Dear Suzieq, The post below has been posted on two other support groups and is long as I have included the very informative article from BMTInfonet as well. Read at your leisure and ask any questions you have.
Best Wishes, Anjana caregiver to Roy Basically, Human Leukocyte Typing or HLA typing is also called tissue typing. There are cells in our body which have specific proteins called antigens and these proteins signal to our immune system to recognize the cells as our own and not foreign. However, when our own cells are killed in a BMT, and new donor cells are infused, these have to be exactly matched in these protein antigens. If they are not, then 2 things can happen: 1. The host cells recognize the donor cells as "foreign" and reject the donor graft. This is called graft rejection. 2. The donor cells recognize the host organs and tissues as "foreign" and begin attacking them giving rise to graft versus host diseases (GVHD) which can sometimes be fatal. Therefore, if there is a perfect match between HLAs of donor and recipient, this will prevent graft rejection and GVHD. There are basically 5 types of HLA: HLA-A, HLA-B, HLA-C, HLA-DR1 and HLA-DQ1. And you get a set from both parents. So, if there is a perfect match in all 5, it is a 10/10 match. With unrelated transplants, doctors will look for a 10/10 match. For sibling transplants, it is okay to go with a 6/6 match at HLA-A, HLA-B and HLA-DR1 as most antigens between siblings are inherited. It will cost more to match at all the major AND minor antigens since a high-resolution mapping is done. For siblings, it will cost less because a low resolution mapping is done. The more the mismatch, the more chances of rejection and GVHD. Therefore, our doc recommended in the case of Roy to do a high-resolution tissue typing since he would always be looking for unrelated transplant. It cost about 1000 over dollars here. The way the donor search is done by the NMDR is described below but look to see they are looking for matches at all 5 antigens, at least as in a 10/10 match. CMV is cytomegalovirus which is a virus that can infect normal people and remain in our body without harming us. However, in a person without immunity as in a patient post-SCT, CMV can reactivate and can be fatal. Don't worry, there are drugs to treat it but nevertheless, you kind of do not want CMV. The symptoms of CMV can be pneumonitis and other manifestations. The patient can be tested serologically for the CMV virus and if negative for CMV, doctors would prefer his donor to also be CMV negative. A test called the ELISA is done to find out the CMV status of patient and donor. Here are some CMV websites to learn more. www.ccm.lsuhsc-s.edu/bugbytes/Volume2/bb-v2n20.htm www.cdc.gov/node.do/id/0900f3ec80006cd2 Hope this all helps. Best Regards, Anjana www.bmtinfonet.org/newsletters/ issue53/perfectdonor.html Finding the Perfect Donor Brian Zikmund-Fisher was 28 years-old when he learned that he needed a bone marrow transplant. Diagnosed with myelodysplasia just three months before he and his wife, Naomi, were to celebrate the birth of their first child, Zikmund-Fisher began his search for an unrelated bone marrow donor. "I expected the process to be straightforward," recalls Zikmund-Fisher. "I assumed that you just checked the donor registry, identified the best few candidates, called them in to be sure, and you were done." Unfortunately for Zikmund-Fisher, the donor search process turned out to be far more complicated. Although Zikmund-Fisher's initial search of the National Marrow Donor Program Registry yielded 800 potential donors, that number quickly diminished when more sophisticated DNA-based testing revealed that most were not a suitable donor for him. It was not until 12 months later that Zikmund-Fisher found his "perfect" match. Twenty years ago, many of the rejected donors might have been deemed a suitable donor for Zikmund-Fisher. But today's technology enables doctors to detect subtle genetic differences between donors and patients-differences that can significantly influence the outcome of the transplant. For this reason, most transplant centers today no longer rely solely on the older "serological" tests that were once used to identify a suitable unrelated donor, but now use sophisticated DNA-based tests (also called molecular testing or high resolution typing) to determine whether a donor and the patient are a good match. What Are They Matching? On the surface of most of our cells lies a set of proteins called Human Leukocyte Antigens (HLA). Like a fingerprint, these proteins enable our immune system to distinguish between cells that belong in our body and cells that do not. If immune system cells encounter a cell with the wrong "fingerprint", they orchestrate an immune system attack to destroy it. Five different HLA proteins on the surface of the cells are believed to play an important role in stem cell transplantation. Each protein is made from a small section of chromosome (the genetic code everyone carries in the cells of their body) called an allele (pronounced uh-léel). The locations or loci of the alleles on the chromosome are referred to as HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1. If an unrelated donor and patient have the same two alleles at HLA-A, HLA-B, HLA-C, HLA-DR1 and HLA-DQ1, the donor is considered a "ten out of ten" or "perfect" match.¹, ² Finding a perfectly matched donor reduces the risk of developing graft rejection and acute graft-versus-host disease (GVHD). Graft rejection occurs when the patient's immune system perceives the donor's cells as foreign matter that should be destroyed. Graft-versus-host disease is a condition in which the donor's cells perceive the patient's organs and tissues as foreign material that should be destroyed. Making the Match The original method used to test whether donors and patients were HLA-matched was serological testing. Serological testing picks up differences in the HLA proteins on the surface of cells, but cannot identify the specific gene that creates those differences. Serological tests can distinguish between 28 different HLA-A genes, 59 HLA-B genes and 21 HLA-C genes. In contrast, high-resolution DNA-based tests, called allele level typing, can distinguish between hundreds of different genes that generate HLA proteins on the cell surface. But while allele level typing is more precise, it is also more time-consuming and expensive. For these reasons, some transplant centers use high resolution DNA testing only if the potential donor is unrelated. Less sophisticated DNA-based testing, called low resolution or intermediate resolution DNA testing, is often used to screen a large pool of donors. If an HLA-matched donor is identified, allele level typing is then performed. In order to speed up the search process, the National Marrow Donor Program requires patients to have high resolution typing at DRB1 and intermediate level typing at HLA-A and HLA-B before beginning a donor search. High resolution DNA-based testing is less critical when the potential donor is a sibling with the same biological parents as the patient. Children inherit HLA alleles from their parents in linked strands called haplotypes-one strand from the mother, the other from the father. Since there are only two possible strands of alleles that can be inherited from each parent, serological or low resolution DNA testing is usually sufficient to determine if a patient's sibling is an HLA match. Typing the Pool of Unrelated Donors The early goal of most registries of unrelated donors was to enroll as many donors as possible in a rapid, cost-effective manner. Thus, most of the donors recruited by the National Marrow Donor Program (NMDP) between 1987 and 1991 were only typed at HLA-A and HLA-B. HLA-DR typing was done later, at the patient's expense, after a preliminary search of the NMDP database identified donors who were HLA-A and HLA-B matched. However, enrollment in the donor registries has far exceeded anyone's expectations and today some patients, like Zikmund-Fisher, find hundreds of HLA-A and HLA-B matched donors in the preliminary search. Paying to have each one DR-typed is prohibitively expensive and time-consuming. "So many of the people we met during transplant had transplants with mis-matched donors because they didn't have time to DR-type all the donors who were preliminary matches at HLA-A and HLA-B," says Naomi Zikmund-Fisher. "If all donors in the registry were DR-typed, more people would have a chance of finding a perfect match." The Zikmund-Fishers have "put their money where their mouth is" by creating the Brian Zikmund-Fisher Fund to raise money for DR-typing. To date, the couple has raised over $90,000 - enough to DR-type approximately 3,000 donors in the National Marrow Donor Program registry. Since 1992, the National Marrow Donor Program (NMDP) has also stepped up efforts to expand the pool of HLA-DR typed donors in the registry by DR-typing newly enrolled donors, as well as a subset of donors already enrolled in the registry. Currently, 61% of the 4.3 million NMDP volunteer donors have been DR-typed using DNA-based typing methods. "Since HLA types are inherited, patients are more likely to find a matched donor from within their own racial/ethnic group," notes Chatchada Karanes MD, Medical Director of the National Marrow Donor Program's Search and Transplant Services Department. "For this reason, NMDP has made a concerted effort over the past few years to recruit more minority donors into the registry. Currently 55 percent of donors in the registry are Caucasian, 8 percent are African-American, 6.1 percent are Asian/Pacific Islander, 8.3 percent are Hispanic, 1.3 percent are Native American, 1.5 percent are of multiple ethnic backgrounds, and 19.4 percent are of unknown origin." Beyond HLA Typing While DNA-based typing enables doctors to more precisely identify the HLA types of donors and patients, not everyone will be able to find a perfectly matched donor. In many cases, it will be necessary for a patient to be transplanted with stem cells from a donor whose HLA-type is very similar, but not identical to the patient's. If a patient has the luxury of selecting between two or more donors, several other factors will enter into the equation. Younger donors are usually preferred over older donors. Donors who have not been exposed to the cytomegalovirus (CMV) are optimal. Some studies suggest that gender is important. Male patients who are transplanted with stem cells from a female donor appear to have an increased risk of developing chronic GVHD. DNA-based testing has become an important tool in the battle to control graft-versus-host disease and eliminate graft-rejection. As more people with rare HLA-types are identified and enrolled in the donor registries, the prospects of finding a "perfect" match will increase for all people, regardless of race or ethnic background. -------------------------------------------------------------------------------- ¹ If the donor is the patient's sibling, HLA-typing is often only done at the HLA-A, HLA-B and HLA-DR loci. A donor who matches at these three loci is referred to as a six out of six match. ² The NMDP requires unrelated donors to be at least a five out of six antigen match. Depending on the urgency of a transplant, the age of the patient and the number of potential donors in the registry, a transplant center will decide to wait for a perfectly matched donor or proceed to transplant with a mismatched unrelated donor. --~--~---------~--~----~------------~-------~--~----~ [CMLHope] A support group of http://cmlhope.com ------------------------------------------------- You received this message because you are subscribed to the Google Groups "CMLHope" group. To post to this group, send email to [email protected] To unsubscribe from this group, send email to [EMAIL PROTECTED] For more options, visit this group at http://groups.google.com/group/CMLHope -~----------~----~----~----~------~----~------~--~---
