Pediatric Chronic Myeloid Leukemia: Targeting Treatment
Researchers argue that children with CML should receive different treatments than adults, which may mitigate long-term side effects.
Differences in the presentation and progression of chronic myeloid leukemia (CML) among children and adults is catalyzing research into prognostic factors specific to pediatric patients and potential adverse events of targeted therapies begun in childhood and continued for decades.
Authors of a recent study of flow cytometric results as a predictor of response to treatment with tyrosine kinase inhibitors (TKIs) in children with CML focused on an analysis of bone marrow in patients between the ages of 3 and 16.1
The results “revealed that granulocyte macrophage progenitor predominance in CML progenitors at diagnosis and elevated cMpl expression in bone marrow progenitors at 3 months may predict poor outcome in children with chronic-phase CML treated with imatinib,” they wrote. We recommend flow cytometric analysis of bone marrow in the early phase of treatment, as it is a convenient tool that may predict treatment response and guide CML management.”
The authors called for further, larger studies to evaluate the potential of the flow cytometric analysis. They concluded by noting present challenges: “the biology of CML differs between adults and children, as it is more aggressive in children and young adults; prognosis scores for adults do not apply to children.”
These authors were, however, hardly the first. An article published in 2016 argued that children with CML should be treated differently than adults. “There are clear differences between CML in children and adults in terms of disease presentation and progression,” they wrote, “along with differences in the underlying CML biology and host factors, which should be considered when treating pediatric patients with CML.”
CML comprises approximately 15% of new adult cases of leukemia and about 3% of newly diagnosed pediatric cases. It is less common in younger children, constituting about 2% of all leukemias in children under 15, and 9% in adolescents between 15 and 19. It affects about 1 out of a million in the younger group, and 2.2 cases per million among adolescents.3 The median age at diagnosis is 60 to 65 years among adults.4
Generally, adult prognostic scores have also been used to predict outcomes in children. Yet as the authors of the 2016 article stated, “the validity of these scores has not been formally evaluated in the pediatric population and their prognostic significance may not apply to these patients.” For example, “the difference in spleen size by age in children should be taken into consideration when applying prognostic scores for CML.”
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The introduction of TKIs such as imatinib, nilotinib, and dasatinib dramatically changed the treatment landscape, and outcomes, for patients with CML. Previously, the standard of care involved stem cell transplantation, which had the advantage of being truly curative, though its success was limited. A 2014 article reported patient mortality rates at 100 days as high as 27%.6 TKIs, however, proved effective in controlling the progression of CML for years, even decades, in the overwhelming majority of patients — as long as the drugs are administered regularly.