Factors Influencing Varicella-Zoster Virus (VZV) Infection after Allogeneic Peripheral Blood Stem Cell Transplantation: Low-Dose Acyclovir Prophylaxis and Pre-Transplant Diagnosis of Lymphoproliferative Disorders.

Introduction: Varicella-zoster virus (VZV) is a frequent opportunistic infection among long-term survivors after allogeneic stem cell transplantation with relatively high incidence of around 30 to 50%. A recent study reported that the cumulative incidence of VZV infection at 5 year reaches up to 63% after allogeneic bone marrow transplantation (Koc, BBMT 2000). It has been suggested that peripheral blood stem cell transplantation (PBSCT) may facilitate immune reconstitution compared to BMT. However, no data has been reported on VZV infection after allogeneic PBSCT. The current study attempted 1) to estimate the incidence of VZV infection, 2) to identify the risk factor for VZV infection, and 3) to analyze the clinical relevance of lymphocyte recovery on VZV infection after allogeneic PBSCT.

Patients and methods: We report a retrospective analysis of VZV infection in 192 recipients of allogeneic PBSCT at Princess Margaret Hospital, Toronto, Canada transplanted between June 2001 and December 2005. The median duration of follow up among survivors was 26 months (2 to 60 months). The pre-transplant diagnoses included AML (77, 40%), ALL (18, 9%), CLL (20, 10%), CML (23, 12%), HD (2, 1%), MDS (15, 8%), myelofibrosis (10, 5%), MM (3, 2%), NHL (22, 12%), and renal cell carcinoma (2, 1%). Twenty-seven patients (14%) received long-term courses of low dose acyclovir prophyaxis (200mg bid po for more than 3 months) for recurrent oral (n=21) or genital HSV infection (n=5) after PBSCT or previous history of recurrent VZV infection before PBSCT (n=1).

Results: Of 192 recipients, 42 patients (22%) developed VZV infection including localized (n=37) and disseminated infections (n=5). The cumulative incidence of VZV infection at 1, 2 and 3 years was 19.3±3.3, 27.0±4.1 and 36.8±5.2%, respectively. Eighteen patients (43%) developed post-herpetic neuralgia for 2 months’ duration (1–21 months). Other complications included secondary bacterial infections (n=3) and intracranial hemorrhage complicated with visceral VZV infection (n=1). One risk factor was identified: pre-translpant diagnosis of a lymphoproliferative disorder (LPD; CLL, HD or NHL) (p=0.021, 52.5±11.7% in LPD group vs 32.6±5.7% in non-LPD group). The use of low dose acyclovir prophylaxis (p=0.007, 0.0% in acyclovir group vs 41.6±6.0% in non-acyclovir group) was found to be protective. While no VZV infection episode were noted in the patients on long-term acyclovir prophyaxis, 3 episodes of VZV infection were noted after cessation of acyclovir. Time-dependent Cox regression analysis confirmed these 2 factors as independent risk factors: 1) diagnosis of LPD (p=0.039, HR 1.965, 95% C.I. 1.033–3.731) and 2) the use of low dose acyclovir prophylaxis (p=0.048, HR 0.305 95% C.I. 0.094–0.991). However, no difference was noted between the group with and without VZV infection in serial lymphocyte counts which has been done before and 3,6,9,and 12 months after transplantation.

Conclusion: The incidence of VZV infection after allogeneic PBSCT still remained quite high on 36.8% at 3 years with patients transplanted for LPDs at higher risk. The use of low dose acyclovir (200mg bid po) seemed to be protective from VZV infection, even though it may not completely prevent late VZV infection. The quantitative serial measurement of lymphocyte count could not predict the risk of VZV infection after allogeneic PBSCT.