Abstract: Eight RCTs were included, with 305 patients in the intervention groups and 288 in the control groups. They evaluated heat-inactivated varicella zoster virus (VZV) vaccine (two trials), influenza vaccines (five trials) and inactivated poliovirus vaccine (IPV) (one trial). Seven trials had high and one trial had moderate risk of bias. VZV vaccine might reduce herpes zoster compared to no vaccine (RR 0.54, 95% CI 0.3 to 1.0, P=0.05), but not statistically significant. Vaccination also demonstrated efficacy in immune response but frequently caused local adverse effects. One trial reported severity score of zoster, which favored vaccination (MD 2.6, 95% CI 0.94 to 4.26, P=0.002). Two RCTs compared inactivated influenza vaccine with no vaccine and reported lower risk of lower respiratory infections (RR 0.39, 95% CI 0.19 to 0.78, P=0.008) and hospitalization (RR 0.17, 95% CI 0.09 to 0.31, P<0.00001) in vaccine recipients. However, vaccine recipients more frequently experienced irritability and local adverse effects. There was no significant difference in seroconversion between one and two doses of influenza vaccine (one trial), or between recombinant and standard influenza vaccine (one trial), or influenza vaccine given with or without re-induction chemotherapy (one trial). The IPV trial comparing vaccination starting at 6 versus 18 months after stem cell transplant (SCT) found no significant difference in seroconversion. Inactivated VZV vaccine might reduce zoster severity in adult SCT recipients. Inactivated influenza vaccine might reduce respiratory infections and hospitalization in adults with multiple myeloma or children with leukemia or lymphoma. However, the quality of evidence is low. Local adverse effects occur frequently. Further high-quality RCTs are needed.

Plain-language summary: In the current systematic review of randomized controlled trials (RCTs) we aimed to evaluate the efficacy and safety of viral vaccines in these patients. The pre-defined primary outcome was incidence of the infection concerned. Secondary outcomes were mortality due to the viral infection, all-cause mortality, incidence of complications, incidence of severe viral infection, hospitalization rate, in vitro immune response and frequency of adverse effects. Eight RCTs were included. They evaluated heat-inactivated varicella zoster virus (VZV) vaccine (two trials), influenza vaccines (five trials) and inactivated poliovirus vaccine (one trial). There were no RCTs on other viral vaccines (hepatitis A, hepatitis B, measles, mumps, rubella). Only the two trials on VZV vaccine reported our pre-defined primary outcome. All trials reported some of the pre-defined secondary outcomes. We found that inactivated VZV vaccine might reduce the severity of herpes zoster when given before and after stem cell transplant in adults with lymphoma or leukemia. Inactivated influenza vaccine might reduce upper and lower respiratory infections and hospitalization in adults with multiple myeloma who are undergoing chemotherapy, or children with leukemia or lymphoma within two years post-chemotherapy. However, the quality of evidence is not high. Local adverse effects occur frequently with the vaccines, although serious adverse effects appear uncommon. Further high-quality RCTs are needed to clarify the benefits and optimal regimens of viral vaccines for patients with blood cancers.