Leukemoid Reaction and Diagnosis (D/D from Chronic Myelocytic leukemia)

Sample

• Blood in EDTA is needed along with fresh blood smear.

Definition

1. If there is a persistent increase in the neutrophils, reactive and excessive leucocytosis with a count of 30,000 to 50,000 / µL, with the presence of immature and mature white cells in the peripheral blood smear is called Leukemoid reaction. Sometimes lymphocytic reaction maybe sen.
2. This is not primary marrow disorder, and this is due to the secondary to infections.
3.   The count varies from 50,000 to 100,000/cmm. with immature cells.
4. Blast cells in the peripheral blood smears are not seen which is helpful to differentiate from leukemia.
5. Extremely elevated count >100,000/cmm are more suggestive of myeloproliferative process, with some exceptions.

Significance

1. This term is used to differentiate between the leucocytosis and leukemia.
2. In leukocytosis or neutrophilia there is an increase in the count from 10,000 to 25,000 / µL (microliter).

Pathogenesis of leukemoid reaction:

1. Leucocytosis results from the release of the cells from the bone marrow under the influence of IL-1 and TNF.
2. There is a shift to the left of the neutrophils.
3. Prolonged infection induces in the bone marrow, the proliferation of the precursor cells and that is also by the IL-1 and TNF.
4. Bacterial infections induce a selective increase in the neutrophils while parasitic infestation induces eosinophilia.
5. Mumps, Rubella and some of the viruses leads to a selective increase in the lymphocytes and cause lymphocytosis.

The differentiating point from leukemia:

1.  In the leukemoid reaction, the neutrophils are mature and not clonally derived.
2. There is a persistent increase in TLC above 50,000/cmm and no evidence of leukemia.
3. Blood count comes to normal after treating the cause.
4. Increased blast cells are not seen in the leukemoid reaction.
5. A count above 100,000 /µL is more suggestive of the myeloproliferative disorder with very few exceptions.
6. Granulocytes show toxic granulations and Dohle bodies.
7. NAP score is high which is low in leukemia.
8. Leukemoid reaction shows:
   1. Toxic granulations.
      

      Leukemoid reaction toxic granules

   2. Toxic vacuolization.
   3. Presence of Dohle bodies. These are light blue to grey, oval and maybe basophilic inclusions in the neutrophils. Usually seen in the peripheral area of the cytoplasm of neutrophils. These consist of ribosomes and endoplasmic reticulum.
      

      Leukemoid reaction Dohle bodies

      

      Leukemoid Reaction with prominent Neutrophils

Differential diagnosis includes:

1. Chronic myeloid leukemia.

Causes of Leukemoid reaction:

1. A severe infection like Clostridium, Tuberculosis, Pertussis and Infectious mononucleosis.
2. Visceral larva migration leads to eosinophilia.
3. Tuberculosis gives rise to monocytosis.
4. Fungal infection also causes neutrophilia with monocytosis.
5. Leukemoid lymphocytosis is seen in Tuberculosis, Whooping cough and infectious mononucleosis.
6. Intoxication.
7. malignancies.
8. Severe hemorrhage.
9. Acute hemolysis.
10. Drugs like Sulfa, Dapsone, Glucocorticoids, and use of the G-CSF factor.
11. Diabetic ketoacidosis.
12. Ischemic colitis.
13. Hepatic necrosis.

Difference between Leukemoid reaction and chronic myelocytic leukemia:

Clinical parameters	Leukemoid reaction	Chronic myeloid leukemia
What are the basis	physiological proces	pathological process
WBC count	usually <50,000/cmm	usually >50,000/cmm
Basophils	absent	usually increased count
platelets	normal	Increased
Eosinophil	normal	Increased
Hemoglobin	usually normal	usually low
Band form	these are prominent	all stages (myelocytes)
Toxic granules and Dohle bodies	these are present	toxic granules ± to 0
Spleen	usually not present	usually enlarged
Philadelphia chromosome	absent	present in 90% of the cases
Leucocytes Alk.phosphatase (LAP) score	normal or increased > 100	< 10
History	short	long
After the treatment	Count becomes normal	This may be still raised

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