Recognizing Endocrinopathies Associated With Tyrosine Kinase Inhibitor Therapy in Children With Chronic Myelogenous Leukemia

Abstract

Side effects of tyrosine kinase inhibitor (TKI) treatment vary in children and adults with chronic myelogenous leukemia (CML). As children have a much longer life expectancy than adults, TKI therapy may continue for decades and with long-term consequences that differ from adults. Children may develop endocrinopathies related to "off-target" effects of TKIs, such as delayed growth, changes in bone metabolism, thyroid abnormalities, and effects on puberty and fertility. These endocrinopathies present additional challenges for pediatric patients with CML. This review critically evaluates the literature on long-term endocrine side effects of TKIs in the pediatric CML population and provides suggested recommendations.

T‐cell‐rich HLA‐haploidentical hematopoietic stem cell transplantation for relapsed/refractory pediatric Philadelphia chromosome‐positive acute lymphoblastic leukemia without posttransplant tyrosine kinase inhibitor therapy

“…There are two major problems underlying posttransplant TKI treatment of relapsed or refractory cases: the first includes the resistance to TKI, whereas the second is the toxicity to physical development of the child. Prolonged exposure to imatinib in children is known to result in growth impairment . In approximately 40% of the patients with relapsed Ph‐ALL, a low level of BCR‐ABL tyrosine kinase domain (TKD) mutations were detected in the pretherapeutic leukemia samples.…”

Helping children with growth failure due to tyrosine kinase inhibitor drugs requires knowledge of the pathogenesis of the problem

“…The recent review by Samis et al . confirms that imatinib and dasatinib inhibit longitudinal growth of children.…”

Childhood Cancer Treatments and Associated Endocrine Late Effects: A Concise Guide for the Pediatric Endocrinologist

“…Children may be treated with imatinib for other conditions such as relapsed solid tumors [57]. Treatment with imatinib has been shown to cause linear growth deceleration [56]. The mechanism of growth failure in children treated with tyrosine kinase inhibitors such as imatinib is not well understood and may involve perturbations of the GH-IGF-I axis and direct skeletal effects [55].…”

“…Imatinib mesylate, a tyrosine kinase inhibitor, has become a frontline therapy option for children with chronic myeloid leukemia, a myeloproliferative disorder with an activated BCR-ABL tyrosine kinase fusion protein [55, 56]. Children may be treated with imatinib for other conditions such as relapsed solid tumors [57].…”