Bone Marrow Transplants: The Search for a Match
A friend of mine recently presented me with a question to use as a place to begin research for this paper. She had been studying blood types in one of her classes, and after asking about my family’s blood types, she inquired, “If you and your brother have different blood types, how could you give him bone marrow?”
First, some background. My little brother had leukemia as a child, and in sixth grade I was his bone marrow donor. He is doing remarkably well today. With that in mind, I was surprised that I had never asked this question before, and it was quite perplexing to realize I did not know the answer. With this very specific question, I began my research into how a donor is matched to a transplant patient.
The issue of donor match is significant in bone marrow transplants. Hopefully the statistics are better now, but in 1998 40% of transplant patients died because a matching donor could not be found. (1) The extent and level of the match also has a huge impact on the success rate of transplant. The best possible scenario is to have a matching sibling donor, as in the case of my brother. There is a 33% survival rate for donation from a matched stranger, and 22% survival rate for donation from an unmatched donor or using umbilical chord stem cells. (2)
Before exploring the issue of donor match more thoroughly, it is important to understand just what a bone marrow transplant is. It is used to treat several conditions, from immune deficiencies to blood diseases to certain types of cancer. First, the bone marrow of the patient is destroyed using high doses of chemotherapy and often total body irradiation. This serves to eliminate abnormal cells and to decrease risk of rejection. Some of the marrow of the donor is removed from the top of the donor’s hip bone, while the donor is under general anesthesia. (3) In my case, bone marrow was harvested by inserting a wide needle into the hip bone and then extracting the marrow with a series of smaller needles. Though initially weak, I recovered from this very quickly. Other donors I saw, however, did not have so quick a recovery time. One girl had to be in a wheel chair for a few days. This type of transplant, where bone marrow is implanted from a donor, is called allogenic; autologous transplants are also possible, where the bone marrow of the patient has been previously stored when healthy and then implanted when needed. (4) I think it is best understood in terms of the immune system of the patient being “reset.” The patient, theoretically, acquires the healthy immune system of the donor in place of his or her own.
Matching is done through a process called a histocompatability antigen blood test. This test compares the proteins that exist in large numbers on the outside of the patient and the potential donor’s white blood cells, called human leukocyte antigens. There are three main groups of this type of protein: HLA-A, HLA-B and HLA-DR, though there are many different proteins in each group. (5) There are six markers examined for a bone marrow transplant match; three inherited from the mother, three from the father. Everyone’s type is relatively unique, but most likely matched to a sibling. (1) When finding a match, it is “important to find a donor of the same ethnic group.” (6) In the US, this has caused complications for African Americans, and Asians in the UK have experienced similar problems. (7) This difference in bone marrow markers reflects an important implication of the clumpiness we have discussed that exists in human diversity. The different characteristics that have developed among different races and ethnicities exist too on the scale of proteins, in such a way that can have a dramatic impact on the lives of individuals. According to an article from CNN, many African Americans hesitate to register to donate any organs, including bone marrow, because of the memory of experiments done in the Tuskegee institute. I am a little skeptical of this, because the article also says that African Americans make up 12% of the population and “only” 8% of registered donors. That does not seem like a big discrepancy to me.
One of the reasons why a close match is important is the risk of rejection, called graft versus host, or GVH disease. In this disease, T-cells recognize transplanted bone marrow as foreign tissue and being to attack. (8) This can be avoided at some risk using drugs that block the T-cells which would attack tissue. However, with this treatment, the patient is put at an even greater risk of infection. If the body rejects the foreign tissue, there is little hope for the patient. Though I was a perfect match for my brother, he was constantly monitored for signs of GVH. Once, his doctors discovered the bottoms of his feet were bright red, and of course sent up an alarm and began tests to find out if he was rejecting my bone marrow. We were relieved later when one of the nurses discovered posters in the play room covered in red paint foot prints; they actually put Richard into one of the Johns Hopkins medical journals for that scare.
There is a lot about bone marrow transplants that is still not understood. As stem cell technology improves, they are becoming less frequent, but finding a matching donor will always be an issue. I encourage everyone to keep an eye out for fliers about Haverford’s annual registration drive and to visit www.marrow.org to find out about registering with the National Marrow Donor Program.
1) http://news.bbc.co.uk/2/hi/health/199442.stm; “Bone marrow breakthrough could cut deaths;” BBC News
2) http://news.bbc.co.uk/2/hi/health/4045699.stm; “Cord blood offers leukaemia hope;” BBC News
3) http://health.nytimes.com/health/guides/surgery/bone-marrow-transplant/overview.html?WT.z_gsac=1; “Bone Marrow Transplant;” New York Times website
4) http://www.mayoclinic.com/health/acute-lymphocytic-leukemia/DS00558/DSECTION=7; “Acute lymphocytic leukemia;” Mayo Clinic
5) http://health.nytimes.com/health/guides/test/histocompatibility-antigen-test/overview.html; “Histocompatability Antigen Test Overview;” New York Times website
6) http://www.cnn.com/2007/HEALTH/02/07/bone.marrow/index.html?iref=newssearch; “Tuskegee’s ghosts: Fear hinders black marrow donation;” CNN.com
7) http://news.bbc.co.uk/2/hi/health/1672558.stm; “Plea for Asian bone marrow boy;” BBC News
8) http://news.bbc.co.uk/2/hi/health/734610.stm; “Bone marrow rejection risk ‘minimised;’” BBC News