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

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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; 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
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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