Clinical Manifestations of Hyperleukocytosis in Children with Acute Leukemia: A Systematic Review and Meta-Analysis

Hyperleukocytosis is a life-threatening oncologic emergency in children with acute leukemia. Leukocyte counts exceeding 100,000/μL may cause increased blood viscosity, leukocyte aggregation, and microvascular obstruction, leading to leukostasis and organ dysfunction. Early recognition of clinical manifestations is essential for timely management. This study aimed to identify the clinical signs and symptoms of hyperleukocytosis in children with acute leukemia. To our knowledge, this is the first meta-analysis on this topic. This systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in PROSPERO with registration number CRD420261307629. Published studies up to January 2026 were retrieved from PubMed Central, SpringerLink, ScienceDirect, and Google Scholar. Eligible studies included observational studies involving pediatric patients with acute leukemia and hyperleukocytosis that reported data on clinical manifestations. A systematic search was conducted using Medical Subject Headings terms combining “hyperleukocytosis,” “acute leukemia,” and “pediatric.” Quantitative data were analyzed using proportional meta-analysis with MedCalc version 22.023. Qualitative assessment of risk of bias (RoB) was performed using the Newcastle–Ottawa Scale. Seven cohort studies were included in this review. Among 3,178 pediatric patients with acute leukemia, 445 (14%) experienced hyperleukocytosis. The identified clinical manifestations were hepatomegaly (68.69%, 95% confidence interval [CI] 4.196–97.474), fever (62.95%, 95% CI 20.339–95.820), splenomegaly (46.41%, 95% CI 0.517–99.997), central nervous system involvement (39.37%, 95% CI 8.706–75.853), respiratory distress (30.65%, 95% CI 7.855–60.312), bleeding (21.62%, 95% CI 1.795–54.733), lymphadenopathy (19.51%, 95% CI 4.85–40.812), renal dysfunction (13.83%, 95% CI 5.939–24.335), and mediastinal mass (10.41%, 95% CI 2.748–22.192). The most common clinical manifestations of hyperleukocytosis in children with acute leukemia were hepatomegaly, fever, and splenomegaly. These findings should be interpreted considering the limited number and retrospective design of included studies.