Sometimes a hematopoietic (blood) stem cell / bone marrow transplant may not be successful because the disease returns or because of severe treatment-related side effects. Side effects that may occur include:
- Graft-vs-host disease (GvHD)
- Graft rejection
- Bacterial, fungal or viral infections
- Problems with the stomach, intestines, liver or lungs
- Complications with the nervous system
- Late effects after transplant
Complications and Side Effects
Gastrointestinal or Liver Complications
Gastric or hepatic diseases are frequent complications that occur after stem cell/bone marrow transplant. Conditioning regimens that usually consist of high-dose chemotherapy, radiation therapy, or both, can cause mucositis. Mucositis is the presence of sores throughout the gastrointestinal tract; signs and symptoms include mouth sores, esophagitis (soreness when swallowing), stomach ulcers, or diarrhea with stomach cramps. Patients sometimes require intravenous narcotic medications and total parenteral nutrition (TPN) until the mucositis has resolved.
The most common hepatic complication that occurs after stem cell transplantation is veno-occlusive disease (VOD) of the liver. Patients with prior liver injury, a history of hepatitis or a high-risk disorder are at greatest risk of VOD, although the disease can develop in any patient after transplantation. VOD is characterized by the elevated concentration of bilirubin (which results in the yellow appearance of the skin and eyes), an enlarged liver and fluid retention or weight gain. VOD is frequently treated by fluid restriction. Preventive measures include the administration of heparin and daily monitoring of weights and fluid balance while the patient is hospitalized. VOD can be severe and, in such instances, can even result in death.
Graft rejection occurs when the infection-fighting system of the patient recognizes the infused donor stem cells as being different and destroys them. High-dose chemotherapy destroys the patient’s bone marrow and it cannot regenerate on its own. Therefore, patients who experience graft rejection can become quite ill and, in some instances, die of complications from the treatment. To prevent graft rejection, the patient receives medications, chemotherapy, total body irradiation and other antibody medications before the donor stem cell is infused. The chances of graft rejection are related to the match between the donor and recipient HLA antigens, the overall genetic relationship between donor and recipient, and the type of disease for which the transplantation is being performed.
Graft vs. Host Disease
Graft-vs-host disease (GvHD) is a complication that is observed after allogeneic stem cell transplant. GvHD occurs when infection-fighting cells from the donor recognize the patient’s body as being different or foreign. These infection-fighting cells then attack tissues in the patient’s body just as if they were attacking an infection. GvHD is categorized as acute when it occurs within the first 100 days after transplantation and chronic if it occurs more than 100 days after transplantation. Tissues typically involved include the liver, gastrointestinal tract and skin.
Symptoms of acute GvHD include rash, yellow skin and eyes due to elevated concentrations of bilirubin, and diarrhea. Acute GvHD is graded on a scale of 1 to 4; grade 4 is the most severe. In some severe instances, GvHD can be fatal. GvHD is more easily prevented than treated. Preventive measures typically include the administration of cyclosporin with or without methotrexate or steroids after stem cell transplant. Alternatively, T lymphocytes are removed from the stem cell graft before it is transplanted.
First-line treatment of GvHD is steroid therapy. Alternative therapies are considered for patients whose GvHD does not respond to steroids. Chronic GvHD occurs approximately in 10-40 percent of patients after stem cell transplant. Symptoms vary more widely than those of acute GvHD and are similar to various autoimmune disorders. Some symptoms include dry eyes, dry mouth, rash, ulcers of the skin and mouth, joint contractures (inability to move joints easily), abnormal test results of blood obtained from the liver, stiffening of the lungs (difficulty in breathing), inflammation in the eyes, difficulty in swallowing, muscle weakness, or a white film in the mouth.
The incidence of GvHD increases with increasing degree of mismatch between donor and recipient HLA antigens, increasing donor age and increasing patient age.
Infection complications are one of the most serious side effects of stem cell transplant. Life-threatening infections can occur in approximately 30 percent of patients receiving allogeneic transplants; the incidence is lower for recipients of autologous transplants. Because the Transplant Program at St. Jude is concerned about infectious complications, recipients of allogeneic stem cell transplants undergo weekly screening for the presence of infectious organisms during their stay in the Transplant Unit while they reside in Memphis. In addition, patients are placed on prophylactic or preventive medications to reduce chances of infections. Recipients of allogeneic stem cell transplants are placed on a restricted or low-bacteria diet to minimize the chance of infection. Because patients who receive autologous transplants have an immune system that is not as weakened by conditioning regimen and post-transplantation therapy, these patients have no dietary restrictions in place. Bacterial, fungal and viral infections can make patients quite ill. Prompt investigation and, in some instances, surgical procedures are required to diagnose and treat these complications.
Neurologic complications associated with stem cell transplantation are significant problems. Certain chemotherapeutic drugs can cause seizures. Therefore, patients who receive chemotherapeutic drugs that are associated with seizures can be given medication to prevent seizures. In addition, patients may experience infection resulting in meningitis or encephalitis. Pain is another complication. Cyclosporin and other medications given to prevent or treat GvHD can cause nerve or neuropathic pain that can be controlled by medications.
Pulmonary or lung complications are significant causes of morbidity and mortality after stem cell transplant. Infectious and non-infectious causes of pneumonitis or lung inflammation after transplantation are well characterized. Pathogens that cause lung infections include bacterial, fungal and viral organisms. Weekly screening measures can be done to monitor patients for early reactivation of certain infectious agents, such as cytomegalovirus (CMV). Prophylactic medication is administered to recipients of allogeneic stem cell transplants at many centers along with weekly monitoring.
Late Effects after Transplant
Patients who receive allogeneic or autologous stem cell transplants are usually observed for a long time after transplantation to determine whether side effects are present. Recipients of conditioning regimens in which total body irradiation was used are at risk of endocrine (gland) problems that include hypothyroidism, adrenal insufficiency or growth hormone insufficiency. Therefore, it is important that the patient’s height and weight be serially evaluated, when necessary, monitored by an endocrinologist.
Survivors of stem cell transplantation are at increased risk of osteoporosis or weakening of the bones. This complication is largely due to the treatment required during the transplant process, and the use of corticosteroids, which are used to treat graft-vs-host disease (GvHD). Pulmonary and cardiac abnormalities should be followed by routine screening examinations. In addition, survivors of transplantation have been shown to be at high risk of second malignancies, which include leukemia, brain tumors and skin cancers. The type of late effects for which a patient is at risk vary according to the type of conditioning regimen administered