Cumulative hepatotoxicity induced by continuous low- dose cyclophosphamide therapy

TO THE EDITOR: Cyclophosphamide (CYC) is an alkylating agent used in the treatment of a number of rheumatological and malignant diseases. Well-documented toxicities include alopecia, mucositis, nausea, vomiting, marrow suppression, cystitis, and gonadal failure. Although hepatotoxicity is not uncommon during high-dose CYC therapy, hepatitis induced by low-dose treatment has rarely been described (1, 2, 3, 4, 5, 6, 7, 8). In the latter cases, hepatotoxicity occurs exclusively within the first 2–8 wk of therapy, at a dosage of 50–180 mg/day. We report a patient with primary Sjogren's syndrome who developed acute hepatitis 2 yr after a total cumulative dose of 40.5 g of CYC. To our knowledge, this cumulative toxic effect of CYC on the liver during continuous low-dose administration has hitherto been undescribed.