Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes
Journal of Clinical Oncology, vol. 42, pp. 2873–2886
Abstract
PURPOSE Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only potentially curative treatment for patients with myelodysplastic syndromes (MDS). Several issues must be considered when evaluating the benefits and risks of HSCT for patients with MDS, with the timing of transplantation being a crucial question. Here, we aimed to develop and validate a decision support system to define the optimal timing of HSCT for patients with MDS on the basis of clinical and genomic information as provided by the Molecular International Prognostic Scoring System (IPSS-M). PATIENTS AND METHODS We studied a retrospective population of 7,118 patients, stratified into training and validation cohorts. A decision strategy was built to estimate the average survival over an 8-year time horizon (restricted mean survival time [RMST]) for each combination of clinical and genomic covariates and to determine the optimal transplantation policy by comparing different strategies. RESULTS Under an IPSS-M based policy, patients with either low and moderate-low risk benefited from a delayed transplantation policy, whereas in those belonging to moderately high-, high- and very high-risk categories, immediate transplantation was associated with a prolonged life expectancy (RMST). Modeling decision analysis on IPSS-M versus conventional Revised IPSS (IPSS-R) changed the transplantation policy in a significant proportion of patients (15% of patient candidate to be immediately transplanted under an IPSS-R–based policy would benefit from a delayed strategy by IPSS-M, whereas 19% of candidates to delayed transplantation by IPSS-R would benefit from immediate HSCT by IPSS-M), resulting in a significant gain-in-life expectancy under an IPSS-M–based policy ( P = .001). CONCLUSION These results provide evidence for the clinical relevance of including genomic features into the transplantation decision making process, allowing personalizing the hazards and effectiveness of HSCT in patients with MDS.
Authors 70
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Affiliation as printed
Department of Biomedical Sciences, Humanitas University, Milan, Italy
Humanitas Clinical and Research Center—IRCCS, Milan, Italy
Humanitas Clinical and Research Center-IRCCS, Milan, Italy
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University of Trieste · Karolinska Institutet · Politecnico di Milano
Affiliation as printed
Biostatistics Unit, Department of Medical Sciences, University of Trieste, Trieste, Italy
Department of Mathematics, MOX—Modelling and Scientific Computing Laboratory, Politecnico di Milano, Milano, Italy
Department of Neurobiology, Care Sciences and Society, Aging Research Center, Karolinska Institutet, Stockholm, Sweden
Department of Mathematics, MOX-Modelling and Scientific Computing Laboratory, Politecnico di Milano, Milano, Italy
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Assistance Publique – Hôpitaux de Paris · Hôpital Saint-Louis · Université Paris Diderot
Affiliation as printed
Department of Hematology and Bone Marrow Transplantation, Hôpital Saint-Louis/Assistance Publique-Hôpitaux de Paris (AP-HP)/University Paris 7, Paris, France
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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University of Rome Tor Vergata · Policlinico Tor Vergata
Affiliation as printed
Hematology, Policlinico Tor Vergata & Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy
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Vanderbilt University · Vanderbilt-Ingram Cancer Center
Affiliation as printed
Vanderbilt University School of Medicine; Vanderbilt-Ingram Cancer Center, Nashville, TN
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Complejo Hospitalario de Salamanca
Affiliation as printed
Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain
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Affiliation as printed
Department of Biomedical Sciences, Humanitas University, Milan, Italy
Humanitas Clinical and Research Center—IRCCS, Milan, Italy
Humanitas Clinical and Research Center-IRCCS, Milan, Italy
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Affiliation as printed
Humanitas Clinical and Research Center—IRCCS, Milan, Italy
Humanitas Clinical and Research Center-IRCCS, Milan, Italy
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Affiliation as printed
Mathematical Institute, Leiden University, Leiden, the Netherlands
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Affiliation as printed
Department of Biomedical Sciences, Humanitas University, Milan, Italy
Humanitas Clinical and Research Center—IRCCS, Milan, Italy
Humanitas Clinical and Research Center-IRCCS, Milan, Italy
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Policlinico San Matteo Fondazione
Affiliation as printed
IRCCS Polilcinico San Matteo, Pavia, Italy
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Affiliation as printed
Humanitas Clinical and Research Center—IRCCS, Milan, Italy
Humanitas Clinical and Research Center-IRCCS, Milan, Italy
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Munich Leukemia Laboratory (Germany)
Affiliation as printed
MLL Munich Leukemia Laboratory, Munich, Germany
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Assistance Publique – Hôpitaux de Paris · Hôpital Saint-Louis · Université Paris Diderot
Affiliation as printed
Department of Hematology and Bone Marrow Transplantation, Hôpital Saint-Louis/Assistance Publique-Hôpitaux de Paris (AP-HP)/University Paris 7, Paris, France
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Affiliation as printed
Department of Biomedical Sciences, Humanitas University, Milan, Italy
Humanitas Clinical and Research Center—IRCCS, Milan, Italy
Humanitas Clinical and Research Center-IRCCS, Milan, Italy
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Affiliation as printed
Humanitas Clinical and Research Center—IRCCS, Milan, Italy
Department of Biomedical Sciences, Humanitas University, Milan, Italy
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Humanitas University · Moffitt Cancer Center
Affiliation as printed
Department of Biomedical Sciences, Humanitas University, Milan, Italy
Humanitas Clinical and Research Center—IRCCS, Milan, Italy
Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL
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Affiliation as printed
Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL
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Moffitt Cancer Center · Josep Carreras Leukaemia Research Institute
Affiliation as printed
Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL
Institut de Recerca Contra la Leucèmia Josep Carreras, Barcelona, Spain
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The University of Texas MD Anderson Cancer Center · Josep Carreras Leukaemia Research Institute
Affiliation as printed
Institut de Recerca Contra la Leucèmia Josep Carreras, Barcelona, Spain
The University of Texas MD Anderson Cancer Center, Houston, TX
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The University of Texas MD Anderson Cancer Center · Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
The University of Texas MD Anderson Cancer Center, Houston, TX
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, University Clinic, Düsseldorf, Germany
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Düsseldorf University Hospital · University Medical Center Hamburg-Eppendorf · Heinrich Heine University Düsseldorf
Affiliation as printed
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, University Clinic, Düsseldorf, Germany
University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Marche Polytechnic University · Guy's Hospital · King's College London · University Medical Center Hamburg-Eppendorf
Affiliation as printed
University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Haematology, Guy's Hospital & Comprehensive Cancer Centre, King's College, London, United Kingdom
Hematology Department & Stem Cell Transplant Unit, DISCLIMO-Università Politecnica delle Marche, Ancona, Italy
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Marche Polytechnic University · Guy's Hospital · King's College London · Azienda Ospedaliero-Universitaria Careggi · University of Florence
Affiliation as printed
Haematology, Guy's Hospital & Comprehensive Cancer Centre, King's College, London, United Kingdom
Hematology Department & Stem Cell Transplant Unit, DISCLIMO-Università Politecnica delle Marche, Ancona, Italy
MDS Unit, Azienda Ospedaliero-Universitaria Careggi & University of Florence, Florence, Italy
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Hospital Universitari i Politècnic La Fe · Azienda Ospedaliero-Universitaria Careggi · University of Florence
Affiliation as printed
MDS Unit, Azienda Ospedaliero-Universitaria Careggi & University of Florence, Florence, Italy
Hematology, Hospital Universitario La Fe, Valencia, Spain
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Hospital Universitari i Politècnic La Fe · Munich Leukemia Laboratory (Germany)
Affiliation as printed
Hematology, Hospital Universitario La Fe, Valencia, Spain
MLL Munich Leukemia Laboratory, Munich, Germany
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Munich Leukemia Laboratory (Germany) · University Hospital Leipzig
Affiliation as printed
MLL Munich Leukemia Laboratory, Munich, Germany
Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany
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Complejo Hospitalario de Salamanca · University Hospital Leipzig
Affiliation as printed
Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany
Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain
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Cleveland Clinic · Complejo Hospitalario de Salamanca
Affiliation as printed
Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH
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Cleveland Clinic · Assistance Publique – Hôpitaux de Paris · Hôpital Saint-Louis · Université Paris Diderot
Affiliation as printed
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH
Department of Hematology and Bone Marrow Transplantation, Hôpital Saint-Louis/Assistance Publique-Hôpitaux de Paris (AP-HP)/University Paris 7, Paris, France
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Assistance Publique – Hôpitaux de Paris · Hôpital Saint-Louis · Université Paris Diderot
Affiliation as printed
Department of Hematology and Bone Marrow Transplantation, Hôpital Saint-Louis/Assistance Publique-Hôpitaux de Paris (AP-HP)/University Paris 7, Paris, France
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Munich Leukemia Laboratory (Germany) · Assistance Publique – Hôpitaux de Paris · Hôpital Saint-Louis · Université Paris Diderot
Affiliation as printed
Department of Hematology and Bone Marrow Transplantation, Hôpital Saint-Louis/Assistance Publique-Hôpitaux de Paris (AP-HP)/University Paris 7, Paris, France
MLL Munich Leukemia Laboratory, Munich, Germany
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Yale Cancer Center · Yale University · Munich Leukemia Laboratory (Germany)
Affiliation as printed
MLL Munich Leukemia Laboratory, Munich, Germany
Section of Hematology, Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT
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Istituto Nazionale di Fisica Nucleare · Yale Cancer Center · Yale University · Istituto Nazionale di Fisica Nucleare, Sezione di Bologna · University of Bologna
Affiliation as printed
Section of Hematology, Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT
Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna, Italy
National Institute of Nuclear Physics (INFN), Bologna, Italy
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Istituto Nazionale di Fisica Nucleare · Moffitt Cancer Center · Istituto Nazionale di Fisica Nucleare, Sezione di Bologna · University of Bologna
Affiliation as printed
Experimental, Diagnostic and Specialty Medicine—DIMES, Bologna, Italy
National Institute of Nuclear Physics (INFN), Bologna, Italy
Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL
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Moffitt Cancer Center · Human Technopole · Politecnico di Milano
Affiliation as printed
Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL
Department of Mathematics, MOX-Modelling and Scientific Computing Laboratory, Politecnico di Milano, Milano, Italy
HDS, Health Data Science Center, Human Technopole, Milan, Italy
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Humanitas University · Human Technopole · Politecnico di Milano
Affiliation as printed
Department of Mathematics, MOX—Modelling and Scientific Computing Laboratory, Politecnico di Milano, Milano, Italy
HDS, Health Data Science Center, Human Technopole, Milan, Italy
Department of Biomedical Sciences, Humanitas University, Milan, Italy
Humanitas Clinical and Research Center—IRCCS, Milan, Italy
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Affiliation as printed
Department of Biomedical Sciences, Humanitas University, Milan, Italy
Humanitas Clinical and Research Center—IRCCS, Milan, Italy
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Affiliation as printed
Department of Biomedical Sciences, Humanitas University, Milan, Italy
Humanitas Clinical and Research Center-IRCCS, Milan, Italy
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Affiliation as printed
Department of Biomedical Sciences, Humanitas University, Milan, Italy
Humanitas Clinical and Research Center-IRCCS, Milan, Italy
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Affiliation as printed
Mathematical Institute, Leiden University, Leiden, the Netherlands
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Marche Polytechnic University · Guy's Hospital · King's College London
Affiliation as printed
Haematology, Guy's Hospital & Comprehensive Cancer Centre, King's College, London, United Kingdom
Hematology Department & Stem Cell Transplant Unit, DISCLIMO-Universit à Politecnica delle Marche, Ancona, Italy
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