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Graft-Versus-Host Disease

Tacrolimus plus sirolimus with or without ATG as GVHD prophylaxis in HLA-mismatched unrelated donor allogeneic stem cell transplantation

Bone Marrow Transplantation volume 52, pages 438–444 (2017)Cite this article

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Abstract

HLA-matched related or unrelated donors are not universally available. Consequently, patients can be offered hematopoietic stem cell transplantation (HSCT) from alternative donors, including mismatched unrelated donors (MMURD), known to cause a higher incidence of acute GVHD (aGVHD) and chronic GVHD. In vivo T-cell-depletion strategies, such as antithymocyte globulin (ATG) therapy, significantly decrease the risk of GVHD. We performed a multicenter, retrospective study comparing tacrolimus (TAC) and sirolimus (SIR) with or without ATG in 104 patients (TAC-SIR=45, TAC-SIR-ATG=59) who underwent MMURD HSCT. Use of ATG was associated with a lower incidence, albeit not statistically significant, of grades 2–4 aGVHD (46% vs 64%, P=0.09), no difference in grades 3–4 aGVHD (10% vs 15%, P=0.43), a trend for a lower incidence of moderate/severe chronic GVHD (16% vs 37%, P=0.09) and more frequent Epstein–Barr virus reactivation (54% vs 18%, P=0.0002). There were no statistically significant differences in 3-year overall survival (OS) (TAC-SIR-ATG=40% (95% confidence interval (CI)=24–56%) vs TAC-SIR=54% (95% CI=37–70%), P=0.43) or 3-year cumulative incidence of relapse/progression (TAC-SIR-ATG=40% (95% CI=28–58%) vs TAC-SIR=22% (95% CI=13–39%), P=0.92). An intermediate Center for International Blood & Marrow Transplant Research disease risk resulted in a significantly lower non-relapse mortality and better OS at 3 years. Our study suggests that addition of ATG to TAC-SIR in MMURD HSCT does not affect OS when compared with TAC-SIR alone.

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Acknowledgements

This work was presented in part at the annual meeting of the American Society of Hematology in Orlando, FL, USA in December 2015 (abstract no. 3142).

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Author notes

  1. M A Kharfan-Dabaja and R Parody: These authors share first authorship.

Authors and Affiliations

  1. Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    M A Kharfan-Dabaja, J Perkins, J Shapiro, J Pidala & C Anasetti

  2. Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)/CSIC, Sevilla, Spain

    R Parody, J Falantes & J A Perez-Simón

  3. College of Pharmacy, University of South Florida, Tampa, FL, USA

    J Perkins

  4. Hospital Universitario de Salamanca, Salamanca, Spain

    O Lopez-Godino, L Lopez-Corral, L Vazquez & D Caballero

  5. Hospital Universitario Vall d'Hebron, Barcelona, Spain

    G Ortí, P Barba & D Valcárcel

  6. Hospital Santa Creu i Sant Pau, Barcelona, Spain

    A Esquirol & R Martino

  7. Hospital Clínico de Valenci, Valencia, Spain

    J L Piñana & C Solano

  8. Center for Evidence-Based Medicine, University of South Florida College of Medicine, Tampa, FL, USA

    A Tsalatsanis

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Correspondence to J A Perez-Simón.

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Kharfan-Dabaja, M., Parody, R., Perkins, J. et al. Tacrolimus plus sirolimus with or without ATG as GVHD prophylaxis in HLA-mismatched unrelated donor allogeneic stem cell transplantation. Bone Marrow Transplant 52, 438–444 (2017). https://doi.org/10.1038/bmt.2016.269

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