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EASIX and mortality after allogeneic stem cell transplantation

Bone Marrow Transplantation volume 55, pages 553–561 (2020)Cite this article

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Abstract

Allogeneic stem cell transplantation (alloSCT) is an effective immunotherapy in patients with hematological malignancies. Endothelial dysfunction was linked to major complications after alloSCT. We asked the question if the “Endothelial Activation and Stress Index” (EASIX; [(creatinine × LDH) ÷ thrombocytes]) can predict mortality after alloSCT. We performed a retrospective cohort analysis in five alloSCT centers in the USA and Germany. EASIX was assessed prior to conditioning (EASIX-pre) and correlated with mortality in 755 patients of a training cohort in multivariable models. The predictive model established in the training cohort was validated in 1267 adult allo-recipients. Increasing EASIX-pre predicted lower overall survival (OS) after alloSCT, and successful model validation was achieved for the validation cohort. We found that EASIX-pre predicts OS irrespective of established scores. Moreover, EASIX-pre was also a significant prognostic factor for transplant-associated microangiopathy. Finally, EASIX-pre correlated with biomarkers of endothelial homeostasis such as CXCL8, interleukin-18, and insulin-like-growth-factor-1 serum levels. This study establishes EASIX-pre based on a standard laboratory biomarker panel as a predictor of individual risk of mortality after alloSCT independently from established clinical criteria.

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Acknowledgements

We thank the following funding agencies for supporting this work: Deutsche Forschungsgemeinschaft (TL820.8-1), Deutsche Krebshilfe (70113519), Wilhelm-Sander-Stiftung (2016.077.1), and EU306240 for supporting TL; José Carreras Leukämie-Stiftung (11R2016, 03 R/2019), Deutsche Krebshilfe (70113519), and Deutsche Forschungsgemeinschaft (PE 1450/7-1) Monika-Kutzner-Stiftung, and Wilhelm-Sander-Stiftung (2014.150.1) for supporting OP; and CA 78902, CA 18029, aCA 15704, HL 122173 for supporting RS, TG, and BMS.

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Authors and Affiliations

  1. Medicine V, University Hospital Heidelberg, Heidelberg, Germany

    Thomas Luft, Aleksandar Radujkovic & Peter Dreger

  2. Division of Biostatistics, German Cancer Research Centre, Heidelberg, Germany

    Axel Benner & Tobias Terzer

  3. Oncology, Hematology, Cincinnati Children’s Hospital Medical Centre, Cincinnati, OH, USA

    Sonata Jodele & Christopher E. Dandoy

  4. Fred Hutchinson Cancer Research Centre, Seattle, WA, USA

    Rainer Storb, Ted Gooley, Brenda M. Sandmaier & Mohamed Sorror

  5. University of Washington, Seattle, WA, USA

    Rainer Storb, Ted Gooley, Brenda M. Sandmaier & Mohamed Sorror

  6. Department of Bone Marrow Transplantation, West German Cancer Centre, University Hospital Essen, University of Duisburg-Essen, Duisburg, Germany

    Lambros Kordelas & Dietrich Beelen

  7. Department of Nephrology, University of Heidelberg, Heidelberg, Germany

    Markus Zeisbrich

  8. Charité Universitätsmedizin Berlin, Hematology, Oncology and Tumorimmunology, Berlin, Germany

    Olaf Penack

  9. Berlin-Brandenburg Centre for Regenerative Therapies, Berlin, Germany

    Olaf Penack

  10. Berlin Institute of Health, Berlin, Germany

    Olaf Penack

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  1. Thomas Luft
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Correspondence to Thomas Luft.

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Luft, T., Benner, A., Terzer, T. et al. EASIX and mortality after allogeneic stem cell transplantation. Bone Marrow Transplant 55, 553–561 (2020). https://doi.org/10.1038/s41409-019-0703-1

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