Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant
| Autor: | Paul Veys, Kanchan Rao, Su Han Lum, Prashant Hiwarkar, Robert Wynn, Ponni Sivaprakasam, Katharine Patrick, Juliana Silva, Sarah Lawson, Toni Petterson, Ciara O'Rafferty, Colin G. Steward, Persis Amrolia, Mary Slatter, Adam Gassas, Hemalatha Doss |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Adolescent Lymphocyte medicine.medical_treatment Adenoviridae Infections 030106 microbiology Immunology Organophosphonates Brincidofovir Viremia Hematopoietic stem cell transplantation Biochemistry Gastroenterology Nephrotoxicity Adenoviridae 03 medical and health sciences chemistry.chemical_compound Cytosine Internal medicine medicine Humans Child business.industry Hematopoietic Stem Cell Transplantation Cell Biology Hematology medicine.disease Allografts 030104 developmental biology medicine.anatomical_structure chemistry Child Preschool Female Viral disease business Viral load medicine.drug Cidofovir |
| Zdroj: | Blood. 129(14) |
| ISSN: | 1528-0020 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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