Cidofovir as primary pre-emptive therapy for post-transplant cytomegalovirus infections.
Pre-emptive antiviral therapy for CMV infection following allogeneic stem cell transplantation is an effective strategy for preventing CMV disease. This entails the logistic difficulty of daily intravenous therapy with ganciclovir or foscarnet to clinically asymptomatic patients. Cidofovir (CDV) is effective against CMV in vitro and has the practical advantage of weekly administration. However, there are limited data on the pre-emptive use of CDV in CMV infections. We carried out a pilot study exploring the efficacy and toxicity of CDV as primary pre-emptive therapy for CMV infections monitored by PCR-based assays. CDV was used at 5 mg/kg with probenecid and hydration, weekly for a maximum of 4 weeks, followed by fortnightly maintenance treatment. Four patients were treated with CDV and two of them responded. Both the non-responders developed CMV disease. There was no renal toxicity noted in any of the patients, but three patients had severe vomiting and one developed uveitis, which precluded maintenance treatment in the two responders. Following failure of CDV, foscarnet was effective in controlling the CMV infection in both patients, although the infection recurred in both. Thus, larger randomised studies are required before CDV can be recommended as a primary pre-emptive therapy for post-transplant CMV infections.
Chakrabarti
S
S
Department of Haematology, Birmingham Heartlands Hospital, Birmingham, UK.
Collingham
K E
KE
Osman
H
H
Fegan
C D
CD
Milligan
D W
DW
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077404:Cidofovir; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000517:prevention & control*; D003596:Cytosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004341:Drug Evaluation; D015828:Eye Infections, Viral / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D005260:Female; D017245:Foscarnet / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000150:complications; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011339:Probenecid / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D012449:Safety; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014606:Uveitis, Anterior / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000209:etiology / Q000517:prevention & control; D014839:Vomiting / Q000139:chemically induced
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D017245:Foscarnet; D016572:Cyclosporine; D003596:Cytosine; D000077404:Cidofovir; D011339:Probenecid