title: An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis.
abstract: 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 complete hematologic responses.
authors.affiliation: Stem Cell Transplant Program of the Section of Hematology and Oncology, Medical Center, Boston University School of Medicine, 88 East Newton Street, Boston, MA 02118, USA.
authors.forename: V
authors.initials: V
authors.lastname: Sanchorawala
authors.forename: D G
authors.initials: DG
authors.lastname: Wright
authors.forename: D C
authors.initials: DC
authors.lastname: Seldin
authors.forename: L M
authors.initials: LM
authors.lastname: Dember
authors.forename: K
authors.initials: K
authors.lastname: Finn
authors.forename: R H
authors.initials: RH
authors.lastname: Falk
authors.forename: J
authors.initials: J
authors.lastname: Berk
authors.forename: K
authors.initials: K
authors.lastname: Quillen
authors.forename: M
authors.initials: M
authors.lastname: Skinner
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000477:Alkylating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000686:Amyloidosis / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D001900:Boston / Q000453:epidemiology; D009202:Cardiomyopathies / Q000209:etiology / Q000473:pathology / Q000628:therapy; D019090:Case Management; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005171:Factor X Deficiency / Q000150:complications / Q000628:therapy; D005260:Female; D005544:Forecasting; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009102:Multiple Organ Failure / Q000209:etiology / Q000401:mortality; D009404:Nephrotic Syndrome / Q000209:etiology / Q000628:therapy; D010348:Patient Care Team; D018579:Patient Selection; D010865:Pilot Projects; D012074:Remission Induction; D006435:Renal Dialysis; D016019:Survival Analysis; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000477:Alkylating Agents; D008558:Melphalan