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Bone Marrow/Stem Cell Transplants (BMT)
Some children diagnosed with cancer undergo a "bone marrow" or a "stem cell" transplant, often referred to in the shorthand "BMT". The goal of a BMT is to replace nonfunctioning or defective bone marrow with healthy stem cells. Healthy stem cells can be obtained from bone marrow, peripheral blood, or umbilical cord blood, which in turn can be either from the child who is undergoing the transplant or a related or unrelated "donor".
Bone marrow transplants are intensive and potentially life-threatening. But, the goal of a BMT is a cure. Quoted from Oncolink (1999): "The goal of BMT is a cure. Cure rates are still low, but are steadily increasing. Even if there is no cure, most transplants result in a period of remission. But you should be aware that there are no guarantees. BMT is an intensive procedure with many risks, and some patients will die despite BMT, from complications of transplant or from relapse of the original disease. The success of BMT will be influenced by a number of factors, including a child's age, general physical condition, diagnosis, and disease stage. Different children respond in different ways."
Scroll down this page for an on-site overview of BMTs. Many external Internet sites provide excellent information on bone marrow and stem cell transplants, so if you need more detail, follow the link below to these sites.
- bone marrow transplant links annotated
The ped-onc page "BMT Parents' Comments" is a collection of writings pages by parents who have ushered their child through a bone marrow transplant. These parents have a wealth of knowledge to share: layman-style explanations, how to keep young children entertained during a BMT, recounts of personal experiences, donor drives, finding a BMT center, what the donor experiences.
The Children's Hospital of Oakland offers a free sibling cord blood donor program. This means that they will store a new sibling's cord blood. This program is sponsored by NCI and is available to families anywhere in the US who have a child with a medical condition that may at some point require a transplant. Labs, typing, collection costs, shipping, and storage are all FREE. There's no need for cancer affected families to pay for this service that they can all use if having another baby. The program can be reached at 510- 450-7605, or www.chori.org/Services/Sibling_Donor_Cord_Blood_Program/indexcord.html.
ViaCord will bank cord blood for free, especially that of a sibling of a child with cancer.
Note: This section has health/medical information. It was not written by a health care professional. The main reference for the following outline was the section on the BMT InfoNet site accessed 2002. This information is now available only as a printed book: Bone Marrow and Blood Stem Cell Transplants: A Guide for Patients. It was one of the best sources which your editor found on the Internet for the nitty-gritty on BMTs in the late 1990s to early 2000s. Today the best reference is:
Quick links to some terms:
- peripheral blood stem cell transplant
- cord blood transplant
Before the transplant begins, your child will undergo a battery of tests to determine whether or not he/she is healthy enough to endure the rigors of transplant. A healthcare team and BMT coordinator will be arranged for your child. These professionals will help you find a donor (if necessary), set up the hospital stay, help you find housing near the hospital, and advise you on insurance and financial issues. The healthcare team should also offer emotional and psychological support for both the child and parents. If it is to be an autologous transplant, stem cells will be harvested during this preparation stage.
The total time in hospital for a bone marrow transplant is about 4-8 weeks, depending on complications.
Conditioning, or preparative regimen (several days to a week or more)
The child first undergoes several days of chemotherapy and/or radiation which destroys bone marrow and cancerous cells and makes room for the new bone marrow. The exact regimen of chemotherapy and/or radiation varies according to the disease being treated and the preferred treatment plan of the facility where the BMT is being performed. The BMT chemotherapy/radiation regimen is much stronger than chemo/radiation regimens for children who do not undergo a BMT.
Transplant (less than an hour)
The transplant itself is given as an IV (usually through the Hickman or mediport) and takes place in the child's room.
Engraftment (two to four weeks)
This is the critical time. The patient is placed in protective isolation since he/she has essentially no immune system at this point, while the new cells are finding homes and beginning to grow. The child is also susceptible to infection from normally harmless pathogens which live in our bodies. They will have few red blood cells or platelets. The BMT team will monitor your child carefully and administer antibiotics and blood products as necessary. If the transplant is from a donor, medications will be given to suppress and control GVHD.
From the BMT news site: "The bone marrow transplant is a debilitating experience. Imagine the symptoms of a severe case of the flu - nausea, vomiting, fever, diarrhea, extreme weakness. Now imagine what it's like to cope with the symptoms not just for several days, but for several weeks. That approximates what a BMT patient experiences during hospitalization."
Recovery continues at home. Your child will continue to be immune suppressed for a varying period of time and will remain closely monitored by the BMT team. The "100 day mark", which is 100 days post-transplant, is generally considered a milestone - by this time, the child is considered past the worst of the procedure and on the path to recovery. Full recovery is slow, with it taking up to two years for the patient to return to full health.
Complications of BMTs include side effects of heavy chemotherapy and radiation, as well as problems that occur when the donated bone marrow is "engrafting".
Chemo/radiation side effects
Side effects of chemotherapy treatments are discussed in general on the ped-onc Treatment side effects page. Since the conditioning therapy for BMTs is very intense, side effects are to be expected. Your child will be immune-suppressed, with an ANC of 0. Blood counts will be low, requiring transfusions of whole blood and platelets (to prevent bleeding). Mucousitis (inflammation of the mucous membranes, both in the mouth and intestine) is common (see the ped-onc Mouth Care page).
Opportunistic infections sometimes invade the patient's body in a BMT procedure. Aspergillus infections are particularly hard to eliminate. The following link takes you to more information on this serious infection:
Graft Versus Host Disease - GVHD
In an allogenic transplant, the newly transplanted stem cells/immune system does not exactly match the patient's own system. What happens is the transplanted cells do not recognize the patient as "self" and they proceed to attack their new host, especially the skin, liver, stomach, and intestines. This is called graft versus host disease, or GVHD. GVHD can be mild or severe (even life-threatening), and occurs less frequently in children than in adults. In leukemias, a small amount of GVHD is felt to be beneficial, as it searches and destroys any residual leukemia cells which are in the patient's body after the preparative regimen.
To combat GVHD, allogeneic transplants are given drug therapy (cyclosporine, prednisone, and/or methotrexate) before and after transplant. If GVHD continues for more than three months, it is considered chronic. Because GVHD may involve the skin, mouth, eyes, liver, muscles, joints and other body parts, these will be examined frequently. In a few children, the damage will be permanent. The most significant effect of chronic GVHD is infection, as the immune system does not return to normal.
Full Text Article: Chronic graft-versus-host disease: where is promise for the future? Leukemia (2005) 19, 1532?1535. doi: 10.1038/sj.leu.2403856; published online 30 June 2005.
Sometimes the patient's own immune system attacks and destroys the donor's cells; this is called "graft rejection". If this happens, a new transplant is usually done immediately.
The bone marrow of the patient is first destroyed and then replaced with healthy stem cells. Hence the name, "transplant". In an allogeneic transplant, post-transplant the recipient has the bone marrow system of the donor; this means that they have the blood type and immune system of the donor.
What's the difference between a bone marrow and a stem cell transplant?
The stem cells can be collected in one of several ways. One source is bone marrow, used because it is rich in "stem cells". Stem cells can also be obtained from umbilical cord blood, which is rich in stem cells. Although circulating (peripheral) blood is not very rich in stem cells, filtration techniques can be used to concentrate the stem cells for a transplant.
Note that the two terms "bone marrow" and "stem cell" transplants are sometimes used interchangeably by nonprofessionals, however, all bone marrow transplants are stem cell transplants but not all stem cell transplants are bone marrow transplants.
Leukemias, aplastic anemia, lymphomas, and neuroblastoma have been successfully treated with BMTs. In cancers of the blood (leukemias), very aggressive chemotherapy is used to kill off the abnormal cells, a process which also kills normal blood and bone marrow. Solid tumors (lymphomas, neuroblastoma) are treated with intensive chemotherapy which kills the bone marrow cells as a side effect; a BMT restores the bone marrow with healthy cells.
The stem cells can come from either the patient or from someone else: a "donor". If they come from a donor, preferably he/she is related to the patient.
How can a patient receive their own stem cells, wouldn't these stem cells be damaged or defective?
True, a patient with a blood cancer like leukemia cannot receive their own stem cells because the bone marrow and peripheral blood are contaminated with cancer cells (although, new techniques are becoming available to "filter out" cancer cells). In other types of cancers, the bone marrow cells are normal, but are destroyed by intense chemo and radiation used to treat the cancer. Thus, they are harvested before the intense chemo/radiation, frozen, and reinfused after treatment to rescue the bone marrow which has been damaged by the treatment.
In allogeneic transplants, the donor and recipient must be "compatible": their HLA types must be close. HLA (Human Leukocyte Antigen) type is determined by a blood test (or sometimes DNA testing).
HLA are antigens on the surface of a person's cells and are easily found on the leukocytes. These mark the cells as being "of self". If the antigens do not match, the donated stem cells will attack all cells of the recipient, because they see the recipient as "foreign". If the antigens match (or nearly match), the donated marrow will peacefully take up residence in the recipient's body and work to supply healthy blood cells.
The antigens named HLA-A, HLA-B, and HLA-DR are known to be important for successful stem cell transplants. There are two of each of these HLA antigens that are important, making a total of 6. (Some centers, especially the military, test for 8 antigens.) A 6/6 match is ideal, although new procedures are developing which allow transplants with 5/6, 4/6, or even 3/6 matches (especially from a relative). Since these antigen types are inherited, it is more likely that a relative (especially a sibling) is a 6/6 match than that a non-relative is a match. People of the same race and ethnic group are more likely to match each other. The genes for HLA antigens are linked together in strands of three: you get three antigens from your mother, and three from your father.
When donors are added to the NMDP Registry, they are usually HLA typed for the A and B antigens only. An initial search of the NMDP registry will designate potential donors, who then are asked to come in for further compatibility testing.
Close family members are typed first. Then, the bone marrow registries throughout the world are searched. These registries store the HLA data on thousands of people.
Becoming registered in the bone marrow registry is an entirely volunteer process. Often people register because they are close to someone who has needed or may need a bone marrow transplant. Sometimes concerned volunteer organizations organize a donor drive in their area. Media stories raise awareness about the need for bone marrow donors and encourage people to sign up.
The marrow is removed with a hollow needle and syringe from the back of the pelvic bone. All donors are given either a general anesthesia (which makes you unconscious) or a regional anesthesia. The marrow is removed through a surgical needle which is inserted multiple times into a few small punctures made in the hip bone. Typically, the donation procedure itself lasts between 45 to 90 minutes. Marrow is constantly regenerating itself so the donor's system completely replaces the donated marrow within several weeks.
More information at:
- NMDP site donor information
Where are BMTs done, and how do we choose a center at which to have the BMT done?
Please see these links:
About $100,000 - $250,000 (NMDP site, accessed 2011)
Most insurance companies cover most of the cost of a bone marrow transplant. If not, or if help is needed for covering what the insurance company does not pay, see financial help for a bmt.
First, the patient's own bone marrow is destroyed by an intensive regimen of chemotherapy and radiation. Then, the donor cells are infused into the bloodstream through the right atrial catheter or mediport (central venous catheter). They travel through the bloodstream and find their way to the marrow, engraft, and (hopefully) begin producing healthy, normal blood cells.
The names for the different types of bone marrow transplants pertain to the source of the stem cells: whether they are from the recipient or from a relative or stranger, and whether they are from bone marrow or blood.
Allogeneic - The donor in an allogeneic transplant is either a relative or someone who is a close genetic match to the patient. The transplant team always looks first to family members, since there is about a 1 in 3 or 4 possibility that a sibling is a close enough genetic match to be a donor. If a brother or sister is used as the donor, it is called a "Matched Sibling BMT". (These were the earliest and are still the safest type of non-autologous marrow transplants.)
If none of a patient's family members is a close genetic match, the bone marrow registries are searched in hopes of finding an unrelated donor. Transplants using unrelated donors as the source of stem cells are called "Matched Unrelated Donor Bone Marrow Transplants" or MUD transplants for short.
Autologous - In an autologous transplant, the patient's own stem cells are used. The patient's stem cells are harvested from the bone marrow or from peripheral blood before the chemo/radiation regimen. These healthy stem cells are frozen and stored until needed. In an autologous transplant, there is no risk of GVHD.
Autologous transplants have limited effectiveness in the treatment of leukemias that infiltrate the marrow, although they can sometimes be used in leukemias after procedures which remove diseased cells. (This is usually only done when no HLA compatible donor can be found.)
Peripheral blood stem cell transplant (PBSCT) - The patient's or a donor's donates cells are collected from the circulating blood system instead of from bone marrow. In PBSCT's, a drug is used to "overstimulate" marrow production. This mobilizes a higher-than-normal number of stem cells into the blood stream. Apheresis is used to filter these excess stem cells from the donor's bloodstream. (Most cancer kids parents are familiar with apheresis, since it is used to filter platelets from donors to be used in supportive treatment for many childhood cancers.) PBSCT's can be either autologous or allogenic, with autologous being the more common of the two. (More info on the NMDP site)
Cord blood transplants (CBT) - The stem cells come from umbilical cord blood, a rich source of stem cells. Cord blood transplants are allogeneic and thus the cells must be matched with the patient. An advantage of cord blood is that the stem cells do not show a significant sense of "self" or a large number of antibodies, so the chances of life-threatening GVHD is greatly reduced. One problem with cord blood use for transplants is that only a small amount of product can be harvested from one umbilical cord, thus, this type of transplant is usually limited to children or small adults.
Cord Blood Transplantation by Leonard Johnson, M.D. - an article in the Fall 1999 Candlelighters Newsletter on the ACCO web site.