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

Abstract

Summary:Primary or AL amyloidosis results from a plasma cell dyscrasia in which fibrillar light chain protein deposition leads to organ failure and death. Standard 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 following diagnosis to 17 months. At Boston University Medical Center, we have developed treatment protocols using high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT) to treat AL amyloidosis, and we have treated over 200 patients with HDM/SCT during the past six years. This extensive experience has shown that patients with AL amyloidosis, despite multisystem involvement and compromised organ function can tolerate 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 treatment is high (overall peri-transplant mortality, 14%), particularly for those patients with clinically significant cardiac involvement. For this reason, 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 amyloidosis who have a good performance status and limited cardiac involvement at the time of diagnosis. HDM/SCT offers the best chance for hematologic remission, 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 broaden the applicability of this therapy by minimizing toxicity and to increase the likelihood of

Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis

“…One must consider the occasional possibility of a monoclonal gammopathy incidentally associated with AF or SSA. The application of chemotherapy to a patient with a nonimmunoglobulin form of amyloid is contraindicated [53], would provide no benefit, and could be harmful to the patient [54].…”

Successful reduced intensity allogeneic stem cell transplantation for systemic AL amyloidosis

“…Numerous reports have described the availability of autologous PBSCT for systemic AL amyloidosis, but some reviews have reported high TRMs (13-39%) in autologous PBSCT for systemic AL amyloidosis [2][3][4][5][6][7]. Comenzo and Gertz [4] described TRM rates approaching 100% in patients with cardiac amyloidosis and clinical congestive heart failure or history of arrhythmia, syncope, or recurrent pleural effusion.…”

Spontaneous rupture of the spleen in AL amyloidosis

“…These are, to our knowledge, the first cases of splenic rupture in AL amyloidosis as a complication of HDM/SCT. HDM/SCT is the treatment of choice for a subset of patients with AL amyloidosis since this treatment has been shown to induce complete hematologic remissions and to reverse amyloid-related disorders [8,34]. G-CSF is widely used to mobilize peripheral progenitor cells for collection by leukapheresis prior to HDM/SCT as well as to accelerate hematopoietic recovery in the peritransplant period.…”

“…He received prophylactic benzylpenicillin for 6 months after HDM/SCT. At 1 year following treatment with HDM/SCT, he was found to have achieved a complete hematologic remission, defined as absence of monoclonal gammopathy in serum and urine by immunofixation electrophoresis and a normal bone marrow biopsy showing less than 5% plasma cells with no evidence of clonal predominance [8].…”