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Improving the EASIX’ predictive power for NRM in adults undergoing allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation (2024)Cite this article

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The Endothelial Activation and Stress Index (EASIX), calculated as creatinine (mg/dL) x lactate dehydrogenase (LDH; U/L) / platelets (x 109/L), is a laboratory-based prognostic index designed for predicting treatment response and survivorship in patients with acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) [1]. Since its definition, several publications have demonstrated that EASIX is an indirect evaluator of endothelial activity and that higher values of EASIX before and during the early post-transplant period have predictive power for non-relapse mortality (NRM) and overall survival (OS) [2,3,4,5,6,7,8]. However, some issues remain on what is the most effective way of using the information of the index, particularly if there is a more appropriate timing on its measurement for prognostic use.

Nawas et al. and our HCT group reported the inherent variations of EASIX values appearing during the post-transplant period, something expected considering that the values of the variables used in its calculation vary during the transplant process secondary to myelotoxicity derived from the conditioning regimen, engraftment process, transfusion support, infections, and specific complications. Interestingly, these studies also concluded that the predictive power of EASIX for NRM and OS persists irrespectively to the timepoint when it is estimated [9,10,11]. Having established the utility of EASIX for the detection of patients with high risk for NRM, the next step is facilitating its use in clinical practice by finding the cut-off value of the index that better classifies patients into high and low-risk groups.

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All data generated or analyzed during this study are included in this published article.

References

  1. Luft T, Benner A, Jodele S, Dandoy CE, Storb R, Gooley T, et al. EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis. Lancet Haematol. 2017;4. https://doi.org/10.1016/s2352-3026(17)30108-4

  2. Luft T, Benner A, Terzer T, Jodele S, Dandoy CE, Storb R, et al. EASIX and mortality after allogeneic stem cell transplantation. Bone Marrow Transpl. 2019;55:553–61. https://doi.org/10.1038/s41409-019-0703-1

    Article  CAS  Google Scholar 

  3. Shouval R, Fein JA, Shouval A, Danylesko I, Shem-Tov N, Zlotnik M, et al. External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation. Blood Adv. 2019;3:1881–90. https://doi.org/10.1182/bloodadvances.2019032268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Peña M, Salas MQ, Mussetti A, Moreno-Gonzalez G, Bosch A, Patiño B, et al. Pretransplantation EASIX predicts intensive care unit admission in allogeneic hematopoietic cell transplantation. Blood Adv. 2021;5:3418–26. https://doi.org/10.1182/bloodadvances.2021004812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Korell F, Schreck N, Müller-Tidow C, Dreger P, Luft T. Pre-transplant EASIX and sepsis after allogeneic stem cell transplantation. Intensive Care Med. 2022;48:753–5. https://doi.org/10.1007/s00134-022-06676-3

    Article  PubMed  PubMed Central  Google Scholar 

  6. Sihe J, Penack O, Terzer T, Schult D, Majer-Lauterbach, Radujkovic A, et al. Predicting sinusoidal obstruction syndrome after allogeneic stem cell transplantation with the EASIX Biomarker panel. Haematologica. 2020;106:446–53. https://doi.org/10.3324/haematol.2019.238790

    Article  CAS  Google Scholar 

  7. Varma A, Rondon G, Srour SA, Chen J, Ledesma C, Champlin RE, et al. Endothelial activation and stress index (EASIX) at admission predicts fluid overload in recipients of Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transpl. 2020;26:1013–20. https://doi.org/10.1016/j.bbmt.2020.01.028

    Article  CAS  Google Scholar 

  8. Dai H, Penack O, Radujkovic A, Schult D, Majer-Lauterbach J, Blau IW, et al. Early bilirubinemia after allogeneic stem cell transplantation—an endothelial complication. Bone Marrow Transpl. 2021;56:1573–83. https://doi.org/10.1038/s41409-020-01186-6

    Article  CAS  Google Scholar 

  9. Nawas MT, Sanchez-Escamilla M, Devlin SM, Maloy MA, Ruiz JD, Sauter CS, et al. Dynamic EASIX scores closely predict nonrelapse mortality after allogeneic hematopoietic cell transplantation. Blood Adv. 2022;6:5898–907. https://doi.org/10.1182/bloodadvances.2022007381

    Article  PubMed  PubMed Central  Google Scholar 

  10. Sanchez-Escamilla M, Flynn J, Devlin S, Maloy M, Fatmi SA, Alarcon Tomas A, et al. EASIX score predicts inferior survival after allogeneic hematopoietic cell transplantation. Bone Marrow Transpl. 2023;58:498–505. https://doi.org/10.1038/s41409-023-01922-8

    Article  CAS  Google Scholar 

  11. Escribano-Serrat S, Rodríguez-Lobato LG, Charry P, Martínez-Cibrian N, Suárez-Lledó M, Rivero A, et al. Endothelial Activation and Stress Index in adults undergoing allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide-based prophylaxis. Cytotherapy. 2024;26:73–80. https://doi.org/10.1016/j.jcyt.2023.10.008

    Article  CAS  PubMed  Google Scholar 

  12. Longato E, Vettoretti M, Di Camillo B. A practical perspective on the concordance index for the evaluation and selection of prognostic time-to-event models. J Biomed Inf. 2020;108:103496.

    Article  Google Scholar 

  13. Ranganathan P, Pramesh C, Buyse M. Common pitfalls in statistical analysis: the perils of multiple testing. Perspect Clin Res. 2016;7:106. https://doi.org/10.4103/2229-3485.179436

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Hematopathology, Pathology Department, CDB, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Silvia Escribano-Serrat & Maribel Díaz-Ricart

  2. Hematopoietic Transplantation Unit and Hematology Department, Clinical Institute of Hematology and Oncology (ICMHO), IDIBAPS, Hospital Clínic, Barcelona, Spain

    Luis Gerardo Rodríguez-Lobato, María Suárez-Lledó, Alexandra Pedraza, Jordi Esteve, Laura Rosiñol, Francesc Fernández-Avilés, Carmen Martínez, Montserrat Rovira & María Queralt Salas

  3. Apheresis & Cellular Therapy Unit, Department of Hemotherapy and Hemostasis, ICMHO, IDIBAPS, Hospital Clínic, Barcelona, Spain

    Paola Charry, Joan Cid & Miquel Lozano

  4. Fundació i Institut de Recerca Josep Carreras contra la leucèmia (Campus Clínic), Barcelona, Spain

    Enric Carreras

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Contributions

MQS designed the study. MQS, LGRL and SES did the statistical analysis, interpreted the results, and wrote the letter. MSL, AP, PC, JC, ML, JE, LR, MDR, FFA, EC, CM, and MR provided valuable input into the study and reviewed and approved the manuscript.

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Correspondence to María Queralt Salas.

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Escribano-Serrat, S., Rodríguez-Lobato, L.G., Suárez-Lledó, M. et al. Improving the EASIX’ predictive power for NRM in adults undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02267-6

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