Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation

Abstract

Culture-based preemptive therapy with ganciclovir was shown to reduce the incidence of cytomegalovirus (CMV) disease after bone marrow transplantation (BMT). Culture techniques did not detect CMV in 12% to 13% of patients before the onset of CMV disease. In a prospective study, 71 patients either received preemptive therapy based on polymerase chain reaction (PCR) technique (37 patients) or on culture assays (34 patients). In both groups, therapy was continued until clinical signs disappeared and PCR negativity was documented. Twenty-two patients in the PCR group and 15 patients in the culture group received antiviral therapy. PCR allowed detection of the virus (median day, +32 v day +49; P = .006) and introduction of antiviral therapy (median day, +44 v day +54; P = .02) earlier than did culture assays. The incidences of CMV disease (2 of 37 v 8 of 34 in PCR group v culture group, respectively; P = .02) and CMV-associated mortality (0 of 37 v 5 of 34 in PCR group v culture group, respectively; P = .02) were decreased, and the duration of ganciclovir therapy (P < .001) was shorter in the PCR-monitored group. Incidence and median duration of severe neutropenia (less than 500/microL) were lower in the PCR group (two v eight episodes, P = .02; median duration, 1.5 v 5 days, P = .04), as was the incidence of nonviral infections during/after antiviral therapy (2 of 37 v 9 of 34; P = .012). Thus, preemptive therapy based on more sensitive detection methods such as the PCR assay reduces the incidence of CMV disease and CMV-related mortality. Additionally, stopping and withholding antiviral therapy in a PCR-negative patient is safe and allows reduction of the duration and side effects of antiviral therapy.

Impact of unrelated donor status on the incidence and outcome of cytomegalovirus infections after non‐myeloablative allogeneic stem cell transplantation

“…We compared these data with those from HCT recipients who had received a similar non-myeloablative HCT conditioning regimen but had received stem cells from HLA MRD. Previous studies have shown that early CMV disease after myeloablative MRD HCT occurs in 3AE8-6% of patients who were at high risk for CMV disease (CMV seropositivity before HCT), if polymerase chain reaction (PCR) or antigenaemia-based preemptive therapy approaches were applied (Einsele et al, 1995;Boeckh et al, 1999). An 11% incidence of early CMV disease has been reported after MUD myeloablative HCT (Small et al, 1999).…”

“…Cytomegalovirus (CMV) infections are the most common viral infections after myeloablative allogeneic haematopoietic cell transplantation (HCT). Although the diagnosis, prophylaxis and treatment have been improved over the last decade (Einsele et al, 1995;Boeckh et al, 1996;Ljungman et al, 1996), CMV infections still contribute significantly to the morbidity and mortality of patients in the early and late post-transplant periods (Husni et al, 1998;Ljungman, 1998). Risk factors for CMV infection after HCT are a positive serostatus for CMV of the recipients before HCT, acute graft-versus-host disease (GVHD), older age and unrelated or related human leucocyte antigen (HLA)mismatched donor transplants (Einsele et al, 1995;Ljungman et al, 1998).…”

Ex vivo generation of human cytomegalovirus‐specific cytotoxic T cells by peptide‐pulsed dendritic cells

“…HCMV-seronegative, HLA-A*0201-expressing donors of buffy coat preparations were blood donors registered at the local blood bank and had been repetitively (more than three times) confirmed to be HCMV-seronegative using an enzyme-linked immunosorbent assay (ELISA) during a period of $ 1 year. No testing by polymerase chain reaction (PCR) assay was performed owing to the fact that, even with our highly sensitive PCR assay (Einsele et al, 1995), we had never been able to detect a blood sample positive for HCMV-DNA using PCR from a donor who was repetitively tested HCMV-seronegative with a sensitive ELISA assay.…”

“…Human cytomegalovirus (HCMV) infection continues to be one of the most important and life threatening infections in patients undergoing allogeneic stem cell transplantation (SCT). This herpesvirus infection still accounts for high morbidity and mortality in this patient cohort despite the introduction of new anti-viral treatment strategies (Ljungman et al, 1992;Einsele et al, 1995;Boeckh et al, 1999). Whereas early onset HCMV disease, occurring during the first 100 d post transplant, can be significantly reduced following the introduction of pre-emptive or prophylactic anti-viral therapy for HCMV infection, HCMV disease occurring after d 100 post transplantation now represents one of the leading causes of mortality after allogeneic SCT (Boeckh et al, 1999;Einsele et al, 2000).…”

Respiratory Infections

“…Consistently identified risk factors for CMV disease include CMV seropositivity, GVHD, lymphopenia, and use of alemtuzumab [47,[72][73][74]. CMV establishes latency; thus, isolation of CMV by viral culture from peripheral sites (e.g., nasopharyngeal, urine, and stool) is poorly predictive in identifying patients who will develop subsequent invasive CMV disease, and some patients who developed disease before peripheral cultures had enough time to grow [75,76]. Although CMV pp65 antigen testing of blood resulted in more rapid identification, it was limited by the need for large blood volumes and could not be used in neutropenic patients [43].…”