Therapeutic decision making in BMT/SCT for amyloidosis

Definition page 157 Disease classification 157 Results of conventional therapy 158 Results of autologous transplantation 158 Indications for transplantation 161 Contraindications to transplantation 161 Follow-up after transplantation 162 Further reading 162 Definition Amyloidosis results from altered protein folding leading to the deposit of insoluble amyloid fibrils in possibly every organ or organ system of the body. Untreated, systemic amyloidosis is generally fatal. Disease classification In this chapter, only the most common form of amyloidosis, AL amyloidosis will be discussed. Primary AL amyloidosis is caused by the proliferation of malignant B cell clones in the absence of a frank plasma cell dyscrasia–like multiple myeloma. Common target organs of AL amyloidosis are the kidneys (nephrotic syndrome, kidney failure), the heart (cardiomyopathy), the liver (hepatomegaly), and the gut (malabsorption or unexplained diarrhea). Other typical manifestations include macroglossia and peripheral neuropathy. Secondary AL amyloidosis is observed in at least 15% of patients with multiple myeloma. Results of conventional therapy The survival of untreated patients with AL amyloidosis is short. In older studies, a median survival time of 7 to 8 months was reported. Later, the treatment with alkylating agents was introduced, which stabilizes the disease, but rarely results in remissions. Conventional treatment consists of cycles of oral prednisone, and melphalan extends the median period of survival to about 12 to 18 months. Recently, a combination of lenalidomide and dexamethasone was introduced for the treatment of systemic amyloidosis and, on the basis of a short follow-up, the combination appears to have promising activity (Dispenzieri et al., 2007).