Leukemia Overview and Types

Leukemia

• Leukemia is a group of malignant diseases of hematopoietic tissue.
• It is characterized by the replacement of normal bone marrow elements with malignant cells.
• Leukemia is known as blood cancer.
• Leukemia is characterized by the over-proliferation of malignant cells.
• The presence of many malignant cells is found in both bone marrow and circulation.
• Leukocytosis is a normal response to infection.
• It may indicate malignancy when it becomes chronic, progressively elevates, or occurs without an obvious cause.

Types of Leukemia

• Acute Leukemia:
  • Characterized by the rapid progression of abnormal expansion of immature cells or blasts.
  • Has a sudden onset and rapid progression.
  • Blood smear shows blast cells or immature cells.
• Chronic Leukemia:
  • Characterized by the slow progression of abnormal expansion of mature cells.
  • Has a gradual onset and slow progression.
  • Mature cells are over-proliferated in bone marrow and circulation.

Classification

• Fab Classification:
  • Based on cellular morphology and cytochemical stains.
  • Defines acute leukemia as greater than 20% bone marrow blasts.
  • Commonly used in academic teaching.
  • Is obsolete but based on the principles of WHO Classification.
• WHO (World Health Organization) Classification:
  • Classification based on:
    • Cellular morphology
    • Cytochemical stains
    • Immunologic probes of cell markers
    • Cytogenetics
    • Molecular abnormalities
    • Clinical syndrome
  • Defines acute leukemia as greater than 20% bone marrow blasts.
  • Uses cell markers, such as cluster of differentiation (CD), which are WBC specific.
  • Anchored on the principle of FAB classification, using cellular morphology and cytochemical stains.
  • More specific because it detects cell markers, clinical syndrome, and genetic defects.

Clinical Manifestations of Leukemia

• Effects of Bone Marrow Suppression:
  • Anemia: Decreased production of red blood cells, especially if the type of leukemia is under myelogenous.
  • Infection risk: Decreased neutrophil count, which is critical for fighting infections.
  • Bleeding risk: Thrombocytopenia leads to decreased clotting factors.
  • Physiological fracture risk: Proliferation of cells in the bone marrow weakens the periosteum.
• Effects of Infiltration of Malignant Cells:
  • Hypertrophy and fibrosis occur in organs like the liver, spleen, and lymph glands.
  • Increased intracranial pressure, ventricular dilation, and meningeal irritation
• Hypermetabolic State:
  • Cells are deprived of nutrients.
  • Causes loss of appetite, weight loss, general fatigue, and muscle atrophy.

Lymphoblastic Leukemia

• Acute Lymphoblastic Leukemia (ALL):
  • Sudden onset with rapid progression.
  • Makes up around 95% of cases of Hodgkin lymphoma in developed countries.
  • Hallmarks:
    • Presence of Reed-Sternberg cells, the cancer cells.
    • Owl's eye appearance.
  • Tests include: CBC, PBS, skin biopsy, immunophenotyping, TCR gene rearrangement test, and flow cytometry.
  • CD markers: CD2, CD3, and CD4 Positive.
• Myelocytic/Myelogenous Leukemia:
  • Acute Myelogenous Leukemia (AML):
    • Sudden onset with rapid progression.
    • Presence of blast cells in peripheral blood and bone marrow.
    • Classified as L1, L2, and L3.
  • Chronic Myelogenous Leukemia (CML):
    • Gradual onset with slow progression.
    • Presence of mature cells in the peripheral blood and bone marrow.
    • Appearance of smudge cells in the peripheral blood smear.

Non-Hodgkin Lymphoma

• Classic Hodgkin Lymphoma (cHL):
  • Accounts for about 95% of all cases of Hodgkin lymphomas in developed countries.
  • Hallmark: Reed-Sternberg cells.
  • Appearance of enlarged lymph nodes may be the first sign.
• Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL):
  • Usually starts in lymph nodes of the neck or armpit.
  • More common in men than women.
  • Treatment differs from classic types.
  • Features:
    • Popcorn cells, variant of Reed-Sternberg cells, are present.
    • Absence of Reed-Sternberg cells.

Chronic Myelogenous Leukemia (CML)

• Diagnosis:
  • WBC count greater than 300 x 10^9/L (Leukocytosis).
  • Positive FISH (Fluorescence In Situ Hybridization).
  • Bone marrow aspirate to assess the bone marrow cell environment.
• Pathogenesis:
  • Affects the BCR-ABL gene, leading to the Philadelphia chromosome.
  • Affects the Common Myeloid Progenitor (CMP), disrupting cell production.

Polycythemia Vera

• Increased blood volume and viscosity, leading to hyperviscosity syndrome.
• Disrupts the production of cells by affecting the Common Myeloid Progenitor (CMP).
• Types:
  • Pseudopolycythemia: Apparent rise in RBC level in the blood due to factors like Burns, Dehydration, and Stress.
  • True Polycythemia: Chronic condition resulting from abnormal bone marrow stem cells.
    • Primary: True Polycythemia.
    • Secondary: Caused by conditions like Gaisbock Syndrome.

FAB Classification Summary

• MPO: Myeloperoxidase
• SBB: Sudan Black B
• PAS: Periodic Acid Schiff