Bone marrow donor-related variables associated with harvest outcome in HLA-haploidentical transplantation with postinfusion cyclophosphamide.

BACKGROUND AND OBJECTIVES: Several transplantation outcomes have been shown to be associated with the infused bone marrow cell dose/kg of the recipient's body weight. The donor bone marrow density is directly related to the infused cell dose. The aim of the present study was to identify donor-related variables that are associated with high donor bone marrow density. MATERIALS AND METHODS: We retrospectively analysed the predictive factors of high marrow density in 65 consecutive HLA-haploidentical bone marrow donors harvested at our centre between 2009 and 2013. RESULTS: Body mass index (BMI) and peripheral white blood cell (WBC) count were directly associated with bone marrow density (regression coefficient ß = 5·33 and ß = 2·93, respectively; P < 0·01). The likelihood of obtaining a collection with a high density was first predicted using BMI (BMI ≥30, mean density = 25·8 TNC/ml × 10(6) ). Second, donors with a BMI <30 were split into two groups according to peripheral WBC count (WBC <8 × 10(3) /mm(3) : mean density = 18·4 TNC/ml × 10(6) ; WBC ≥8 × 10(3) /mm(3) : mean density = 23·1 TNC/ml × 10(6) ). We also observed that the density of the first collected bag directly correlated with the overall density (R(2) = 0·69, P < 0·01). CONCLUSION: The donor-related features BMI and WBC count affect the cell quantity obtainable with the harvest and should be taken into account when choosing the donor.

Self-assessment of color categories and its relationship with HLA profiling in Brazilian bone marrow donors.

The Brazil Ministry of Health maintains a Registry of Bone Marrow Donors that corresponds to approximately 12% of the Bone Marrow Donors Worldwide registry. This registry contains information on ethnicity (by self-assessment of color) and HLA-A, -B, and -DRB1 type. The self-assessment of color tool has been extensively used for admixed population characterization. In this context, Brazil represents a highly admixed population, resulting from 5 centuries of colonization and interbreeding, mainly, but not exclusively, among Native Americans, Europeans, and Africans. Here we evaluated self-assessed skin color and HLA genetic information from 71,291 bone marrow donors of southern Brazil to verify how likely is the HLA profiling correspondence within and between self-assessed color groups. We found that HLA itself was a better ancestry indicator than was self-assessed color. Therefore, self-assessment of color in highly admixed populations, such as that of Brazil, is not indicative of higher correspondence in the HLA profiles within skin color groups.

HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central Europe.

Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA-A, -B, and -DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central-European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA-A accurately depicts the effects of genetic drift, HLA-B, and -DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection.

Knowledge and attitude of Lublin universities students' toward the opportunity of becoming unrelated bone marrow donor.

Hematopoietic Stem Cell Transplantation (HSCT) is a very important life-saving procedure to treat many disorders. In August 2014, there were more than 24.5 million donor registered in the Worldwide Bone Marrow Donor Register. In the Polish Register of Unrelated Bone Marrow and Umbilical Cord Blood Donors at the end of 2013 there were almost 540 thousand registered bone marrow donors. Despite increasing numbers of registered donors, the amount of requests also increased. It shows that the number of donors is still insufficient. The analysis of knowledge and attitude of Lublin universities students' toward the opportunity to become an unrelated bone marrow donor was the aim of our study. 1609 Lublin students from non-medical universities from different years and specializations of study, of both sexes, aged 19-35 took part in the survey. It consisted of 16 questions. There were knowledge-testing questions, and also personal ones. Among interviewees, 16% were registered as potential bone marrow donors. The reason for not being registered registration chosen most often was that the surveyed did not take this into consideration. Correct answers to all of the questions were given by 21% of students. The biggest number of incorrect answers was given to the question about a place from bone marrow is harvested - nearly 49%. Registered students showed a better level of knowledge than the unregistered. We noted a low level of knowledge about bone marrow donation and possibility of becoming potential bone marrow donor among Lublin universities students.

HLA-B27 positivity in a large miscegenated population of 5,389,143 healthy blood marrow donors in Brazil.

BACKGROUND: The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil. AIM: To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database. METHODS: This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence. RESULTS: From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population. CONCLUSIONS: Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.

HLA-B27 positivity in a large miscegenated population of 5,389,143 healthy blood marrow donors in Brazil

Abstract Background The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil. Aim To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database. Methods This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence. Results From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population. Conclusions Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.

The HLA-A, -B and -DRB1 polymorphism in a large dataset of South Brazil bone marrow donors from Rio Grande do Sul.

Human leukocyte antigen (HLA) genes are very informative in population genetics studies and their variability has been widely used to reconstruct the history of geographic and/or demographic expansions of human populations. The characterization of HLA diversity at the population level is also fundamental in clinical studies, particularly for bone marrow transplantation programs. In this study, we investigated the HLA molecular variation in Rio Grande do Sul, South Brazil, in order to identify possible regional differences across this state. More than 97,000 bone marrow donors were typed at the HLA- A, -B and -DRB1 loci and analyzed by considering two kinds of subdivisions based on both self-identified ethnicity and place of residence: (a) the official geographic subdivision defined by the Brazilian Institute of Geography and Statistics and (b) known information about the colonization history of the state. HLA allele and haplotype frequencies were estimated and compared among the defined subgroups. The results indicate a lack of correlation between genetic variation and geography and thus no clear HLA genetic structure based on geographic criteria. On the other hand, major differences were observed regarding ethnicity. In addition, local populations from Rio Grande do Sul were found to be genetically similar to their corresponding parental European populations from Germany, Italy and Portugal, as documented by historical data. Overall, this study provides a thorough characterization of the HLA genetic variation in Rio Grande do Sul and a better understanding of its demographic history, being most useful for the development of more efficient strategies in bone marrow donors' recruitment.

Mapping the HLA diversity of the Iberian Peninsula.

The polymorphism of HLA genes can be used to reconstruct human peopling history. However, this huge diversity impairs successful matching in stem cell transplantation, a situation which has led to the recruitment of millions of donors worldwide. In parallel to the increase of recruitment, registries are progressively relying on information from population genetics to optimize their donor pools in terms of HLA variability. In this study, the HLA data of 65,000 Spanish bone marrow donors were analyzed together with 60,000 Portuguese individuals to provide a comprehensive HLA genetic map of the Iberian Peninsula. The frequencies of many alleles were shown to vary continuously across the Peninsula, either increasing or decreasing from the Mediterranean coast to the Atlantic domain or from the Strait of Gibraltar to the Pyrenees and Bay of Biscay. Similar patterns were observed for several haplotypes. In addition, within some regions neighboring provinces share a close genetic similarity. These results outline the genetic landscape of the Iberian Peninsula, and confirm that the analysis of the HLA polymorphism may reveal relevant signatures of past demographic events even when data from donor registries are used. This conclusion stimulates future developments of the Spanish registry, presented here for the first time.

[Suitability of autologous blood donation before bone marrow donation]. / Pertinence du prélèvement sanguin autologue et de sa transfusion lors d'un don de moelle osseuse.

We assessed the benefit of predeposite autologous blood donation (PAD) before bone marrow (BM) donation on transfusion requirements, haemoglobin concentrations (Hb) and the occurrence of adverse events (AE). We collected data retrospectively from 50 donors of BM with PAD from 2010 to 2014. An autologous transfusion (AT) was given to 50% of the donors (group 1). In the group 2, the products from PAD were not used. The total volume median of marrow harvested was 17.7 mL/k (range 12.3-21.4) in the group 1 and 13.3 mL/k (8.6-22.6) in the group 2. The female ratio was higher in the group 1 (60%) than in the group 2 (16%). Bone marrow harvest led to a decline in Hb (from PAD to first day after BM donation) by 2.9 g/dL (1.5-5.5) in the group 1 and by 3.5 g/dL (1.2-5) in the group 2. The post-harvest Hb (D+1) median was identical in the two groups: 10.9 g/dL (7.6-13.5) in the group 1 versus 11.5 g/dL (9.3-13.4) in the group 2. Six AE were reported in each group. In the group with AE, the median weight was lower: 58 k (50-71) versus 75 k (52-110); and the median total volume of marrow harvested was higher: 20.1 mL/k (9.9-21.4) versus 14.3 mL/k (8.6-22.6). All post-harvest Hb were ≥ 7.6g/dL. This study shows the high loss of Hb after BM donation but not enough to prove a blood transfusion in BM donors with median age of 36 years (16-62) and without comorbidity. The occurrence of AE (25% of BM donors) justifies a careful surveillance after the BM donation. The PAD should not be routinely offered to bone marrow donors.

HLA-A, HLA-B and HLA-DRB1 haplotype frequencies in Piauí's volunteer bone marrow donors enrolled at the Brazilian registry.

This study aimed to report the antigen and haplotype frequencies (HFs) of volunteer bone marrow donors (VBMDs) from the state of Piauí who were enrolled in the National Volunteer Bone Marrow Donor Registry (REDOME). The research subjects were 21,943 volunteer bone marrow donors, predominantly young adult women (53.3%). The most frequent allelic group was HLA-A2, followed by -DRB1*13, -DRB1*04, -DRB1*07, -B*15, -B∗35, -B*44, -A*24 and -A*03. Of the 2,704 haplotypes observed, the three most frequent haplotypes were A*29 B*44 DRB1*07 (1.45%), A*01 B*08 DRB1*03 (1.4%) and A*03 B*07 DRB1*15 (0.92%). These three haplotypes were in linkage disequilibrium. PCA showed that 98% of the VBMDs have HLA allele frequencies that are very similar to those from Teresina, the capital city of Piauí. According to the PCA results, these municipalities are distributed with a close proximity to Teresina, which in turn has a close genetic proximity to the Hispanic ethnicity, intermediate proximity to Caucasians and Africans and a distant kinship to Amerindians. The hierarchical proximity of the population of Piauí to the Portuguese and Hispanic populations to shows the strong influence of the latter on the former.