Safety and efficacy of brincidofovir for Adenovirus infection in children receiving allogeneic stem cell transplantation: an AIEOP retrospective analyses

Perruccio, Katia; Menconi, Mariacristina; Galaverna, Federica; Pagliara, Daria; Carraro, Francesca; Calore, Elisabetta; Biffi, Alessandra; Baretta, Valentina; Massei, Maria Speranza; Capolsini, Ilaria; Faraci, Maura; Verna, Marta; Soncini, Elena; Caniglia, Maurizio; Locatelli, Franco; Cesaro, Simone

doi:10.1038/s41409-021-01285-y

Cited by 7 publications

(9 citation statements)

References 12 publications

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“…Several retrospective or prospective phase II studies have documented the efficacy of BCV in reducing AdV replication regardless of lymphocyte count, patient immune recovery status, and previous treatments with CDV, both in adult and pediatric patients. 4,11,[52][53][54][55] In a pediatric series of 30 allogeneic HCTs who developed 44 episodes of AdV infection or disease, the complete response was observed in 36% of episodes treated with CDV and in 53% of episodes treated with BCV. Noteworthy, while CDV was used as firstline treatment, BCV was used in 67% of episodes as rescue treatment after CDV failure; moreover, the median time of response was shorter:…”

Section: Treatmentmentioning

confidence: 99%

Adenovirus infection in allogeneic hematopoietic cell transplantation

Cesaro

2023

Transplant Infectious Dis

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Adenovirus (AdV) infection occurs in 0–20% of patients in the first 3–4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than in adult patients. About 50% of AdV infections involve the blood, which in turn, correlates with an increased risk developing AdV diseases, end‐organ damage, and 6‐month overall mortality. The main risk factors for AdV infection are T‐cell depletion of the graft by ex vivo selection procedures or in vivo use of alemtuzumab or antithymocyte serum, development of graft versus host disease (GVHD) grade III–IV, donor type (haploidentical or human leucocyte antigen mismatched related donor > cord blood> unrelated matched donor) and severe lymphopenia (<0.2 × 109/L). The prevention of AdV disease relies on early diagnosis of increasing viral replication in blood or stool and the pre‐emptive start of cidofovir as viral load exceeds the threshold of ≥102–3 copies/mL in blood and/or 106 copies/g stool in the stool. Cidofovir (CDV), a cytosine monophosphate nucleotide analog, is currently the only antiviral recommended for AdV infection despite limited efficacy and moderate risk of nephrotoxicity. Brincidofovir, a lipid derivative of CDV with more favorable pharmacokinetics properties and superior efficacy, is not available and currently is being investigated for other viral infections. The enhancement of virus‐specific T‐cell immunity in the first few months post‐HCT by the administration of donor‐derived or third‐party‐donor‐derived virus‐specific T‐cells represents an innovative and promising modality of intervention and data of efficacy and safety of the ongoing prospective randomized studies are eagerly awaited.

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Section: Treatmentmentioning

confidence: 99%

Adenovirus infection in allogeneic hematopoietic cell transplantation

Cesaro

2023

Transplant Infectious Dis

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“…In small case series, Brincidofovir has been shown to be safe in children with adenovirus infection. 127,128 Brincidofovir and cidofovir should only be considered for very severe infections, infections with progression despite tecovirimat treatment or when tecovirimat is contraindicated or unavailable. 97…”

Section: Brincidofovir and Cidofovirmentioning

confidence: 99%

Monkeypox—What Pediatricians Need to Know

Zimmermann

Curtis

2022

Pediatric Infectious Disease Journal

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Monkeypox is a zoonotic disease, presenting with fever, lymphadenopathy and vesicular-pustular skin lesions, that historically has rarely been reported outside the endemic regions of Central and West Africa. It was previously thought that human-to-human transmission was too low to sustain spread. During 2022, the number of cases of monkeypox, caused by clade II, rose rapidly globally, predominantly among men who have sex with men. In previous outbreaks with monkeypox clade 1 in endemic areas, children were disproportionately more affected with higher morbidity and mortality. It is unclear whether children are at similarly higher risk from monkeypox clade II. Nonetheless, children and pregnant women are considered high-risk groups and antiviral treatment should be considered for those affected. While smallpox vaccination offers good protection against monkeypox, the duration of protection is unknown, and infection occurs in vaccinated individuals. Should the current outbreak spread to children, authorities should be prepared to rapidly implement vaccination for children. In this review, we summarize epidemiological and clinical features, as well as the pathogenesis, treatment, and prevention options for monkeypox with a focus on considerations for children.

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“…This lipid conjugation results in good intestinal absorption, higher intracellular concentrations of active drug, reduced uptake by renal tubular cells, and increased antiviral potency against several double-stranded DNA viruses such as cytomegalovirus, HAdV, BK polyomavirus, vaccinia virus, and Molluscum contagiosum virus. Several retrospective or prospective phase II studies documented the efficacy of brincidofovir in reducing HAdV replication irrespective of lymphocyte count, patient immune recovery status, and previous treatments with other antivirals, including cidofovir, both in adult and pediatric patients [ 40 , 41 , 42 ]. Interestingly, brincidofovir has no significant nephrotoxicity or myelotoxicity while the most common adverse effect is intestinal toxicity (diarrhea) that, in HCT patients, is not easily distinguishable from intestinal GVHD.…”

Section: Treatmentmentioning

confidence: 99%

Adenovirus Infection in Pediatric Hematopoietic Cell Transplantation: A Challenge Still Open for Survival

Cesaro

Porta

2022

JCM

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Human Adenovirus (HAdV) infection occurs in 14–16% of patients in the early months after pediatric hematopoietic cell transplantation (HCT) and this correlates with a higher risk of developing HAdV disease and overall 6-month mortality. The main risk factors for HAdV infection are T-cell depletion of the graft by ex vivo CD34+ selection or in vivo use of alemtuzumab or anti-thymocyte serum, the development of grade III-IV graft versus host disease (GVHD), the type of donor (unrelated donor, cord blood, haploidentical, or HLA mismatched parent), and severe lymphopenia (<0.2 × 109/L). The prevention of HAdV disease is based on early intervention with antivirals in the asymptomatic patient when the permitted viral load threshold in the blood (≥102–3 copies/mL) and/or in the stool (109 copies/g stool) is exceeded. Cidofovir, a monophosphate nucleotide analog of cytosine, is the primary drug for preemptive therapy, used at 5 mg/kg/week for 2 weeks followed by 3–5 mg/kg every 2 weeks. The alternative schedule is 1 mg/kg every other day (three times/week). Enhancing virus-specific T-cell immunity in the first months post-HCT by donor-derived or third-party-derived virus-specific T cells represents an innovative and promising way of intervention, applicable both in prevention and therapeutic settings.

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Safety and efficacy of brincidofovir for Adenovirus infection in children receiving allogeneic stem cell transplantation: an AIEOP retrospective analyses

Cited by 7 publications

References 12 publications

Adenovirus infection in allogeneic hematopoietic cell transplantation

Adenovirus infection in allogeneic hematopoietic cell transplantation

Monkeypox—What Pediatricians Need to Know

Adenovirus Infection in Pediatric Hematopoietic Cell Transplantation: A Challenge Still Open for Survival

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