Treatment protocol of the first international study for Langerhans Cell Histiocytosis in Adults

LCH-A1 study is an international multicenter study for Langerhans Cell Histiocytosis.
This is a rare, tumor-like disease thas has an unpredicatable course and can be fatal. The cause of this disease is unknown.
The targeted number of participants is 1200 patients; for the Netherlands the targeted number is 20 patients.
The study is designed for 3 groups of patients.
Patient population in group 1 are patients with single system multifocal bone lesions or localized special site involvement.
Group 2 consists of patients with multisystem disease and group 3 consists of patients with isolated pulmonary disease.
Treatment for group 1 is 6 months of treatment with Prednisone, Vinblastine and Mercaptopurine.
Treatment for group 2 is the same as in group 1. Patients are randomized for 6 months treatment versus 12 months.
Treatment in group 3 is an observation phase for 6 months after smoking cessation. In case of progression of the symptoms or pulmonary dysfunction 6 months steroid monotherapy is given.
Duration of treatment is for all patients 6 months till 12 months and a follow up period of 6 years.

Improvement of standardization in diagnosis and treatment of adult LCH

pre-treatment, at week 6 and every 3 months during treatment (i.e. month 3, month 6 and 9 when appropriate) and then at treatment completion.
thereafter every 6 months for the first 3 years. and once a year during the following 3 years.

- Patients in group 1 (single system disease at risk): treatment with Prednisone, Vinblastine and Mercaptopurine.

Initial treatment: Prednisone 1 mg/kg/day ( not to exceed 60 mg) as a 4-week course, tapering over a period of 2 weeks.
Vinblastine 6 mg/m2 iv bolus (not to exceed 10 mg), day 1,8,15,22,29,36.

Continuation treatment: starting at day 43 after initial treatment. Mercaptopurine: 30 mg/m2(not to exceed 50 mg) daily until completion of treatment. Prednisone: 1 mg/kg/day (not to exceed 60 mg) day 1-5 every 3 weeks until completion of treatment.
Vinblastine: 6 mg/m2 iv bolus (not to exceed10 mg) day 1 every 3 weeks until completion of treatment. (starting 3 weeks after the last vinblastine injection of the initial treatment.

total duration of treatment is 6 months.

- Patients in group 2, multisystem LCH:treatment with Prednisone, Vinblastine and Mercaptopurine for 6 months versus treatment with Prednisone, Vinblastine and Mercaptopurine for 12 months.
Intervention for group 2 is the same as for group 1; total duration of treatment will be the object of randomization: 6 months vs 12 months.

- Patients in group 3 (isolated pulmonary disease): an observational period of 6 months afer cigarette smoke withdrawal. In case of progression of the symptoms of pulmonary dysfunction, treatment phase will be started with Prednisone monotherapy for 6 monthsat the following dosage:

- 1mg/kg/day (not to exceed 60 mg), daily for 1 month.

- 0.5 mg/kg/day, daily for 1 month.

- 0.25 mg/kg/day daily for 2 months.

- 0.125 mg/kg/day daily for 2 months.