leukemoid reaction
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Leukemoid Reaction
Definition
A leukemoid reaction is an excessive leukocytic response in the peripheral blood that mimics leukemia but is reactive (non-neoplastic) in origin. It is defined as a WBC count >50,000/μL (50 × 10⁹/L) with a pronounced left shift - the appearance of immature granulocytes (bands, metamyelocytes, myelocytes) in the circulation.
The peripheral blood smear can be virtually indistinguishable from chronic myelogenous leukemia (CML) on morphology alone - distinction depends on specific lab and molecular testing.
Peripheral Blood Smear
Peripheral blood from a patient with leukemoid reaction. From this smear, it would be impossible to distinguish a leukemoid reaction from chronic phase CML. Distinction depends on the presence or absence of BCR-ABL fusion. (Goldman-Cecil Medicine)
Types
Depending on the predominant cell type:
| Type | Description |
|---|---|
| Neutrophilic | Most common type; reactive neutrophils with left shift, toxic granulation, Döhle bodies, cytoplasmic vacuoles |
| Eosinophilic | Mainly in children; frequently caused by parasitic infection |
| Lymphocytic | Very high counts of normal lymphocytes (e.g., pertussis, infectious lymphocytosis) |
| Monocytic | Less common |
Causes
Neutrophilic leukemoid reactions occur in:
- Severe bacterial infections (e.g., Clostridioides difficile, tuberculosis - WBC can exceed 30,000/μL in ~1/4 of patients, reaching leukemoid threshold)
- Bacterial toxin-mediated infections (e.g., diphtheria)
- Malignancy with bone marrow involvement (e.g., Hodgkin lymphoma, metastatic carcinoma)
- Hemolysis and hemorrhage
- Myelofibrosis
- Severe burns
- Eclampsia
- Rebound granulocytosis
Lymphocytic leukemoid reactions: infectious lymphocytosis, pertussis, infectious mononucleosis (though with atypical cells, distinguishing from leukemia can be difficult)
Morphological Features (Granulocytic Type)
- Left shift: bands, metamyelocytes, myelocytes in peripheral blood
- Toxic granulation - prominent dark cytoplasmic granules
- Döhle bodies - pale blue cytoplasmic inclusions
- Cytoplasmic vacuoles
- These changes indicate a reactive, stressed marrow, not clonal proliferation
Leukoerythroblastosis
When circulating normoblasts (nucleated RBCs) accompany a neutrophilic leukemoid reaction, the term leukoerythroblastic reaction applies. This pattern is seen in:
- Metastatic carcinoma involving the bone marrow
- Marrow fibrosis or infection
- Benign conditions: GI bleeding, hemolytic anemia
Distinguishing Leukemoid Reaction from CML
This is the most clinically important distinction. CML can present identically on the smear.
| Feature | Leukemoid Reaction | CML |
|---|---|---|
| WBC pattern | Left shift, predominantly neutrophils/bands | "Panmyelosis" - all stages of neutrophil series; myelocyte "peak" (more myelocytes than metamyelocytes) |
| Basophilia | Absent | Present (independent adverse prognostic factor) |
| Eosinophilia | Absent | Present |
| Neutrophil Alkaline Phosphatase (NAP/LAP score) | Normal or elevated | Decreased (classic finding) |
| Thrombocytosis + anemia | Usually absent | Often present |
| Splenomegaly | Absent | Common |
| BCR-ABL (Philadelphia chromosome) | Absent | Present (definitive test) |
| Cause | Reactive - identifiable trigger | Clonal neoplasm |
Key mnemonic: In a leukemoid reaction, NAP/LAP score is high (the marrow is working hard reactively). In CML, the leukocytes are clonal and relatively lazy - NAP/LAP is low.
Distinguishing from Chronic Neutrophilic Leukemia (CNL)
CNL is rare: WBC ≥25,000/μL with >80% being segmented neutrophils/bands, <10% immature granulocytes, and hepatosplenomegaly. At least 50% harbor CSF3R mutations. Absence of BCR-ABL is shared with leukemoid reaction, but CSF3R testing and clinical context differentiate them.
Diagnostic Workup
- CBC with peripheral smear - assess morphology, presence of toxic changes
- NAP/LAP score - elevated in leukemoid reaction, low in CML
- BCR-ABL by PCR or FISH - the definitive test; if negative, rules out CML
- Acute phase reactants (CRP, procalcitonin) - elevated in reactive leukocytosis; CRP is an early, sensitive marker
- Bone marrow biopsy - rarely needed for leukemoid reaction alone, but indicated if leukocytosis is unexplained or leukoerythroblastic reaction suggests marrow infiltration; should include cultures for TB/fungi, cytogenetics, flow cytometry
Sources:
- Henry's Clinical Diagnosis and Management by Laboratory Methods, pp. 132, 734
- Goldman-Cecil Medicine, pp. 1763-1764
- Harrison's Principles of Internal Medicine 22E, p. 656
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