sirolimus and Erdheim-Chester-Disease

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, to whose pathogenesis neoplastic and immune-mediated mechanisms contribute. Mammalian target of rapamycin (mTOR)-inhibitors have antiproliferative and immunosuppressive properties. We tested in this study, the efficacy and safety of the mTOR-inhibitor sirolimus (SRL) plus prednisone (PDN) in patients with ECD. PDN was given initially at 0.75 mg/kg per day, tapered to 5 to 2.5 mg per day by month 6. Target SRL blood levels were 8 to 12 ng/mL. Treatment was continued for at least 24 months in patients who showed disease stabilization or improvement. Ten patients were enrolled; 8 achieved stable disease or objective responses, whereas 2 had disease progression. Responses were mainly observed at the following sites: retroperitoneum in 5/8 patients (62.5%), cardiovascular in 3/4 (75%), bone in 3/9 (33.3%), and central nervous system (CNS) in 1/3 (33.3%). The median follow-up was 29 months (interquartile range, 16.5-74.5); 2 patients died of progressive CNS disease and small-cell lung cancer, respectively. Treatment-related toxicity was mild. Using immunohistochemistry and immunofluorescence on ECD biopsies, we detected expression in foamy histiocytes of the phosphorylated forms of mTOR and of its downstream kinase p70S6K, which indicated mTOR pathway activation. In conclusion, SRL and PDN often induce objective responses or disease stabilization and may represent a valid treatment of ECD. The trial is registered at the Australia-New Zealand Clinical Trial Registry as #ACTRN12613001321730.

Topics: Adult; Aged; Erdheim-Chester Disease; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prednisone; Sirolimus; Treatment Outcome

Topics: Cytarabine; Erdheim-Chester Disease; Humans; Interferon-alpha; Sirolimus; Treatment Failure

Topics: Aged; Erdheim-Chester Disease; Humans; Male; Middle Aged; Sirolimus

Topics: Aged; Ascites; Cough; Drug Therapy, Combination; Erdheim-Chester Disease; Female; Fever; Glucocorticoids; Humans; Immunosuppressive Agents; Middle Aged; Prednisolone; Radionuclide Imaging; Sirolimus; Tomography, X-Ray Computed

Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytic disorder. We report a 76-years-old man who suffered a cardiac tamponade secondary to ECD. A pericardial window was made and during the operation the surgeons observed that the myocardium was diffusely infiltrated. Twenty-eight months before, ECD was clinically diagnosed and prednisone and methotrexate were prescribed. Due to disease progression which culminated in the cardiac tamponade, methotrexate was changed to sirolimus aiming to obtain plasma levels between 5-8 ng/ml. This treatment stabilized his cardiac function allowing a survival of 52 months after its initiation, with fewer side effects.

Topics: Aged; Anti-Inflammatory Agents; Cardiac Tamponade; Disease-Free Survival; Erdheim-Chester Disease; Humans; Immunosuppressive Agents; Male; Methotrexate; Prednisone; Sirolimus; Treatment Outcome

Topics: Erdheim-Chester Disease; Female; Humans; Immunosuppressive Agents; Male; Prednisone; Sirolimus

Erdheim-Chester disease is a rare non-Langerhans form of systemic histiocytosis of unknown origin. We describe a 45-year-old man presenting with bilateral hydronephrosis suggestive of extrinsic urinary tract obstruction. Computed tomography revealed extensive hypodense soft tissue infiltration in the retroperitoneum surrounding the kidneys. Needle biopsy of the retroperitoneal soft tissue revealed aggregates of lipid-laden histiocytes expressing CD68 but negative for CD1a and S100 protein. The diagnosis of Erdheim-Chester disease was supported by typical radionuclide bone scinitigraphic findings. Treatment with prednisolone, sirolimus, and regular ureteric stent revision was initiated to achieve adequate urinary tract drainage. To our knowledge, this is the second patient with Erdheim-Chester disease reported in Hong Kong. A high index of suspicion is required to avoid delay in the diagnosis of this rare disease.

Topics: Biopsy, Needle; Erdheim-Chester Disease; Hong Kong; Humans; Hydronephrosis; Male; Middle Aged; Prednisolone; Retroperitoneal Space; Sirolimus; Stents; Tomography, X-Ray Computed; Ureteral Obstruction