High Incidence of Herpes Zoster After Cord Blood Hematopoietic Cell Transplant Despite Longer Duration of Antiviral Prophylaxis

Abstract

Background: Cord blood transplant (CBT) recipients have a high incidence of herpes zoster (HZ) in the context of short-term peritransplant antiviral prophylaxis. In 2009, international guidelines recommended HZ prophylaxis for at least 1 year after hematopoietic cell transplant. The impact of longer-term antiviral prophylaxis on HZ incidence after CBT is unknown.

Methods: We retrospectively analyzed varicella zoster virus (VZV)-seropositive CBT recipients who were transplanted between 2006 and 2016. We abstracted HZ events and other variables for up to 5 years post-CBT. We calculated the cumulative incidence of HZ and used Cox proportional hazards regression to identify variables associated with HZ.

Results: The study cohort consisted of 227 patients. Among 1-year survivors, 91% were still receiving prophylaxis, for a median duration of 20.6 months. HZ occurred in 44 patients (19%) at a median of 23.6 months. The cumulative incidence of HZ by 1 year after CBT was 1.8% (95% confidence interval [CI], .1%-4%), but increased to 26% (95% CI, 19%-33%) by 5 years. In a multivariable analysis, acute graft-vs-host disease was associated with increased risk, whereas antiviral prophylaxis was associated with reduced risk for HZ (adjusted hazard ratio, 0.19 [95% CI, .09-.4]). There was no association between CD4+ T-cell counts at 1 year post-CBT and subsequent risk for HZ.

Conclusions: We found a high incidence of HZ after CBT despite antiviral prophylaxis for > 1 year. Based on these findings, we suggest longer duration of prophylaxis for HZ after CBT. Compliance with antiviral prophylaxis, VZV-specific immune monitoring, and vaccination to mitigate HZ after CBT also require further study.

Keywords: antiviral; cord blood; hematopoietic cell transplant; prophylaxis; varicella zoster virus.

Figure 1.

Consolidated Standards of Reporting Trials (CONSORT) diagram. Fifty-nine patients who received Varivax were excluded a priori. Abbreviations: CBT, cord blood transplant; VZV, varicella zoster virus.

Figure 2.

Cumulative incidence plot of time to herpes zoster (HZ) episode and mortality after cord blood transplant. In this plot, the lower curve shows the cumulative incidence of HZ, with death and subsequent hematopoietic cell transplant (HCT) treated as competing risk events. The upper curve shows the cumulative incidence of overall mortality in patients who did not develop HZ, and the middle section illustrates the proportion of individuals alive and free of HZ.