• Diagnosis/disease status:

‣ Patients with newly diagnosed Langerhans cell histiocytosis (LCH) OR

⁃ Patients with relapsed or refractory disease OR

⁃ Patients with newly diagnosed or relapsed/refractory disease who are receiving the liquid formula of trametinib OR

⁃ Patients who have been receiving trametinib as a treatment for LCH since January 1, 2020 may be included in the observational chart review to track long-term follow-up. Eligibility for chart review cohort will include receiving trametinib as treatment.

• Diagnosis confirmed with biopsy prior to start of treatment

• Patient must have adequate cardiac function evident through Echocardiogram (ECHO) and Electrocardiogram (EKG) within 30 days of starting treatment.

‣ Shortening fraction of ≥ 27% by echocardiogram or

⁃ Ejection fraction of ≥ 50% by gated radionuclide study

⁃ QTC \< 480 msec

• Performance status: Patients must have a performance status corresponding to ECOG scores of 0, 1, or 2. Use Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥50% for patients ≤16 years of age.

• Adequate organ and marrow function as defined below:

‣ Absolute Neutrophil count ≥ 1,500/μL

⁃ Platelets ≥ 100x103/μL

⁃ Total bilirubin ≤ 1.5X ULN for age

⁃ AST/ALT ≤ 2.5 X ULN for age

⁃ Serum creatinine based on age/gender

⁃ Hemoglobin ≥ 8 g/dL

∙ Patients with bone marrow disease must have hemoglobin ≥ 8 g/dL with transfusion support allowed

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after the last dose. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• Ability to understand study procedures and to comply with them for the entire length of the study.