Leukemoid reaction
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Overview
- The term leukemoid reaction, also referred to as transient myeloproliferative disorder, describes an elevated white blood cell count, or leukocytosis, that is a physiologic response to stress or infection (as opposed to a primary blood malignancy, such as leukemia).
Historical Perspective
- [Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
- The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
- In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
- In [year], [gene] mutations were first implicated in the pathogenesis of [disease name]
Classification
Leukemoid reaction can be classified according to the course of the disease and the type of hematopoietic lineage of the bone marrow.
- According to the course of the disease:
- Phase of expressed manifestations
- Phase of recession
- Phase of normalization with trace reactions.
- According to the type of hematopoietic lineage of the bone marrow :
1. Reactions of myeloid type
1.1. Neutrophilicleukemoid reactions
1.2. Eosinophilic leukemoid reactions
2. Reactions of lymphoid type
2.1. Lymphomonocytic leukemoid reactions
2.2. Lymphocytic leukemoid reactions
2.3. Plasmocyticleukemoid reactions
2.4. Leukemoid reaction with blast cells
3. Secondary (reactive) thrombocytosis
4. Secondary erythrocytosis
5. Mixed forms of leukemoid reactions
6. Rare forms of leukemoid reaction
6.1. Cytopenia
6.2. Leukemoid reactions of basophilic type.
Pathophysiology
- Leukemoid reaction is a reversible increase in production of white blood cells in response to a stimulus.
- Leukemoid reaction is classified acoording to the type of hematopoietic lineage of the bone marrow.
- It is a reactive, functional condition of hematopoietic, lymphatic and immune systems secondary to various diseases accompanied by the development of immature white blood cells in the peripheral blood, the number may exceed 50000 per 1 mm3
- Leukemoid reaction is diagnosed after the exclusion of a malignant hematological disorder.
- Changes in blood are transient and blood levels return to normal when the causes disappear.
- There are no signs of inhibition of normal hematopoiesis.
- Leukemoid reactions are mostly triggered by bacterial or viral infections, emergency stress irritants and also by various bacterial and nonbacterial stimulants causing sensitization.
- The sensitization causes upregulation of growth or survival factors (eg, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, c-kit ligand), adhesion molecules (eg, CD11b/CD18), and various cytokines (eg, interleukin-1, interleukin-3, interleukin-6, interleukin-8, tumor necrosis factor).
- There is activation of normal hematopoiesis and excessive blood cells output to peripheral blood (reactive hyperplasia of leukopoietic tissue) and output of immature blood cells into peripheral blood.
- Reactions of myeloid type are characterized by a shift to the left, from an increased number of stab cells to singular blast cells with presence of all intermediate forms.
- There is an increase in immature granulocytes of myeloid lineage.
- Neutrophilic leukemoid reactions develop in Infections (sepsis, scarlet fever, purulent processes, diphtheria, lobar pneumonia, tuberculosis, dysentery, etc), exposure to ionizing radiation, Injuries of the skull, intoxication (uremia, CO poisoning), bone marrow metastases of malignant tumors.
- Eosinophilic reactions develop in allergic processes or in diseases with allergies, as well as in parasitic diseases. They are characterized by the development of a great number of eosinophils, about 90% of leukocytes.
- Lymphomonocytic leukemoid reactions develop in infectious mononucleosis, there are atypical mononuclear cells, called "lymphomonocytes" which are modulated T- and NK-lymphocytes, which get to the bloodstream by initiation of B lymphocytes.The number of atypical mononuclear cells can be increased in any viral infection.
- Lymphocytic leukemoid reactions develop in acute viral and bacterial infections and are characterized by leukocytosis with absolute lymphocytosis.
- Plasmocytic leukemoid reactions occur in diseases caused by protozoa (toxoplasmosis), viral infections (chickenpox, measles, rubella). Increased level of plasma cells (2%) in splenomegaly, blood and bone marrow.
- Leukemoid reactions with blast cells develop in severe viral infections (cytomegalovirus, etc.). Blast transformation of B-lymphocytes may be observed in the bone marrow, lymph nodes and peripheral blood.
- Secondary absolute erythrocytosis is caused by increased erythropoiesis, relative hemoconcentration and polycythemia. It is characterized by increased red blood cell count.
- Secondary thrombocytosis is possible in malignant tumors, inflammatory diseases, following bleeding, hemolytic crises, after surgical operations and splenectomy.
Causes
- Neutrophilic leukemoid reactions :
- Infections - sepsis, scarlet fever, purulent processes, diphtheria, lobar pneumonia, tuberculosis and dysentery.
- Exposure to ionizing radiation.
- Injuries of the skull.
- Intoxication (uremia, CO poisoning).
- Bone marrow metastases of malignant tumors - Lymphogranulomatosis
- Steroid hormones therapy
- Eosinophilic reactions :
- Allergic processes or in diseases with allergies, as well as in parasitic diseases.
- Lymphomonocytic leukemoid reactions:
- Infectious mononucleosis.
- Lymphocytic leukemoid reaction:
- Acute viral and bacterial infections
- Plasmocytic leukemoid reactions:
- Diseases caused by protozoa (toxoplasmosis), and viral infections (chickenpox, measles, rubella).
- Thrombocytosis:
- Primary thrombocytosis- chronic myeloproliferative diseases.
- Secondary thrombocytosis-
- Malignant tumors
- Inflammatory diseases
- Following bleeding
- Hemolytic crises
- After surgical operations and splenectomy.
- Leukemoid reactions of basophilic type:
- Allergic reactions
- Hemolytic anemia
- Ulcerative colitis
- Hypothyroidism
- Leukemia.
Differentiating Leukemoid reaction from Other Diseases
Leukemoid reaction is differentiated from leukemia by following ways:
| 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 |
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
Natural History
Complications
Prognosis
Diagnosis
Diagnostic Criteria
History and Symptoms
Physical Examination
Laboratory Findings
Conventionally, a leukocytosis exceeding 50,000 WBC/mm3 with a significant increase in early neutrophil precursors is referred to as a leukemoid reaction.[1] The peripheral blood smear may show myelocytes, metamyelocytes, promyelocytes, and even myeloblasts; however, there is a mix of early mature neutrophil precursors, in contrast to the immature forms typically seen in acute leukemia. The bone marrow in a leukemoid reaction, if examined, may be hypercellular but is otherwise typically unremarkable.
Leukemoid reactions are generally benign and are not dangerous in and of themselves, although they are often a response to a significant disease state (see Causes below). However, leukemoid reactions can resemble more serious conditions such as chronic myelogenous leukemia (CML), which can present with identical findings on peripheral blood smear.
Historically, various clues including the leukocyte alkaline phosphatase score and the presence of basophilia were used to distinguish CML from a leukemoid reaction. However, at present the test of choice in adults to distinguish CML is an assay for the presence of the Philadelphia chromosome, either via cytogenetics and FISH, or via PCR for the Bcr/abl fusion protein. The LAP (Leukocyte Alkaline Phosphatase) score is high in reactive states but is low in CML. In cases where the diagnosis is uncertain, a qualified hematologist or oncologist should be consulted.
Electrocardiogram
X-Ray
Echocardiograph and Ultrasound
CT
MRI
Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
See also
References
- ↑ Ronald Hoffman; et al. (2005). Hematology: basic principles and practice. St. Louis, Mo: Elsevier Churchill Livingstone. ISBN 0-443-06628-0. p. 803.