Thalidomide, Cyclophosphamide and Dexamethasone for Recurrent/Refractory Adult Langerhans Cell Histiocytosis

Inclusion Criteria:

• • Histologically confirmed diagnosis of LCH.
• Patients were recurrent/refractory or at least receive one line of systemictreatment of LCH
• Age ≥18 years and ≤75 years.
• LCH involved multisystem or multifocal single system.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Patients must have adequate renal, liver, and bone marrow function as defined bythe following criteria:
• Absolute neutrophil count ≥1500 cells per mm3 or ≥500 cells per mm3 in thecase of known hematopoietic system involvement by LCH.
• Platelet count ≥100000 cells per mm3 or ≥20000 cells per mm3 in the case ofknown hematopoietic system involvement by LCH.
• Creatinine clearance [according to Cockcroft formula] ≥60 mL/min.
• Aspartate aminotransferase and alanine aminotransferase ≤2·5×upper limit ofnormal [ULN], and total bilirubin ≤2·5×ULN; or ≤10×ULN in the case of knownliver involvement by LCH.
• No active or untreated infection.
• No cardiac abnormalities.
• Subject provide written informed consent.
• A female is eligible to enter and participate in this study if she is of:
• Non-childbearing potential including ω Any female who has had a surgicalprocedure rendering her incapable of becoming pregnant.

ω Subjects have experienced total cessation of menses for more than 1 year and be greaterthan 45 years in age.

⎫ Childbearing potential, including any female who has had a negative serum pregnancy testwithin 2 weeks prior to the first dose of study treatment, and agrees to use adequatecontraception.

• Male subjects must use an effective barrier method of contraception during the study andfor 90 days following the last course of MA if sexually active with a childbearingpotential

Exclusion Criteria:

• • Non-langerhans cell histiocytosis.
• Patients had concurrent malignancies.
• Patients who were newly diagnosed LCH.
• History of myocardial infarction, or unstable angina, or New York HeartAssociation (NYHA) Grade III-IV within 6 months prior to Day 1.
• Women who were pregnant or of childbearing potential.
• Known HIV seropositive, active hepatitis C infection, and/or hepatitis B (definedas HCV RNA ≥103 copies or HBV DNA ≥103 copies at screening).
• Major surgical procedure within 28 days prior to the first dose of studytreatment.
• Presence of uncontrolled infection.
• Evidence of active bleeding or bleeding diathesis.
• Any serious and/or unstable pre-existing medical, psychiatric, or other conditionthat could interfere with subject's safety, provision of informed consent, orcompliance to study procedures.