Cidofovir for the Treatment of Adenoviral Infection in Pediatric Hematopoietic Stem Cell Transplant Patients

Yusuf, Usman; Hale, Gregory A.; Carr, Jeanne; Gu, Zheng; Benaim, Ely; Woodard, Paul; Kasow, Kimberly A.; Horwitz, Edwin M.; Leung, Wing; Srivastava, Deo Kumar; Handgretinger, Rupert; Hayden, Randall T.

doi:10.1097/01.tp.0000209195.95115.8e

Cited by 210 publications

(169 citation statements)

References 33 publications

Supporting

Mentioning

163

Contrasting

Unclassified

Order By: Relevance

“…However, renal dysfunction was transient in the majority of patients with serum creatinine returning to baseline after cessation of CDV therapy. While some studies have reported no toxicities related to the use of CDV 14, 16, 17, 19, 25 , the transient nature of nephrotoxicity observed has been reported by other studies 20, 24 . We were unable to detect any increased risk of nephrotoxicity associated with concomitant administration of additional nephrotoxic agents but this may reflect our small number of study participants.…”

Section: Discussionmentioning

confidence: 72%

Use of cidofovir in pediatric patients with adenovirus infection

et al. 2016

View full text Add to dashboard Cite

Background: Adenoviruses contribute to morbidity and mortality among immunocompromised pediatric patients including stem cell and solid organ transplant recipients. Cidofovir (CDV), an antiviral compound approved by the FDA in 1996, is used for treatment of adenoviral (ADV) infections in immunocompromised patients despite concern of potential nephrotoxicity. Methods: We conducted a retrospective 5-year review at Boston Children’s Hospital of 16 patients (mean age = 6.5 years) receiving 19 courses of CDV. During therapy all pertinent data elements were reviewed to characterize potential response to therapy and incidence of renal dysfunction. Results: Of the 19 CDV courses prescribed, 16 courses (84%) were in patients who had a positive blood ADV Polymerase chain reaction (PCR) alone or in combination with positive ADV PCR/ Direct Immunofluorescence Assay (DFA) at another site. Respiratory symptoms with or without pneumonia were the most common presentation (10/19, 53%). In the majority of blood positive courses (10/16, 63%), viral clearance was also accompanied by clinical response. This was not the case in four courses where patients expired despite viral clearance, including one in which death was directly attributable to adenovirus. There was reversible renal dysfunction observed during the use of CDV. Conclusions: CDV appeared safe and reasonably tolerated for treatment of ADV in this pediatric population and was associated with viral response and clinical improvement in the majority of patients but reversible renal dysfunction was a side effect. Further studies of the efficacy of CDV for immunocompromised children with ADV infection are warranted.

show abstract

Section: Discussionmentioning

confidence: 72%

Use of cidofovir in pediatric patients with adenovirus infection

et al. 2016

View full text Add to dashboard Cite

show abstract

“…29,[31][32][33] However, the observations made at our and other institutions indicate that initiation of antiviral treatment at the time of first detection of viremia may not prevent progression to severe AdV disease in many instances, and that earlier initiation of preemptive treatment could therefore be beneficial. 1,7,11,21,30,[33][34][35][36] Adenoviruses are known to persist in epithelial cells and lymphoid tissue, and AdV infections occurring during the posttransplant period appear to result from virus reactivation in most instances. Our observations revealed that virtually all patients who experienced systemic AdV infection had the virus detectable in serial stool specimens, with or without clinical symptoms of enteritis, before the onset of viremia.…”

Section: Discussionmentioning

confidence: 99%

Monitoring of adenovirus load in stool by real-time PCR permits early detection of impending invasive infection in patients after allogeneic stem cell transplantation

et al. 2010

View full text Add to dashboard Cite

Invasive adenovirus (AdV) infections are associated with high morbidity and mortality in allogeneic stem cell transplant recipients. We observed that molecular detection of the virus in stool specimens commonly precedes AdV viremia, suggesting that intestinal infections may represent a common source of virus dissemination. To address this notion, we have investigated 153 consecutive allogeneic transplantations in 138 pediatric patients by quantitative monitoring of AdV in stool specimens and peripheral blood by a pan-adenovirus real-time (RQ)-PCR approach. AdV was detectable in serial stool specimens in all cases of AdV viremia during the post-transplant course (Po0.0001). The incidence of AdV viremia in individuals with peak virus levels in stool specimens above 1 Â 10E6 copies per gram (n ¼ 22) was 73% vs 0% in patients with AdV levels in stool specimens below this threshold (n ¼ 29; Po0.0001). Serial measurement of AdV levels in stool specimens by RQ-PCR permitted early diagnosis of impending invasive infection with a sensitivity and specificity of 100% (95% confidence interval (CI) 96-100%) and 83% (95% CI 67-92%), respectively. The median time span between detection of AdV loads in stool specimens above 1 Â 10E6 copies per gram and first observation of viremia was 11 days (range 0-192). Quantitative monitoring of the AdV load in stool specimens therefore provides a rationale for early initiation of antiviral treatment with the aim of preventing progression to life-threatening invasive infection.

show abstract

“…As expected, in patients with dAdV, the rate of remission was lower than previously reported in patients with adenoviral disease or infection. 18,19 The apparent slow response to cidofovir raises questions about the real efficacy of cidofovir. But 2 patients who had treatment discontinuation because of uncontrolled GVHD had rapid progression of viral load followed by death.…”

confidence: 99%

Disseminated adenovirus infections after allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcome

Robin¹,

Marque-Juillet²,

Scieux³

et al. 2007

Haematologica

119

104

View full text Add to dashboard Cite

We analyzed the factors and outcome of patients with disseminated adenovirus infection (dAdV) after allogeneic hematopoeitic stem cell transplantation (HSCT). Thirty patients with dAdV were identified among 620 allogeneic HSCT recipients. Primary diseases were leukemia (n=17), Fanconi anemia (n=12) or others (n=1). Source of stem cells was unrelated in 28 and related in 2 patients. The graft consisted of peripheral blood (n=3), bone marrow (n=12) and unrelated cord-blood (UCB, n=15). Risk factors for dAdV in unrelated HSCT recipients were previous Fanconi disease (p=0.03) and GVHD (p=0.02) in children, and cord blood source of stem cells (p=0.029) and GVHD (0.024) in adults.

show abstract

Cidofovir for the Treatment of Adenoviral Infection in Pediatric Hematopoietic Stem Cell Transplant Patients

Cited by 210 publications

References 33 publications

Use of cidofovir in pediatric patients with adenovirus infection

Use of cidofovir in pediatric patients with adenovirus infection

Monitoring of adenovirus load in stool by real-time PCR permits early detection of impending invasive infection in patients after allogeneic stem cell transplantation

Disseminated adenovirus infections after allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcome

Contact Info

Product

Resources

About