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Etiology, Clinical Presentations, Classifications And Diagnosis Of The Various Types Of Leukemia

Updated on January 20, 2014

Leukemia Symptoms


An Overview

Leukemias are muticentric in origin. An abnormal stem cell undergoes mutation and proliferates in a disorderly and unrestrained manner so as to fill the marrow, spill into the peripheral blood and infiltrate almost all organs in the body. The clone of malignant cells proliferates by division but fails to differentiate and hence immature forms persists in the marrow and peripheral blood. Though the exact stimulus for the mutation is not clear in an individual case, several factors are known to induce leukemia in experimental animals and humans.

  1. Genetic factors are important as evidenced by the increased incidence of leukemia in mongolisms and Fanconi’s anemia.
  2. RNA viruses such as the retrovirus and DNA viruses such as Epstein-Barr virus may induce leukemogenic changes in cells.
  3. Exposure to ionizing radiation (accidental and therapeutic) and drugs and chemicals which depress bone marrow (benzol, chloramphenicol and cytotoxic drugs such as alkylating agents) have been incriminated to be leukemogenic by clinical, experimental and epidemiological observations.
  4. Occurrence of cases in close relatives or in successive generations and in clustered in closed communities have strengthened the role of environmental factors in leukemogenesis.
  5. Diseases like multiple myeloma and lymphomas transform into actue myelogenous leukemia in some cases. It is likely that the development of leukemia is the total effect of the environmental factors on the genetically predisposed individual. The clone of leukemic cells multiples in exponential rates. The cell cycle time is generally longer for leukemias than for many tumours (AML 80-84 hours, CML is 120 hours).

Hairy Cell Leukemia


Peripheral blood film samples

The diagnosis of acute leukemia is suggested by the presence of significant numbers of blast cells, which are the precursors of leucocytes. Blast cells are characterized by deep blue non-granular cytoplasm and a rounded or oval nucleus showing pale stained inclusions- the nucleoli- which vary in number from 2 to 5. Though some idea about the nature of the blast can be obtained by morphology, further identification is done by cytochemical methods.

Peroxidase and sudan black are stains which detect the presence of lysosomes containing the primary granules of the neutrophilic and monocytic series. Terminal deoxynucleotidyl transferase (TdT) is seen most commonly in ALL, occasionally in the blastic phase of CML and rarely in AML.

Cytological differentiation is important since the treatment, complications and prognosis are different. Even with a battery of tests, 5-10% of acute leukemias may defy final identification initially. Follow up helps to reveal their true type. Bone marrow examination is mandatory in all cases. Presence of blasts in excess of 30% of the total cells in the marrow confirms the diagnosis of acute leukemia. Elevation above 5% should be noted with suspicion. In the case of chronic leukemias, diagnosis is easy by examining the blood film, since the cells show typical differentiating features. In chronic myeloid leukemia, neutrophils and myelocytes predominate in the peripheral blood. In chronic lymphatic leukemia, mature lymphocytes predominate. Though, the vast majority of leukemias show leukocytosis, in 10-20%, the count may be normal or low even though immature cells are present. These are termed as subleukemic leukemias. When there are no abnormal cells in the peripheral blood, the term aleukemic leukemia is used. Bone marrow is hypercellular in most cases and shows infiltration by abnormal cells irrespective of the leucocyte count in peripheral blood.

Serum uric acid is elevated during the active phase of leukemias. Uric acid levels are elevated further during treatment with cytotoxic drugs due to rapid cell destruction. Leukemias have to be differentiated from leukemoid reactions which are less common.

Differences Between Lymphoblasts And Myeloblasts

Number of nucleoli
Accompanying cells
Lymphocytes and non-granular cells
Promyelocytes, myelocytes and neutrophils
Peroxidase staining
Promyelocyte, myelocytes and neutrophils are positive; early blasts are negative
Sudan black staining
PAS staining (periodic acid Schiff)
Coarsely positive
Finely Positive
TdT (terminal-deoxytransferase)
Generally Positive
Generally positive

Differences Between Acute And Chronic Leukemias

Acute Leukemia
Chronic Leukemia
Age Group
More in the first and second decades
Mostly in the 4th, 5th and 6th decases
Sex ratio
M:F is 2:1
M:F is 1:1
Duration of symptoms
Weeks to Months
Several months to one year
Presenting Complaints
Anemia, fever, infections, hemorrhagic tendencies or complications, especially neurological
Vague symptoms, loss of weight, mass in the abdomen or lymph nodular masses
Liver, spleen and lymph nodes are moderately enlarged in 70-80% of cases
Moderate to gross splenomegaly is the rule in CML. Gross lymphadenopathy occurs in CLL
Blood picture
Total leucocyte count is moderately elevated (15-30 X 109/liter- 15-30,000/cmm). Blast cells form 10-90% of the total. Platelets are often reduced.
Total leucocyte count is grossly elevated, 150-250 X 109/liter (150-250.000/cmm)
Bone Marrow
Shows depression of erythroid cells, myeloid cells and megakaryocytes and infiltration by the abnormal cells. Blast cells form more than 30% and may be even up to 90%
CML shows increase in myeloid cells, especially myelocytes, metamyelocytes and neutrophils. Infitration by small lymphocytes is seen in CLL.
Chromosomal Studies
Ph’ Chromosome is demonstrable in 90-95% cases of CML
Course And Prognosis
Untreated, fatal within weeks to six months due to infections, hemorrhage, anemia or other complications
Untreated, CML has a median survival of 18-24 months, CLL has a generally more prolonged course.
Response to treatment
Remissions occur in 60-90% of the cases cure may occur in 10% of cases of ALL, but only in a much smaller proportion of AML
Present methods of treatment of CML are unsatisfactory and invariably all cases go to blast crises; in CLL also the disease is ultimately fatal after a prolonged course.

An Infant Suffering From Leukemia


Acute Monocytic Leukemia

Acute monocytic leukemia. These lesions are rarely found in chronic leukemia but are a common finding in acute forms. They appear as erythematous infiltrations of the skin, forming papules, macules, and plaques. Pruritus may be present.
Acute monocytic leukemia. These lesions are rarely found in chronic leukemia but are a common finding in acute forms. They appear as erythematous infiltrations of the skin, forming papules, macules, and plaques. Pruritus may be present. | Source

Symptomatology and diagnosis of Leukemias

Finally, symptoms differ between acute and chronic leukemias. These are summarized in the table below. Acute leukemia should be suspected in all cases of rapidly developing anemia, prolonged fevers, hepatosplenomegaly, lymph node enlargement, hemorrhage tendency, local tumour formation, neurological manifestations and other bizarre clinical presentations. Acute lymphatic leukemia may be mistaken for rheumatic or rheumatoid arthritis in children. Early diagnosis is possible only if the clinical suspicion is strong. Since early institution of treatment is more effective in curing the disease, specific investigations should not be delayed. Rarely, leukemias may be brought out by routine investigations in asymptomatic individuals. Clinical diagnosis has to be followed up with hematological confirmation.

© 2014 Funom Theophilus Makama


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