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Acquired hypogammaglobulinemia is common in chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). No previous systematic reviews (SR) have compared different approaches to infection prevention. We aimed to assess the efficacy and safety of prophylactic immunoglobulin (Ig), antibiotics and vaccinations in these patients. We performed a SR and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of prophylactic Ig, antibiotics and vaccinations in adult patients with hematological malignancies commonly associated with acquired hypogammaglobulinemia, specifically CLL, NHL and MM. We searched Pubmed (MEDLINE), EMBASE and Cochrane Registry to 01/09/2021. Results for dichotomous data were expressed as relative risks (RR) with 95% confidence intervals (CI) and pooled using a random effects model. This review was registered with PROSPERO CRD42017070825. From 10,576 studies screened, there were 21 completed and one ongoing RCT. Of these, eight evaluated prophylactic Ig (n=370, seven published before 2000); five evaluated prophylactic antibiotics (n=1587), seven evaluated vaccinations (n=3996) and one compared Ig to antibiotics (n=60). Prophylactic Ig reduced the risk of clinically documented infections (CDIs) by 28%, (n=2 trials; RR 0.72 [95% CI 0.54-0.96]) and vaccinations reduced risk of CDIs by 63%, RR 0.37 (95% CI 0.30-0.45). Prophylactic antibiotics did not reduce the risk of CDIs. No interventions reduced all-cause mortality. Prophylactic Ig and antibiotics increased risk of adverse events. Findings should be interpreted with caution given high risk of bias in many studies. There is a clear need for high-quality contemporary trials to establish the effectiveness of different approaches to prevent infections.

Original publication




Journal article


Blood advances

Publication Date



Monash University, Melbourne, Australia.