High‐risk adenovirus‐infected pediatric allogeneic hematopoietic progenitor cell transplant recipients and preemptive cidofovir therapy

Anderson, Evan J.; Guzman-Cottrill, Judith A.; Kletzel, Morris; Thormann, K.; Sullivan, Christine; Zheng, Xiaotian; Katz, Ben Z.

doi:10.1111/j.1399-3046.2007.00851.x

Cited by 82 publications

(84 citation statements)

References 36 publications

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“…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

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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.

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Section: Discussionmentioning

confidence: 72%

Use of cidofovir in pediatric patients with adenovirus infection

et al. 2016

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“…41 In view of the considerable nephrotoxicity of cidofovir and the high cost of treatment, preemptive therapy for all patients with AdV-positive stool samples is not generally recommended. 1,2,4,21,31,33,42 Prospective quantitative PCR screening in stool specimens and PB in this study of 153 pediatric allogeneic SCTs revealed that virtually all patients with AdV viremia showed rising virus copy numbers in serial stool specimens exceeding the threshold of 10E6 viral particles per gram before first appearance of the virus in PB (Po0.0001). The only exception in this series was a patient with onset of viremia very early after transplant (day þ 11) in whom detection of AdV in PB coincided with first observation of the virus in stool specimens.…”

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

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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.

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“…En pacientes sometidos a trasplante de hígado, una serie de 484 niños reportó una incidencia de infección de 10% 3 . En pacientes sometidos a trasplante de pulmón, se ha asociado neumonía por ADV con pérdida de injerto, muerte y progresión a bronquiolitis 5 ; en cualquier caso, se ha reportado 6,5 a 58% de viremia asintomática y esta situación no se ha asociado a enfermedad progresiva 16 .…”

Section: Epidemiologíaunclassified