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Leukemoid Reaction

Leukemoid Reaction is a marked reactive leukocytosis, usually with a white blood cell count above 50 × 10⁹/L, caused by severe infection, inflammation, malignancy, or other stressors. It is a reactive process, not leukemia, and usually resolves when the underlying cause is treated

Also called

Reactive Leukocytosis

ICD-10

D72.8

Specialty

Hematology

Onset

Acute

Reviewed

August 2026

On This Page

Overview

Leukemoid Reaction is an exaggerated increase in white blood cells, mainly mature neutrophils, in response to conditions such as severe infection, inflammation, tissue injury, or malignancy. It can resemble Chronic Myeloid Leukemia (CML), but it is reactive and usually resolves after treatment of the underlying condition.

Etiology & Risk Factors

Leukemoid Reaction occurs because severe infection, inflammation, tissue injury, or malignancy stimulates increased production and release of neutrophils from the bone marrow.

-Common Causes

Severe Infections

  • Sepsis
  • Pneumonia
  • Clostridioides difficile infection
  • Tuberculosis

Inflammatory Conditions

  • Severe pancreatitis
  • Vasculitis
  • Severe inflammatory disorders

Tissue Injury

  • Major trauma
  • Burns
  • Surgery
  • Myocardial infarction

Malignancy

  • Solid tumors
  • Cytokine-producing tumors

Other Causes

  • Severe hemorrhage
  • Hemolysis
  • Corticosteroid therapy
  • G-CSF therapy

Pathophysiology

Severe infection, inflammation, malignancy, or physiological stress → increased cytokine production, particularly G-CSF and GM-CSF → increased granulopoiesis and accelerated release of neutrophils from the bone marrow → marked neutrophilic leukocytosis with a left shift → resolution after treatment of the underlying cause.

Clinical Presentation

Symptoms

Symptoms usually result from the underlying condition:

  • Fever

  • Chills

  • Fatigue

  • Cough

  • Dyspnea

  • Abdominal pain

  • Dysuria

  • Weight loss

Signs

  • Fever

  • Tachycardia

  • Signs of infection

  • Localized inflammation

  • Features of the underlying disease

Splenomegaly is usually absent or mild.

History Taking

-Ask about:

  • Fever
  • Recent infection
  • Trauma
  • Surgery
  • Medication use
  • Corticosteroid use
  • G-CSF therapy
  • Weight loss
  • Night sweats
  • Smoking
  • Known malignancy
  • Constitutional symptoms

Physical Examination

-General Examination

Look for:

  • Fever

  • Tachycardia

  • Signs of sepsis

  • Dehydration

-Systemic Examination

Assess for:

  • Source of infection

  • Inflammatory focus

  • Splenomegaly

  • Signs of malignancy

  • Tissue injury

Investigations

-Complete Blood Count

Typical findings:

  • WBC often >50 × 10⁹/L

  • Predominant neutrophilia

  • Left shift

  • Variable anemia and thrombocytopenia

-Peripheral Blood Film

May show:

  • Mature neutrophils

  • Band forms

  • Metamyelocytes

  • Myelocytes

  • Toxic granulation

  • Döhle bodies

  • Cytoplasmic vacuoles

Leukocyte Alkaline Phosphatase Score

  • High in Leukemoid Reaction

  • Low in Chronic Myeloid Leukemia

Molecular Testing

BCR-ABL1 testing:

  • Negative in Leukemoid Reaction

  • Positive in Chronic Myeloid Leukemia

-Additional Investigations

To identify the underlying cause:

  • CRP

  • ESR

  • Blood cultures

  • Urine culture

  • Chest X-ray

  • CT scan when indicated

  • Liver and renal function tests

Diagnosis

Diagnosis is based on:

  • Marked reactive leukocytosis
  • Predominant neutrophilia
  • Left shift
  • Evidence of an underlying cause
  • Peripheral blood film findings
  • Exclusion of leukemia when necessary
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Management

-Main Treatment

Treat the underlying cause.

Examples:

  • Appropriate antibiotics for infection

  • Treatment of inflammatory disease

  • Management of malignancy

  • Correction of hemorrhage

  • Treatment of tissue injury

-Supportive Care

  • IV fluids when required

  • Monitoring of CBC

  • Treatment of sepsis

  • Correction of electrolyte abnormalities

Complications

  • Sepsis
  • Multi-organ failure
  • Severe inflammation
  • Tissue injury
  • Misdiagnosis as leukemia

Prognosis

The prognosis depends mainly on the underlying cause. Leukemoid Reaction itself is generally reversible and resolves when the precipitating condition is successfully treated.

Key Points / Clinical Pearls

  • Leukemoid Reaction is a reactive leukocytosis, not leukemia.
  • WBC count is often >50 × 10⁹/L.
  • Neutrophilia with a left shift is typical.
  • Peripheral blood may show toxic granulation and Döhle bodies.
  • Leukocyte alkaline phosphatase is usually high.
  • BCR-ABL1 is negative.
  • Severe infection is an important cause.
  • Treatment focuses on the underlying condition.
  • It usually resolves after successful treatment.
  • The major differential diagnosis is Chronic Myeloid Leukemia.
  •  
  • National Center for Biotechnology Information (NIH). Leukocytosis, StatPearls.
  • Sakka V, Tsiodras S, Giamarellos-Bourboulis EJ, Giamarellou H. An Update on the Etiology and Diagnostic Evaluation of a Leukemoid Reaction. Eur J Intern Med. 2006;17:394-398. PMID: 16962944.
  • National Center for Biotechnology Information (NIH). Chronic Myelogenous Leukemia, StatPearls.
  • Mishra AK, Mehra K, Manikandan R, Dorairajan LN. Leukemoid Reaction: A Rare Paraneoplastic Event in a Case of Advanced Penile Cancer and Its Management. BMJ Case Rep. 2019;12:e230826. PMC6700585.
  • MedlinePlus, National Library of Medicine (NIH). Leukemoid Reaction: Medical Encyclopedia.