Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL): An acute (sudden onset), rapidly progressing form of leukemia that is characterized by the presence in the blood and bone marrow of large numbers of unusually immature white blood cells destined to become lymphocytes. Acute lymphoblastic leukemia is also called acute lymphocytic leukemia and is abbreviated ALL (spoken not as the word “all”, but as the three letters A-L-L). ALL is the most common cancer occurring in children, representing almost 25% of cancer among children. There is a sharp peak in the incidence of ALL incidence among children ages 2 to 3. This peak is approximately fourfold greater than that for infants and is nearly 10-fold greater than that for youths who are 19 years old.

For unexplained reasons, the incidence of ALL is substantially higher for white children than for black children, with a nearly threefold higher incidence at 2 to 3 years of age for white children compared to black children. The incidence of ALL appears to be highest in Hispanic children.

Factors associated with an increased risk of ALL have been identified. The main environmental factor is radiation, namely prenatal exposure to x-rays or postnatal exposure to high doses of radiation. Children with Down syndrome (trisomy 21) also have an increased risk for both ALL and acute myeloid leukemia (AML). About two-thirds of acute leukemia in children with Down syndrome is ALL. Increased occurrence of ALL is also associated with certain genetic conditions, including neurofibromatosis, Shwachman syndrome, Bloom syndrome, and ataxia telangiectasia.

The malignant lymphoblasts from a particular ALL patient carry antigen receptors unique to that patient. There is evidence to suggest that the specific antigen receptor may be present at birth in some patients with ALL, suggesting a prenatal origin for the leukemic clone. Similarly, some patients with ALL characterized by specific chromosome translocations have been shown to have cells containing the translocation at the time of birth.

Seventy-five to 80% of children with ALL now survive at least 5 years from diagnosis with current treatments that incorporate systemic therapy (e.g., combination chemotherapy) and specific central nervous system (CNS) preventive therapy (i.e., intrathecal chemotherapy with or without cranial irradiation). Ten-year event-free survival of multiple large prospective trials conducted in different countries for children treated primarily in the 1980s is approximately 70%.

Since nearly all children with ALL achieve an initial remission, the major obstacle to cure is bone marrow and/or extramedullary (e.g., CNS, testicular) relapse. Relapse from remission can occur during therapy or after completion of treatment. While the majority of children with recurrent ALL attain a second remission, the likelihood of cure is generally poor, particularly for those with bone marrow relapse occurring while on treatment.