Acute lymphoblastic leukemia (ALL) is characterized by the expansion and proliferation of lymphoid cells in the bone marrow, blood, and other organs. ALL occurs with an incidence of 1 to 1.5 per 100,000 population, although with a bimodal distribution: an early peak at around the age of 4 to 5 years where the incidence may be as high as 4 to 5 per 100,000 population, followed by a second gradual increase at around age 50 years where it reaches up to 2 per 100,000 population. ALL represents the most common childhood pediatric leukemia representing about 80% of acute leukemias, while it comprises only 20% of adult leukemias. The median age of ALL patients in most registry studies is between 25 and 35 years. ALL is the most common type of cancer in children aged 0 to 14 years and is relatively uncommon in late childhood, adolescence, and young adulthood (1–4).
The etiology of ALL remains unknown (5,6). Chromosomal translocations occurring in utero during fetal hematopoiesis have been suggested as the primary cause for pediatric ALL, whereas postnatal genetic events are suggested as secondary contributors. A higher incidence of ALL is noted among mono and dizygotic twins of patients with ALL, reflecting possible genetic predisposition (7–9). Patients with trisomy 21, Klinefelter syndrome, and inherited diseases with excessive chromosomal fragility such as Fanconi anemia, Bloom syndrome, and ataxia-telangiectasia have a higher risk of developing ALL (10–14). Implications have also been made toward infectious etiologies (15,16). Associations between human T-cell lymphotropic virus type 1 and adult T-cell leukemia/lymphoma, as well as HIV and lymphoproliferative disorders have been established (17,18). In addition, associations with varicella and influenza viruses have also been suggested (19).
Clinical presentation of ALL is usually nonspecific. Symptoms typically include fatigue, lack of energy, easy bruising or obvious bleeding, dyspnea, dizziness, and infections. "B-symptoms" such as fever, night sweats, or weight loss can occur. Extremity and joint pain may be the only presenting symptoms in children. Whereas symptoms related to hyperleukocytosis can occur in acute myeloid leukemia (AML), they are rare in ALL, even in the presence of high white cell counts. Central nervous system (CNS) involvement (cranial neuropathies, meningeal infiltration) at presentation, common in mature B-ALL (Burkitt leukemia) occurs in 5 to 8% of patients (20). Abdominal masses and significant spontaneous tumor lysis syndrome are more likely with mature B-ALL. Lymphadenopathy and hepatosplenomegaly, rarely symptomatic, are noted in 20% of the patients, with a higher incidence in T-cell ALL and mature B-cell ALL. The combination of hypercalcemia and lytic bone lesions is suggestive of adult T-cell leukemia/lymphoma (ATLL). Chin numbness (mental nerve involvement), when elicited in the history or exam, is suggestive or mature B-cell ALL (Burkitt).
The diagnosis of ALL relies on assessment of morphology, flow cytometry immunophenotyping, and identification of cytogenetic-molecular abnormalities (Fig. ...