Table 1.

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

HSCT, hematopoietic stem cell transplantation; ICU, intensive care unit; IRM, infection-related mortality; Rd, lenalidomide and dexamethasone.