Anna T. Meadows, M.D.
Director, Division of Oncology and Cancer Research Center
Nancy J. Bunin, M.D.
Clinical Director, Bone Marrow Transplantation
Ann M. Leahey, M.D.
Diana S. Wheeler
The Children's Hospital of Philadelphia
Copyright 1994, Armour Pharmaceutical Company
Bone marrow transplantation (BMT) is used to treat a number of cancers, blood diseases, and immune disorders that were once considered incurable. Since it was first used successfully in 1986, BMT has become one of the most promising treatments for a number of serious illnesses. In 1991, more than 7,500 people in the US underwent the procedure, and BMT now saves thousands of lives each year.
BMT has been recommended as the best treatment for your child at this time. This booklet was designed to provide you and your family with basic information about the procedure, so you will know what to expect. Undoubtedly, studying this booklet will lead to more questions, which you should feel free to discuss with your child's health care team. It is important to remember that transplantation affects all family members, and the more you know, the more you will be able to support each other throughout this challenging experience.
Bone marrow is the spongy tissue inside bones that produces stem cells, specialized cells that grow and divide to form the body's blood cells. There are three major types of blood cells.
White blood cells, or leukocytes, fight infection; red blood cells, or erythrocytes, carry oxygen,; and platelets help to control blood clotting.
Bone marrow transplantation (BMT) was first used experimentally to treat people exposed to radiation following a nuclear accident. Transplanted bone marrow effectively replaced marrow that had been destroyed by radiation. This same procedure was found to be effective in treating certain malignant and nonmalignant diseases that cause the marrow to produce either abnormal blood cells or very low numbers of normal cells. Drugs and radiation are used to destroy both abnormal and normal cells, and BMT replaces the diseased or damaged marrow with healthy marrow. BMT is not a surgical procedure, but a painless infusion, similar to a blood transfusion, that is done in the hospital room. The procedure will be described later.
Table 1 lists a number of cancers, blood diseases, and immune disorders for which BMT has been shown effective or has the potential to be effective. With each patient treated, scientists learn more about this exciting and still evolving treatment method.
Table 1 - Selected Uses for Bone Marrow Transplantation
Whether the diagnosis is a malignant or nonmalignant disease, 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.
The type of transplant your child will receive is based on the diagnosis and the availability of a donor.
One type of transplant is allogeneic, in which the child receives marrow from a genetically matched or genetically similar donor. Often this is a family member, but may be an unrelated donor found through a bone marrow registry. For self-donation, or an autologous graft, the child's own bone marrow is removed, sometimes treated to kill disease cells, and then reinfused. Rarely, a child may receive a syngeneic graft, from an identical twin.
Donors are matched through blood tests that determine the match of certain human leukocyte antigens, called HLA typing. It is rare that a parent is suitable as a donor. Non-identical sibling match is only about 25-30% of cases, while identical twins are a 100% match. If no family donor is suitable, your child may receive marrow from an unrelated donor located through the National Marrow Donor Program. This network maintains files listing more than 700,000 potential donors.
The BMT procedure can require up to six months of hospitalization and extensive care that can cost $100,000 to $250,000 or more. While health insurance usually covers most of these expenses, the family may still be responsible for a considerable amount. Your hospital family counselor can help to process insurance claims, and may suggest ways to pay expenses not covered by insurance.
After your child is referred to the transplant center, the BMT coordinator will work closely with you and your family to help arrange the many aspects of your child's hospitalization, transplantation, and follow-up care. The coordinator will contact the donor registry if an unrelated donor is required, and will set up a tentative date for transplant once a donor has been identified. Hospital staff members will help to process paperwork and track the hundreds of details involved in transplantation.
Throughout the transplantation process, your child's care will be directed by a health care team that includes the BMT coordinator, physicians, nurse practitioners and nurses, physical therapists, pharmacists, dietitians, laboratory technologists, and social workers. Each team member is familiar with the effects of BMT not only on the patient, but on the family as well, and will be available if you have questions about any of the procedures.
As you spend time at the hospital with your child, you will meet other parents and families, who will help to support you and your family by sharing their experiences with BMT.
About two to four weeks before transplant, your child will visit the transplant center to undergo heart, lung and kidney tests and other tests that may be needed to evaluate general health. The results of these tests, along with your child's medical history and proposed treatment plan, will be discussed by your child's health care team. Your child's physician will inform you about the results of the tests, recommend treatment plans, and explain the potential risks and benefits of various treatments. Once you understand the treatment plan, you will be asked to sign consent forms stating that you agree to the treatment.
From admission until after transplant, your child will stay in a private hospital room that is part of the BMT unit. If you are from out of town, the BMT coordinator may arrange for you and your family to stay nearby. Some hospitals have special facilities or can arrange low rates at nearby hotels.
An important part of your child's therapy is the placement of a central venous (CV) line, sometimes called by the trade name Hickman or Broviac. This is a flexible tube that is inserted into your child's chest so that blood can be drawn and medications given without the need for additional needle sticks. The CV line will be placed before any pre-transplant therapy is begun, and will remain in place at least throughout the hospital stay, and maybe longer. The bone marrow will be given through the CV line, which will be used for intravenous nutrition and to infuse blood and platelets as well.
In preparation for transplant, your child's immune system will be suppressed, greatly increasing the risk of infection. To help reduce this risk, some form of protective isolation will be practiced. This procedure varies at different hospitals, but many require visitors and staff to wear surgical masks when inside the child's room. No fresh fruits, vegetables, flowers, or plants will be permitted in the room. Persons with colds, flu or other infectious diseases will be asked to stay away until they recover. Your child will be confined to the room, but may participate in play therapy, and other activities.
Hand washing is an important part of protective isolation, and proper hand washing is the single most effective way to prevent the spread of infection. Staff and visitors will be required to wash their hands frequently, and always when entering the child's room.
Throughout the hospital stay, your child will undergo many tests to determine disease status and overall health. These many include blood tests, X-rays, heart and lung tests, liver and kidney function tests, computed tomography (CT) or magnetic resonance imaging (MRI) scans, bone marrow aspiration, and spinal tap. Vital sign -- temperature, pulse, blood pressure, and respirations, or numbers of breaths per minute -- will be checked frequently. Other tests also will be performed.
Your child will undergo three kinds of blood tests. Blood counts will help to determine disease status and the success of BMT. Blood chemistries will monitor your child's general physical condition. If infection is suspected, blood cultures will identify the organism involved.
Before transplantation, your child will received a conditioning treatment. This includes the use of powerful drugs, or chemotherapy, to destroy any remaining cancer cells. if your child does not have cancer, chemotherapy may be used to suppress the immune system and prevent rejection of an allogeneic transplant. Usually the regimen, or treatment plan, includes more than one drug, given by mouth or through the CV line. Your child's chemotherapy regimen will be determined after careful analysis of the diagnosis and disease stage.
In addition to chemotherapy, some children will also require X-ray therapy, more properly called radiation therapy. Like chemotherapy, radiation may be given to destroy any remaining cancer cells and to suppress the immune system, preventing transplant rejection.
Your child may undergo a more extensive form of radiation known as total body irradiation, or TBI. This is usually done in 15 to 30-minute segments over a period of three or four days. The child must remain still during TBI, but a doctor, technician and parent will watch on a video monitor and through a window.
Chemotherapy and radiation may have Unpredictable short-term and long-term side effects, which are sometimes life-threatening (Table 2). Short-term side effects may include diarrhea, fluid buildup, bloody urine, mouth sores, and skin rashes. Temporary hair loss occurs in all patients. TBI may also cause temporary skin darkening similar to sunburn, salivary gland swelling, or loss of taste. Long-term side effects of chemotherapy and radiation include sterility, cataracts, and decreased growth. Damage to the vital organs -- liver, lungs, kidneys, or heart -- may be life-threatening.
Bone marrow for transplantation is collected, or harvested, in the operating room while the patient or donor is under general anesthesia. Marrow is removed from the hip bone through a long needle, and collected in a large sterile container. The amount of marrow removed will depend on the amount required for transplant.
After harvest, autologous bone marrow may be treated to reduce the risk of certain complications. The marrow may be transplanted immediately after processing, or frozen and stored for later use. Donors usually remain in the hospital overnight, but may resume normal activities upon returning home. There will be some discomfort in the areas where marrow has been withdrawn; usually this can be controlled with a mild painkiller.
The bone marrow transplant will take place in your child's hospital room, where the marrow will be given through the central venous line. The procedure is similar to a blood transfusion, and does not hurt. While the marrow is being infused, your child will be checked frequently for fever, chills, chest pain, or other signs of any adverse reactions.
After infusion, the marrow travels through the bloodstream into the bone marrow spaces, where the basic stem cells grow, divide, and begin to produce new red blood cells, white blood cells, and platelets.
Before transplant, the old marrow is destroyed, and for a few weeks after, the new marrow cannot produce mature cells. This condition is called aplasia, and it is a time when your child is at greatest risk for infection and bleeding. While your child is aplastic, you can expect a number of things to happen. There is an increased risk of infection. Your child may feel tired and weak due to anemia, and may bleed or bruise more easily. Red blood cell and platelet transfusions will be necessary until the new bone marrow has grown sufficiently, and growth factors may be used to stimulate white blood cell production. Intravenous immunoglobulin may be given to lessen the risk of certain infections.
Antibiotics will be given to treat infections that may occur during aplasia. Even when treated with antibiotics, some infections may be life-threatening. Pain medication will relieve mouth sores, and IV nutrition will help restore nutrients lost to diarrhea or poor appetite. Fluid buildup also may be treated with drugs. These symptoms will usually improve as the bone marrow starts to grow. New marrow growth will be monitored by daily blood counts.
After transplant, the white blood cells regenerate first, usually followed within a few weeks by red blood cells, and platelets. Signs of this new growth or engraftment, should occur within two or four weeks after allogeneic transplant, but may be delayed after autologous transplant. A low white blood cell count increases the risk of infection. If there is a decrease in red blood cells, or anemia, the body receives less oxygen. A decrease in platelets causes impaired clotting.
A potentially serious complication of allogeneic transplant is graft-versus-host disease or GVHD. This occurs when the "graft" -- the donated marrow -- recognizes the "host" -- the recipient -- as foreign, and begins to attack certain organs, such as the skin, liver and intestines. GVHD can be mild or severe, and occurs less frequently in children than in adults. There is no risk of GVHD after an autologous transplant.
All patients who receive allogeneic transplants are given drug therapy to reduce the chance of developing GVHD. While it can usually be controlled with medication, including cyclosporine or prednisone, GVHD may be life-threatening. There is one positive effect of GVHD; in some patients who develop this condition, there is a lower relapse rate of the original disease.
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.
Recovery after BMT is slow, and for several weeks afterward your child may have nausea, vomiting, fever, diarrhea, and extreme weakness. It may be months before your child regains pre-illness energy levels. Good nutrition is particularly important to recovery, and food supplements or other nutrients may be given until a healthy appetite returns.
After transplant, your child will require many kinds of medication, and some of these drugs will be continued after leaving the hospital. Your child's health care team will explain how to use these medications, and help with any questions about the prescribed treatment plan.
Your child will be discharged from the hospital about four to six weeks after transplant. The health care team will continue to be concerned about your child's care, and about the impact of the disease and treatment on all the members of your family. The team will help you decide when your child should return to school and other activities. Your local physician will be given details about your child's post-transplant care, and will monitor medications.
For two or three months after leaving the hospital, your child will require frequent follow-up examinations and treatments. If your home is far away, you and your child may stay near the hospital in a special residence.
It will be six months to a year, or more, before your child's immune system recovers, and during that time there will be an increased risk of contracting infections. You can help lessen the risk of infection after discharge by keeping your child away from large crowds of people. Follow-up exams will continue for many years, to check for relapse of disease and to detect any late effects of drugs or radiation treatment.
Bone marrow transplantation is an intensive procedure that has a profound effect on the family, as well as on the patient. While BMT provides the best opportunity for a cure, it also provides an opportunity for families to become closer and more supportive of each other than ever before. The more you and your family know about this procedure, the more you will be able to help your child and support each other throughout this time.
This booklet was produced in cooperation with The Children's Hospital of Philadelphia, and is based on current practice at the time the booklet was written. Bone marrow transplantation is an evolving treatment method, and procedures change often. You should rely on the physicians at your local institution for the latest information. If you would like to know more about bone marrow transplantation, ask your doctor to recommend additional reference sources.