Management of Chronic Myeloid Leukemia in Children and Young Adults

Abstract

Purpose of Review Due to lack of pediatric-specific data, the management of chronic myeloid leukemia (CML) in pediatric, adolescents, and young adults is guided by adult CML evidence-based recommendations. Pediatric CML presents differently than adult CML and is often a more aggressive disease with different biological and host factors, yet there is sparse literature on how to address those differences. Recent Findings Over the past two decades, tyrosine kinase inhibitors (TKIs) have changed the way CML is treated. There are currently three FDA-approved TKIs (imatinib, dasatinib, and nilotinib) for pediatric patients. When choosing which TKI to begin treatment with, there are many factors that should be considered on a case-to-case basis to obtain optimal outcomes. The safety profiles for long-term TKI use in pediatrics require further study. Unlike adults, children are still actively growing during TKI use, and the effect on development can be detrimental. TKI therapy is not recommended during pregnancy with variable but significant risk of fetal abnormalities and miscarriage, warranting counseling for young female patients prior to beginning TKIs. Attempts for treatment-free remission (TFR) by planned TKI cessation in eligible adult patients in deep and sustained molecular remission are now done as a standard of practice. However, data is sparse in the pediatric population. There is currently an ongoing Children’s Oncology Group (COG) study to determine the feasibility of TFR as a treatment goal. Summary Further research and additional pediatric trials are needed to characterize the unique aspects of CML in children and adolescents and optimize outcomes.

Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921

“…Chronic myeloid leukemia (CML) is a rare disease in children, accounting for 3% of all pediatric leukemias. 1,2 CML is caused by the t(9;22)(q34;q11.2) translocation, resulting in the BCR::ABL1 fusion oncogene (Ph+). 3…”

“…15 GI toxicity (mainly diarrhea) may lead to dose reduction during treatment. 2,3,15,16 Animal models showed that bosutinib does not cross the blood-brain barrier, differently from dasatinib. 14…”

“…Chronic myeloid leukemia (CML) is a rare disease in children, accounting for 3% of all pediatric leukemias. 1,2 CML is caused by the t(9;22)(q34;q11.2) translocation, resulting in the BCR::ABL1 fusion oncogene (Ph1). 3 The introduction of tyrosine kinase inhibitors (TKIs) targeting the BCR::ABL1 protein, such as imatinib, has drastically improved the prognosis of Ph1 CML.…”

Skin reactions to tyrosine kinase inhibitors in pediatric patients with chronic myeloid leukemia

“…2 Currently, only the first-generation TKI, imatinib, and secondgeneration TKIs, dasatinib and nilotinib, are approved by the Food and Drug Administration for pediatric patients. 3 Given the rarity of CML in children, data on long-term treatment profiles and efficacy of TKIs, especially the newer second-and third-generation TKIs, in childhood CML remains scarce. 1 While pediatric oncologists often follow treatment guidelines intended for adults and are increasingly prescribing TKIs in children, there is limited data supporting the generalizability of adult guidelines to children.…”

“…TKIs, which inhibit the fusion oncogene BCR‐ABL1 , have significantly improved survival 2 . Currently, only the first‐generation TKI, imatinib, and second‐generation TKIs, dasatinib and nilotinib, are approved by the Food and Drug Administration for pediatric patients 3 . Given the rarity of CML in children, data on long‐term treatment profiles and efficacy of TKIs, especially the newer second‐ and third‐generation TKIs, in childhood CML remains scarce 1 .…”