Histiocytosis is considered a rare disease but doctors at Baylor College of Medicine and Texas Children’s Cancer Center and Hematology Service would argue the accuracy of that label. They are seeing more and more patients with the disease and that has led to important research advances.

"Our knowledge of this disease has skyrocketed over the last three years," said Dr. Kenneth McClain, professor of pediatrics – hematology/oncology at BCM and director of the Histiocytosis Program at Texas Children’s Cancer Center and Hematology Service. "Until that time, we were limited by several things, including the number of patients and tissue specimens available for research."

Family of diseases

Histiocytosis occurs when white blood cells called histiocytes and lymphocytes gather together and attack the skin, bones, brain, gastrointestinal system, major organs, mouth and ears. It is actually a family of diseases, with the two most common forms being Langerhans cell histiocytosis (LCH) and hemophagocytic lymphohistiocytosis (HLH). The disease affects children and adults and can range from a single skin lesion to multi-organ involvement. It can be chronic and debilitating and, in some cases, fatal.

At Texas Children’s Cancer Center and Hematology Service, doctors see more than 120 new patients annually, up from only 30 new patients about 10 years ago, and follow more than 400 patients.

"Even though it’s a rare disease, it’s not rare here at Texas Children’s Cancer Center and Hematology Service," said Dr. Carl Allen, assistant professor of pediatrics – hematology and oncology. "We’ve been able to make a lot of progress in understanding the disease."

Challenging current model

Allen and McClain have developed a strategy to study global gene expression and cellular communication pathways in the cells that cause LCH.

"We are getting closer to understanding the cell of origin of LCH and the problems with cellular maturation and migration that lead to lesion formation," he said. "Our data suggests that the current model of LCH, where Langerhans cells in the skin become malignant and form tumors, is not correct. We are testing the hypothesis that LCH, in fact, has little to do with Langerhans cells, but arises from misguided circulating cells called dendritic cells."

Looking at complications of histiocytosis

Active research at Texas Children’s continues to focus on the role of these dendritic cells. Other ongoing research is centered on the causes of devastating complications of histiocytosis. For example, some patients with LCH can develop progressive destruction of nerves in their brain even 10 years after initially developing the disease. If not caught early this can lead to unrelenting neurologic deterioration. McClain has found a chemotherapy strategy that is the first reported to stabilize this condition, however he and Allen hope to develop clinical protocols to prevent this complication by early diagnosis as well as treatment to eventually cure LCH central nervous system disease.

Research efforts are also ongoing to determine why some histiocytosis patients do not respond well to treatment and to uncover the biology that causes the disease to vary vastly in severity.

"Some people have a single skin or bone lesion, and that’s the extent of the disease for them. But for others, the disease involves lymph nodes and bone marrow, which is more like leukemia. While the overall survival rate is 80 percent, there are those who don’t respond well and have poorer outcomes," Allen said. "We are still trying to sort out if there is the same biology involved in the disease at the two ends of the spectrum. We are also trying to identify early biomarkers in patients at higher risk, who have poor initial response to therapy or eventually develop recurrent disease. There is a wealth of information we can now uncover as we gain access to new tools in the lab and clinic."

Grants propel research

Allen and McClain have several active grants to support their research, including grants from the National Cancer Institute, the Histiocytosis Association of America, the American Society of Hematology, which awarded Allen the Junior Faculty Research Scholar Award, and the American Society for Clinical Oncology, which honored Allen the Young Investigator Award.

To learn more about the program, the patients and its outcomes, please see the latest from Texas Children’s Hospital.

The Texas Children’s Cancer Center is a joint program of Texas Children’s Hospital and Baylor College of Medicine and is the pediatric program of the NCI-designated Dan L Duncan Cancer Center at BCM.