Management of Leukemoid Reaction
The primary management of leukemoid reaction is to identify and treat the underlying cause, as the leukocytosis itself is a reactive phenomenon rather than a primary hematologic malignancy requiring chemotherapy. 1, 2
Diagnostic Approach
The initial critical step is distinguishing leukemoid reaction from chronic myelogenous leukemia (CML) and chronic neutrophilic leukemia (CNL), as these require fundamentally different treatment approaches. 1
Key Diagnostic Features:
- Leukemoid reaction is defined as persistent neutrophilic leukocytosis above 50,000 cells/μL when the cause is other than leukemia 1, 2
- Peripheral blood smear shows predominantly mature neutrophils with left shift 3
- Absence of BCR-ABL fusion (Philadelphia chromosome) excludes CML 1
- Bone marrow examination may be necessary to exclude primary hematologic malignancy 1
Treatment Strategy
Primary Management: Treat the Underlying Cause
The most common etiologies requiring specific intervention include: 1, 2
Severe Infections (most common cause - 56% of cases):
- Clostridium difficile colitis
- Tuberculosis
- Severe bacterial sepsis
- COVID-19 infection 3
- Appropriate antimicrobial therapy targeting the specific pathogen is the definitive treatment 2
Malignancies (second most common - 16% of cases):
- Paraneoplastic leukemoid reaction from solid tumors 2
- Treatment of the underlying malignancy is required 1
Other causes:
- Severe hemorrhage
- Acute hemolysis
- Drug intoxications 1
Cytoreductive Therapy: When Indicated
Hydroxyurea is the recommended cytoreductive agent when symptomatic leukocytosis requires urgent reduction, similar to management principles for hyperleukocytosis in acute leukemia. 4
- Dosing: 50-60 mg/kg per day until WBC decreases to 10-20 × 10⁹/L 4
- Indication: Reserve for patients with symptoms of leukostasis (pulmonary infiltrates, neurologic symptoms, or hemorrhagic complications) 4
Critical Management Considerations
Avoid excessive red blood cell transfusions until WBC is reduced, as this increases blood viscosity and risk of leukostasis complications. 4
Monitor for tumor lysis syndrome if cytoreductive therapy is initiated:
- Aggressive hydration
- Allopurinol or rasburicase for uric acid control
- Monitor urine pH and electrolytes 4
Prognostic Implications
Leukemoid reaction carries a poor prognosis with high mortality, particularly when associated with: 2
- Severe infection or sepsis
- Paraneoplastic syndrome from advanced malignancy
- Lower hemoglobin levels
- Advanced age
- Higher segmented neutrophil counts 2
The mortality reflects the severity of the underlying condition rather than the leukocytosis itself, reinforcing that treatment must focus on the primary disease process. 2
Common Pitfalls to Avoid
- Do not initiate chemotherapy for leukemoid reaction—this is a reactive process, not leukemia 1
- Do not delay treatment of the underlying infection or malignancy while pursuing extensive hematologic workup 2
- Leukapheresis has no proven impact on long-term outcomes in leukemoid reaction and should not be routinely employed 4
- Corticosteroids may paradoxically worsen monocytic leukemoid reactions in patients with underlying myelodysplastic syndrome 5