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

Antonio M Jimenez Jimenez¹, Marcos De Lima², Krishna V Komanduri³, Trent P Wang³, Mei-Jie Zhang^{4

5}, Karen Chen⁴, Hisham Abdel-Azim⁶, Muhammad Bilal Abid⁷, Mahmoud Aljurf⁸, Hassan Alkhateeb⁹, Amer Assal¹⁰, Ulrike Bacher¹¹, Frédéric Baron¹², Minoo Battiwalla¹³, Amer Beitinjaneh³, Nelli Bejanyan¹⁴, Vijaya Raj Bhatt¹⁵, Michael Byrne¹⁶, Jean-Yves Cahn¹⁷, Mitchell Cairo¹⁸, Paul Castillo¹⁹, Edward Copelan²⁰, Zachariah DeFilipp²¹, Miguel Angel Diaz Perez²², Mahmoud Elsawy²³, Robert Peter Gale²⁴, Biju George²⁵, Michael R Grunwald²⁰, Gerhard C Hildebrandt²⁶, William J Hogan²⁷, Christopher G Kanakry²⁸, Ankit Kansagra²⁹, Mohamed A Kharfan-Dabaja³⁰, Nandita Khera³¹, Maxwell M Krem³², Aleksandr Lazaryan¹⁴, Joseph Maakaron³³, Rodrigo Martino³⁴, Joseph McGuirk³⁵, Fotios V Michelis³⁶, Giuseppe Milone³⁷, Asmita Mishra¹⁴, Hemant S Murthy³⁰, Alberto Mussetti^{38

39}, Sunita Nathan⁴⁰, Taiga Nishihori¹⁴, Richard F Olsson^{41

42}, Neil Palmisiano⁴³, Sagar Patel⁴⁴, Ayman Saad⁴⁵, Sachiko Seo⁴⁶, Akshay Sharma⁴⁷, Melhem Solh⁴⁸, Leo F Verdonck⁴⁹, Baldeep Wirk⁵⁰, Jean A Yared⁵¹, Mark Litzow⁵², Partow Kebriaei⁵³, Christopher S Hourigan⁵⁴, Wael Saber⁴, Daniel Weisdorf³³

Affiliations

¹ Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL, USA. amjimenez@med.miami.edu.
² Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.
³ Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL, USA.
⁴ (CIBMTR)® Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵ Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI, USA.
⁶ 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.
⁷ Divisions of Hematology/Oncology & Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
⁸ Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.
⁹ Mayo Clinic Rochester, Rochester, MN, USA.
¹⁰ Columbia University Irving Medical Center, Department of Medicine, Bone Marrow Transplant and Cell Therapy Program, New York, NY, USA.
¹¹ Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹² CHU and University of Liege, Liege, Belgium.
¹³ Sarah Cannon Blood Cancer Network, Nashville, TN, USA.
¹⁴ Department of Blood & Marrow Transplant and Cellular Immunotherapy (BMT CI), Moffitt Cancer Center, Tampa, FL, USA.
¹⁵ The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
¹⁶ Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁷ Department of Hematology, CHU Grenoble Alpes, Université Grenoble Alpes, Grenoble, France.
¹⁸ Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
¹⁹ UF Health Shands Children's Hospital, Gainesville, FL, USA.
²⁰ Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
²¹ Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA, USA.
²² Department of Hematology/Oncology, Hospital Infantil Universitario Niño Jesus, Madrid, Spain.
²³ Division of Hematology, Department of Medicine, Dalhousie University, Halifax, Canada.
²⁴ Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK.
²⁵ Christian Medical College, Vellore, India.
²⁶ Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
²⁷ Division of Hematology/BMT, Mayo Clinic, Rochester, MN, USA.
²⁸ Experimental Transplantation and Immunotherapy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
²⁹ UT Southwestern Medical Center, Blood and Marrow Transplant Program, Dallas, TX, USA.
³⁰ Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL, USA.
³¹ Department of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA.
³² Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, USA.
³³ Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
³⁴ Divison of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
³⁵ Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Minneapolis, MN, USA.
³⁶ Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, Toronto, Canada.
³⁷ Azienda Ospedaliera Universitaria Policlinico-San Marco, Catania, Italy.
³⁸ Hematology Department, Institut Catalá d' Oncologia-Hospitalet, Barcelona, Spain.
³⁹ IDIBELL-Institut Catalá d' Oncologia, l'Hospitalet de Llobregat, El Prat de Llobregat, Spain.
⁴⁰ Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, Chicago, IL, USA.
⁴¹ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁴² Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden.
⁴³ Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
⁴⁴ Blood and Marrow Transplant Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
⁴⁵ Division of Hematology, Ohio State University, Columbus, OH, USA.
⁴⁶ Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.
⁴⁷ Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.
⁴⁸ The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA, USA.
⁴⁹ Department of Hematology/Oncology, Isala Clinic, Zwolle, the Netherlands.
⁵⁰ Bone Marrow Transplant Program, Penn State Cancer Institute, Hershey, Pennsylvania, USA.
⁵¹ Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, USA.
⁵² Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, MN, USA.
⁵³ Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA.
⁵⁴ Laboratory of Myeloid Malignancies, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD, USA.

PMID: 34584240
PMCID: PMC8758206
DOI: 10.1038/s41409-021-01450-3

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

Antonio M Jimenez Jimenez et al. Bone Marrow Transplant. 2021 Dec.

. 2021 Dec;56(12):3068-3077.

doi: 10.1038/s41409-021-01450-3. Epub 2021 Sep 28.

Authors

Affiliations

¹ Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL, USA. amjimenez@med.miami.edu.
² Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.
³ Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL, USA.
⁴ (CIBMTR)® Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵ Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI, USA.
⁶ 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.
⁷ Divisions of Hematology/Oncology & Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
⁸ Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.
⁹ Mayo Clinic Rochester, Rochester, MN, USA.
¹⁰ Columbia University Irving Medical Center, Department of Medicine, Bone Marrow Transplant and Cell Therapy Program, New York, NY, USA.
¹¹ Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹² CHU and University of Liege, Liege, Belgium.
¹³ Sarah Cannon Blood Cancer Network, Nashville, TN, USA.
¹⁴ Department of Blood & Marrow Transplant and Cellular Immunotherapy (BMT CI), Moffitt Cancer Center, Tampa, FL, USA.
¹⁵ The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
¹⁶ Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁷ Department of Hematology, CHU Grenoble Alpes, Université Grenoble Alpes, Grenoble, France.
¹⁸ Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
¹⁹ UF Health Shands Children's Hospital, Gainesville, FL, USA.
²⁰ Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
²¹ Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA, USA.
²² Department of Hematology/Oncology, Hospital Infantil Universitario Niño Jesus, Madrid, Spain.
²³ Division of Hematology, Department of Medicine, Dalhousie University, Halifax, Canada.
²⁴ Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK.
²⁵ Christian Medical College, Vellore, India.
²⁶ Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
²⁷ Division of Hematology/BMT, Mayo Clinic, Rochester, MN, USA.
²⁸ Experimental Transplantation and Immunotherapy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
²⁹ UT Southwestern Medical Center, Blood and Marrow Transplant Program, Dallas, TX, USA.
³⁰ Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL, USA.
³¹ Department of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA.
³² Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, USA.
³³ Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
³⁴ Divison of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
³⁵ Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Minneapolis, MN, USA.
³⁶ Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, Toronto, Canada.
³⁷ Azienda Ospedaliera Universitaria Policlinico-San Marco, Catania, Italy.
³⁸ Hematology Department, Institut Catalá d' Oncologia-Hospitalet, Barcelona, Spain.
³⁹ IDIBELL-Institut Catalá d' Oncologia, l'Hospitalet de Llobregat, El Prat de Llobregat, Spain.
⁴⁰ Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, Chicago, IL, USA.
⁴¹ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁴² Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden.
⁴³ Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
⁴⁴ Blood and Marrow Transplant Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
⁴⁵ Division of Hematology, Ohio State University, Columbus, OH, USA.
⁴⁶ Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.
⁴⁷ Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.
⁴⁸ The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA, USA.
⁴⁹ Department of Hematology/Oncology, Isala Clinic, Zwolle, the Netherlands.
⁵⁰ Bone Marrow Transplant Program, Penn State Cancer Institute, Hershey, Pennsylvania, USA.
⁵¹ Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, USA.
⁵² Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, MN, USA.
⁵³ Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA.
⁵⁴ Laboratory of Myeloid Malignancies, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD, USA.

PMID: 34584240
PMCID: PMC8758206
DOI: 10.1038/s41409-021-01450-3

Erratum in

Correction to: An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis.
Jimenez Jimenez AM, De Lima M, Komanduri KV, Wang TP, Zhang MJ, Chen K, Abdel-Azim H, Abid MB, Aljurf M, Alkhateeb H, Assal A, Bacher U, Baron F, Battiwalla M, Beitinjaneh A, Bejanyan N, Bhatt VR, Byrne M, Cahn JY, Cairo M, Castillo P, Copelan E, DeFilipp Z, Perez MAD, Elsawy M, Gale RP, George B, Grunwald MR, Hildebrandt GC, Hogan WJ, Kanakry CG, Kansagra A, Kharfan-Dabaja MA, Khera N, Krem MM, Lazaryan A, Maakaron J, Martino R, McGuirk J, Michelis FV, Milone G, Mishra A, Murthy HS, Mussetti A, Nathan S, Nishihori T, Olsson RF, Palmisiano N, Patel S, Saad A, Seo S, Sharma A, Solh M, Verdonck LF, Wirk B, Yared JA, Litzow M, Kebriaei P, Hourigan CS, Saber W, Weisdorf D. Jimenez Jimenez AM, et al. Bone Marrow Transplant. 2022 May;57(5):852. doi: 10.1038/s41409-022-01625-6. Bone Marrow Transplant. 2022. PMID: 35297406 No abstract available.

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.

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Figures

**Figure 1.**
OS (A), DFS (B) and cumulative incidence of disease relapse (C) for AML transplant recipients within favorable/intermediate vs. adverse aELN cohorts Abbreviations: DFS, disease-free survival; aELN, adapted European LeukemiaNet; OS, overall survival.

See this image and copyright information in PMC

References

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

Affiliations

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

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