Key Terms: ABO antigen, AML, Allogeneic, Anemia, Antigen, Aplastic anemia, Autologous, Blank, Blast cells, Blast crisis, Bone marrow, Bone marrow transplant, Chemotherapy, Chronic myelogenous leukemia, Cytomegalovirus, Conditioning, Confirmatory typing, Donor, Graft versus host disease, Histocompatibility, HLA, Hodgkin's disease, Immunodeficiency, Leukemia, Lymphoma, Match, Mixed lymphocyte culture, Neuroblastoma, Platelets, Recipient, Red blood cells, Sickle cell disease, Syngeneic, Thalassemia.
Definition
The bone marrow—the sponge-like tissue found in the center of certain bones—contains stem cells that are the precursors of white blood cells, red blood cells, and platelets. These blood cells are vital for normal body functions, such as oxygen transport, defense against infection and disease, and clotting. Blood cells have a limited lifespan and are constantly being replaced; therefore, healthy stem cells are vital.
In association with certain diseases, stem cells may produce too many, too few, or otherwise abnormal blood cells. Also, medical treatments may destroy stem cells or alter blood cell production. The resultant blood cell abnormalities can be life threatening.
Bone marrow transplantation involves extracting bone marrow containing normal stem cells from a healthy donor, and transferring it to a recipient whose body cannot manufacture proper quantities of normal blood cells. The goal of the transplant is to rebuild the recipient's blood cells and immune system and hopefully cure the underlying ailment.
Purpose
A person's red blood cells, white blood cells, and platelets may be destroyed or may be abnormal due to disease. Also, certain medical therapies, particularly chemotherapy or radiation therapy, may destroy a person's stem cells. The consequence to a person's health is severe. Under normal circumstances, red blood cells carry oxygen throughout the body and remove carbon dioxide from the body's tissues. White blood cells form the cornerstone of the body's immune system and defend it against infection. Platelets limit bleeding by enabling the blood to clot if a blood vessel is damaged.
A bone marrow transplant is used to rebuild the body's capacity to produce these blood cells and bring their numbers to normal levels. Illnesses that may be treated with a bone marrow transplant include both cancerous and noncancerous diseases.
Cancerous diseases may or may not specifically involve blood cells; but, cancer treatment can destroy the body's ability to manufacture new blood cells. Bone marrow transplantation may be used in conjunction with additional treatments, such as chemotherapy, for various types of leukemia, Hodgkin's disease, lymphoma, breast and ovarian cancer, and other cancers. Noncancerous diseases for which bone marrow transplantation can be a treatment option include aplastic anemia, sickle cell disease, thalassemia, and severe immunodeficiency.
Precautions
Bone marrow transplants are not for everyone. Transplants are accompanied by a risk of infection, transplant rejection by the recipient's immune system, and other complications. The procedure has a lower success rate the greater the recipient's age. Complications are exacerbated for people whose health is already seriously impaired as in late-stage cancers. Therefore, a person's age or state of health may prohibit use of a bone marrow transplant. The typical cut-off age for a transplant ranges from 40 to 55 years; however, a person's general health is usually the more important factor.
Even in the absence of complications, the transplant and associated treatments are hard on the recipient. Bone marrow transplants are debilitating. A person's ability to withstand the rigors of the transplant is a key consideration in deciding to use this treatment.
Description
Autologous and Allogeneic Transplants
Two important requirements for a bone marrow transplant are the donor and the recipient. Sometimes, the donor and the recipient may be the same person. This type of transplant is called an autologous transplant. It is typically used in cases in which a person's bone marrow is generally healthy but will be destroyed due to medical treatment for diseases such as breast cancer and Hodgkin's disease. Most bone marrow transplants are autologous. If a person's bone marrow is unsuitable for an autologous transplant, the bone marrow must be derived from another person in an allogeneic transplant.
Allogeneic transplants are more complicated because of proteins called human lymphocyte antigens (HLA) that are on the surface of bone marrow cells. If the donor and the recipient have very dissimilar antigens, the recipient's immune system regards the donor's bone marrow cells as invaders and launches a destructive attack against them. Such an attack negates any benefits offered by the transplant.
Hla Matching
There are only five major HLA classes or types—designated HLA–A,–B, –C,–D, and class III—but much variation within the groupings. For example, HLA–A from one individual may be similar to, but not the same as, HLA–A in another individual; such a situation can render a transplant from one to the other impossible.
HLA matching is more likely if the donor and recipient are related, particularly if they are siblings; however, an unrelated donor may be a potential match. Only in rare cases is matching HLA types between two people not an issue: if the recipient has an identical twin. Identical twins carry the same genes; therefore, the same antigens. A bone marrow transplant between identical twins is called a syngeneic transplant.
Peripheral Blood Stem Cell Transplants
A relatively recent development in stem cell transplantation is the use of peripheral blood stem cells instead of cells from the bone marrow. Peripheral blood stem cells (PBSCs) are obtained from circulating blood rather than from bone marrow, but the amount of stem cells found in the peripheral blood is much smaller than the amount of stem cells found in the bone marrow. Peripheral blood stem cells can be used in either autologous or allogeneic transplants. The majority of PBSC transplants are autologous. However, recent clinical studies indicate that PBSCs are being used more frequently than bone marrow for allogeneic bone marrow transplantation.
The advantages of PBSC transplants when compared to bone marrow transplants are: in allogeneic transplantation, haematopoietic and immune recovery are faster with PBSCs. In autologous transplantation, the use of PBSCs can result in faster blood count recovery. Also, some medical conditions exist in which the recipient cannot accept bone marrow transplants, but can accept PBSC transplants. Some possible disadvantages to PBSC transplant versus bone marrow transplantation are: so much more fluid volume is necessary to collect enough PBSCs that, at the time that the new stem cells are infused into the recipient, the fluid can collect in the lungs. Also, the time commitment for the donor for a PBSC transplant is considerable. When the PBSCs are being collected, several outpatient sessions are needed and each session lasts approximately two–four hours.
The Transplant Procedure
BONE MARROW TRANSPLANTATION The bone marrow extraction, or harvest, is the same whether for an autologous or allogeneic transplant. Harvesting is done under general anesthesia (i.e., the donor sleeps through the procedure), and discomfort is usually minimal afterwards. Bone marrow is drawn from the iliac crest (the part of the hip bone to either side of the lower back) with a special needle and a syringe. Several punctures are usually necessary to collect the needed amount of bone marrow, approximately 1–2 quarts. (This amount is only a small percentage of the total bone marrow and is typically replaced within four weeks.) The donor remains at the hospital for 24–48 hours and can resume normal activities within a few days.
If the bone marrow is meant for an autologous transplant, it is stored at–112 to–320°F (–80 to–196°C) until it is needed. Bone marrow for an allogeneic transplant is sometimes treated to remove the donor's T cells (a type of white blood cell) or to remove ABO (blood type) antigens; otherwise, it is transplanted without modification.
The bone marrow is administered to the recipient via a catheter (a narrow, flexible tube) inserted into a large vein in the chest. From the bloodstream, it migrates to the cavities within the bones where bone marrow is normally stored. If the transplant is successful, the bone marrow begins to produce normal blood cells once it is in place, or engrafted.
Peripheral Blood Stem Cell Transplantation
Before collection for a PBSC transplant, donors receive daily four injections of the drug G-CSF, or filgrastim. (Patients can give it to themselves at home if need be.) These pretreatments stimulate the body to release stem cells into the blood. After these pretreatments, the donors' experience is similar to that of a whole blood donor's experience—PBSC donors' blood is collected at a clinic or hospital as an outpatient procedure. The differences are that several sessions will be needed over days or weeks and the blood is collected in a process called apheresis. The blood travels from one arm into a blood cell separator that removes only the stem cells, and the rest of the blood is returned back to the donor, in the other arm. The cells are then frozen for later use.
The PBSCs are administered to the recipient using the same methods as those used in bone marrow transplantation. As stated, the amount of fluid with PBSCs infused into the recipient's body can be an issue.
Costs
Bone marrow transplantation is an expensive procedure. (Bone marrow donors are volunteers and do not pay for any part of the procedure.) Insurance companies and health maintenance organizations (HMOs) may not cover the costs.
Preparation
A bone marrow transplant recipient can expect to spend 4–8 weeks in the hospital. In preparation for receiving the transplant, the recipient undergoes "conditioning"—a preparative regimen in which the bone marrow and abnormal cells are destroyed. Conditioning rids the body of diseased cells and makes room for the marrow to be transplanted. It typically involves chemotherapy and/or radiation treatment, depending on the disease being treated. Unfortunately, this treatment also destroys healthy cells and has many side effects such as extreme weakness, nausea, vomiting, and diarrhea. These side effects may continue for several weeks.
Aftercare
A two- to four-week waiting period follows the marrow transplant before its success can begin to be judged. The marrow recipient is kept in isolation during this time to minimize potential infections. The recipient also receives antibiotic medications and blood and platelet transfusions to help fight off infection and prevent excessive bleeding. Further side effects, such as nausea and vomiting, can be treated with other medications. Once blood counts are normal and the side effects of the transplant abate, the recipient is taken off antibiotics and usually no longer needs blood and platelet transfusions.
Following discharge from the hospital, the recipient is monitored through home visits by nurses or out-patient visits for up to a year. For the first several months out of the hospital, the recipient needs to be careful in avoiding potential infections. For example, contact with other people who may be ill should be avoided or kept to a minimum. Further blood transfusions and medications may be necessary, but barring complications, the recipient can return to normal activities about six to eight months after the transplant.
Risks
Bone marrow transplants are accompanied by serious and life-threatening risks. Furthermore, they are not always an absolute assurance of a cure for the underlying ailment; a disease may recur in the future. Approximately 30% of people receiving allogeneic transplants do not survive. Autologous transplants have a much better survival rate—nearly 90%—but are not appropriate for all types of ailments requiring a bone marrow transplant. Furthermore, they have a higher failure rate with certain diseases, specifically leukemia.
In the short term, there is the danger of pneumonia or other infectious disease, excessive bleeding, or liver disorder caused by blocked blood vessels. The transplant may be rejected by the recipient's immune system, or the donor bone marrow may launch an immune-mediated attack against the recipient's tissues. This complication is called acute graft-versus-host disease, and it can be a life-threatening condition. Characteristic signs of the disease include fever, rash, diarrhea, liver problems, and a compromised immune system.
Approximately 25–50% of bone marrow transplant recipients develop long-term complications. Chronic graft-versus-host disease symptoms include skin changes such as dryness, altered pigmentation, and thickening; abnormal liver function tests; dry mouth and eyes; infections; and weight loss. Other long-term complications include cataracts (due to radiation treatment), abnormal lung function, hormonal abnormalities resulting in reduced growth or hypothyroidism, secondary cancers, and infertility.
Questions to Ask the Doctor
- What is allogenic bone marrow transplantation (BMT)?
- What is syngenic bone marrow transplantation?
- What is autologous bone marrow transplantation?
- What is Graft-versus-Host disease (GVHD) and can it be prevented?
- What diseases are treated by BMT?
- What is HLA/histocompatibility matching?
Normal Results
In a successful bone marrow transplant, the donor's marrow migrates to the cavities in the recipient's bones and produces normal numbers of healthy blood cells. Bone marrow transplants can extend a person's life, improve quality of life, and may aid in curing the underlying ailment.
Resources
Periodicals
Dreger, P., and N. Schmitz. "Allogeneic transplantation of blood stem cells: coming of age?" Annals of Hematology 80, no. 3 (March 2001): 127-36.
Nuzhat, Iqbal, Donna Salzman, Audrey J. Lazenby, et al. "Diagnosis of Gastrointestinal Graft-Versus-Host Disease." The American Journal of Gastroenterology 95 (November 2000): 3034-3038.
Organizations
American Society for Blood and Marrow Transplantation (ASBMT). 85 W. Algonquin Road, Suite 550 Arlington Heights, IL 60005. (847) 427-0224. mail@asbmt.org. Founded in 1990, a national professional association that promotes advancement of the field of blood and bone marrow transplantation in clinical practice and research.
Blood & Marrow Transplant Newsletter (Formerly BMT Newsletter). 2900 Skokie Valley Road, Suite B, Highland Park, IL 60035 (847) 433-3313. 1-888-597-7674. help@bmtinfonet.org.
BMT Information.
Health Resources and Services Administration. 5600 Fishers Lane, Rm. 14-45, Rockville, MD 20857, 301-443-3376, comments@hrsa.gov.
International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry N. America. Health Policy Institute, Medical College of Wisconsin, 8701 Watertown Plank Road, P.O. Box 26509, Milwaukee, WI 53226 USA, 414-456-8325, ibmtr@mcw.edu. Voluntary organizations of more than 400 institutions in 47 countries that submit data on their allogeneic and autologous blood and marrow transplant recipients to the IBMTR/ABMTR Statistical Center at the Medical College of Wisconsin in Milwaukee.
Leukemia & Lymphoma Society, Inc. 1311 Mamaroneck Avenue White Plains, NY 10605, 914-949-5213
National Marrow Donor Program. Suite 500, 3001 Broadway Street Northeast, Minneapolis, MN 55413-1753. (800) MARROW-2.
National Organ and Tissue Donation Initiative.
—Julia Barrett; Laura Ruth, Ph.D.
