Final results of the phase II study of rabbit anti-thymocyte globulin, ciclosporin, methylprednisone, and granulocyte colony-stimulating factor in patients with aplastic anaemia and myelodysplastic syndrome.

Abstract

This report describes the final results of a Phase II clinical trial investigating the efficacy of rabbit antithymocyte globulin (rATG), ciclosporin, steroids, and granulocyte colony-stimulating factor (GCSF) in patients with untreated aplastic anaemia (AA), or low to intermediate-risk and hypocellular myelodysplastic syndrome (MDS). We treated 24 patients each with AA and MDS with rATG (3·5 mg/kg/d × 5; reduced to 2·5 mg/kg/d × 5 in patients with MDS ≥ 55 years), ciclosporin (5 mg/kg orally daily × 6 months), steroids (1 mg/kg daily, tapered off over 1 month), and GCSF. The overall response rate in AA patients was 64% compared to 25% in MDS patients. The median time to response was 3 months in AA patients and 4 months in MDS patients. Pretreatment clinical characteristics, such as age, sex, blood counts, cellularity, cytogenetics, or HLA-DR15 status, did not predict for response. Response to therapy, however, predicted for improved overall survival (OS), with a 3-year OS of 89% vs. 43% in responders versus non-responders, respectively (P < 0·001). Infusion reactions occurred in about half the patients and were manageable. Myelosuppression, elevation in liver enzymes, and infections were common. The early mortality in MDS patients was 13% vs. 0% in AA patients.

• Authors: Tapan M Kadia, Gautam Borthakur, Guillermo Garcia-Manero, Stefan Faderl, Elias Jabbour, Zeev Estrov, Sergerrne York, Xuelin Huang, Sherry Pierce, Mark Brandt, Charles Koller, Hagop M Kantarjian, Farhad Ravandi
• Journal: British journal of haematology (Br J Haematol) Vol. 157 Issue 3 Pg. 312-20 (May 2012) ISSN: 1365-2141 [Electronic] England
• PMID: 22360602 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

• Antilymphocyte Serum
• Glucocorticoids
• Immunosuppressive Agents
• Granulocyte Colony-Stimulating Factor
• Cyclosporine
• Methylprednisolone

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anemia, Aplastic (drug therapy)
• Antilymphocyte Serum (administration & dosage, adverse effects, therapeutic use)
• Cyclosporine (administration & dosage, adverse effects, therapeutic use)
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Glucocorticoids (administration & dosage, adverse effects, therapeutic use)
• Granulocyte Colony-Stimulating Factor (administration & dosage, adverse effects, therapeutic use)
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects, therapeutic use)
• Male
• Methylprednisolone (administration & dosage, adverse effects, therapeutic use)
• Middle Aged
• Myelodysplastic Syndromes (drug therapy)
• Survival Analysis
• Treatment Outcome
• Young Adult