Potential Hematopoietic Stem Cell Donors Research Articles

Long-term follow-up of cancer and catastrophic diseases in hematopoietic stem cell donors: a comprehensive matched cohort study.

Hematopoietic stem cell (HSC) transplantation, using either bone marrow (BM) or peripheral blood stem cells (PBSC), is a well-established therapy for various hematologic and non-hematologic diseases. However, the long-term health outcomes after HSC donation remain a major concern for several potential donors. Thus, we aimed to conduct a matched cohort study of 5003 unrelated donors (1099 BM and 3904 PBSC) and randomly selected 50,030 matched controls based on age, sex, and resident area from the donor registry between 1998 and 2018. The medical insurance claims of all the participants were retrieved from the Taiwan National Health and Welfare Data Science Center after de-identification. Our findings revealed no differences in the incidence of cancer, death, and catastrophic diseases between HSC donors and matched healthy participants during long-term follow-up. Kaplan-Meier curves depicting the cumulative incidence of cancer and overall mortality throughout the follow-up period also demonstrated similar outcomes between donors and non-donors. In conclusion, our results indicate that HSC donation, whether through BM or PBSC, is safe and not associated with an increased risk of cancer, death, or catastrophic diseases. These findings provide valuable information for counseling potential HSC donors and for long-term management of HSC donor health.

Recruiting refugees and migrants as potential hematopoietic stem cell donors to serve patients of comparable ethnicities with rare human leucocyte antigen patterns - The BluStar.NRW project in North Western Germany

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.

The novel HLA-A*74:46 allele detected in a potential hematopoietic stem cell donor.

One nucleotide substitution in codon 67 of HLA-A*74:41 results in the novel allele, HLA-A*74:46.

Characterization of the novel HLA-C*07:402:02 allele detected in a potential hematopoietic stem cell donor.

The novel HLA-C*07:402:02 allele was characterized using next-generation sequencing technology.

Recognition of the novel HLA-A*24:602 allele detected in a potential hematopoietic stem cell donor.

The novel HLA-A*24:602 allele differs by one nucleotide change from HLA-A*24:02:01:01.

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 &gt; 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 &gt; 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.

Nomenclature for factors of the HLA system, update January, February, and March 2023.

Nomenclature for factors of the HLA system, update January, February, and March 2023.

Characterization of the novel HLA-B*27:05:57 allele detected in a potential hematopoietic stem cell donor.

The novel HLA-B*27:05:57 allele differs by two nucleotide changes from HLA-B*27:05:02:01.

Characterization of the novel HLA-A*03:444 detected in a potential hematopoietic stem cell donor.

The novel HLA-A*03:444 allele was characterized using next generation sequencing technology.

Identification of the novel HLA-C*12:349 allele in a potential hematopoietic stem cell donor.

The novel HLA-C*12:349 allele was characterized using next generation sequencing technology.

Генетическое разнообразие потенциальных доноров гемопоэтических стволовых клеток российского и белорусского регистров

Трансплантация гемопоэтических стволовых клеток крови широко используется для лечения онкогематологическихзаболеваний и некоторых состояний, связанных с дефицитом кроветворения и иммуногенеза. Эффективный донорский поиск является одной из важнейших составляющих успеха трансплантации. Совпадение пар «донор – реципиент» по 10/10 HLA-аллелям (гены HLA-A, -B, -C, -DRB1 и -DQB1) – «золотой стандарт» успешного поиска совместимого донора для проведения аллогенной неродственной трансплантации стволовых клеток. Регистры играют ключевую роль в организации взаимодействия между врачами трансплантационного центра и специалистами, контактирующими с донором. Международное сотрудничество регистров доноров костного мозга способствует повышению эффективности поиска доноров для пациентов, нуждающихся в проведении аллогенной трансплантации гемопоэтических стволовых клеток. В статье представлены результаты сравнительного анализа иммуногенетических характеристик потенциальных доноров гемопоэтических стволовых клеток крови и костного мозга регистра ФГБУ РосНИИГТ ФМБА России и регистра Республики Беларусь. Показаны общие закономерности и характерные особенности профиля групп HLA-аллелей и HLA-гаплотипов в сравниваемых регистрах. Hematopoietic blood stem cell transplantation is widely used for the treatment of hematological malignancies and some conditions associated with deficiency of hematopoiesis and immunogenesis. An effective donor search is one of the essential components of the success of transplantation. Matching donor-recipient pairs by 10/10 HLA alleles (HLA-A, -B, -C, -DRB1 and -DQB1 genes) is the gold standard for successful search for a compatible donor for allogeneic unrelated stem cell transplantation. The registries play a key role in organizing the interaction between the doctors of the transplant center and the specialists in contact with the donor. International cooperation of bone marrow donor registries contributes to improving the efficiency of donor search for patients requiring allogeneic hematopoietic stem cell transplantation. The article presents the results of a comparative analysis of the immunogenetic characteristics of potential hematopoietic stem cell donors in the Register of the FSBI RosNIIHT FMBA of Russia and the Register of the Republic of Belarus, demonstrates the general patterns and features of the profile of HLA-alleles groups and HLA-haplotypes in the compared registers.

The novel HLA-A*03 allele, HLA-A*03:440, identified in a potential hematopoietic stem cell donor.

The novel HLA-A*03:440 allele was characterized using next generation sequencing technology.

Worries and Psychological Well-Being in Potential Hematopoietic Stem Cell Donors Before Donation—A Swedish National Study

The physical risks involved in donating hematopoietic stem cells have been thoroughly studied, but little is known about the psychological risks potential donors might face before donation. The aim of this study was to describe potential the pre-donation worries and psychological well-being of hematopoietic stem cell donors and investigate possible associations between donor characteristics and psychological well-being. In a cross-sectional, national cohort study, we describe pre-donation worries and psychological well-being and investigate possible associations between donor characteristics and psychological well-being. A questionnaire was sent to prospective adult hematopoietic stem cells donors. The study included 210 participants, 47% of whom were related and 53% unrelated to the recipient. Of the participants, 39% reported great worry about the recipient and 12% great worry about themselves as potential donors. Symptoms of anxiety were expressed by 21%, whereas symptoms of depression were uncommon and perceived general mental health was slightly lower than in the Swedish population. Great worry about oneself, lower age, and female sex were related to increased anxiety and lower mental health. This study highlighted that some potential donors report high levels of pre-donation worry and that greater worry about oneself, lower age, and female sex are associated with lower psychological well-being. Although further studies are needed to investigate this psychological risk over time, it is clear that some potential donors are particularly vulnerable.

Recognition of the novel HLA-C*07:1002 allele identified in a potential hematopoietic stem cell donor.

The novel HLA-C*07:1002 allele was characterized using next-generation sequencing technology.

Identification of the novel HLA-C*02:212 allele detected in a potential hematopoietic stem cell donor.

The novel HLA-C*02:212 allele was characterized using next generation sequencing technology.

Post-Transplant Cyclophosphamide, Abatacept and Short Course of Tacrolimus (CAST) for Graft-Versus-Host Disease Prevention Following Haploidentical Peripheral Blood Stem Cell Transplantation

Background: Haploidentical blood and marrow transplantation (BMT) substantially expands the pool of potential hematopoietic stem cell donors, including for minority groups. However, the outcomes of haploidentical transplantation remain inferior to matched unrelated donor (MUD) transplants when a standard post-transplant cyclophosphamide (PTCy)-based graft versus host disease (GvHD) prophylaxis regimen is employed in both settings. To address this issue, we sought to develop a more effective GvHD prevention regimen in haploidentical transplantation. While abatacept (Aba) seems to decrease the incidence of acute GvHD, PTCy is particularly effective in the prevention of chronic GvHD. Therefore, we designed a regimen that combines the merits of both agents and examined whether such approach can allow early withdrawal of tacrolimus (Tac). Methods: We enrolled 46 adult patients with hematological malignancies receiving haploidentical transplantation from a relative in a prospective single center pilot phase Ib-II clinical trial. Patients received non-myeloablative, reduced-intensity or myeloablative preparative regimens followed by G-CSF mobilized peripheral blood transplants and a combination of PTCy (50mg/kg on days +3 and +4), Aba (10mg/kg on days +5, +14 and +28) and Tac at a dose adjusted based on blood level. Tac taper was initiated on day +60 and completed by day +90. After treating 30 patients, the study was amended to administer an additional dose of Aba on day +56 based on the noted timing of acute GvHD development and Aba terminal ½ life. Patients received standard supportive care by institutional practice including G-CSF and anti-microbial prophylaxis. Serologically CMV positive patients also received letermovir prophylaxis. Results: Patient characteristics are summarized in table 1. Importantly, 19 out of 46 (41.3%) patients were from racial or ethnic minorities. The data cutoff date was July 29th, 2022. Three patients were excluded from this analysis due to short follow-up. For the remaining patients, median follow-up was 8.9 months. Median time to neutrophil engraftment was 18 days (13-30). One patient died before achieving platelet (plt) engraftment and 2 patients have not yet achieved plt engraftment. For the remaining 40 patients, median time to plt engraftment was 29 days (16-52). All patients achieved full donor chimerism at the time of count recovery. Tac was successfully tapered off as planned in all but 5 patients. Cumulative incidence of acute GvHD grades II-IV, III-IV and IV with death as competing event was 12.8%, 5.1% and 0%, respectively. One-year (y) cumulative incidence of moderate to severe chronic GvHD was 17.1%. All cases of acute GvHD except 1 grade II acute GvHD were observed in the first 30 patients. Cases of chronic GvHD included 2 cases of overlap syndrome. There was no case of steroid-refractory acute GvHD or GvHD-related death. One-y cumulative incidence of relapse (non-relapse mortality as competing event) was 8.3% (95% CI 0%-17.1%). KM estimates of 1-year relapse-free survival (RFS), overall survival (OS) and GRFS (composite end point of grade III-IV acute GvHD-, chronic GvHD requiring systemic therapy- and relapse-free survival) were 91.7% (95% CI 83%-100%), 90.6% (95% CI 80.9%-100%) and 71.8% (95% CI 57.2%-90%), respectively. None of the safety stopping rules was triggered. There was 1 case of thrombotic microangiopathy due to Tac and 2 cases of sinusoidal occlusive disease, 1 requiring treatment with defibrotide; all 3 patients recovered. There were 2 cases of respiratory failure of undetermined etiology. One-y cumulative incidence of non-relapse mortality (relapse as competing event) was 2.6% (95% CI 0%-7.8%). The incidence of CMV and EBV reactivation was 39.5% and 2.3%, respectively. There was no case of adenovirus or HHV-6 virus reactivation. BK viruria occurred in 27.9% of patients with limited symptomatology (1 patient required treatment with cidofovir). Immune reconstitution results are summarized in figure 1. Conclusion: CAST is a new GvHD prevention regimen that seems safe and effective, yielding excellent outcomes. CAST also allows early discontinuation of Tac. Outcomes with longer follow-up will be presented at the meeting. If the results are confirmed, CAST might be a step forward toward closing an important health disparity gap in BMT, equalizing the outcomes of haploidentical transplantation and MUD transplants. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparative analysis of immunogenetic characteristics of potential hematopoietic stem cell donors from the registries of two Russian megapolises

Efficacy of search for the unrelated compatible transplant donors depends on a number of factors. Of most importance are the standards of primary HLA typing, and the immunogenetic diversity of the donor pool. Timely donor selection guarantees the optimal timing for stem cell transplantation. This factor exerts positive influence upon the transplantation outcomes. In 2019, The Bone Marrow Donors Registry at the Russian Research Institute of Haematology and Transfusiology has implemented HLA-typing for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 genes as a standard for primary immunogenetic examination, in order to reduce the donor search period. The aim of our study was to evaluate the HLA typing results for potential stem cell donors at our Registry as compared with immunogenetic profile of donors at the Registries arranged in two Russian megapolises. All currently known groups of HLA-C, HLA-DRB1, HLA-DQB1 gene alleles, 19 of 21 open groups of HLA-A gene alleles, 34 of 36 known groups of HLA-B gene alleles were screened in the donors from our Registry. The most common HLA alleles groups were as follows: A*02 (0.2957), A*03 (0.1432), A*01 (0.1155), A*24 (0.1128); B*07 (0.1282), B*35 (0.1084), B*44 (0.0921), B*18 (0.0745); C*07 (0.2738), C*04 (0.1361), C*12 (0.1202), C*03 (0.1134), C*06 (0.1127); DRB1*15 (0.1445), DRB1*07 (0.1420), DRB1*13 (0.1271), DRB1*01 (0.1269), DRB1*11 (0.1216); DQB1*03 (0.3517), DQB1*06 (0.2269). A total of 1702 HLA-A*-B*-C*-DRB1*-DQB1*-haplotypes were revealed in our donor pool. The frequency of nine HLA-haplotypes exceeded 0.01: A*01-B*08-C*07-DRB1*03-DQB1*02 (0.0366), A*03-B*07-C*07-DRB1*15-DQB1*06 (0.0269), A*03-B*35-C*04-DRB1*01-DQB1*05 (0.0238), A*02-B*13-C*06-DRB1*07-DQB1*02 (0.0204), A*02-B*07-C*07-DRB1*15-DQB1*06 (0.0184), A*25-B*18-C*12-DRB1*15-DQB1*06 (0.0127), A*02-B*18-C*07-DRB1*11-DQB1*03 (0.0126), A*02-B*15-C*03-DRB1*04-DQB1*03 (0.0123), A*02-B*41-C*17-DRB1*13-DQB1*03 (0.0109). We carried out a comparative analysis of the HLA-haplotypes distribution for the donors of three Russian registers: Russian Research Institute of Haematology and Transfusiology (St. Petersburg); First St. Petersburg State I. Pavlov Medical University (St. Petersburg); National Medical Research Center for Hematology (Moscow). The six most common HLA-haplotypes among the donors from three Russian registers had the same rank positions and frequencies. The differences of some less common HLA-haplotypes distribution were determined. The results of our study indicate the immunogenetic diversity of the donor pool the Registry of Russian Research Institute of Haematology and Transfusiology. This fact, along with usage of international standards for primary immunogenetic examination is a prerequisite for effective donor search for the patients requiring stem cell transplantation.

The detection of the novel HLA-C*04:469 allele identified in a potential hematopoietic stem cell donor.

The novel HLA-C*04:469 allele was characterized using next generation sequencing technology.

Two novel HLA-A alleles detected in a potential hematopoietic stem cell donors: HLA-A*03:418 and -A*26:220.

HLA-A*03:418 and -A*26:220, two novel alleles detected by next generation sequencing.

Characterization of the novel HLA-B*35:547 allele detected in a potential hematopoietic stem cell donor.

The novel HLA-B*35:547 allele was characterized using next generation sequencing technology.