12- Acute Leukemia

Section 12: Acute Leukemia

Definition

  • Acute Leukemia: Neoplastic proliferation of >20% blasts in the bone marrow.

    • Blasts: Large immature cells often characterized by punched-out nucleoli.

    • Accumulation: Caused by mutations preventing white blood cell maturation.

    • Consequences: High white blood cell count due to immature blasts entering the bloodstream.

Pathophysiology

  • Immature blasts fail to perform normal functions, leading to perceived deficiencies.

    • Hematopoiesis Inhibition: The accumulation of blasts disrupts the production of other blood cells.

    • Effects on Blood Cells:

      • RBCs: Decreased production leads to anemia.

      • Megakaryocytes: Decreased leads to thrombocytopenia (bleeding).

      • Myelocytes (Neutrophils): Decreased leads to neutropenia (increased infection risk).

Clinical Presentation

  • Symptoms:

    • Fatigue (anemia).

    • Bleeding (thrombocytopenia).

    • Infection (neutropenia).

Types of Acute Leukemia

  • Main Types:

    • Acute Lymphoblastic Leukemia (ALL)

    • Acute Myelogenous Leukemia (AML)

Acute Lymphoblastic Leukemia (ALL)

  • Defined as the presence of lymphoblasts in the bone marrow (>20%).

    • Common in Children: Especially those with Down syndrome over age 5.

    • Subtypes:

      • B-cell ALL (B-ALL)

        • Markers: TdT, CD10, CD19, CD20 (CD10 differentiates immature B cells).

        • Prognosis:

          • Good: Translocation between chromosomes 12 and 21.

          • Poor: Translocation between chromosomes 9 and 22.

      • T-cell ALL (T-ALL)

        • Markers: TdT, CD2 to CD8.

        • Clinical Presentation: Often presents as a mediastinal mass in teens; potential for dysphagia and dyspnea due to mass effect.

Acute Myelogenous Leukemia (AML)

  • Defined as accumulation of immature myeloid cells.

    • Typical Age: Adults aged 50-60.

    • Histological Features: Presence of Auer rods (myeloperoxidase positive).

    • Subtypes:

      • Acute Promyelocytic Leukemia (APL)

        • Due to translocation of chromosomes 15 and 17 affecting retinoic acid receptor.

        • Treatment: All-trans retinoic acid (ATRA) which promotes maturation of blasts.

        • Complications: Associated with DIC (Disseminated Intravascular Coagulation).

      • Acute Monocytic Leukemia

        • Involves proliferation of monoblasts.

        • Characteristic swelling of gums due to blast infiltration.

      • Acute Megakaryoblastic Leukemia

        • Proliferation of megakaryoblasts; associated with Down syndrome under age 5.

Key Distinctions

  • Markers Summary:

    • B-ALL: TdT, CD10, CD19.

    • T-ALL: TdT, CD2 through CD8.

    • AML: Auer rods (myeloperoxidase positive).

    • APL: Myeloperoxidase positive; thrombotic complications.

    • Acute Monocytic and Megakaryoblastic leukemia: Myeloperoxidase negative.

Case Review Questions

  • Example Question for T-ALL:

    • 15-year-old male: Symptoms and lab findings suggestive of T-ALL; likely markers TdT, CD2 to CD8.

  • Example Question for APL:

    • 40-year-old male: Symptoms and lab findings indicating acute promyelocytic leukemia; identified by myeloperoxidase crystals.

Conclusion

  • Recap key points from various types of acute leukemia, highlighting symptoms, complications, and diagnostic markers for each subtype.