Kalamara TV, Dodos K, Georgakopoulou VE. Immunoglobulin replacement therapy and infection risk in chronic lymphocytic leukemia: A systematic review and meta-analysis. World J Clin Cases 2026; 14(9): 118210 [DOI: 10.12998/wjcc.v14.i9.118210]
Corresponding Author of This Article
Vasiliki E Georgakopoulou, MD, Department of Pathophysiology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, 17 Agiou Toma Street, Athens 11527, Greece. vaso_georgakopoulou@hotmail.com
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
Meta-Analysis
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World J Clin Cases. Mar 26, 2026; 14(9): 118210 Published online Mar 26, 2026. doi: 10.12998/wjcc.v14.i9.118210
Immunoglobulin replacement therapy and infection risk in chronic lymphocytic leukemia: A systematic review and meta-analysis
Tsampika-Vasileia Kalamara, Konstantinos Dodos, Vasiliki E Georgakopoulou
Tsampika-Vasileia Kalamara, Konstantinos Dodos, Laboratory of Physiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Kentrikí Makedonía, Greece
Vasiliki E Georgakopoulou, Department of Pathophysiology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens 11527, Greece
Author contributions: Kalamara TV conducted the statistical analysis and drafted the manuscript; Kalamara TV and Dodos K conceived and designed the study, performed the literature search, study selection, data extraction, and risk-of-bias assessment; Dodos K contributed to data interpretation and critical revision of the manuscript for important intellectual content; Georgakopoulou VE supervised the study, resolved methodological disagreements, and critically revised the manuscript. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Vasiliki E Georgakopoulou, MD, Department of Pathophysiology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, 17 Agiou Toma Street, Athens 11527, Greece. vaso_georgakopoulou@hotmail.com
Received: December 28, 2025 Revised: February 1, 2026 Accepted: March 5, 2026 Published online: March 26, 2026 Processing time: 87 Days and 21 Hours
Abstract
BACKGROUND
Chronic lymphocytic leukemia (CLL) is characterized by progressive humoral immune dysfunction, particularly hypogammaglobulinemia, leading to increased infection risk. While immunoglobulin replacement therapy (IgRT) is commonly used for infection prevention, its efficacy remains debated due to conflicting evidence.
AIM
To evaluate the association between IgRT and infection outcomes in patients with CLL by synthesizing evidence from randomized controlled trials (RCTs) and observational studies, using complementary dichotomous and rate-based meta-analytic approaches.
METHODS
We conducted a systematic review and meta-analysis (International Prospective Register of Systematic Reviews-registered, Preferred Reporting Items for Systematic Reviews and Meta-analyses-compliant) of RCTs and observational studies comparing IgRT vs no IgRT in CLL patients assessing the outcome of infections. Dual analytical approaches were employed: Dichotomous analysis [risk ratios (RRs) for ≥ 1 infection] and rate-based analysis (rate ratios for infections/patient-year). Risk of bias was assessed using Cochrane risk of bias 2 and risk of bias in nonrandomized studies of interventions version I tools.
RESULTS
Nine studies were included in our meta-analysis. The dichotomous analysis (5 studies) showed a 40% reduction in infection risk with IgRT (RR = 0.60, 95% confidence interval: 0.41-0.88, P = 0.008; I2 = 57.2%). Conversely, rate-based analysis (5 studies) revealed a 65% increase in recurrent infections (rate ratio: 1.65, 95% confidence interval: 1.33-2.04, P < 0.001; I2 = 88.6%). Subgroup analyses demonstrated consistent effects across intravenous immunoglobulin (RR = 0.61) and subcutaneous immunoglobulin (RR = 0.52) formulations. Observational studies showed stronger protective effects than RCTs, though both designs had limitations: RCTs were underpowered, while observational studies had residual confounding.
CONCLUSION
IgRT reduces initial infections in CLL patients but may not prevent recurrences and could paradoxically increase infection rates in some settings. These findings support selective use in high-risk patients (such as patients with severe hypogammaglobulinemia) while highlighting the need for standardized outcome reporting and studies evaluating IgRT alongside modern therapies (e.g., Bruton’s tyrosine kinase inhibitors).
Core Tip: Immunoglobulin replacement therapy (IgRT) is widely used to prevent infections in patients with chronic lymphocytic leukemia, yet its clinical benefit remains controversial. By applying a dual analytical approach that distinguishes between first infection risk and recurrent infection burden, this meta-analysis demonstrates that IgRT reduces the likelihood of experiencing at least one infection but does not prevent, and may even increase, recurrent infection rates. These findings support a selective, risk-stratified use of IgRT in chronic lymphocytic leukemia rather than routine administration and highlight the need for standardized infection reporting and contemporary trials alongside modern targeted therapies.
