DOSE-INTENSIVE MELPHALAN WITH BLOOD STEM-CELL SUPPORT FOR THE TREATMENT OF AL (AMYLOID LIGHT-CHAIN) AMYLOIDOSIS - SURVIVAL AND RESPONSES IN25 PATIENTS

AL (amyloid light-chain) amyloidosis is an uncommon plasma cell disord er in which depositions of amyloid light-chain protein cause progressi ve organ failure and death in a median of 13 months. Autologous stem-c ell transplantation is effective therapy for multiple myeloma and ther efore, we evaluated its efficacy for AL amyloidosis. Patients with ade quate cardiac, pulmonary, and renal function had stem cells mobilized with granulocyte-colony stimulating factor and were treated with dose- intensive intravenous melphalan (200 mg/m(2)). Response to therapy was determined by survival and improvement of performance status, complet e response or persistence of the clonal plasma cell disorder, and chan ge in the function of organs involved with amyloid at baseline. We enr olled 25 patients with a median age of 48 years (range, 29-60), all of whom had biopsy-proven amyloidosis with clonal plasma cell disorders. Twenty-two (88%) were Southwest Oncology Group performance status 1 o r 2 within a year of diagnosis, and 16 (64%) had received no prior the rapy. Predominant amyloid-related organ involvement was cardiac (n = 8 ), renal (n = 7), hepatic (n = 6), neuropathic (n = 3), and lymphatic (n = 1). Fifteen patients had one or two organ systems involved, where as 10 had three or more involved. With a median follow-up of 24 months (12-38), 17 of 25 patients (68%) are alive, and the median survival h as not been reached. Thirteen of 21 patients (62%) evaluated 3 months posttransplant had complete responses of their clonal plasma cell diso rders. Currently, two thirds of the surviving patients (11 of 17) have experienced improvements of amyloid-related organ involvement in all systems, whereas 4 of 17 have stable disease. The improvement in the m edian performance status of the 17 survivors at follow-up (0 [range, 0 -3]) is statistically significant versus baseline (2 [range, 1-3]; P < .01). Significant negative prognostic factors with respect to overall survival include amyloid involvement of more than two major organ syst ems and predominant cardiac involvement. Three patients have experienc ed relapses of the clonal plasma cell disorder at 12 and 24 months. Do se-intensive therapy should currently be considered as the preferred t herapy for patients with AL amyloidosis who meet functional criteria f or autologous transplantation. (C) 1998 by The American Society of Hem atology.