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Graft-Versus-Host Disease

Predictors of overall survival among patients treated with sirolimus/tacrolimus vs methotrexate/tacrolimus for GvHD prevention

Bone Marrow Transplantation volume 52, pages 1003–1009 (2017)Cite this article

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Abstract

Sirolimus (SIR)/tacrolimus (TAC) is an alternative to methotrexate (MTX)/TAC. However, rational selection among these GvHD prophylaxis approaches to optimize survival of individual patients is not possible based on current evidence. We compared SIR/TAC (n=293) to MTX/TAC (n=414). The primary objective was to identify unique predictors of overall survival (OS). Secondary objective was to compare acute and chronic GvHD, relapse, non-relapse mortality, thrombotic microangiopathy (TMA), hepatic veno-occlusive disease (VOD/SOS), and acute kidney injury. Day 100 grades II–IV acute GvHD was significantly reduced in SIR/TAC vs MTX/TAC group (63 vs 73%, P=0.02). An interaction between GvHD prophylaxis groups and comorbidity index (hematopoietic cell transplantation (HCT)-CI) significantly impacted OS. Patients with HCT-CI⩾4 had significantly worse OS with MTX/TAC (HR 1.86, 95% CI 1.14–3.04, P=0.01) while no such effect was seen for SIR/TAC (HR 0.78, 95% CI 0.48–1.26, P=0.31). Other end points did not significantly differ between groups except TMA and VOD/SOS were increased in the SIR/TAC group, but excess death from these complications was not observed. We conclude, GvHD prophylaxis approach of SIR/TAC is associated with reduced grades II–IV acute GvHD, comparable toxicity profile to MTX/TAC, and improved OS among patients with HCT-CI⩾4.

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Acknowledgements

Author contributions

FK, JK, LC, ED, VR, CA, JP contributed in designing the research, data collection, analyzing the data and writing the manuscript. BB, TN, FL, AM, LP, EA, MK-D, MN and HF contributed in research design, the data analysis critical review and manuscript writing.

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Authors and Affiliations

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

    F Khimani, B Betts, T Nishihori, F Locke, A Mishra, L Perez, E Ayala, M Kharfan-Dabaja, M Nieder, H Fernandez, C Anasetti & J Pidala

  2. Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    J Kim & L Chen

  3. Department of Medicine, University of South Florida, Tampa, FL, USA

    E Dean

  4. Division of Hematology and Medical Oncology, University of South Florida, Tampa, FL, USA

    V Rizk

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  1. F Khimani
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Correspondence to J Pidala.

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Khimani, F., Kim, J., Chen, L. et al. Predictors of overall survival among patients treated with sirolimus/tacrolimus vs methotrexate/tacrolimus for GvHD prevention. Bone Marrow Transplant 52, 1003–1009 (2017). https://doi.org/10.1038/bmt.2017.63

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