Molecular International Prognostic Scoring System for Myelodysplastic Syndromes

Elsa Bernard; Heinz Tuechler; Peter L Greenberg; Robert P Hasserjian; Juan E Arango Ossa; Yasuhito Nannya; Sean M Devlin; Maria Creignou; Philippe Pinel; Lily Monnier; Gunes Gundem; Juan S Medina-Martinez; Dylan Domenico; Martin Jädersten; Ulrich Germing; Guillermo Sanz; Arjan A van de Loosdrecht; Olivier Kosmider; Matilde Y Follo; Felicitas Thol; Lurdes Zamora; Ronald F Pinheiro; Andrea Pellagatti; Harold K Elias; Detlef Haase; Christina Ganster; Lionel Ades; Magnus Tobiasson; Laura Palomo; Matteo Giovanni Della Porta; Akifumi Takaori-Kondo; Takayuki Ishikawa; Shigeru Chiba; Senji Kasahara; Yasushi Miyazaki; Agnes Viale; Kety Huberman; Pierre Fenaux; Monika Belickova; Michael R Savona; Virginia M Klimek; Fabio P S Santos; Jacqueline Boultwood; Ioannis Kotsianidis; Valeria Santini; Francesc Solé; Uwe Platzbecker; Michael Heuser; Peter Valent; Kazuma Ohyashiki; Carlo Finelli; Maria Teresa Voso; Lee-Yung Shih; Michaela Fontenay; Joop H Jansen; José Cervera; Norbert Gattermann; Benjamin L Ebert; Rafael Bejar; Luca Malcovati; Mario Cazzola; Seishi Ogawa; Eva Hellström-Lindberg; Elli Papaemmanuil

doi:10.1056/EVIDoa2200008

Molecular International Prognostic Scoring System for Myelodysplastic Syndromes

NEJM Evid. 2022 Jul;1(7):EVIDoa2200008. doi: 10.1056/EVIDoa2200008. Epub 2022 Jun 12.

Authors

Elsa Bernard¹, Heinz Tuechler, Peter L Greenberg², Robert P Hasserjian³, Juan E Arango Ossa¹, Yasuhito Nannya^{4

5}, Sean M Devlin¹, Maria Creignou⁶, Philippe Pinel¹, Lily Monnier¹, Gunes Gundem¹, Juan S Medina-Martinez¹, Dylan Domenico¹, Martin Jädersten⁶, Ulrich Germing⁷, Guillermo Sanz^{8

9

10}, Arjan A van de Loosdrecht¹¹, Olivier Kosmider¹², Matilde Y Follo¹³, Felicitas Thol¹⁴, Lurdes Zamora¹⁵, Ronald F Pinheiro¹⁶, Andrea Pellagatti¹⁷, Harold K Elias¹⁸, Detlef Haase¹⁹, Christina Ganster¹⁹, Lionel Ades²⁰, Magnus Tobiasson⁶, Laura Palomo²¹, Matteo Giovanni Della Porta²², Akifumi Takaori-Kondo²³, Takayuki Ishikawa²⁴, Shigeru Chiba²⁵, Senji Kasahara²⁶, Yasushi Miyazaki²⁷, Agnes Viale²⁸, Kety Huberman²⁸, Pierre Fenaux²⁰, Monika Belickova²⁹, Michael R Savona³⁰, Virginia M Klimek¹⁸, Fabio P S Santos³¹, Jacqueline Boultwood¹⁷, Ioannis Kotsianidis³², Valeria Santini³³, Francesc Solé²¹, Uwe Platzbecker³⁴, Michael Heuser¹⁴, Peter Valent^{35

36}, Kazuma Ohyashiki³⁷, Carlo Finelli³⁸, Maria Teresa Voso³⁹, Lee-Yung Shih⁴⁰, Michaela Fontenay¹², Joop H Jansen⁴¹, José Cervera⁴², Norbert Gattermann⁷, Benjamin L Ebert⁴³, Rafael Bejar⁴⁴, Luca Malcovati⁴⁵, Mario Cazzola⁴⁵, Seishi Ogawa^{4

46

47}, Eva Hellström-Lindberg⁶, Elli Papaemmanuil¹

Affiliations

¹ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York.
² Stanford University Cancer Institute, Stanford, CA.
³ Department of Pathology, Massachusetts General Hospital, Boston.
⁴ Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan.
⁵ Division of Hematopoietic Disease Control, Institute of Medical Science, University of Tokyo, Tokyo.
⁶ Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm.
⁷ Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University, Düsseldorf, Germany.
⁸ Department of Hematology, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
⁹ CIBERONC, Instituto de Salud Carlos III, Madrid.
¹⁰ Health Research Institute La Fe, Valencia, Spain.
¹¹ Department of Hematology, Amsterdam University Medical Center, Vrije University Medical Center, Amsterdam.
¹² Department of Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin and Université de Paris, Université Paris Descartes, Paris.
¹³ Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
¹⁴ Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
¹⁵ Hematology Department, Hospital Germans Trias i Pujol, Institut Català d'Oncologia, Josep Carreras Leukaemia Research Institute, Barcelona.
¹⁶ Drug Research and Development Center, Federal University of Ceara, Ceara, Brazil.
¹⁷ Radcliffe Department of Medicine, Oxford BRC Haematology Theme, University of Oxford, Oxford, United Kingdom.
¹⁸ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York.
¹⁹ Clinics of Hematology and Medical Oncology, University Medical Center, Göttingen, Germany.
²⁰ Department of Hematology, Hôpital St Louis, and Paris University, Paris.
²¹ Myelodysplastic Syndromes Group, Institut de Recerca Contra la Leucèmia Josep Carreras, Barcelona.
²² Cancer Center, Humanitas Research Hospital & Humanitas University, Milan.
²³ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
²⁴ Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.
²⁵ Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
²⁶ Department of Hematology, Gifu Municipal Hospital, Gifu, Japan.
²⁷ Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
²⁸ Integrated Genomics Operation, Memorial Sloan Kettering Cancer Center, New York.
²⁹ Department of Genomics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
³⁰ Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville.
³¹ Oncology-Hematology Center, Hospital Israelita Albert Einstein, São Paulo.
³² Department of Hematology, Democritus University of Thrace Medical School, Alexandroupolis, Greece.
³³ Myelodysplastic syndromes Unit, Department of Experimental and Clinical Medicine, Hematology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy.
³⁴ Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University of Leipzig, Leipzig, Germany.
³⁵ Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna.
³⁶ Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna.
³⁷ Tokyo Medical University, Tokyo.
³⁸ Institute of Hematology "Seràgnoli," Istituti di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
³⁹ Myelodysplastic syndromes Cooperative Group Gruppo Laziale Mielodisplasie (GROM-L), Department of Biomedicine and Prevention, Tor Vergata University, Rome.
⁴⁰ Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taiwan.
⁴¹ Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
⁴² Department of Hematology and Genetics Unit, University Hospital La Fe, Valencia, Spain.
⁴³ Department of Medical Oncology, Howard Hughes Medical Institute, Dana-Farber Cancer Center, Boston.
⁴⁴ University of California San Diego Moores Cancer Center, La Jolla, CA.
⁴⁵ Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy.
⁴⁶ Institute for the Advanced Study of Human Biology, Kyoto University, Kyoto, Japan.
⁴⁷ Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm.

PMID: 38319256
DOI: 10.1056/EVIDoa2200008

Abstract

MDS Molecular International Prognostic Scoring SystemSamples from over 2500 patients with MDS were profiled for gene mutations and used to develop the International Prognostic Scoring System-Molecular (IPSS-M). TP53^multihit, FLT3 mutations, and MLL^PTD were identified as top genetic predictors of adverse outcomes. IPSS-M improves prognostic discrimination across all clinical end points versus prior versions.