Can hyperleukocytosis be caused by a non-hematologic condition? A 10-year retrospective tertiary-care center cohort study

Background Hyperleukocytosis (HL) is defined as a white blood cell counts typically exceeding 100 G/L and is commonly associated with hematologic malignancies. Efforts to identify and characterize non-hematologic causes of HL have been limited and insufficiently addressed in the literature.Methods We conducted a retrospective analysis of adult patient records from 2013 to 2023, screened for cases of HL with a primary focus on the characterization of non-hematologic causes.Results Out of 878,967 adult patients, 375 patients had HL; 90 were excluded due to opting out of general consent, leaving 285 (median age 66.8 years; 32% female) for analysis. Of these, 276 (97%) had an underlying hematologic malignancy, most frequently chronic lymphocytic leukemia (35.4%), followed by other B-cell lymphomas, acute myeloid leukemia, and chronic myeloid leukemia. Non-hematologic causes accounted for the remaining 3% (n = 9), all associated with advanced solid tumors and predominantly paraneoplastic in nature. Isolated infection-related HL was not observed in this cohort.Conclusions The presence of HL should immediately raise the possibility of a hematologic disease, though a small subset stems from non-hematologic causes. Consequently, HL should prompt immediate peripheral blood smear review and early hematology consultation. Isolated infection-related HL was not observed in this cohort and should be interpreted as a cohort-specific observation.