Clinical-genomic profiling of MDS to inform allo-HCT: recommendations from an international panel on behalf of the EBMT
Abstract
Abstract For patients with myelodysplastic neoplasm/syndrome (MDS), allogeneic hematopoietic cell transplantation (allo-HCT) represents the only potentially curative treatment, capable of eradicating disease-related mutant hematopoietic cells and establishing normal donor hematopoiesis. Biologic-assignment clinical trials have indicated that in eligible patients, allo-HCT is associated with superior clinical outcomes compared with nontransplant therapy. However, this therapeutic option is only available to a subset of patients, and the outcome is influenced by multiple factors inherent to the patient, the MDS subtype, and the allo-HCT procedure itself. In 2017, the European Society for Blood and Marrow Transplantation (EBMT) published recommendations for allo-HCT in MDS to guide practical decision making. In the contemporary era, genomic profiling has become routine clinical practice in many centers, and the most recent classification systems include MDS entities that are defined by genetic abnormalities. In particular, the molecular International Prognostic Scoring System offers more precise prognostication across all clinical end points and currently represents the standard tool for estimating patient survival in the absence of disease-modifying treatment. Evidence from multiple sources increasingly indicates that allo-HCT should be considered at the time of diagnosis in all eligible patients with MDS. Therefore, genomic profiling for somatic mutations and testing for germ line predisposition variants are integral to determining a patient’s eligibility for transplantation. Although all patients with higher-risk MDS are potential candidates for immediate transplantation, a subset of those with lower-risk MDS may also derive benefit from this procedure at an earlier disease stage. Comprehensive recommendations on behalf of an expert international panel for clinical practice and future clinical studies of relevance are presented.
Article Details
Authors (45)
Carmelo Gurnari
1Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH
Marie Robin
9Hôpital Saint Louis (APHP), Service d'hématologie, Paris, France
Lionel Adès
Mahmoud Aljurf
Antonio Almeida
6Hospital Da Luz, Lisboa, Portugal
Fernando Barroso Duarte
16Hospital Universitário Walter Cantídio, Fortaleza, Brazil
Elsa Bernard
2Institut Gustave Roussy, Computational Clinical Oncology Lab, UMR 981, Villejuif, France
Corey Cutler
1Dana Farber Cancer Institute, Boston, United States
Matteo Giovanni Della Porta
Theo De Witte
10Department of Tumor Immunology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
Amy DeZern
1Johns Hopkins University School of Medicine, Oncology, Baltimore, United States
Joanna Drozd-Sokolowska
1Medical University of Warsaw, Department of Hematology, Transplantation and Internal Medicine, Warsaw, Poland
Eric Duncavage
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States
Pierre Fenaux
Nico Gagelmann
From the Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Guillermo Garcia-Manero
Claudia Haferlach
8Munich Leukemia Laboratory, Munich, Germany
Torsten Haferlach
7Munich Leukemia Laboratory, Munich, Germany
Robert Hasserjian
13Massachusetts General Hospital, Department of Pathology, Boston, United States
Eva Hellström-Lindberg
Meagan Jacoby
1Washington University School of Medicine in St Louis, Hematology-Oncology, St Louis, United States
Austin Kulasekararaj
22King's College Hospital NHS Foundation Trust, London and King's College London, London, United Kingdom
R. Coleman Lindsley
Dana-Farber Cancer Institute, Boston, Massachusetts, United States
Jaroslaw P. Maciejewski
1Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH
Hideki Makishima
21Department of Hematology and Medical Oncology, Shinshu University School of Medicine, Matsumoto, Japan
Luca Malcovati
Moshe Mittelman
9Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Anders E. Myhre
24Department of Haematology, Oslo University Hospital, Oslo, Norway
Seishi Ogawa
Francesco Onida
22ASST Fatebenefratelli-Sacco, University Milan, Milan, Italy
Elli Papaemmanuil
Jakob Passweg
8University Hospital Basel, Basel, Switzerland
Uwe Platzbecker
Lisa Pleyer
Kavita Raj
20University College London Hospitals NHS Trust, London, United Kingdom
Valeria Santini
7DMSC University of Florence, AOUC, MDS Unit, Hematology, Florence, Italy
Anna Sureda
Institut Català d'Oncologia, Barcelona, Spain
Magnus Tobiasson
18Department of Hematology, Karolinska University Hospital, and Centre of Hematology and Regenerative Medicine, Institution of Medicine, Karolinska Institute, Huddinge, Sweden
Maria Teresa Voso
Ibrahim Yakoub-Agha
9CHU de Lille, Univ Lille, INSERM U1286, Infinite, 59000 Lille, Lille, France
Amer Zeidan
18Yale School of Medicine - Yale Cancer Center, New Haven, United States
Matthew Walter
11Washington University School of Medicine, St. Louis, United States
Nicolaus Kröger
From the Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Donal P. McLornan
14Department of Haematology and Stem Cell Transplantation, University College London Hospitals NHS Foundation Trust, London, United Kingdom
Mario Cazzola
6Department of Molecular Medicine, University of Pavia, Pavia, Italy