Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant.
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.
Department of Haematology and Bone Marrow Transplantation, Birmingham Children's Hospital, Birmingham, United Kingdom.
Prashant
0000-0001-7504-3521
P
Hiwarkar
Department of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
Persis
P
Amrolia
Department of Bone Marrow Transplantation, Royal Hospital for Children, Bristol, United Kingdom.
Ponni
P
Sivaprakasam
Department of Bone Marrow Transplantation, Royal Manchester Children's Hospital, Manchester, United Kingdom.
Su Han
SH
Lum
Department of Bone Marrow Transplantation, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
Hemalatha
H
Doss
Department of Haematology and Bone Marrow Transplantation, Birmingham Children's Hospital, Birmingham, United Kingdom.
Ciara
C
O'Rafferty
Department of Bone Marrow Transplantation, Royal Marsden Hospital, Sutton, United Kingdom; and.
Toni
T
Petterson
Department of Bone Marrow Transplantation, Sheffield Children's Hospital, Sheffield, United Kingdom.
Katharine
K
Patrick
Department of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
Juliana
J
Silva
Department of Bone Marrow Transplantation, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
Mary
M
Slatter
Department of Haematology and Bone Marrow Transplantation, Birmingham Children's Hospital, Birmingham, United Kingdom.
Sarah
S
Lawson
Department of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
Kanchan
K
Rao
Department of Bone Marrow Transplantation, Royal Hospital for Children, Bristol, United Kingdom.
Colin
C
Steward
Department of Bone Marrow Transplantation, Royal Hospital for Children, Bristol, United Kingdom.
Adam
A
Gassas
Department of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
Paul
P
Veys
Department of Bone Marrow Transplantation, Royal Manchester Children's Hospital, Manchester, United Kingdom.
Robert
R
Wynn
D000256:Adenoviridae; D000257:Adenoviridae Infections / Q000188:drug therapy* / Q000209:etiology; D000293:Adolescent; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D003596:Cytosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D014766:Viremia / Q000188:drug therapy* / Q000209:etiology
D063065:Organophosphonates; C525733:brincidofovir; D003596:Cytosine