Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party.

Abstract

Rabbit antithymocyte globulin (rATG; thymoglobulin, Genzyme) in combination with cyclosporine, as first-line immunosuppressive therapy, was evaluated prospectively in a multicenter, European, phase 2 pilot study, in 35 patients with aplastic anemia. Results were compared with 105 age- and disease severity-matched patients from the European Blood and Marrow Transplant registry, treated with horse ATG (hATG; lymphoglobulin) and cyclosporine. The primary end point was response at 6 months. At 3 months, no patients had achieved a complete response to rATG. Partial response occurred in 11 (34%). At 6 months, complete response rate was 3% and partial response rate 37%. There were 10 deaths after rATG (28.5%) and 1 after subsequent HSCT. Infections were the main cause of death in 9 of 10 patients. The best response rate was 60% for rATG and 67% for hATG. For rATG, overall survival at 2 years was 68%, compared with 86% for hATG (P = .009). Transplant-free survival was 52% for rATG and 76% for hATG (P = .002). On multivariate analysis, rATG (hazard ratio = 3.9, P = .003) and age more than 37 years (hazard ratio = 4.7, P = .0008) were independent adverse risk factors for survival. This study was registered at www.clinicaltrials.gov as NCT00471848.

• Authors: Judith C Marsh, Andrea Bacigalupo, Hubert Schrezenmeier, Andre Tichelli, Antonio M Risitano, Jakob R Passweg, Sally B Killick, Alan J Warren, Theodora Foukaneli, Mahmoud Aljurf, H A Al-Zahrani, Britta Höchsmann, Philip Schafhausen, Alexander Roth, Anke Franzke, Tim H Brummendorf, Carlo Dufour, Rosi Oneto, Philip Sedgwick, Alain Barrois, Shahram Kordasti, Modupe O Elebute, Ghulam J Mufti, Gerard Socie, European Blood and Marrow Transplant Group Severe Aplastic Anaemia Working Party
• Journal: Blood (Blood) Vol. 119 Issue 23 Pg. 5391-6 (Jun 07 2012) ISSN: 1528-0020 [Electronic] United States
• PMID: 22544699 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antilymphocyte Serum
• Immunosuppressive Agents
• Cyclosporine

Topics

• Adolescent
• Adult
• Aged
• Anemia, Aplastic (drug therapy)
• Animals
• Antilymphocyte Serum (adverse effects, therapeutic use)
• CD4-Positive T-Lymphocytes (drug effects)
• Cyclosporine (adverse effects, therapeutic use)
• Drug Therapy, Combination
• Europe
• Female
• Horses
• Humans
• Immunosuppressive Agents (adverse effects, therapeutic use)
• Male
• Middle Aged
• Pilot Projects
• Prospective Studies
• Rabbits
• Survival Analysis
• Young Adult