Use of machine learning techniques to predict poor survival after hematopoietic cell transplantation for myelofibrosis.

Journal: Blood
Published Date:

Abstract

With the incorporation of effective therapies for myelofibrosis (MF), accurately predicting outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) is crucial for determining the optimal timing for this procedure. Using data from 5183 patients with MF who underwent first allo-HCT between 2005 and 2020 at European Society for Blood and Marrow Transplantation centers, we examined different machine learning (ML) models to predict overall survival after transplant. The cohort was divided into a training set (75%) and a test set (25%) for model validation. A random survival forests (RSF) model was developed based on 10 variables: patient age, comorbidity index, performance status, blood blasts, hemoglobin, leukocytes, platelets, donor type, conditioning intensity, and graft-versus-host disease prophylaxis. Its performance was compared with a 4-level Cox regression-based score and other ML-based models derived from the same data set, and with the Center for International Blood and Marrow Transplant Research score. The RSF outperformed all comparators, achieving better concordance indices across both primary and postessential thrombocythemia/polycythemia vera MF subgroups. The robustness and generalizability of the RSF model was confirmed by Akaike information criterion and time-dependent receiver operating characteristic area under the curve metrics in both sets. Although all models were prognostic for nonrelapse mortality, the RSF provided better curve separation, effectively identifying a high-risk group comprising 25% of patients. In conclusion, ML enhances risk stratification in patients with MF undergoing allo-HCT, paving the way for personalized medicine. A web application (https://gemfin.click/ebmt) based on the RSF model offers a practical tool to identify patients at high risk for poor transplantation outcomes, supporting informed treatment decisions and advancing individualized care.

Authors

  • Juan Carlos Hernández-Boluda
    Hematology Department, Hospital Clínico Universitario, Instituto de Investigación Sanitaria del Hospital Clínico de Valencia, University of Valencia, Valencia, Spain.
  • Adrián Mosquera-Orgueira
    Hematology Department. University Hospital of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
  • Luuk Gras
    European Group for Blood and Marrow Transplantation Leiden Study Unit, Leiden, The Netherlands.
  • Linda Koster
    European Group for Blood and Marrow Transplantation Leiden Study Unit, Leiden, The Netherlands.
  • Joe Tuffnell
    European Group for Blood and Marrow Transplantation Leiden Study Unit, Leiden, The Netherlands.
  • Nicolaus Kroger
    Roni Shouval, Hila Mishan-Shamay, Avichai Shimoni, and Arnon Nagler, The Chaim Sheba Medical Center, Tel-Hashomer; Roni Shouval, Ori Bondi, and Ron Unger, Bar-Ilan University, Ramat-Gan, Israel; Myriam Labopin, Norbert C. Gorin, Emmanuelle Polge, Arnon Nagler, and Mohamad Mohty, European Group for Blood and Marrow Transplantation; Myriam Labopin and Mohamad Mohty, Sorbonne Universités, Centre de Recherche (CDR) Saint-Antoine; Myriam Labopin and Mohamad Mohty, Institut National de la Santé et de la Recherche Médicale, CDR Saint-Antoine; Myriam Labopin and Mohamad Mohty, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France; Fabio Ciceri, San Raffaele Scientific Institute, Milan; Andrea Bacigalupo, Ospedale San Martino, Genoa, Italy; Jordi Esteve, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; Sebastian Giebel, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; Christoph Schmid, Ludwig-Maximilians-University, Munich; Nicolaus Kroger, University Medical Center Hamburg Eppendorf, Hamburg, Germany; Mahmoud Aljurf, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; Charles Craddock, Queen Elizabeth Hospital, Birmingham, United Kingdom; Jan J. Cornelissen, Erasmus University Medical Center, Rotterdam, the Netherlands; and Frederic Baron, University of Liège, Liège, Belgium.
  • Massimiliano Gambella
    Ematologia e Terapie Cellulari, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
  • Thomas Schroeder
    CSIRO Environment, Brisbane, Australia.
  • Marie Robin
    Hematology Department, Saint-Louis Hospital, Bone Marrow Transplantation Unit, Paris, France.
  • Katja Sockel
    Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
  • Jakob Passweg
    Hematology Department, University Hospital Basel, Basel, Switzerland.
  • Igor Wolfgang Blau
    Medizinische Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie, Berlin, Germany.
  • Ibrahim Yakoub-Agha
    Hematology Department, Centre Hospitalier Universitaire de Lille, INSERM U1286, Infinite, Lille, France.
  • Ruben Van Dijck
    Hematology Department, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
  • Mattias Stelljes
    Hematology Department, University of Muenster, Muenster, Germany.
  • Henrik Sengeloev
    Hematology Department, Rigshospitalet, Copenhagen, Denmark.
  • Jan Vydra
    Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
  • Uwe Platzbecker
    Medical Clinic and Polyclinic I, University Hospital, Technical University Dresden, Dresden, Germany.
  • Moniek de Witte
    Hematology Department, University Medical Centre, Utrecht, The Netherlands.
  • Frederic Baron
    Roni Shouval, Hila Mishan-Shamay, Avichai Shimoni, and Arnon Nagler, The Chaim Sheba Medical Center, Tel-Hashomer; Roni Shouval, Ori Bondi, and Ron Unger, Bar-Ilan University, Ramat-Gan, Israel; Myriam Labopin, Norbert C. Gorin, Emmanuelle Polge, Arnon Nagler, and Mohamad Mohty, European Group for Blood and Marrow Transplantation; Myriam Labopin and Mohamad Mohty, Sorbonne Universités, Centre de Recherche (CDR) Saint-Antoine; Myriam Labopin and Mohamad Mohty, Institut National de la Santé et de la Recherche Médicale, CDR Saint-Antoine; Myriam Labopin and Mohamad Mohty, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France; Fabio Ciceri, San Raffaele Scientific Institute, Milan; Andrea Bacigalupo, Ospedale San Martino, Genoa, Italy; Jordi Esteve, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; Sebastian Giebel, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; Christoph Schmid, Ludwig-Maximilians-University, Munich; Nicolaus Kroger, University Medical Center Hamburg Eppendorf, Hamburg, Germany; Mahmoud Aljurf, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; Charles Craddock, Queen Elizabeth Hospital, Birmingham, United Kingdom; Jan J. Cornelissen, Erasmus University Medical Center, Rotterdam, the Netherlands; and Frederic Baron, University of Liège, Liège, Belgium.
  • Kristina Carlson
    Hematology Department, University Hospital Uppsala, Uppsala, Sweden.
  • Javier Rojas
    Hematology Department. University Hospital of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
  • Carlos Pérez Míguez
    Hematology Department. University Hospital of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
  • Davide Crucitti
    Hematology Department. University Hospital of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
  • Kavita Raj
    Hematology Department, University College London Hospitals National Health Service Trust, London, United Kingdom.
  • Joanna Drozd-Sokolowska
    Hematology Department, Central Clinical Hospital, The Medical University of Warsaw, Warsaw, Poland.
  • Giorgia Battipaglia
    Hematology Department, Federico II University of Naples, Naples, Italy.
  • Nicola Polverelli
    Unit of Bone Marrow Transplantation, Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Tomasz Czerw
    Hematology Department, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice, Poland.
  • Donal P McLornan
    Hematology Department, University College London Hospitals National Health Service Trust, London, United Kingdom.