Leukemias and Lymphomas

Acute vs Chronic Leukemia

Overview of Leukemia Types

  • Acute
    • Usually affects 'younger' people
    • Abrupt onset of symptoms
    • More severe symptoms
    • Immature cell forms
  • Chronic
    • Usually affects 'older' people
    • Gradual onset of symptoms
    • Less severe symptoms
    • Differentiated cell forms

Major Types of Leukemia

  1. Acute Myeloid Leukemia (AML)

    • Myeloid (Granulocytic)
    • Characteristics:
      • Malignant cells are myeloblasts with Auer rods, which are linear structures within the blast cells
      • Symptoms include:
      • Anemia
      • Fatigue
      • Fever
      • Weight loss
      • Bleeding
      • Hepatosplenomegaly (enlargement of the liver and spleen)
      • Lymphadenopathy (swelling of lymph nodes)
    • Cellular Changes:
      • Malignant cells demonstrate alterations in chromosome structure and number including:
      • Absence or deletion of chromosomes
      • Translocation of genetic material
    • Prognosis:
      • Approximately 60% achieve complete remission with chemotherapy
      • Only 15% to 30% remain free from disease for 5 years
      • Bone marrow transplantation during the first remission yields a cure rate of 50-60%
    • Treatment:
      • Chemotherapy involving:
      • Mitotic inhibitors such as vincristine and l-asparaginase
      • Corticosteroids like prednisone for induction of remission
      • Maintenance phase with cytotoxic agents such as methotrexate and 6-mercaptopurine
      • CAR-T therapy may be used

  2. Acute Lymphoblastic Leukemia (ALL)

    • Lymphocytic (Agranulocytic)
    • Characteristics:
      • Peak incidence between 2-4 years of age
      • Accumulation of leukemic lymphoblasts in the bone marrow and blood
      • Symptoms include:
      • Anemia
      • Fatigue
      • Fever
      • Weight loss
      • Bleeding
      • Hepatosplenomegaly
      • Lymphadenopathy
    • Cellular Changes:
      • Alterations in chromosome structure such as:
      • Hyperdiploidy (more than 50 chromosomes)
      • Translocation of genetic material
    • Prognosis:
      • 90% of children achieve complete remission with modern chemotherapy
      • Approximately two-thirds can be considered cured
    • Treatment: Similar to AML with induction and maintenance phases

  3. Chronic Lymphocytic Leukemia (CLL)

    • Lymphocytic (Agranulocytic)
    • Characteristics:
      • Neoplastic disorder primarily of B lymphocytes; leukemic lymphocytes are more differentiated compared to ALL
      • Symptoms include:
      • Anemia
      • Fatigue
      • Fever
      • Weight loss
      • Bleeding
      • Hepatosplenomegaly
      • Lymphadenopathy
    • Cellular Changes:
      • Causes hypogammaglobulinemia, leading to increased susceptibility to bacterial infections
      • Over-expression of the bcl-2 gene, which immortalizes CLL cells
      • Trisomy 12 is the most common chromosomal abnormality found
    • Treatment:
      • Radiation and chemotherapy for long-term control
      • Corticosteroids to reduce high lymphocyte counts
      • CAR-T therapy may also be used

  4. Chronic Myelocytic Leukemia (CML)

    • Myeloid (Granulocytic)
    • Characteristics:
      • More common in middle-aged and older adults
      • Derived from malignant transformation of granulocytic precursors
      • Presence of Philadelphia chromosome in over 90% of cases, due to a reciprocal translocation between chromosome 9 and 22 (t(9:22))
      • Symptoms include:
      • Anemia
      • Fatigue
      • Fever
      • Night sweats
      • Weight loss
      • Bleeding
      • Hepatosplenomegaly
      • Lymphadenopathy
      • Markedly elevated leukocyte count (100,000 to 500,000 cells/uL)
    • Prognosis:
      • Slow progression of disease, with about 3-year survival without treatment
      • After 3 years, symptoms accelerate leading to a blast crisis, characterized by acute leukemia onset
      • Chemotherapy and radiation have little effect on survival; only bone marrow transplantation is curative
    • Treatment:
      • Gleevec (STI571), a drug that selectively targets CML cells by inhibiting a specific protein expression, minimizing side effects compared to traditional chemotherapy

Lymphoma

Overview of Lymphomas

  • Lymphomas are malignant neoplasms that result from genetic mutations or viral infections. These tumors are characterized by:
    • The proliferation of lymphocytes, histiocytes (macrophages), and their derivatives in the lymphoid tissues.
    • Uncontrolled and excessive growth of these cells leads to accumulation in lymph nodes.

Classification of Lymphomas

  1. By Predominant Neoplastic Cell:

    • B-cell lymphomas
    • T-cell lymphomas
    • Histiocytic lymphomas (rare)

  2. By Growth Pattern of Cells:

    • Nodular: clusters surrounded by fibrotic collagen bands
    • Diffuse: cells scattered throughout the node without fibrosis

  3. Staging:

    • Stage I: Malignant cells confined to a single node.
    • Stage II: Two or more lymph nodes affected on one side of the diaphragm.
    • Stage III: Lymph nodes involved above and below the diaphragm.
    • Stage IV: Multiple or disseminated foci of involvement.

Types of Lymphomas

1. Hodgkin's Lymphoma
  • Characteristics:
    • Notably features Reed-Sternberg cells, which are malignant transformed lymphocytes and the hallmark of Hodgkin's disease.
    • Nodular sclerosis is the most common appearance of lymph nodes affected by Hodgkin's lymphoma.
  • Symptoms:
    • Enlarged non-tender lymph nodes (e.g., cervical or inguinal)
    • Dry cough
    • Fever
    • Night sweats
  • Treatment:
    • Radiation and chemotherapy showing cure rates of about 90%
    • Stem cell transplant and immunotherapy may be options as well.