by Dr. Meenakshy Varier on  February 18, 2017 at 2:58 PM Health Watch
  • Histiocytoses are a group of disorders in which there is abnormal increase and accumulation of white blood cells.
  • Though it can successfully treated through chemotherapy in some, many develop resistance.
  • New study states that genomic testing can be used to identify genes that trigger the disease and they can be successfully treated with targeted molecular durgs.

Treatment Resistant Cancerous Disorders Treated by Gene-Guided Targeted Therapy
Genomic testing of biopsies from patients with deadly, treatment-resistant cancerous blood syndromes called histiocytoses helped doctors to identify genes that trigger the disease. They were then able to use targeted molecular drugs to treat them successfully.

Researchers from the Cincinnati Children's Cancer and Blood Diseases Institute recommend the regular use of comprehensive genomic profiling at diagnosis so that appropriate clinical care can be given.

Histiocytoses are a group of disorders in which there is abnormal increase and accumulation of white blood cells called histiocytes. This leads to formation of tumors on vital organs, leading to systemic organ damage or death.

The most common type that primarily affects children is Langerhans cell histiocytosis (LCH) wherein the abnormal cells resemble epidermal Langerhans cells. Adults are more frequently affected by Erdheim-Chester disease (ECD).

Though half of the people can be treated using local control and combination therapy, many others become treatment resistant.

Still others develop irreversible end-organ injury associated with significant morbidity such as diabetes insipidus and anterior pituitary dysfunction, neurodegeneration, and end-stage hepatic cirrhosis.


For the study, researchers conducted genomic profiling of biopsies from 72 child and adult patients who were suffering from a variety of treatment-resistant histiocytoses.

Fifteen patients (21%) carried the known BRAF mutation, and 11 patients (15%) carried various mutations in MAP2K1 that directly activate the MAP-kinase cancer pathway..

Researchers determined such patients would benefit from the targeted molecular therapies dabrafenib or trametinib, which block the MAP kinase pathway.

The approved cancer drugs were prescribed to the histiocytosis patients.

"In the last year, three patients we treated were infants with disease that was resistant to several rounds of intense chemotherapy. In the past, these children either would have suffered serious complications including death or would have had to endure more intensive treatments and the ensuing toxicities, including the risk of death," said lead investigator, Ashish Kumar, MD, PhD.

"All three are thriving now on one oral medication that put their disease into remission." Kumar added.

Future Work

Researchers plan to test methodologies that could expand the use of genomic profiling of patient biopsies and targeted molecular therapies in more patients with recurrent, treatment-resistant disease.

"It's important for physicians and patients to know that LCH and other forms of histiocytosis are not that mysterious anymore," Kumar said. "We now have new treatments that dramatically improve outcomes for these patients."

The findings are reported in Journal of Clinical Investigation Insight (JCI Insight).


  1. Ashish Kumar et al. Real-time genomic profiling of histiocytoses identifies early-kinase domain BRAF alterations while improving treatment outcomes. Journal of Clinical Investigation Insight; (2017)

Source: Medindia

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