title: Effect of treatment with amifostine used as a single agent in patients with refractory anemia on clinical outcome and serum tumor necrosis factor alpha levels.
abstract: Amifostine increases in vitro burst-forming unit-erythroid and colony-forming unit-granulocyte/granulcoyte-macrophage cultured from bone-marrow cells from patients with myelodysplastic syndrome (MDS). Several small clinical studies give divergent informations about the potential of amifostine as single agent to improve hematopoiesis in MDS patients. In these studies, patients with refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-T) were analyzed together, resulting in response rates varying from 8% to 30%. The present multi-center study evaluated whether treatment with amifostine is of clinical benefit in patients with RA who are transfusion dependent. The effect on transfusion frequency as well as on platelets and absolute neutrophil count (ANC) was examined in 14 patients with RA [median age 67 years (55-72 years), male:female 9:5]. Four treatment cycles were planned, each consisting of intravenous amifostine at 200 mg/m2/day three times per week followed by a 2-week interval. Since tumor necrosis factor (TNF) alpha is a main suppressive cytokine for hematopoiesis in RA patients, serum samples for analyzing endogenous levels of TNF alpha were collected prior to the study and after four treatment cycles. In three patients (21%), reduced transfusion requirement with prolongation of the transfusion interval from 4 weeks to 8 weeks (two patients) and 4 weeks to 6 weeks was seen. An increase in ANC from 400/microliter to 2600/microliter and 200/microliter to 3400/microliter was observed in two patients. Platelets increased from 129,000/microliter to 277,000/microliter in an additional patient. In one patient, disease progression from RA to RAEB was observed. Serum TNF alpha levels were increased in MDS patients compared with normal controls (18.8 pg/ml vs 9.1 pg/ml), and there was no change during the treatment with amifostine (17.5 pg/ml). In conclusion, treatment with amifostine as a single agent was of limited benefit in patients with RA. The serum TNF alpha levels were unchanged during treatment with amifostine in RA patients.
authors.affiliation: Department of Hematology and Oncology, Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany. W.K.Hofmann@em.uni-frankfurt.de
authors.forename: W K
authors.initials: WK
authors.lastname: Hofmann
authors.forename: G
authors.initials: G
authors.lastname: Seipelt
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: U
authors.initials: U
authors.lastname: Kalina
authors.forename: S
authors.initials: S
authors.lastname: Koschmieder
authors.forename: J
authors.initials: J
authors.lastname: Brücher
authors.forename: N
authors.initials: N
authors.lastname: Frickhofen
authors.forename: M
authors.initials: M
authors.lastname: Klausmann
authors.forename: P S
authors.initials: PS
authors.lastname: Mitrou
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
mesh_terms: D000368:Aged; D004999:Amifostine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000753:Anemia, Refractory / Q000097:blood* / Q000188:drug therapy*; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020246:Venous Thrombosis / Q000139:chemically induced
chemical_list: D014409:Tumor Necrosis Factor-alpha; D004999:Amifostine