title: Prospective phase II Study on 5-days azacitidine for treatment of symptomatic and/or erythropoietin unresponsive patients with low/INT-1-risk myelodysplastic syndromes.
abstract: OBJECTIVE
  This phase II prospective study aimed to evaluate the efficacy and safety of 5-days azacytidine (5d-AZA) in patients with low-risk myelodysplastic syndromes (MDS). Second, single-nucleotide polymorphism (SNP) genetic profile and phosphoinositide-phospholipase C (PI-PLC) β1 levels were studied to evaluate possible biologic markers able to predict the hematologic response.
  
  
  METHODS
  The study tested a lower intensity schedule of azacytidine. The treatment plan consisted of 75 mg/sqm/d subcutaneous administered for 5 days every 28 days, for a total of 8 cycles.
  
  
  RESULTS
  Thirty-two patients were enrolled in the study. The overall response rate was 47% (15 of 32) on intention-to-treat and 58% (15 of 26) for patients completing the treatment program. In this latter group, 5 (19%) achieved complete remission (CR) and 10 (38%) had hematologic improvement, according to the International Working Group (IWG) criteria. Three patients have maintained their hematologic improvement after 37, 34, and 33 months without other treatments. Moreover, 21 and 2 of 26 cases completing 8 cycles were transfusion-dependent for red blood cells and platelets at baseline, respectively. Of these, 7 (33%) and 2 (100%) became transfusion-independent at the end of the treatment program, respectively. Grade 3-4 neutropenia occurred in 28% of patients and 4 patients died early due to infections or hemorrhage. SNP results were not significantly correlated to the clinical outcome, whereas PI-PLCβ1 level anticipated either positive or negative clinical responses.
  
  
  CONCLUSIONS
  5d-AZA is safe and effective in a proportion of patients with low-risk MDS. PI-PLCβ1 gene expression is a reliable and dynamic marker of response that can be useful to optimize azacytidine therapy.
authors.affiliation: Chair of Hematology, Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Brescia, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Filì
authors.forename: Michele
authors.initials: M
authors.lastname: Malagola
authors.forename: Matilde Y
authors.initials: MY
authors.lastname: Follo
authors.forename: Carlo
authors.initials: C
authors.lastname: Finelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Iacobucci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Federica
authors.initials: F
authors.lastname: Cattina
authors.forename: Cristina
authors.initials: C
authors.lastname: Clissa
authors.forename: Anna
authors.initials: A
authors.lastname: Candoni
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Monica
authors.initials: M
authors.lastname: Bocchia
authors.forename: Marzia
authors.initials: M
authors.lastname: Defina
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Spedini
authors.forename: Cristina
authors.initials: C
authors.lastname: Skert
authors.forename: Lucia
authors.initials: L
authors.lastname: Manzoli
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006403:Hematologic Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D054799:Phospholipase C beta / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D016896:Treatment Outcome; D051155:Wnt1 Protein / Q000235:genetics*
chemical_list: D051155:Wnt1 Protein; D004921:Erythropoietin; D054799:Phospholipase C beta; D001374:Azacitidine