Leukemoid reaction

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2] Associate Editor(s)-in-Chief: Jogeet Singh Sekhon, M.D. [3]

Overview

Leukemoid reaction is a reversible increase in production of white blood cells in response to a stimulus, with white blood cell count of more than 25,000-30,000 per mm3 . Leukocytosis is increase in white blood cell count of more than 10,000 per mm3 and when the count exceeds 25,000 per mm3, with more than 2% immature white blood cells but absence of any blast cells, differentiating it from leukemias. Leukemoid reaction is classified according to the type of hematopoietic lineage of the bone marrow. Leukemoid reactions are mostly triggered by bacterial or viral infections. Leukemoid reaction is differentiated from leukemias by the absence of blast cells on peripheral blood film and high LAP score. Leukemoid reaction can lead to serious complications such as tumor lysis syndrome and DIC. The treatment includes treating the underlying cause and leukapheresis.

Historical Perspective

  • Leukemoid reaction was discovered in 1926 by Krumbharr.

Classification

Leukemoid reaction can be classified according to the type of hematopoietic lineage of the bone marrow[1].

Pathophysiology

Hematopoietic growth factors in leukocytosis, By Hematopoietic_growth_factors.svg: Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007) Rang & Dale's pharmacology, Churchill Livingstone ISBN: 0-443-06911-5.User:Mikael Häggström and A. Radderivative work: Furfur - This file was derived from: Hematopoietic growth factors.svg:, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=31083166


Causes

Differentiating Leukemoid reaction from Other Diseases

Leukemoid reaction is differentiated from leukemia by following ways[11][12]:

Differential diagnosis of leukemia vs leukemoid reaction
Differentiating features Leukemia Leukemoid reaction
Causes Carcinogens Infectious agents, biologically active substances and

products of tissue destruction

Pathogenesis The transformation of normal haematopoietic

cells to a tumor

Activation of normal hematopoiesis and exit of immature leukocytes

into the bloodstream

Duration Chronic Temporary and reversible
Genetic level Defect No defect
Splenomegaly Present Not present
Peripheral blood Immature cells, pancytopenia Mature and immature granulocytes with left shift
Bone marrow Increase in blasts and immature cells Myeloid hyperplasia and normal morphology
LAP score Low High
Toxic granules (suggestive of infection) Absent Present
Dohle inclusion bodies Absent Present

Leukemoid reaction should be differentiated from other causes of leucocytosis. The below table discusses different causes of leucocytosis:

Category Condition Etiology Mechanism Congenital Acquried Clinical manifestations Para−clinical findings Gold standard Associated findings
Demography History Symptoms Signs
Lab Findings
Physiologic Increased bone marrow production Demargination of peripheral blood neutrophils Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other CBC PBS Bone marrow exam ESR/CRP BUN/Cr LFT
Autonomous Reactive WBC HB Plt
Hematologic Hereditary neutrophilia[13] + + Rare autosomal dominant genetic disorder
  • Positive family history
Normal Nl + Nl Nl Nl Nl Nl Nl Molecular testing
Myeloproliferative neoplasms[14] + + + Elderly Exposure to ± + Nl + ↑/↓ ↑/↓ Nl Nl Bone marrow examination + clinical manifestation
Polycythemia vera[15] + + Mean age >60 years old + + Nl to ↑
  • Elevated normochromic, normocytic RBCs
  • Thrombocytosis
  • ≥ 10% immature myeloid precursors
  • Leukoerythroblastic picture
Nl Nl Nl Bone marrow examination + clinical manifestation
Microangiopathic hemolytic anemia (MAHA)[16] + + + Any + + + NA Bone marrow examination + clinical manifestation
Leukoerythroblastosis[17] + + Any + Nl + Nl Bone marrow biopsy
Immunology/

Rheumatology

Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings
Leukocyte adhesion deficiency[18] + + Rare autosomal recessive, LAD II more in Middle East and Brazil
  • Positive family history
+ Nl ↓/↑
  • Leukocytosis
  • Leukocytosis
Nl Nl Nl Flow cytometry
Cryopyrin-associated periodic syndromes[19] + + Autosomal dominant autoinflammatory syndrome
  • Positive family history
+ Nl + ↓/↑
  • Leukocytosis
  • Leukocytosis
Nl Genetic tests
Rheumatoid arthritis[20][21] + + Any, more in young women, between 30-60 years old + Nl +
  • Leukocytosis
NA Nl Nl Clinical manifestation + positive anti-CCP antibodies
Juvenile onset rheumatoid arthritis[22] + + Children under the age of 16
  • Positive family history
  • Blotchy rash on a child's arms and legs
+ Nl + +
  • Leukocytosis
NA Nl Nl Clinical manifestation + laboratory findings
Adult Still's disease[23] + + Rare autoimmune disease NA + Nl + +
  • Leukocytosis
NA Nl Nl Diagnosis of exclusion
Kawasaki disease[24] + + Autoimmune disease, more in Asian ethnicity boys NA + + Nl + +
  • Leukocytosis
NA Nl Nl Diagnostic criteria
IBD[25] + + Autoimmune disease, more in young
  • Stress
  • Positive family history
+ + Nl + + +
  • Leukocytosis
NA Nl Nl Colonoscopy and biopsy
Sarcoidosis[26] + + Autoimmune disease, more in young African American women
  • Positive family history
+ + Nl + +

Bilateral hilar adenopathy

+
  • Leukocytosis
NA Nl Nl Diagnosis of exclusion
Chronic hepatitis[27] + + Elderly + + + + +
  • Leukocytosis
NA Liver biopsy
Sweet syndrome[28] + + Rare + + Nl + +
  • Leukocytosis
Nl Nl Diagnostic criteria
Acute gout[29] + + Older males + +
  • Leukocytosis
NA Nl Clinical manifestation
Medication Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings
Steroid[30] + + + Any + Nl to ↓ Nl to ↓ Nl Clinical manifestation + history of drug consumption
Filgrastim (Myeloid growth factor)[31] + + + Any + Nl to ↓ + Nl to ↓ NA NA Nl Nl Clinical manifestation + history of drug consumption
Lithium[32]
  • Unknown
+ + + Any Nl Nl to ↓ NA NA Nl Nl Clinical manifestation + history of drug consumption
Catecholamines

(epinephrine)[33]

  • Stimulation of bone marrow myelopoiesis
  • Egress into the circulation
+ + + Any Nl to ↓ Nl Nl Clinical manifestation + history of drug consumption
ATRA[34] + + + Any Nl Nl Nl NA NA Nl Clinical manifestation + history of drug consumption
Other Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings
Infections[35] + + + + Any
  • Acutely ill
+ + Nl to ↓ ± ± ± Nl Nl Clinical manifestation+ culture
  • Depends on etiology
Allergy[36]
  • Unknown
  • Activation of chloride transport
+ + + + Any Nl to ↓ Nl Nl Clinical manifestation
Post splenectomy[37]
  • Unknown
+ + + Any
  • Normal
± Nl + Nl Nl Clinical manifestation
Cigarette smoking[38] + + + Any Nl NA NA Nl Nl Nl Clinical manifestation
Stress/exercise[39]
  • Reduced plasma volume
+ + + Athlete
  • Normal
Nl Nl Nl Clinical manifestation
Infancy[40] Physiologic + + Infancy
  • Normal
Nl NA NA Nl Nl Nl Clinical manifestation
Pregnancy[41] Physiologic + + Pregnancy
  • Normal
Nl NA NA Nl Nl Nl Clinical manifestation
Platelet clumping[42] Spurious + Any
  • Normal
Nl Nl Nl Nl Nl Nl Clinical manifestation
Mixed cryoglobulinemia[43] Spurious + Any Nl + Nl to ↓ Nl Nl Nl Nl Skin biopsy
Category Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings

Epidemiology and Demographics

Age

  • Patients of all age groups may develop leukemoid reaction[1][44].
  • Normal white blood cell count changes with age.
  • Leukemoid reaction in neonates is more common, compared to children and adults.

Gender

  • Leukemoid reaction affects men and women equally.

Race

  • There is no racial predilection for the development of leukemoid reaction.

Risk Factors

Screening

No screening is done for leukemoid reaction.

Natural History, Complications, and Prognosis

History

The majority of patients with leukemoid reaction have the following complaints[45][46]

Complications

Prognosis

  • Prognosis generally depends on the underlying etiologies.
  • If the white blood cell count reaches more than 50,000 per mm3, life threatening complications can occur.

Diagnosis

Symptoms

  • Obtain history of the following:

Laboratory findings

Electrocardiogram

No specific ECG changes in leukemoid reaction.

X-Ray

No specific x ray changes in leukemoid reaction.

Echocardiography and Ultrasound

No echocardiography and ultrasound findings.

CT

No CT scan findings in leukemoid reaction.

MRI

No specific MRI findings in leukemoid reaction.

Treatment

Medical Therapy

Surgery

The treatment depends on the underlying cause. In general, there is no role for surgery.

Primary prevention

Prevention and treatment of infections.

Secondary prevention

Treatment of underlying cause and reduction of white blood cell count.

See also

References

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