Allogeneic stem cell transplant is the best, and occasionally the only, curative treatment option for certain cancers. For these patients, a timely search for the best available stem cell donor can be life-saving.
The goal of selecting a stem cell donor is to provide the best “match” between the donor and the patient (host). The body’s immune defense system consists of white blood cells that travel continuously throughout the body in surveillance of foreign substances or cells. They destroy what they perceive as “non-self”. When donor stem cells are transplanted into a new host, several donor-host interactions may occur. On one end of the spectrum, the host’s immune system may reject the donor’s cells (i.e., graft rejection or failure). On the other end, the donor’s cells may attack (reject) the recipient’s tissues in what is called graft-versus-host reaction.
Cells have surface antigens that can recognize and reject foreign tissues. These are called human leukocyte antigens or HLAs. Donors are selected on the basis of blood testing (tissue typing) for HLA antigens. The major HLA antigens determine tissue compatibility and are located on the 6th chromosome. Four sets of HLA antigens have so far been identified: A, B, C, D. To ensure the best possible acceptance of donor stem cells, it is best to match all of the four HLA antigen sites.
HLA-Matched Family Members
Originally, donor and recipient were exclusively siblings who had inherited the identical 6th chromosomes from the father and mother. In this situation, all of the HLA antigens (and all other antigens) located on the 6th chromosome are identical between donor and recipient. However, in some instances a parent can be matched with a child or a child with a parent. In addition, if the mother and father have similar HLA antigens siblings can be a suitable matches without inheriting the same 6th chromosome. It is therefore important to test blood samples from the entire immediate family ,i.e., parents, siblings and children.
More recently, there has been considerable success in using unrelated individuals as bone marrow or blood stem cell donors. An unrelated donor is obtained by a computerized search carried out by the National Marrow Donor Program (NMDP), which is sponsored by the National Institutes of Health. This search is initiated by the transplant center that will provide your treatment. You can get an immediate estimate of the probability of finding a donor for a given patient by using the “World Book,” which is a registry of all of the potential donors in the NMDP plus all of the other international unrelated donor banks. Your HLA type is submitted to this service by your transplant center at no cost and the number and location of potential donors is immediately available. This is helpful at the outset, as it provides you with important information about the likelihood of finding a donor and how long it will take.
Once potential donors are identified by the NMDP, detailed blood testing has to be performed to confirm compatibility between donor and recipient. This requires obtaining blood samples from the patient and the prospective donor. Some donors will turn out not to be compatible on more extensive testing and some donors may be more compatible than others. This extensive testing makes identification of a donor a much longer procedure than that necessary to identify a family member donor.
The National Marrow Donor Program was established in the mid-1980’s and had less than 250,000 donors in 1990. As of January 1998, more than 3 million donors were listed in the registry and over 7,000 marrow transplants have been performed using unrelated donors provided by the NMDP. With the current number of donors in the registry, more than 70% of patients are able to find a suitable match. Donor identification is significantly lower for patients in racial minorities. For example, the identification of a potential donor for African-Americans is less than 35%. Similar results are observed in other minorities. The relative difficulty in identifying potential donors for minority population has more to do with genetic diversity than with donor participation. For example, in Japan, a nation relatively geographically isolated, it is estimated that it would only require 100,000 individuals to provide 90% of the population with a donor. In contrast, if all African-Americans were to enroll in the NMDP, only 50% would have suitable donors.
One limitation of the NMDP is the time it takes to locate a donor. The median time from initiation of a search to donor identification is now approximately 10 weeks, which is an improvement from the 6-month searches of the past. Therefore, it is important to initiate a search early in the disease course, especially for diseases that are rapidly progressive, such as the acute leukemias. Donors can be found more rapidly for patients with common HLA types than for patients with less common HLA types. Sometimes it is helpful to do a quick survey of donor availability by performing a “World Book” search as mentioned above. For more information about the NMDP, visit www.marrow.org
Umbilical Cord Blood
Human umbilical cord blood is a rich source of the stem and progenitor cells that are present in bone marrow. Cord blood from related donors has been successfully transplanted in many children worldwide. In addition, cord blood from unrelated donors has recently been successfully transplanted into children. However, there is still controversy over use in adults due to the relatively small number of cells infused per kilogram of body weight. Recent studies suggest that cord blood can be “expanded” in culture and can be used for adult transplants. In general, cord blood is utilized when no suitable family member or unrelated donor is available. Parents can also have the cord blood cryopreserved at the time of delivery of a child. This has been useful when a prior child has a disease treatable by marrow or blood tem cell transplantation and there is no other donor available.
Umbilical cord blood is cryopreserved in “cord blood banks”. HLA typing is performed and available for computer matching in the same way that the NMDP performs unrelated donor searches. Approved transplant centers are provided with the frozen cells when needed.
Currently the majority of units of cord blood has been provided by the New York Blood Center, which is funded by the National Heart Lung and Blood Institute (NHLBI). Participating Centers in the NHLBI study include the Dana Farber Cancer Research Center; the Fred Hutchinson Cancer Research Center, Seattle, WA; the University of California (UCLA) in Los Angeles; Children’s Hospital of Orange Co. Orange, CA; Indiana University, Indianapolis, IND; Duke University Medical Center, Durham NC; and the University of Minnesota, Minneapolis.
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