Low Dosage Cidofovir Without Probenecid as Treatment for Bk Virus Hamorrhagic Cystitis After Hemopoietic Stem Cell Transplant

Faraci, Maura; Cuzzubbo, Daniela; Lanino, Edoardo; Marco, Eddi Di; Cirillo, C.; Dallorso, Sandro; Morreale, Giuseppe; Moroni, C.; Castagnola, Elio

doi:10.1097/inf.0b013e3181812cb9

Cited by 33 publications

(23 citation statements)

References 13 publications

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“…BKV-HC is responsible for a two-fold and three-fold increase in RBC and platelet transfusions, respectively, which represents 10% of the additional cost. Regarding the cost/efficiency of cidofovir treatment, lowering the dose from 5 mg/kg, as used in our study, to 0.5-1 mg/kg as proposed by other studies 37,38 would save 4-4.5% of the cost of this complication.…”

Section: Discussionmentioning

confidence: 99%

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation

Gilis

Morisset

Billaud

et al. 2014

Bone Marrow Transplant

122

153

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on behalf of the Lyon BK virus Study group 5 BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P ¼ 0.028), unrelated donor (P ¼ 0.0178), stem cell source (P ¼ 0.0001), HLA mismatching (P ¼ 0.0022) and BU in conditioning regimen (P ¼ 0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P ¼ 0.0005) and peripheral blood stem cells (P ¼ 0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P ¼ 0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (Po0.0001), more RBC (P ¼ 0.0003) and platelet transfusions (Po0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at h2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

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Section: Discussionmentioning

confidence: 99%

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation

Gilis

Morisset

Billaud

et al. 2014

Bone Marrow Transplant

122

153

View full text Add to dashboard Cite

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“…19,20 Moreover, to reduce the risk of renal tubular toxicity, probenecid is generally associated with CDV when it is used at dosage of 3-5 mg/kg every 1-2 weeks while lower doses of 1 mg/kg 1-3 times a week without probenecid was shown to be efficacious and safe in single-center series. 13,21 Esterification of CDV with lipid ester derivative (hexadecyoxypropil, octadecyloxyethil and Probenecid was used in 7 out of 7 patients. c Probenecid was used in 1 out of 6 patients.…”

Section: Discussionmentioning

confidence: 99%

Relationship between clinical and BK virological response in patients with late hemorrhagic cystitis treated with cidofovir: a retrospective study from the European Group for Blood and Marrow Transplantation

Cesaro

Pillon

Tridello

et al. 2012

Bone Marrow Transplant

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To investigate the relationship between clinical response and modification of BK viremia, we assessed retrospectively 32 cases of hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT that were treated with i.v. cidofovir (CDV). They were 22 men (69%) and 10 women (31%) with a median age of 24 years, range 3-62. The median number of CDV doses was 3, range 1-8, and the treatment lasted for a median of 3 weeks, range 1-10. Clinical improvement of HC was observed in 27 patients (84%). In 12 of 32 episodes (37.5%), BK viremia was determined before every CDV administration and a complete clinical response was observed in 10 of 12 patients (83%), the reduction of BK viremia load being X1 log by 2 weeks after starting CDV. Nephrotoxicity related to CDV was observed in nine patients. Among 26 patients with 100-day follow-up, 4 of 4 patients who had a complete clinical response by 30 days were alive vs 16 of 22 (73%) who did not have the resolution of HC in this time frame. We conclude that in patients with HC, the response to CDV treatment is usually associated with a significant reduction of BK viremia load.

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“…[1][2][3][4][5] Better understanding of the pathogenesis has led to searching for specific antiviral agents that can inhibit BKV replication. 5,6 Several antiviral drugs, such as fluoroquinolones, cidofovir and leflunomide, have been reported to treat patients with BKV-associated HC (BKV-HC). 5 Among 5 patients receiving leflunomide therapy, median interval of HC onset was 34 days after HSCT (range 20-37 days).…”

Section: Resultsmentioning

confidence: 99%

“…With better understanding of its pathogenesis, many studies aimed to inhibit BKV replication for such patients. 5,6 During the recovery process, several studies suggested that BK viral load in blood was a more specific indicator than BK viral load in urine. 2,3 In the present study, BK viral loads in blood decreased significantly after leflunomide therapy, even to undetectable levels in 4 of 5 patients.…”

Section: Discussionmentioning

confidence: 99%

Effective Treatment Of Severe Bk Virus-Associated Hemorrhagic Cystitis With Leflunomide In Children After Hematopoietic Stem Cell Transplantation

Wu¹,

Weng

et al. 2014

Pediatric Infectious Disease Journal

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Leflunomide, an immunosuppressant with antiviral activity, was used to treat 5 children with severe BK virus-associated hemorrhagic cystitis after hematopoietic stem cell transplantation. Without severe side effects, BK viral loads in blood and urine decreased significantly after leflunomide treatment. Compared with 7 historical controls, duration of BK virus-associated hemorrhagic cystitis was significantly shorter in patients receiving leflunomide therapy (P < 0.01).

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Low Dosage Cidofovir Without Probenecid as Treatment for Bk Virus Hamorrhagic Cystitis After Hemopoietic Stem Cell Transplant

Cited by 33 publications

References 13 publications

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation

Relationship between clinical and BK virological response in patients with late hemorrhagic cystitis treated with cidofovir: a retrospective study from the European Group for Blood and Marrow Transplantation

Effective Treatment Of Severe Bk Virus-Associated Hemorrhagic Cystitis With Leflunomide In Children After Hematopoietic Stem Cell Transplantation

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