Synonyms

ALL

Definition

Acute lymphoblastic leukemia (ALL) is a form of cancer of the white blood cells (leukocytes). ALL is the most common type of childhood leukemia and is distinguished from chronic lymphoblastic leukemia (CLL) and acute myeloid (or myelogenous) leukemia, which are more prevalent in adults.

Current Knowledge

Symptoms

ALL is characterized by the rapid proliferation of immature blood cells (lymphoblasts), which crowd out mature, functional cells. It is associated with the enlargement of lymphoid tissue in areas including the lymph nodes, spleen, bone marrow, and lungs and with increased lymphocytic cells circulating in blood and in various tissues and organs. Persons afflicted will experience weakness and fatigue, anemia, unexplained fever and infections, weight loss, or loss of appetite.

Pathophysiology

Cancer, including ALL, is caused by damage to DNA.

Treatment

The earlier the ALL is detected, the more effective is its treatment. The goal is to induce a lasting remission, considered to be a prevalence of less than 5% of lymphoblasts in bone marrow. Advances made in the ability to match the genetic properties of the blast cells to treatment options, in association with the availability of new drugs and improvements made in bone marrow and stem cell transplantation, have changed the prognosis for ALL from a zero to a 75% survival rate over the past 40 years.

Most (if not all) patients with a childhood history of ALL have brain atrophy. MRI has also demonstrated white matter changes in a minority of children. A large study identified reduced cortical gray and white matter, caudate nucleus, amygdala, and hippocampus in adult survivors in both those who were not treated with cranial irradiation and those who were. Whereas atrophy is associated with treatment-effects of cranial irradiation therapy and intrathecal chemotherapy (usually methotrexate), it can also occur as a result of the condition, itself, rather than as an outcome of treatment, as it appears to cause atrophy of the brain, which is not specific to certain brain tissues (Lucy Rorke, M.D., personal communication); however, few children with ALL are naïve to chemotherapy and radiotherapy, and the effects of time are not controlled in studies so that the developmental effects of damage from the disease and from the treatments both magnify over time. A study to discriminate the effects of treatment versus disease would require studies of children with ALL at diagnosis and prior to treatments. Nonetheless, the strongest detrimental impacts on cognition are attributable to treatment effects and their damaging influence on the biological substrates of core neurocognitive abilities, including executive functions (self-regulation, inhibitory control, cognitive flexibility, problem-solving), memory, verbal skills, and information processing. Such impacts disrupt the secondary abilities, i.e., those that are acquired and knowledge-based. The main approaches to alleviating neurocognitive effects of treatment include cognitive remediation, pharmacology, and ecological alterations in the classroom.

The presentation of survivors in adulthood is highly variable in both IQ and neuropsychological tests, with clinical factors intermediating, including polymorphisms that regulate inflammatory cytokine expression, cumulative dose, intensity of cancer therapy, age at diagnosis, years since diagnosis, and gender. Adult survivors are at heightened risk of neurocognitive disorders.

Cross-References