Hematopoietic Stem Cell Donor Registries Research Articles

Глобальные и национальные регистры доноров костного мозга: опыт использования, основные трудности и перспективы

The paper provides the summary of foreign literature data on the organizational and methodological aspects of functioning of the bone marrow and hematopoietic stem cell donor registries, the issues of HLA typing, the technical algorithms for compatibility degree ranking. The changes in the citizens’ motivations in response to the bone marrow donating program popularization are described, along with the features of arranging recruitment, approaches to determining the requirements for the registry population considering the multinationality and heterogeneity of ethnic composition, and the statistical approximation algorithms. Furthermore, attention is paid to the so-called specific aspects of the functioning of bone marrow and hematopoietic stem cell registries and biobanks. The latter is important in terms of ensuring national security, adaptation of the population to the effects of the disasters, emergencies, and terrorist attacks associated with the development of bone marrow syndrome in a large number of victims.

Factors Associated with Opting Out of an Unrelated Hematopoietic Stem Cell Donor Registry: Differences and Similarities across Five Key Groups of Young Race/Ethnically Diverse Potential Donors in the United States

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.

Immunogenetic characteristics of hematopoietic stem cell donors representing the most numerous ethnic groups in Russia

Development of criteria for the optimal donor selection based on the analysis of the allo-HSCT results, high-resolution HLA typing for the donor and recipient resulted in decreased incidence of immunological complications, primarily an acute «graft-versus-host reaction». However, due to the pronounced allelic polymorphism of the main histocompatibility complex (MHC) genes, the search for an optimal donor is ineffective in a number of patients. To increase the chances of selecting a donor for patients with rare HLA genotypes, the hematopoietic stem cell donor registries recruit the persons of various nationalities. An increased number of donors from different ethnic groups provide a broader immunogenetic diversity of the donor cohort. Currently, the registry of hematopoietic stem cell donors at the Russian Research Institute of Hematology and Transfusiology includes representatives of 49 nationalities, most of which, are considered themselves Russians. The third largest ethnic group in the registry comprises Tatars. The purpose of this study is a comparative analysis of immunogenetic characteristics of potential hematopoietic stem cells donors in the registry, who have self-identified as Russians and Tatars. As a result of the study, we have not found significant differences in frequencies of HLA allelic groups in the compared cohorts, a trend for higher frequency of the HLA-B*27 group was noted in Tatars. However, significant differences have been revealed for the distribution of HLA haplotypes in Russians and Tatars. The most common HLA haplotype among Tatars was A*02-B*44-DRB1*07, being much less common in Russians (4.61% vs 0.55%, p = 0.002). HLA haplotype A*03-B*13-DRB1*07, belonging to the ten most common among Tatars, was significantly less frequently detected in Russians (1.62% vs 0.08%, p = 0.026). HLA haplotype A*03-B*08-DRB1*03 was also significantly more common in Tatars compared to Russians (1.42% vs 0.06%, p = 0.026). HLA haplotypes A*02-B*18-DRB1*11, A*02-B*15-DRB1*04, A*02-B*15-DRB1*13, presented in Russians at a frequency of > 1%, were not determined among the tested Tatars. HLA haplotypes A*31-B*58-DRB1*04, A*24-B*44-DRB1*01, presented in Tatars at a frequency of > 1%, were not detectable in Russians. The results of our study indicate a need for recruiting more representatives of the Tatar ethnicity to the registry, thus increasing immunogenetic diversity of the donor pool and resulting into increased chances of compatible unrelated donor selection for the patients with HLA haplotypes, which are now underrepresented in our registry.

New global reporting system for serious (product) events and adverse reactions in hematopoietic stem cell donation and transplantation.

Annually more than 21,000 volunteer unrelated hematopoietic stem cell donations are performed worldwide for patients with life-threatening diseases such as acute leukaemia. Donor safety issues and donor protection is one of the top priorities for the international cooperation of unrelated hematopoietic stem cell donor registries represented by the World Marrow Donor Association (WMDA). With this new global reporting system for serious events and adverse reactions (S(P)EARs), the WMDA aims to become the global leading online platform for hematopoietic stem cell donor organisations to report their S(P)EARs from both unrelated and family donors. Software developer Cogapp developed the platform using a Knack environment based on requirements of experienced reporters and reviewers. On July 1st WMDA launched a robust online reporting system for S(P)EARs in order to provide accurate information about potential risks to donors. The collected data about S(P)EARs occurring in donors will be analysed and used to provide statistics on the type of reports being submitted and to put in place best practices to mitigate such effects and occurrences. Via the annual S(P)EAR reports the results will be disseminated worldwide.

An assessment of the effectiveness of the search for unrelated hematopoietic stem cell donors for russian patients in the registry of Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical and Biological Agency of Russia

We assessed the effectiveness of the registry of Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical and Biological Agency of Russia, with a total of 35,117 hematopoietic stem cell donors recruited in 22 regions of the Russian Federation (as of 01 January 2019). It was established that a relatively small registry would be sufficient to find at least one fully matched donor for 43% of Russian patients. The sufficient representativeness of this hematopoietic stem cell donor registry is confirmed by the high concordance of established HLA haplotype profiles between the population of donors and the cohort of patients for whom a search of a matching donor was performed. This study was approved by the Independent Ethics Committee and Scientific Council of Kirov Research Institute of Hematology and Blood Transfusion, FMBA of Russia.

Central Unrelated Potential Bone Marrow and Cord Blood Registry in Poland: Structure and Numbers

Poland’s Central Unrelated Potential Bone Marrow Donor and Cord Blood Registry (CBMDR Poltransplant) was established in 2011. Affiliated with the World Marrow Donor Association (WMDA) as PL5, the CBMDR is an internationally recognized hematopoietic stem cell donor registry with a large, high-quality donor database. Overall, Polish resources in this domain are the second largest in Europe and the fourth largest in the world, accounting for 4.8% of the WMDA Register of over 33.5 million records. In the last 10 years, the number of potential hematopoietic stem cell donors registered in Poland has increased more than 10-fold, from about 146,000 to 1,579,809 at the end of 2018. Such a growing number of donors in the CBMDR is contributing to an increase in overall numbers of donor searches in Polish databases, as well as in donations from Polish donors.

Urgent need for a South Asian hematopoietic stem cell donor registry

For over four decades, Haematopoietic Stem Cell Transplantation remains the only form of curative treatment of patients with blood cancers, Thalassemia and certain congenital immune deficiencies. Poor representation of Asian population in the global donor database and absence of a regional registry for South Asian population is responsible for loss of lives. Hence there is an urgent need for member countries in the SAARC region to work together to enable quick and affordable access to matching stem cells for patients in this region.

HLA Haplotype Frequency Estimation from Real-Life Data with theHapl-o-Mat Software.

HLA haplotype frequencies are of use in a variety of settings. Such data is typically derived either from family pedigree data by targeted typing or statistical analysis of large population-specific genotype samples. As established tools for the latter approach lacked ability to treat the amount, ambiguity, and inhomogeneity found in genotype data in hematopoietic stem cell donor registries, we developed Hapl-o-Mat to alleviate these specific shortcomings.

P223 Adding class II to a one step Sanger sequencing with phasing probe hybridization workflow_a rapid and complete HLA typing at G-group resolution

Aim In order to reduce the time and effort required to produce a single high resolution HLA class I genotype, a workflow combining one-step Sanger sequencing with probe hybridization has been successfully used in HLA-A, -B, -C typing for a hematopoietic stem cell donor registry (Tu et al. HLA 89:90, 2017). This workflow has now been applied to type HLA-DRB1, -DQB1 and -DPB1. Methods DNA was prepared from buccal swabs from 184 registry donors. Sanger sequencing used Thermo Fisher Scientific SeCore® HLA-DRB1, -DQB1, and -DPB1 kits. Simultaneous hybridization used One Lambda LABType® probes. Assignments were merged with in-house software. Interpretation used IPD-IMGT/HLA database 3.19. Results Use of both DNA sequencing and SSO (without additional phasing probes) hybridization resulted in assignment of a single G-level genotype for the majority of samples compared to sequencing alone (Table). Ambiguous genotypes observed for DRB1 and DQB1 will be addressed by additional phasing probes to raise the frequency of single genotype resolution for these loci closer to 100%. Conclusions This workflow complements that described by us for HLA class I alleles and provides a comprehensive strategy for complete HLA typing. The SBT+SSO combination workflow with genotype assignments at the level of the antigen recognition domain is a powerful typing strategy, merging strengths of both methods and improving accuracy and reducing turnaround time and typing cost. While applied to registry typing, this workflow also can be applied to a small number of samples. Download : Download high-res image (155KB) Download : Download full-size image

No gender differences in the frequencies of HLA-DRB3/B4/B5 heterozygotes in newborns and adults in Koreans

HLA class II haplotypes often contain a second expressed HLA-DRB locus tightly linked to the classical HLA-DRB1 locus on the haplotype, which can be either HLA-DRB3, -DRB4 or -DRB5. These encode the HLA-DR51, -DR52 or -DR53 supertypic specificities and mark the ancestral lineages. HLA-DRB3/B4/B5 heterozygote excess in Welsh male newborns has been reported, suggesting a possibility of male-specific major histocompatibility complex (MHC)-mediated prenatal selection. However, it has not been confirmed in newborns of other ethnic groups or in adult populations. We analyzed the HLA-DRB1 and HLA-DRB3/B4/B5 genes in Korean newborns and healthy adults to examine whether MHC-mediated prenatal or postnatal selection exists. A total of 1,038 newborns (cord blood registry, 516 males and 522 females) and 2,082 healthy adults (hematopoietic stem cell donor registry, 1,111 males and 971 females) were HLA typed. HLA-DRB1/B3/B4/B5 DNA typing was performed using Dynal RELI HLA-DRB SSO Kit (Dyanl Biotech, Wirral, U.K.). Genotype frequencies and homozygosity and heterozygosity rates for DRB3/B4/B5 supertypic loci were compared between males and females in newborns and adults. There were no significant differences in the HLA-DRB3/B4/B5 homozygosity and heterozygosity rates between males and females in both newborns and adults. In the comparison between newborns and adults, homozygosity rate was significantly higher in newborn females than in adult females (31.0% vs 25.0%, p=0.01). Whether there is an age-related change from newborns toward adults has not been well studied in other populations, and further studies are warranted. In conclusion, male-specific heterozygosity excess reported in Welsh newborns has not been observed in Korean population, and there might be some ethnic differences in the gender-specific prenatal selection events.

European Marrow Donor Information System: Concept and Praxis

Hematopoietic stem cell transplantation is an increasingly used treatment option for patients with severe disorders of hematopoiesis. In roughly two thirds of the cases, an unrelated donor must be sought in international databases. These searches would nowadays be unimaginable without the support of information technologies. Reliable communication and data transfer of donor and patient records between all partners in this huge network is one of the most important success factors in stem cell transplantation. The European Marrow Donor Information System (EMDIS) is an open computer network for data exchange among different unrelated hematopoietic stem cell donor registries that covers 85% of all potential unrelated stem cell donors and cord blood units worldwide. The network has spread also to North America, Australia, Asia, and Africa. The Czech Stem Cell Registry in Prague became a member of the EMDIS community at the end of 2003, when it manually processed about 300 preliminary search requests per year and exported 32 stem cell products to other countries. In 2008, it has automatically processed >14,000 preliminary requests with a doubled 63 number of exported stem cell products.

Collaboration Between Hematopoietic Stem Cell Donor Registry and Cord Blood Banks

Despite the huge number of volunteer donors registered worldwide, only a mean of 50% of patients not having a family donor are transplanted with an unrelated donor. Since 1990, a network has been implemented among some European registries. With the help of the European Community, a more sophisticated network has been developed, the European Marrow Donor Information System (EMDIS). 10 A new project underwent development by registries and the Bone Marrow Donor Worldwide: the EMDIS Cord Blood Registry. It will in the future permit to obtain after a search request, one report containing all of the best donors worldwide and best umbilic cord blood for each patient, taking into account possible double cord blood transplantations and other factors, such as number of nucleated cells, number of CD34+ cells, and methods of reduction. Only a strong collaboration between all hematopoietic stem cell registries and cord blood banks would allow a Registry to propose the best donor/cord blood unit for each patient in each country. Progress in the field of hematopoietic stem cell transplantation may be obtained by the parallel development of cord blood banks worldwide and bone marrow donor registries among countries that include minorities.

World Marrow Donor Association framework for the implementation of HLA matching programs in hematopoietic stem cell donor registries and cord blood banks

A major goal of the World Marrow Donor Association (WMDA) is to foster international transplants of hematopoietic stem cells through the establishment of guidelines and recommendations in this field. In this tradition, this study defines a comprehensive framework for HLA matching programs, which use intricate algorithms to rapidly select potential donors for a patient from a database and to present these donors in a prioritized list. Starting with the comparison of single HLA markers of the donor and the patient possibly obtained using different testing methodologies at different resolutions, the more complex matching of loci and phenotypes is inductively built up. The consensus of this international collaborative group describes the state of the art in the field and points out many important design options compatible with the best practice. This should help existing registries to review and validate the most critical part of their IT systems and newly created donor registries around the world to tackle one of their real challenges.

Standards, regulations and accreditation for registries involved in the worldwide exchange of hematopoietic stem cell donors and products

The World Marrow Donor Association (WMDA) is working closely with other international organizations working in cellular therapy such as the Worldwide Network for Blood and Marrow Transplantation (WBMT) to develop and maintain global recommendations and requirements for a standardized practice. WMDA launched its registry accreditation program in September 2003. Since then, 17 of the 71 hematopoietic stem cell donor registries worldwide have been accredited. These accredited registries list over 80% of the hematopoietic stem cell donors and umbilical cord blood units listed in the database of BM Donors Worldwide. The goal of the WMDA Standards and Accreditation process is to protect donors while serving the needs of patients who are urgently seeking histocompatible donors in worldwide searches. These activities address the increasing governmental regulations regarding the quality and safety of stem cells collected internationally for national patients.

World Marrow Donor Association guidelines for use of HLA nomenclature and its validation in the data exchange among hematopoietic stem cell donor registries and cord blood banks

Since the advent of the European Marrow Donor Information System in the first half of the last decade, fully automated data exchange between registry computer systems has been playing an ever-increasing role in the international search for unrelated donors of blood progenitor cells. This exchange, however, was hampered by different local conventions used to present HLA data and complicated by the need to extend the official WHO nomenclature to accommodate the registries' information systems and to cross-validate HLA data obtained with different methods and/or at different loci. The guidelines presented here have been developed by the World Marrow Donor Association to standardize the nomenclature to be used and the validation checks to be applied in the international electronic exchange of HLA-typing data among unrelated volunteer hematopoietic stem cell donor registries and umbilical cord blood banks. Two reference web sites have been designated to maintain and update the approved HLA nomenclature and all the ancillary information needed by the conventions described here.

Advances in HLA: Practical Implications for Selecting Adult Donors and Cord Blood Units

HLA plays a critical role in hematopoietic cell ransplantation, but a full understanding of this role is onstantly in flux because of changing technologies nd burgeoning amounts of clinical transplantation esults. Today the clinician considering unrelated donor ransplantation must also consider stem cell source: an dult donor or an umbilical cord blood unit (CBU). In he context of cord blood, the task is further compliated by the strong interaction of cell dose. Each individual carries from 10 to 12 genes that ncode the HLA-A, HLA-B, HLA-C, HLA-DR, HLAQ, and HLA-DP molecules. Most of these genes are ighly polymorphic, ranging from 13 (HLA-DRB4) to 99 (HLA-B) alleles at a locus [1]. Most of the allelic ifferences result in changes in the HLA protein seuences, thus producing potential targets for allorecogition [2]. The frequency of alleles differs in different opulations: some are common in most populations, nd others are found predominantly in only 1 or a few opulations. The same is true for HLA haplotypes—the ollection of multiple HLA alleles within a short reion of chromosome 6—which are typically inherited s a single block of genetic information. Table 1 proides examples. DNA-based testing methods provide an accurate nd powerful approach to identify HLA diversity, and hese are replacing serologic testing [3,4]. DNA testng detects specific nucleotide differences that distinuish alleles or sets of alleles. The ability to distinuish among particular alleles at a locus (ie, the esolution) depends on the methodology, the set of ligonucleotide reagents used in the assay, or both. he choice of assay depends on the purpose of the yping, eg, initial testing of newly recruited volunteers r CBUs for a registry (low to intermediate resoluion) compared with testing of transplantation candiates and a few selected potential donors or CBUs high or allele-level resolution). C

Donor and liability insurance of donor registries, donor centers, and collection centers – recommendations

The article presents views and recommendations of the World Marrow Donor Association regarding the need for donor and liability insurance for hematopoietic stem cell donor registries, and donor and collection centers.