DOSE-INTENSIVE MELPHALAN WITH BLOOD STEM-CELL SUPPORT FOR THE TREATMENT OF AL AMYLOIDOSIS - ONE-YEAR FOLLOW-UP IN 5 PATIENTS

The morbidity and lethality of AL amyloidosis is caused by the deposit ion of Ig light chains as fibrillar amyloid protein in vital organs, d isrupting their function, and not by the generally low burden of clona l plasma cells that produce the paraproteins. Survival of patients wit h AL amyloidosis is no more than 1 to 2 years from the time of diagnos is with current management approaches. Clearly, more effective therapi es are needed for this rapidly lethal disease. Five patients were trea ted with dose-intensive melphalan and blood stem cell support and foll owed for a period of 1 year. Patients were diagnosed with AL amyloidos is by tissue biopsy and categorized by performance status and organ in volvement. Their plasma cell dyscrasias were evaluated with immunofixa tion electrophoresis of serum and urine specimens, quantitative serum Igs, and immunohistochemical staining of bone marrow biopsy specimens. After treatment with dose-intensive intravenous melphalan followed by infusion of autologous growth-factor-mobilized blood stem cells, clin ical evaluations and plasma cell studies were repeated at 3 and 12 mon ths. Three men and 2 women aged 38 to 53 years were treated. Median pe rformance status (SWOG) was 2 (1 to 3), and clinical presentations inc luded nephrotic syndrome (n = 1), symptomatic cardiomyopathy (n = 1), gastrointestinal involvement with polyneuropathy (n = 2), and hepatome galy (n = 1). With a median followup of 13 months (12 to 17 months), a ll five patients are well and have shown stable or improved performanc e status and clinical remission of organ-related dysfunction, includin g a 50% reduction in daily proteinuria with no change in creatinine, r eversal of symptoms of cardiomyopathy and reductions of posterior wall and septal thickening, reversal of polyneuropathy and gastric atony, and resolution of hepatomegaly by computed tomographic scan. In 3 of t he 5 patients (60%) at 12 months after treatment, plasma cell dyscrasi as could not be detected. Dose-intensive chemotherapy with intravenous melphalan and growth-factor-mobilized blood stem cell support is feas ible therapy for patients with AL amyloidosis, even when there is clin ical evidence of cardiac involvement. At least some patients with AL a myloidosis achieve complete remission of their plasma cell dyscrasia, improvement in performance status, and clinical remission of organ-spe cific disease after this form of treatment. (C) 1996 by The American S ociety of Hematology.