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


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


METHODS
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 Overall, the therapy with CDV was well tolerated, but it was withdrawn in one patient due to a two-fold increase in the baseline creatinine level.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.


CONCLUSIONS
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.
Cesaro
S
S
Pediatric Hematology-Oncology Clinic, Department of Pediatrics, University of Padova, 35128 Padova, Italy. simone.cesaro@unipd.it
Zhou
X
X
Manzardo
C
C
Buonfrate
D
D
Cusinato
R
R
Tridello
G
G
Mengoli
C
C
Palù
G
G
Messina
C
C
D000293:Adolescent; D000956:Antigens, Viral / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D000077404:Cidofovir; D003404:Creatinine / Q000097:blood; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D003596:Cytosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D017245:Foscarnet / Q000627:therapeutic use; D015774:Ganciclovir / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D011292:Premedication; D014775:Virus Activation
D000956:Antigens, Viral; D000998:Antiviral Agents; D063065:Organophosphonates; D017245:Foscarnet; D003596:Cytosine; D003404:Creatinine; D000077404:Cidofovir; D015774:Ganciclovir