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      Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index: A Center for International Blood and Marrow Transplant Research Study.

      1 , 2 , 2 , 3 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 20 , 21 , 22 , 23 , 24 , 19 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 9 , 37 , 38 , 25 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 23 , 2 , 46
      Transplantation and cellular therapy
      Elsevier BV
      AML, DRI, MDS, Myeloablative, RIC

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          Abstract

          Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR], .74; 95% confidence interval [CI], .62 to .88; P < .001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P < .001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P = .001). In the high/very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR, .83; 95% CI, .68 to 1.00; P = .051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P = .002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/very-high risk DRI group.

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          Author and article information

          Journal
          Transplant Cell Ther
          Transplantation and cellular therapy
          Elsevier BV
          2666-6367
          2666-6367
          January 2021
          : 27
          : 1
          Affiliations
          [1 ] Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida. Electronic address: nelli.bejanyan@moffitt.org.
          [2 ] Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin.
          [3 ] Adult Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota.
          [4 ] Memorial Sloan Kettering Cancer Center, New York, New York.
          [5 ] Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida.
          [6 ] Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
          [7 ] Division of Hematology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
          [8 ] Beth Israel Deaconess Medical Center, Boston, Massachusetts.
          [9 ] Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina.
          [10 ] Department of Hematology/Oncology, Johns Hopkins All Children's Hospital, St Petersburg, Florida.
          [11 ] Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK.
          [12 ] Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, Georgia.
          [13 ] Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, Florida.
          [14 ] Department of Hematology/Oncology, Hospital Infantil Universitario Nino Jesus, Madrid, Spain.
          [15 ] Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City, Kansas.
          [16 ] Section of Medical Oncology, Department of Internal Medicine, Yale New Haven Hospital, New Haven, Connecticut.
          [17 ] Department of Hematology/Oncology, Isala Clinic, Zwolle, The Netherland.
          [18 ] Stem Cell Transplant Program, Division of Hematology/Oncology, Department of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois.
          [19 ] Blood & Marrow Transplant Program, Department of Medicine, Ottawa Hospital Ottawa, Ontario, Canada.
          [20 ] Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
          [21 ] Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
          [22 ] Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, New York.
          [23 ] Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
          [24 ] Department of Hematology, Academische Ziekenhuis, Maastricht, The Netherlands.
          [25 ] Division of Medical Oncology, Markey Cancer Center, University of Kentucky School of Medicine, Lexington, Kentucky.
          [26 ] Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio.
          [27 ] Department of Hematology, CHU Grenoble Alpes, Grenoble, France.
          [28 ] Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
          [29 ] Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, North Carolina.
          [30 ] Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland.
          [31 ] Hematopoietic Stem Cell Transplant Program, Texas Transplant Institute, San Antonio, Texas.
          [32 ] Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts.
          [33 ] Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.
          [34 ] Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
          [35 ] Blood and Marrow Transplantation Program, Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
          [36 ] Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Switzerland.
          [37 ] Section of Bone Marrow Transplantation and Cellular Therapy, Division of Hematology, Oncology and Cell Therapy, Department of Internal Medicine, Rush Medical College, Chicago, Illinois.
          [38 ] Bone Marrow Transplant Program, Penn State Cancer Institute, Hershey, Pennsylvania.
          [39 ] Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.
          [40 ] Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Sormland, Uppsala University, Sweden.
          [41 ] Department of Haematology, Christian Medical College, Vellore, India.
          [42 ] Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
          [43 ] Laboratory of Myeloid Malignancies, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
          [44 ] Division of Medical Oncology, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
          [45 ] Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, Minnesota.
          [46 ] Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, 96.
          Article
          S1083-8791(20)30618-2 NIHMS1645413
          10.1016/j.bbmt.2020.09.026
          8015679
          33010430
          3091fbeb-3b34-4277-bfa5-447a74b6b2e1
          History

          RIC,AML,DRI,MDS,Myeloablative
          RIC, AML, DRI, MDS, Myeloablative

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