Abstract Background: Extreme leukocytosis (EL), defined as an abnormally high white blood cell (WBC) count, is a critical clinical indicator associated with various underlying conditions, such as infections and malignancies. This study investigated the etiological factors and clinical profiles of patients presenting with EL at Mbeya Zonal Referral Hospital (MZRH). Methods: A retrospective cohort study was conducted among patients with WBC counts of 50*10^9/L and above who attended MZRH between January 2021 and December 2022. Data were retrieved from electronic health records and analyzed using Stata Version 16. Results: A total of 178 patients with EL were included in the study. Malignant conditions accounted for 47.2% of cases, with haematological malignancies comprising 89.3%, predominantly chronic myeloid leukaemia (CML). Infections were the second most frequent cause (43.2%). Patients with malignancies had significantly higher median WBC counts (221 vs. 56*10^9/L, p<0.0001) and were more likely to present with symptoms such as bleeding, bone pain, B symptoms, splenomegaly, hepatomegaly, and lymphadenopathy. Severe thrombocytopenia (platelet count <50*10^9/L) was more common in the malignant group (p=0.0008). Conclusion: Malignant etiologies, particularly haematological malignancies, are a leading cause of EL in patients with WBC counts of 50*10^9/L and above. Clinicians should maintain a high suspicion of malignancies in such patients and conduct thorough diagnostic evaluations to ensure optimal management. Keywords Extreme leukocytosis, haematological malignancies, leukemoid reaction, severe leukocytosis, hyperleukocytosis

The authors have declared no competing interest.

This study did not receive any funding

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Mbeya Medical Research Ethics Committee of Mbeya Zonal Referral Hospital gave ethical approval for this work (Ref No: SZEC-2439/R.A/24/01)

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All data produced in the present study are available upon reasonable request to the authors.