Prevention of Hemorrhagic Cystitis in Chemotherapy Patients
For patients receiving cyclophosphamide or ifosfamide chemotherapy, hemorrhagic cystitis prevention requires three essential components: mesna administration, aggressive hydration (2-3 L/24 hours), and frequent bladder emptying, especially upon waking. 1, 2, 3, 4
Mesna Administration Protocol
For Ifosfamide
- Administer mesna as IV bolus at 20% of the ifosfamide dose at the time of ifosfamide administration 1, 2, 5
- Follow with oral mesna at 40% of the ifosfamide dose at 2 and 6 hours after each ifosfamide dose 1, 2, 5
- The total daily mesna dose equals 100% of the ifosfamide dose 1
- Critical caveat: If the patient vomits within 2 hours of taking oral mesna, repeat the dose or switch to IV mesna 1, 2, 5
For Cyclophosphamide
- Mesna plus saline diuresis or forced saline diuresis is recommended for high-dose cyclophosphamide (≥1500 mg/m²/day), particularly in stem-cell transplantation settings 1, 4
- For doses <1500 mg/m²/day, vigorous hydration alone may be sufficient if fluid infusion rate is ≥125 mL/m²/hour 6
Hydration Requirements
Maintain aggressive hydration with at least 2-3 liters of oral or intravenous fluid per 24 hours 2, 3, 4
- For low- to intermediate-dose cyclophosphamide (<1500 mg/m²/day): target fluid infusion rate of ≥125 mL/m²/hour 6
- For high-dose cyclophosphamide (≥1500 mg/m²/day): combine mesna with vigorous hydration at approximately 115 mL/m²/hour 6
- Forced diuresis with >8 glasses of water daily is recommended for patients on cyclophosphamide 2
Bladder Emptying Strategy
Instruct patients to urinate frequently throughout treatment, with particular emphasis on emptying the bladder immediately upon waking in the morning 1, 2
This prevents the toxic metabolite acrolein from dwelling in the bladder overnight, which is when the highest concentration accumulates 1, 2
Monitoring During Treatment
- Check urinary sediment regularly for erythrocytes and other signs of urotoxicity 4
- Monitor urine output and appearance continuously for signs of hematuria 2, 5
- Perform monthly monitoring of urine for red blood cells in patients on cyclophosphamide 2, 5
- Exclude or correct any urinary tract obstructions before starting treatment 4
Common Pitfalls to Avoid
Do not use cyclophosphamide in patients with active urinary tract infections without treating the infection first 4
The evidence shows that despite prophylaxis, hemorrhagic cystitis still develops in approximately 27% of bone marrow transplant patients, with 6% experiencing severe cases requiring aggressive intervention 7. However, proper prophylaxis significantly reduces both incidence and severity 8, 7.
For patients receiving lymphodepletion before CAR T-cell therapy, alternative regimens should be considered if the patient has pre-existing hemorrhagic cystitis or resistance to cyclophosphamide 1
The combination of mesna with adequate hydration is more effective than either measure alone, particularly for high-dose regimens 1, 6. Research demonstrates that patients receiving mesna but inadequate hydration (<125 mL/m²/hour) still developed hemorrhagic cystitis, emphasizing that both components are essential 6.