Successful Preemptive Cidofovir Treatment for CMV Antigenemia After Dose-Reduced Conditioning and Allogeneic Blood Stem Cell Transplantation

Platzbecker, Uwe; Bandt, Dirk; Thiede, Christian; Helwig, A; Freiberg-Richter, Jens; Schuler, Ulrich S.; Plettig, R.; Geissler, G; Rethwilm, Axel; Ehninger, Gerhard; Bornhäuser, Martin

doi:10.1097/00007890-200104150-00010

Cited by 38 publications

(20 citation statements)

References 21 publications

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“…Two were nonresponders; one died from CMV pneumonia, and one developed CMV pneumonia that eventually responded to foscarnet. The less favorable outcome in the last two reports is in concordance with recent prospective results described by Platzbecker et al (75). In that study, only one of seven SCT recipients showed a transient clearance of pp65 Ag after treatment with CDV at 5 mg/kg/week for 2 weeks and thereafter every 2 weeks.…”

Section: CDVsupporting

confidence: 89%

“…In that study, only one of seven SCT recipients showed a transient clearance of pp65 Ag after treatment with CDV at 5 mg/kg/week for 2 weeks and thereafter every 2 weeks. In contrast, those authors (75) showed that preemptive treatment with CDV was very successful in 10 SCT recipients treated with a nonmyeloablative conditioning regimen. Toxicity was moderate and consisted of reversible renal impairment (n ϭ 4), proteinuria (n ϭ 1), and nausea or vomiting (n ϭ 3).…”

Section: CDVmentioning

confidence: 92%

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Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants

2003

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The main risk factors for cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants (SCT) are recipient CMV seropositivity and acute graft-versus-host disease. Currently, two antiviral strategies, prophylactic or preemptive antiviral treatment, are used for prevention of CMV disease. Preemptive treatment is most favorable when short-term (14-day) treatment is applied. Several methods are available for monitoring of CMV reactivation. PCR-based CMV DNA detection assays are the most sensitive methods; however, the clinical benefit of this high sensitivity is unclear. Even more, there is lack of clarity whether PCR tests can better be performed with plasma, whole blood, or peripheral blood leukocyte samples. Recovery of a CMV-specific CD8+ cytotoxic-T-lymphocyte (CTL) response is necessary for preventing CMV reactivation and disease. Reconstitution of absolute CMV-specific CTL counts to values above 10 × 106 to 20 × 106 CTLs/liter is associated with protection from CMV disease. In the near future, preemptive therapy might be withheld in patients with CMV reactivation who are shown to have adequate CMV-specific cytotoxic T-cell levels. Antiviral therapy with (val)acyclovir has been studied only as prophylactic treatment for prevention of CMV infection. High-dose oral valacyclovir is more effective than acyclovir when used in addition to preemptive treatment of CMV reactivation with ganciclovir or foscarnet. Three antiviral drugs have been tested for preemptive therapy of CMV reactivation and/or treatment of CMV disease. Although intravenous ganciclovir is considered the drug of choice, foscarnet has similar efficacy and less toxicity, especially hematologic toxicity. Cidofovir has not been tested extensively, but so far the results are disappointing. Oral valganciclovir for preemptive treatment of SCT recipients is currently being studied. In addition to antiviral therapy, adoptive immunotherapy with CMV-specific cytotoxic T cells as prophylactic or preemptive therapy is a very elegant strategy; however, generation of these cells is expensive and time-consuming, and therefore the therapy is not available at every transplantation center. Magnetic selection of CMV-specific CD8+ T cells from peripheral blood by using HLA class I-peptide tetramers may be very promising, making this strategy more accessible

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Section: CDVsupporting

confidence: 89%

Section: CDVmentioning

confidence: 92%

Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants

2003

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“…150,151 Cidofovir (generally used as a second-line anti-CMV agent) can be associated with substantial nephrotoxicity. 152,153 Acyclovir and valacyclovir have an excellent safety profile but are only weakly active against CMV.…”

Section: 133mentioning

confidence: 99%

Prevention and Treatment of Cancer-Related Infections

Baden¹,

Bensinger²,

Angarone³

et al. 2012

J Natl Compr Canc Netw

179

146

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“…In clinical trials cidofovir has proven efficacious not only against CMV retinitis but also against other manifestations of CMV disease, e.g., intravenously against asymptomatic CMV infection in HIV-infected patients (121,165). Cidofovir can be recommended as a preemptive treatment for CMV disease (i.e., treatment initiated if CMV antigen or DNA is detected in the blood) after allogeneic blood stem cell transplantation (163). In the study reported by Platzbecker et al (163), 9 (90%) of 10 patients showed a response to cidofovir treatment, with 7 of the 9 experiencing a complete clearance of the virus (pp65 negative, PCR negative); treatment-related toxicity was moderate, with 4 patients developing reversible renal impairment.…”

Section: Clinical Usefulness Cidofovirmentioning

confidence: 99%

Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

2003

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The acyclic nucleoside phosphonates HPMPC (cidofovir), PMEA (adefovir), and PMPA (tenofovir) have proved to be effective in vitro (cell culture systems) and in vivo (animal models and clinical studies) against a wide variety of DNA virus and retrovirus infections: cidofovir against herpesvirus (herpes simplex virus types 1 and 2 varicella-zoster virus, cytomegalovirus [CMV], Epstein-Barr virus, and human herpesviruses 6, 7, and 8), polyomavirus, papillomavirus, adenovirus, and poxvirus (variola virus, cowpox virus, vaccinia virus, molluscum contagiosum virus, and orf virus) infections; adefovir against herpesvirus, hepadnavirus (human hepatitis B virus), and retrovirus (human immunodeficiency virus types 1 [HIV-1] and 2 [HIV-2], simian immunodeficiency virus, and feline immunodeficiency virus) infections; and tenofovir against both hepadnavirus and retrovirus infections. Cidofovir (Vistide) has been officially approved for the treatment of CMV retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) has been approved for the treatment of HIV infections (i.e., AIDS), and adefovir dipivoxil (Hepsera) has been approved for the treatment of chronic hepatitis B. Nephrotoxicity is the dose-limiting side effect for cidofovir (Vistide) when used intravenously (5 mg/kg); no toxic side effects have been described for adefovir dipivoxil and tenofovir disoproxil fumarate, at the approved doses (Hepsera at 10 mg orally daily and Viread at 300 mg orally daily)

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Successful Preemptive Cidofovir Treatment for CMV Antigenemia After Dose-Reduced Conditioning and Allogeneic Blood Stem Cell Transplantation

Abstract: Our data suggest the feasibility of CDV administration in patients after allogeneic transplantation. In the recommended dose, it might be used successfully for low-risk patients, e.g., after DRC or organ transplantation, in an outpatient setting.

Cited by 38 publications

References 21 publications

Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants

Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants

Prevention and Treatment of Cancer-Related Infections

Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

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