Ashish Kumar.

Ashish Kumar, MD, PhD, directs the Langerhans Cell Histiocytosis Center at Cincinnati Children’s.


These PET-CT images show disease activity in a 10-month-old child with Langerhans cell histiocytosis (LCH). The image on the right shows a decrease in activity three months after treatment with dabrafenib.

In another advance for personalized medicine, physicians at Cincinnati Children’s report using genomic profiling to reverse the course of disease for three children and one adult who were battling treatment-resistant histiocytoses.

These cancerous blood syndromes cause abnormal accumulations of white blood cells that form potentially lethal tumors on vital organs. Current forms of chemotherapy work in about 50 percent of cases, but in other patients the tumors become resistant.

In a study led by Ashish Kumar, MD, PhD, researchers analyzed tumor biopsies for 72 patients with resistant disease. In 26 cases, the team detected mutations involving either the BRAF or MAP2K1 genes. This finding suggested that some patients could benefit from drugs that block the MAP-kinase cancer pathway.

Kumar and colleagues report dramatic improvements in responses to off-label uses of the approved cancer drugs dabrafenib or trametinib. Details were published Feb. 9, 2017, in the Journal of Clinical Investigation Insight.

Within two weeks, treatment eliminated tumors and seizures affecting a 36-year-old woman with Langerhans cell histiocytosis. Meanwhile, three infants who had endured several unsuccessful rounds of chemotherapy are thriving now on one oral medication that put their disease into remission.”

The study authors say their findings support conducting genomic profiles in all histiocytosis cases. They also suggest launching a larger clinical trial of MEK inhibitors as a potential treatment for these disorders.