1. Academic Validation
  2. Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant

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

  • Blood. 2017 Apr 6;129(14):2033-2037. doi: 10.1182/blood-2016-11-749721.
Prashant Hiwarkar 1 Persis Amrolia 2 Ponni Sivaprakasam 3 Su Han Lum 4 Hemalatha Doss 5 Ciara O'Rafferty 1 Toni Petterson 6 Katharine Patrick 7 Juliana Silva 2 Mary Slatter 5 Sarah Lawson 1 Kanchan Rao 2 Colin Steward 3 Adam Gassas 3 Paul Veys 2 Robert Wynn 4 United Kingdom Paediatric Bone Marrow Transplant Group
Affiliations

Affiliations

  • 1 Department of Haematology and Bone Marrow Transplantation, Birmingham Children's Hospital, Birmingham, United Kingdom.
  • 2 Department of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
  • 3 Department of Bone Marrow Transplantation, Royal Hospital for Children, Bristol, United Kingdom.
  • 4 Department of Bone Marrow Transplantation, Royal Manchester Children's Hospital, Manchester, United Kingdom.
  • 5 Department of Bone Marrow Transplantation, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
  • 6 Department of Bone Marrow Transplantation, Royal Marsden Hospital, Sutton, United Kingdom; and.
  • 7 Department of Bone Marrow Transplantation, Sheffield Children's Hospital, Sheffield, United Kingdom.
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.

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