Approximately 70% of patients with life-threatening diseases treatable with allogeneic blood stem cell transplantation do not have matched related donors. The National Marrow Donor Program (NMDP) was established in 1986 to provide human leukocyte antigen (HLA)-matched, volunteer unrelated donors for these patients. The NMDP performs this task by maintaining a registry of more than 4.9 million volunteer donors of marrow and peripheral blood stem cells (PBSC) and 12 cord blood banks containing more than 25,000 units of umbilical cord blood. Background The NMDP is a nonprofit organization that operates the congressionally mandated National Bone Marrow Donor Registry under contract from the Health Resources Services Administration, a division of the US Department of Health and Human Services. The NMDP Registry is the largest, most diverse registry of potential hematopoietic stem cell donors in the world. To carry out its mission of providing HLA-matched stem cells for patients, the NMDP operates a worldwide network of medical organizations that cooperate together to locate, procure, and transport stem cells to waiting patients. The wide range of medical organizations in the NMDP network are shown in Table 1. The NMDP also provides resources for patients and physicians, collects patient outcome data, and conducts research to improve the outcomes of stem cell transplantation. A graphic representation of the NMDP network is shown in Figure 1. The national coordinating center of the NMDP, located in Minneapolis, Minnesota, houses the computerized NMDP registry of unrelated stem cell donors, including data on the inventories of NMDP-affiliated cord blood banks. Searches of the NMDP Registry for HLA-matched donors or umbilical cord blood units are accomplished through secure electronic communications between the NMDP and its network of donor centers, apheresis centers, collection centers, transplant centers, and HLA laboratories. The NMDP Registry
Stem cell transplants, whether related or unrelated, require precise HLA matching between donor and patient. Because HLA antigens are inherited, patients are more likely to find a matching donor within their own racial or ethnic communities. To provide patients of every ethnic community a better chance at finding a matched donor, the NMDP has ongoing recruitment programs to bring more African-American, American Indian/Alaska Native, Asian/Pacific Islander, and Hispanic donors to the NMDP Registry. Currently, approximately 31% of the volunteer donors listed in the NMDP Registry are from racial and ethnic minority groups. NMDP Cord Blood Program
The NMDP currently lists more than 25,000 units of donated umbilical cord blood from a growing partnership with cord blood banks. The addition of cord blood banks to the NMDP Network was vital to provide more transplant options for patients. All cord blood units at NMDP cord blood banks are listed in the NMDP Registry and are automatically included in every patient search. The NMDP's cord blood program is a clinical trial developed in 1998 under an Investigational New Drug application (IND) with the US Food and Drug Administration (FDA). The NMDP continues to work with existing cord blood banks to establish new contacts and list more cord blood units in the NMDP Registry. NMDP Office of Patient Advocacy
The NMDP's Office of Patient Advocacy (OPA) works with patients to remove barriers to obtaining an unrelated donor transplant. The OPA connects patients to transplant-related resources, helps patients find a transplant center, and assists them with financial and insurance matters. In addition, the OPA assists patients, their families, and physicians with any concerns or questions they may have regarding an NMDP-facilitated search and stem cell transplant. NMDP Research Program
The NMDP collects detailed medical data on patients who receive a transplant from an NMDP donor. These data are part of a comprehensive research database the NMDP maintains to assist medical researchers in the field of unrelated stem cell transplantation. The NMDP research program develops and promotes research aimed at increasing opportunities for and improving outcomes of unrelated donor stem cell transplants. NMDP resources available to researchers include:

• The largest database of HLAtyped individuals in the world (more than 4.9 million volunteer donors).
• Outcome, histocompatibility data, donor search, and donation sideeffects data on approximately 90% of the more than 16,000 unrelated donor stem cell transplants the NMDP has coordinated since 1987.
• The largest unrelated stem cell donor and recipient HLA database in the world (more than 7,600 paired samples).

The NMDP, in collaboration with the International Bone Marrow Transplant Registry (IBMTR) and the EMMES Corporation, recently received a 5-year NIH grant to coordinate a newly established Blood and Marrow Transplant Clinical Research Network. Funding for this network is being provided by both the National Heart, Lung and Blood Institute and the National Cancer Institute. When the network begins operations, a data coordinating center will manage a national network of centers performing clinical trials focused on hematopoietic stem cell transplantation. Additional goals of the network include developing consensus guidelines for diagnosing, monitoring, and grading important transplant-related end points, and the development and use of novel study designs to increase the efficiency and scientific validity of clinical trials in blood and marrow transplantation. The NMDP and Unrelated Donor Stem Cell Transplantation Approximately 75% of the stem cell transplants facilitated by the NMDP are for patients with some form of leukemia. Indications for unrelated donor stem cell transplant are constantly changing. Since 1999, NMDP-facilitated transplants for adults with acute myelogenous leukemia have increased 66%, and transplants for myelodysplastic syndromes have increased by 50%. Since the development of imatinib(Drug information on imatinib) mesylate (Gleevec) to treat chronic myelogenous leukemia (CML), NMDP-facilitated transplants for CML have decreased by 45%. Current research is exploring the use of reduced-intensity (nonmyeloablative) regimens in allogeneic stem cell transplantation. This has resulted in an increase in the number of stem cell transplants for non-Hodgkin's lymphoma, multiple myeloma, and hemoglobinopathies such as sickle cell disease.[1,2] Researchers are also investigating the use of stem cell transplantation in breast cancer[3,4] and renal cell carcinoma.[3,5] Table 2 shows the diseases for which unrelated stem cell donor transplants have been performed by transplant centers in the NMDP Network Obtaining an NMDP-Facilitated Stem Cell Transplant Initiating a preliminary search of the NMDP Registry to locate an HLAmatched donor or umbilical cord blood is free and available to any physician. Interpreting the results of a preliminary search and efficiently moving forward through the many steps to a transplant requires an understanding of the clinical aspects of stem cell transplantation and knowledge of the operations of the NMDP. The HLA System
Lymphocytes differentiate between self and nonself cells by examining the HLA antigens expressed on the surface of cells. To prevent graft rejection and other posttransplant complications, stem cell donors and recipients must be closely HLA matched.[6] The HLA antigens are encoded on the short arm of human chromosome 6, on a segment called the major histo- compatibility complex (MHC). There are 3.5 million bases in the MHC, but only a small number are currently matched in stem cell transplantation. The relevant portions of the MHC are further divided into two regions- class I and class II. Class I antigens (HLA-A, -B, and -C) and class II antigens (HLA-DRB1, -DP, and -DQ) are the antigens most frequently examined when matching potential stem cell donors and transplant recipients. The NMDP requires that donors and patients have no more than a one-antigen mismatch at the HLA-A, -B or -DRB1 locations. Because there are two HLA antigens at each of these three locations, a perfect match is referred to as a 6 of 6 match, and a one-antigen mismatch is termed a 5 of 6 match. Using this terminology, the NMDP will allow a 5/6 match or a 6/6 match for marrow and peripheral blood stem cell transplants, but not a 4/6 match or less. The NMDP will allow a 4/6 match for cord blood transplants, provided the mismatched antigens are not at the same loci. This less stringent HLA matching for cord blood is permitted because of the lowered immunologic competence of cord blood T cells.[7-9] Some transplant centers require additional matching at the HLA-C, -DP, and/or DQ loci. Newer DNA-based methods of HLA typing have proven to be more accurate than serologic methods and have largely superseded them.[10] Impact of HLA Match on Transplant Outcome
In allogeneic stem cell transplantation, the degree of donor/recipient HLA match is an important factor in engraftment, the development of graftvs- host disease (GVHD), and overall survival.[11,12] The association of HLA class I allele disparity with graft failure was examined by the Seattle group, who retrospectively analyzed data from 21 patients experiencing graft failure and 42 case-matched controls. Complete allele- level matching for class I was identified in 45% of controls and 10% of graft failure cases.[13] The effect of the number of HLA disparities was subsequently studied in unrelated- donor stem cell transplant for CML patients. Among allele-matched donors/recipients and donors/recipients mismatched for a single class I allele, the graft failure rate was 2%. When two or more class I disparities at HLA-A, -B, and/or -C were present, the graft failure rate increased to 29%.[14] In unrelated-donor stem cell transplantation, the risk of clinically significant GVHD is also influenced by the extent of HLA disparity between the donor and recipient. GVHD is a potentially life-threatening complication involving an immunologic reaction in recipients that is mediated by the transplanted T cells.