An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis

Primary or AL amyloidosis results from a plasma cell dyscrasia in which fib rillar light chain protein deposition leads to organ failure and death. Sta ndard treatment for AL amyloidosis has been oral melphalan and prednisone. However, this form of treatment modifies the natural history of this lethal disease only marginally, extending median survival from 13 months followin g diagnosis to 17 months. At Boston University Medical Center, we have deve loped treatment protocols using high-dose intravenous melphalan with autolo gous peripheral blood stem cell transplantation (HDM/SCT) to treat AL amylo idosis, and we have treated over 200 patients with HDM/SCT during the past six years. This extensive experience has shown that patients with AL amyloi dosis, despite multisystem involvement and compromised organ function can t olerate this aggressive form of treatment. Furthermore, HDM/SCT results in durable hematologic responses in a substantial proportion of patients, and such responses are associated with clinical improvement, decreased amyloid- related organ dysfunction, and prolonged survival. However, toxicity from t reatment is high (overall peri-transplant mortality, 14%), particularly for those patients with clinically significant cardiac involvement. For this r eason, we believe a multidisciplinary management approach is essential when using HDM/SCT for treatment of AL amyloidosis. Based on our experience, we believe that HDM/SCT is the treatment of choice for patients with AL amylo idosis who have a good performance status and limited cardiac involvement a t the time of diagnosis. HDM/SCT offers the best chance for hematologic rem ission, prolongation of survival, and reversal of amyloid-related disease. At the same time, we believe that HDM/SCT should continue to be examined in the context of clinical trials, directed at developing approaches to broad en the applicability of this therapy by minimizing toxicity and to increase the likelihood of complete hematologic responses.