Bone Marrow Transplants

Emergency physicians can expect to care for increasing numbers of bone marrow transplant patients due to the rising prevalence and survivability of this procedure. Bone marrow transplants are currently performed for malignant conditions such as leukemia, lymphoma, and selected solid tumors as well as for nonmalignant conditions such as aplastic anemia, thalassemia, and sickle cell anemia.

Bone marrow transplants can be categorized as either allogeneic or autologous. In an allogeneic transplant, bone marrow is first obtained from an HLA-matched donor, preferably a sibling. The patient then receives high-dose chemotherapy or radiotherapy to eliminate native bone marrow and destroy residual cancer cells. The donor marrow is then administered to the recipient intravenously. The recipient is profoundly myelosuppressed for a period of 1 to 3 weeks until the transplanted cells assume their place in the recipient's bone marrow by a process known as engraftment. Autologous transplantation is performed in a similar manner, although a sample of a patient's own marrow is taken before high-dose chemotherapy, and it is this sample that is used to reestablish hematopoetic cell function.

Emergency physicians are unlikely to encounter the acute complications of bone marrow transplantation because these patients often are kept in the hospital for several weeks following their transplant until engraftment occurs. However, emergency physicians should be aware of the long-term complications and consequences of bone marrow transplantation. Like solid-organ transplant recipients, bone marrow recipients are at increased risk of infection. This risk is not just confined to the period of granulocytopenia preceding engraftment. Even with a normal neutrophil count, bone marrow transplant patients have a residual cellular and humoral immunodeficency that persists for 12 to 24 months after transplantation. Return of immune function generally is slower in allogeneic transplant recipients than in autologous transplant recipients. Bone marrow transplant patients are at particular risk of infection from encapsulated bacteria, Pneumocystis carinii, cytomegalovirus (CMV), varicella-zoster virus, Candida, and Aspergillus. CMV pneumonitis is the most common infectious cause of death after bone marrow transplantation and typically occurs 1 to 6 months following the transplant. To decrease the risk of opportunistic infection, bone marrow transplant patients are often prophylactically administered penicillin, trimethoprim-sulfamethoxazole, and ganciclovir for the first 3 to 6 months following their transplant. A fever or other sign of infection should be taken very seriously in a bone marrow transplant patient (even if the neutrophil count is normal), and a treatment plan should be developed in conjunction with the patient's hematologist.

A complication unique to bone marrow transplant patients is graft-versus-host disease. This disorder occurs only in allogeneic transplant patients. It is caused by immunologically competent donor cells attacking target antigens in the recipient. Patients develop rash, diarrhea, and an elevated serum bilirubin level. The diagnosis is confirmed histologically by appropriate biopsy. Without treatment, the condition is often fatal. Treatment with prednisone, cyclosporine, antithymocyte globulin, or thalidomide improves the long-term prognosis of these patients. Unfortunately, these drugs also delay immunologic recovery and increase the risk of opportunistic infection.

Another unusual complication of bone marrow transplantation is hepatic venoocclusive disease. This condition usually occurs within 30 days of transplantation and is caused by thrombotic obstruction of small intrahepatic venules with resulting damage to the surrounding centrilobular hepatocytes. The exact precipitant of this disease is unknown. The diagnosis should be considered in patients with jaundice, tender hepatomegaly, and ascites. Up to 20 percent of all bone marrow transplant recipients have some degree of hepatic venoocclusive disease. In severe cases, progressive hepatic and renal failure occur. Treatment is largely supportive, although thrombolytic therapy has shown some promise.

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