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Stem Cell Transplantation

Cancer therapy (chemotherapy, radiation therapy, etc.) can damage or destroy normal cells, as well as cancer cells. Many chemotherapeutic drugs, in particular, can harm rapidly dividing cells such as the blood-forming stem cells of the bone marrow. Yet high drug doses are needed to treat leukemia effectively. So what can be done?

Physicians have begun to solve this problem by performing stem cell transplantation (SCT). Stem cells are blood-forming (hematopoietic) cells of the bone marrow; they continuously divide to form the new blood cells that populate the arteries and veins. The SCT procedure enables physicians to give chemotherapy and radiotherapy in doses that are strong enough to eliminate leukemia cells. The injured bone marrow then is replenished by a transplant of stem cells, which can manufacture the necessary new blood cells.

Stem cells for SCT can be gathered from different sources:

• aspiration (suctioning) directly from the bone marrow at the back of the hip crest;
• leukapheresis (also known as apheresis), separation of white blood cells in blood from the bloodstream; or
• umbilical cord cells (stem cells obtained from umbilical cord blood), usually from donations made by normal siblings who are born after a child who has leukemia.

The cells are carefully frozen and stored until the patient has completed high-dose treatments for leukemia. Such treatments usually consist of a 3-day course of chemotherapy (for example, with cyclophosphamide, cytarabine, etoposide, melphalan, or busulfan) with/without a 3-day course of total body irradiation (TBI). After therapy, the stem cells are thawed and given to the patient by means of a blood transfusion.

SCT are classified as autologous or allogeneic, based on characteristics of the cell donor. Autologous SCT, also known as autologous bone marrow transplant (autoBMT), is a procedure in which a patient's own stem cells (immature cells from which all blood cells develop) are removed from the bone marrow. This type of transplant is not frequently used, because it is very difficult to guarantee that normal stem cells have been separated from leukemic cells, even after purging, that is treatment of stem cells with drugs, immunologic agents, heat, or other substances/methods to kill or remove leukemic cells.

Another form of autologous SCT is peripheral blood stem cell transplantation, or leukapheresis. The patient's blood is passed through a machine that removes the stem cells, then returns the blood to the patient. This procedure usually takes 3 or 4 hours to complete. The stem cells may or may not be treated with drugs to kill any remaining leukemia cells. The stem cells are stored until they are transplanted back into the patient. Leukapheresis may be performed alone or with autoBMT, although most physicians prefer to use leukapheresis by itself.

Allogeneic SCT, also known as allogeneic bone marrow transplant (alloBMT), is a form of transplant in which the stem cells are gathered from a donor whose tissue type closely matches the patient's tissue type. Such donors usually are relatives (brother, sister, child) or, occasionally, a matched unrelated donor (MUD). AlloBMT usually is reserved for individuals who are younger than 55 and who have a compatible family donor - that is, a donor with compatible human leukocyte antigen (HLA), a protein found on the surface of some cells, such as leukocytes). Allogeneic donor cells actually may help to fight leukemia cells because they initiate a response known as the "graft versus leukemia" reaction.

If the person receives an allogeneic transplant, he or she must be treated with drugs that suppress rejection reactions (e.g., cyclosporine, methotrexate, prednisone, and antilymphocyte globulin [ALG] or antithymocyte globulin [ATG]). For example, "graft-versus-host disease" (GVHD) is a result of rejection reactions that occur in 25 to 50% of cases. The leukemia patient should ensure that SCT is performed at a qualified medical facility. The treatment staff should be experienced in all types of transplants, including MUD transplants, as well as patient care during the recovery period.

Transplant patients typically are kept in protective isolation in the hospital until their total white blood cell (WBC) count is above 500. During this time, the individual receives supportive care, such as intravenous nutrition, treatment with antibacterial and antifungal medications, and transfusions with red blood cells and platelets. Within 2 to 3 weeks, the stem cells usually begin to make white blood cells. Next, platelets are produced, followed several weeks later by the manufacture of red blood cells. Once the WBC count approaches 1000, the patient generally can be discharged from the hospital. Daily outpatient check-ups may be scheduled for several weeks, followed by regular appointments over a 6-month period. The individual's oncologist usually will schedule an exam at the SCT clinic 1 year after treatment; thereafter, clinic appointments are made only if symptoms return.

Side effects due to SCT may occur shortly after treatment, or they may develop much later. Early complications usually are related to the cellular injury caused by high-dose chemotherapy and radiotherapy (for example, temporary hair loss, anemia, leukopenia, thrombocytopenia, and gastrointestinal symptoms like nausea, vomiting, and diarrhea. Long-term or chronic complications may include:

• Chronic graft-versus-host disease—or GVHD that occurs after 100 days. This autoimmune disorder develops when donor stem cells make immune cells that attack tissues of the patient's skin, gut, mouth, genitalia, and other organs. Typical features include dry mouth and eyes; skin changes such as thickening, hair loss, dryness, and rashes; fatigue; muscle pain and weakness; and infection.
• Irreversible sterility in men and women who have received total body irradiation (TBI) or high-dose busulfan chemotherapy. Women will experience radiation-induced menopause and will require gynecological observation after the first 100 days. Hormone replacement therapy (HRT) will be needed in pre-menopausal women.
• Endocrine (hormonal) system malfunction, particularly of the thyroid gland. Hypothyroidism (low thyroid activity) is frequent, so regular thyroid screening is needed after SC.
• Bone marrow toxicity (poisonous damage), especially when manifested as asceptic necrosis - bone cell death without infection. Severe bone and/or joint damage may require surgical replacement.
• Respiratory symptoms and impairment (e.g., shortness of breath) due to radiation-related lung damage.
• Cataract, an abnormality of the lens of the eye which blocks light and impairs vision.
• Thrombotic microangiopathy (TM), clot formation in the small blood vessels), a condition that includes hemolytic uremic syndrome (HUS; bloody urine) and thrombocytopenic purpura (TTP; purplish discoloration of the skin caused by internal hemorrhaging related to a low platelet count). TM has multiple causes and, unfortunately, often does not respond well to therapy.

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