Leukemia

Chapter 8 Hematology

1. Acute Leukemia

  • Definition: Neoplastic proliferation of blasts (>20% in bone marrow).

  • Consequences: Crowding out normal hematopoiesis leads to anemia, thrombocytopenia, and neutropenia.

  • Presentation: Elevated WBC count with large, immature blasts.

A. Acute Lymphoblastic Leukemia (ALL)

  • Characteristics: Neoplastic accumulation of lymphoblasts.

  • Diagnosis: Positive nuclear staining for TdT.

  • Demographics: Common in children, associated with Down syndrome (post-5 years).

  • Subtypes: B-ALL, T-ALL (based on surface markers).

B. Acute Myelogenous Leukemia (AML)

  • Characteristics: Neoplastic accumulation of myeloblasts.

  • Diagnosis: Positive cytoplasmic staining for myeloperoxidase (MPO); Auer rods present.

  • Demographics: Common in adults (average age 50-60).

2. Clinical Presentation of Acute Leukemia

  • Symptoms of bone marrow failure: Fatigue, bleeding, infections.

  • Pancytopenia: Can occur despite WBC elevation.

  • Organ involvement: Liver, spleen, lymph nodes enlarged; bone pain common.

  • CNS involvement: Especially in M4/M5 monocytic leukemia.

  • Leukostasis syndrome: Severe elevation in WBC leading to headaches, confusion, dyspnea.

3. Diagnosis

  • Initial test: CBC often shows elevated WBC, anemia, thrombocytopenia.

  • Definitive test: Bone marrow biopsy (>20% blasts).

  • Flow cytometry distinguishes leukemic subtypes.

4. Treatment

  • Initial Therapy: Chemotherapy for remission; >99.9% reduction in leukemic cells.

  • Prognosis Indicators: Cytogenetics.

  • Special Considerations: APL (acute promyelocytic leukemia) treated with ATRA due to high DIC risk.

5. Chronic Leukemias

A. Chronic Myelogenous Leukemia (CML)

  • Characteristics: High WBC with basophilia; Philadelphia chromosome (BCR-ABL).

  • Symptoms: Fatigue, night sweats, splenomegaly.

  • Leukostasis possible from high WBC count.

  • Diagnosis: PCR for BCR-ABL, confirm with peripheral blood findings.

B. Chronic Lymphocytic Leukemia (CLL)

  • Characteristics: Clonal proliferation of B lymphocytes; often asymptomatic.

  • Demographics: Most common leukemia in the US, primarily older adults (>50).

  • Symptoms: Lymphadenopathy, splenomegaly; fatigue.

  • Diagnosis: Elevated WBC with 80-98% lymphocytes; smudge cells.

6. Hairy Cell Leukemia

  • Characteristics: Proliferation of B cells with hair-like projections; primarily in older adults.

  • Symptoms: Pancytopenia, splenomegaly.

  • Diagnosis: Peripheral smear and flow cytometry for hairy cells.

  • Treatment: Purine analogs like cladribine.

7. Myelodysplastic Syndrome (MDS)

  • Definition: Preleukemic disorder with pancytopenia and hypercellular bone marrow.

  • Characteristics: 5q deletion common with better prognosis.

  • Diagnosis: CBC reveals elevated MCV, bone marrow shows hypercellularity.

  • Treatment: Supportive care, specific agents like lenalidomide.

8. Myeloproliferative Disorders

  • Definition: Neoplastic proliferation of mature myeloid cells.

  • Common Disorders:

    • Polycythemia Vera: RBC overproduction due to JAK2 mutation.

    • Essential Thrombocythemia: Elevated platelets.

    • Myelofibrosis: Bone marrow fibrosis, often seen in older adults.

  • Symptoms: Hyperviscosity, hypertension, splenomegaly for PV.

  • Diagnosis: Elevated RBC count, low EPO in PV; JAK2 mutation key.

  • Treatment: Phlebotomy, hydroxyurea for PV; symptom management.