Rare Cyclophosphamide-Induced Hemorrhagic Cystitis in a Chinese Population with Rheumatic Diseases

OBJECTIVE The aim of this study was to investigate the prevalence, severity, risk factors, and treatment outcomes of cyclophosphamide (CYC)-induced hemorrhagic cystitis (HC) in patients with rheumatic diseases. METHODS We collected the clinical data from 1284 consecutive patients admitted to The First Affiliated Hospital of Sun Yat-Sen University who were treated with CYC between 2006 and 2016, and then conducted a retrospective analysis. RESULTS The mean cumulative dose of CYC was 18.3 ± 13.4 g, and the mean treatment duration of CYC was 10.0 ± 7.2 months. We identified four patients with HC, yielding a crude prevalence of 0.3%. The average time from initial primary diagnosis to HC onset was 51.6 months (33-86 months). All of the four patients with HC were exposed to a high cumulative CYC dose (>60 g). Severity was assessed as grade II in one, grade III in one and grade IV in two patients. One had resolution of hematuria after hydration, and one case resolved after combination therapy of clot removal by cystoscopy, hydration, and bladder irrigation. The other two were unresponsive to the above treatment and finally had resolution after cystectomy. The average resolution time of hematuria was 39.5 days (7-56 days). There were no deaths in our cohort. CONCLUSION CYC-induced HC was rare and highly variable in Chinese patients with rheumatic diseases. Individualized treatment should be performed according to the severity of HC for each patient. More aggressive treatment strategies might improve the outcomes of patients with high-grade HC (grades III and IV). Our findings strengthened the link between HC events and higher cumulative CYC exposure (>60 g).