5.2Chronic Myelogenous Leukemia (Adult Type)

•Incidence of chronic myelogenous leukemia (CML) in children and adolescents aged 0–20 years is approximately 1:100,000/year

•Male-to-female ratio: 1.8

•Should be differentiated from atypical BCR-ABL1-negative chronic myeloid leukemia

5.2.1Clinical Manifestations

Often systemic symptoms such as fever and weight loss. Splenomegaly and pain are often present at initial presentation.

5.2.2Laboratory Findings

•Peripheral blood: hyperleukocytosis (more than 100×109 leukocytes/l),frequently with the risk of cerebral leukostasis affecting consciousness. Thrombocytosis frequently observed; thrombocytopenia less common. Anemia is not frequently observed

•Bone marrow: Increase in granulocytes as well as basophils and/or eosinophils. Myelodysplastic changes may be observed. Excess percentages of leukemic blasts are uncommon in the chronic phase (less than 5%), but are increased during the accelerated phase and, particularly, during blast crisis

•Philadelphia chromosome t(9;22)(q34;q11) is pathognomoni and results in the expression of the fusion gene product, BCR-ABL1, resulting in increased tyrosine kinase activity, which plays a central etiologic role. May be inhibited by the specific tyrosine kinase inhibitors, such as imatinib mesylate, dasatinib, and nilotinib

•A different translocation of chromosomes 9 and 22 is observed in some forms of acute lymphoblastic leukemia (ALL) and results in a 210 kDa fusion protein compared to the 190 kDa product of CML. Philadelphia chromosome-positive AML does occur and is thought to represent in most cases blast transformation of CML

5.2.3Natural History

•Chronic phase: usually asymptomatic or with minimal symptoms such as splenic pain associated with enlargement; may persist usually 3–5 years

•Accelerated phase: characterized by an increase in the size of the spleen and with occurrence of blood count abnormalities (leukocytosis, thrombocytopenia, but also thrombocytosis and anemia). The accelerated phase lasts frequently no lon- ger than 6 months and heralds blast crisis

•Blast crisis: Mimics acute leukemia and is usually of myeloid or B lineage immunophenotype; T lineage blast crisis is rare