title: Treatment of severe aplastic anemia with antilymphocyte globulin, cyclosporine and two different granulocyte colony-stimulating factor regimens: a GITMO prospective randomized study.
abstract: OBJECTIVE
  In a previous study we showed that patients with severe aplastic anemia (SAA) treated with anti-lymphocyte globulin (ALG), cyclosporin (CyA) and granulocyte colony-stimulating factor (G-CSF) 5 micro g/kg/day had an encouraging outcome. However, failure to respond, delayed responses, partial responses, relapses and early deaths remain significant problems. The aim of the present study was to test whether a higher dose of G-CSF (10 micro g/kg/day) would reduce these complications.
  
  
  METHODS
  This was a multicenter prospective trial in 77 SAA patients treated with horse ALG (15 mg/kg/day day1-5) and CyA (5 mg/kg/day day 1-180). Patients were randomized to receive G-CSF 5 micro g/kg/day (n=38, group A) or 10 micro g/kg/day (n=39, group B) from day +1 to day +30. All patients then received G-CSF 5 micro g/kg/day from day +31 to day +90. The primary end point of this study was response at day +120. Secondary end points were early deaths, blood counts at day +120, and survival.
  
  
  RESULTS
  At day +120 responses were classified as absent, partial, and complete in 12, 22, and 4 patients in group A and in 23, 7, and 9 patients in group B (p=0.001). At last follow-up these figures were respectively 9, 12, and 17 vs 19, 2, and 18 (p=0.004). Thirteen patients (5 in group A and 8 in group B) died before day 120 (p=0.3). Median peripheral blood counts on day 120 were comparable in the two groups: Hb 10.5 and 9.5 g/dL in group A and B, respectively (p=0.6), Neutrophil counts were 2.4 vs 1.9x10(9)/L in groups A and B (p=0.4) and platelet counts were, respectively, 42 vs 36x10(9)/L (p=0.3). The actuarial survival at 4 years is 72% in group A and 67% in group B (p=0.3).
  
  
  CONCLUSIONS
  Increasing the dose of G-CSF does not appear to reduce early deaths, does not improve peripheral blood counts nor survival, and may reduce the response rate in patients with SAA receiving ALG and CyA.
authors.affiliation: Ematologia e Trapianto di Midollo, Ospedale San Camillo, Circonvallazione Gianicolense 87, 00152 Rome, Italy. annabri@libero.it
authors.forename: Anna
authors.initials: A
authors.lastname: Locasciulli
authors.forename: Barbara
authors.initials: B
authors.lastname: Bruno
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Paola
authors.initials: P
authors.lastname: Saracco
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.forename: Carlo
authors.initials: C
authors.lastname: Finelli
authors.forename: Simona
authors.initials: S
authors.lastname: Sica
authors.forename: Stefania
authors.initials: S
authors.lastname: Varotto
authors.forename: William
authors.initials: W
authors.lastname: Arcese
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Davide
authors.initials: D
authors.lastname: Soligo
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001772:Blood Cell Count; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization; D006736:Horses; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015993:Life Tables; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine; D008775:Methylprednisolone