Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant
Hiwarkar, P., Amrolia, P., Sivaprakasam, P., Lum, S. H., Doss, H., O'Rafferty, C., Petterson, T., Patrick, K., Silva, J., Slatter, M., Lawson, S., Rao, K., Steward, C., Gassas, A., Veys, P., Wynn, R., United Kingdom Paediat Bone, Marr
(2017)
Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant.
BLOOD, 129 (14).
pp. 2033-2037.
ISSN 0006-4971
Full text not available from this repository.
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; CR513 (80%) vs 8 (35%); median lymphocyte count = 320/mu l vs 910/mu l; 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.
Item Type: | Article |
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All Authors: | Hiwarkar, P., Amrolia, P., Sivaprakasam, P., Lum, S. H., Doss, H., O'Rafferty, C., Petterson, T., Patrick, K., Silva, J., Slatter, M., Lawson, S., Rao, K., Steward, C., Gassas, A., Veys, P., Wynn, R., United Kingdom Paediat Bone, Marr |
Additional Information: | ISI Document Delivery No.: ER4ML Times Cited: 1 Cited Reference Count: 17 Hiwarkar, Prashant Amrolia, Persis Sivaprakasam, Ponni Lum, Su Han Doss, Hemalatha O'Rafferty, Ciara Petterson, Toni Patrick, Katharine Silva, Juliana Slatter, Mary Lawson, Sarah Rao, Kanchan Steward, Colin Gassas, Adam Veys, Paul Wynn, Robert 1 0 AMER SOC HEMATOLOGY WASHINGTON BLOOD |
Uncontrolled Keywords: | MARROW-TRANSPLANTATION DOUBLE-BLIND RECONSTITUTION THERAPY DISEASE INFECTIONS PREVENTION CIDOFOVIR VIREMIA |
Research teams: | Clinical Units > Paediatrics Unit |
Depositing User: | Barry Jenkins |
Date Deposited: | 12 May 2017 14:47 |
Last Modified: | 12 May 2017 14:47 |
URI: | http://publications.icr.ac.uk/id/eprint/15894 |
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