Efficacy of low-dose zoster prophylaxis in patients undergoing allogeneic hematopoietic cell transplantation

Abstract

Reactivation of varicella zoster virus (VZV) can occur in 20-53% of patients during the first year after allogeneic HCT, contributing to a high burden of infectious complications after HCT, and increasing utilization of medical resources and healthcare costs [1]. Accordingly, current guidelines recommend antiviral prophylaxis (e.g., acyclovir) for a minimum of 1 year after HCT, or until discontinuation of immunosuppression, whichever occurs later [1]. The recommended dose of acyclovir (800 mg twice daily [BID]) was derived from at least two randomized studies that demonstrated efficacy (≤5% reactivation) in the first year after HCT [1,2]. However, this strategy is limited by a high risk of nephrotoxicity brought on by the concurrent use of antimicrobials or immunosuppressive medications used to treat graft versus host disease (GVHD) [1]. Currently, there is variability in clinical practice across transplant centers, with studies suggesting short-term efficacy of lower dose acyclovir in solid organ transplant and select patients undergoing HCT [3,4]. As such, VZV prophylaxis at our institution has been acyclovir 400 mg BID, with a duration of at least 1 year after HCT or 3 months after discontinuation of immunosuppressive medications, whichever occurs later. The long-term efficacy of this approach has not been well-described.We conducted a retrospective cohort study of patients who underwent allogenic HCT as adults (≥18 years old) at City of Hope (COH) between January 1, 2010 and December 31, 2015. COH and non-COH medical records were the primary source of information. We abstracted demographic data (age at HCT, sex, race/ethnicity), CMV serostatus, diagnosis (acute myeloid leukemia [AML], acute lymphoid leukemia [ALL], myelodysplastic syndrome [MDS], other), HCT comorbidity-age index (HCT-CI), Karnofsky performance score (KPS), HCT details (donor source, conditioning intensity [5]), relapse risk at HCT [6], severity of acute GVHD, and vital status per an established protocol [7,8]. GVHD prophylaxis was tacrolimus/sirolimus-based or tacrolimus with a short course of methotrexate. Grading of acute GVHD was per established criteria [9]. The Institutional Review Board at COH approved the protocol. Informed consent was provided according to the Declaration of Helsinki.The primary endpoint was VZV infection, categorized as dermatomal (involvement of 1-2 dermatomes) or disseminated (involvement of >2 dermatomes or extracutaneous involvement) per established definitions [10]. Patients were followed until the first episode of VZV infection or a competing risk event, whichever occurred first.Univariate analyses were performed to compare between patients who developed VZV and those who did not. Relapse/ progression or death was considered as a competing event. Time was calculated from the date of HCT to date of death, relapse/progression, or last contact (censored: December 31, 2018). Cumulative incidence of VZV infection was calculated taking into consideration competing risk for right-censored data [11]. Multivariable log...

Late‐occurring infections in a contemporary cohort of hematopoietic cell transplantation survivors

“…We previously reported how a sizeable proportion (21.5%) of patients who had VZV reactivation may not have been on optimal dosing as a result of concurrent infections that necessitated the use of other antivirals, renal insufficiency, or possible malabsorption due to gastrointestinal GVHD, while 25.5% had breakthrough VZV infection during a period of scheduled prophylaxis. 37 The findings from the current study may help emphasize the need to consider safe revaccination or longer prophylaxis strategies in HCT survivors. While the inactivated or recombinant zoster vaccine (RZV) has demonstrated efficacy after autologous HCT, 38 the results have been mixed in patients with hematological malignancies receiving immunosuppressive cancer treatment.…”

Towards a personalized preventive strategy of Herpes zoster infection in patients with hematologic diseases or hematopoietic stem cell transplant recipients: a position paper from an <i>ad hoc</i> Italian expert panel

“…In MM patients who received various schedules of AVP (acyclovir 200 mg/day to 400 mg twice daily or valacyclovir 500 mg/day) no or less than 1% instances of infection were observed for the whole duration of bortezomib treatment and in the follow-up. [27][28][29][30][31] . Patients in whom AVP was interrupted before the end of cancer treatment had a higher risk of developing HZ infection, compared to those who continued AVP (adjusted HR 3.09) 32 .…”

Two Waves of Specific B Cell Memory Immunoreconstruction Observed in Anti-HHV1–3 IgG Kinetics after Hematopoietic Stem Cell Transplantation

“…Furthermore, concentrations of specific IgGs have been used to estimate immunity against varicella zoster virus (VZV) in solid organ transplant (SOT) recipients only [ 6 ]. However, in hematopoietic stem cell transplantation (HSCT), the situation is more problematic: HHV1–3 serostatus is not evaluated and acyclovir is overused [ 7 ]. The relationship between preexisting anti-VZV levels and clinical VZV reactivation in HSCT recipients was studied in a small group of 13 subjects without a significant difference found between sick and healthy subjects; however, VZV reactivation was arbitrarily diagnosed with a non-validated, semi-quantitative immune adherence hemagglutination method.…”

“…Retrospective analysis of 300 patients’ histories and selection of patients with bona fide HSV/VZV reactivation. In order to avoid biases that appear in cohort studies on HSV and VZV (HHV1–3) reactivation (e.g., [ 7 ]), an in-depth data selection and finally a case–control study were conducted (see [ 12 ]). From 300 suspected patients, the two rounds of differential diagnosis were based on exclusion criteria (the most important are presented on the right side).…”