Management of Hemorrhagic Cystitis

Prevention Strategies

The American Society of Clinical Oncology recommends mesna administration when using cyclophosphamide or ifosfamide to prevent hemorrhagic cystitis by binding to the toxic metabolite acrolein 1
For ifosfamide, the American Society of Clinical Oncology recommends mesna administration as an IV bolus at 20% of the ifosfamide dose at the time of administration, followed by oral mesna at 40% of the ifosfamide dose at 2 and 6 hours after each ifosfamide dose 1
Adequate hydration (2-3 L in 24 hours) is crucial to dilute toxic metabolites in the urine, as recommended by medical guidelines 2
Patients should be instructed to urinate frequently, especially upon waking, to prevent acrolein from inducing hemorrhagic cystitis, as suggested by the Mayo Clinic 3
Forced diuresis with >8 glasses of water daily and monthly monitoring of urine for red blood cells is recommended for patients on cyclophosphamide, according to the American Thoracic Society 4

A focused medical history and complete physical examination, including digital rectal examination, should be performed to rule out other causes of hematuria, as recommended by the World Journal of Emergency Surgery 5
Vital signs, hemoglobin, hematocrit, and coagulation parameters should be checked to evaluate bleeding severity, as suggested by the World Journal of Emergency Surgery 5
Urine analysis and culture should be performed to rule out infection as a cause, as recommended by Radiologia Medica 6

Hydration with forced diuresis and frequent bladder emptying can reduce bladder toxicity, as suggested by the Journal for ImmunoTherapy of Cancer 7
Non-steroidal anti-inflammatory drugs can be used for pain management, as recommended by Radiologia Medica 6
Anticholinergic agents such as oxybutynin can be used for urinary symptoms, as suggested by Radiologia Medica 6
Botulinum toxin A injection into the detrusor muscle can be used when drug therapy is ineffective, as recommended by Radiologia Medica 6

Urine output and appearance should be monitored for signs of hematuria, as recommended by medical guidelines 2
Regular assessment of renal function is necessary, especially in patients with pre-existing renal impairment, as suggested by medical guidelines 2
Patients should be monitored for signs of infection, as hemorrhagic cystitis can predispose to urinary tract infections, as recommended by Radiologia Medica 6
Monthly monitoring of urine for red blood cells or other abnormalities is recommended for patients on cyclophosphamide, according to the American Thoracic Society 4

Patients who vomit within 2 hours of taking oral mesna should repeat the dose or receive IV mesna, as recommended by the American Society of Clinical Oncology 1
Conservative management is preferred for intracystic hemorrhage, and interventions such as aspiration or laparoscopic procedures should be avoided during active hemorrhage, as suggested by the Journal of Hepatology 8
Steroids should be avoided for prevention of gastrointestinal symptoms in patients receiving TIL therapy to prevent possible adverse effects on the infused TIL, as recommended by the Journal for ImmunoTherapy of Cancer 7

The American Society of Clinical Oncology recommends administering mesna as IV bolus at 20% of the ifosfamide dose at the time of ifosfamide administration, followed by oral mesna at 40% of the ifosfamide dose at 2 and 6 hours after each ifosfamide dose, with a total daily mesna dose equal to 100% of the ifosfamide dose 9
For high-dose cyclophosphamide (≥1500 mg/m²/day), mesna plus saline diuresis or forced saline diuresis is recommended, particularly in stem-cell transplantation settings 9
If the patient vomits within 2 hours of taking oral mesna, the dose should be repeated or switched to IV mesna 9

Instruct patients to urinate frequently throughout treatment, with particular emphasis on emptying the bladder immediately upon waking in the morning, to prevent the toxic metabolite acrolein from dwelling in the bladder overnight 10

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 11