Abstract
This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III–IV acute GVHD was associated with a worse OS (HR=0.4, P<0.0.001) owing to high risk of nonrelapse mortality (NRM; HR=5.2, P<0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR=0.72; P=0.07) translating into a better OS (HR=1.8; P<0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR=0.65; P=0.02) but also with higher NRM (HR=3.5; P<0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (P<0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR=0.65; P=0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD.
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Acknowledgements
We thank Emmanuelle Polge, Bénédicte Samey, Betty Bouveur and Raoni Rocha from the office of the ALWP of EBMT. FB is Senior Research Associate at the National Fund for Scientific Research (FNRS) Belgium. Centers that contributed patient data are listed in the Supplementary Appendix.
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MM has received lectures honoraria and research support from Genzyme and Fresenius whose products are discussed in this manuscript. FB has received lectures honoraria and research support from Genzyme. DB has received honoraria from Genzyme. AN has received research grants from Fresenius and Genzyme, took part in some of their clinical trials (Fresenius and Genzyme), participated in their investigator meeting and advisory board (Genzyme) and lectured for them (satellite meeting and special meeting+honorarium).
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The study has been presented in part as an oral abstract at the 53rd Annual Meeting of the American Society of Hematology, 10–13 December 2011, San Diego, CA, as well as in the 2012 meeting of the European group for Blood and Marrow Transplantation, Geneva 1-4.
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Baron, F., Labopin, M., Niederwieser, D. et al. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation. Leukemia 26, 2462–2468 (2012). https://doi.org/10.1038/leu.2012.135
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DOI: https://doi.org/10.1038/leu.2012.135
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