| Extreme Matchmaking | ||
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By Prateek Lala, MD
Even more inspiring are his numerous contributions to the community. Dr. Guha is a co-founder of the National Neurosciences Centre at Peerless Hospital in Kolkata, India, which provides patients with (below-cost) life-saving surgical services. He works with Sashibhusan Karma Kendra, an NGO providing social services for women and children living in poverty in villages around Krishnanagar, India. For these philanthropic works, Dr. Guha was honoured in 2005 with the Indo-Canadian Chamber of Commerce Humanitarian of the Year award. Fate, however, seemed unimpressed by a stellar CV or tireless humanitarian work. After a routine blood test in July 2008, Dr. Guha and his family were shocked to learn that the fatigue he had been feeling lately wasn’t due to his busy schedule, but rather to acute myelogenous leukemia, a cancer of the blood and bone marrow. He was promptly admitted to the Princess Margaret Hospital, a world-class local cancer centre, for further tests. The subsequent course of chemotherapy he underwent, however, failed to control the rapid growth of the cancer cells and prevent them from crowding out the healthy cells in his bone marrow. A second, more intense round of chemo yielded the same unfortunate result—the cancer continued to grow unchecked. With all other possibilities exhausted, a bone marrow transplant was his only chance to survive (video link). _____ According to the National Cancer Institute, in 2008 more than 130,000 people in the U.S. were diagnosed with leukemia, lymphoma, and myeloma (cancers of blood and bone marrow). About 53,000 patients died from these diseases last year: this means that someone died from blood cancer every 10 minutes in the U.S. alone, including many children. Similarly, in Canada (which has one-tenth the population of the U.S.) the Public Health Agency estimates that 14,100 people will be diagnosed with blood cancers in 2009, and 7,100 patients (20 people every day) will lose their battles this year. Just as there are many different types of leukemia, so are there several ways to treat them. Initially, chemotherapy combines a series of toxic drugs in an attempt to kill the rapidly dividing cancer cells more quickly than normal ones; but make no mistake, these drugs are toxic to all cells, and their side-effects can sometimes be as difficult to deal with as the disease itself. Radiation therapy is sometimes used to treat blood cancers, but only in certain cases, and almost always in combination with other therapies. A third and often curative treatment available for patients with blood cancers is bone marrow transplantation (BMT), also known as stem cell transplantation (SCT).
If you are among the generous minority of people who donate blood, you will know that for a transfusion to work, the blood type of the donor must be compatible with that of the recipient. Finding a compatible unit of blood for a patient is a relatively easy task (though there is always a need for more blood donors), since in the familiar ABO-Rh typing system, there are only eight major blood groups. Matching stem cell donors to recipients is much more complex than blood typing, and uses a set of markers found on most cells in the body, called “human leukocyte antigens” (HLA). These cell-surface proteins distinguish cells belonging to our own bodies from those that don’t, so that our immune systems can attack foreign invaders while leaving our own cells alone. We each inherit six major pairs of HLA markers from our parents, half of each pair from our fathers, the other half from our mothers. Each marker, however, can have hundreds of different forms in the general population. If each of these 12 markers were inherited independently, there would be over 900 trillion possible combinations, and nobody would ever find a match. Fortunately, HLA is inherited in sets, which considerably improves the odds of matching. Still, the odds could be much better: the current likelihood of an American or Canadian patient finding a match ranges from 32% to 88%, depending on the patient’s race—with ethnic minorities at the low end of this range.
Registries are organizations that help recruit potential stem cell donors, perform the necessary tests to identify a donor’s HLA type, and store this information in databases that allow patients to search for matches. The first stem cell registry (The Anthony Nolan Trust) was established in England in 1974 by Shirley Nolan, whose infant son was diagnosed with a rare immune system disorder. Although Anthony passed away at age seven, Ms. Nolan’s vision has spread globally, and many countries now operate at least one registry; these include the Be The Match RegistrySM operated by the National Marrow Donor Program (NMDP) in the U.S., and the OneMatch registry in Canada. An international organization, Bone Marrow Donors Worldwide (BMDW), collects data from national registries which can be viewed by all member registries globally. In March 2009, BMDW reported that it has data on 13 million prospective donors. Ethnicity plays an important role in the process of finding donors. Since HLA markers are inherited from both parents, there are strong ethnic ties to a person’s HLA pattern. In other words, while anyone, anywhere can potentially be a match, the best chance for a good HLA match comes from a donor who shares a patient’s ethnic background. Some ethnic groups have greater diversity of HLA types than others, however, and less-common tissue types are more challenging to find a match for. A 2008 NMDP study indicates that even when ethnic minorities do find donors, they are 2-3 times more likely to have a less-matched donor—and thus, worse prognosis—than Caucasian patients, due to the wider diversity of HLA types. Currently, South Asians represent just 2% of registered donors, both in the U.S. and Canada (figure, below).
Why are minorities underrepresented in donor registries? Primarily, most people do not know that such registries even exist until someone close to them needs a transplant. Understanding this, the NMDP and OneMatch have recently developed broad programs to help improve public knowledge. Secondly, there are many misunder-standings about the “risks” of the registration and donation procedures. A 2005 study conducted by researchers at the University of Pittsburgh found that Asian Americans are more ambivalent about joining registries, and those who join are more anxious about the donation process than any other ethnic group. So let’s clear the air here. The actual registration process is very simple and completely painless. The only restrictions are age (18-60 in the U.S., 17-50 in Canada), that you are in generally good health, and are willing to donate to anyone in need. Simply complete a short questionnaire with your contact information and yes/no answers to basic health questions. This can be done online or in person at a donor clinic or a recruitment drive, which is often coordinated through a blood bank affiliated with one of the registries. In the U.S., the cost for donor testing is, on average, $52. You may be asked to pay all or part of this tax-deductible cost when you join; sponsors sometimes provide funds to offset the cost of typing (visit www.BeTheMatch.org or call 1-800-MARROW-2 for information). In Canada, registration is free for all residents (go to www.OneMatch.ca or call 1-888-2-DONATE). The whole process takes 5-10 minutes.
So, what happens if you are found to be a match for a patient in need? In this event, you will be contacted by a registry representative, and if you are still able and willing to be a donor, guided through the whole donation process by a case manager. First, a nurse or other health care worker will determine if you are generally in good health. Your blood will be tested for infectious diseases and a physician will perform a physical exam to make sure you are healthy enough to donate stem cells; these steps ensure the safety of both the donor and the recipient. At this time, potential risks and benefits will be explained to you, and with your consent, the donation process will go ahead. There are two ways to donate stem cells; which one is chosen depends on the needs of the patient. Peripheral blood stem cell (PBSC) donation is now the preferred method: HSCs released from the marrow into the bloodstream are collected in a painless process much like an extended session of blood donation. Prior to the procedure, donors receive once-daily injections for five days of a medication that stimulates the body’s production and release of HSCs. Then, over a 4-6 hour period at an outpatient clinic, blood is drawn out of one arm and run through a machine that separates and collects the required stem cells, and returns the rest of the blood through the other arm in a continuous circuit. All the while, donors are free to read, watch a movie, or do pretty much anything else they choose. Most donors experience just mild bone pain, headache, and/or nausea from the injections, and these symptoms subside shortly after donation. Between 5-15% of PBSC donors require placement of a central catheter in a large vein to complete the process. The older method, bone marrow donation, involves using a special needle to collect liquid marrow from the donor’s hipbone. Rest your hands on your hips—the spots on the back of your hipbones under where your thumbs rest are the areas from which marrow is collected. This procedure is performed under anesthesia (so it is painless), and takes two to three hours from start to finish. Donors typically arrive at the hospital in the morning and leave by afternoon. Though there are risks involved with any medical procedure, most people only experience some hip discomfort at the puncture sites; mild painkillers are usually sufficient. Just 3-5% of your body’s total marrow is withdrawn, and this will completely regenerate in 4-6 weeks. Bone marrow donation, however, is only used about 20% of the time these days. Thus, both PBSC and bone marrow donation are safe and simple procedures that can save the lives of patients with a wide variety of illnesses. In leukemia patients, stem cell transplant increases the long-term survival rate by 2-3 times over chemotherapy alone. In addition to blood cancers, SCT can potentially cure other bone marrow diseases like thalassemias—some of which are common in South Asians—and sickle cell anemia; disorders of the immune system, such as SCID (“bubble boy disease”); and inborn errors of metabolism, including adrenoleukodystrophy (see “Lorenzo’s Oil”). Since its inception in 1987, the NMDP has facilitated transplants for more than 35,000 people. The Canadian registry has made possible more than 2,000 transplants since 1988. But, according to the NMDP, at any given time physicians are searching for donors on behalf of 6,000 patients worldwide. So, regardless of your ethnic background, by registering as a donor, you could become (as OneMatch says) an “extreme lifesaver”. A third, even easier way of donating stem cells applies to expectant mothers. Usually, when a baby is born and the umbilical cord is clipped and cut, the cord and placenta are discarded as medical waste. However, scientists have found that blood from the cord is a rich source of HSCs, and cord blood use is growing in both adult and pediatric populations. Physicians may consider umbilical cord blood a good choice particularly for patients who need an unrelated donor and have an uncommon HLA type or are in urgent need of a transplant. A cord blood unit is collected at the time of delivery, so parental consent must be provided to doctors and midwives well beforehand. In the U.S., the NMDP is affiliated with more than 20 cord blood banks that facilitate cord blood collection and storage. In Canada, OneMatch expects to implement a public cord blood program within the next year. Until then, Canadians can register with the Alberta Cord Blood Bank, which operates coast-to-coast, or with Héma-Québec, which collects cord blood at several Montréal hospitals. _____ Dr. Guha was fortunate to find a well-matched donor late last year, and after further treatment at the City of Hope National Medical Center near Los Angeles, underwent a transplant in December 2008. Now, 150 days later, he is slowly recovering at home in Toronto, very grateful for his second chance at life. “As our medical knowledge increases,” Dr. Guha says, “we’re finding unique genetic characteristics among different ethnic groups that have significant impact on not only the type of diseases that are common in those groups, but also on therapies that are most beneficial. This includes bone marrow [stem cell] transplant, which can potentially cure many diseases, including leukemias. To this end, we need communities to come together to help each other out, as the need may occur in any one of us.” Join your national registry right now: in the U.S., visit www.BeTheMatch.org or call 1-800-MARROW2; in Canada, go to www.onematch.ca or call 1-888-2DONATE. Please remember to update your contact information with your registry if you move or change your name. Also, consider donating blood, or making a financial gift. Acknowledgments:
Thanks also to John Bromley, MaryLynn Pride, and Beth Amer at OneMatch, and Catherine Claeys at the NMDP for providing helpful information and feedback.
References: American Cancer Society. Cancer Facts & Figures, 2008. Atlanta: American Cancer Society, 2008. Canadian Cancer Society’s Steering Committee. Canadian Cancer Statistics, 2009. Toronto: Canadian Cancer Society, 2009. Mori M, et al. HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry. Transplantation, 64(7):1017-1027, 1997. Switzer GE, et al. Ethnic differences in donation-related characteristics among potential hematopoietic stem cell donors. Transplantation, 80(7): 890-896, 2005. Dehn J, et al. Unrelated donor hematopoietic cell transplantation: factors associated with a better HLA match. Biology of Blood and Marrow Transplantation, 14(12):1334-1340, 2008.
Additional weblinks and information: There are presently only two, small registries operating in India. The Asian Indian Donor Marrow Registry operates at the All-India Institute of Medical Science (AIIMS) in New Delhi, and although it is affiliated with Bone Marrow Donors Worldwide, it consists mainly of family members of patients, and has not filed its data with BMDW since 1991. The Marrow Donor Registry (India) (MDR(I)) is operated from the Tata Memorial Hospital in Mumbai. Like the North American registries, it is comprised entirely of volunteer donors. Mumbai residents who want to enroll as donors, volunteer towards recruitment efforts, or make financial contributions can contact the MDR(I) during work hours at 91-22-2417-7000, extension 4654, and speak to Ms. Nikhat Khan, Technical Coordinator, or any staff member in the HLA division. Voluntary donor registration is free at this time. Although MDR(I) does not yet forward data to BMDW, physicians looking for a match can contact them directly with typing results. MDR(I) is working to expand their efforts within Mumbai and in other cities in India. Currently, there are no BMDW-affiliated registries operating in other South Asian countries (Bangladesh, Bhutan, Maldives, Nepal, Pakistan, or Sri Lanka). However, several registries are administered in East and Southeast Asia (China, Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand) and other regions of the world. Please visit the BMDW website for their contact details, and encourage friends and relatives around the world to join their national registries. In addition to the national registries, several North American grassroots organizations have formed to help spread the message of the need for ethnic minority stem cell donors. Many of these groups also hold frequent awareness events and donor drives where attendants can join the registries on-site, usually free of charge. If you would like to attend a drive, or are a patient or family who would like to organize your own drive, contact your national registry or visit the websites of the independent organizations listed below: § U.S.A.: National Registry: NMDP’s Be The Match Registry: http://www.BeTheMatch.org/ · South Asian Marrow Association of Recruiters (SAMAR): http://www.samarinfo.org/ · MatchPia: http://www.matchpia.org/ · Asian American Donor Program (AADP): http://www.aadp.org/ · Asians for Miracle Marrow Matches (A3M): http://www.asianmarrow.org/ § Canada: National Registry: OneMatch: http://www.onematch.ca/ · Coming soon: South Asians For Life (SA4L): http://www.SA4L.org/ · Other Half – Chinese Stem Cell Initiative: http://www.chinesestemcell.ca/ § U.K.: National Registry: Anthony Nolan Trust: http://www.anthonynolan.org.uk/ · African Caribbean Leukemia Trust (ACLT): http://www.aclt.org/
For information on leukemia and other cancers, visit the following sites: § Leukemia & Lymphoma Society: http://www.leukemia-lymphoma.org/ § American Cancer Society: http://www.cancer.org/ § Canadian Cancer Society: http://www.cancer.ca/
For patients and families looking for clinical trials to treat leukemia and other cancers, visit: § National Cancer Institute: http://www.cancer.gov/clinicaltrials
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