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For further information, see CMDT Part 15-29: Acute Leukemia

KEY FEATURES

Essentials of Diagnosis

  • Symptoms, including fatigue, fever, and bleeding, are of short duration

  • Cytopenias or pancytopenia

  • Blasts in peripheral blood in 90% of cases

  • > 20% blasts in bone marrow

General Considerations

  • A malignancy of the hematopoietic progenitor cell; cells proliferate in uncontrolled fashion and replace normal bone marrow elements

  • Most cases arise with no clear cause

  • Radiation and some toxins (benzene) are leukemogenic; chemotherapeutic agents (cyclophosphamide, melphalan, other alkylating agents, and etoposide) may cause leukemia

  • Acute myeloid leukemia (AML) is primarily categorized based on recurrent structural chromosomal and molecular abnormalities

  • Acute promyelocytic leukemia (APL)

    • Characterized by chromosomal translocation t(15;17)

    • Has different biology and treatment

  • Acute lymphoblastic leukemia (ALL) is classified by immunologic phenotype as B- or T-cell lineage

  • Cytogenetics are single most important prognostic factor

  • Acute leukemia of ambiguous lineage (ALAL)

    • Consists of blasts that lack differentiation along the lymphoid or myeloid lineage or blasts that express both myeloid and lymphoid lineage-specific antigens

    • Considered very-high risk and has a poor prognosis

Demographics

  • ALL comprises 80% of acute leukemias of childhood; peak incidence is between ages 3 and 7 years

  • ALL is also seen in adults, causing ∼20% of adult acute leukemias

  • AML chiefly occurs in adults with median age at presentation of 60 years and increasing incidence with advanced age

CLINICAL FINDINGS

Symptoms and Signs

  • Clinical findings are due to replacement of normal bone marrow or infiltration of organs (skin, gastrointestinal tract, meninges)

  • Gingival bleeding, epistaxis, or menorrhagia common

  • Less commonly, widespread bleeding from disseminated intravascular coagulation (DIC) (in APL and monocytic leukemia)

  • Increased susceptibility to infection when neutrophil count < 500/mcL (0.5 × 109/L)

    • Death may occur within a few hours if treatment is delayed

    • Signs of infection may be absent

    • Common presentations include cellulitis, pneumonia, and perirectal infections

    • Fungal infections (eg, Candida, Aspergillus) are also commonly seen

  • Pallor, purpura, and petechiae are common

  • Hepatosplenomegaly and lymphadenopathy are variable

  • Bone tenderness, particularly of the sternum, tibia, and femur

  • Hyperleukocytosis

    • Seen in patients who complain of gum hypertrophy and bone and joint pain

    • Circulating blast count is markedly elevated (total white blood cell (WBC) count > 100,000/mcL [100 × 109/L])

    • Leads to impaired circulation, presenting as headache, confusion, and dyspnea

Differential Diagnosis

  • AML

    • Chronic myeloid leukemia

    • Myelodysplastic neoplasms

    • Left-shifted bone marrow recovering from toxic insult

  • ALL

    • Chronic lymphocytic leukemia

    • Small lymphocyte lymphoma

    • Hairy cell leukemia

    • Atypical lymphocytosis of mononucleosis or pertussis

DIAGNOSIS

Laboratory Tests

  • Combination of pancytopenia with circulating blasts on peripheral smear

  • Blasts absent from peripheral smear in up to 10% ("aleukemic leukemia")

  • Hyperuricemia may occur

  • DIC

    • Serum ...

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