title: Once-weekly dosing of recombinant human erythropoietin alpha in patients with myelodysplastic syndromes unresponsive to conventional dosing.
abstract: BACKGROUND
  Once-weekly dosing of recombinant human erythropoietin (rhEPO) in patients with myelodysplastic syndromes (MDS) has not been investigated thoroughly. We performed a clinical trial to evaluate the effects of this new dosing regimen in patients with MDS who were unresponsive to the conventional three-times-weekly schedule.
  
  
  METHODS
  Forty-eight patients with low- or intermediate-risk MDS were enrolled in a 12-week study. rhEPO alpha (rhEPOalpha) was administered once-weekly by subcutaneous injection with a starting dose of 40,000 U fixed dose. The drug dosage was increased to 60,000 U fixed dose if after 6 weeks there was no or suboptimal erythroid response.
  
  
  RESULTS
  Clinically significant responses were seen in 13 (27%) patients, with 11 improving their response after dose escalation of rhEPOalpha. Only one patient (case 23) maintains a response after a follow-up period of 14 months. All other patients had responses lasting between 10 and 43 weeks, with a median time to relapse of 20 weeks. Treatment was well tolerated, with no relevant adverse events. Response to therapy was associated with significantly higher concentrations of circulating erythroid blast-forming units and a decrease of the bone marrow fraction of apoptic CD34+ cells.
  
  
  CONCLUSIONS
  Once-weekly rhEPOalpha therapy results in an improvement of erythropoiesis in a subset of MDS patients who are unresponsive to conventional dosing, and may act by inhibiting apoptosis of erythroid precursors. These results warrant further investigation of this dosing regimen either alone or in combination with other agents.
authors.affiliation: Department of Medical Sciences, Regina Apostolorum Hospital, Albano Laziale, Italy. roberto.stasi@uniroma2.it
authors.forename: R
authors.initials: R
authors.lastname: Stasi
authors.forename: M
authors.initials: M
authors.lastname: Brunetti
authors.forename: E
authors.initials: E
authors.lastname: Terzoli
authors.forename: E
authors.initials: E
authors.lastname: Abruzzese
authors.forename: S
authors.initials: S
authors.lastname: Amadori
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D011379:Prognosis; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D011994:Recombinant Proteins; D004921:Erythropoietin