Cytomegalovirus pp65 antigenemia-guided pre-emptive treatment with ganciclovir after allogeneic stem transplantation: a single-center experience

Abstract

Summary:The optimal prophylactic strategy for cytomegalovirus (CMV) disease after allogeneic hematopoietic stem cell transplantation has not yet been established. The aim of this study was to analyze our single-center experience with a uniform protocol of CMV antigenemia-guided pre-emptive treatment with ganciclovir (GCV) after allografting. Fifty-two consecutive adult patients, 48 of them transplanted from HLA-identical matched related donors were included. T cell-depleted marrow or peripheral blood were used in 21 cases. After engraftment, weekly blood samples were tested for CMV pp65 antigenemia and viremia (conventional cultures) until day +100. GCV was started if CMV antigenemia and/or CMV viremia were detected. CMV infection (CMV-I) was found in 19 patients (37%). Seven patients suffered from CMV disease (CMV-D), three colitis and four pneumonias. There was one death directly related to CMV-D and three further cases died from refractory GVHD with CMV-D. Only one patient developed CMV pneumonia without any previous positive antigenemia and/or viremia. Multivariate analysis identified grades II-IV acute GVHD (P = 0.02) and peripheral blood stem cell transplantation (P = 0.03) to be risk factors for developing CMV-I. In conclusion, this monitoring protocol allowed early treatment of CMV-I without progression to CMV-D. Pre-emptive therapy had the additional advantage of avoiding GCV administration in most of our allograft recipients. Keywords: CMV infection; antigenemia; BMT Cytomegalovirus (CMV) infection (CMV-I) remains a frequent cause of serious morbidity after allogeneic stem cell transplantation despite the introduction of ganciclovir (GCV). The systematic use of GCV following engraftment is effective in preventing infection and disease by CMV. However, prophylactic use of GCV remains controversial due to its toxicity and the indiscriminate treatment of many patients who would not develop CMV-I or CMV-D. avoid overtreating 30-65% of patients who will not develop CMV-I, sensitive detection methods have been developed to identify CMV reactivation at an early stage, thereby allowing for early (pre-emptive) treatment of the infection before the onset of disease. 1 These methods include direct detection of CMV pp65 antigen (antigenemia) in peripheral blood leukocytes (PBL) 3 and detection of CMV DNA by the polymerase chain reaction in PBL, plasma or serum. 4 Based on encouraging early reports with the use of antigenemia, 1 we designed a uniform protocol of CMV antigenemia-guided pre-emptive treatment with GCV used in all our allografted adults since January 1993. It was our hypothesis that the CMV antigenemia assay could be used to initiate GCV treatment in patients with CMV-I early enough to prevent progression to overt CMV-D, thereby limiting the use of GCV and thus preventing GCV-related neutropenia and its complications. Patients and methodsSixty-four consecutive adults received an allograft in our Division between January 1993 and October 1997. Twelve patients were considered non-evaluable for the develo...

Dose-adjusted preemptive therapy for cytomegalovirus disease based on real-time polymerase chain reaction after allogeneic hematopoietic stem cell transplantation

“…Furthermore, in order to assess whether the dose of ganciclovir could safely be reduced using this sensitive assay, the initial dose of ganciclovir, which was adjusted according to the viral load after initiating the treatment, was reduced by 50% (5 mg/kg/day) as compared to previous reports. 6,[12][13][14] Of 39 high-risk patients, 30 patients had positive results in real-time PCR. The dose of ganciclovir was increased to 10 mg/kg/day in about 40% of preemptively treated patients because of progressively increasing viral load.…”

“…11 CMV antigenemia is one of the most widely used methods to detect CMV infection, and antigenemia-guided preemptive therapy has been shown to be effective in preventing CMV diseases. 6,[12][13][14] However, we and others have demonstrated that antigenemia-guided preemptive therapy did not completely prevent the occurrence of CMV diseases other than pneumonitis. 6,13 In addition, the assay has some other disadvantages.…”

High-dose acyclovir and pre-emptive ganciclovir in prevention of cytomegalovirus disease in pediatric patients following peripheral blood stem cell transplantation

“…The induction period is between 1 and 2 weeks. 6,23,[25][26][27] Kanda et al 6 used antigenemia-guided preemptive therapy with initial low-dose GCV in a cohort with a risk stratification. The incidence of CMV disease in that study was 1.4% for both early and late disease.…”

Cytomegalovirus infection and disease after reduced intensity conditioning allogeneic stem cell transplantation: single-centre experience

“…Among the available screening techniques to detect CMV replication (infection), the most commonly used are the pp65 antigenemia (pp65Ag) assay, and several qualitative and quantitative polymerase chain reaction (PCR) analyses for CMV DNA or CMV mRNA 9,[11][12][13][14][15] At our institution, since 1993 all AlloHSCT recipients at risk for developing CMV-I were monitored with the detection of pp65Ag in peripheral blood polymorphonuclear granulocytes. 16 The progressive switch to quantitative PCR (quantPCR) for the diagnosis and follow-up of numerous viral pathogens led to the implementation of a validated quantPCR for monitoring CMV in immunocompromised hosts, and, thus, in late 2003 we switched to a PCR-based pre-emptive therapy. The growing numbers of RIC allografts allowed us to analyse the characteristics of CMV infection and disease as well as the risk factors for CMV-D in a large homogeneous (with respect to the type of conditioning regimen and supportive care) single-centre patient cohort.…”