Anti-herpesvirus prophylaxis, pre-emptive treatment or no treatment in adults undergoing allogeneic transplant for hematological disease: systematic review and meta-analysis.

BACKGROUND: Herpesvirideae infections incur significant morbidity and indirect effects on mortality among allogeneic hematopoietic cell transplant (allo-HCT) recipients.

OBJECTIVES: To study the effects of antivirals prevention strategies among hemato-oncological individuals undergoing allo-HCT.

DATA SOURCES: Cochrane Central Register of Controlled Trials, MEDLINE, Embase and LILACS. We further searched for conference proceedings and trial registries.

STUDY ELIGIBILITY: Randomized-controlled trials.

PARTICIPANTS: Adults with hematological malignancy undergoing allo-HCT.

INTERVENTIONS: Anti-viral prophylaxis vs. no treatment/placebo or pre-emptive treatment and pre-emptive treatment vs. prophylaxis with the same agent.

METHODS: Random-effects meta-analysis was conducted computing pooled risk ratios (RR) with 95% confidence intervals (CI) and the inconsistency measure (I2 ). The certainty of the evidence was appraised by GRADE.

RESULTS: We included 22 RCTs. Anti-viral prophylaxis reduced all-cause mortality (RR 0.83, 95% CI 0.7 to 0.99; N trials=15, I2 =0%), CMV disease (RR 0.54, 95% CI 0.34 to 0.85; N=15, I2 =20%) and HSV disease (RR 0.29, 95% CI 0.2 to 0.43; N=13, I2 =18%) compared to no treatment/placebo or pre-emptive treatment, all with high-certainty evidence. Furthermore, antivirals reduced HSV infection, CMV pneumonitis, CMV infection and VZV disease. Anti-CMV prophylaxis (+/- pre-emptive treatment) compared to pre-emptive treatment alone reduced non-significantly all-cause mortality (RR 0.78, 95% CI 0.6 to 1.02; N=8, I2 =0%), CMV disease (RR 0.47, 95% CI 0.23 to 0.97; N=9, I2 =30%) and HSV disease (RR 0.41, 95% CI 0.24 to 0.67; N=4, I2 =0%) with high-certainty evidence, as well CMV and HSV infections. Antiviral prophylaxis did not result in increased adverse event rates overall or more discontinuation due to adverse events.

CONCLUSIONS: Antiviral prophylaxis directed against herpesviruses is highly effective and safe, reducing mortality, HSV and CMV disease, as well as herpesvirus reactivations among allogeneic HCT recipients. Anti-CMV prophylaxis is more effective than pre-emptive treatment alone with respect to HSV and CMV disease and infection.