Intravesical cidofovir to treat BK virus‐associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation

Rascon, Jelena; Verkauskas, Gilvydas; Pasaulienė, Ramunė; Zubka, Vytautas; Bilius, Vytautas; Ragelienė, Lina

doi:10.1111/petr.12477

Cited by 16 publications

(18 citation statements)

References 17 publications

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“…This review additionally identified 13 articles with a total of 219 patients who had received cidofovir therapy for BK-HC in allo-HCT: 195 via intravenous, 19 via intravesical, and 5 via both intravenous and intravesical. Complete response was observed in 60% to 100% of cases, independent of cidofovir dose and administration route [9,11,12,15,17,18,[20][21][22][23][24][25][26].…”

Section: Literature Reviewmentioning

confidence: 99%

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

Coomes

Wolfe

Michelis

et al. 2018

Biology of Blood and Marrow Transplantation

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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.

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Section: Literature Reviewmentioning

confidence: 99%

“…Cidofovir may be administered intravenously but is associated with potential nephrotoxicity. Intravesical administration has been used to limit systemic toxicity [13,17,18]. The aim of the present retrospective study is to assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC.…”

Section: Introductionmentioning

confidence: 99%

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

Coomes

Wolfe

Michelis

et al. 2018

Biology of Blood and Marrow Transplantation

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“…Thirteen articles were found that reported use of cidofovir in BKV-HC after allo-HSCT since 2005 [13,[22][23][24][25][26][27][28][29][30][31][32][33]. In total, 219 patients were treated (Table 4): 153 adults and 66 children, with various HC severity grades (grades 1 to 4).…”

Section: Literature Reviewmentioning

confidence: 99%

Cidofovir in the Treatment of BK Virus–Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Philippe

Ranchon

Gilis

et al. 2016

Biology of Blood and Marrow Transplantation

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After allogeneic hematopoietic stem cell transplantation (HSCT), BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication. Although supportive measures have been the standard of care for many years, several studies suggested the efficacy of cidofovir. The aim of this study was to assess the safety profile and efficacy of cidofovir. A retrospective study was conducted on all patients treated with cidofovir in our HSCT unit between March 2011 and May 2013. Data for efficacy (partial [PR] or complete response [CR]), prescription (dose, frequency, number of doses, and administration route), and toxicity were collected from published reports and medical files. Renal toxicity was evaluated using creatinine clearance calculated with the Cockcroft and Gault formula. A parallel literature search using PubMed (last search, May 2015) was performed. From March 2011 to June 2013, 27 of 181 patients undergoing allogeneic HSCT in our department received cidofovir for BKV-HC: 24 (88.9%) intravenously, 1 intravesically, and 2 via both routes. Mean dose was 5 mg/kg per administration, for a median of 4 injections (range, 1 to 11), from twice a week to once every 2 weeks. CR was achieved in 22 patients (81.5%), PR in 2, and no response in 2 patients. Eight patients presented renal failure (29.6%): 6 moderate (creatinine clearance < 60 mL/min) and 2 severe (creatinine clearance < 30 mLmin). Mean decrease in creatinine clearance after cidofovir was 27% (35 mL/min; range, 2 to 159). In 3 cases renal insufficiency and hematologic toxicity led to discontinuation of treatment or switch to intravesical instillation. For 3 patients cidofovir dose was reduced because of nephrotoxicity. Thirteen studies have reported on the use of cidofovir for BKV-HC (204 patients) since 2005. Intravenous cidofovir was used for 91.3% of patients, with doses ranging from .5 to 5 mg/kg. The main toxicity reported was renal failure (9% to 50% in 9 studies). Between 60% and 100% of CRs were observed independently of cidofovir dose or administration route. Cidofovir is an effective therapy for BKV-HC but requires very precise renal function management to avoid toxicity. Cidofovir treatment modalities (high dose, intravesical instillation, or low dose [≤1 mg/kg]) needs to be investigated in randomized controlled trials.

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“…Mostly given at 5 mg/kg/week in both primary or secondary pre-emptive therapy for CMV infection with response rates of 50% for CMV disease and 62% to 66% for CMV infection, significant renal toxicities were reported [39]. Several applications of CDF against different viral pathogens in pediatric patients [40] have been reported in recent years, in particular against adenovirus [41], BK virus-associated hemorrhagic cystitis [42,43] and poxvirus [44].…”

Section: Cidofovir (Cdf) -The Last Resortmentioning

confidence: 99%

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

Madon

Giaccone

Festuccia

et al. 2016

Expert Review of Hematology

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Intravesical cidofovir to treat BK virus‐associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation

Cited by 16 publications

References 17 publications

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

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

Cidofovir in the Treatment of BK Virus–Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

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