High Incidence of Herpes Zoster in Nonmyeloablative Hematopoietic Stem Cell Transplantation

Abstract

Background Nonmyeloablative (NMA) stem cell transplant (HSCT) regimens have expanded in the past decade, but little data exists to support antiviral prophylaxis to prevent zoster in recipients seropositive for varicella-zoster virus in this population. The objectives of this study were to describe the clinical features, incidence and risk factors for herpes zoster (HZ) in a homogeneous cohort of NMA allogeneic HSCT recipients. Methods Retrospective cohort study assessing all patients undergoing sibling NMA HSCT at Hôpital Maisonneuve-Rosemont (Montréal, Canada) between 7/2000-12/2008. All patients transplanted received the same conditioning regimen, immunoprophylaxis and graft-versus-host therapy. Herpes zoster diagnosis was defined clinically. Factors associated with HZ occurrence were identified using a Cox proportional hazards model. Results A total of 179 patients were followed for 33 months (median, IQR: 21-59). Zoster developed in 66 patients (37%) at a median of 8.3 months post-HSCT; the incidence rate was 175 cases/1,000 person-years. Estimated cumulative HZ incidence was 27, 36, and 44% at 1, 2, and 3 years respectively. Thoracic dermatomes were most frequently involved (30%); dissemination occurred in 5 patients. No death resulted from HZ, but 23% developed post-herpetic neuralgia. In multivariate analysis, CMV and HSV reactivations were associated with a reduced likelihood of HZ (hazard ratios=0.54 and 0.33, respectively). Conclusion The incidence of HZ in our cohort of NMA allogeneic transplant recipients is similar to the incidence reported following myeloablative regimens. Antiviral prophylaxis or treatment for CMV and HSV reactivations were protective against HZ. Given the observed high risk, we conclude that recommendations for antiviral prophylaxis should also apply, at least for the first year, to the NMA HSCT population.

Infectious complications following allogeneic stem cell transplantation: reduced‐intensity vs. myeloablative conditioning regimens

“…However, the RIC regimen relies more heavily on potent graft‐versus‐leukemia effects for tumor eradication and results in a slow recovery of the pathogen‐specific T‐cell response. For these reasons, RIC allo‐SCT recipients may remain susceptible to opportunistic infections after engraftment . These findings are consistent with the results of our study.…”

“…The published literature on infectious complications after RIC allo‐SCT is limited and has shown a piecemeal approach . Our study was based on the long‐term follow‐up results of a larger number of patients in comparison with previous reports.…”

“…Infectious complications after RIC allo‐SCT may be different from those observed after MAC allo‐SCT. However, the results remain controversial and few data have been reported regarding infection‐related mortality (IRM) and its risk factors . In this study, we thoroughly reviewed the infectious complications following allo‐SCT, based on the intensity of conditioning regimens, and analyzed the risk factors for infection‐related death.…”

Zeroing in on zoster: A tale of many disorders produced by one virus

“…VZV infection incidence among AIDS patients is several times higher than in healthy individuals of the same age, and 50 to 100 times higher among children with leukemia than their same age counterparts [39]. The prevalence of zoster among recipients of hematopoietic stem cell transplantation is 30 - 53% [27,77-79]. Antiviral therapy provides a variable duration of prophylaxis for VZV reactivation, but individuals receiving stem cell transplantation remain at increased risk when antiviral treatments are discontinued [28,76,81].…”

Duration of Antiviral Prophylaxis and Risk of Herpes Zoster among Patients Receiving Autologous Hematopoietic Stem Cell Transplants: A Retrospective, Observational Study

“…The conditioning chemotherapy prior to autologous hematopoietic stem cell transplants (auto-HSCT) targeting underlying malignancies causes immunosuppression, which increases patients’ risk of HZ. Within the first 12 months of post-transplantation, HZ occurs in approximately 17–50% of patients receiving allogeneic hematopoietic stem cell transplants and 16–28% of patients receiving auto-HSCT [8, 9]. The incidence of HZ among auto-HSCT patients is 100–200/1000 person-years (PY) [9, 10] compared to 4/1000 PY in the general population [11].…”