LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis

Inclusion Criteria: * Stratum I * Patients must be less than 18 years of age at the time of diagnosis. * Patients must have histological verification of the diagnosis of Langerhans cell histiocytosis according to the criteria described in Section 6.1 * Signed informed consent form * Stratum II * Patients of Stratum I who have: * Progressive disease (AD worse) in non-risk organs after 6 weeks (Initial Course * AD intermediate or worse in non-risk organs or AD better in risk organs after 12 weeks (Initial Course 2) * Disease progression (AD worse) in non-risk organs at any time during continuation treatment * Active disease at the end of Stratum I treatment * Disease reactivation in non-risk organs at any time after completion of Stratum I treatment * Stratum III * Patients from Stratum I who fulfill the following criteria: * AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2). * Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as * Hb \<70 g/L (\<7.0 g/dl) and/or transfusion dependency * PLT \<20 x109/L (20,000/μL) and/or transfusion dependency (both criteria have to be fulfilled) AND/OR * Liver dysfunction (or digestive involvement with protein loss) * Total protein \<55 g/L or substitution dependency * Albumin \<25 g/L or subst…