Immunosuppressive Therapy: Exploring an Underutilized Treatment Option for Myelodysplastic Syndrome

Clin Lymphoma Myeloma Leuk. 2016 Aug;16 Suppl:S44-8. doi: 10.1016/j.clml.2016.02.017.


Background: Immunosuppressive therapy (IST) in low risk myelodysplastic syndrome (MDS) is known to achieve hematologic improvement but remains an underutilized treatment option. We report our experience using antithymocyte globulin (ATG) and cyclosporine A (CSA) to explore clinical predictive response factors.

Patients and methods: Patients treated with IST identified in the Moffitt Cancer Center MDS database were analyzed using baseline data, IST details, and response rates.

Results: Sixty-six patients treated with IST were identified. The median age was 61 years; the majority were at low risk and had a good karyotype. The median time to start IST was 1 year. All patients received ATG, 60% rabbit (r-ATG), 32% equine ATG (e-ATG), and 60% received CSA. Overall hematologic improvement was 42% with a trend favoring e-ATG over r-ATG (52% vs. 39%; P = .09). Erythroid improvement was evaluated in 30 patients, and 60% responded; neutrophil improvement was evaluated in 15, and 39% responded; platelet improvement was evaluated in 18, and 57% responded. Six of 18 pancytopenic patients experienced trilineage response. Mean time from ATG to next therapy was 12 months. None of the patients with very high risk or high risk revised International Prognostic Scoring System (IPSS-R) responded. Poor karyotype had a lower response rate, 25%, compared to 41% for intermediate and 44% for good karyotype. No difference in predicting response was found based on the National Institutes of Health Response Model; 38% with low and 45% with high probability responded. A trend favored treatment within 2 years from diagnosis, with 46% responding compared to 33% treated after 2 years. First-line ATG or after lenalidomide responded better than after azacitidine or third-line therapy. CSA provided an advantage: the disease of 51% responded compared to 27% with ATG alone (P = .05). Ten patients experienced transformation to acute myeloid leukemia, 7% with disease that responded to therapy and 24% with disease that did not respond to therapy (P = .08). Overall survival was 67.2 months without difference between those with and without response. Adverse events were reported in 55 patients. Infusion reactions occurred in 85% but was similar between ATG types. Infection rate was 25% and higher with e-ATG. Serum sickness was reported in 18% and significantly higher with r-ATG.

Conclusion: IST has a hematologic improvement response rate in the range of other therapies approved for lower risk MDS. High risk IPSS-R, poor karyotype, and treatment after 2 years from diagnosis have unfavorable response trend. ATG with CSA has higher response than ATG alone. First-line ATG or after lenalidomide had better response trend compared to third-line therapy or azacitidine therapy.

Keywords: ATG; Cyclosporine; IPSS-R; Low risk MDS; NIH response model.

MeSH terms

  • Adult
  • Aged
  • Bone Marrow / pathology
  • Female
  • Humans
  • Immunosuppression Therapy* / methods
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / immunology
  • Myelodysplastic Syndromes / mortality
  • Severity of Illness Index
  • Survival Analysis
  • Treatment Outcome


  • Immunosuppressive Agents