title: A randomized controlled study in patients with newly diagnosed severe aplastic anemia receiving antithymocyte globulin (ATG), cyclosporine, with or without G-CSF: a study of the SAA Working Party of the European Group for Blood and Marrow Transplantation.
abstract: We evaluated the role of granulocyte colony-stimulating factor (G-CSF) in patients with severe aplastic anemia (SAA) treated with antithymocyte globulin (ATG) and cyclosporine (CSA). Between January 2002 and July 2008, 192 patients with newly diagnosed SAA not eligible for transplantation were entered into this multicenter, randomized study to receive ATG/CSA with or without G-CSF. Overall survival (OS) at 6 years was 76% ± 4%, and event-free survival (EFS) was 42% ± 4%. No difference in OS/EFS was seen between patients randomly assigned to receive or not to receive G-CSF, neither for the entire cohort nor in subgroups stratified by age and disease severity. Patients treated with G-CSF had fewer infectious episodes (24%) and hospitalization days (82%) compared with patients without G-CSF (36%; P = .006; 87%; P = .0003). In a post hoc analysis of patients receiving G-CSF, the lack of a neutrophil response by day 30 was associated with significantly lower response rate (56% vs 81%; P = .048) and survival (65% vs 87%; P = .031). G-CSF added to standard ATG and CSA reduces the rate of early infectious episodes and days of hospitalization in very SAA patients and might allow early identification of nonresponders but has no effect on OS, EFS, remission, relapse rates, and mortality. This study was registered at www.clinicaltrials.gov as NCT01163942.
authors.affiliation: Hematology, University Hospital Basel, Basel, Switzerland. tichelli@datacomm.ch
authors.forename: André
authors.initials: A
authors.lastname: Tichelli
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.forename: Judith
authors.initials: J
authors.lastname: Marsh
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.forename: Anke
authors.initials: A
authors.lastname: Franzke
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Martin
authors.initials: M
authors.lastname: Wilhelm
authors.forename: Britta
authors.initials: B
authors.lastname: Höchsmann
authors.forename: Alain
authors.initials: A
authors.lastname: Barrois
authors.forename: Kim
authors.initials: K
authors.lastname: Champion
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Passweg
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine