Simple SummaryHyperleukocytosis (WBC > 100 × 109/L) has been associated with unfavorable outcomes. Few studies have focused on childhood acute leukemia with hyperleukocytosis in developing countries, where the treatment outcomes remain poorer than in developed countries. Our study reviewed the medical records of 690 children who were diagnosed with acute leukemia between January 1998 and December 2017. The incidence of hyperleukocytosis was 16.6% in acute lymphoblastic leukemia (ALL) patients and 20.3% in acute myeloid leukemia (AML) patients. Hyperleukocytosis, extreme hyperleukocytosis (WBC > 200 × 109/L), age less than 1 year, age greater than 10 years, and male sex were independently associated with overall survival in the ALL group, while extreme hyperleukocytosis and age less than 1 year were independently associated with overall survival in the AML group. We believe that to improve survival outcomes for children with hyperleukocytosis, the recommended treatment regimen must be modified, while early treatment-related complications, which are more likely to develop, should raise concerns.AbstractHyperleukocytosis and extreme hyperleukocytosis, defined as initial white blood cell counts greater than 100 × 109/L and 200 × 109/L, respectively, have been associated with unfavorable outcomes. This study aimed to determine the early complications and survival outcomes of childhood leukemia patients with hyperleukocytosis. The medical records of 690 children newly diagnosed with acute leukemia between January 1998 and December 2017 were retrospectively reviewed. The Kaplan–Meier method and log-rank test were used to assess and compare the survival outcomes. Multivariate Cox proportional hazards regression was used to determine associated risk factors for overall survival. We found that 16.6% of 483 childhood acute lymphoblastic leukemia (ALL) patients and 20.3% of 207 childhood acute myeloid leukemia (AML) patients had hyperleukocytosis at diagnosis. ALL patients with hyperleukocytosis had more early complications than those without hyperleukocytosis (p< 0.05). Among the ALL group, the 5-year overall survival rate for those with hyperleukocytosis was significantly lower than for those without hyperleukocytosis (37.2% vs. 67.8%,p< 0.0001), while the difference was not statistically significant in the AML group (19.0% vs. 30.2%, respectively,p= 0.26). Hyperleukocytosis (hazard ratio [HR]: 2.04), extreme hyperleukocytosis (HR: 2.71), age less than 1 year (HR: 3.05), age greater than 10 years (HR: 1.64), and male sex (HR: 1.37) were independently associated with poorer overall survival in childhood ALL patients. Extreme hyperleukocytosis (HR: 2.63) and age less than 1 year (HR: 1.82) were independently associated with poorer overall survival in AML patients. Hyperleukocytosis was associated with adverse survival outcomes in childhood leukemia.