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

Antonio M. Jimenez Jimenez, Marcos De Lima, Krishna V. Komanduri, Trent P. Wang, Mei Jie Zhang, Karen Chen, Hisham Abdel-Azim, Muhammad Bilal Abid, Mahmoud Aljurf, Hassan Alkhateeb, Amer Assal, Ulrike Bacher, Frédéric Baron, Minoo Battiwalla, Amer Beitinjaneh, Nelli Bejanyan, Vijaya Raj Bhatt, Michael Byrne, Jean Yves Cahn, Mitchell CairoPaul Castillo, Edward Copelan, Zachariah DeFilipp, Miguel Angel Diaz Perez, Mahmoud Elsawy, Robert Peter Gale, Biju George, Michael R. Grunwald, Gerhard C. Hildebrandt, William J. Hogan, Christopher G. Kanakry, Ankit Kansagra, Mohamed A. Kharfan-Dabaja, Nandita Khera, Maxwell M. Krem, Aleksandr Lazaryan, Joseph Maakaron, Rodrigo Martino, Joseph McGuirk, Fotios V. Michelis, Giuseppe Milone, Asmita Mishra, Hemant S. Murthy, Alberto Mussetti, Sunita Nathan, Taiga Nishihori, Richard F. Olsson, Neil Palmisiano, Sagar Patel, Ayman Saad, Sachiko Seo, Akshay Sharma, Melhem Solh, Leo F. Verdonck, Baldeep Wirk, Jean A. Yared, Mark Litzow, Partow Kebriaei, Christopher S. Hourigan, Wael Saber, Daniel Weisdorf

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalBone marrow transplantation
Early online dateSep 28 2021
DOIs
StatePublished - Sep 28 2021

Bibliographical note

Funding Information:
AA reports grants and personal fees from Incyte Corporation, personal fees from Boston Biomedical, personal fees from Alpha Insights, outside the submitted work. NB reports personal fees from Magenta therapeutics, outside the submitted work. J-YC reports Advisory Boards with Agios, AbbVie, Otsuka, Race Oncology. VRB reports personal fees from Agios, grants and personal fees from Incyte, personal fees from Takeda, personal fees from Partner Therapeutics, personal fees from Omeros, grants and personal fees from Abbvie, grants from Jazz, grants from National Marrow Donor Program, other from Oncoceutics, personal fees from Partnership for health analytic research, LLC, grants and other from Pfizer, personal fees from CSL Behring, grants from Tolero Pharmaceuticals, personal fees from Rigel Pharmaceuticals, other from Novartis, personal fees from Genentech, outside the submitted work. MdL reports grants from Pfizer, grants from Celgene, personal fees from Kadmon, personal fees from Pfizer, personal fees from Incyte, personal fees from BMS, outside the submitted work. RPG is a consultant to BeiGene Ltd., Kite Pharma Inc., Fusion Pharma LLC, LaJolla NanoMedical Inc., Mingsight Parmaceuticals Inc., and CStone Pharmaceuticals; Medical Director, FFF Enterprises Inc.; Partner, AZCA Inc.; Board of Directors, RakFond Foundation for Cancer Research Support; Scientific Advisory Board, Antegene Biotech LLC and StemRad Ltd. MRG reports personal fees from Abbvie, personal fees from Agios, personal fees from Amgen, personal fees from Cardinal Health, personal fees from BMS/Celgene, personal fees from Daiichi Sankyo, personal fees and other from Incyte, personal fees from Merck, personal fees from Pfizer, personal fees from Premier, personal fees from Karius, other from Forma Therapeutics, other from Genentech/Roche, other from Janssen, personal fees from Astellas, personal fees from Trovagene, personal fees from Stemline, personal fees from Gilead, outside the submitted work. GCH reports other from Pfizer, other from Kite Pharma, other from Incyte, other from Jazz Pharmaceuticals, other from Alexion Pharmaceutical, other from Karyopharm, other from Pharmacyclics, other from Takeda, other from Jazz Pharmaceuticals, other from Kite Pharma, other from Incyte, other from Pfizer, other from Falk Foundation, other from Astellas Pharma, outside the submitted work. CSH reports other from Sellas, outside the submitted work. AK reports other from Takeda, other from Jansen, other from Pfizer, other from Celgene/BMS, other from Sanofi, other from Alynylam, other from GSK, other from Karyopharm, other from Oncopeptide, outside the submitted work. MAK-D reports other from Daiichi Sankyo, other from Pharmacyclics, outside the submitted work. JM reports grants and personal fees from AlloVir HCP, grants and personal fees from Juno Therapeutics, Inc, grants and personal fees from Gilead-Kite Pharmaceuticals, grants and other from Magenta Therapeutics, other from EcoR1 Cap, outside the submitted work. AM reports grants from Novartis, from null, outside the submitted work. AM reports grants from Gilead, personal fees from Novartis, Brystol-Myers Squibb, outside the submitted work. SP reports personal fees from Kite Pharma, outside the submitted work. RFO reports personal fees from AstraZeneca, outside the submitted work. AS reports personal fees from Magenta Therapeutics, personal fees from Incyte Pharmaceuticals, personal fees from CareDx, outside the submitted work. AS reports clinical trial salary support from Vertex Pharmaceuticals, CRISPR Therapeutics, Novartis paid to his institution, and personal consultancy fees from Spotlight Therapeutics, outside the submitted work. All other authors declare no potential competing interests.

Funding Information:
The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); U24HL138660 from NHLBI and NCI; OT3HL147741, and U01HL128568 from the NHLBI; HHSH250201700006C, and HHSH250201700007C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, UG1HL06924, and BARDA. Support is also provided by Be The Match Foundation, Boston Children’s Hospital, Dana Farber, St. Baldrick’s Foundation, Stanford University, the Medical College of Wisconsin the National Marrow Donor Program, and from the following commercial entities: Actinium Pharmaceuticals, Inc.; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; Incyte Corporation; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Stemcyte; Takeda Pharma; Vor Biopharma; Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA), or any other agency of the U.S. Government.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.

PubMed: MeSH publication types

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