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A prospective, randomised, phase II study of horse antithymocyte globulin vs rabbit antithymocyte globulin as immune-modulating therapy in patients with low-risk myelodysplastic syndromes

Leukemia volume 18, pages 460–465 (2004)Cite this article

Abstract

Immunosuppression has recently been proposed for low-risk myelodysplastic syndromes (MDS) to reverse bone marrow failure by inhibiting intramedullary secretion of proapoptotic cytokines. We treated 35 MDS patients (24 refractory anaemia (RA), 10 RA with excess blasts and one chronic myelomonocytic leukaemia) with either horse antithymocyte globulin 15 mg/kg/day or rabbit antithymocyte globulin 3.75 mg/kg/day, each for 5 days. Median age was 63 years (range: 41–75). After 1 to 34+ months of follow-up (mean: 15+), four patients experienced complete haematological responses (CR), six good responses (GR) and two minor responses. All CRs and GRs occurred in patients with RA, in whom both horse and rabbit ATG yielded five responses out of 12 (42%). Time to response varied between 1 and 10 (mean: 3) months. The median duration of response was 9+ (1–17+) months; five patients are in continuing response. In all, 23 patients suffered side effects >°II WHO (the degree of toxicity encountered according to the internationally accepted WHO toxicity grading); one patient died 2 weeks after rabbit ATG from rhinocerebral mucormycosis. Parameters that correlated with response were duration of disease and RA subgroup. In our experience, immune-modulating therapy with either horse or rabbit ATG is feasible in patients with RA and short duration of disease.

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Acknowledgements

We are grateful to Professor Hartmut Hecker, Department of Biometry, Hannover Medical School, for his invaluable help with the statistical analyses, to Dietmar Klose, Department of Hematology and Oncology, Hannover Medical School, for graphical assistance and to Michael Morgan, Department of Hematology and Oncology, Hannover Medical School, for critical reading of the manuscript. This work was supported in part by Imtix SangStat GmbH, Leimen, Germany, to AG.

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Authors and Affiliations

  1. Department of Haematology and Oncology, Medizinische Hochschule, Hannover, Germany

    M Stadler, W Verbeek & A Ganser

  2. Department of Haematology and Oncology, Heinrich-Heine-Universität, Düsseldorf, Germany

    U Germing

  3. Department of Haematology and Oncology, Friedrich-Schiller-Universität, Jena, Germany

    K-O Kliche

  4. Department of Haematology and Oncology, Deutsche Klinik für Diagnostik, Wiesbaden, Germany

    K M Josten

  5. Department of Haematology and Oncology, St Georgs-Hospital, Hamburg, Germany

    R Kuse

  6. Department of Haematology and Oncology, JW Goethe-Universität, Frankfurt, Germany

    W-K Hofmann

  7. Department of Haematology and Oncology, Freie Universität, Berlin, Germany

    H Schrezenmeier

  8. Department of Haematology and Oncology, Universität Essen, Germany

    J Novotny

  9. Department of Haematology and Oncology, Klinikum Südstadt, Rostock, Germany

    O Anders

  10. Department of Haematology and Oncology, St Marien-Hospital, Hagen, Germany

    H Eimermacher

  11. Department of Pathology, Medizinische Hochschule, Hannover, Germany

    H-H Kreipe

  12. Department of Haematology and Oncology, Universität Ulm, Germany

    H Heimpel

  13. Department of Haematology and Oncology, St Johannes-Hospital, Duisburg, Germany

    C Aul

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  1. M Stadler
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Correspondence to A Ganser.

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Stadler, M., Germing, U., Kliche, KO. et al. A prospective, randomised, phase II study of horse antithymocyte globulin vs rabbit antithymocyte globulin as immune-modulating therapy in patients with low-risk myelodysplastic syndromes. Leukemia 18, 460–465 (2004). https://doi.org/10.1038/sj.leu.2403239

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