Treatment of <scp>BK</scp> virus‐associated hemorrhagic cystitis in pediatric hematopoietic stem cell transplant recipients with cidofovir: a single‐center experience

Kwon, Hi Jeong; Kang, Jin Han; Lee, Jae Whan; Chung, Nack‐Gyun; Kim, H.-K.; Cho, Byung-Sik

doi:10.1111/tid.12136

Cited by 48 publications

(48 citation statements)

References 30 publications

(37 reference statements)

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“…To our knowledge, prospective studies of the treatment for BKV-HC are not available, and there are no standard treatment guidelines for post-HSCT HC. Treatment modalities are limited, particularly in children, partly owing to few reports on children receiving pharmaceutical and surgical treatments [4,[18][19][20]. Intravenous hydration with forced diuresis is conducted; however, this is supportive treatment only without reliable efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Intravenous hydration with forced diuresis is conducted; however, this is supportive treatment only without reliable efficacy. At present, cidofovir is the only commercially available antiviral agent against BKV, and its efficacy for BKV-HC has been investigated only in retrospective studies [19][20][21]. In the report from the European Group for Blood and Marrow Transplantation, intravenous or intravesical cidofovir was administered to 62 patients with BKV-HC [21].…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the baseline creatinine level appeared to be elevated after treatment. Another pediatric cohort included 12 children with BKV-HC treated by intravenous and/or intravesical cidofovir [20]. The median duration of symptoms was 25 days (range, 9 to 73 days) and no persistent nephrotoxicity was observed.…”

Section: Discussionmentioning

confidence: 99%

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Choreito Formula for BK Virus–associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Kawashima

Ito

Sekiya

et al. 2015

Biology of Blood and Marrow Transplantation

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Therapy for BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is limited after hematopoietic stem cell transplantation (HSCT). We examined whether choreito, a formula from Japanese traditional Kampo medicine, is effective for treating BKV-HC. Among children who underwent allogeneic HSCT between October 2006 and March 2014, 14 were diagnosed with BKV-HC (median, 36 days; range, 14 to 330 days) after HSCT, and 6 consecutive children received pharmaceutical-grade choreito extract granules. The hematuria grade before treatment was significantly higher in the choreito group than in the nonchoreito group (P = .018). The duration from therapy to complete resolution was significantly shorter in the choreito group (median, 9 days; range, 4 to 17 days) than in the nonchoreito group (median, 17 days; range, 15 to 66 days; P = .037). In 11 children with macroscopic hematuria, the duration from treatment to resolution of macroscopic hematuria was significantly shorter in the choreito group than in the nonchoreito group (median, 2 days versus 11 days; P = .0043). The BKV load in urine was significantly decreased 1 month after choreito administration. No adverse effects related to choreito administration were observed. Choreito may be a safe and considerably promising therapy for the hemostasis of BKV-HC after HSCT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Choreito Formula for BK Virus–associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Kawashima

Ito

Sekiya

et al. 2015

Biology of Blood and Marrow Transplantation

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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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“…Consequently, children undergoing HSCT are at profound risk for serious and potentially fatal viral infections. Viruses that commonly complicate HSCT include adenoviruses, cytomegalovirus (CMV), herpes simplex virus (HSV), human herpesvirus 6 (HHV-6), BK virus, and other community-acquired respiratory and gastrointestinal (GI) viruses (2)(3)(4)(5)(6). Furthermore, the need for protracted antiviral therapy due to impaired immune clearance increases the risk of antiviral resistance to first-line agents (4).…”

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confidence: 99%

Pharmacokinetics and Safety of Intravenous Cidofovir for Life-Threatening Viral Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients

Brown

Cohen

Tong

et al. 2015

Antimicrob Agents Chemother

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fChildren undergoing hematopoietic stem cell transplantation (HSCT) are at risk for life-threatening viral infections. Cidofovir is often used as a first-line agent for adenovirus infections, despite the absence of randomized controlled trials with HSCT patients, and as a second-line agent for resistant herpesvirus infections. The frequency and severity of adverse effects, particularly nephrotoxicity, in pediatric HSCT recipients are unclear, and pharmacokinetics (PK) of cidofovir in children have not previously been reported. This study was an open-label, nonrandomized, single-dose pilot study to determine the safety and PK of cidofovir in pediatric HSCT recipients with symptomatic adenovirus, nucleoside-resistant cytomegalovirus (CMV) or herpes simplex virus (HSV), and/or human papovavirus infections. Subsequent dosing and frequency were determined by clinical response and side effects, as assessed by the treating physician. Blood and urine samples were obtained from patients for PK studies and assessment of toxicity and virologic response. Twelve patients were enrolled (median age, 9 years; 33.5 days posttransplantation). Four of seven patients with adenovirus infection were successfully treated and eventually cleared their infections. Four of twelve patients died of disseminated viral disease and multiorgan failure. Two of twelve patients had evidence of acute kidney injury after the first dose, and one of these patients developed chronic kidney disease; two other patients developed late nephrotoxicity. The mean drug half-life was 9.5 h. There was no correlation between nephrotoxicity and plasma maximum concentration, clearance, or half-life. PK were similar to those reported for adults, although the drug half-life was significantly longer than that for adults. Cidofovir was well tolerated in the majority of patients. However, effective therapeutic strategies are urgently needed to support patients until immune reconstitution is achieved.A utologous and allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignant and nonmalignant hematological and immunological disorders results in a variable period of compromised immunity (1). T-lymphocyte numbers and function are decreased by chemotherapeutic conditioning regimens, certain stem cell processing techniques, and immunosuppressive agents used to prevent or treat graft-versus-host disease (GVHD) in allogeneic HSCT recipients (1). In addition, the graft source, such as cord blood, peripheral blood stem cells, or marrow, impacts the pace and quality of immune reconstitution. Consequently, children undergoing HSCT are at profound risk for serious and potentially fatal viral infections. Viruses that commonly complicate HSCT include adenoviruses, cytomegalovirus (CMV), herpes simplex virus (HSV), human herpesvirus 6 (HHV-6), BK virus, and other community-acquired respiratory and gastrointestinal (GI) viruses (2-6). Furthermore, the need for protracted antiviral therapy due to impaired immune clearance increases the risk of antiviral resis...

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Treatment of BK virus‐associated hemorrhagic cystitis in pediatric hematopoietic stem cell transplant recipients with cidofovir: a single‐center experience

Abstract: CDV appears to be an effective and safe treatment for BKV-HC in pediatric HSCT recipients, but prospective trials are warranted to support its use.

Cited by 48 publications

References 30 publications

Choreito Formula for BK Virus–associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Choreito Formula for BK Virus–associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

Pharmacokinetics and Safety of Intravenous Cidofovir for Life-Threatening Viral Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients

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