Leukemoid Reaction: Findings and Management
A leukemoid reaction is characterized by an extreme elevation in white blood cell count exceeding 50,000 cells/μL, predominantly with mature neutrophils and immature granulocytic forms, that is not caused by leukemia. 1
Diagnostic Findings
Definition and Laboratory Features
- Leukocytosis >50,000 cells/μL with predominance of mature neutrophils and presence of immature granulocytic forms (left shift) in peripheral blood 1
- May include toxic granulations and bandemia in severe cases 2
- Must be distinguished from chronic myeloid leukemia (CML) and other hematologic malignancies 1
Diagnostic Workup
- Complete blood count with differential to document degree of leukocytosis 3
- Peripheral blood smear examination to assess for immature forms and exclude leukemic blasts 3
- Bone marrow aspirate/biopsy may be required in unclear cases to rule out leukemia 3
- Cytogenetic analysis to exclude Philadelphia chromosome (t(9;22)) which would indicate CML 3
- RT-PCR to rule out BCR-ABL transcripts found in CML 3
Common Etiologies
- Infections (59% of non-hematologic cases) - bacterial, viral, or fungal 4
- Malignancies (non-hematologic) - solid tumors causing paraneoplastic reaction 5
- Severe hemorrhage or acute hemolysis 1
- Metabolic disorders such as severe diabetic ketoacidosis 6
- Severe inflammatory conditions 4
Management Approach
Initial Management
- Aggressive hydration is the first-line intervention with intravenous fluids at 2.5-3 liters/m²/day, particularly in patients with hyperleukocytosis. 7
- Identify and treat the underlying cause (infection, malignancy, etc.) 4
- Rehydration alone may normalize white blood cell counts in dehydration-induced cases 7
Management of Hyperleukocytosis
- For WBC counts >100,000/μL with symptoms of leukostasis, immediate medical treatment is required 3
- Consider hydroxyurea at dosages up to 50-60 mg/kg per day until WBC decreases to <10-20 × 10⁹/L 3
- Leukapheresis may be considered for initial management of severe hyperleukocytosis, though its impact on long-term outcomes is not established 3
Prevention of Complications
- Monitor for and prevent tumor lysis syndrome in cases of malignancy-associated leukemoid reaction 3
- Ensure adequate hydration, control uric acid production using allopurinol or rasburicase, and monitor urine pH 3
- Avoid excessive red blood cell transfusions until WBC has been reduced, as this can increase blood viscosity 3
Supportive Care
- Transfusion support may be required, with maintenance of hemoglobin above 8 g/dL 3
- Provide platelet transfusions if count falls below 10 × 10⁹/L or if there is active bleeding 3
- Monitor for signs of organ dysfunction related to hyperleukocytosis 3
Prognosis
- Prognosis is primarily determined by the underlying cause 4
- Infection-related and paraneoplastic leukemoid reactions are associated with high mortality 4
- Lower hemoglobin, older age, and increased segmented neutrophil count are associated with increased risk of death 4
- WBC count typically normalizes after successful treatment of the underlying condition 6
Special Considerations
- In pregnant patients with leukemoid reaction, management should be coordinated between hematologists, obstetricians, and neonatologists 3
- Distinguish from leukemia-related leukocytosis, which requires different management approaches 3
- Serial monitoring of WBC counts is essential to assess response to treatment of underlying cause 3