The diagnosis of acute leukemia is confirmed by findings of immature blast cells on either the peripheral blood smear, bone marrow aspirate, or both. Most patients have abnormal blood counts; anemia and thrombocytopenia are common. The WBC count may be low, normal, or high; 15% to 20% of patients have a WBC count greater than 50,000/mm3. Definitive diagnosis requires the evaluation of cell surface markers (immunophenotype) by flow cytometry and evaluation of cytochemical staining patterns. Cytogenetic analysis should be undertaken in all cases of acute leukemia. Certain types of both lymphoid and myeloid leukemias have specific chromosomal abnormalities. In ALL, the t(12;21) translocation is most common (approximately 20% of all cases) and is associated with a favorable prognosis. The t(9;22) translocation occurs in less than 5% of cases and is associated with a poor prognosis. The t(4;11) translocation (and other translocations involving the MLL gene on chromosome 11) often occurs in infants and patients with secondary AML and is generally associated with a poor prognosis. Fluorescent in situ hybridization or polymerase chain reaction techniques are now used in most cases of leukemia because many chromosomal abnormalities may not be apparent on routine karyotypes. DNA microarray techniques are gaining relevance and will likely become standard in the future. A lumbar puncture should always be performed at the time of diagnosis to evaluate the possibility of CNS involvement. A chest x-ray should be obtained in all patients to exclude an anterior mediastinal mass, which is commonly seen in T-cell ALL. Electrolytes, calcium, phosphorus, uric acid, and renal and hepatic function should be monitored in all patients.
The differential diagnosis of acute leukemia includes nonmalignant and malignant diseases. Infection is probably the most common mimicker of acute leukemia, particularly the Epstein-Barr virus infection. Other infections (cytomegalovirus, pertussis, mycobacteria) also can produce signs and symptoms common to leukemia. Noninfectious diagnostic considerations include aplastic anemia, histiocytosis, juvenile rheumatoid arthritis, immune thrombocytopenic purpura, and congenital or acquired conditions that lead to neutropenia or anemia. Several malignant diagnoses also can mimic leukemia, including neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma. Newborns with trisomy 21 may have a condition known as transient myeloproliferative disorder, which produces elevated WBC counts with peripheral blasts, anemia, and thrombocytopenia. It usually resolves with supportive care only, but these children have a significantly increased risk (30%) of developing true acute leukemia (ALL or AML)within the next few months and years of life.