Cidofovir for cytomegalovirus reactivation in pediatric patients after hematopoietic stem cell transplantation

Cesaro, S.; Zhou, X.; Manzardo, C.; Buonfrate, D.; Cusinato, R.; Tridello, G.; Mengoli, C.; Palù, G.; Messina, C.

doi:10.1016/j.jcv.2005.02.009

« Previous Next »Journal of Clinical Virology
Volume 34, Issue 2 , Pages 129-132, October 2005

Cidofovir for cytomegalovirus reactivation in pediatric patients after hematopoietic stem cell transplantation

S. Cesaro
- Pediatric Hematology-Oncology Clinic, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova, Italy
- Corresponding author. Tel.: +39 049 821 3579/1461 (secretary)/8032 (O); fax: +39 049 821 3510/1462.
X. Zhou
- Pediatric Hematology-Oncology Clinic, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova, Italy
- Present address: Hematology Center of Beijing Children's Hospital, Nan Lishi Road 56#, Beijing Children's Hospital, Beijing 100045, China.
C. Manzardo
- Service for Infectious Disease in the Pediatric Immunocompromised Host, University of Padova, Padova, Italy
D. Buonfrate
- Service for Infectious Disease in the Pediatric Immunocompromised Host, University of Padova, Padova, Italy
R. Cusinato
- Institute of Microbiology and Virology, University of Padova, Padova, Italy
G. Tridello
- Pediatric Hematology-Oncology Clinic, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova, Italy
C. Mengoli
- Institute of Microbiology and Virology, University of Padova, Padova, Italy
G. Palù
- Institute of Microbiology and Virology, University of Padova, Padova, Italy
C. Messina
- Pediatric Hematology-Oncology Clinic, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova, Italy

Received 5 November 2004; received in revised form 7 February 2005; accepted 16 February 2005. published online 18 April 2005.

Abstract

Background:

Cidofovir (CDV) is a nucleotide analogue with broad antiviral activity. This drug has a very favorable pharmacokinetic profile that enables intermittent dosing, but the potential for nephrotoxicity has hitherto restricted its use in stem cell transplant recipients. Data on pediatric patients are limited.

Objectives:

To report the efficacy and toxicity of CDV in a group of pediatric patients with cytomegalovirus (CMV) reactivation after allogeneic stem cell transplantation.

Study design:

Prospective evaluation of safety and efficacy of CDV used pre-emptively for CMV reactivation in 10 out of 30 children who underwent allogeneic hematopoietic stem cell transplantation from January 2000 to December 2001. In all the patients but one, CDV was used as second-line therapy (after foscarnet or ganciclovir) of CMV reactivation.

Results:

Overall, 12 courses of CDV were administered with a median 5 doses per course, range 1–6 (two patients were treated twice). Considering the first CDV treatment episode, 8 out of 10 patients had positive CMV antigenemia assay when they started CDV. Five of eight antigenemic patients responded completely while three were switched to foscarnet or ganciclovir, respectively, due to increasing (one) or persistent CMV antigenemia (two). Overall, the therapy with CDV was well tolerated, but it was withdrawn in one patient due to a two-fold increase in the baseline creatinine level. This patient concurrently had a high tacrolimus blood level.

Conclusion:

Safety is the major concern regarding the use of CDV but the adoption of probenicid, intravenous hydration and anti-emetic therapy improved its tolerability profile. Our data suggest that CDV has an acceptable toxicity and would deserve further controlled studies in the setting of pre-emptive therapy for CMV.

Abbreviations: CDV, cidofovir, GCV, ganciclovir, FSC, foscarnet, CMV, cytomegalovirus, allo-SCT, allogeneic hematopoietic stem cell transplantation