Impact of treatment-induced thrombosis on the prognosis of acute lymphoblastic leukaemia : a protocol for a systematic review and meta-analysis

Abstract

INTRODUCTION : Therapy-associated thrombosis remains a challenge in the management of patients with acute lymphoblastic leukaemia (ALL). Thrombosis associated with asparaginase-containing chemotherapy complicates patient management strategies, prompting the need for effective prophylaxis. Assessing the relationship between chemotherapy-induced thrombosis and patient outcomes is crucial for optimising ALL management strategies. The aim of this systematic review is to provide a synthesis on whether the development of thrombosis during asparaginase-containing chemotherapy regimens impacts the overall and event-free survival of patients with ALL. METHODS AND ANALYSIS : Data sources: to identify relevant studies, a comprehensive search will be conducted on the major electronic databases, including MEDLINE (PubMed), Web of Science (Clarivate), Academic Search Complete (EBSCOhost), clinicaltrial.gov and the Cochrane Central Register of Controlled Trials from inception to 30 January 2026. INCLUSION CRITERIA FOR SELECTING STUDIES : randomised and non-randomised clinical studies evaluating the impact of asparaginase-containing chemotherapy-associated thrombosis on survival outcomes in patients with ALL will be included. Two reviewers will independently screen the retrieved studies, extract data and assess study quality using a predefined criteria. A narrative synthesis will be undertaken, and if feasible, meta-analyses will be conducted. A subgroup and sensitivity analysis will be performed to explain the sources of heterogeneity. The quality of cumulative evidence will be assessed using the grading of recommendations assessment, development and evaluation tool. The findings from this systematic review will inform evidence-based clinical guidelines for thrombosis risk assessment and management in patients with ALL, potentially improving treatment outcomes and reducing thrombosis-related morbidity.

STRENGTHS AND LIMITATIONS OF THIS STUDY • The review will be conducted according to a predefined protocol with systematic searching, dual independent screening, data extraction and risk-of-bias assessment. • Both narrative synthesis and meta-analysis will be undertaken where appropriate, with statistical heterogeneity assessed and explored using predefined subgroup and sensitivity analyses. • Randomised controlled trials and non-randomised cohort studies involving participants across all age groups will be included. • Mortality outcomes will be synthesised using reported overall survival and event-free survival at comparable follow-up time points. • Variability in thrombosis definitions, diagnostic criteria and outcome reporting across studies may limit study comparability and the precision of pooled estimates.