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Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant

Hiwarkar, P; Amrolia, P; Sivaprakasam, P; Lum, SH; Doss, H; O'Rafferty, C; Petterson, T; ... United Kingdom Paediatric Bone Marrow Transplant Group; + view all (2017) Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant. Blood , 129 (14) pp. 2033-2037. 10.1182/blood-2016-11-749721. Green open access

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Abstract

Cidofovir is preemptively used for controlling adenoviremia and preventing disseminated viral disease in hematopoietic cell transplant (HCT) recipients but does not lead to resolution of viremia without T-cell immune-reconstitution. The lipid-conjugated prodrug of cidofovir, brincidofovir, has improved oral bioavailability and achieves higher intracellular concentrations of active drug. We present retrospective multicenter data comparing the kinetics of viremia and toxicities following preemptive treatment with and brincidofovir in children and adolescents diagnosed with HCT-related adenoviremia. Forty-one episodes (18 = brincidofovir; 23 = cidofovir) of antiviral therapy were observed in 27 patients. The 2 groups had comparable immune-reconstitution and viral burden. Major (≥2 log-reduction in 2 weeks; n = 13) and minor (≥1 to ≤2 log-reduction in 2 weeks; n = 2) virological responses were observed in 15 (83%) brincidofovir episodes compared to only 2 (9%) major virological responses with cidofovir (P < .0001). Brincidofovir mediated major responses in 9 of 11 cidofovir-unresponsive patients and resulted in complete responses (CR) despite significant lymphopenia (Brincidofovir vs cidofovir; CR = 13 (80%) vs 8 (35%); median lymphocyte count = 320/μl vs 910/μl; P < .05). One patient experienced abdominal cramps and diarrhea necessitating interruption of brincidofovir and none developed nephrotoxicity with brincidofovir. Thus, brincidofovir is well-tolerated and highly efficacious in controlling adenoviremia during the lymphopenic phase of HCT.

Type: Article
Title: Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/blood-2016-11-749721
Publisher version: http://doi.org/10.1182/blood-2016-11-749721
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1540784
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