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S2 E078 Leukemia

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Leukemia

  • Leukemia is a disease characterized by the overproduction of a particular type of blood cell.
  • This process often inhibits the production of normal blood cells
  • These leukemia cells do not function as proper cells
  • Leukemia does not form a solid tumor. Rather it produces blood cells which may infiltrate tissue.
  • Leukemic cells have unusually long lives and avoid preprogramed cell death or apoptosis
  • Swollen lymph glands and an enlarged spleen are often seen due to collecting WBC’s
  • Acute leukemia is when the overproduction occurs rapidly and there is a fast increase in the number of WBCs. These cells tend to be immature blasts.
  • Chronic Leukemia is the slower build up of mature but abnormal and non-functioning WBCs.
  • The type of leukemia depends on the specific type of cell being produced.
  • Multipotential hematopoietic stem cells produce either myeloid progenitor cells or lymphoid progenitor cells
    • Lymphoid progenitor cells produce
      • B lymphocytes
      • Plasma cells
      • T lymphocytes
      • Natural killer cells
    • Myeloid progenitor cells produce
      • Megakaryocytes
      • Thrombocytes
      • Erythrocytes
      • Mast cells
      • Myeloblasts
      • Basophils
      • Neutrophils
      • Eosinophils
      • Macrophages
  • Lymphocytic leukemia is characterized by the overproduction of lymphocytes
  • Myelogenous leukemia is characterized by the overproduction of red blood cells as well as some white blood cells and platelets
  • You can then pair the two cell types of with the two time frames
  • Acute lymphocytic leukemia (ALL)
  • Chronic lymphocytic leukemia (CLL)
  • Acute myelogenous leukemia (AML)
  • Chronic myelogenous leukemia (CML)
Leukemia

Acute lymphocytic leukemia (ALL)

  • Excessive lymphoblasts
  • Abnormal cells produced have unusually long lives
  • These leukemia cells have the ability to infiltrate organs and the Central Nervous System
  • Most commonly found between the ages of 2 & 5 but can effect any age group
  • This is the most common form of leukemia in children
  • Overcrowding of the bone marrow is the main issue

Clinical Presentation

  • Anemia
    • Weakness
    • Fatigue
    • Tachycardia
  • Thrombocytopenia
    • Petechia
    • Epistaxis
    • Bleeding gums
  • Organ infiltration
    • Bone and joint pain
    • Enlarged lymph nodes and liver
    • Headaches
    • Visual and audio disturbances
  • Infections / Fever

Labs & Studies & Physical Exam Findings

  • Enlarged lymph nodes
  • CBC
    • Elevated white blood cell count
    • Pancytopenia
  • Peripheral blood smear
    • Elevated blasts
    • Pancytopenia with circulating blasts
  • Bone marrow biopsy with elevated blast cells
  • Cytogenetics – Looking for B and T lymphocytes
  • Cytogenetics, cytochemical stains and flow cytometry are used to determine subtypes and distinguish AML from ALL
  • CT or ultrasound may be used to determine organ infiltration

Treatment

  • Supportive care
    • Deal promptly with infections
    • Maintain good hydration
    • Transfusions
  • Chemotherapy
  • Steroids and methotrexate
  • Bone marrow transplant
  • Survival rates range from 20-75% depending on the characteristics and subtype of disease

Chronic Lymphocytic Leukemia (CLL)

  • Chronic lymphocytic leukemia is also known as B cell leukemia because it is usually monoclonal malignant B cells
  • The most common type of leukemia
  • Most commonly diagnosed in men over 50 years old

Clinical Presentation

  • Routine physical exam – most patients are asymptomatic early in the disease process
  • Vague symptoms
    • Fatigue
    • Weakness
    • Weight loss
    • Night sweats

Labs, Studies and Physical Exam Findings

  • Lymphadenopathy
  • Splenomegaly
  • Hepatomegaly
  • CBC with with WBCs greater than 20,000 and lymphocytes greater than 5,000
  • Flow cytometry can be used to test for monoclonal B cells
  • Bone marrow biopsy showing small lymphocytes
  • Lymph Node biopsy

Treatment

  • Supportive care
    • Deal promptly with infections
    • Maintain good hydration
  • Transfusions
  • Chemotherapy
  • Radiation
  • Bone marrow transplant
  • Splenectomy
  • Prognosis is between 2 and 20 years depending on subtype

Acute Myelogenous Leukemia (AML)

  • AML is more often seen in adults

Clinical Presentation

  • Anemia
    • Weakness
    • Fatigue
    • Tachycardia
  • Thrombocytopenia
    • Petechia
    • Epistaxis
    • Bleeding gums
  • Organ infiltration (less frequent than ALL)
    • Bone and joint pain
    • Enlarged lymph nodes and liver
    • Headaches
    • Visual and audio disturbances

Labs, studies and Physical Exam Findings

  • Enlarged lymph nodes are rare
  • CBC
    • Elevated white blood cell count
    • Pancytopenia
  • Peripheral blood smear
    • Elevated blasts (may make up to 90% of WBCs)
    • Pancytopenia
  • Bone marrow biopsy with elevated blast cells
  • Peripheral blood smear
    • Auer rods are pathognomonic for AML
  • Cytogenetics, cytochemical stains and flow cytometry are used to determine subtypes and distinguish AML from ALL

Treatment

  • Supportive care
    • Deal promptly with infections
    • Maintain good hydration
  • Transfusions
  • Chemotherapy
  • Stem cell transplant

Chronic myelogenous leukemia (CML)

  • Mean age of diagnosis is 65 years old
  • An abnormal pluripotent hematopoietic progenitor cell starts reproducing
  • Unregulated growth of many different types of cells are possible
    • Red Blood Cells
    • Neutrophils
    • Eosinophils
    • Basophils
    • Megakaryocytes
    • etc
  • Three phases
    • Chronic
      • Stable period last about five years
    • Accelerated
      • Symptoms become difficult to treat
    • Blast
      • Similar to acute leukemia with an overwhelming number of blasts
  • The Philadelphia Chromosome is present in almost all cases
  • CML will end in blast phase which is much like an acute leukemia

Clinical Presentation

  • Most patients are asymptomatic and in the Chronic phase
  • As a patient enters the accelerated phase vague symptoms begin to appear
    • Fatigue
    • Weakness
    • Abdominal fullness
    • Weight loss
    • Night sweats
    • Splenomegaly
      • Enlarged spleen may cause left upper quadrant pain or loss of appetite
  • Enlarged lymph nodes
  • Bleeding and bruising
  • Pallor
  • Shortness of breath

Labs, studies and physical exam findings

  • CBC with WBC’s as high as 150,000 with elevated granulocytes
    • neutrophils
    • eosinophils
    • basophils
  • Peripheral blood smear
  • Bone marrow biopsy – Philadelphia Chromosome is pathognomonic for CML

Treatment

  • Bone marrow transplant or stem cell transplant may be curative
  • Tyrosine kinase inhibitors
  • Myelosuppressive therapy
  • Splenectomy
  • Median survival had been between 3 & 5 years. With tyrosine kinase inhibitors and other medical treatment 7-10 years is more normal today.

Key terms and ideas

  • Acute lymphocytic leukemia (ALL)
    • Found in kids 2-5
    • Lots of circulating blasts
  • Chronic lymphocytic leukemia (CLL)
    • Patients are usually men over 50
    • Patients typically have no symptoms
  • Acute myelogenous leukemia (AML)
    • Found in adults
    • Pancytopenia with circulating blasts
    • Auer rods are pathognomonic for AML
  • Chronic myelogenous leukemia (CML)
    • Found in adults
    • Most patients are asymptomatic at diagnosis
    • Radiation exposure is a risk factor
    • Philadelphia Chromosome is pathognomonic for CML