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It is preferable that patients be treated on clinical trials so the biology and therapy of these rare patients can be advanced. The Histiocyte Society, the Children’s Oncology Group, and the North American Consortium for Histiocytosis sponsor these trials as well as some individual centers such as Texas Children’s Cancer and Hematology Centers in Houston, TX. Treatments vary depending on the extent of disease and involve chemotherapy with prednisone, velban with or without 6-mercaptopurine and methotrexate have been the standards for several decades and are still being studied by the Histiocyte Society in the LCH-IV trial. Texas Children’s Histiocytosis Center has a randomized trial comparing the efficacy of vinblastine and prednisone versus cytarabine in newly diagnosed patients. Those patients with liver, spleen, lung, or bone marrow involvement are considered to be of “higher risk” for not responding to therapy. Patients with lesions in multiple bones or more than one “non-risk” organ have an excellent chance for responding to combination chemotherapy. Mastoid, orbit, temporal and sphenoid bones represent a special group known as “CNS Risk” because of the high incidence of diabetes insipidus and subsequent anterior pituitary hormone deficiencies and neurologic involvement. The latter could mean mass lesions or a nerve damage leading to only changes on the MRI brain scan or neurologic problems such as ataxia, dysmetria, dysarthria, learning difficulties and psychologic problems.

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