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Conditioning Regimens

The increase from 2.5 to 5 mg/kg of rabbit anti-thymocyte-globulin dose in reduced intensity conditioning reduces acute and chronic GVHD for patients with myeloid malignancies undergoing allo-SCT

Bone Marrow Transplantation volume 47, pages 639–645 (2012)Cite this article

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Abstract

We previously reported that reduced intensity conditioning (RIC) regimen with fludarabine, BU and 2.5 mg/kg of rabbit anti-thymocyte globulin (r-ATG) was effective but associated with a high rate of acute and chronic GVHD. Therefore, we increased the dose of r-ATG to 5 mg/kg. In this report, we analyzed 87 patients with AML or myelodysplastic syndrome (MDS) undergoing allo-SCT from an HLA-identical sibling donor from 2000 to 2010. RIC consisted of fludarabine, BU and r-ATG 2.5 mg/kg on 1 day (r-ATG1; n=53) or 2.5 mg/kg per day over 2 days (r-ATG2; n=22). Grade 2–4 acute GVHD incidence at day 100 was 30.2% and 8.8% in the r-ATG1 and r-ATG2 groups, respectively (P=0.038). Extensive chronic GVHD incidence was 60.4% and 12% in the r-ATG1 and r-ATG2 groups, respectively (P<0.001). The relapse incidences (RI) at 24 months were 18.9% and 28.5% in r-ATG1 and r-ATG2 groups, respectively (P=0.640). Overall and PFS were not different between the r-ATG1 and r-ATG2 groups. r-ATG dose at 5 mg/kg in the setting of RIC seems a good balance allowing GVHD prevention and antitumor effect with a remarkable reduction of GVHD incidence without an identical level of increased relapse rate.

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Acknowledgements

This work was supported by the following Grants: Pole ARECA from the Association pour la Recherche Contre le Cancer (ARC) (2001) and Programme Hospitalier de Recherche Clinique from ministry of health (2001). We are highly indebted to Pr William I Bensinger (FHCRC, Seattle, WA, USA) for his advices and critical review of this manuscript. We thank the nursing staff for providing excellent care for our patients. We also thank the following physicians at the Institut Paoli-Calmettes for their important study contributions and dedicated patient care: A Charbonnier, E D’incan, J Rey, C Oudin and A Granata.

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  1. Department of Hematology, Transplantation Program, Gene and Cell Therapy program, Institut Paoli Calmettes, Marseille, France

    R Devillier, R Crocchiolo, L Castagna, S Fürst, J El Cheikh, C Faucher, T Prebet, A Etienne, C Chabannon, N Vey & D Blaise

  2. Université de la Méditerranée, Marseille, France

    C Chabannon & D Blaise

  3. Department of Clinical Trial, Institut Paoli Calmettes, Marseille, France

    B Esterni

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Pr Blaise has contributed to educational events sponsored by Genzyme. The other authors declare no conflict of interest.

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Devillier, R., Crocchiolo, R., Castagna, L. et al. The increase from 2.5 to 5 mg/kg of rabbit anti-thymocyte-globulin dose in reduced intensity conditioning reduces acute and chronic GVHD for patients with myeloid malignancies undergoing allo-SCT. Bone Marrow Transplant 47, 639–645 (2012). https://doi.org/10.1038/bmt.2012.3

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