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Ethical issues in bone marrow transplantation.

Ethical issues in health care arise from the perspectives of individual rights and clinical research. The advances in technologies for the treatment of cancer that come from clinical research have created new ethical issues. Bone marrow transplantation is such a case where research has the potential to benefit, but our resources to provide this lifesaving option are scarce. Ethical issues that nurses face in BMT include informed consent, concerns about the rights of donors, and the allocation of resources.

Adult↗

Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines.

For the past two decades, hematopoietic cell transplantation (HCT) has been used as effective therapy for selected inherited metabolic diseases (IMD) including Hurler (MPS IH) and Maroteaux-Lamy (MPS VI) syndromes, childhood-onset cerebral X-linked adrenoleukodystrophy (X-ALD), globoid-cell leukodystrophy (GLD), metachromatic leukodystrophy (MLD), alpha-mannosidosis, osteopetrosis, and others. Careful pre-HCT evaluation is critical and coordinated, multidisciplinary follow-up is essential in this field of transplantation. The primary goals of HCT for these disorders have been to promote long-term survival with donor-derived engraftment and to optimize the quality of life. Guidelines for HCT and monitoring are provided; a brief overview of long-term results is also presented.

Carbohydrate Metabolism, Inborn Errors↗

Unrelated marrow transplantation for children with acute lymphoblastic leukemia in second remission.

Allogeneic bone marrow transplantation (BMT) may be curative for more patients than chemotherapy for the child with relapsed acute lymphoblastic leukemia. This study reviewed the outcomes of 363 children with acute lymphoblastic leukemia in second remission who received unrelated donor BMT from 1988 to 2000 in order to define prognostic factors that affect leukemia-free survival (LFS). Median patient age was 9 years (range, 0-19 years), and median follow-up 29 was months (range, 0-125 months). The median duration of first remission was 24 months (range, 0-109 months). Prognostic factors, including age, duration of first remission, HLA matching, and graft-versus-host (GVH) disease, were analyzed using both univariate and multivariate analyses. Overall survival was 38%, and LFS was 36% at 5 years. LFS was significantly worse for patients 15 years or older (log-rank, P =.009). HLA matching was associated with improved LFS. Acute GVH disease developed in 71%, with 29% having grades III-IV. The incidence of chronic GVH disease was 39% for patients who survived more than 80 days and was significantly higher for female patients receiving marrow from female donors (P =.0009). Transplantation-related mortality was 42% and was associated with HLA mismatches, age 15 years and older, and first remission less than 12 months. The 5-year estimate for relapse was 22%, with first remission at least 6 months associated with a lower risk. Results of unrelated donor BMT appear similar to multi-institutional studies of matched related donor BMT, and this approach appears to be curative for many patients. However, innovative approaches are needed for patients with initial remissions of less than 6 months and for older teenagers.

Adolescent↗

French national bone marrow donor registry and interaction with foreign files.

A program to obtain volunteer bone marrow donors has been developed. A total of 33.000 HLA-A, B typings were performed. A search for 527 patients has been initiated. Among these, 44% are suffering from chronic myelogenous leukemia. For 23% of the patients no HLA-A, B identical donor has been identified. Out of the 401 patients who had HLA-A, B identical donor 35% (139/401) had one or more HLA-A, B, DR identical donors. In one of the transplant center, when the mixed lymphocyte culture (MLR) was carried out between 219 donors and 79 patients, a transplantation for 20/79 patients has been proposed. Up to now, transplantation has been carried out in 31 patients whom donor searches were initiated.

Bone Marrow Transplantation↗

Current status of Japan marrow donor program (JMDP) and its roles in international cooperation.

Transplants for patients lacking an HLA identical sibling donor have become possible, and thank to the establishment of large registries of HLA typed volunteers. Japan Marrow Donor Program (JMDP) now stands at about 152,339 volunteer donors, and have provided 4,013 marrows nationally and internationally. Advancements in HLA typing technology and greater precision in donor recipient matching have greatly increased the safety of unrelated donor transplants. In the JMDP retrospective study the strongest risk factor for acute GVHD and mortality was found to be mismatching for the BLA-A locus. Better matching criteria using molecular typing, however, will reduce the likelihood of identification of donors, especially in minorities. The chance of finding a matched unrelated donor is likely to be higher in the registries which share the same ethnic background of a recipient. There are five marrow donor registries have been established in Asia and are actively functioning. The expansion of volunteer donor pool of those registries and their efficient collaboration is very important to increase the probability of finding a match. The identification of permissive antigens may increase flexibility in donor-recipient pair matching may also be achieved through integration of international efforts and the creation of larger HLA data base.

Bone Marrow Transplantation↗

Registry of unrelated bone marrow donors.

Reports of successful transplantation of bone marrow obtained from unrelated donors who were histocompatibility leukocyte antigen (HLA) identical prompted the Canadian Red Cross Blood Transfusion Service in Ottawa to assess the possibility of developing a bone marrow donor registry in Canada. We sent a pamphlet that explained the program to 1568 people who had undergone apheresis and asked them to reply, stating their interest. At the same time the pamphlets and a poster were placed in the blood donor clinic. We received 1232 replies (78.6%) from the apheresis donors, 838 (68.0%) of which indicated a willingness to attend information sessions. Of the 7158 people who gave blood during the 3-month study period, 225 (3.1%) were interested. At the time this paper was written 47 information sessions had been held, and 721 people had attended, 624 (86.5%) of whom had signed a consent form. This indicates a clear interest in a bone marrow donation program. We believe that the ethical issues are overcome by requesting the donation before identification of any patient. From our experience a national registry of unrelated donors seems feasible, and steps are being taken to implement such a program.

Blood Component Removal↗

Unrelated bone marrow transplantation in Canada, the national experience. Canadian Red Cross Society.

The Canadian Unrelated Bone Marrow Donor Registry (UBMDR) of the Canadian Red Cross Society (CRCS) was officially funded as of April 1, 1989 for an initial three year period with a mandate to recruit 50,000 unrelated bone marrow donors and to conduct the search activities for unrelated bone marrow donors worldwide on behalf of Canadian patients. Since February of 1988, 162 unrelated bone marrow transplants have been carried out in Canada. The registry now stands at an enrollment of 35,705 with approximately 1,200 donors being added monthly. Recruitment of unrelated bone marrow donors is now established in fourteen Canadian cities, and an active ethnic recruitment is now in progress.

Bone Marrow Transplantation↗

Transplantation statistics in the UK--an agenda for the next quinquennium.

Our next quinquennial plan for transplantation studies extends MPI to corneal and unrelated marrow transplantation. It applies Bayesian hierarchical modelling to regional variation in donor procurement and continues a program of special studies to augment national databases with respect to kidney, corneal, heart and liver transplantation. It promotes research collaboration among European and other organ exchange organizations as pioneered in the Council of Europe 1986 Study on High Sensitization, which showed the effectiveness of the network of European organ exchange organizations in liaising with transplant units.

Bayes Theorem↗

[Setting-up a national file of bone marrow volunteer donors].

The lack of HLA matched sibling donors has become a problem. Recent improvements suggest the feasibility of marrow transplantation from unrelated donors. A program to obtain volunteer bone marrow donors has been developed. A total of 3,853 HLA A B typings were performed. A search for 83 patients was initiated; 51 of them had one or more HLA A and B (61%), 8 HLA A, B and DR antigen identical donors, 2 did not react in mixed lymphocyte culture. This experience confirms the necessity of increasing the donor file but the size remains to be established.

Bone Marrow Transplantation↗

Marrow transplants from HLA matched unrelated donors: an NMDP update and the Seattle experience.

It is now possible to access more than one million HLA-A, B typed volunteer individuals willing to donate marrow and a preliminary search through the NMDP registry provides access to more than 200,000 HLA-A, B, DR typed donors. Fifty-four percent of preliminary searches yield at least one potentially HLA-matched donor but the majority of these successful searches involve patients of Caucasian origin. Substantially greater recruitment must occur among different racial and ethnic groups if minority patients are to have a better chance of finding an HLA match. This can be accomplished by recruiting diverse donors within each regional registry or by expanding worldwide the existing international registry network. Molecular typing and matching for alleles in the HLA-D region improve the precision of donor selection and the timeliness of the donor search process. Although the risk of GVHD in unrelated donor transplants remains higher than in HLA-identical sibling transplant is not as good as HLA-identical sibling transplants, newer methods of supportive care and GVHD control are providing and gradual improvement in both the safety of the procedure and long-term relapse-free survival.

Adult↗

Bone marrow transplantation in Hong Kong.

Comprehensive programmes for BMT started in Hong Kong in 1990. As of September 1993, there are a total of 13 BMT beds in Government-funded University Hospitals performing about 110 transplants per year or 18 transplants per million population per year. So far, 194 transplants were performed: allogeneic BMT (72.2%), autologous BMT (11.8%), matched unrelated donor BMT (8.8%), identical twin BMT (1.5%), mismatched BMT (2.1%) and second BMT (3.6%). The major indication was haematological malignancy (84%). About 40% of the patients were prepared by chemotherapy alone. A combination of CsA and short MTX was the commonest GVHD prophylaxis. The incidence of GVHD was the same as in the Caucasians. Results of transplant outcome were comparable to those reported by the International Bone Marrow Transplant Registry.

Bone Marrow Transplantation↗

Quality control of a national bone marrow donor registry: results of a pilot study and proposal for a standardized approach.

Unrelated hematopoietic stem cell transplantation (HSCT) is a recognized therapy for hematological diseases and over 8 million HLA-typed donors are ready to donate. Increased international exchanges and rapid requests through the Bone Marrow Donor Worldwide (BMDW) ask for standardized quality assurance. Since no such standards have been established to date, we tested a pilot program in order to evaluate donor availability and quality of HLA typing of the Swiss Registry. The 18500 donors of the registry have been analyzed by serology for HLA-AB and by molecular typing for HLA-DR. Through three successive annual quality control (QC) exercises, a total of 114 donor requests were sent to 13 blood transfusion centers responsible for donor recruitment asking for a blood sample. Donors were randomly selected according to recruitment periods (1988-1993; 1994-1997; 1998-2000), and to homozygosity for HLA-A and/or -B antigens. An additional 80 frozen blood samples from the repository corresponding to the three periods (n=26) and to the 2001 period (n=54) were also included in the HLA study. HLA-AB typings were done by polymerase chain reaction-sequence specific primers (PCR-SSP) and all discrepancies were retyped. The results showed that 79 samples provided by 69.3% of the requested donors were received within 14 days, and 19 samples (16.7%) were received in >14 days. Altogether, an 86% rate of donor availability was observed, independent of the recruitment period. Among the requested donors, 16 (14%) were not available: for medical reasons (two), for personal reasons (eight), for loss (one), and for an unknown reason (five). The HLA-A/B DNA typing results of 166 homozygous and 12 heterozygous blood samples showed that 437/439 (99.5%) of the assigned A/B antigens were correct. However in 36/178 donors (20.2%) an HLA-A or -B antigen had been missed (34 donors) or misassigned (two donors) by serology, with a decreasing discrepancy rate of 30% (1988-1993) to 18.5% in 2001. Assuming that HLA-A or -B homozygotes are found in 10-15% of the donors and that correct assignments have been observed in nearly 100% of the donors, an overall error rate of 4-5% would be expected for the national registry HLA-AB typing. These data show that standardized quality control for donor availability and HLA typing is feasible, and we propose that this model could be applied to the registries participating in bone marrow donor worldwide.

Bone Marrow Transplantation↗

Health-related quality of life of unrelated bone marrow donors in Japan.

To promote bone marrow donation, both the safety and well-being of healthy unrelated volunteer donors must be protected. This prospective cohort study evaluated donors' health-related quality of life (HRQOL) and identified factors associated with it. Using the Medical Outcomes Study Short Form 36 Health Survey (SF-36) before bone marrow harvesting (BMH), and again 1 week and 3 months after the donors' discharge, we evaluated HRQOL of 565 donors (329 men, 236 women) registered with the Japan Marrow Donor Program (JMDP). We also examined the data routinely collected by the JMDP, such as BMH-related problems and other demographic and medical variables, to determine whether such data could be used to predict donors' HRQOL after discharge. Mean scores of all pre-BMH SF-36 subscales showed better functioning than the national norm. One week after discharge, mean scores on physical functioning (PF) and role-physical (RP) subscales, indicative of physical states, and bodily pain (BP) were approximately 1 SD lower than the national norm; however, mental health (MH) and general health perception (GH) remained above normal; the most frequent BMH-related problems were pain at the donation site and lower back pain, which were associated with lower PF, RP, and BP scores. Female gender and duration of procedure predicted lower PF, RP, and BP. Three months after discharge, mean scores of all SF-36 subscales had returned to baseline levels. These data show that the adverse effects of BMH on donors' HRQOL are transient and can be minimized by better management of pain.

Adult↗

Collection of sibling donor cord blood for children with thalassemia.

Bone marrow transplantation has curative potential for patients with thalassemia major who have a matched sibling marrow donor, but usefulness of alternative stem cell sources is undergoing investigation. Cord blood (CB) from a sibling has different characteristics from marrow and has potential advantages and disadvantages as a stem cell source. Whereas many families caring for a child with thalassemia major (or other transplant-treatable condition) experience an additional pregnancy, most give birth at hospitals without the infrastructure needed to collect and process the new infant's CB. To address this, and with funding from the National Institutes of Health, we have developed the first noncommercial CB program, operating across the United States, designed specifically to facilitate medically indicated CB collections from sibling donors. Using a case-management model, we have collected CB for 25 thalassemia families in eight states. Three of these CB units have now been used for transplantation; two others are human leukocyte antigen-identical and contain adequate nucleated cell dose to perform transplantation in their intended recipient. We conclude that a CB bank focused on sibling donations may be a useful stem cell resource and that families with specific medical need, such as a child with thalassemia, should consider preserving CB from siblings.

Blood Specimen Collection↗

[The bone-marrow transplantation program in Hungary: report from the period 1990-1995].

The article summarises the statistical data of bone marrow transplantation (BMT) carried out in Hungary between 1990-1995 in yearly distribution. Since the first BMT up to the end of 1995, 168 BMT were performed. The number of transplantations since 1990 to our days was gradually increasing. As a result of this activity in the three transplantation centers (National Institute of Haematology and Immunology, St. László Hospital and County Hospital in Miskolc) 36 allogeneic and 12 autologous BMT were performed in 1995. Out of the allogeneic BMT cases, 14% of them were completed with unrelated, donors in the last three years. The most frequent indications for allogenic BMT are: chronic myeloid leukaemia (CML), acute lymphoid leukaemia (ALL), acute myeloid leukaemia (AML), myelodysplasia, severe aplastic anaemia. Child allogenic BMTs are carried out on pediatric patients in St. László Hospital in leukaemia, severe aplastic anaemia cases and children born with immunodeficiency. Autologous BMTs started in an organised way in 1995 for adult patients in cases of non-Hodgkin lymphoma, Hodgkin lymphoma and for children with solid tumour indication in the Miskolc Centre. BMT activity in Hungary compared with international data, especially within Europe, shows a significant drop behind. To calculate for ten million inhabitants, the optimal BMT activity should be between 100-200 transplantations (allogeneic and autologous BMT together) in 1994. Among the Central European countries Hungary and Poland fall most behind. Autologous BMTs in most countries of Europe are above of allogeneic BMTs in numbers as indication in cases of lymphoma and solid tumours (first of all mamma carcinoma) comes into focus. This summary emphasises the most important difficulties in connection with the development of the National BMT program.

Adolescent↗