title: Activity of sirolimus in patients with myelodysplastic syndrome--results of a pilot study.
abstract: The pathophysiology of the myelodysplastic syndromes (MDS) involves disturbed regulation of angiogenesis, apoptosis, proliferation and differentiation as well as immune surveillance. Increasing data suggest that sirolimus might affect these pathways positively, thus being of possible therapeutic benefit in patients with this disease. Nineteen patients (n = 19) with a median age of 72 years (range 54-80 years) diagnosed with MDS received sirolimus orally with a target blood concentration of 3-12 ng/ml. Sirolimus was administered for a median of 3.7 months (range 0.3-11 months). Three patients [1 x refractory anaemia with excess blasts (RAEB)-2, 1 x RAEB-1, 1 x refractory cytopenia with multilineage dysplasia] showed either a major (1 x platelet, 1 x neutrophil) or a minor (1 x erythroid, 2 x platelet) haematological response according to International Working Group criteria. Major side-effects were hyperlipidaemia (n = 4), stomatitis (n = 3), thrombocytopenia (n = 2) and urinary tract infection (n = 1). These data suggest that sirolimus has activity in a subset of patients with more advanced MDS.
authors.affiliation: Medizinische Klinik und Poliklinik I des Universitätsklinikum Carl Gustav Carus Dresden, 01307 Dresden, Germany. uwe.platzbecker@uniklinikum-dresden.de
authors.forename: U
authors.initials: U
authors.lastname: Platzbecker
authors.forename: M
authors.initials: M
authors.lastname: Haase
authors.forename: R
authors.initials: R
authors.lastname: Herbst
authors.forename: A
authors.initials: A
authors.lastname: Hänel
authors.forename: K
authors.initials: K
authors.lastname: Voigtmann
authors.forename: C H
authors.initials: CH
authors.lastname: Thiede
authors.forename: B
authors.initials: B
authors.lastname: Mohr
authors.forename: E
authors.initials: E
authors.lastname: Schleyer
authors.forename: T
authors.initials: T
authors.lastname: Leopold
authors.forename: M
authors.initials: M
authors.lastname: Orth
authors.forename: M
authors.initials: M
authors.lastname: Hänel
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.forename: M
authors.initials: M
authors.lastname: Bornhäuser
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000754:Anemia, Refractory, with Excess of Blasts / Q000097:blood / Q000188:drug therapy; D004906:Erythrocyte Count; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy*; D010865:Pilot Projects; D010976:Platelet Count; D020123:Sirolimus / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus