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Asia Pac J Clin Oncol. 2018 Jul 10. doi: 10.1111/ajco.13048. [Epub ahead of print]

Cyclophosphamide-induced hemorrhagic cystitis in young patients with solid tumors: A single institution study.

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Department of Pharmacy, National Cancer Center Hospital, Tokyo, Japan.
Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.



Although hemorrhagic cystitis (HC) is a significant complication in young patients who undergo chemotherapy with cyclophosphamide (CPA), risk factors and supportive care to prevent HC are unclear. This study attempted to identify optimal supportive care to prevent CPA-induced HC.


Patients (< 30-year-old) with malignant solid tumors who had been treated with CPA-containing chemotherapy in inpatient treatment were eligible. Vigorous hydration to increase urine output and intravenous 2-mercaptethane sulfonate (mesna) were used for prophylaxis of CPA-induced HC. We retrospectively analyzed 81 patients who had been treated with CPA-containing chemotherapy over (collectively) 486 cycles, and examined relationships between HC and various factors, especially CPA dosage, use of mesna, and fluid infusion volume/rate.


HC occurred in four patients (4.9%) and five cycles (1%). When stratifying by doses and methods of administration of CPA, HC occurred in 3/323 low- and intermediate-dose (< 1500 mg/m2 /day) cycles and mesna was used in all three cycles with HC. Patients who were given mesna had a lower flow rate than those given hydration alone in the low- and intermediate-dose CPA (126 ± 25 vs 106 ± 16 mL/m2 /h; P < 0.01). All patients who received high-dose CPA (≥1500 mg/m2 /day) were also given mesna and vigorous hydration (115 ± 16 mL/m2 /h).


Our supportive care measures may be effective in preventing CPA-induced HC. Patients who receive CPA doses < 1500 mg/m2 /day should get ≥125 mL/m2 /h of infused fluid, regardless of mesna usage; those who receive of CPA ≥1500 mg/m2 /day should also receive mesna and vigorous hydration.


cyclophosphamide; hemorrhagic cystitis; hydration; mesna; pediatric


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