Cytogenetic Abnormalities Do Not Affect Prognosis in Pediatric CML

Chromosomal abnormalities such as a variant t(9;22) translocation do not appear to have significant prognostic impact on children with chronic myeloid leukemia (CML), according to a new study. This is in contrast to outcomes seen in adult CML patients.

“Recent reports have highlighted the role of cytogenetic analysis at diagnosis and during treatment in determining the prognosis of the disease,” wrote study authors led by Frédéric Millot, MD, of INSERM Clinical Investigation Centre in Poitiers, France. “Variant translocations (one or more additional chromosomes involved in the translocation) or additional cytogenetic abnormalities have been reported in 5% to 10% of the adult population with newly diagnosed CML.”

In adults, some of those variants have been associated with poorer survival; the rarity of CML in children, however, has made it difficult to study in the pediatric population. The new study included 301 children with CML in the chronic phase enrolled in the International Registry for Chronic Myeloid Leukemia in Children and Adolescents. Results of the analysis were published in Cancer.

A total of 282 patients (93.7%) had the classic translocation t(9;22)(q34;q11), without additional abnormalities or variants. Thirteen children (4.3%) had additional cytogenetic abnormalities in addition to the standard translocation, five children (1.7%) had a variant on the t(9;22) translocation, and one child had both the variant translocation and additional cytogenetic abnormalities. A total of 268 patients were treated with imatinib as frontline therapy, while others were treated with dasatinib, nilotinib, or others.

Among those treated with imatinib, the 3-year progression-free survival probability was 95% for children with a classic translocation; for those with additional cytogenetic abnormalities, the 3-year progression-free survival probability was 100%, and for those with a variant t(9;22) translocation it was 75%. The 3-year overall survival rates were 98%, 100%, and 75%, respectively. These differences were not significant.

“With the limitation of the small number of patients, additional cytogenetic abnormalities at diagnosis could not be considered an adverse prognostic factor in children and adolescents with CML in the chronic phase under imatinib,” the authors concluded. “Therefore, the current work does not support a different and specific treatment for pediatric CML with additional cytogenetic abnormalities or variant Ph translocations at diagnosis but suggests that careful monitoring should be performed for these children.”