Epidemiology

• More common in Hispanics and whites and is less common in Asian/Pacific Islanders and blacks.

• Rare cases of familial ALL have been identified to be caused by TP53 mutations associated with the Li–Fraumeni syndrome. Approximately 50% of children with low-diploid ALL have this mutation.
• Somewhat more relevant to adult ALL is the association between occupational exposure to low-dose ionizing radiation and a slightly increased risk for leukemia, although findings were inconsistent across populations.
• Approximately 75% of cases are B-ALL, and 25% are T-ALL.
  • Compared with adults, children less often present with T-lineage ALL.
  • There is also a slightly higher incidence of myeloid antigen expression in adult ALL patients.

Clinical Presentation

• Virtually all adults diagnosed with ALL present with symptoms of only a few weeks duration.

• Marrow expansion by leukemic blasts may produce bone pain and arthralgias, but marrow necrosis is much less frequently found in adults as compared with children who have ALL.
• One-third of patients have bleeding symptoms at diagnosis, which is less frequent than in patients presenting with acute myeloid leukemia.
• The fewer than 10% of ALL patients who have CNS involvement infrequently present with referable symptoms, such as headache, vomiting, neck stiffness, alteration in mental status, and focal neurologic abnormalities.
  • ↑ risk with leukocytosis at diagnosis.
  • CNS 1: no blasts on cytospin
  • CNS 2: blasts on cytospin but CSF WBC < 5 cells/ml
  • CNS 3: blasts on cytospin with WBC ≥ 5 cells/ml
  • In case of traumatic tapping: CSF WBC/CSF RBC > 2x Blood WBC/Blood RBC
• Approximately one-third of patients have a platelet count less than 25000/μL, which is approximately the same proportion that present with bleeding symptoms. Circulating leukemic blasts may not be evident on examination of the peripheral smear in a significant number of patients.

Prognosis

• Traditionally, age (≥30-35), WBC count at presentation, immunophenotype, and time to CR were strong predictors of disease-free survival (DFS) and OS.
  • WBC ≥30000/μL in B-ALL or ≥100000/μL in T-ALL.
  • T-ALL was previously considered an unfavorable prognostic subgroup, but changes in treatment regimens have improved outcomes.
  • Failure to achieve CR within 4 weeks of starting treatment or after one course of induction chemotherapy has been considered an independent unfavorable prognostic factor.
    • 5-year OS rate 45% in CR patients vs. 5% who did not achieve CR.
    • Evaluation for persistence of leukemic blasts at even earlier time points, between days 7 and 21 of induction, was established as an important prognostic indicator for outcome in pediatric ALL, although risk-adapted therapy that results in later CR after consolidation often overcomes the negative predictive value of delayed blast clearance.

Classification

WHO 2016

FAB