BMT is often described as a journey, as it is a long process with many steps and phases, not just a single , one-time event. Parents can better help their child throughout the journey when they are educated about what to expect along the way. Highly-specialized education is needed, comparable to learning to speak a new language in a new culture. We present here details on what every patient family needs to know about the BMT process.
What is a BMT
A BMT is literally the transfer of a new immune system from donor to recipient to replace one that is diseased or malfunctioning. The immune system protects the body against infections and other foreign bodies which can cause malfunction of any of its systems The transfer, or transplant, takes place after the recipient’s defective immune system has been eliminated through specific regimens of high-dose chemotherapy and/or radiation.
In other words, the recipient is brought literally to the brink of death—all of his or her marrow is destroyed and no blood cells are being formed– In order for a healthy new immune system to take hold and start to function, the recipient’s body must be able to accept it, countering the natural tendency to fight off what are perceived as outside invader cells. Therein lies the importance of finding a donor immune system that is a “match” to the recipient’s.
The immune system cells which are transplanted can be taken from a donor’s bone marrow (which is extracted during a procedure done in the operating room) or from the donor’s blood stream (where the donor’s cells are collected by filtering the blood) or from the blood contained by the umbilical cord and placenta of a newborn baby right. Called “cord blood”, this cell source can be collected right after the baby’s birth. Recent scientific research indicates that use of cord blood may enable many more patients to undergo unrelated BMTs with less-precisely matched donor cells. The theory is that the less “educated” cord blood cells, which have not yet been exposed to common infections that would lead them to mount a reactive response, can be better accepted by the recipient’s body, which will not fight them off so strongly. As will be explained further in greater detail, since the factors that determine the “match” are genetically based, a patient has the best chance of finding a donor within his/her biological family. However, due to the laws of probability that govern human genetics, only 25 – 30% of patients are able to find a related (family) donor. The rest of the patients must rely on finding a donor that is unrelated to them; most likely to occur with someone of a similar ancestral genetic or ethnic background.
After receiving medical recommendations, each family must make a decision about whether or not their child will undergo a BMT. Parents need thorough information on this treatment option, as well as an understanding when a BMT should be done. A face-to-face conference will be set up for the parents (and the child also, if age appropriate) with the attending physician and other BMT team members to discuss the pro’s and con’s, and to go over details of the planned BMT protocol, its risks. Parents will be given a protocol document to take with them to read over (with a chance to discuss further or use to seek other medical opinions), which they will asked to sign to agree for the BMT to take place. This is called the informed consent process. The signed legal document is sometimes informally also referred to as the” informed consent” as well.
Timing of Transplant
Increasingly, medical recommendations are being made for a BMT to be considered as part of treatment soon after a patient’s diagnosis. In the early days of BMT, it was considered to be a drastic last step only to be undertaken after other treatments had failed. The experience of the past 2 decades has shown that, at least in some cases, earlier transplants may offer a better chance of a cure and/or that patient can better withstand BMTs if they have not been subjected to many other toxic treatments beforehand. While much progress has been made in controlling or eradicating certain cancers with new medications, many diseases are presently cured only with transplant. Better methods have also been developed to prevent or better control many of the devastating side effects of BMT that also affect survival Therefore patient families may want to find out early on if a BMT might be indicated for their child. Some experts feel that if patients from demographic groups under-represented in the registries do not have a sibling donor, then this factor may indicate the need for an earlier referral, as more time will likely be necessary for searching for an unrelated donor.
Some experts feel that if patients from demographic groups under-represented in the registries do not have a sibling donor, then this factor may indicate the need for an earlier referral, as more time will likely be necessary for searching for an unrelated donor.
The American Society for Blood & Marrow Transplantation and the NMDP have created a BMT referral timing tool, which patients and physicians can discuss together.
Choosing the Donor Cell Source
The oncologist’s office or transplant center (if patient is already being seen there) will assist patients in making arrangement for HLA testing of the basic A, B, and DR antigens for themselves and their sibling(s). Special arrangements can be made for testing of siblings living out of area and/or out of country. These tests are often, but not always, covered by insurance plans, public or private. See the FAQ page for more information about insurance overage of HLA testing.
HLA typing is reported as a series of numbers. For example, an HLA type will appear on the report as A 3, 32; B 7, 37; DR 1, 15.
Role of Genetics
Each of the HLA proteins or antigens is inherited from one’s biological parents, and they tend to be inherited in a group called a haplotype. The six different antigens then are paired up in different arrangements, whose general pairing patterns are hereditary. Because the transmission of the haplotypes is genetic, matching of the patterns is most likely between biological siblings, and next among people of similar ancestral genetic / historical ethnic origins. Due to the odds of any particular combinations of haplotypes being inherited, there is about a 1 in 4, or 25% chance of finding match between a patient and a biological brother or sister.
What is a match?
A BMT “match” is made by matching up as closely as possible certain proteins called antigens, found on the surface of most cells, that regulate the ability of the immune system to recognize cells as “self” that belong in the body and to fight off those which are “foreign” which do not belong there. Antigens mount a reaction to “invader” cells by stimulating antibodies to fight them off. The antigens important to the BMT procedure are the HLA or Human Leukocyte Antigens. These found in especially high concentrations in white blood cells.
What HLA Testing Shows
The HLA system includes many different types or groups of HLA antigens that are identified by different letters of the alphabet. There are specific groupings of HLA antigens important to solid organ transplants, hematopoeitic cell transplants, and platelet transfusions. The principal groups of importance for transplants of all 3 stem cells sources: bone marrow, peripheral blood, or cord blood include:
As shown above, specific HLA antigens are identified by a letter for their group (A, B, or DR), and then by a number, in order to distinguish antigens from the same group. An example of this pattern of identification is: HLA-A1, B8, DR17 for one person; and HLA-A2, B7, DR15 for another person. There are patterns to the occurrence of, and to the frequency of occurrence, of specific HLA antigens among distinct ancestral-origin population groups of the world.
HLA antigens can also be separated into Class I and Class II molecules. Each class has a different structure and different function in the immune system. Class I molecules include the HLA-A, B, and C antigens and are found on nearly all cells in the body. Class II molecules include the HLA-DR, DP, and DQ antigens and are typically only found on cells of the immune system although all cells with a nucleus have the ability to express these molecules.
Selecting the Cell Source for BMT
After these test results are received, the treating physician can discuss what type of transplant is indicated: either one using the patient’s own cells (autologous transplant) or using cells from a donor. This will depend on the patient’s specific disease, and present medical condition. While in some cases autologous BMTs may be done routinely, many times the decision on type of transplant is based on whether or not the patient has a matching biological sibling donor available, or if a search will need to be made for an unrelated donor. The treatment plan will also include estimated timing for a transplant, and referral to a BMT center.
The Search Request
Once the decision has been made that a patient should move forward with the plan to undergo a BMT, s/he will be referred to a transplant center (TC). For many, if not most patients whose parents are reading this website, this will be the BMT program run by the Seattle Cancer Care Alliance or SCCA. SCCA, which is a consortium of the Fred Hutchinson Cancer Research Center, the University of Washington Medical Center, and Children’s Hospital and Regional Medical Center, operates the sole pediatric BMT center in Washington state. In most cases, the BMT itself will take place at Children’s. Once the patient has been accepted for the BMT workup, the formal search process can begin.
Only a transplant center may make request that a formal search be started for a specific patient. Usually the request is made by a search coordinator who is assigned to each patient in need of an unrelated BMT donor. S/he is also responsible for monitoring the results found from the search of databases of national and international donor registries, and for conferring about them on a regular basis, with the patient’s transplant physicians. AT SCCA, an HLA Attending Physician works closely with the search coordinator to select the donor candidate(s).
The process of searching for an unrelated donor (URD) for a specific patient begins with research into the holdings of databases of donor HLA typings that have been collected by registries in the US and around the world.
Selecting a BMT Center
The selection of a BMT center for your child is usually made on the basis of what is available based on both medical and practical criteria. On the medical side, the important issue is to find a center experienced in treating your child’s disease with unrelated-donor BMTs. Points to consider also include:
- outcomes of transplants performed
- degree of HLA matching required for a BMT
- how patients are selected for acceptance into the program
- availability of cord blood transplantation
- support services offered
On the practical side, are factors including insurance coverage (center(s) covered and extent of benefits), and practical matters like where will the family live so that their child will get the round-the-clock caregiving needed while taking care of, at the same time, family living expenses, other children or dependents, and all other personal responsibilities. Factors to consider include:
- fees charged, insurance plans accepted, financial arrangements available
- location of center and need for family relocation, daily travel, or housing alternatives
- availability of caregiver(s) and helping network for patient and family needs
Sometimes there is no time for any research into choosing a BMT center as a child’s illness requires almost-immediate treatment. And some parents of children with very rare diseases may learn that only one specific center has much experience in treatment of the disease. There is no one right answer as to which is the “best” BMT center for all patients, as everyone’s situation is different.
Donation and Transplantation
Donation of Cells from Marrow or Blood
After all levels of Confirmatory Typing (CT) have been completed, and the donor has received medical clearance based on results of physical exams, the donation takes place. Usually it is timed to occur at the precise when the recipient has completed the BMT chemotherapy and/or radiation protocol (called the conditioning regime), so that the transplant will take place as soon as the donor stem cells arrive.
In most cases, the donor goes to a donor center or hospital credentialed to conduct the stem cell or marrow harvest, in or near to his/her home community. Once the stem cells are collected and stored in a blood bag, they are hand-carried by courier directly to the recipient’s TC. Occasionally due to special logistical circumstances, a donor may be brought to a center or hospital in the community where the recipient is located. However, the donor and recipient do not meet, due to confidentiality regulations governing unrelated BMT donations. For more detailed information about the donation process, see: Steps of Marrow and PBSC Donation
Transplanting Cord Blood
If the transplant will be of umbilical cord blood, the CB unit (CBU) will usually be shipped frozen its crypreserved state, using a specialized medical courier service. The CBU will be shipped in advance of the completion of the receipient’s conditioning phase, so that the thawing process may be precisely timed at the transplant center. The cord blood needs to to be transfused at the exact time that the patient is ready for it. More detailed information on the collection, testing, freezing, and transplantation of cord blood may be found on the website of one of the public cord blood banks, which is located in New York.
BMT Takes Place
The donated stem cells, no matter what their source, are infused into the recipient, whose diseased immune system as been eradicated through chemotherapy and/or radiation. The transplant is often called a “rescue” therapy, as it restores life to a patient who has literally been bought to the brink of death. The transplant itself is similar in appearance to a blood transfusion, except that the cells usually infused through a central venous catheter, or central line, that has been surgically implanted in the patient. The day of transplant is called Day Zero, and starts off a countdown measured in days to track the patient’s recovery. The transplant process is very complex, is different for each patient, and carries with it many risks and many hopes. Despite the challenges, it has become a treatment that offers increased chances of survival to more patients.