1044 q 2001 Blackwell Science Ltd SHORT REPORT A modified high-dose dexamethasone regimen for primary systemic (AL) amyloidosis Giovanni Palladini, 1 Ernesto Anesi, 1 Vittorio Perfetti, 1 Laura Obici, 2 Rosangela Invernizzi, 1 Carlo Balduini, 1 Edoardo Ascari 1 and Giampaolo Merlini 2 1 Internal Medicine and Medical Oncology, and 2 Biotechnology Research Laboratories, Policlinico San Matteo, Pavia ± Department of Biochemistry, University of Pavia, Pavia, Italy Received 24 February 2001; accepted for publication 27 February 2001 Summary. High-dose dexamethasone (HD-Dex) has been reported to benefit AL amyloidosis patients with varying response rates. Our preliminary experience with the usual HD-Dex schedule indicated that the induction phase was rather toxic in AL patients. We therefore adopted a milder schedule consisting of dexamethasone 40 mg on d 1±4 q21 d for up to eight cycles. Overall 8 out of 23 (35%) treated patients responded to treatment in a median time of 4 months (range 2±6 months) without significant toxicity. This regimen may be considered front-line therapy when autologous stem cell transplantation is not feasible and when a rapid response is particularly important. Keywords: AL amyloidosis, high-dose dexamethasone, response time, survival. The prognosis of patients with AL amyloidosis is poor: the Mayo Clinic Group reported a median survival of 13± 18 months (Kyle & Gertz, 1995; Kyle et al, 1997). At present, the most efficient approach to treating AL amyloidosis is high-dose chemotherapy followed by auto- logous stem cell transplantation aimed at annihilating the amyloidogenic clone. However, treatment-related toxicity limits this approach to a small proportion of patients. Dexamethasone has been shown to induce apoptosis in myeloma cells in vitro (Chauhan et al, 1997). High-dose dexamethasone (HD-Dex) is effective in the management of multiple myeloma (Alexanian et al, 1992) and has been reported to benefit AL patients with varying response rates and a rapid response time (Dhodapkar et al, 1997; Gertz et al, 1999a, b; Merlini et al, 1999). Our preliminary experience with the usual HD-Dex schedule indicated that the induction phase (40 mg on d 1±4, d 9±12, d 17±20 q35 d for three cycles) was rather toxic in AL patients, as two treatment-related fatal arrhythmias occurred in the first series of five patients treated. We therefore adopted a milder schedule consisting of dexamethasone 40 mg on d 1±4 q21 d for up to eight cycles. Here we report the results obtained with this schedule. PATIENTS AND METHODS Patients with a histological diagnosis of amyloidosis and evidence of plasma cell dyscrasia, but without overt myeloma, were entered into the study. Patients in whom complex ventricular arrhythmiae (couplets and/or ventri- cular tachycardia) were detected using 24-h electrocardio- gram (ECG) Holter monitoring were excluded, as were patients with endoscopically documented peptic ulcer. Patients were treated with 40 mg HD-Dex given by intrave- nous infusion on d 1±4 every 21 d. Parenteral administration was preferred to oral administration because it was better tolerated by the patients. Response was assessed after three cycles; treatment was continued for up to eight cycles in patients with stable or responsive disease. Patients were evaluated every 3 months until death or disease progression. No patient received concomitant therapy with interferon or cytotoxic agents. Patients received ranitidine to prevent peptic ulceration, and ciprofloxacin and itraconazole as prophylaxis against infections. Response to the HD-Dex was assessed on the basis of organ function improvement, as previously reported by Gertz et al (1999b). Toxicity and adverse events were recorded according to the National Cancer Institute Common Toxicity Criteria version 2´0. Kaplan and Meier survival curves were plotted. RESULTS Twenty-three patients (18 men, five women), 13 of whom had British Journal of Haematology , 2001, 113, 1044±1046 Correspondence: Giampaolo Merlini, MD, Biotechnology Research Laboratories, University Hospital IRCCS ± Policlinico San Matteo, Piazzale Golgi, 2, 27100 Pavia, Italy. E-mail: gmerlini@smatteo.pv.it