title: Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care--SAKK 33/99.
abstract: OBJECTIVE
  Immunosuppressive treatment is reported to improve cytopenia in some patients with myelodysplastic syndrome (MDS). Combined antithymocyte globulin (ATG) and cyclosporine (CSA) is most effective in patients with immune-mediated marrow failure.
  
  
  METHODS
  This trial was designed to assess the impact of immunosuppression on hematopoiesis, transfusion requirements, transformation, and survival in patients with MDS randomly assigned to 15 mg/kg of horse ATG for 5 days and oral CSA for 180 days (ATG+CSA) or best supportive care (BSC), stratified by treatment center and International Prognostic Scoring System (IPSS) risk score. Primary end point was best hematologic response at 6 months. Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤ 2 and transfusion dependency of less than 2 years in duration.
  
  
  RESULTS
  Between 2000 and 2006, 45 patients received ATG+CSA (median age, 62 years; range, 23 to 75 years; 56% men) and 43 patients received BSC (median age, 65 years; range, 24 to 76 years; 81% men). IPSS score was low, intermediate-1, intermediate-2, high, and not evaluable in eight, 24, seven, one, and five patients on ATG+CSA, respectively, and eight, 25, five, zero, and five patients on BSC, respectively. Refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess of blasts (RAEB) -I, RAEB-II, and hypoplastic disease were present in 21, six, nine, zero, and nine patients on ATG+CSA, respectively, and 18, eight, 11, two, and four patients on BSC, respectively. By month 6, 13 of 45 patients on ATG+CSA had a hematologic response compared with four of 43 patients on BSC (P = .0156). Two-year transformation-free survival (TFS) rates were 46% (95% CI, 28% to 62%) and 55% (95% CI, 34% to 70%) for ATG+CSA and BSC patients, respectively (P = .730), whereas overall survival (OS) estimates were 49% (95% CI, 31% to 66%) and 63% (95% CI, 42% to 78%), respectively (P = .828).
  
  
  CONCLUSIONS
  This open-label randomized phase III trial demonstrates that ATG+CSA treatment seems to be associated with hematologic response in a subset of patients without apparent impact on TFS and OS.
authors.affiliation: Medecin-Chef de Service, Service d'Hématologie, Departement Medecine Interne, Hôpitaux Universitaires de Geneve, Rue Micheli-du-Crest 24, 1211 Geneva 14, Switzerland. jakob.passweg@bluewin.ch
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Passweg
authors.forename: Aristoteles A N
authors.initials: AA
authors.lastname: Giagounidis
authors.forename: Mathew
authors.initials: M
authors.lastname: Simcock
authors.forename: Carlo
authors.initials: C
authors.lastname: Aul
authors.forename: Christiane
authors.initials: C
authors.lastname: Dobbelstein
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.forename: Gert
authors.initials: G
authors.lastname: Ossenkoppele
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.forename: Kristina
authors.initials: K
authors.lastname: Schilling
authors.forename: André
authors.initials: A
authors.lastname: Tichelli
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
mesh_terms: D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006296:Health Services / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine