Title

An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis

Authors

Antonio M. Jimenez Jimenez, Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL, USA. amjimenez@med.miami.edu.
Marcos De Lima, Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.
Krishna V. Komanduri, Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL, USA.
Trent P. Wang, Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL, USA.
Mei-Jie Zhang, (CIBMTR)® Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Karen Chen, (CIBMTR)® Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Hisham Abdel-Azim, Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
Muhammad Bilal Abid, Divisions of Hematology/Oncology & Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Mahmoud Aljurf, Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.
Hassan Alkhateeb, Mayo Clinic Rochester, Rochester, MN, USA.
Amer Assal, Columbia University Irving Medical Center, Department of Medicine, Bone Marrow Transplant and Cell Therapy Program, New York, NY, USA.
Ulrike Bacher, Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Frédéric Baron, CHU and University of Liege, Liege, Belgium.
Minoo Battiwalla, Sarah Cannon Blood Cancer Network, Nashville, TN, USA.
Amer Beitinjaneh, Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL, USA.
Nelli Bejanyan, Department of Blood & Marrow Transplant and Cellular Immunotherapy (BMT CI), Moffitt Cancer Center, Tampa, FL, USA.
Vijaya Raj Bhatt, The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Michael Byrne, Vanderbilt University Medical Center, Nashville, TN, USA.
Jean-Yves Cahn, Department of Hematology, CHU Grenoble Alpes, Université Grenoble Alpes, Grenoble, France.
Mitchell Cairo, Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
Paul Castillo, UF Health Shands Children's Hospital, Gainesville, FL, USA.
Edward Copelan, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
Zachariah DeFilipp, Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA, USA.
Miguel Angel Perez, Department of Hematology/Oncology, Hospital Infantil Universitario Niño Jesus, Madrid, Spain.
Mahmoud Elsawy, Division of Hematology, Department of Medicine, Dalhousie University, Halifax, Canada.
Robert Peter Gale, Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK.
Biju George, Christian Medical College, Vellore, India.
Michael R. Grunwald, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
Gerhard C. Hildebrandt, Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
William J. Hogan, Division of Hematology/BMT, Mayo Clinic, Rochester, MN, USA.
Christopher G. Kanakry, Experimental Transplantation and Immunotherapy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ankit Kansagra, UT Southwestern Medical Center, Blood and Marrow Transplant Program, Dallas, TX, USA.
Mohamed A. Kharfan-Dabaja, Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL, USA.

Abstract

Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes in acute myeloid leukemia (AML) but data assessing the prognostic value of combined genetic models in the HCT setting are limited. We developed an adapted European LeukemiaNet (aELN) risk classification based on available genetic data reported to the Center for International Blood and Marrow Transplant Research, to predict post-transplant outcomes in 2289 adult AML patients transplanted in first remission, between 2013 and 2017. Patients were stratified according to aELN into three groups: favorable (Fav, N = 181), intermediate (IM, N = 1185), and adverse (Adv, N = 923). Univariate analysis demonstrated significant differences in 2-year overall survival (OS) (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p < 0.001); disease-free survival (DFS) (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p < 0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p < 0.001). Multivariate analysis (MVA) revealed no differences in outcomes between the Fav and IM groups, thus they were combined. On MVA, patients in the Adv risk group had the highest risk of relapse (HR 1.47 p ≤ 0.001) and inferior DFS (HR 1.35 p < 0.001) and OS (HR 1.39 p < 0.001), even using myeloablative conditioning or in those without the pre-HCT measurable-residual disease. Novel approaches to mitigate relapse in this high-risk group are urgently needed.

Publication Title

Bone marrow transplantation

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