Chapter 55: The Acute Lymphocytic Leukemias

DEFINITION

• Acute lymphocytic (syn. 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.

• Treatment of ALL has progressed incrementally, beginning with the development of effective therapy for central nervous system (CNS) disease, followed by intensification of early treatment.

• Based on National Cancer Institute statistics, patients with ALL <45 years of age have a 5-year survival of 75 percent, which is heavily influenced by the approximately 80 percent cure rate in children with the disease. The 5-year survival is approximately 25 percent in the age group 45 to 54 and decreases in each succeeding decade to approximately 6 percent in patients over 65 years.

ETIOLOGY AND PATHOGENESIS

• 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).

• Chemical carcinogens have been studied for a potential role in causation but no unambiguous associations have been found.

• High-dose ionizing radiation, as experienced by atomic bomb survivors, may increase the risk for ALL.

• Nonionizing electromagnetic radiation is not a causal factor.

Incidence

• The age-adjusted incidence rate of ALL is 1.6 per 100,000 men and women per year in the United States.

  — It is estimated that 5430 cases (3220 males and 2210 females) were diagnosed with ALL in 2008 in the United States.

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

  — ALL is the most common malignancy diagnosed in patients younger than age 15 years, accounting for 23 percent of all cancers and 76 percent of all leukemias in this age group.

• Only 20 percent of adult acute leukemias are ALL.

• 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.

• Incidence rises again in the sixth decade and reaches a second, smaller peak in the elderly.

• 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.

• Hyperleukocytosis (>100 × 10⁹ white cells/L) occurs in 12 percent of white children, and 23 percent of black children and in 16 percent of adults.

Risk Factors

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