Long-term acyclovir for prevention of varicella zoster virus disease after allogeneic hematopoietic cell transplantation—a randomized double-blind placebo-controlled study

Abstract

Varicella-zoster virus (VZV) disease occurs in 30% of allogeneic hematopoietic cell transplant recipients who had a history of VZV infection. A safe and effective prevention strategy has not been established. In a double-blind controlled trial, 77 hematopoietic cell transplant recipients at risk for VZV reactivation were randomized to acyclovir 800 mg twice daily or placebo given from 1 to 2 months until 1 year after transplantation. VZV disease at 1 year was the primary end point; VZV disease after discontinuation of prophylaxis, VZV-specific T-cell immunity, herpes simplex virus (HSV) infection, cytomegalovirus (CMV) disease, survival, and safety were secondary end points. Acyclovir significantly reduced VZV infections at 1 year after transplantation (HR, 0.16; 95% CI, 0.035-0.74; P ‫؍‬ .006). In the postintervention observation period, this difference was not statistically significant (2 years: HR, 0.52; 95% CI, 0.21-1.3; 5 years: HR, 0.76; 95% CI, 0.36-1.6). There was no statistically significant difference in reconstitution of VZVspecific T-helper cell responses, HSV infections, CMV disease, chronic graftversus-host disease, and overall survival between the groups. Acyclovir was well tolerated. Post-study VZV disease predominantly occurred in patients with continued need for systemic immunosuppression. In conclusion, acyclovir effectively and safely prevents VZV disease during the first year after hematopoietic cell transplantation. Periods of prophylaxis longer than 12 months may be beneficial for those hematopoietic cell transplant recipients on continued immune suppression.

Varicella zoster virus reactivation after autologous SCT is a frequent event and associated with favorable outcome in myeloma patients

“…The incidence of HZ at 1 year following SCT was reported to vary between 5 and 53%, 4,17,19,22,23 and specifically after autologous SCT between 8 and 30%. 3,[12][13][14][15][16] The increased risk of HZ in SCT recipients is highest during the first year following transplantation because of the diminished T-cell Varicella zoster virus reactivation C Kamber et al immunity, 3,12,15 and reaches a plateau by 2 or 3 years after transplantation.…”

“…2,3,[17][18][19][20] Clearly, live attenuated VZV vaccination is contraindicated in severely immunocompromised patients undergoing ASCT. In general, patients routinely receive oral antiviral prophylaxis after ASCT to reduce the risk of herpes virus-associated diseases, including HZ.…”

Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation

“…Two patients died from disseminated varicella zoster infection. Boeckh et al 54 recently showed that 800 mg acyclovir given b.i.d. for 12 months effectively prevented zoster reactivation.…”

“…Several of the identified risk factors have previously been shown to be correlated. Acute GVHD increases the risk of CMV infection, 54,55 the CMV viral load 56 and subsequent chronic GVHD. 38,40 The use of alternative donors increases the risk of CMV infection and acute GVHD.…”

Pretransplant vaccinations in allogeneic stem cell transplantation donors and recipients: an often-missed opportunity for immunoprotection?

“…Long-term acyclovir prophylaxis is effective in preventing reactivation. [24][25][26] Most episodes of herpes zoster in the absence of acyclovir prophylaxis occur within the first 2-10 months after transplantation and T-cell responses to VZV Ag encountered pretransplant can be detected as early as 1-6 months post transplant. 23,27 Therefore, vaccination of both donors and recipients could be a strategy worth studying further.…”