Bone Marrow Transplantation, (1999) 23 , 469–474  1999 Stockton Press All rights reserved 0268–3369/99 $12.00 http:/ / www.stockton-press.co.uk/ bmt Varicella zoster virus infection associated with high-dose chemotherapy and autologous stem-cell rescue S Bilgrami, NG Chakraborty, F Rodriguez-Pinero, AM Khan, JM Feingold, RD Bona, RL Edwards, D Dorsky, J Clive, B Mukherji and PJ Tutschka Bone Marrow Transplant Program, University of Connecticut Health Center, Farmington, CT, USA Summary: A retrospective evaluation of 215 consecutive recipients of high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) was conducted to ascertain the inci- dence, temporal course, and outcome of varicella zoster virus (VZV) infection. Herpes zoster was identified in 40 individuals at a median of 69 days following ASCR. Six of these cases occurred at a median of 33 days prior to ASCR but following the initiation of high doses of stem cell mobilization chemotherapy. Twenty-five per- cent of patients demonstrated cutaneous or systemic dis- semination and 32.5% required medical intervention for post-herpetic neuralgia. All except two individuals received antiviral chemotherapy. One patient with active VZV infection died of multiorgan failure 39 days after ASCR. Multivariate analysis of risk factors dis- closed the significance of prophylactic acyclovir use in Herpes simplex virus seropositive individuals in reduc- ing the risk of VZV infection. Moreover, the use of bus- ulfan, thiotepa and carboplatin as the conditioning chemotherapy regimen was associated with an increased risk of subsequent VZV infection. The incidence of VZV reactivation after HDC and ASCR is similar to that observed following bone marrow transplantation but has an earlier onset. This may be related to an earlier induction of immunosuppression by stem cell mobiliz- ation chemotherapy administered prior to ASCR. We demonstrated a marked reduction in the proliferative and synthetic capacities of peripheral blood mono- nuclear cells obtained prior to and following stem cell mobilizing chemotherapy. Moreover, greater than 80% of VZV infections occurred within 6 months following ASCR and late cases were seldom observed compared to allogeneic and autologous bone marrow transplan- tation. The role of antiviral chemoprophylaxis during the period of maximum immunocompromise needs to be studied further in the HDC-ASCR setting. Keywords: varicella zoster virus; autologous stem cell rescue Correspondence: Dr S Bilgrami, MC-1315, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030 USA Received 20 April 1998; accepted 26 September 1998 Varicella zoster virus (VZV), a human alpha-herpes virus, is the etiologic agent of varicella in childhood after which it assumes dormancy in the dorsal root ganglia. The virus may reactivate in the elderly or during periods of immuno- suppression such as that following allogeneic, syngeneic, or autologous bone marrow transplantation (BMT). In the latter setting, VZV reactivation may be associated with con- siderable morbidity and occasional mortality. A recent trend has been the increasing use of high-dose chemo- therapy and autologous stem cell rescue (HDC-ASCR) for a variety of hematologic malignancies and solid tumors. It has been suggested that the duration and severity of immunosuppression may be less following HDC-ASCR compared to BMT. 1–3 Since the incidence of VZV reacti- vation increases with the degree of immunosuppression, 4 it could be postulated that the incidence of VZV reactivation may be lower after HDC-ASCR compared to BMT. Fur- thermore, HDC-ASCR may be preceded by one or more courses of relatively high-dose stem cell mobilization chemotherapy which may itself be significantly immuno- suppressive. This could lead to an earlier manifestation of VZV than that observed following BMT. The aim of this study was to ascertain the incidence, temporal course, and outcome of VZV reactivation following HDC-ASCR. Materials and methods Patients Two hundred and fifteen consecutive patients underwent HDC-ASCR between March 1993, and January 1997, at the University of Connecticut Health Center (Farmington, CT, USA) and were eligible for retrospective evaluation. Clinical data were obtained from comprehensive chart reviews (Table 1). Localized herpes zoster was defined as Table 1 Patient characteristics Number of patients 215 Number of patients with VZV reactivation 40 Median day of onset of VZV reactivation after + 69 (-108 to + 488) ASCR Male:Female 58:157 Median age (years) (range) 44 (2–65) Solid tumor:hematologic malignancies 122:93 Median duration of corticosteroid administration 43 (days) VZV = varicella zoster virus; ASCR = autologous stem cell rescue.