PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “National Marrow Donor Program”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

Outcome of unrelated transplants in patients with multiple myeloma.

The outcome of patients with multiple myeloma treated with standard therapy is disappointing, with a historical median survival of 3 years. Although high-dose therapy with autologous stem cell transplant has improved treatment outcomes, cure is unlikely. Allogeneic transplant provides a tumor-free graft and a graft-versus-myeloma effect. However, only a minority of patients has a compatible sibling donor. Unrelated hematopoietic stem cell transplant is another option. We analyzed the outcome of patients who received an unrelated bone marrow transplant facilitated by the National Marrow Donor Program (NMDP). Between 1989 and 2000, 71 patients received a myeloablative unrelated transplant for multiple myeloma; 70 patients consented for this analysis. The median recipient age was 44 years. A total of 31% of patients had received a prior autologous transplant. In all, 91% of patients engrafted. The 3-year cumulative incidence estimate of relapse was 34+/-10%. The incidence of Grade II-IV GVHD was 47%. The Kaplan-Meier estimate for overall survival at 5 years was 9+/-7%. The 100-day treatment-related mortality was 42%. In multivariate analysis, only a male donor was a significant predictor for survival. Better strategies are needed to treat patients with multiple myeloma, perhaps by using less-toxic, nonmyeloablative conditioning regimens.

Adult↗

The HLA Dictionary 2001: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens.

This report presents the serological equivalents of 123 HLA-A, 272 HLA-B and 155 HLA-DRB1 alleles. The equivalents cover over 64% of the presently identified HLA-A, -B and -DRB1 alleles. The dictionary is an update of the one published in 1999 (<1>Schreuder et al., 1999, Tissue Antigens, 54, 409) and also includes equivalents for HLA-C, DRB3, DRB4, DRB5 and DQB1 alleles. The data summarize information obtained by the WHO Nomenclature Committee for Factors of the HLA System, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP) and individual laboratories. In addition, a listing is provided of alleles that are expressed as antigens with serological reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated hematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. These equivalents will also serve typing and matching procedures for organ transplant programmes where HLA typings from donors and from recipients on waiting lists represent mixtures of serological and molecular typings. The tables with HLA equivalents and a questionnaire for submission of serological reaction patterns for poorly identified allelic products will also be available on the WMDA web page: www.worldmarrow.org

Alleles↗

Common human leucocyte antigen haplotypes in Indians--its implications in finding unrelated compatible bone marrow donors.

All over the world there have been efforts to make unrelated stem cell registries to cater for patients who do not have a compatible family donor and are in need of allogenic stem cell transplantation. Donors of Indian origin are poorly represented all these registries. Approximately 10 million Indians live outside India, and a substantial number of them live in the developed West. Hence when some of these patients of Indian origin need unrelated stem cell donor, they search the available National Marrow Donor Program (NMDP) registry database and invariably do not get a human leucocyte antigen (HLA) matched donor. They come to India, where a haphazard search for the donor ensues and it invariably ends in failure. Hence, we have compiled the data of our laboratory and other published reports in population HLA studies from India and abroad to show several common haplotypes from these studies. It is hoped that this will give the busy clinician an idea whether a search for prospective unrelated stem cell donor for an Indian patient is likely to succeed or not.

Bone Marrow Transplantation↗

HLA class I and II antigen phenotypes of North American Indians from Minnesota: implications for marrow transplants using unrelated donors.

As a result of an appeal for a bone marrow donor for a North American Indian (Native American) patient, 261 Native Americans from our community were typed for HLA-A,B,DR antigens, and 51 were typed for HLA-A,B antigens only. The HLA antigen frequencies of the Native Americans were compared with those of 12,881 white bone marrow donors and were found to differ markedly. To investigate the implications these differences in HLA antigen frequencies would have for the location of unrelated bone marrow donors, the HLA types of 12 Native American bone marrow transplant patients from our institution were used to search among 5389 HLA-A,B,DR-typed white donors in the National Marrow Donor Program file and the file of 261 HLA-A,B,DR-typed Native American donors. In the white donor file, at least two donors were found that matched at all HLA-A,B,DR antigen loci of one Native American patient (8%). Using the Native American donor file, which was less than one-twentieth the size of the white donor file, and HLA-A,B,DR-matched donor was also found for one (8%) of the patients. These results suggest that although donors for nonwhites can be identified in a file of HLA-typed white volunteers, the probability of finding a suitably matched donor for such individuals is enhanced if donors representing racial or ethnic minorities are included in unrelated donor registries.

Bone Marrow Transplantation↗

Obtaining an accepted Investigational New Drug application to operate an umbilical cord blood bank.

BACKGROUND: The residual blood left in the placenta, previously considered a biologic waste, contains sufficient hematopoietic stem and progenitor cells to consistently engraft at least a small recipient. Over the past several years, more than 500 HLA-matched, related and unrelated, allogeneic cord blood transplants have been performed. Consequently, public and private cord blood banks are being developed to meet future demands. Thus, the definition of a suitable and effective cord blood component needs to be critically defined. In February 1997, the US Food and Drug Administration (FDA) proposed that cord blood banks should operate under an Investigational New Drug (IND) license. STUDY DESIGN AND METHODS: Standard operating procedures were designed using standards from the Foundation for Accreditation of Hematopoietic and Cellular Therapy, the American Association of Blood Banks, and the National Marrow Donor Program and in accordance with current good manufacturing practices. The standard operating procedures were field-tested and submitted to the FDA. RESULTS: Issues of the utmost concern to the FDA dealt with transplant recipient outcome data collection, donor recruitment, sample tracking, the use of unlicensed materials, and the reporting of positive infectious disease results. After three attempts, an IND application was approved. CONCLUSIONS: To obtain approval of an IND application, cord blood banks need a set of standard operating procedures that describe cord blood collection, processing, freezing, and storage. Issues relating to potential cord blood recipient identification, cord blood shipping, and reporting of transplant recipient outcomes are also needed. The IND process provides an opportunity for outside reviewers to make suggestions that may be included in the standard operating procedures.

Blood Banks↗

Racial and ethnic composition of volunteer cord blood donors: comparison with volunteer unrelated marrow donors.

BACKGROUND: Umbilical cord blood is an alternative peripheral blood progenitor cell source for patients who need transplantation. A presumed advantage of cord blood is the ability to increase minority recruitment. STUDY DESIGN AND METHODS: The racial composition of five member cord blood banks of the National Marrow Donor Program (NMDP) was compared, representing 9020 cord blood donors with NMDP marrow donors from comparable geographic areas, representing 417,676 donors. Cord blood and marrow donors self-reported racial designations on questionnaires. Donor statistics were compared with baseline racial data of deliveries from participating hospitals for cord blood donors and with geographic census data for marrow donors. RESULTS: The California, Florida, and Massachusetts cord blood banks recruited a lower percentage of minorities than the corresponding marrow donor centers. In New York and Colorado, minority recruitment was equivalent. In California, Florida, Massachusetts, and New York, the cord blood banks recruited a lower percentage of minorities than those delivering at the respective hospitals. The cord blood banks in California, Colorado, Florida, and Massachusetts recruited a lower percentage of minorities compared with delivery data than the corresponding marrow donor centers compared with census population (p < 0.001). In New York, the percentages were similar. CONCLUSION: The problem of insufficient minority recruitment of cord blood has not yet been solved. Better strategies are needed to recruit minority donors.

Adult↗

Marrow transplantation from unrelated donors for patients with severe aplastic anemia who have failed immunosuppressive therapy.

Allogeneic marrow transplantation offers curative therapy for patients with aplastic anemia. We analyzed retrospective results in 141 patients with severe aplastic anemia who received transplants between 1988 and 1995 from an unrelated volunteer donor identified through the National Marrow Donor Program (NMDP). All patients had failed one or more courses of immunosuppressive therapy. Of the patients, 121 (86%) received a radiation-containing conditioning regimen, and 20 (14%) were given chemotherapy only. Based on serologic human leukocyte antigen (HLA) typing (class I and II), 105 patients (74%) received HLA-matched marrow, and 36 (26%) received marrow mismatched for at least one HLA-A, -B, or -DR antigen. Allele-level (molecular) typing for HLA-DRB1 was available in 108 donor-recipient pairs; 77 patients received DRB -matched and 31 DRB1-mismatched transplants. All but 13% of patients were given a cyclosporine-containing regimen for graft-vs.-host disease (GVHD) prophylaxis, and 45 patients (32%) received marrow that was T cell-depleted. Among 131 evaluable patients, 116 (89%) achieved sustained engraftment and 15 (11%) did not. Among patients with engraftment, acute GVHD of grades II-IV developed in 60 patients (52%) and extensive chronic GVHD in 24 patients at risk (31%). Currently, 51 patients (36%) are surviving at 11-94 months (median 36) after transplantation. All but five have Karnofsky scores > or =80. Patients who received a serologically matched transplant fared somewhat better than did patients given a serologically mismatched transplant p = 0.03). Patients with donors matched by both serology and allele-level DRB1 typing had significantly better survival than DRB1-mismatched patients with 56 vs. 15% surviving at 3 years p = 0.001). Outcome in patients transplanted within 3 years of diagnosis was superior to that among patients transplanted with greater delay. Major causes of death were graft failure, GVHD, and infections. These data suggest that unrelated marrow transplantation offers successful therapy for a proportion of patients who have failed immunosuppressive therapy.

Adolescent↗

Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem Meetings of the International Bone Marrow Transplant Registry and the American Society of Blood and Marrow Transplantation.

Approaches to the measurement of lymphohematopoietic chimerism have evolved from laboratory research to important clinical tools. However, there has been no logical, consistent, and uniform set of recommendations for the measurement of chimerism in clinical transplantation. The National Marrow Donor Program and the International Bone Marrow Transplant Registry (IBMTR) sponsored a workshop to discuss the use of chimerism analysis after allogeneic transplantation. The workshop was organized in an effort to make reasonable recommendations regarding laboratory techniques, the types of specimens to be studied, and the frequency of analysis. The panel recommended the following guidelines: 1. Chimerism analysis should use sensitive, informative techniques. At present, short tandem repeats (STR) or variable number tandem repeats (VNTR) analysis is the approach most likely to give reproducible informative data. 2. Peripheral blood cells are generally more useful than bone marrow cells for chimerism analysis. 3. Lineage-specific chimerism should be considered the assay of choice in the setting of nonmyeloablative and reduced-intensity conditioning. 4. The use of T-cell depletion, nonmyeloablative or reduced-intensity conditioning, or novel graft-versus-host disease (GVHD) prophylactic regimens warrants chimerism analysis at 1, 3, 6, and 12 months, because interventions such as donor lymphocyte infusions may depend on chimerism status. 5. In nonmyeloablative transplantation, the early patterns of chimerism may predict either GVHD or graft loss. Therefore, more frequent (every 2-4 weeks) peripheral blood analysis may be warranted. 6. For nonmalignant disorders, chimerism generally should be measured 1, 2, and 3 months after transplantation. Interventions to enhance donor engraftment must be considered on a disease-specific basis in relation to concurrent GVHD and, ultimately, clinical rationale.

Blood Cells↗

Pediatric bone marrow transplantation.

Bone marrow transplantation has become well established in the treatment of malignant and nonmalignant disorders. Steady progress continues in improving survival after transplantation, but many problems remain to be solved. Relapsed disease is a major limitation, and new, more intensive preparative regimens are being evaluated in an effort to improve efficacy and reduce toxicity. The availability of unrelated donors has been improved with continued expansion of the National Marrow Donor Program. Additional alternative sources of marrow actively being investigated include partially matched family members and peripheral blood stem cells. Improved marrow purging techniques are also being studied to allow expanded use of autologous marrow for various malignancies. The use of cytokines to minimize regimen toxicity and as therapeutic agents is also promising. The late effects of bone marrow transplantation, including relapse, chronic graft-versus-host disease, secondary malignancies, and effects on growth and development, are important considerations in the design of new therapeutic strategies.

Anemia, Aplastic↗

Marrow transplantation from unrelated donors.

The use of an HLA-compatible unrelated donor is an option for patients who require an allogeneic transplant but lack a family member match. Grafts from unrelated volunteer donors have provided long-term disease-free survival for a variable proportion of patients, depending on degree of HLA matching with the donor, patient's disease, disease stage, and age. The number of volunteers in marrow donor registries worldwide has increased to more than 2.5 million. The number of unrelated donor transplants facilitated by the US National Marrow Donor Program alone will exceed 900 this year. Progress in HLA-typing technology results in a more precise definition of donor and recipient matching and new assays have been developed with initial success to measure alloreactive T-cell precursors for selection of donors with less antihost reactivity. Prevention and treatment of graft failure, graft-versus-host disease, opportunistic infections, and Epstein-Barr virus-associated lymphoproliferative disease remain a challenge.

Bone Marrow Transplantation↗

Low frequency of telomerase RNA mutations among children with aplastic anemia or myelodysplastic syndrome.

Mutations in TERC, the RNA component of telomerase, result in autosomal dominant dyskeratosis congenita (DC), a rare bone marrow failure syndrome. TERC mutations have been detected in a subset of patients previously diagnosed with aplastic anemia and myelodysplastic syndrome (MDS), and these TERC mutations are clinically relevant as patients with DC respond poorly to conventional therapies. We aimed to determine the frequency of TERC mutations in pediatric patients with aplastic anemia and MDS who required a hematopoietic stem cell transplant. We obtained 284 blood samples from the National Donor Marrow Program Research Sample Repository from children and adolescents with bone marrow failure who underwent an unrelated stem cell transplant. We screened these samples for mutations in the TERC gene using direct DNA sequencing. We found 2 patients with sequence alterations in TERC. We identified a 2 base pair deletion (-240delCT) in a 4-year-old child with MDS and a single nucleotide alteration (-99-->CG) in a 1-year-old child with juvenile myelomonocytic leukemia. Screening for TERC gene mutations is unlikely to diagnose occult DC in children with severe bone marrow failure who require a hematopoietic stem cell transplant.

Adolescent↗

Factors associated with ambivalence about bone marrow donation among newly recruited unrelated potential donors.

BACKGROUND: Previous research has indicated that feelings of ambivalence about donation are associated with donors' decisions not to donate and with less positive physical and psychosocial outcomes among donors who donated despite feeling ambivalent. The current study examines the prevalence of ambivalence among newly recruited potential bone marrow donors and identifies factors associated with greater ambivalence. METHODS: Using a cross-sectional design, questionnaires were mailed to a stratified random sample of individuals newly recruited to the National Marrow Donor Program registry at 71 local donor centers. A total of 426 new recruits (63%) completed and returned the questionnaire. RESULTS: Bivariate analyses indicated that multiple recruitment experience and donor perception variables were significantly associated with ambivalence. Multivariate analysis revealed that the following eight variables were uniquely associated with higher levels of ambivalence after adjusting for the effects of other key indicators: participating in other volunteer activities, joining at a drive for a specific patient, perceiving the recruitment staff as less informative, being discouraged from joining by others, not having an intrinsic commitment to donate, being encouraged by one's culture or religion to join, believing there are risks to donation, and having a greater number of medical, work, and family concerns about donation. CONCLUSIONS: Potential donors who are motivated by an intrinsic commitment to donate, rather than extrinsic pressure, are less ambivalent about donating. In addition, recruitment staff have a potentially critical role in reducing ambivalence among new recruits by providing information that may allay any unrealistic concerns recruits may have about the medical risks and impact of donation on work and family.

Adolescent↗

The association of donor center characteristics with attrition from the national marrow donor registry.

BACKGROUND: The National Marrow Donor Program (NMDP) has approximately 5 million registered potential donors and continues to add more than 30,000 new recruits to the registry monthly. However, more than 30% of potential donors are not available or decline to donate at key decision points in the donation process. Although previous researchers have examined the association of individual donor characteristics with attrition from the registry, no published studies have investigated the role of donor center characteristics or features of the donor centers' environment on attrition rates. METHODS: Donor center coordinators from 72 NMDP centers completed questionnaires that included items regarding donor center location and organization, recruitment strategies, and registry management. Center-specific registry composition data and attrition rates were gathered from the NMDP database. RESULTS: Analyses indicated that higher attrition was found at larger centers that needed more center staff and volunteers to deal with larger workloads and more DR-typing requests. Attrition was also higher among centers located in highly populated, urban environments, with larger minority and less stable populations. CONCLUSIONS: The results indicate that the NMDP may need to tailor donor center retention expectations to account for certain unchangeable characteristics (e.g., center size and population stability) and to develop internal strategies to address the unique characteristics of each donor center (e.g., current performance level or improvement needs).

Databases, Factual↗

Attrition of potential bone marrow donors at two key decision points leading to donation.

BACKGROUND: The National Marrow Donor Program (NMDP) has had remarkable success at recruiting potential bone marrow donors and recently has become increasingly focused on the retention of registered volunteers. This study extends the authors' work examining factors associated with attrition from the registry. Its goal was to determine which characteristics from six psychosocial domains were associated with attrition at two key stages leading to donation. METHODS: Questionnaires were mailed to potential donors after they were contacted as a potential match and had decided whether or not to continue toward donation. Our final sample included 1,727 volunteers who decided to continue with typing at the DR stage and 195 volunteers who decided to continue at the confirmatory typing (CT) stage as well as 179 and 169 individuals, respectively, who declined further participation in the registry at DR and CT stages. RESULTS: Bivariate analyses indicated that multiple factors in all six domains (demographics, volunteer-related, general psychosocial, recruitment-related, donation-related, and contact with center staff) were associated with discontinued registry participation. Logistic regression indicated that unique associations were concentrated in volunteer-related, donation-related, and contact with center domains. CONCLUSIONS: Findings suggested that intrinsic commitment to donation, more realistic expectations, fewer medical concerns, and greater contact with the donor center were all associated with lower attrition. Possible interventions to reduce attrition are discussed.

Bone Marrow Transplantation↗

Assessment of optimal size and composition of the U.S. National Registry of hematopoietic stem cell donors.

BACKGROUND: The National Marrow Donor Program (NMDP) receives federal funding to operate a registry of over 4 million volunteer donors for patients in need of a hematopoietic stem cell transplant. Because minority patients are less likely to find a suitably matched donor than whites, special efforts have been aimed toward recruitment of minorities. Significant financial resources are required to recruit and tissue type additional volunteer donors. METHODS: Population genetics models have been constructed to project likelihoods of finding a human leukocyte antigen (HLA)-matched donor for patients of various racial/ethnic groups. These projections have been made under a variety of strategies for expansion of the NMDP Registry. Cost-effectiveness calculations incorporated donor unavailability and other barriers to transplantation. RESULTS: At current recruitment rates, the probability of an available HLA-A,B,DRB1 matched donor is projected to increase from 27% to 34%; 45% to 54%; 75% to 79%; and 48% to 55%, for blacks, Asians/Pacific Islanders, whites and Hispanics, respectively, by the year 2007. Substantial increases in minority recruitment would have only modest impacts on these projections. These projections are heavily affected by donor availability rates, which are less than 50% for minority volunteers. CONCLUSIONS: Continued recruitment of additional volunteers can improve the likelihood of finding an HLA-matched donor, but will still leave significant numbers of patients of all racial/ethnic groups without a match. Efforts to improve donor availability (especially among minorities) and to increase the number of patients with access to the NMDP Registry may prove to be more cost-effective means of increasing transplants.

Genetics, Population↗

Ethnic differences in donation-related characteristics among potential hematopoietic stem cell donors.

BACKGROUND: Although the National Marrow Donor Program has been highly successful at recruiting ethnic minorities as potential hematopoietic stem cell donors, there have been no systematic investigations of whether donor characteristics that might be linked to the donation experience vary by ethnicity. METHODS: Questionnaires assessing four domains-demographic, volunteer-related, general psychosocial, and donation-related-were mailed to potential donors after they were contacted as a preliminary match for a patient and had agreed to donate. In all, 1,679 potential donors completed and returned a predonation questionnaire. Data from potential donors belonging to five major ethnic groups were analyzed; white, black, Asian/Pacific Islander, Hispanic, and Native American. RESULTS: Bivariate analyses indicated that virtually all factors in the four domains were associated with ethnicity. Direct discriminant function analysis identified three significant functions. The most striking of the three functions indicated that Asian Americans were more highly educated, more ambivalent (reluctant about donation), more concerned (medical, work/family), and more anxious and depressed than all other ethnic groups. Key differences among other ethnic group members were also identified. CONCLUSIONS: This study provides the first evidence of ethnic group differences in key predonation variables. Findings suggest that Asian/Pacific Islanders possess a number of characteristics that are known psychosocial risk factors for less positive postdonation outcomes and that more intensive pre and postdonation contact with this group may be necessary. Strategies for improving future research in this area are discussed.

Ethnicity↗

Treatment of advanced acute leukaemia with allogeneic bone marrow transplantation from unrelated donors.

Bone marrow transplantation from a histocompatible sibling donor may produce complete remission in patients with induction failure or relapsed acute leukaemia. Through the National Marrow Donor Program, histocompatible bone marrow from unrelated donors has become available for high-risk patients. In this study we analyse the results of matched unrelated bone marrow transplant in 55 patients with highly advanced acute myelogenous and acute lymphoblastic leukaemia. 28 patients with advanced acute lymphoblastic leukaemia and 27 patients with advanced acute myelogenous leukaemia, age 2-51, were treated with high-dose chemoradiotherapy and transplantation of 6/6 HLA matched (n = 46) or one antigen mismatched (n = 9) unrelated donor bone marrow. After a median follow-up of 36 months, 13 patients remain alive 17-74 months after transplant for a 2-year actuarial disease-free and overall survival of 23 +/- 12% (median disease-free survival 3.5 months). The actuarial risk of relapse is 24 +/- 16% at 1 year. Moderate to severe graft-versus-host disease occurred in 27/47 evaluable patients (57%). Significant prognostic factors for poor leukaemia-free survival include age > 21, abnormal karyotype, and active leukaemia at the time of transplant. Other pretreatment characteristics such as gender or type of leukaemia were not significant prognostic factors. Our results show that matched unrelated bone marrow transplant for patients with advanced acute leukaemia may provide long-term leukaemia-free survival, but transplant-related complications produce a significant impact on survival with older age and adverse disease characteristics predicting for poor prognosis.

Adolescent↗

Large-scale oligonucleotide typing for HLA-DRB1/3/4 and HLA-DQB1 is highly accurate, specific, and reliable.

DNA typing of HLA class II alleles of the DRB1/3/4 and DQB1 loci using sequence-specific oligonucleotide probes and polymerase chain reaction-amplified DNA was used for the large-scale typing of donors for the National Marrow Donor Program unrelated donor registry. The results of quality control analysis for the first 7 months of the project show the typing to be highly accurate, specific, and reliable. The percent of correctly classified HLA oligotypes based on 1652 DRB1 and 1652 DQB1 assignments was greater than 99% for DRB1/DRB3/DRB4 and greater than 98% for DQB1. This level of accuracy is particularly remarkable because the quality control samples could not be distinguished from 9011 donor samples tested at the same time by the laboratories.

Alleles↗