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Definition of acute leukemia

  1. This is a malignant neoplasm of hematopoietic cells particularly stem cells.
  2. There is diffuse infiltration of the bone marrow by these neoplastic cells.
  3. These cells enter the blood and may infiltrate the liver, spleen, lymph nodes and other organs.

Classification of Acute Leukemias

  1. Acute lymphocytic leukemia (ALL)
  2. Acute myelocytic leukemia (AML)
  3. The following diagram shows how these leukemias develop from the blast cells.

FAB (French-American-British) classification of Acute Lymphocytic Leukemia

L1                    Lymphoblasts with uniform, round nuclei, and scant cytoplasm
Nucleoli are not prominent.                                                                      
L2 More variable lymphoblast and cytoplasm is abundant.          
Nucleoli are large and may see one or more nucleoli.        
L3 Lymphoblasts with fine nuclear chromatin and blue to deep blue cytoplasm that contains vacuoles.
Lymphoblast is large and has prominent nucleoli and these are one or more than one.

FAB of Acute Myelocytic Leukemia

M1 Undifferentiated myeloblastic. No cytoplasmic granulation
Also called acute myeloblastic leukemia with no differentiation (20 %)
M2 Differentiated myeloblastic cells and sparse granules in the cytoplasm
Also called AML with maturation
M3 Acute Promyelocytic Leukemia
Granules are  typical of promyelocytic morphology (5 to 10 %)
M4  Acute Myeloid Monoblastic Leukemia
The mixed population of  myeloblastic and monocytic morphology (15 to 20 %)
M5 Acute Monoblastic Leukemia
Pure monobasic morphology (10 )
M6 Acute Erythroleukemia
Predominantly immature erythroblast morphology, sometimes megaloblastic appearance ( 5)
M7  Acute Megakaryoblastic leukemia
Megakaryocytic  Cells with shaggy borders that may show some budding ( 1%)

Pathophysiology

  1. The malignant transformation is at the level of pluripotential cells like stem cell and these are the committed stem cells, so this is stem cell disorder.
  2. There is abnormal proliferation, monoclonal expansion, and decreased apoptosis of these cells leads to the replacement of normal bone marrow cells by these malignant cells or immature cells.
  3. Acute Leukemias has little or no maturation and may see mainly blast cells.
  4. Acute Leukemias are diagnosed on the percentage of blast cells in the bone marrow.
  5. 30% or more blast cells are needed to classify the disorder as acute leukemia.

Acute Leukemias signs and symptoms

  1. Appears suddenly.
  2. There are weakness and fatigue.
  3. The patient may have a low-grade fever.
  4. There may be bruising and mild bleeding from the gums.
  5. There is a bone pain due to the expansion of the marrow.

Diagnosis of Acute Leukemia

  1. These are more common in the younger age group.
    1. These are more frequent in children.
    2. Mostly seen before the age of 20 years.
  2. Onset is an abrupt and fatal outcome.
    1. There is a fever.
  3. There is the rapid development of anemia.
    1. There is normochromic and normocytic anemia.
    2. May see nucleated RBCs.
  4. There is thrombocytopenia.
    1. May see petechiae and purpura in the skin and mucous membranes.
  5. Leukocytes count is variable.
    1. Mostly leucocytes count is less than 100,000/cmm.

Acute Myelocytic Leukemia

  1. Age: This is seen during the first month of life and then in the later age group.
    1. 10% cases found in the children.
  2. Sex: More common in the male than women. Male: female ratio is 3:2.
  3. Signs and symptoms:
    1. Mostly these patients present with varying degree of bone marrow failure.
    1. So clinical symptoms and signs are due to anemia, leukopenia, thrombocytopenia, and infections.
    2. Fever and fatigue are present in most of the patient.
    3. Acute promyelocytic leukemia (M3) causes disseminated intravascular coagulopathy (DIC) and bleeding.
    4. Acute myelomonocytic leukemia (M4) and acute monocytic leukemia (M5) causes gum hypertrophy.
  4. Lab. findings : 
    1. WBC count is variable. 25% of the patient has >50,000/cmm, 25% has <5000/cmm and 5 to 10% has count between 5000 to 10,000/cmm.
    2. WBC morphology. These are morphologically abnormal and immature cells.
    3. Uric acid in 50% of the cases is raised.
    4. Lactate dehydrogenase (LDH) about 50% show raised a level.
    5. Bone marrow shows >20% blast cells. Promyelocytes are numerous particularly in M3.
      1. Auer rods can be seen in the cytoplasm.
      2. Cytochemical stains, peroxidase reaction and Sudan black are positive.
    6. Nucleated RBCs may be seen.
    7. Platelet count may be low and may see count between 30,000 to 100,000/cmm.
    8. Coagulation abnormalities are also seen. PT, PTT and Thrombin time are prolonged.

 Acute Lymphocytic Leukemia

  1. Age: This is most common in childhood. Mostly occur before the age of 4 years. The peak is between 2 to 10 years.
    1. These are rare after the age of 30 years.
    2. The second peak may be seen in middle and old age group.
  2. Signs and symptoms: 
    1. Onset is sudden. There is no preleukemic stage.
    2. There are fatigue and fever.
    3. There may be bleeding and infections.
    4. There is enlargement of lymph nodes, spleen, and liver.
    5. There may be involvement of the central nervous system (CNS). This shows as leukemic meningitis
    6. Bone pain is due to infiltration of the leukemic cells.
  3. Lab. Findings:
    1. WBC count is variable from very high to low count.
    2. There are anemia and thrombocytopenia.
  4. Bone marrow: Very few leucocytes are seen.
    1. Difficult to find normal WBCs or RBCs in the bone marrow.
    2. Characteristically there are blast cells.
    3. Auer rods are absent.
    4. Sudan black and peroxidase reaction are negative.

Difference between Acute Myelocytic Leukemia and Acute Lymphocytic Leukemia

Characteristic Features                    Acute Myelocytic Leukemia      Acute Lymphocytic Leukemia
Origin of the cells Myeloid series cells Lymphoid  series cells
Features of Blast cells Large is size,  Small in size
  Cytoplasm is moderate  Cytoplasm is scanty
  Chromatin is fine and lacy Chromatin is dense
  Nucleoli are prominent and >2  Nucleoli are indistinct and <2
Auer rods Present Absent
Sudan black and peroxidase Positive Negative
Bone marrow A mixed population of myeloid cells and blast cells               Mainly blast cells and very few  WBCs or RBCs
Leukocyte Alkaline phosphatase (ALP) Positive  (differentiate CML from the leukemoid reaction. Negative
Periodic Acid-Schiff (PAS) Positive in Erythroblast in M6 leukemia 

Positive (block patterns) in L1 and L2 

Negative in L3

Test value for the layman:

  1. Blood examination is advised if the patient has high TLC.
  2. If the patient has anemia.
  3. If the patient has enlarged lymph nodes.
  4. In case of patients has a fever and weakness.

Possible References Used

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