Bone Marrow Registry Research Articles

Exploring the role of gender and risk perceptions in people's decisions to register as a bone marrow donor

Increasing the number of bone marrow (BM) donors is important to ensure sufficient diversity on BM registries to meet the needs of patients. This study used an experimental approach to test the hypothesis that providing information about the risks of BM donation to allay unsubstantiated fears would reduce male and female participants' perceptions of risk for donation and joining the Australian Bone Marrow Donor Registry (ABMDR). Males' and females' intentions to register on the ABMDR and their attitudes, norms and perceived behavioural control (efficacy) in relation to registering were also explored. Participants were allocated randomly to either a risk (exposed to risk information about BM donation) or no-risk (not exposed to risk information) condition. In partial support of hypotheses, exposure to risk information did reduce perceived risk for registering on the ABMDR for males only. Participants in the risk condition also demonstrated lower scores on attitude (males only) and intention compared with participants in the no-risk condition. These findings highlight the complex role of risk perceptions and gender differences in understanding people's decisions to join a BM registry.

Ethical and regulatory issues surrounding umbilical cord blood banking in South Africa

Recent medical advances in the field of regenerative medicine and tissue transplantation have highlighted the importance of umbilical cord blood (UCB) as a valuable alternative source of haematopoietic stem cells, which are potentially life-saving in a vast array of clinical applications. Although less controversial than the use of embryonic stem cells obtained from fetal tissue, the practice of UCB biobanking presents several ethical and regulatory challenges surrounding its procurement and use, especially in developing countries like South Africa, where the majority of the population is vulnerable and prone to exploitation. Currently only private umbilical cord banking is practised in South Africa and the regulatory framework for human tissue use is still rudimentary with no clear guidelines. This environment raises ethical questions about consent and ownership of tissues, the cost-effectiveness of harvesting and storage of UCB, undue influence on donors, and issues of distributive justice such as the fact that UCB, which is potentially life-saving and could be easily obtained, may become a resource unfairly restricted only to the wealthy. In view of the fact that UCB has become a valuable, non-invasive source of stem cells for regenerative therapy, establishment of a public cord blood bank (CBB) in South Africa would vastly improve the availability of haematopoietic stem cells for research and therapeutic uses, and increase the tissue genetic diversity that currently impedes the South African bone marrow registry.

Cord blood banking and transplantation

The availability of umbilical cord blood (UCB) as a source of haematopoietic stem cells (HSC) for transplantation has met an important niche in the field of HSC transplantation (HSCT) as patients unable to find a HLA‐matched sibling or unrelated donor have been able to receive less well‐matched UCB transplantation (UCBT) with equivalent outcomes. This has led to significant growth in this field resulting in more than 20 000 unrelated donor UCBTs performed to date with about 3000 more performed annually. Growth of UCBT has been further supported by the proliferation of public cord blood banks throughout the world which store UCB at no cost to the donor, making these available for patients all round the world through global search registries like the US National Marrow Donor Program (NMDP), NetCord and the Bone Marrow Donors Worldwide (BMDW). International organizations like the World Marrow Donor Association have also helped to steer these efforts through the formulation and distribution of guidelines and protocols for these cord blood banks and bone marrow registries. The US Food and Drug Administration (FDA) has also stepped in to regulate publicly banked UCB as an Investigational New Drug (IND).The key limiting factor in UCBT is in the limited number of cells for transplantation (about 10‐fold less than donated bone marrow) resulting in delayed engraftment and even non‐engraftment, particularly for adult patients for whom UCB cell doses may be insufficient relative to the patient’s body size. Efforts to overcome this barrier include the use of concurrent infusion of two differing cord blood units in order to raise the cumulative cell dose. Interestingly, this does not lead to mutual rejection of the CBUs, but appears to result in an additive effect on enhancing engraftment. Other efforts to overcome cell dose constraints of cord blood include direct bone marrow injection, use of homing molecules and ex vivo cord blood expansion.Cell dose is also an important consideration for cord blood banking as donated UCB that is collected with cell count <800 million nucleated cells has very low chance of utilization by many transplant centres which demand the best cell doses for their patients. As such, not all UCB collected is banked, although many of the low volume cords can still be reassigned to research. Strategies to increase the number of cells collected from each delivery include the use of ex utero devices which apply suction, perfusion or pressure to delivered placenta and umbilical cord in order to maximize HSC collection. Devices which enhance cell recovery during cord blood processing also help to minimize cell loss. Other strategies which might influence obstetric practice are not advised.As the worldwide experience in UCBT and UCB banking grows, patient outcomes have continued to improve such that UCBT now has a firm place in the HSCT spectrum of care with even greater potential for growth in the years to come. The challenge is for these advances to stay cost‐effective so that the majority of patients can still have access to them.

Immunitary bioeconomy: The economisation of life in the international cord blood market

This paper examines an emerging bioeconomy centred on the international banking and trade in cord blood. Since the late 1980s cord blood has been used in an expanding range of treatments and as an alternative to the use of bone marrow stem cells. This is particularly the case in treating ethnic minority populations who have historically been under-represented in bone marrow registries. The paper explores the mobilisation and commercialisation of an increasingly important bioeconomic resource with cord blood units trading internationally at high prices. This is a market mediated through a sophisticated global network of immunologically typed and matched bodily matter in which immunity has become a form of ‘corporeal currency’. Based on recent international figures we reflect upon the balance of trade between imports and exports across the world’s cord blood bioeconomy. Theoretically, this case is, we suggest, an extension of what Roberto Esposito (2008) has termed an ‘immunitary paradigm’ in which immunity has become the basis for new forms of bioeconomic flow, circulation and exchange. Esposito (2008). Bios: Biopolitics and Philosophy. Minnesota, MN: University of Minnesota Press.

Genetic differentiation of Jewish populations

The Jewish diaspora can be viewed as a natural process in population dispersion and differentiation. We extend genetic studies on the Jewish diaspora to an analysis of human leukocyte antigen (HLA) haplotype distributions in the Jewish peoples, and show the value of this information for the design of Jewish marrow donor registries. HLA data from the Hadassah Bone Marrow Registry having parental country-of-origin information comprise samples of geographically discrete regions. We analyzed the HLA allele and haplotype frequencies for each national sample using population genetic and clustering methods. Population differentiation among diaspora populations was shown on the basis of HLA haplotype frequencies, including differences within the more recently diverged European groups. A method of haplotype and population clustering showed patterns of unique haplotype affinities associated with specific Jewish populations. The evidence showed that diaspora Jewish populations can be sorted into distinct clades of which the Ashkenazi are but one. Relationships among Jewish populations are interpretable in light of the historical record. We suggest that a major contributing factor to the genetic divergence between Jewish groups may have been admixture with local host populations, while, at the same time, threads of Eastern Mediterranean ancestry remain evident.

HDAC2 expression and variable number of repeats in exon 1 of the HDAC2 gene in corticotroph adenomas

Alterations in protein expression of histone deacetylase 2 (HDAC2) have been demonstrated in various neoplasms, and lack of nuclear expression of HDAC2 has previously been shown in some human and canine corticotroph adenomas. This study aimed to examine HDAC2 expression in a Norwegian cohort of corticotroph adenomas, screen for exonic HDAC2 gene variants in the adenomas and correlate the results with clinical data. Forty-four patients with verified Cushing's disease or Nelson's syndrome, positive ACTH staining and tissue available for immunohistochemistry and/or DNA sequencing were included. Ninety-four controls were chosen from the Norwegian Bone Marrow Registry. Histone deacetylase 2 expression examined by immunohistochemistry was strongly reduced in 3/30 adenomas. There were no association between HDAC2 expression and clinical variables. A previously unidentified insertion of three bases in a region coding for a polyserine cluster in exon 1 of the HDAC2 gene was identified in 6/32 adenomas. No other mutations in HDAC2 exons were found. Examination of DNA extracted from peripheral blood confirmed germ-line origin of the exon 1 insertion. The same insertion was also found in 28/94 of the controls (i.e., not significantly different from the patients). Strongly reduced HDAC2 protein expression was confirmed in a small portion of corticotroph tumours. Mutations in HDAC2 exons are unlikely to play an important role in the development of corticotroph adenomas.

149-P: Evaluation of novel HLA alleles discovered during typing for the Singapore Bone Marrow Registry(SBMR)and Singapore Cord Blood Bank (SCBB)

149-P: Evaluation of novel HLA alleles discovered during typing for the Singapore Bone Marrow Registry(SBMR)and Singapore Cord Blood Bank (SCBB)

Correlation between characteristics of unrelated bone marrow donor and cell density of total nucleated cell in bone marrow harvest

The relationship between the features of bone marrow donor and the quality of marrow harvest has been unclear because most of bone marrow registries have multiple collection centers with somewhat different harvest procedures. We are able to address this issue for Tzu Chi General Hospital is the only collection center affiliated with Tzu Chi Taiwan Bone Marrow Registry. Between November 1997 and March 2002, data of 286 healthy unrelated donors was analyzed to correlate with the cell density of total nucleated cell in bone marrow harvests. The harvest procedure was standardized by single-hole harvest needle under general anesthesia. The operation staffs were restricted within the members of Oncology-Hematology division. The results showed that the cell density of bone marrow harvest was positively correlated with donor body weight and peripheral white blood cell count P = 0.0475, P < 0.0001, but negatively correlated with the total volume of bone marrow harvest P < 0.0001. We recommend that if multiple human leukocyte antigen-matched donors are available, donor with higher body weight and/or higher white blood cell count be selected for allogeneic bone marrow transplantation.

A retrospective analysis of chronic myeloid leukaemia (CML) in Papua New Guinea (PNG) 2001–2008

Aim The aim of the study was to analyse all recorded cases of CML in PNG from 2001 to 2008 at Port Moresby General Hospital (PMGH). Methods This study was retrospective. Data on leukaemia cases in PNG from 2001 to 2008 were accessed from the bone marrow registry in PMGH, the key tertiary referral hospital for the country. Data were analysed, tabulated and graphed using Epi Info and Microsoft Excel. Results CML comprised 27% of all leukaemias with 53 registered cases from 2001 to 2008. Most cases of CML presented in the age range 26–30 years with an equal sex ratio. Fifty-two per cent of CML cases presented in chronic phase, and 28% in accelerated phase. The majority of cases were diagnosed using bone marrow morphology at PMGH. Conclusions In PNG a younger population is diagnosed with CML, possibly because of inaccurate age estimates and reduced the life expectancy. Definitive estimates of incidence and prevalence are significantly underestimated due to voluntary registration, non-national coordination and hospital rather than population based data collection. With sparse clinical data and the absence of effective treatment, the study quantifies a great need for innovative programs such as the Glivec International Patient Assistance Program.

Cord Blood Transplantation

Hematopoietic stem cell transplant (HSCT) can be curative for many cancers and inherited non-malignant diseases, including bone marrow failure syndromes, hemoglobinopathies, and inborn errors of metabolism. While, in most settings, matched sibling transplantation confers best results, more than two-thirds of patients lack a suitable donor. Donor searches from National bone marrow registries are time-consuming and not always successful. Cord blood transplantation now offers a viable option. Cord blood is even more valuable for countries where there is no national registry to provide a pool of potential donors. In the past two decades, over 6000 cord blood transplants have been performed. The data so far indicate that not only is it feasible but in certain situations may offer an advantage over matched unrelated donors. There is also massive interest today about the role of umbilical cord blood cells in regenerative medicine. This article gives an overview of cord blood transplantation and cord blood banking.

Umbilical cord blood banking: public good or private benefit?

Haematopoietic stem cell transplantation (HSCT) is an accepted curative therapy for many malignant and non-malignant conditions affecting children and adults. Where possible, stem cells for HSCT are provided by human leukocyte antigen (HLA)-matched, related donors. Only 30% of patients have a suitable matched donor; for other patients, donors are sought from bone marrow registries or public umbilical cord blood (UCB) banks. While public UCB banks have been established to support transplant programs in Australia and internationally, parents also have the option of storing their child's UCB in a private commercial UCB bank for personal or family use. In contrast with public UCB banks, there is little social or medical justification for private UCB banking, as it provides no benefit to the community and little benefit to parents (other than reassurance and amelioration of regret), due to the very low likelihood of requiring autologous UCB later in life. Should UCB prove to be beneficial for tissue repair or replacement in the management of degenerative disorders, such as diabetes and Parkinson's disease, then a stronger case may be made in support of commercial banking of UCB for personal use. This may have a major impact on public UCB programs.

Re-creation of the genetic composition of a founder population.

Human ethnic groups are frequently comprised of two or more founder populations. One of these founding populations is often available for contemporary sampling. We describe a method for reconstructing the composition of a missing founder population using the highly informative haplotypes comprising the HLA system. An application of the method is demonstrated using bone marrow registry samples of African Americans. We use contemporary samples of African Americans and European Americans to derive haplotypes of the West African founder populations. This approach may also be useful for reconstructing ancestral haplotypes for regions elsewhere in the genome.

Immunohematopoietic stem cell transplantation: introduction and 35 years of development in South Africa—the historical and scientific perspective

Bone marrow was the traditional graft source when we introduced these procedures to South Africa. Technical details were established using rabbits as the experimental model with translation into a formally structured clinical programme at the University of Cape Town, based in the Groote Schuur Hospital, in 1972. Lack of any infrastructure was overcome by the acquisition of the first continuous-flow cell separator in sub-Sahara to provide for granulocyte transfusions. This was shortly followed by creating a dedicated platelet donor panel and establishing a specialized laboratory for clonogenic assays, flow cytometry, and programmed freezing and by including cryopreservation. Development was constant and seamless but four distinct periods are recognizable. First, guided and constantly encouraged by Professor E Donnall Thomas, was the use of an unfractionated mononuclear population derived from multiple sternal and iliac crest aspirations where complications, as in other centres, included rejection and, particularly troublesome, acute as well as chronic GVHD. The second was centred on CsA in association with Professor Jean Borel at Sandoz in Basle, leading to a decrease in the incidence and severity of the latter immunologic phenomena but not to their abrogation. Third was the opportunity of working with Professor Herman Waldmann and Dr Geoff Hale, first in Cambridge and latterly in Oxford, on immunosuppression achieved by ex vivo T-cell depletion within the broad ambit of the Campath users group. It was here that there was pioneered the alternative new approach of adding the anti-CD 52 MoAb only to the graft in what has become known as the in-the-bag technique. The fourth, securely based on early laboratory and clinical experiences, was a switch to the use of PBSCs mobilized into the circulation with stimulatory peptides. In 1995, this original transplant team relocated to a new academic centre in the private sector and has continued to actively refine the programme over the subsequent decade: the facility at Groote Schuur hospital continues independently. Early recognition that accountability for these expensive and high profile procedures was an important obligation led to consecutive transplants being reported to the International and Autologous registries and now continuing to the Centre for Bone Marrow Transplant Research concurrently with the European Bone Marrow Transplant Registry. This disciplined approach has ensured that all data undergo constant audit and, on such a basis, underpin the unbroken accreditation extending over more than three and a half decades. With difficulties in finding sibling donors, a further achievement was the creation of The South African Bone Marrow Registry and now a proposal to also start a national transplant registry that will complement the survey currently being conducted, on a worldwide basis, by the European Group for Blood and Marrow Transplantation. It is concluded that a properly constituted and functioning multidisciplinary team can cost-effectively carry out immunohematopoietic stem cell grafting even in an under-resourced country with an outcome approximating that reported from recognized First World reference centres. The caveat is that, outside such comprehensive units, results may be less impressive, thereby arguing for resource allocation being directed to academically designated, rather than incentive-driven, preferred providers.

HLA‐A, ‐B and ‐DRB1 allele frequencies in the Bangladeshi population

Population genetic studies have become an invaluable tool because of the extreme polymorphism found at some of the loci of the human leukocyte antigen (HLA) system. In this study, we are reporting for the first time the genetic polymorphism of 141 healthy unrelated Bangladeshi Bangalees living in central region of Dhaka. We studied the HLA-A, -B and -DRB1 loci using polymerase chain reaction with sequence-specific primers. The allelic frequencies, two and three locus haplotype frequencies were statistically analyzed. A total of 16 HLA-A alleles, 26 HLA-B alleles and 14 HLA-DRB1 alleles were detected. A*33-B*44 (8.15%) was the most common two loci class 1 haplotype, whereas A*33-B*44-DRB1*07 (6.38%) was the most frequent three loci haplotype. The most common HLA-A, HLA-B and HLA-DRB1 alleles were A*33 (17.02%), B*15 (19.5%) and DRB1*15 (29.07%), respectively. Construction of phylogenetic tree using average linkage between groups and correspondence analysis showed close associations with Indian non-tribal random Dravidians, north Indian Hindus and some relations with Mongolian and Pakistani populations. We believe this data will provide useful information for bone marrow registry, legal medicine, disease association and anthropological studies.

The South African Bone Marrow Registry (SABMR) and allogeneic bone marrow transplantation.

In 1939 Osgood et al. reported infusing bone marrow into patients with severe aplastic anaemia without any clinical benefit. Rekers and Coulter attempted to reconstitute marrow function in irradiated dogs by marrow infusions. Both failed because of insufficient irradiation to produce immunosuppression necessary for engraftment. In 1957 Donnall Thomas and co-workers showed that marrow can be collected, stored in significant quantities and safely administered.

The use of granulocyte–colony‐stimulating factor in volunteer unrelated hemopoietic stem cell donors

Granulocyte-colony-stimulating factor (G-CSF) is used for the mobilization of hemopoietic stem cells in healthy donors. It has a number of common side effects such as bone pain, which resolve rapidly after administration is discontinued. Recent publications have raised concern that it might act as a trigger for the development of hematologic malignancy in susceptible individuals, possibly by causing genomic instability, but to date there is no evidence that healthy volunteer donors who receive G-CSF are at any increased risk. Ongoing studies aim to confirm whether or not G-CSF can cause chromosomal abnormalities in healthy donors. In the UK, the British Bone Marrow Registry and Anthony Nolan Trust give G-CSF to donors who have agreed to donate peripheral blood stem cells. It is recommended by the UK Registries at present that all stem cell donors are given updated information explaining the current uncertainties with regard to the use of G-CSF before they give informed consent to its administration. This information is based on a statement agreed by the World Marrow Donor Association for use by individual donor registries. Further, it is our current practice that all donors who have received G-CSF, as well as marrow donors who do not, should be under regular review for at least 10 years to allow the occurrence of any long-term adverse events to be documented.

Factors That Influence Greeks' Decision to Register as Potential Bone Marrow Donors

Hemopoietic stem cells can be used from bone marrow or blood or umbilical cord blood of matched siblings or appropriately matched unrelated volunteers. Today, large bone marrow registries have been established to help identify volunteer unrelated bone marrow donors for patients lacking a family donor. Despite there being almost 10 million registered potential bone marrow donors (PBMD) worldwide, only 50% of white patients have a suitable bone marrow match. Growth in the number of PBMD increases the likelihood of finding a compatible donor for a patient. The attitudes and knowledge of 250 registered PBMD and 315 not registered PBMD toward bone marrow donation, tissues and organs donation, and blood donation were surveyed, using a questionnaire with 27 items. Multivariate logistic regression identified gender (females more often than males), regular blood donation, having a relative or a friend who has already been registered as PBMD, having a relative or a friend who needs bone marrow transplantation, family discussion about tissue and organ donation, knowledge about bone marrow transplantation, information about bone marrow transplantation, and trust in health professionals were independent predictive factors influencing people's decision to register as PBMD. Knowledge of these factors is important to target recruitment efforts.

One Chance in a Million: Altruism and the Bone Marrow Registry.

Stem cell transplants save lives of many patients with blood diseases. Donation is painful, but rarely has lasting adverse effects. Patients can accept transplants only from donors with compatible immune systems. Those lacking a sibling match must seek donations from the general population. The probability that two unrelated persons are compatible is less than 1/10,000. Health authorities maintain a registry of several million genetically tested potential donors who agree to donate if asked. We find that the benefits of adding registrants of every race exceed costs. We also explore the peculiar structure of voluntary public good provision that faces potential donors.

Myelodysplastic syndromes. The epidemiological and etiological aspects

From a total of 18,416 bone-marrow biopsy reports entered into the Düsseldorf Bone Marrow Registry between 1975 and 1990 those of patients diagnosed as having preleukaemia, myeloid dysplasia, panmyelopathy with hypercellular bone marrow, refractory anaemia, sideroblastic anaemia or smoldering leukaemia were reanalyzed together with patient-data. If the diagnosis of myelodysplastic syndrome (MDS) was confirmed, the original blood and bone-marrow smear was re-examined and classified, 584 cases in all (3.2%). During the same period acute myeloid leukaemia had been diagnosed in 506 patients (2.8%). The average annual incidence of MDS in the Düsseldorf area was 3.65 per 100,000 inhabitants. Over 80% of cases occurred from the age of 60 years, while 7% were younger than 50 years. The sex ratio was the same in all subgroups of MDS, except chronic myelomonocytic leukaemia (male:female ratio 1:1.57). 31 patients (5.3%) had received ionizing radiation and/or cytostatic or immunosuppressive treatment for various underlying diseases before MDS had been diagnosed (secondary MDS). Preceding occupational contact with organic solvents could not be excluded with certainty in 12 patients. These data suggest that MDS is a relatively frequent disease of hematopoiesis among the older age groups. The proportion of secondary (treatment-induced) forms is small and does not explain the recently observed increased incidence.

Improving communication among the HLA typing laboratories, transplant centers, and coordinating center

Good communication between the bone marrow registries, the donor centres, tissue typing laboratories and clinical units is paramount to ensure timely identification, testing and selection of donors for unrelated bone marrow transplants. This panel session focussed on how to improve communication so that there was a clear understanding of prioritization of requests from clinicians, typing strategies in the laboratories and requests for donors to the registries. This paper outlined some of the strategies discussed in this session.