Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML

Kamal Menghrajani, Leukemia Service and.
Alexandra Gomez-Arteaga, Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Rafael Madero-Marroquin, Department of Medicine, Icahn School of Medicine, Mount Sinai St Luke's and Mount Sinai West, New York, NY.
Mei-Jie Zhang, Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine and.Follow
Khalid Bo-Subait, Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine and.
Jonathan Sanchez, Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine and.
Hai-Lin Wang, Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine and.Follow
Mahmoud Aljurf, Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh, Saudi Arabia.
Amer Assal, Department of Medicine, Bone Marrow Transplant and Cell Therapy Program, Columbia University Irving Medical Center, New York, NY.Follow
Vera Ulrike Bacher, Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Switzerland.
Sherif M. Badawy, Division of Hematology, Oncology and Stem Cell Transplant, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.Follow
Nelli Bejanyan, Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.Follow
Vijaya Raj Bhatt, The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE.Follow
Christopher Bredeson, The Ottawa Hospital Blood and Marrow Transplant Program, Ottawa ON, Canada.Follow
Michael Byrne, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN.
Paul Castillo, Division of Hematology & Oncology, Department of Pediatrics in the College of Medicine, UF Health Shands Children's Hospital, Gainesville, FL.Follow
Jan Cerny, Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester, MA.
Saurabh Chhabra, Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine and.Follow
Stefan Octavian Ciurea, Division of Cancer Medicine, Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX.
Zachariah DeFilipp, Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, MA.Follow
Nosha Farhadfar, Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, FL.Follow
Shahinaz Gadalla, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI) Clinical Genetics Branch, National Institutes of Health (NIH), Rockville, MD.Follow
Robert Peter Gale, Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.Follow
Siddhartha Ganguly, Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City, KS.Follow
Lohith Gowda, Section of Hematology, Department of Medicine, Yale University School of Medicine, Yale Comprehensive Cancer Center, Yale New Haven Hospital, New Haven, CT.Follow
Michael R. Grunwald, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC.
Shahrukh Hashmi, Department of Internal Medicine, Mayo Clinic, Rochester, MN.
Gerhard Hildebrandt, Markey Cancer Center, University of Kentucky, Lexington, KY.
Christopher G. Kanakry, Experimental Transplantation and Immunology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD.Follow
Ankit Kansagra, UT Southwestern Medical Center, Blood and Marrow Transplant Program, Dallas, TX.
Farhad Khimani, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Maxwell Krem, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY.
Hillard Lazarus, Department of Medicine, University Hospitals Case Medical Center and Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH.

Abstract

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

Publication Title

Blood advances

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