title: Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome.
abstract: We hypothesized that sirolimus, an mTOR inhibitor, may be effective in patients with autoimmune lymphoproliferative syndrome (ALPS) and treated patients who were intolerant to or failed other therapies. Four patients were treated for autoimmune cytopenias; all had a rapid complete or near complete response. Two patients were treated for autoimmune arthritis and colitis, demonstrating marked improvement. Three patients had complete resolution of lymphadenopathy and splenomegaly and all patients had a reduction in double negative T cells, a population hallmark of the disease. Based on these significant responses, we recommend that sirolimus be considered as second-line therapy for patients with steroid-refractory disease.
authors.affiliation: Pediatric Hematology and Oncology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia PA 19104, USA. teacheyd@email.chop.edu
authors.forename: David T
authors.initials: DT
authors.lastname: Teachey
authors.forename: Robert
authors.initials: R
authors.lastname: Greiner
authors.forename: Alix
authors.initials: A
authors.lastname: Seif
authors.forename: Edward
authors.initials: E
authors.lastname: Attiyeh
authors.forename: Jack
authors.initials: J
authors.lastname: Bleesing
authors.forename: John
authors.initials: J
authors.lastname: Choi
authors.forename: Catherine
authors.initials: C
authors.lastname: Manno
authors.forename: Eric
authors.initials: E
authors.lastname: Rappaport
authors.forename: Dirk
authors.initials: D
authors.lastname: Schwabe
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sheen
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
authors.forename: Hongming
authors.initials: H
authors.lastname: Zhuang
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Wechsler
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Grupp
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D049268:Positron-Emission Tomography; D011859:Radiography; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus