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

J Clin Oncol. 2011 Jan 20;29(3):303-9. doi: 10.1200/JCO.2010.31.2686. Epub 2010 Dec 13.


Purpose: 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.

Patients and 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).

Conclusion: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antilymphocyte Serum / adverse effects
  • Antilymphocyte Serum / therapeutic use*
  • Cell Transformation, Neoplastic / drug effects
  • Cross-Over Studies
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Health Services / statistics & numerical data
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Intention to Treat Analysis
  • Logistic Models
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Prospective Studies
  • Survival Analysis


  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Cyclosporine