Hematology· Topic 6.3 Leukocyte disorders· 6.3.2

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia is a clonal proliferation of lymphoid precursor blasts that replace the bone marrow, the most common cancer in children, diagnosed when TdT-positive lymphoblasts make up 20% or more of the marrow and classified by flow cytometry immunophenotype and cytogenetics. Treatment is multi-phase chemotherapy (induction, consolidation, CNS prophylaxis, maintenance for up to 2 years), with a tyrosine kinase inhibitor added for Philadelphia-chromosome-positive disease and aggressive tumor lysis prophylaxis at the start of therapy.

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What this article covers

  • Overview

    Definition: acute lymphoblastic leukemia (ALL) is a clonal, uncontrolled proliferation of an immature lymphoid precursor cell (lymphoblast) that infiltrates and replaces the bone marrow, spills into…

  • Epidemiology

    Peak incidence in early childhood: ALL is far more common in children than adults; adults account for a minority of cases but have inferior outcomes even with pediatric-style regimens.

  • Risk factors

    Down syndrome (trisomy 21): the strongest recognized genetic association; ALL is the more likely acute leukemia after age 5, whereas AML predominates before age 5.

  • Pathophysiology

    Clonal arrest of a lymphoid precursor: an acquired genetic alteration blocks normal maturation of a B- or T-lymphoid progenitor at an immature (blast) stage while allowing unchecked proliferation.

  • Clinical features

    Marrow-failure triad: fatigue and pallor from anemia, bleeding (gingival, petechiae, epistaxis) from thrombocytopenia, and fever or infection from functional neutropenia, developing over days to weeks.

  • Differential diagnosis

    Acute myeloid leukemia: also ≥ 20% marrow blasts and marrow failure, but blasts are myeloperoxidase-positive, may show Auer rods, and lack TdT; gingival hyperplasia suggests a monocytic AML subtype (acute myeloid leukemia).

  • Diagnosis

    Establish the diagnosis by marrow blast percentage plus lineage-defining immunophenotype: the defining threshold is ≥ 20% lymphoblasts in peripheral blood or bone marrow, with the blasts confirmed as…

  • Management

    Stabilize oncologic emergencies before or alongside induction: treat symptomatic leukostasis (WBC typically 50,000-100,000/mm³) with urgent cytoreduction (induction chemotherapy, leukapheresis, or…

  • Complications

    Tumor lysis syndrome: hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, and acute kidney injury, most likely with bulky, high-blast-count disease at the start of cytoreductive therapy.

  • Prognosis

    Age is the dominant prognostic factor: ALL in children is often curable, whereas survival in adults remains inferior despite pediatric-style regimens.

  • Prevention

    No proven primary prevention: no established modifiable-risk-factor strategy prevents de novo ALL; prevention efforts instead target complications of disease and treatment.

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