Acute leukemia represents 30–40 % of childhood cancers in the western population. Of leukemia, 75–80 % are of lymphoid types. ALL occurs with high frequency in the 2–5-year age group, while AML occurs more frequently in infants and adolescents. Undifferentiated or bilinear forms are seen in about 5 % of cases.

Hereditary predisposing factors to the types of leukemia are rarely found. However, a higher incidence of leukemia has been reported in patients with congenital agammaglobulinemia, Bloom syndrome, Shwachman syndrome, ataxia-telangiectasia, Li–Fraumeni syndrome, neurofibromatosis, Blackfan-Diamond syndrome, and Kostmann disease. The risk of developing leukemia is 10–20 times higher in children with Down syndrome compared to the general childhood population.

Among the environmental predisposing factors, exposure to in-utero ionizing radiation or treatment of primary cancer with radiotherapy and/or chemotherapy, particularly alkylating (cyclophosphamide) agents and inhibitors of topoisomerases II (VP16), are the most reported ones. Other factors such as exposure to electric or magnetic fields, the consumption of alcohol, marijuana, or tobacco during pregnancy , and exposure to pesticides have not been confirmed.

Symptoms and signs of acute types of leukemia are related to bone-marrow failure caused by replacement of normal bone marrow by leukemia cells and by blast infiltration of lymphoid and non-lymphoid organs and tissues.

Pallor, fatigue, lethargy (sometimes), and headaches are manifestations of anemia; and a fever with or without chills and sometimes mouth ulcers are related to neutropenia. While severe hemorrhagic syndrome with petechiae, bruising, and epistaxis, gingival bleeding and sometimes visceral or cerebro-subarachnoid hemorrhage are more or less attributable to thrombocytopenia. Thrombocytopenia may be the result of bone marrow failure, but also of consumptive coagulopathy, better known as disseminated intravascular coagulation (DIC) . Infiltration of lymphoid organs is inconstant (not always present) and peripheral, non-inflammatory lymph nodes located deep in subcutaneous tissue can be enlarged on palpation. Abdominal or mediastinal lymphadenopathies may also be observed, however they rarely cause compression of the regional organs or vessels. Splenomegaly and hepatomegaly are very frequently associated with lymph node infiltration.

Bone pains have been reported in 20–25 % of patients. They reflect leukemic bone infiltration and can be mistaken for rheumatoid- or sickle cell disease.

Involvement of other tissue or organs is less frequent, though seen in some leukemia subtypes. Testicular (Fig. 16.2) or central nervous system (CNS) infiltration (Fig. 16.3) is more frequently seen in ALL, whereas gingival infiltration is seen in myeloblastic leukemia. A malignant tumor, chloroma , usually found in the orbital part of the brain can reveal or accompany an acute myelogenous leukemia.

A high leukocyte count can induce a leukostasis secondary to abnormal aggregation and clumping and occluded microcirculation, particularly in the lungs and the brain. Clinical expression is usually dyspnea with or without neurological symptoms that may be life-threatening in severe cases.

The diagnosis of acute leukemia is based on the characterization of leukemic cells in the blood, and in the bone marrow.

In most cases complete blood count usually shows normochromic normocytic anemia, leukocytosis mainly consisting of blast cells with neutropenia and thrombocytopenia. The bone marrow aspiration shows a rich smear and blast cell infiltration. The diagnosis of acute leukemia is made when blast cells exceed 20 % of the bone marrow cellularity. When specific cytogenetic abnormality is found the diagnosis of acute leukemia can be accepted even at a reduced percentage of blast cells in the bone marrow. This diagnosis requires additional cytochemistry, and mostly in immunology and cytogenetic studies.

Analysis of bone marrow smears after May-Grunwald-Giemsa and myeloperoxidase (MPO) staining is mandatory for initial diagnosis evaluation. Lymphoblasts are often small-sized and characterized by dense chromatin, little or no nucleolus and sparse and non-granular cytoplasm. The myeloblasts are typically larger in size, have a loose chromatin nucleus with several nucleoli and relatively abundant cytoplasm-containing MPO positive granules. Auer rods, representing abnormal condensation of cytoplasmic granules, may be observed in myeloblasts. Additional characterization of leukemia using immunophenotyping assays and genetic analysis is highly recommended. However, these techniques are rarely available in most parts of Africa, which make microscopic morphology the only available diagnostic tool.

WHO classification of ALL is based on the immunophenotyping identification of membrane and cytoplasmic markers using flow cytometry (Table 16.1). Because different treatment approaches are proposed for children with B-cell leukemia, their identification is of great importance. The mature B-cell ALL (L3) in most cases is identified via microscopic morphology as large lymphoblasts with cytoplasmic vacuoles resembling those found in Burkitt’s lymphoma.