Optimal management for pediatric chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is rare among childhood leukemias. Its incidence increases with age, from 0.09/100 000 at ≤15 years old to 7.88/100 000 at ≥75 years old. There are several biological and clinical differences between pediatric and adult CML. Markedly increased leukocyte count and a higher incidence of splenomegaly are characteristic features at diagnosis in pediatric patients. The therapeutic approach to CML has changed since the introduction of the tyrosine kinase inhibitor (TKI) imatinib, followed by dasatinib and nilotinib. Given the efficacy of TKI in adult CML, TKI are regarded as the established first-line treatment in adult patients. In 2011, a prospective phase IV study in pediatric patients showed the excellent efficacy and safety of imatinib. Imatinib is also accepted as a first-line option for childhood chronic phase CML. Although the efficacy of dasatinib and nilotinib reported in adult studies seems very attractive for pediatric patients, neither drug has been prospectively investigated in a large pediatric cohort. TKI are designed to inhibit BCR-ABL1 kinase, but they have unfavorable effects, so-called "off-target" complications, such as growth impairment. Long-term morbidity due to TKI is unknown. Furthermore, the adverse effects on growing children have not been clearly elucidated, even though the exposure period to imatinib is relatively short. To establish the standard therapeutic management for pediatric CML, it is important to prospectively confirm the attractive outcomes obtained in adult studies via pediatric clinical trials with a careful monitoring system for TKI-induced adverse effects, especially in growing children.