Clinical Trial Shows Reduction In Mortality For Children With Severe Langerhans Cell Histiocytosis

The study, published in the March 1 edition of Blood, the journal of the American Association of Hematology, is the second in a series of international randomized clinical trials for Langerhans cell histiocytosis coordinated by the Histiocyte Society. The LCH clinical trial series are the first-ever randomized clinical trials for the treatment of LCH.

“The incidence of this particular disorder is so rare, without the cooperation of researchers and participants across the globe, the trial could not have been conducted on a large enough scale to see such positive, and definitive outcomes,” noted senior author Stephan Ladisch, MD, Bosworth Chair for Cancer Biology and Director of the Center for Cancer and Immunology Research at Children’s National Medical Center. “The value of international collaborations such as this is incalculable to the research of so-called ‘orphan diseases’ that receive little government funding support, but still have a significant effect on the lives of children around the world.” 

The trial induced a rapid response to the application of chemotherapy—involving prednisone, vinblastine, and for some participants, the addition of etopisode. As a result, the research team observed a statistically significant improved prognosis for children with multi-system LCH. Study leaders observed this significant effect in both study groups of the second clinical trial.

The authors conclude, “There is a strong indication that increasing treatment intensity was associated with higher rapid respond and survival rates. This suggests that therapy intensification…may be essential for successful treatment of high-risk disease.”

The results were based on the findings in 193 pre-identified LCH patients identified as “risk patients”—those with LCH affecting risk organs including the liver, lungs, hematopoeitic system, and spleen, or patients with disease onset younger than 2 years of age. For these high risk groups, mortality rates had been as high as 60 to 70 percent (and are now well below 30 percent).

The results of the first LCH clinical trial (LCHI) were published in 2001 by the Journal of Pediatrics. This new study builds on the findings of LCHI, which focused on the effectiveness of two of the most common treatments of LCH in children.

About Langerhans cell histiocytosis (LCH)

Langerhans cell histiocytosis (LCH) is a rare disorder that primarily affects children, involving clonal proliferation of abnormal cells deriving from bone marrow. Clinically, its manifestations range from isolated bone lesions to multisystemic disease. These cells accumulate in different organs and can result in a variety of symptoms. The cause of LCH is unknown. It is not a known infection or cancer. In severe cases affecting “risk organs” including the liver, lungs and the hematopoeitic system, the disease is fatal. Usually these cases are in very young children.

It is estimated that 9 of every 1,000,000 children under the age of 15 have histiocytosis at various severity levels. Three-quarters of the cases occur before age 10, but the disease also occurs in adults. Because of its rare occurrence, LCH is often referred to as an “orphan” disease.

Journal reference: Blood, 1 March 2008, Vol. 111, No. 5, pp. 2556-2562. Prepublished online as a Blood First Edition Paper on December 18, 2007; DOI 10.1182/blood-2007-08-106211. http://bloodjournal.hematologylibrary.org/cgi/content/abstract/111/5/2556