The nature and severity of the side effects from high-dose chemotherapy and autologous stem cell transplantation are directly related to the type of high-dose chemotherapy treatment regimen used and are further influenced by the condition and age of the patient. The safety of autologous transplant has improved a great deal thanks to advancements in supportive care to manage the many potential side effects. While high doses of chemotherapy and radiation therapy can potentially affect any of the body’s normal cells or organs, the more common side effects are well described and include the following:
Bone Marrow Suppression
High-dose chemotherapy directly destroys the bone marrow’s ability to produce white blood cells, red blood cells and platelets. Patients experience side effects caused by low numbers of white blood cells (neutropenia), red blood cells (anemia) and platelets (thrombocytopenia). Patients usually need blood and platelet transfusions to treat anemia and thrombocytopenia until the new graft beings producing blood cells. The duration of bone marrow suppression can be shortened by infusing an optimal number of stem cells and administering growth factors that hasten the recovery of blood cell production.
During the two to three weeks it takes the new bone marrow to grow and produce white blood cells, patients are susceptible to infection and require the administration of antibiotics to prevent bacterial and fungal infections. Bacterial infections are the most common during this initial period of neutropenia. Stem cells collected from peripheral blood tend to engraft faster than bone marrow and may reduce the risk of infection by shortening the period of neutropenia. The growth factor Neupogen® (filgrastim) also increases the rate of white blood cell recovery and has been approved by the Food and Drug Administration for use during autologous stem cell transplant.
The immune system takes even longer to recover than white blood cell production, with a resulting susceptibility to some bacterial, fungal and viral infections for weeks to months. After initial recovery from autologous stem cell transplant, patients are often required to take antibiotics for weeks to months to prevent infections from occurring. Prophylactic antibiotic administration can prevent Pneumocystis carinii pneumonia and some bacterial and fungal infections. Prophylactic antibiotics can also decrease the incidence of herpes zoster infection, which commonly occurs after high-dose chemotherapy and autologous stem cell transplant.
Veno-Occlusive Disease of the Liver (VOD)
High-dose chemotherapy can result in damage to the liver, which can be serious and even fatal. This complication is increased in patients who have substantial amounts of previous chemotherapy and/or radiation therapy, a history of liver damage or hepatitis. Veno-occlusive disease (VOD) of the liver typically occurs in the first two weeks after high-dose chemotherapy treatment. Patients typically experience symptoms of abdominal fullness or swelling, liver tenderness and weight gain from fluid retention. Development of strategies to prevent or treat VOD is an active area of clinical investigation.
Interstitial Pneumonia Syndrome (IPS)
High-dose chemotherapy can directly damage the cells of the lungs. This may be more frequent in patients treated with certain types of chemotherapy and/or radiation therapy given prior to the transplant. This complication of transplant may occur anytime, from a few days after high-dose chemotherapy to several months after treatment. This often occurs after a patient has returned home from a transplant center and is being seen by a local oncologist.
Patients typically experience a dry non-productive cough or shortness of breath. Both patients and their doctors often misinterpret these early symptoms. Patients experiencing shortness of breath or a new cough after autologous transplant should bring this to the immediate attention of their doctor since this can be a serious and even fatal complication.
Graft failure is extremely unusual in autologous stem cell transplantation. Graft failure occurs when bone marrow function does not return. The graft may fail to grow in the patient—resulting in bone marrow failure—with the absence of red blood cells, white blood cells and platelet production. This results in infection, anemia and bleeding. Graft failure may also occur in patients with extensive marrow fibrosis before transplantation, a viral illness or from the use of some drugs (such as methotrexate). In leukemia patients, graft failure often is associated with a recurrence of cancer; the leukemic cells may inhibit the growth of the transplanted cells. In some cases, the reasons for graft failure are unknown.
Long-Term Side Effects of Autologous Stem Cell Transplant
There are several long-term or late side effects that result from the chemotherapy and radiation therapy used in autologous stem cell transplant. The frequency and severity of these problems depends on the radiation or chemotherapy used to treat the patient. It is important to have the doctors providing your care explain the specific long-term side effects that can occur with the actual proposed treatment. Some examples of complications you should be aware of include the following:
Cataracts: Cataracts occur in the overwhelming majority of patients who receive total body irradiation in their treatment regimen. In patients who receive chemotherapy without total body irradiation, cataracts are much less frequent. The onset of cataracts begins at 18 to 24 months following treatment. Patients who have received large doses of steroids will have an increased frequency and earlier onset of cataracts. Patients are advised to have slit lamp eye evaluations annually with early correction with artificial lenses.
Infertility: The overwhelming majority of women who receive total body irradiation will be sterile. However, some prepubertal and adolescent females do recover ovulation and menstruation. In patients who receive chemotherapy-only preparative regimens, the incidence of sterility is more variable and more age related (i.e., the older the woman is at the time of treatment, the more likely chemotherapy will produce anovulation). These are important considerations because of the need for hormone replacement. All females should have frequent gynecologic follow-up examinations.
The overwhelming majority of men who receive total body irradiation will become sterile. Sterility is much more variable after chemotherapy-only regimens. Men should have sperm counts performed to determine whether or not sperm are present and should be examined over time, as recovery can occur.
New Cancers: Treatment with chemotherapy and radiation therapy is known to increase the risk of developing a new cancer. These are called “secondary cancers” and may occur as a late complication of high-dose chemotherapy. For patients with breast cancer treated with high-dose chemotherapy, the risk of developing a secondary cancer has been reported to be less than 2 percent. Patients with lymphoma treated with high-dose chemotherapy and autologous stem cell transplant appear to have about an 8 to 10 percent chance of developing a secondary cancer if treated with total body irradiation and 2 to 4 percent if treated with high-dose chemotherapy and no radiation. Patients with lymphoma treated with conventional chemotherapy have also been reported to have a 4 to 8 percent risk of developing a secondary cancer. How much additional risk occurs from high-dose chemotherapy is unclear; however, high-dose radiation clearly increases the risk of developing a secondary cancer.
High-dose chemotherapy and autologous stem cell transplant is increasingly used to treat certain cancers because it improves cure rates. Patients should be aware of the risk of secondary cancer following high-dose chemotherapy treatment and discuss the benefits and risks of high-dose chemotherapy with their primary cancer physician.