Efficacy of Cidofovir in Treatment of BK Virus-Induced Hemorrhagic Cystitis in Allogeneic Hematopoietic Cell Transplant Recipients.

Abstract

BK virus-associated hemorrhagic cystitis (BK-HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), with incidences up to 70%. Cidofovir is an antiviral agent with growing evidence as a therapeutic intervention. To assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC, a retrospective study was undertaken of the allo-HCT cohort who received cidofovir for symptomatic BK-HC (hematuria with BK viruria or viremia) from January 2010 until March 2017 in a single transplant center in Ontario, Canada. The primary outcome measure was a reduction in BK-HC severity (graded from 1 to 4); secondary outcomes included overall survival, BK virus titers, and the onset of acute kidney injury. Twelve allo-HCT patients received cidofovir for BK-HC, with pretreatment clinical severity of 3 (50%) or 4 (50%). Cidofovir was administered via intravenous (33%), intravesical (58%), or both modalities (8%). After a median cumulative dose of 10 mg/kg (range, 1 to 37), mean BK-HC grade decreased significantly by 1.8 (3.5 precidofovir, 1.7 postcidofovir, P < .01). Sixty-six percent of patients had at least partial response to cidofovir, with similar response rates between intravenous (66%) and intravesical (62%) administration. Sixty-seven percent of patients died, and 33% of patients experienced renal toxicity, including 2 patients receiving intravesical therapy. In this retrospective series, there was a significant reduction in BK-HC severity after cidofovir administration; most patients achieved at least partial response after cidofovir administration. Even with intravesical instillation, acute kidney injury remains a potential complication of cidofovir. Although cidofovir may be an efficacious therapy for BK-HC, albeit with potential demonstrated toxicities, further prospective trials are needed.

• Authors: Eric A Coomes, Amanda Wolfe Jacques, Fotios V Michelis, Dennis Dong Hwan Kim, Santhosh Thyagu, Auro Viswabandya, Jeffrey H Lipton, Hans A Messner, Uday Deotare
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 24 Issue 9 Pg. 1901-1905 (09 2018) ISSN: 1523-6536 [Electronic] United States
• PMID: 29679772 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antiviral Agents
• Cidofovir

Topics

• Adult
• Aged
• Antiviral Agents (pharmacology, therapeutic use)
• BK Virus (pathogenicity)
• Cidofovir (pharmacology, therapeutic use)
• Cystitis (chemically induced, drug therapy)
• Female
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Hemorrhagic Disorders (chemically induced, drug therapy)
• Humans
• Male
• Middle Aged
• Transplantation Conditioning (adverse effects, methods)