Review

Bone Marrow Transplantation (2008) 42, S3–S5; doi:10.1038/bmt.2008.102

The US National Marrow Donor Program role in unrelated donor hematopoietic cell transplantation

D Confer1 and P Robinett1

1The University of Minnesota and Membership Services, National Marrow Donor Program (NMDP), Minneapolis, MN, USA

Correspondence: P Robinett, National Marrow Donor Program, 3001 Broadway St. N.E., Suite 500, Minneapolis, MN 55413, USA. E-mail: probinet@nmdp.org

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Abstract

The National Marrow Donor Program® (NMDP) is headquartered in Minneapolis, Minnesota, USA. Established in 1986, the NMDP currently operates the world's largest registry of unrelated adult donors and umbilical cord blood (UCB) units. Since its inception, the NMDP has benefited from continuous financial support provided by the US government through a series of contracts and grant awards. This funding has supported a large network of donor centers and the recruitment of millions of potential adult hematopoietic cell (HC) donors. More recently, the federal government has also supported a national registry for UCB units and expansion of the available UCB inventories. Today, the NMDP registry lists more than 6.7 million adult donors and 68000 UCB units. Seventy-seven percent (5.2 million) of the adult donors and virtually all of the UCB units are fully typed for HLA A, B and DR. An additional 5 million donors are available for search through international collaborations. The NMDP currently facilitates more than 3600 recipients each year totaling more than 29000 transplants since 1987.

Keywords:

NMDP, registry, UCB

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NMDP history and status

The National Marrow Donor Program® (NMDP) is headquartered in Minneapolis, Minnesota. It was established in 1986 through the combined efforts of families and physicians whose goal was a US national registry of adult, volunteer unrelated hematopoietic cell (HC) donors. Initial funding was provided through a grant to the American Red Cross. The history of NMDP's development has been recently reviewed.1

Currently, the NMDP receives contracts from the US federal government to operate the CW Bill Young Cell Transplantation Program. This new program, named after Congressman Young who has been an ardent supporter of unrelated donor HCT and the NMDP, continues congressional support for a national BM donor registry and additionally calls for the development of enhanced capabilities to provide UCB units for transplantation. Funding provided under these contracts allows for the continued recruitment and support of adult donors as well as the collection, processing and storage of UCB units. The contracts further specify requirements for the identification and delivery of HC grafts, support of patients and the collection of comprehensive donor and recipient outcome data.

In fulfillment of its mission and the government mandates, the NMDP functions as a network of participating organizations that perform the various functions involved in facilitating unrelated donor HC transplantation (HCT). The organizations include donor centers, which currently number 73 and are involved in the recruitment and subsequent management of adult volunteer donors. Donor centers are assisted in their recruitment efforts by 10 recruitment groups, which focus upon targeted recruitment within the US racial and ethnic minority populations. When an adult donor is matched with a recipient and a transplant occurs, the donor will donate either BM or PBSC, depending upon the wishes of the transplant physician. PBSC have been collected since 1999 and currently comprise nearly 70% of adult donor donations. BM collections occur at collection centers, which currently number 97, while PBSC collections occur at apheresis centers, which number 89. Twenty-four CB banks, which collect, store and manage UCB units, are currently participating with the NMDP. Transplant centers, which number 169, are typically based at major universities or large private hospitals. Among the many participating organizations are several headquartered outside the US, including seven donor centers and 43 transplant centers. To further facilitate the international exchange of HC products, the NMDP has established formal cooperative registry relationships with 26 organizations. The NMDP is an accredited registry of the World Marrow Donor Association (WMDA) and a supporter of Bone Marrow Donors Worldwide (BMDW).2, 3, 4

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NMDP activity

Each month, the NMDP receives over 1200 search requests for new patients. However, not all of these searches result in a ‘formal search,’ which is a request for additional testing (typically high-resolution HLA typing) from the donor or UCB unit. Not all formal searches result in a transplant either; currently, NMDP facilitates just over 300 transplants per month (Figure 1). There has been steady growth in the number of transplants facilitated by NMDP averaging more than 10% annually for the past several years. Estimates show that the number of potential HCT candidates in the United States alone is at least three times the current number of recipients, which suggests continued annual growth for the foreseeable future.

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Annual transplants from the unrelated donors facilitated by the National Marrow Donor Program since its inception. Annual figures are by fiscal year (October–September) and include products collected outside the United States of America and imported, as well as those collected within the United States of America and exported. Before July 1999, only BM was used for initial transplantation, but PBSC were available in the setting of retransplantation. Stippled bars—BM, solid bars—PBSC and open bars—umbilical cord blood units. 2007 numbers are estimated.

Full figure and legend (73K)

The most common diseases for which unrelated donor HCT is chosen are AML, ALL, myelodysplastic syndrome, non-Hodgkin's lymphoma and CML. There has been an increase in the use of unrelated transplants performed for acute leukemias and myelodysplastic syndrome, coupled with a decline for CML. CML was previously the most common diagnosis of unrelated HCT recipients, but transplants for CML have declined by about half since the introduction of tyrosine kinase inhibitors, such as imatinib. Another trend that has occurred is an increase in the percentage of older adults who are HCT recipients. In the late 1990s, less than 5% of HCT recipients were more than 55 years of age, but currently this age group comprises more than 20% of the total recipient population.

As shown in Figure 1, graft source selection for unrelated HCT has also changed dramatically over time. For the first 10 years of its operation, the NMDP facilitated only BM collections. The capacity to administer growth factors for mobilization and the collection of PBSC was developed by NMDP in 1999. Since that time, PBSC has become the preferred HCT graft source in the eyes of transplant physicians. In contrast to the sibling setting, NMDP data have failed to show any clear advantages for unrelated donor PBSC.5, 6 An additional study by Eapen et al.,7 demonstrated higher mortality among children who were recipients of unrelated donor PBSC grafts compared with BM. These observations led the US Blood and Marrow Transplant Clinical Trials Network (BMT CTN) to initiate a randomized comparison of BM vs PBSC in unrelated donor HCT. The trial has accrued more than 320 donor–recipient pairs en route to its target of 550. Accrual is expected to be completed in 2009. Also shown in Figure 1 is the rapid growth in UCB HCT. Currently, UCB recipients comprise 17% of all NMDP-facilitated transplants. On account of the increasing use of double UCB transplant protocols, UCB units represent 20% of all grafts procured by NMDP.

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NMDP donor and cord blood unit recruitment

Not only has the number of transplants continued to increase in the past 20 years, but also the number of unrelated donors available on the registry has risen as well. The NMDP accepts donors in good health between the ages of 18 and 60 years to join the registry, although transplant centers prefer to select younger male donors. The NMDP expected to recruit 350000 new adult donors in 2007. Increasing emphasis is being placed on recruitment within the US racial and ethnic minority populations; these donors were expected to comprise nearly half of the new recruits in 2007. Each newly recruited donor is typed at the intermediate level for HLA-A, B and DRB1. Most donors now need only to provide a buccal swab sample for DNA-based testing rather than a blood sample. Buccal swabs from donors are stored for further testing as necessary, and have significantly reduced the effort and cost of donor recruitment.

Most donors join the NMDP Registry as a result of community donor drives, as opposed to donors who are recruited at blood centers. NMDP donor centers and recruitment groups plan and conduct hundreds of drives each month.

Although all newly recruited donors are HLA DRB1-typed at recruitment, there remain about 1.6 million donors who joined the NMDP in the early years that have been typed only for HLA A and B. This group of donors is functionally inactive because analysis shows that 99% of all transplants that NMDP currently facilitates utilize a donor who is selected from the A, B and DRB1-typed pool.

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The search process

The process for identifying an unrelated donor or UCB starts with the transplant center. Each transplant center designates a transplant coordinator to be the primary communicator with the NMDP. The coordinator submits a search request through NMDP TRANS Link (described below) or through facsimile (fax) request. The request includes the age and diagnosis of the patient as well as the highest resolution of HLA typing available. This information is used to immediately search the 6 million NMDP donors and for an overnight search of several international registries. NMDP has published recommendations about how to search for adult BM donors, and a similar set of recommendations concerning UCB units is in preparation.8

NMDP provides software to transplant centers (TRANS Link®) that allow real-time searching of the complete NMDP inventory of adult donors and UCB units. TRANS Link produces a donor/UCB list that is sorted with the best of the potential donors/UCB at the top. Within HLA match grades, UCB is prioritized according to total nucleated cell content, whereas adult donors are prioritized by HLA-matching likelihood alone. An NMDP innovation called HapLogicSM predicts the likelihood of allele-level matching based on calculated HLA haplotype frequencies within major racial and ethnic populations.9 Currently, HapLogic predicts high-resolution matching at HLA A, B and DRB1, but a future release in active development will also consider HLA C and DQ. TRANS Link allows the user to further customize the search results by prioritizing specific HLA loci or donor/UCB characteristics (age, sex, CMV status and so on). Currently, using TRANS Link requires that a software program be installed on the user's computer that accesses the NMDP databases through the Internet. A future release of NMDP-matching software will allow access through a standard www browser interface (for example, Internet Explorer, Firefox).

Although the NMDP lists more than 1.5 million non-US donors from its participating international donor centers in the upfront TRANS Link search, an additional 5 million non-US donors are accessible only through cooperative registry agreements. Searching for a match among these donors is more cumbersome and difficult. BMDW provides its online search as a convenient way to target registries for further inquiries, so NMDP automatically searches BMDW with every new search submission.2 Several registries, including NMDP, also automatically exchange donor and UCB search information using the messaging protocol, EMDIS (European Marrow Donor Information System, www.zkrd.de/emdis.html). For registries that have not implemented EMDIS, the searching process is largely manual, involving facsimile transmissions and e-mail messages.

The donor search process typically takes 3 months from the time the unit or donor is selected for additional testing to the date the transplant occurs. Some searches have taken as little as 2 weeks, but other searches may involve the testing of several CB units or donors and may take several months.

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Research

The NMDP believes that research is essential for improving the outcomes of unrelated donor HCT. Controlling the complications of unrelated donor HCT (regimen-related toxicity, graft failure, acute and chronic GVHD) and preventing disease recurrence are the goals of carefully designed and conducted research projects. In 2004, the NMDP merged its research activities with the International Bone Marrow Transplant Registry (IBMTR) in Milwaukee, Wisconsin. The new research organization was dubbed the CIBMTR (Center for International Blood and Marrow Transplant Research) with a mission to conduct observational and interventional research in transplant outcomes, health services, immunobiology of transplantation and statistical methodologies. CIBMTR and NMDP jointly participate in the operation of the data coordinating center for the US national HCT clinical trials network, BMT CTN. In addition, CIBMTR has created a division for supporting smaller clinical trials to supplement the opportunities available through BMT CTN. Websites that present research information relevant to NMDP are www.cibmtr.org, www.bmtctn.net, www.nmdpresearch.org and bioinformatics.nmdp.org.

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Summary

In summary, the NMDP continues to grow and expand, seeking to facilitate more transplants, to improve the success of transplantation, to increase the number of transplant options available for each patient and to provide the best possible graft at precisely the right moment. These goals will be met through continued recruitment of high-quality HLA-diverse donors and UCB units, through improved processes that facilitate worldwide real-time communications and through a comprehensive program of carefully designed research initiatives.

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Conflict of interest

Neither author declared any financial interests.

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References

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