Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation

Korean J Intern Med. 2015 Mar;30(2):212-8. doi: 10.3904/kjim.2015.30.2.212. Epub 2015 Feb 27.

Abstract

Background/aims: BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses.

Methods: Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade.

Results: Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment.

Conclusions: Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.

Keywords: BK virus; Cidofovir; Hemorrhagic cystitis.

MeSH terms

  • Administration, Intravenous
  • Adult
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • BK Virus / drug effects*
  • BK Virus / immunology
  • Cidofovir
  • Cystitis / diagnosis
  • Cystitis / drug therapy*
  • Cystitis / immunology
  • Cystitis / virology
  • Cytosine / administration & dosage
  • Cytosine / adverse effects
  • Cytosine / analogs & derivatives*
  • Drug Administration Schedule
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunocompromised Host
  • Male
  • Organophosphonates / administration & dosage*
  • Organophosphonates / adverse effects
  • Polyomavirus Infections / diagnosis
  • Polyomavirus Infections / drug therapy*
  • Polyomavirus Infections / immunology
  • Polyomavirus Infections / virology
  • Retrospective Studies
  • Time Factors
  • Transplantation, Homologous
  • Treatment Outcome
  • Tumor Virus Infections / diagnosis
  • Tumor Virus Infections / drug therapy*
  • Tumor Virus Infections / immunology
  • Tumor Virus Infections / virology
  • Viral Load

Substances

  • Antiviral Agents
  • Organophosphonates
  • Cytosine
  • Cidofovir