Foscarnet vs ganciclovir for cytomegalovirus (CMV) antigenemia after allogeneic hemopoietic stem cell transplantation (HSCT): a randomised study

Moretti, Simone; Zikos, P; Lint, MT Van; Tedone, Elisabetta; Occhini, D; Gualandi, Francesca; Lamparelli, Teresa; Mordini, Nicola; Berisso, Giovanni; Bregante, Stefania; Bruno, Benedetto; Bacigalupo, Andrea

doi:10.1038/sj.bmt.1701302

Cited by 70 publications

(49 citation statements)

References 22 publications

(20 reference statements)

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“…First results suggest that preemptive foscarnet treatment mediates protection from CMV disease in SCT recipients. 19,21 We report the results of a prospective randomized multicenter trial in which foscarnet and ganciclovir were compared in the preemptive therapy of CMV infection after allogeneic SCT. In this study, antiviral treatment was initiated upon detection of CMV by antigenemia assay or by PCR in peripheral blood leukocytes, and was given for no longer than 4 weeks.…”

Section: Introductionmentioning

confidence: 99%

Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation

Reusser

Einsele²,

Lee³

et al. 2002

Blood

287

185

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The present study compared foscarnet with ganciclovir for preemptive therapy of cytomegalovirus (CMV) infection after allogeneic blood or marrow stem cell transplantation (SCT). Patients with CMV infection, as detected by weekly antigenemia or polymerase chain reaction (PCR) in blood leukocytes, were randomized to intravenous therapy for 2 weeks with either foscarnet at 60 mg/kg or ganciclovir at 5 mg/kg administered every 12 hours; if CMV infection remained detectable, patients received an additional 2 weeks of intravenous foscarnet at 90 mg/kg or ganciclovir at 6 mg/kg given once daily for 5 days per week, after which therapy was stopped. Primary efficacy endpoint was the occurrence of CMV disease or death from any cause within 180 days after SCT. A total of 213 patients were treated with either foscarnet (n ‫؍‬ 110) or ganciclovir (n ‫؍‬ 103). Kaplan-Meier estimates of event-free survival within 180 days after SCT were similar in the 2 treatment groups (P ‫؍‬ .6). During study treatment, severe neutropenia (< 0.5 ؋ 10 9 /L) occurred in 11 (11%) patients on ganciclovir versus 4 (4%) patients on foscarnet (P ‫؍‬ .04), and impaired renal function was observed in 5 (5%) patients on foscarnet versus 2 (2%) patients on ganciclovir (P ‫؍‬ .4). Neutropenia or thrombocytopenia required discontinuation of ganciclovir in 6 (6%) patients but in no foscarnet-treated patient (P ‫؍‬ .03). After allogeneic SCT, preemptive therapy of CMV infection with foscarnet shows similar efficacy as with ganciclovir, but is associated with a lower proportion of patients who develop severe neutropenia and who require discontinuation of antiviral therapy due to hematotoxicity. IntroductionCytomegalovirus (CMV) remains a leading cause of infectious complications after allogeneic bone marrow or peripheral blood stem cell transplantation (SCT). In the absence of preventive measures, the incidence of CMV infection is 60% to 70% in the first 3 months after allogeneic SCT when graft donor or patient are pretransplantation CMV seropositive, and one third of patients with evidence of CMV infection develop CMV pneumonia. 1-3 CMV pneumonia is a serious condition, which, with the best presently available therapy, is associated with a high mortality. 4 Therefore, major emphasis must be placed on the prevention of CMV disease in allograft recipients.For CMV-seropositive patients or seronegative patients with a seropositive graft donor, 2 main strategies are currently used to prevent CMV disease in the posttransplantation course. Prophylactic drug treatment is aimed at suppressing CMV reactivation, and is given to all patients irrespective of the results of virologic monitoring. [5][6][7][8] Alternatively, preemptive therapy consists of initiating antiviral treatment only when active CMV infection is documented in order to prevent the development of CMV disease. [9][10][11][12] Thus, with the preemptive therapy approach, the use of potentially toxic drugs against CMV, such as ganciclovir and foscarnet, is restricted to patients at highest risk for CMV ...

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Section: Introductionmentioning

confidence: 99%

Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation

Reusser

Einsele²,

Lee³

et al. 2002

Blood

287

185

View full text Add to dashboard Cite

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“…Using antigenemia-based assays, 60-85% of patients have been reported to clear viremia after 2 weeks of therapy. 10,12,16,19 When PCRbased surveillance strategies are employed, clearance rates of 37-50% have been reported after 2 weeks. 9,11 In our series, 36/58 patients (62%) had negative shell vial cultures recorded on day 14 of LDSC GCV therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Previous series using abbreviated inductionmaintenance schedules of GCV have reported a much higher incidence of neutropenia with about a third of patients developing an ANCo1000/ml and up to 20% of patients exhibited a decline in their ANC to o500/ml. [9][10][11]13,14,16,17 A substantial proportion of patients in these series also required growth-factor support that adds substantially to the overall cost of therapy. More importantly, Salzberger et al 5 have shown that neutropenia in patients receiving GCV is an independent risk factor for poor long-term outcome.…”

Section: Discussionmentioning

confidence: 99%

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Low-dose short-course intravenous ganciclovir as pre-emptive therapy for CMV viremia post allo-PBSC transplantation

Vij

Khoury

Brown

et al. 2003

Bone Marrow Transplant

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Summary:In contrast to allogeneic bone marrow transplantation (allo-BMT), there is a paucity of data on cytomegalovirus (CMV) infection and pre-emptive therapy (PT) strategies following allogeneic peripheral blood stem cell (allo-PBSC) transplantation. We report here on the patterns of CMV infection in a cohort of 225 patients following sibling donor allo-PBSC transplantation. In an attempt to reduce neutropenia, we used intravenous low-dose shortcourse (LDSC) ganciclovir (GCV) 5 mg/kg once daily for 21 days as preemptive therapy. A total of 165 recipientdonor pairs were CMV seropositive. An initial episode of viremia (detected by shell vial/tube culture) occurred in 75/165 (45%) at a median of day þ 35 (17-445) post allo-PBSC. In all, 58 patients received PT with LDSC GCV. Among 58, 55 (94%) completed the 21-day course of PT. A second episode of viremia occurred in 19/58 (33%) at day þ 80 (50-174) and a third episode in 5/58 (9%) at day þ 134 (103-218). Among patients receiving LDSC GCV, 5/58(9%) developed disease (four pneumonia, one colitis) at day þ 211 . No patient on LDSC GCV exhibited a decline in their ANC below 500/ll and none required growth factors. LDSC GCV is extremely well tolerated and cost-effective as PT for CMV viremia following allo-PBSC transplantation.

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“…4,7) Three studies have so far identified risk factors for ganciclovir-induced neutropenia. Tomonari et al reported that reduced renal function was a risk factor for ganciclovir-induced neutropenia following cord blood transplantation.…”

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confidence: 99%

Risk Factors for Ganciclovir-Induced Thrombocytopenia and Leukopenia

Matsumoto

Shigemi

Ikawa

et al. 2015

Biological & Pharmaceutical Bulletin

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Ganciclovir is a nucleoside guanosine analogue that exhibits therapeutic activity against human cytomegalovirus infection, and is primarily excreted via glomerular filtration and active tubular secretion. The adverse effects induced by ganciclovir therapy are generally of a hematological nature and include thrombocytopenia and leukopenia. Low marrow cellularity and elevated serum creatinine have been identified as risk factors for ganciclovir-induced neutropenia. However, the risk factors for thrombocytopenia have yet to be determined. Therefore, this study investigated patients administered ganciclovir to determine the risk factors for thrombocytopenia and leukopenia. Thrombocytopenia occurred in 41 of these patients (30.6%). Multivariate logistic regression analysis identified three independent risk factors for thrombocytopenia: cancer chemotherapy (odds ratio (OR) 3.1), creatinine clearance (<20 mL/min) (OR 12.8), and the ganciclovir dose (≥12 mg/kg/d) (OR 15.1). Leukopenia occurred in 36 patients (28.6%), and white blood cell count (<6000 cells/mm 3 ) (OR 3.7) and the ganciclovir dose (≥12 mg/kg/d) (OR 7.8) were identified as risk factors. These results demonstrated that several factors influenced the occurrence of ganciclovir-induced thrombocytopenia and leukopenia, and suggest that special attention should be paid to patients receiving cancer chemotherapy with a low creatinine clearance (<20 mL/min) and high dose (≥12 mg/kg/d) in order to avoid ganciclovir-induced thrombocytopenia.

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Foscarnet vs ganciclovir for cytomegalovirus (CMV) antigenemia after allogeneic hemopoietic stem cell transplantation (HSCT): a randomised study

Cited by 70 publications

References 22 publications

Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation

Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation

Low-dose short-course intravenous ganciclovir as pre-emptive therapy for CMV viremia post allo-PBSC transplantation

Risk Factors for Ganciclovir-Induced Thrombocytopenia and Leukopenia

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