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.
Sinusoidal Obstructive Syndrome (SOS)-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. Sinusoidal Obstructive Syndrome 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. A new drug called defibrotide has has shown some promise in treating patients with SOS, defibrotide is currently available in Europe and is being evaluated in clinical trials in the United States.
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.