Phase II study of rabbit anti-thymocyte globulin, cyclosporine and granulocyte colony-stimulating factor in patients with aplastic anemia and myelodysplastic syndrome

Leukemia. 2009 Jul;23(7):1297-302. doi: 10.1038/leu.2009.28. Epub 2009 Feb 26.

Abstract

We investigated efficacy and safety of rabbit anti-thymocyte globulin (rATG), cyclosporine and granulocyte colony-stimulating factor (G-CSF) as first-line therapy for patients with aplastic anemia (AA) and low or intermediate-1 or hypoplastic myelodysplastic syndrome (MDS). rATG 3.5 mg/kg (or 2.5 mg/kg per day for patients >or=55 years with MDS) was given for 5 days. Cyclosporine (5 mg/kg) and G-CSF (5 microg/kg) were given daily and continued for up to 6 months or longer. Responses were assessed about 3 and 6 months after therapy. Thirty-six patients have been enrolled on study and 32 patients treated; 25 were evaluable for a response (13 with AA, 12 with MDS); the rest are too early. The median age was 62 years (range, 20-83) for patients with AA and 63 (range, 42-80) for patients with MDS. Of 13 patients, 12 (92%) patients with AA responded (5 complete response (CR), 7 partial response (PR)), whereas of 12 patients, 4 (33%) patients with MDS responded (1 CR, 3 PR). For patients with AA, the median time to response (TTR) was 93 days (range, 79-623), whereas in the MDS group the median TTR was 111 days (range, 77-139). Grade III/IV toxicities were mainly cytopenias and neutropenic fever. Combination of rATG, cyclosporine and G-CSF is safe and effective as first-line treatment of AA and has significant activity in low-risk MDS.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia, Aplastic / drug therapy*
  • Animals
  • Antilymphocyte Serum / administration & dosage
  • Antilymphocyte Serum / adverse effects
  • Antilymphocyte Serum / therapeutic use*
  • Cyclosporine / administration & dosage
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use*
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Rabbits

Substances

  • Antilymphocyte Serum
  • Granulocyte Colony-Stimulating Factor
  • Cyclosporine