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

Introduction Herpes zoster (HZ) after hematopoietic cell transplant (HCT) is a well-known complication with a peak incidence during the first year post-HCT. Cord blood transplant (CBT) recipients are at increased risk for viral infections and historically have a cumulative incidence of HZ approaching 80% by 2.5 years in the context of short-term peri-HCT antiviral prophylaxis. In 2009, international guidelines for prevention of infections after HCT recommended maintaining HZ prophylaxis for at least 1 year after HCT. We retrospectively studied the impact of longer-term antiviral prophylaxis on the incidence of HZ after CBT. Methods Between 2006 and 2016, we performed 360 CBT at our Institution. Patients who were seronegative for varicella zoster virus (VZV) or received the live varicella vaccine (i.e. Varivax®) pre-CBT without a history of chickenpox or HZ were excluded. From 2006-2008, CBT recipients received acyclovir (ACV) 800 mg BID or valacyclovir (VACV) 500 mg BID for HSV and VZV prophylaxis. From 2008-2016, patients who were CMV seropositive received higher-dose prophylaxis with VACV 2g TID through day +100. Before 2009, institutional guidelines recommended to continue prophylaxis until the end of immunosuppression; after 2009, prophylaxis was recommended for at least 1 year and until 8 months after immunosuppression ends. For patients discharged from our center, data were collected through standardized questionnaires and medical records. We abstracted HZ events and other variables for up to 5 years post-CBT. We calculated the cumulative incidence of HZ after CBT, treating death and second HCT as competing risk events. Variables were evaluated for an association with development of HZ using Cox proportional hazards regression; those of biological interest and with a P value ≤ 0.3 in univariable analyses were considerate for multivariable model. Results The study cohort consisted of 227 CBT recipients with a median follow up of 25.4 months (interquartile range [IQR], 6.8 - 49). Follow up time was truncated at the time of death (n=113), second HCT (n=13) or last available records (n=32). Cohort characteristics are shown in Table 1. Among 1-year survivors, 91% were still receiving prophylaxis for a median duration of 20.6 months post-CBT (IQR, 14.1 - 29.4). HZ occurred in 44 patients (19%) at a median of 23.6 months (IQR, 16.1 - 30.3). Most patients (n=31/44, 70%) were not taking antiviral prophylaxis when HZ developed. The cumulative incidence of HZ b