Characteristics of the included studies
| Number . | Study . | Study design, years conducted . | Types of intervention . | Dose and schedule of interventions . | Types and number of participants (n), multicenter or single center . | Outcomes . |
|---|---|---|---|---|---|---|
| 1 | Boughton et al13 | RCT, not stated | Prophylactic immunoglobulin compared with placebo | IVIg 18 g (sandoglobulin) vs placebo (0.6 g albumin) every 3 wk for 12 mo | CLL, serum IgG <5.5 g /L and 2 or more documented infections in the preceding 12 mo; N = 42, multicenter | Patients with ≥1 CDI, patients with ≥1 MDI, number of MDIs, patients with ≥3 infections, patients with ≥3 serious infections, number of CDIs (overall but not by treatment arm), adverse effects, adverse events leading to treatment discontinuation |
| 2 | Chapel et al14 | RCT, not stated | Prophylactic immunoglobulin compared with placebo | IVIg 0.4 g/kg (Gammagard) vs placebo (4% albumin) every 4 wk for 12 mo | MM in stable phase; N = 83, multicenter | All-cause mortality, IRM, patients with ≥1 CDI, number of CDIs, number of MDIs, number of serious infections, time to first major infection, adverse events, adverse events leading to treatment discontinuation |
| 3 | Cooperative CLL16 | RCT, not stated | Prophylactic immunoglobulin compared with placebo | IVIg 0.4 g/kg (Gammagard) vs placebo (0.9% sodium chloride) every 4 wk for 12 mo | CLL, serum IgG level < 50% of lower limit of normal or a history of serious infections; N = 84, multicenter | All-cause mortality, patients with ≥1 infections, patients with ≥3 infections, patients with ≥1 serious infections, patients with ≥1 MDI, number of MDIs, number of CDIs, number of serious infections, adverse events, adverse events leading to treatment discontinuation |
| 4 | Dagnew et al26 | RCT, 2013-2015 | Vaccination compared with placebo | Adjuvanted recombinant zoster vaccine (2 doses) vs placebo 1-2 mo apart | CLL, lymphoma, MM, receiving or had just finished immunosuppressive cancer treatments; N = 562, multicenter | All-cause mortality, patients with ≥1 CDI, patients with ≥1 MDI, number of CDI, number of MDIs, adverse events |
| 5 | Drayson et al21 | RCT, 2012-2016 | Prophylactic antibiotics compared with placebo | Levofloxacin 500 mg daily vs placebo for 12 wk | MM, newly diagnosed with planned antimyeloma treatment; N = 977, multicenter | All-cause mortality, IRM, patients with ≥1 CDI, number of CDIs, number of MDIs, number of hospitalizations, number of ICU admissions, adverse events |
| 6 | Gamm et al15 Chapel et al14 | RCT, not stated | Prophylactic immunoglobulin comparing differing doses | IVIg 0.5 g/kg vs IVIg 0.25 g/kg (Gammagard) every 4 wk for 12 mo | CLL and lymphoma, serum IgG below lower limit of normal or a recent history of serious infections; N = 36, multicenter | All-cause mortality, IRM, patients with ≥1 CDI, number of CDIs, number of MDIs, number of serious infections, adverse events |
| 7 | Gregersen et al22 | RCT, not stated | Prophylactic antibiotics compared with placebo | Clarithromycin 500 mg BD vs placebo for 3 mo | MM, newly diagnosed and receiving VCD induction chemotherapy; N = 58, multicenter | All-cause mortality, patients with ≥1 CDI, patients with ≥1 MDI, patients with ≥1 serious infection, adverse events |
| 8 | Griffiths et al17 | RCT Crossover, 1984-1987 | Prophylactic immunoglobulin compared with placebo | IVIg 0.4 g/kg (Gammagard) vs placebo (saline) every 3 wk for months, then crossover for another 12 mo | CLL, serum IgG level <3.5 g/L or a history of serious infections; N=12, single center | Number of CDIs, adverse events |
| 9 | Hata et al27 | RCT, 1997-2000 | Vaccination compared with placebo | Heat-inactivated, live attenuated varicella vaccine vs placebo given within 30 d before transplantation and 30, 60, and 90 d after transplantation | Lymphoma, autologous stem cell transplant; N = 119, multicenter | All-cause mortality, patients with ≥1 CDI, number of CDIs, adverse events (treatment group only) |
| 10 | McQuilten et al35 | RCT, 2017-2020 | Prophylactic antibiotics compared with prophylactic immunoglobulin | IVIg 0.4 g/kg every 4 wk or SCIg 0.1 g/kg every week vs oral antibiotics (trimethoprim-sulfamethoxazole 160 mg/800 mg daily) for 12 mo | CLL, MM, lymphoma, other hematological malignancy, serum IgG level <4 g/L or a history of serious infections; N = 60, multicenter | Time to first major infection, patients with ≥1 serious infection |
| 11 | Molica et al18 | RCT, crossover, not stated | Prophylactic immunoglobulin compared with no treatment | IVIg 0.3g/kg (Vena-N) every 4 wk vs no treatment for 6 mo, then switched to observation or IVIg for another 12 mo; then IVIG or no therapy for 6 more months. | CLL, serum IgG level <6 g/L or a history of serious infections; N = 42, multicenter | All-cause mortality, IRM, number of CDIs, number of MDIs |
| 12 | Musto et al19 | RCT crossover, not stated | Prophylactic immunoglobulin compared with no treatment | IVIg 0.3 g/kg (Vena-N) every 4 wk vs no treatment for 6 mo, then switched to observation or IVIg for another 12 mo; then IVIG or no therapy for 6 more months | MM, serum IgG below lower limit of normal or a recent history of serious infections; N = 25, not stated | All-cause mortality, IRM, number of CDIs, number of serious infections |
| 13 | Musto and Carotenuto28 | RCT, 1995-1996 | Vaccination compared with no treatment | Influenza vaccine (trivalent subvirion containing antigens from the component strains A/Singapore/6/86, A/Johannesburg/33/94 and B/Bijing/184/93) vs no treatment | MM undergoing chemotherapy; N = 50, not stated | IRM, patients with ≥1 CDI, number of hospitalizations, adverse events (treatment group only), adverse events leading to treatment discontinuation (treatment group only) |
| 14 | Oken et al23 1996 | RCT, not stated | Prophylactic antibiotics compared with no treatment | Oral antibiotics (trimethoprim-sulfamethoxazole 160mg/800mg bd) vs no treatment for 2 mo | MM, newly diagnosed undergoing chemotherapy; N = 54, multicenter | IRM, patients with ≥1 CDI, patients with ≥1 serious infection, number of CDIs, IRM, adverse events, adverse events leading to treatment discontinuation. number of major infections |
| 15 | Puig et al24 | RCT, 2015-2019 | Prophylactic antibiotics with standard care | Oral antibiotics (clarithromycin 500 mg bd) vs placebo until disease progression or unacceptable toxicity | MM, newly diagnosed, ≥65 y of age undergoing RD chemotherapy; N = 286, multicenter | All-cause mortality, IRM, patients with ≥1 CDI, patients with ≥1 serious infection, adverse events |
| 16 | Stadtmauer et al29 | RCT, 2009-2012 | Vaccination compared with placebo or differing doses | Three doses of 50 mg VZV glycoprotein E (gE) adjuvanted with AS01B vs 3 doses of gE adjuvanated with AS01E vs dose of saline followed by 2 doses of gE/AS01B vs 3 doses of saline at months 0, 1, 3. | CLL, MM, lymphoma, AML, had autologous stem cell transplant; N = 121, multicenter | Patients with ≥1 CDI, adverse events |
| 17 | Stadtmauer et al30 Bastidas et al39 | RCT, 2012-2017 | Vaccination compared with placebo | Adjuvanted recombinant zoster vaccine vs placebo with the first dose given 50-70 d after transplantation and the second dose 1-2 mo thereafter. | Post autologous HSCT; N = 1846, multicenter | All-cause mortality, patients with ≥1 CDI, number of CDIs, adverse events |
| 18 | Teh et al31 | RCT, 2019-2020 | Vaccination, comparing different doses | High-dose (HD) inactivated influenza vaccine followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 wk apart | MM, lymphoma, post autologous stem cell transplant; N = 68, single center | Patients with one or more CDIs, patients with ≥1 MDI, number of CDIs, number of MDIs, adverse events |
| 19 | Vacca et al20 | RCT, not stated | Prophylactic immunoglobulin compared with no treatment | SCIg 0.1 g-0.2 g/kg weekly (Hizentra) vs no treatment | MM, serum IgG level < 5 g/L; N = 46, single center | Number of CDIs, number of serious infections, incidence of hospitalization, adverse events, adverse events requiring treatment discontinuation |
| 20 | Vesole et al25 | RCT, 1998-2008 | Prophylactic antibiotics compared with no treatment | Ciprofloxacin 500 mg twice daily vs trimethoprim sulfamethoxazole (160/800 mg twice daily) vs no treatment for 2 mo | MM, receiving front-line chemotherapy; N = 212, not stated | All-cause mortality, IRM, patients with ≥1 infection, patients with ≥1 serious infection |
| 21 | Winston et al32 | RCT, 2010-2013 | Vaccination compared with placebo | Four doses of inactivated zoster vaccine or placebo, with the first dose 5-60 d before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 d after transplantation | MM, lymphoma, acute leukemia; autologous stem cell transplant; N = 1230, multicenter | Patients with ≥1 CDI, number of CDIs, adverse events, adverse events leading to treatment discontinuation |
| Number . | Study . | Study design, years conducted . | Types of intervention . | Dose and schedule of interventions . | Types and number of participants (n), multicenter or single center . | Outcomes . |
|---|---|---|---|---|---|---|
| 1 | Boughton et al13 | RCT, not stated | Prophylactic immunoglobulin compared with placebo | IVIg 18 g (sandoglobulin) vs placebo (0.6 g albumin) every 3 wk for 12 mo | CLL, serum IgG <5.5 g /L and 2 or more documented infections in the preceding 12 mo; N = 42, multicenter | Patients with ≥1 CDI, patients with ≥1 MDI, number of MDIs, patients with ≥3 infections, patients with ≥3 serious infections, number of CDIs (overall but not by treatment arm), adverse effects, adverse events leading to treatment discontinuation |
| 2 | Chapel et al14 | RCT, not stated | Prophylactic immunoglobulin compared with placebo | IVIg 0.4 g/kg (Gammagard) vs placebo (4% albumin) every 4 wk for 12 mo | MM in stable phase; N = 83, multicenter | All-cause mortality, IRM, patients with ≥1 CDI, number of CDIs, number of MDIs, number of serious infections, time to first major infection, adverse events, adverse events leading to treatment discontinuation |
| 3 | Cooperative CLL16 | RCT, not stated | Prophylactic immunoglobulin compared with placebo | IVIg 0.4 g/kg (Gammagard) vs placebo (0.9% sodium chloride) every 4 wk for 12 mo | CLL, serum IgG level < 50% of lower limit of normal or a history of serious infections; N = 84, multicenter | All-cause mortality, patients with ≥1 infections, patients with ≥3 infections, patients with ≥1 serious infections, patients with ≥1 MDI, number of MDIs, number of CDIs, number of serious infections, adverse events, adverse events leading to treatment discontinuation |
| 4 | Dagnew et al26 | RCT, 2013-2015 | Vaccination compared with placebo | Adjuvanted recombinant zoster vaccine (2 doses) vs placebo 1-2 mo apart | CLL, lymphoma, MM, receiving or had just finished immunosuppressive cancer treatments; N = 562, multicenter | All-cause mortality, patients with ≥1 CDI, patients with ≥1 MDI, number of CDI, number of MDIs, adverse events |
| 5 | Drayson et al21 | RCT, 2012-2016 | Prophylactic antibiotics compared with placebo | Levofloxacin 500 mg daily vs placebo for 12 wk | MM, newly diagnosed with planned antimyeloma treatment; N = 977, multicenter | All-cause mortality, IRM, patients with ≥1 CDI, number of CDIs, number of MDIs, number of hospitalizations, number of ICU admissions, adverse events |
| 6 | Gamm et al15 Chapel et al14 | RCT, not stated | Prophylactic immunoglobulin comparing differing doses | IVIg 0.5 g/kg vs IVIg 0.25 g/kg (Gammagard) every 4 wk for 12 mo | CLL and lymphoma, serum IgG below lower limit of normal or a recent history of serious infections; N = 36, multicenter | All-cause mortality, IRM, patients with ≥1 CDI, number of CDIs, number of MDIs, number of serious infections, adverse events |
| 7 | Gregersen et al22 | RCT, not stated | Prophylactic antibiotics compared with placebo | Clarithromycin 500 mg BD vs placebo for 3 mo | MM, newly diagnosed and receiving VCD induction chemotherapy; N = 58, multicenter | All-cause mortality, patients with ≥1 CDI, patients with ≥1 MDI, patients with ≥1 serious infection, adverse events |
| 8 | Griffiths et al17 | RCT Crossover, 1984-1987 | Prophylactic immunoglobulin compared with placebo | IVIg 0.4 g/kg (Gammagard) vs placebo (saline) every 3 wk for months, then crossover for another 12 mo | CLL, serum IgG level <3.5 g/L or a history of serious infections; N=12, single center | Number of CDIs, adverse events |
| 9 | Hata et al27 | RCT, 1997-2000 | Vaccination compared with placebo | Heat-inactivated, live attenuated varicella vaccine vs placebo given within 30 d before transplantation and 30, 60, and 90 d after transplantation | Lymphoma, autologous stem cell transplant; N = 119, multicenter | All-cause mortality, patients with ≥1 CDI, number of CDIs, adverse events (treatment group only) |
| 10 | McQuilten et al35 | RCT, 2017-2020 | Prophylactic antibiotics compared with prophylactic immunoglobulin | IVIg 0.4 g/kg every 4 wk or SCIg 0.1 g/kg every week vs oral antibiotics (trimethoprim-sulfamethoxazole 160 mg/800 mg daily) for 12 mo | CLL, MM, lymphoma, other hematological malignancy, serum IgG level <4 g/L or a history of serious infections; N = 60, multicenter | Time to first major infection, patients with ≥1 serious infection |
| 11 | Molica et al18 | RCT, crossover, not stated | Prophylactic immunoglobulin compared with no treatment | IVIg 0.3g/kg (Vena-N) every 4 wk vs no treatment for 6 mo, then switched to observation or IVIg for another 12 mo; then IVIG or no therapy for 6 more months. | CLL, serum IgG level <6 g/L or a history of serious infections; N = 42, multicenter | All-cause mortality, IRM, number of CDIs, number of MDIs |
| 12 | Musto et al19 | RCT crossover, not stated | Prophylactic immunoglobulin compared with no treatment | IVIg 0.3 g/kg (Vena-N) every 4 wk vs no treatment for 6 mo, then switched to observation or IVIg for another 12 mo; then IVIG or no therapy for 6 more months | MM, serum IgG below lower limit of normal or a recent history of serious infections; N = 25, not stated | All-cause mortality, IRM, number of CDIs, number of serious infections |
| 13 | Musto and Carotenuto28 | RCT, 1995-1996 | Vaccination compared with no treatment | Influenza vaccine (trivalent subvirion containing antigens from the component strains A/Singapore/6/86, A/Johannesburg/33/94 and B/Bijing/184/93) vs no treatment | MM undergoing chemotherapy; N = 50, not stated | IRM, patients with ≥1 CDI, number of hospitalizations, adverse events (treatment group only), adverse events leading to treatment discontinuation (treatment group only) |
| 14 | Oken et al23 1996 | RCT, not stated | Prophylactic antibiotics compared with no treatment | Oral antibiotics (trimethoprim-sulfamethoxazole 160mg/800mg bd) vs no treatment for 2 mo | MM, newly diagnosed undergoing chemotherapy; N = 54, multicenter | IRM, patients with ≥1 CDI, patients with ≥1 serious infection, number of CDIs, IRM, adverse events, adverse events leading to treatment discontinuation. number of major infections |
| 15 | Puig et al24 | RCT, 2015-2019 | Prophylactic antibiotics with standard care | Oral antibiotics (clarithromycin 500 mg bd) vs placebo until disease progression or unacceptable toxicity | MM, newly diagnosed, ≥65 y of age undergoing RD chemotherapy; N = 286, multicenter | All-cause mortality, IRM, patients with ≥1 CDI, patients with ≥1 serious infection, adverse events |
| 16 | Stadtmauer et al29 | RCT, 2009-2012 | Vaccination compared with placebo or differing doses | Three doses of 50 mg VZV glycoprotein E (gE) adjuvanted with AS01B vs 3 doses of gE adjuvanated with AS01E vs dose of saline followed by 2 doses of gE/AS01B vs 3 doses of saline at months 0, 1, 3. | CLL, MM, lymphoma, AML, had autologous stem cell transplant; N = 121, multicenter | Patients with ≥1 CDI, adverse events |
| 17 | Stadtmauer et al30 Bastidas et al39 | RCT, 2012-2017 | Vaccination compared with placebo | Adjuvanted recombinant zoster vaccine vs placebo with the first dose given 50-70 d after transplantation and the second dose 1-2 mo thereafter. | Post autologous HSCT; N = 1846, multicenter | All-cause mortality, patients with ≥1 CDI, number of CDIs, adverse events |
| 18 | Teh et al31 | RCT, 2019-2020 | Vaccination, comparing different doses | High-dose (HD) inactivated influenza vaccine followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 wk apart | MM, lymphoma, post autologous stem cell transplant; N = 68, single center | Patients with one or more CDIs, patients with ≥1 MDI, number of CDIs, number of MDIs, adverse events |
| 19 | Vacca et al20 | RCT, not stated | Prophylactic immunoglobulin compared with no treatment | SCIg 0.1 g-0.2 g/kg weekly (Hizentra) vs no treatment | MM, serum IgG level < 5 g/L; N = 46, single center | Number of CDIs, number of serious infections, incidence of hospitalization, adverse events, adverse events requiring treatment discontinuation |
| 20 | Vesole et al25 | RCT, 1998-2008 | Prophylactic antibiotics compared with no treatment | Ciprofloxacin 500 mg twice daily vs trimethoprim sulfamethoxazole (160/800 mg twice daily) vs no treatment for 2 mo | MM, receiving front-line chemotherapy; N = 212, not stated | All-cause mortality, IRM, patients with ≥1 infection, patients with ≥1 serious infection |
| 21 | Winston et al32 | RCT, 2010-2013 | Vaccination compared with placebo | Four doses of inactivated zoster vaccine or placebo, with the first dose 5-60 d before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 d after transplantation | MM, lymphoma, acute leukemia; autologous stem cell transplant; N = 1230, multicenter | Patients with ≥1 CDI, number of CDIs, adverse events, adverse events leading to treatment discontinuation |
HSCT, hematopoietic stem cell transplantation; ICU, intensive care unit; IRM, infection-related mortality; Rd, lenalidomide and dexamethasone.