Hematological System Notes

Basics of Leukocytes and Lymphatic Systems

  • Leukocytes: White blood cells.
  • Types of White Blood Cells:
    • Eosinophils
    • Basophils
    • Neutrophils
    • Monocytes
    • Lymphocytes
      • B cells: Mature into plasma cells, secrete antibodies.
      • T cells: Mature into helper T cells, regulatory T cells, or killer T cells.
  • Production: All white blood cells are produced in the bone marrow.

Lymphoid System

  • Function: Sites for white blood cell residence, proliferation, differentiation, or function.
  • Primary Lymphoid Organs:
    • Bone marrow
    • Thymus
  • Secondary Lymphoid Organs:
    • Spleen: Filters old, injured, or dead white and red blood cells.
    • Lymph nodes: High concentrations of WBCs, filter interstitial fluid to trap pathogens before they spread to the blood stream.
    • Tonsils
    • Peyer patches

Alterations of Leukocytes and Lymphatic Systems

  • Leukocytosis: Higher than normal amounts of leukocytes.
    • Normal response to infection or physiological stress.
    • Pathological in malignancies and hematologic disorders.
  • Leukopenia: Deficiencies in the quality or quantity of leukocytes.
    • Decreased quantity: Decreased production in bone marrow, accelerated destruction of leukocytes, or in response to infection.
    • Decreased quality: Alterations to leukocytes so that they lose their function.
    • Leukopenia is never normal and is always pathological.

Alterations in Neutrophil Quantity

  • Neutrophilia/Granulocytosis: High levels of neutrophils.
    • Commonly occurs in response to infections, inflammation, or steroid medications.
    • Left shift: Production of immature neutrophils associated with infection or leukemia.
  • Neutropenia/Granulocytopenia: Low levels of neutrophils.
    • May be caused by infection, decreased production, increased destruction, or sequestration.
    • Agranulocytosis: Complete absence of granulocytes.
    • Associated with increased risk of life-threatening persistent and recurrent infections.

Alterations in Eosinophil/Basophil Quantity

  • Eosinophilia/Basophilia: High eosinophil/basophil counts.
    • Typically associated with hypersensitivity reactions, anaphylaxis, or parasitic infections.
  • Eosinopenia: Low eosinophil counts.
    • Typically seen due to migration of cells to inflammatory site.
    • Other causes: stress, surgery, trauma, shock, burns.
  • Basopenia: Low basophil counts.
    • Typically occurs in acute infections, hyperthyroidism, and long-term steroid therapy.

Alterations in Monocyte Quantity

  • Monocytosis: High monocyte counts.
    • Typically associated with bacterial infections, later stage infections, or chronic infections.
  • Monocytopenia: Low monocyte counts.
    • Rare and not well-known.

Alterations in Lymphocyte Quantity

  • Lymphocytosis: High lymphocyte counts.
    • Typically associated with viral infections.
    • May also see in leukemias and lymphomas.
  • Lymphocytopenia: Low lymphocyte counts.
    • Immune deficiencies, drug destruction, viral destruction, radiation, or acquired immunodeficiency syndrome (AIDS).

Complete Blood Count (CBC) with Differential

  • Includes various tests with results, flags, units, and reference intervals.
  • Key components include:
    • WBC (White Blood Cell count)
    • RBC (Red Blood Cell count)
    • Hemoglobin
    • Hematocrit
    • MCV (Mean Corpuscular Volume)
    • MCH (Mean Corpuscular Hemoglobin)
    • MCHC (Mean Corpuscular Hemoglobin Concentration)
    • RDW (Red Cell Distribution Width)
    • Platelets
    • Neutrophils
    • Lymphocytes
    • Monocytes
    • Eosinophils
    • Basophils
    • Immature Granulocytes

Leukemias

  • Malignant disorders of leukocytes in the bone marrow and blood.
  • Uncontrolled proliferation of malignant leukocytes leads to overcrowding of bone marrow.
    • Decreased production and function of normal hematopoietic cells (less red blood cells, less platelets, and less normal white blood cells - pancytopenia).
  • Malignant cells may infiltrate and accumulate in other organs such as liver, spleen, and lymph nodes.

Leukemia Classification

  • Based on:
    • Predominant cell of origin: lymphoid (lymphocytes) or myeloid (all WBCs other than lymphocytes).
    • Rate of progression: acute or chronic.
  • Four main types:
    • Acute lymphocytic leukemia (ALL)
    • Acute myeloid leukemia (AML)
    • Chronic lymphocytic leukemia (CLL)
    • Chronic myeloid leukemia (CML)

Leukemia: Acute vs. Chronic

  • Acute:
    • Presence of immature blast cells.
    • Rapidly progressing.
    • Shorter life expectancy after diagnosis (can be improved with new treatment modalities).
  • Chronic:
    • Presence of mature cells rather than immature blast cells.
    • Slower progression.
    • Longer life expectancy.
    • Note: Chronic leukemias may evolve into acute leukemias.

Leukemia Symptoms

  • Acute:
    • Common clinical manifestations: bone pain due to infiltrates, weight loss, night sweats, frequent infections, anemia, bleeding, and liver/spleen/lymph node enlargement.
  • Chronic:
    • Clinical manifestations are similar to acute leukemia, but onset of symptoms will be insidious and slow (most are asymptomatic on diagnosis).

Acute Lymphocytic Leukemia (ALL)

  • Aggressive and fast-growing leukemia characterized by more than 30% lymphoblasts in blood or bone marrow.
  • Most common childhood leukemia.
  • Risk factors: exposure to prenatal diagnostic radiation, high dose radiation, chemotherapy, genetic disorders, positive family history.
  • Pathophysiology:
    • Chromosomal abnormalities lead to uncontrolled expression of transcription factors regulating B and/or T cell development.
    • B and/or T cells stop maturing, leading to proliferation of more immature B and T cells.
  • Treatment:
    • Consult an experienced oncologist/hematologist!
    • Need to distinguish between ALL and AML due to differences in medications and prognosis.
    • Mainstay of treatment is through chemotherapy, stem cell and bone marrow transplant, and supportive care (antibiotics, antivirals, antifungals, blood transfusions, increased nutrition).
  • Prognosis:
    • Depends on a multitude of factors, including the type of ALL and the type of genetic abnormality.
    • Overall 5-year survival for ages >20 is 37%.
    • Overall 5-year survival for ages <20 is 89%.

Acute Myeloid Leukemia (AML)

  • Aggressive and fast-growing leukemia characterized by excessive myeloblasts.
  • Most common acute leukemia in adults older than 50 years of age.
  • Risk factors: exposure to radiation, benzene, chemotherapy, and positive family history.
  • Pathophysiology:
    • Chromosomal abnormalities lead to uncontrolled expression of transcription factors regulating leukocyte development.
    • Leukocytes stop maturing, leading to proliferation of more immature leukocytes.
  • Treatment:
    • Consult an experienced oncologist/hematologist!
    • Need to distinguish between ALL and AML due to differences in medications and prognosis.
    • Mainstay of treatment is through chemotherapy, stem cell and bone marrow transplant, and supportive care (antibiotics, antivirals, antifungals, blood transfusions, increased nutrition).
  • Prognosis:
    • Depends on a multitude of factors, including the type of AML and the type of genetic abnormality.
    • Overall 5-year survival for ages >20 years is 25%.
    • Overall 5-year survival for ages <20 is 67%.

Chronic Lymphocytic Leukemia (CLL)

  • Slow and insidious leukemia characterized by excessive lymphocytes.
  • Most common leukemia in western countries.
  • Primarily affects adults.
  • Typically results from malignant proliferation and progressive accumulation of monoclonal B lymphocytes (less commonly results due to T cells).
    • Malignant B cells are unable to fully mature into plasma cells, which leads to hypogammaglobulinemia à increased risk of infection.
  • Treatment:
    • Based on type of CLL and overall prognosis.
    • May start with observation period with supportive care (treat infections, and bleeding complications).
    • More aggressive treatments may be used for later stage CLL including chemotherapy and/or stem cell and/or bone marrow transplant.
    • No survival advantage comparing immediate vs delayed treatment of early stage disease.
  • Prognosis:
    • Depends on multitude of factors including type and stage of CLL.
    • Overall 5-year survival rate is 85%.

Chronic Myeloid Leukemia (CML)

  • Slow and insidious leukemia characterized by excessive myeloid cells.
    • Myeloid cells can refer to all white blood cells that are not lymphocytes.
  • Belongs to a family of myeloproliferative diseases.
    • Red blood cells (polycythemia vera) or platelets (essential thrombocytosis).
  • Primarily affects adults (peak incidence from ages 40s to 50s).
  • Commonly associated with the bcr-abl protein on the Philadelphia chromosome.
  • Different stages of CML:
    • Chronic phase: mild to no symptoms.
    • Accelerated phase: development of symptoms.
    • Blast phase (blast crisis): life-threatening complications from excessive proliferation of malignant cells leading to symptoms similar to AML.
  • Treatment is based on type of CML and stage:
    • Includes observation periods, chemotherapy, stem cell and/or bone marrow transplant.
  • Prognosis:
    • Depends on multitude of factors including type and stage of CML.
    • Overall 5-year survival rate is 69%.

Lymphomas

  • Diverse group of neoplasms that develop from the proliferation of malignant lymphocytes in the lymphoid system.
  • Typically originate from lymph nodes or lymphoid tissues of the stomach or intestines.
  • Incidence of lymphoma is associated with genetic mutations or viral infections.
    • Risk of developing lymphoma increases with immunodeficiency syndromes.
  • Two main types of lymphomas:
    • Hodgkin lymphoma
    • Non-Hodgkin lymphoma

Lymphadenopathy

  • Normal lymph nodes should not be palpable or painful.
  • Lymphadenopathy refers to an enlarged lymph node.
    • These lymph nodes are typically also painful to touch.
  • Lymphadenopathy may be a sign of inflammation, infection, or malignancy.
    • While lymphadenopathy may occur in leukemias, they are more common in lymphomas.

Hodgkin Lymphoma

  • Malignant lymphomas are characterized by the presence of abnormal B cells called Reed-Sternberg cells.
    • B cells that are exposed to factors such as Epstein Barr virus which trigger that cell to undergo malignant transformation into Reed-Sternberg cells.
    • These cells then secrete cytokines and growth factors that induce local and systemic inflammation.
    • Inflammation causes obstruction of the lymph node which then leads to a build up of pressure à lymphadenopathy.
  • Presence of Reed-Sternberg cells are not specific to Hodgkin but they are required for diagnosis.
  • This pressure and obstruction can cause lymphadenopathy in any of the lymph nodes leading to clinical manifestations of:
    • Localized lymphadenopathy (typically painless).
    • Unexplained mediastinal or abdominal masses.
  • Other common signs and symptoms include fever, weight loss, night sweats, itchy skin (pruritis).
  • Treatment:
    • 75% cure rate with appropriate treatment.
    • Combination of radiation, chemotherapy, and/or bone marrow or stem cell transplantation.
  • Prognosis:
    • 5-year survival is 75-90% depending on stage of lymphoma at time of diagnosis.
    • Key is early detection!
    • Consider in patients with fever of unknown origin or unexplained persistent lymphadenopathy.

Non-Hodgkin Lymphoma

  • Recently reclassified and re-named as B-cell neoplasms and T-cell and NK-cell neoplasms.
  • Do not contain Reed-Stenberg cells.
  • Risk factors include exposure to mutagens, infections from certain viruses including Epstein-Barr virus, and immunodeficiency.
  • B cells, T cell, or NK cells experience chromosomal translocations that lead to activation of oncogenes and suppression of tumor-suppression genes.
    • Results in uncontrolled proliferation and cell growth.
  • Clinical manifestations are similar to Hodgkin lymphoma (must biopsy lymph node to differentiate).
    • Tends to have more generalized lymphadenopathy than Hodgkin.
  • Treatment depends on type of non-Hodgkin lymphoma.
    • Usually combination of radiation, chemotherapy, and monoclonal antibodies.
  • Prognosis:
    • Dependent on type.
    • Overall 5-year survival is 59%.

Lymphoma Mimics

  • Certain conditions may mimic lymphoma and cause clinical confusion such as:
    • Tuberculosis
    • Syphilis
    • Systemic lupus erythematosus
    • Lung and bone cancers
    • Leukemias

Other Blood Cancers

  • Plasma Cell Malignancies:
    • Multiple myeloma
    • Waldenstrom macroglobinemia (now considered a type of Non-Hodgkins lymphoma)