Immune-related adverse events associated with the use of immunotherapy in patients with B-cell lymphoblastic leukemia: A protocol for a systematic review and meta-analysis

Background: B-cell acute lymphoblastic leukemia (B-ALL) is a neoplasm of immature B-cells that is more prevalent in children. Despite successful remission rates in patients with B-ALL on chemotherapy, the risk of relapse is high. This has paved way for highly active immune and cell therapies to be intensively explored. However, the efficacy and immune-related adverse events (AE) associated with the use of immunotherapies remain elusive.Methods: This protocol has been prepared in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines. Cochrane Central Register of Controlled Trials, MEDLINE, and Embase electronic databases will be searched to retrieve relevant interventional studies. Two reviewers (BKK and EH) will autonomously search and identify relevant studies using a preset inclusion and exclusion criteria. A predefined data extraction sheet will be used to extract relevant data items. The risk of bias will be assessed by 2 reviewers (BKK and BBN) using the Cochrane risk-of-bias tool for randomized controlled trials and the Downs and Black Checklist for nonrandomized controlled trials. A third reviewer (TMN) will be consulted for any discrepancies. The Grading of Recommendations Assessment Development and Evaluation will be used to assess the strengths of evidence by 2 reviewers (BBK and TMN). The I-2 and Chi-squared statistical tests will be used to investigate statistical heterogeneity across studies. An I-2 value of > 50% will be considered substantial heterogeneity and a random-effects model will be used. Data analysis will be performed using Review Manager (RevMan V.5.3) statistical software.