Hemorrhagic cystitis in children treated with alkylating agent cyclophosphamide: The experience of a medical center in Taiwan

J Formos Med Assoc. 2015 Aug;114(8):691-7. doi: 10.1016/j.jfma.2013.06.004. Epub 2013 Jul 20.


Background/purpose: Hemorrhagic cystitis is a common complication with chemotherapeutic alkylating agents. We investigated the possible prognostic factors of cyclophosphamide-induced hemorrhagic cystitis in children.

Methods: Medical records of children (< 18 years old) with cyclophosphamide-related hemorrhagic cystitis were collected retrospectively from January 2000 to December 2010 in a tertiary care center. We also prospectively enrolled children (< 18 years old) with cyclophosphamide treatment.

Results: The retrospective study consisted of 23 patients whose median age was 11 years. The median day of onset time was 1 day after cyclophosphamide usage. The hemato-oncological diseases included acute leukemia (39.1%), lymphoma (13%), blastoma (13%), sarcoma (13%), aplastic anemia (13%), and others (8.7%). Patients who received bone marrow transplantation (BMT) had significantly longer duration of hemorrhagic cystitis than those who did not receive BMT (p < 0.05). Serum uric acid, checked prior to and after the onset of hemorrhage cystitis, was significantly lower after the development of hemorrhagic cystitis (p < 0.05). In the prospective study, 11 children were enrolled with a median age of 5 years. The urinary nitrite/nitrate and 8-iso-prostaglandin F2α levels increased significantly after cyclophosphamide usage (p < 0.05).

Conclusion: Alteration serum uric acid level and BMT could be indicators for severe hemorrhagic cystitis. The elevated levels of urinary nitrite/nitrate and 8-iso-prostaglandin F2α may indicate the essential roles played by nitric oxide syntheses and reactive oxidative stress in cyclophosphamide-induced hemorrhagic cystitis. These findings may help clinicians formulate a better strategy for treating cyclophosphamide-induced hemorrhagic cystitis.

Keywords: cyclophosphamide; hemorrhagic cystitis; nitric oxide; uric acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Bone Marrow Transplantation / adverse effects
  • Child
  • Child, Preschool
  • Cyclophosphamide / adverse effects*
  • Cystitis / chemically induced*
  • Female
  • Hemorrhage / chemically induced*
  • Humans
  • Male
  • Pilot Projects
  • Prospective Studies
  • Retrospective Studies
  • Taiwan
  • Tertiary Care Centers
  • Uric Acid / blood*
  • Urinary Bladder / drug effects*


  • Antineoplastic Agents, Alkylating
  • Uric Acid
  • Cyclophosphamide