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PubMed1996

Representation of Hispanics in the National Marrow Donor Program.

Since less than one-third of patients in need of a BMT find related donors, most patients will rely on registries of volunteer donors. For patients from minority ethnic groups the chances of finding matched unrelated donors are lower, in part due to the smaller representation of minorities in the registries. Our purpose was to determine the representation of Hispanics in the National Marrow Donor Program (NMDP), the largest registry of volunteer marrow donors in the United States. We analyzed a database provided by the NMDP that contained information on minorities. The number of Hispanic volunteer donors has increased 110-fold in the last 6 years. The proportion of Hispanics in the registry has also increased from 1.1% to 6%. Nevertheless, the proportion of Hispanic patients that received unrelated marrow transplants facilitated by the NMDP has increased only from 2.8% to 3.9% since 1989. Only 19.7% of the formal searches initiated by Hispanic patients resulted in transplants compared to the 30.4% observed in the Caucasian population. Despite increments in the number and proportion of Hispanic volunteer donors, the proportion of Hispanics that receive BMT from unrelated donors remains low. We conclude that, in addition to increased recruitment efforts, other strategies will be necessary in order to find enough marrow donors to meet the needs of the Hispanic population.

Bone Marrow Transplantation↗
PubMed2000

The extent of HLA class II allele level disparity in unrelated bone marrow transplantation: analysis of 1259 National Marrow Donor Program donor-recipient pairs.

A comprehensive analysis of the HLA-D region loci, DRB1, DRB3, DRB5, DQA1, DQB1, DPA1 and DPB1, was performed to determine allelic diversity and underlying HLA disparity in 1259 bone marrow recipients and their unrelated donors transplanted through the National Marrow Donor Program. Although 43.0% of DRB1 alleles known to exist at the beginning of the study were found in this predominantly Caucasian transplant population, a few alleles predominated at each locus. In recipients, 67.1% of DRB1 alleles identified were one or two of six common DRB1 alleles. Only 118 (9.4%) donor-recipient pairs were matched for all alleles of DRB1, DQA1, DQB1, DPA1 and DPB1. While 79.4% of the pairs were matched for DRB1, only 13.2% were matched for DPB1 alleles. Almost 66% of pairs differed by more than one allele mismatch and 59.0% differed at more than one HLA-D locus. DQB1 was matched in 85.9% of DRB1-matched pairs. In contrast, only 13.9% of the pairs matched for DRB1, DQA1 and DQB1 were also matched for DPA1 and DPB1. This database, highlighting the underlying HLA disparity within the pairs, forms the foundation of an ongoing study to establish the relationship between HLA matching and successful outcome in unrelated allogeneic stem cell transplant.

Alleles↗
PubMed1989

The National Marrow Donor Program: how it works, accomplishments to date.

As the use of bone marrow transplantation increases, the lack of a suitable matched sibling donor for approximately 60% of patients is a growing problem. Recently, marrow transplantation has been done successfully using HLA-matched unrelated donors. In an effort to provide more donors, the National Marrow Donor Program (NMDP) was established. It involves 50 blood banks and 20 marrow transplant centers throughout the United States. More than 20,000 HLA-typed apheresis donors from these blood banks have agreed to be listed in the NMDP registry. A preliminary search for donors has been carried out for 1,116 patients. Donors suitably matched for HLA-A and B antigens were located for 99% of the patients.

Bone Marrow Transplantation↗
PubMed2001

Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program.

Human leukocyte antigen (HLA)-identical sibling bone marrow transplantation is an effective treatment for Wiskott-Aldrich syndrome. However, most children with this disease lack such donors and many patients receive transplants from alternative donors. This study compared outcomes of HLA-identical sibling, other related donor, and unrelated donor transplantation for Wiskott-Aldrich syndrome. The outcome of 170 transplantations for Wiskott-Aldrich syndrome, from 1968 to 1996, reported to the International Bone Marrow Transplant Registry and/or National Marrow Donor Program were assessed. Fifty-five were from HLA-identical sibling donors, 48 from other relatives, and 67 from unrelated donors. Multivariate proportional hazards regression was used to compare outcome by donor type and identify other prognostic factors. Most transplant recipients were younger than 5 years (79%), had a pretransplantation performance score greater than or equal to 90% (63%), received pretransplantation preparative regimens without radiation (82%), and had non-T-cell-depleted grafts (77%). Eighty percent received their transplant after 1986. The 5-year probability of survival (95% confidence interval) for all subjects was 70% (63%-77%). Probabilities differed by donor type: 87% (74%-93%) with HLA-identical sibling donors, 52% (37%-65%) with other related donors, and 71% (58%-80%) with unrelated donors (P =.0006). Multivariate analysis indicated significantly lower survival using related donors other than HLA-identical siblings (P =.0004) or unrelated donors in boys older than 5 years (P =.0001), compared to HLA-identical sibling transplants. Boys receiving an unrelated donor transplant before age 5 had survivals similar to those receiving HLA-identical sibling transplants. The best transplantation outcomes in Wiskott-Aldrich syndrome are achieved with HLA-identical sibling donors. Equivalent survivals are possible with unrelated donors in young children.

Actuarial Analysis↗
PubMed2003

Unrelated donor stem cell transplantation: the role of the National Marrow Donor Program.

Since its founding in 1986, the NMDP has facilitated more than 16,000 transplants for patients with blood disorders such as leukemia and aplastic anemia, as well as immune system disorders and genetic disorders. The donors who provided the blood stem cells for these transplants came from the NMDP Registry, the world's largest and most diverse registry of potential blood stem cell donors. Initiating a search of the NMDP Registry for an HLA-matched unrelated donor is as simple as submitting to the NMDP a patient's HLA typing results along with basic demographic and disease information. If a suitable donor is identified, the NMDP coordinates the steps needed to bring the donated stem cells--whether they be marrow, PBSC, or cord blood--to a patient. After reading this article, physicians should have a greater understanding of the complicated process needed to bring about an unrelated donor stem cell transplant. A better understanding of the role the NMDP plays in unrelated donor stem cell transplantation reduces the chances that physicians and patients will have unrealistic expectations about the process. To initiate a preliminary search of the NMDP Registry, contact the NMDP Office of Patient Advocacy toll-free at 1-888-999-6743. A preliminary search reqest form can also be submitted via the NMDP website:www.marrow.org

Blood Specimen Collection↗
PubMed2001

Effect of HLA class II gene disparity on clinical outcome in unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia: the US National Marrow Donor Program Experience.

The clinical importance of HLA class II gene disparity in unrelated stem cell transplantation is not entirely known. The impact was evaluated of matching donors and recipients for HLA-DR, HLA-DQ, and HLA-DP genes on clinical outcome after stem cell transplantation for chronic myeloid leukemia (CML) performed between 1988 and 1997. HLA-DRB1, -DQA1, -DQB1, -DPA1, and -DPB1 alleles were identified in 831 transplant pairs using a combination of sequence-specific oligonucleotide probes, sequence-specific priming, and sequencing methods. Among the 831 pairs, 696 (84%) were HLA-A and -B serologically matched; of these, 565 (81%) were also matched for HLA-DRB1. HLA-DRB1 matching correlated with significantly improved survival (relative risk [RR], 1.29 [95% confidence interval (CI), 1.02-1.64; P =.04]) independently of HLA-DQA1 or HLA-DQB1 (RR, 1.01 [95% CI, 0.81-1.26; P =.94]) and HLA-DPA1 or HLA-DPB1 (RR, 1.11 [95% CI, 0.84-1.48; P =.46]). Single-locus HLA-DQ or HLA-DP disparity was not associated with significantly poorer survival. For patients who underwent transplantation in the first chronic phase (CP) from HLA-A, B matched donors, the presence of DRB1 allele mismatching was independently associated with increased incidence of grades III-IV acute graft-versus-host disease (GVHD). No significant associations of class II allele mismatching with risk for delayed engraftment or chronic GVHD disease were detected. This study clearly demonstrates the importance of precise matching of HLA-DRB1 alleles for successful transplantation. Furthermore, a good-risk population of patients whose transplantations were performed in the first CP of disease from HLA-A, B, DRB1 matched unrelated donors can be shown to have superior survival.

Alleles↗
PubMed1995

Unrelated-donor marrow transplants: the experience of the National Marrow Donor Program.

As of January 1996, more than 4,000 marrow transplants have been performed using unrelated donors provided by the NMDP. With more than 1.9 million donors listed in the registry, over 70% of patients now find an HLA-A, -B, -DR phenotypic match at the initial search. The success rate is dramatically lower for patients in racial minorities. For instance, African-Americans find donors only 34% of the time on the initial search. Analysis of the first 462 transplants, showed disease-free survival rates at 2 years to be approximately 40% in low-risk patients, and 20% in high-risk patients. A more recent analysis in single centers shows an increase in the probabilities to 60-70%. This increase in success is likely related to a number of factors, including the ability to control complications, such as GVHD, plus an increase in accuracy of HLA typing primarily based on DNA-based methodology.

Bone Marrow Transplantation↗
PubMed1994

The changing activities of a regional marrow donor program.

BACKGROUND: A regional marrow donor program was established in 1982. Following the establishment of the National Marrow Donor Program (NMDP) in 1987, the activities of this regional program changed. STUDY DESIGN AND METHODS: To better understand the changes that occurred in the regional marrow donor program, its donor recruitment and marrow collection activities through 1991 were studied retrospectively. Data analyzed included the total number of potential donors, the number and types of potential donors recruited each year, the number of searches performed, the number of samples collected for HLA-DR typing and mixed lymphocyte culture testing, and the number of transplants in both programs from 1987 through 1991. Statistical analysis was performed by using chi-square. RESULTS: Initially, only persons who donated platelets by apheresis were enrolled into the program. In 1986, the regional program's first drive to recruit people who were not apheresis donors occurred. The number of such drives increased each year, and in 1991, 12 drives occurred, which resulted in the recruitment of 1313 potential marrow donors. From 1987 to 1991, the number of potential donors in the regional program grew from 3252 to 9146, but the proportion of apheresis donors in the program decreased. In 1987, 91.9 percent of marrow donors at the regional center had been apheresis donors, but in 1991, 41.7 percent had been apheresis donors. The number of marrows donated at the regional center increased from 11 in 1987 to 29 in 1989, but then fell to 24 per year in 1990 and 1991. The decrease in the number of donations at the regional program was due to the rapid growth in the NMDP file of potential marrow donors and the selection of donors whose HLA antigens were more compatible with those of the transplant recipients. In 1989, the regional program contained 4.6 percent of all HLA-A,B-typed and 11.2 percent of all HLA-A,B,DR-typed potential donors in the NMDP and collected 15.3 percent of all marrows. However, in 1991, the regional program contained 2.0 percent of HLA-A,B-typed donors and 4.1 percent of HLA-A,B,DR-typed donors and collected 5.3 percent of marrows. In 1987, 18 percent of the people who donated marrow at the regional center were phenotypically HLA-A,B,DR identical with the recipient, but in 1991, 92 percent of donor-recipient pairs were phenotypically HLA-A,B,DR identical. CONCLUSION: Recruitment activities became an increasingly larger part of the Regional Marrow Donor Program's activities. Increasing the size of the file of potential donors was necessary to maintain a constant number of donations. Persons who were not regular blood donors were an important part of the marrow donor program.

Blood Donors↗