the available financial resources.
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We estimated HLA haplotype frequencies based on individuals homozygous for 4, 5 or 6 loci. Validation of our approach using a sample of over 3.4 million German individuals was successful. Compared to an expectation-maximization algorithm, the errors were larger. However, our approach allows the unequivocal detection of rare haplotypes.
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Antígenos HLA , Alelos , Frequência do Gene , Antígenos HLA/genética , Haplótipos/genética , Humanos , Sistema de RegistrosRESUMO
In Italy, an HLA-matched unrelated donor is currently the primary donor when a HLA matched sibling is not found for allogeneic haematopoietic stem cell transplantation (HSCT). Better outcomes for transplantation require optimal matching between donor and recipient at least at the HLA-A, -B, -C, and -DRB1 loci; therefore, the availability of HLA-matched unrelated donors is important. The enormous HLA polymorphism has always necessitated registries with a large number of individuals in order to be able to provide well-matched donors to a substantial percentage of patients. In order to increase the efficiency of the Italian Bone Marrow Donor Registry (IBMDR) in providing Italian patients with a suitable donor, the probability of finding an HLA-A, -B, -C, and -DRB1 allele-matched (8/8) or a single mismatch unrelated donor (7/8) was estimated in this study according to IBMDR size. Using a biostatistical approach based on HLA haplotype frequencies of more than 100,000 Italian donors enrolled in the IBMDR and HLA-typed at high-resolution level, the probability of finding an 8/8 HLA-matched donor was 23.8%; 33.4%; and 41.4% in simulated registry sizes of 200,000; 500,000; and 1,000,000 donors; respectively. More than 2 million recruited donors are needed to increase the likelihood of identifying an HLA 8/8 matched donor for 50% of Italian patients. If one single mismatch at HLA I class loci was accepted, the probability of finding a 7/8 HLA-matched donor was 62.8%; 73.7%; and 80.3% in 200,000 donors; 500,000; and 1,000,000 donors; respectively. Using the regional haplotype frequencies of IBMDR donors, the probability of recruiting a donor with a new HLA phenotype, in the different Italian regions, was also calculated. Our findings are highly relevant in estimating the optimal size of the national registry, in planning a cost-effective strategy for donor recruitment in Italy, and determining the regional priority setting of recruitment activity in order to increase the phenotypic variability of IBMDR as well as its efficiency.
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Alelos , Genética Populacional , Antígenos HLA/genética , Haplótipos , Sistema de Registros , Doadores de Tecidos , Algoritmos , Frequência do Gene , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade/métodos , Humanos , Itália , Funções Verossimilhança , Modelos Teóricos , Probabilidade , Doadores não RelacionadosRESUMO
The only effective way to provide individuals with herd immunity against the novel coronavirus [SARS-CoV-2] is to administer an effective vaccine that will help check the current pandemic status. In India, the central drugs standard control organization (CDSCO) has granted the emergency-use authorization [EUA] to three vaccines namely, Covishield (live vaccine, Oxford AstraZeneca, United Kingdom being manufactured by the Serum Institute of India), Covaxin (inactivated vaccine, Bharat Biotech, India) and Sputnik V (live vaccine, Gamaleya, Russia). However, there is a rising need for the efficacy of the vaccines to be proven against the "SARS-CoV-2 viral variants." Also, human plasma is polyclonal in nature with an inherent propensity to identify multiple epitopes of either an antigen or pathogen. With this context in mind, the researchers hypothesize that using COVID-19 convalescent plasma [CCP] harvested from the locally recovered individuals [i.e. potential CCP donors] may be particularly beneficial in combating not only the founder SARS-CoV-2 virus but also the geographically determined SARS-CoV-2 variants among the regionally affected COVID-19 patients.
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Anticorpos Antivirais/uso terapêutico , COVID-19/terapia , Geografia Médica , Pandemias , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/virologia , Controle de Doenças Transmissíveis/métodos , Previsões , Humanos , Imunização Passiva , Índia/epidemiologia , Mutação , SARS-CoV-2/genética , Soroterapia para COVID-19RESUMO
The impact of the coronavirus disease 2019 (COVID-19) pandemic on hematopoietic cell transplant (HCT) donor registries and transplant center (TC) practices is underreported. This article reports on the National Marrow Donor Program (NMDP) Be The Match Registry and its coordinating the provision of unrelated donor (URD) products to domestic and international TCs during the initial 3 months of the COVID-19 pandemic (March through May 2020). Specifically, NMDP data are presented for disease indications for transplant, URD search volumes and availability, graft requests and processing, courier utilization and performance, and conversion rates from formal donor search and workup to graft collection and shipment. Data following the onset of COVID-19 are compared to the immediate 3 months prior to the COVID-19 pandemic (December 2019 through February 2020) and the same quarter 1 year prior to COVID-19 (March through May 2019). During the initial onset of COVID-19 and compared to 1 year prior, TCs requested and the NMDP performed less donor searches. More multiple URD and direct to workup requests were processed by the NMDP, which likely reflected reductions in donor availability. Yet TCs continued to perform allogeneic transplants for acute disease indications like acute leukemia and myelodysplasia, using more cryopreserved grafts than before COVID-19. In comparison to prepandemic patient cycle conversion rates and durations, the NMDP was able to convert patient cycles at nearly the same or higher rates and in similar or shorter periods of time. Last, despite significant challenges caused by the pandemic, including interruptions in domestic courier services and travel restrictions, graft products were delivered to and received by TCs in similar periods of time than before COVID-19. Taken together, these data show that NMDP service line operations continued to function effectively during the early phases of the COVID-19 pandemic, ensuring requests for and delivery of URD products to domestic and international allogeneic HCT recipients.
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COVID-19/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Pandemias , SARS-CoV-2 , Doadores não Relacionados/provisão & distribuição , Humanos , Sistema de Registros , Transplante HomólogoRESUMO
We developed a cost-efficient workflow for genotyping HLA-E by NGS and applied it for genotyping more than 2.5 million potential stem cell donors. The data obtained were used to determine HLA-E allele frequency distributions for 104 populations. Our results confirm the known dominance of the alleles E*01:01 and E*01:03, which have a combined frequency of more than 0.99 in 97 of the 104 populations. E*01:01 is more frequent in Africa and the western part of South America, E*01:03 in Southeast and East Asia. E*01:03 shows a pronounced regional substructure at the high-resolution level with E*01:03:01G being particularly common in a large connected region extending from Turkey to China, E*01:03:02G in Northwestern Europe and E*01:03:03 in Central and Eastern Europe as well as Central Asia. The presented results are relevant both as a basis for further population genetics studies and for optimizing stem cell donor searches.
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Alelos , Antígenos HLA/genética , Células-Tronco Hematopoéticas/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Teste de Histocompatibilidade , Doadores de Tecidos , Frequência do Gene , Humanos , Antígenos HLA-ERESUMO
We estimated HLA allele and haplotype frequencies of the Saudi Arabian population from a sample of 45,457 registered stem cell donors. The most frequent HLA alleles were A*02:01g (18.5%), C*06:02g (16.1%), B*51:01g (14.1%), DRB1*07:01g (16.2%), DQB1*02:01g (30.5%), and DPB1*04:01g (33.6%). The most frequent 5-locus haplotypes were A*02:05g~C*06:02g~B*50:01g~DRB1*07:01g~DQB1*02:01g (1.73%), A*02:01g~C*06:02g~B*50:01g~DRB1*07:01g~DQB1*02:01g (1.66%), and A*26:01g~C*07:02g~B*08:01g~DRB1*03:01g~DQB1*02:01g (1.38%). Furthermore, we used the calculated haplotype frequencies to estimate stem cell donor matching probabilities for Saudi Arabian donor and patient populations under various matching requirements. These results are relevant for strategic donor registry planning in the Kingdom of Saudi Arabia.
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Seleção do Doador/métodos , Antígenos HLA-D/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Antígenos de Histocompatibilidade Classe I/genética , Alelos , Árabes/genética , Conjuntos de Dados como Assunto , Frequência do Gene , Genética Populacional/estatística & dados numéricos , Antígenos HLA-D/imunologia , Haplótipos , Antígenos de Histocompatibilidade Classe I/imunologia , Teste de Histocompatibilidade , Humanos , Sistema de Registros/estatística & dados numéricos , Arábia Saudita , Doadores de TecidosRESUMO
The National Marrow Donor Program (NMDP) operates the Be The Match Registry to serve patients who require an allogeneic hematopoietic cell transplant (alloHCT). The factors that result in progression of an active donor search (ie, request for tissue typing or stem cell donation) to alloHCT are poorly understood. Some factors, such as differences in access by ethnic group, are known; however, deeper understanding of other patient and search factors is needed. Our study sought to identify the likelihood of patient progression from initiation of an active search for an unrelated adult donor/umbilical cord blood to transplant and to evaluate factors associated with proceeding to transplantation within 6 months. A retrospective cohort of US donor searches (ie, transplant center's first request of donor/cord blood unit testing; N = 8816) of the Be The Match Registry from January to December 2016 was analyzed. An adult unrelated donor search prognosis score, which categorizes the prognosis of the donor search as good, fair, or poor based on the patient HLA type and race/ethnic group, was included. At 6 months, 3744 (42%) patients had received a transplant. White patients were more likely to receive a transplant (n = 2590 of 5687, 45%) compared to black/African American patients (n = 187 of 700, 27%; P < .001). In multivariate analysis, the adult unrelated donor search prognosis score was associated with proceeding to adult donor or cord blood transplant within 6 months across all patient populations. A poor search prognosis score had an odds ratio (OR) of 0.32 (95% confidence interval [CI], 0.26 to 0.39, P < .001), 0.22 (95% CI, 0.09 to 0.54, P = .001), 0.39 (95% CI, 0.23 to 0.65, P < .001), and 0.26 (95% CI, 0.14 to 0.45, P < .001) for adults with malignant disease, adults with nonmalignant disease, children with malignant disease, and children with nonmalignant disease, respectively. This study identified important factors in the likelihood of a patient proceeding to HCT and suggests areas for future intervention to reduce the barriers to transplant.