New Drug Therapy of Amyloidoses: Resorption of AL-Type Deposits With

Treatment scheme. The first patient was treated with a single high dose of I-DOX (100 mg/m2) as part of a high-dose chemotherapy program before bone marrow transplantation (BMT). The following three patients (nos. 2, 3, and 4) were given 80 to 100 mgl m* of I-DOX, repeated two times every 4 weeks. Patient 4 first received a lower I-DOX dosage (30 mg/m*/wk four times) to avoid massive mobilization of the huge amyloid deposits in her liver, and then higher doses were administered in an attempt to maintain the transient clinical improvement that was observed. In the meantime it became clear that I-DOX activity was not caused by its cytotoxic effects on the amyloidogenic clone. Therefore, we treated the remaining patients with relatively low doses (30 mg/m2), repeated every 7 to 10 days three to four times to avoid unnecessary toxicities. This dosage was further reduced and the intervals extended in the case of severe hematologic toxicity (blood neutrophil count <OS X 109/L). No other chemotherapy besides I-DOX has been administered to any patient. Pharmacokinetic studies. The plasma pharmacokinetics of IDOX and its major metabolite 13-dihydro-I-DOX (I-DOXOL) was studied in three patients for seven cycles. The two anthracyclines