There is no established standard treatment protocol for pediatric chronic myeloid leukemia (CML) and many questions remain regarding long-term outcomes with tyrosine kinase inhibitor (TKI) therapy.1

Pediatric CML is rare, with a rate of 2.2 per million persons.2 Most CML cases occur in adults, with a median age at diagnosis of 60 to 65.1 As a result, there are no established treatment guidelines and many clinicians apply adult guidelines to their pediatric patients. However, many of the studies used to develop these guidelines excluded children and adolescents, indicating that this is not an ideal approach. There are few studies about the optimal use of TKIs and long-term outcomes among pediatric patients.

Differences Between Pediatric and Adult CML

“We used to think that pediatric CML is just like adult CML, but they are obviously different. We are presently working on showing their different biology, but there are very little data out there so far,” Nobuko Hijiya MD, of the Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital of Chicago in Chicago, Illinois, told Cancer Therapy Advisor.

The underlying biology is thought to be different because the presentation and treatment outcomes vary between children and adults.1 Pediatric CML is often more aggressive than the adult disease, and evidence suggests that fewer children achieve complete cytogenic response or major molecular response compared with adults.1,3 It is now thought that variations in the underlying biology and host factors may contribute to these differences.

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Both pediatric and adult CML harbor the BCR-ABL1 fusion gene, but the breakpoint distribution is different among pediatric patients compared with adult patients.4 More research is needed to fully elucidate the differences between pediatric and adult CML, and how this affects treatment outcomes.

Treatment of Pediatric CML

The National Comprehensive Cancer Network (NCCN) guideline recommends 4 different TKIs or a clinical trial for the primary treatment of adult CML in chronic phase.5 Three of these options are now available for pediatric CML.

The U.S. Food and Drug Administration recently approved 2 second-generation TKIs for pediatric patients positive for the Philadelphia (Ph) chromosome and in chronic phase in 2017 and 2018, expanding options to now include the second-generation TKIs, dasatinib and nilotinib in addition to the first-generation TKI, imatinib.6,7

Dr Hijiya noted that these approvals provide patients with options if they are intolerant or acquire resistance to initial treatment.