An International Comparison of Current Strategies to Prevent Herpesvirus and Fungal Infections in Hematopoietic Cell Transplant Recipients

Abstract

Herpes virus (CMV, HSV, VZV) and invasive fungal infections continue to cause significant morbidity and mortality in allogeneic hematopoietic cell transplant (HCT) recipients despite the availability of effective therapies. In this study, we developed an internet-based survey, which was distributed to all HCT centers participating in the CIBMTR program, to gather information on strategies utilized for the prevention of disease due to herpes virus and fungal infections between 1999 and 2003. The survey response rate was 72%, representing 175 programs from 32 countries. Generally, reported center strategies were in accord with the CDC guidelines published in 2000, with 81% of programs using low-dose acyclovir prophylaxis for HSV seropositive patients, 99% of programs reporting use of a CMV prevention strategy during the first 100 days post-transplant for all patients at risk of CMV disease, and 90% of programs using antifungal prophylaxis. Seventy percent of programs reported routine use of a CMV prevention strategy in high-risk patients after day 100. The greatest departure from published guidelines was the use of acyclovir prophylaxis for VZV seropositive recipients in 75% of programs. There were very few reported changes within centers in practices over the study time period. Significant regional variations were found with regard to surveillance procedures and treatment durations. There were no significant differences in treatment practices by center size and very few differences found between those centers that reported treating primarily pediatric patients versus primarily adult patients. In summary, our survey demonstrates overall agreement with published guidelines for the prevention of disease due to herpesviruses and fungal infections with significant regional differences found in duration of antiviral prophylaxis, duration of preemptive therapy, and duration and dosing of antifungal prophylaxis. Center size and age of primary patient population were not associated with many reported differences in strategies.

Zoster prophylaxis after allogeneic hematopoietic cell transplantation using acyclovir/valacyclovir followed by vaccination

“…Other experts have suggested specific immunologic parameters prevaccination, most commonly a CD4 count .200 cells/mL. 15,17 It is likely that the vast majority of patients in our new strategy group had a CD4 count .200 cells/mL before vaccination as we have previously shown that the median CD4 count at 2 years post-HCT at our center is 345 cells/mL (25th-75th percentile, 267-443). 40 From a postvaccination perspective, we do not routinely assess anti-VZV antibody titers at our center because they are known to correlate poorly with risk of VZV reactivation.…”

“…The median duration of prophylaxis in the old strategy group was ;1 year, a relatively common duration of VZV prophylaxis among North American HCT centers. 14,15 The old and new strategy groups were balanced with respect to age, underlying disease, VZV serostatus, and conditioning regimen. In addition, the length of follow-up after discontinuation of antivirals was similar in both groups.…”

“…As a result, there is no consensus on VZV prophylaxis strategy, with significant variation in practice across transplant centers. 15 VZV-specific T-cell immunity, even in the absence of VZV prophylaxis, does not reconstitute post-allo-HCT in the absence of a clinical VZV reactivation event. 16 This finding is in keeping with the rebound effect described above and suggests that a prophylaxis strategy that includes vaccination is required.…”

Cytomegalovirus: pathogen, paradigm, and puzzle

“…Today, the use of preemptive antiviral therapy or prophylaxis is the standard of care in HCT recipients (78). These strategies have reduced the incidence of CMV disease during the first 3 months from approximately 25%-30% to 5% in seropositive recipients; however, late CMV disease may occur and requires continued surveillance in high-risk patients (79).…”

Cytomegalovirus Infection Management in Allogeneic Stem Cell Transplant Recipients: a National Survey in Spain

“…reemptive antiviral therapy has been adopted by most centers as the mainstay strategy for the prevention of cytomegalovirus (CMV) end-organ disease in the allogeneic stem cell transplantation (Allo-SCT) setting (1). Despite the publication of several guideline recommendations for the management of CMV infection in Allo-SCT recipients (2)(3)(4)(5), the strategies deployed at various centers differ notably.…”