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  • Acute lymphoblastic leukemia (ALL) is a neoplastic disease of immature lymphocytes or lymphocyte progenitor cells of either the B- or T-cell lineage.

  • The immune phenotype of the leukemia cells reflects the cell lineage and differentiation stage of the transformed clone.

  • At diagnosis, the leukemia cells typically have replaced normal cells in the marrow and have disseminated to various extramedullary sites, accounting for many of the clinical manifestations.

  • Both immunologic and genetic subgroups have therapeutic implications.

  • Survival for patients with ALL has improved, with nearly 90% of children and 40% of adults achieving long-term disease-free survival, although patients older than 60 years of age still have a poor prognosis.


  • Initiation and progression of ALL are driven by successive mutations that alter cellular functions, including an enhanced ability of self-renewal, a subversion of control of normal proliferation, a block in differentiation, and an increased resistance to death signals (apoptosis).

  • Ionizing radiation has been implicated as a risk factor for ALL, largely based on the studies conducted at Hiroshima and Nagasaki following the atomic bomb detonations. High birth weight has been associated with an increased risk in the first 5 years of life. Certain congenital (Down syndrome) or inherited abnormalities may increase the risk of later developing ALL. There is ambiguous, inconclusive, or little evidence for other risk factors for this disease (eg, prior chemotherapy, smoking, chemical exposures).


  • Between 1975 and 2016 the age-adjusted incidence rate of ALL was 1.6 per 100,000 men and 1.2 per 100,000 women per year in the United States.

    — It is estimated that 5930 cases (3280 males and 2650 females) were diagnosed in 2019 in the United States.

    — The median age at diagnosis for ALL is 13 years, and approximately 61% of cases are diagnosed before the age of 20 years.

    — ALL is the most common malignancy diagnosed in patients younger than age 20 years, accounting for 23% of all cancers and 76% of all leukemias in this age group.

  • Only 20% of adult acute leukemias have a lymphoblastic phenotype.

  • Age-specific incidence patterns are characterized by a peak between the ages of 2 and 4 years, followed by falling rates during later childhood, adolescence, and young adulthood (Figure 55–1).

  • Incidence rises again in the sixth decade.

  • The incidence of ALL differs substantially in different geographic areas.

    — Rates are higher among populations in northern and western Europe, North America, and Oceania, with lower rates in Asian and African populations.


Age-specific incidence rates for acute lymphoblastic leukemia by sex. (Data from SEER Cancer Statistics Review, 1975–2012, National Cancer Institute. Bethesda, MD,

Risk Factors

  • Children with Down syndrome have a 10- to 30-fold increased risk of acute leukemias, including ALL.

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