Molecular International Prognostic Scoring System for Myelodysplastic Syndromes.

Autor: Bernard E; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Tuechler H, Greenberg PL; Stanford University Cancer Institute, Stanford, CA., Hasserjian RP; Department of Pathology, Massachusetts General Hospital, Boston., Arango Ossa JE; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Nannya Y; Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan.; Division of Hematopoietic Disease Control, Institute of Medical Science, University of Tokyo, Tokyo., Devlin SM; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Creignou M; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm., Pinel P; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Monnier L; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Gundem G; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Medina-Martinez JS; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Domenico D; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Jädersten M; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm., Germing U; Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University, Düsseldorf, Germany., Sanz G; Department of Hematology, Hospital Universitario y Politécnico La Fe, Valencia, Spain.; CIBERONC, Instituto de Salud Carlos III, Madrid.; Health Research Institute La Fe, Valencia, Spain., van de Loosdrecht AA; Department of Hematology, Amsterdam University Medical Center, Vrije University Medical Center, Amsterdam., Kosmider O; Department of Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin and Université de Paris, Université Paris Descartes, Paris., Follo MY; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy., Thol F; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany., Zamora L; Hematology Department, Hospital Germans Trias i Pujol, Institut Català d'Oncologia, Josep Carreras Leukaemia Research Institute, Barcelona., Pinheiro RF; Drug Research and Development Center, Federal University of Ceara, Ceara, Brazil., Pellagatti A; Radcliffe Department of Medicine, Oxford BRC Haematology Theme, University of Oxford, Oxford, United Kingdom., Elias HK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York., Haase D; Clinics of Hematology and Medical Oncology, University Medical Center, Göttingen, Germany., Ganster C; Clinics of Hematology and Medical Oncology, University Medical Center, Göttingen, Germany., Ades L; Department of Hematology, Hôpital St Louis, and Paris University, Paris., Tobiasson M; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm., Palomo L; Myelodysplastic Syndromes Group, Institut de Recerca Contra la Leucèmia Josep Carreras, Barcelona., Della Porta MG; Cancer Center, Humanitas Research Hospital & Humanitas University, Milan., Takaori-Kondo A; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Ishikawa T; Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan., Chiba S; Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan., Kasahara S; Department of Hematology, Gifu Municipal Hospital, Gifu, Japan., Miyazaki Y; Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan., Viale A; Integrated Genomics Operation, Memorial Sloan Kettering Cancer Center, New York., Huberman K; Integrated Genomics Operation, Memorial Sloan Kettering Cancer Center, New York., Fenaux P; Department of Hematology, Hôpital St Louis, and Paris University, Paris., Belickova M; Department of Genomics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic., Savona MR; Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville., Klimek VM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York., Santos FPS; Oncology-Hematology Center, Hospital Israelita Albert Einstein, São Paulo., Boultwood J; Radcliffe Department of Medicine, Oxford BRC Haematology Theme, University of Oxford, Oxford, United Kingdom., Kotsianidis I; Department of Hematology, Democritus University of Thrace Medical School, Alexandroupolis, Greece., Santini V; Myelodysplastic syndromes Unit, Department of Experimental and Clinical Medicine, Hematology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy., Solé F; Myelodysplastic Syndromes Group, Institut de Recerca Contra la Leucèmia Josep Carreras, Barcelona., Platzbecker U; Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University of Leipzig, Leipzig, Germany., Heuser M; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany., Valent P; Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna.; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna., Ohyashiki K; Tokyo Medical University, Tokyo., Finelli C; Institute of Hematology 'Seràgnoli,' Istituti di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Voso MT; Myelodysplastic syndromes Cooperative Group Gruppo Laziale Mielodisplasie (GROM-L), Department of Biomedicine and Prevention, Tor Vergata University, Rome., Shih LY; Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taiwan., Fontenay M; Department of Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin and Université de Paris, Université Paris Descartes, Paris., Jansen JH; Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands., Cervera J; Department of Hematology and Genetics Unit, University Hospital La Fe, Valencia, Spain., Gattermann N; Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University, Düsseldorf, Germany., Ebert BL; Department of Medical Oncology, Howard Hughes Medical Institute, Dana-Farber Cancer Center, Boston., Bejar R; University of California San Diego Moores Cancer Center, La Jolla, CA., Malcovati L; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy., Cazzola M; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy., Ogawa S; Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan.; Institute for the Advanced Study of Human Biology, Kyoto University, Kyoto, Japan.; Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm., Hellström-Lindberg E; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm., Papaemmanuil E; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York.
Jazyk: angličtina
Zdroj: NEJM evidence [NEJM Evid] 2022 Jul; Vol. 1 (7), pp. EVIDoa2200008. Date of Electronic Publication: 2022 Jun 12.
DOI: 10.1056/EVIDoa2200008
Abstrakt: BACKGROUND: Risk stratification and therapeutic decision-making for myelodysplastic syndromes (MDS) are based on the International Prognostic Scoring System–Revised (IPSS-R), which considers hematologic parameters and cytogenetic abnormalities. Somatic gene mutations are not yet used in the risk stratification of patients with MDS. METHODS: To develop a clinical-molecular prognostic model (IPSS-Molecular [IPSS-M]), pretreatment diagnostic or peridiagnostic samples from 2957 patients with MDS were profiled for mutations in 152 genes. Clinical and molecular variables were evaluated for associations with leukemia-free survival, leukemic transformation, and overall survival. Feature selection was applied to determine the set of independent IPSS-M prognostic variables. The relative weights of the selected variables were estimated using a robust Cox multivariable model adjusted for confounders. The IPSS-M was validated in an external cohort of 754 Japanese patients with MDS. RESULTS: We mapped at least one oncogenic genomic alteration in 94% of patients with MDS. Multivariable analysis identified TP53multihit, FLT3 mutations, and MLLPTD as top genetic predictors of adverse outcomes. Conversely, SF3B1 mutations were associated with favorable outcomes, but this was modulated by patterns of comutation. Using hematologic parameters, cytogenetic abnormalities, and somatic mutations of 31 genes, the IPSS-M resulted in a unique risk score for individual patients. We further derived six IPSS-M risk categories with prognostic differences. Compared with the IPSS-R, the IPSS-M improved prognostic discrimination across all clinical end points and restratified 46% of patients. The IPSS-M was applicable in primary and secondary/therapy-related MDS. To simplify clinical use of the IPSS-M, we developed an open-access Web calculator that accounts for missing values. CONCLUSIONS: Combining genomic profiling with hematologic and cytogenetic parameters, the IPSS-M improves the risk stratification of patients with MDS and represents a valuable tool for clinical decision-making. (Funded by Celgene Corporation through the MDS Foundation, the Josie Robertson Investigators Program, the Edward P. Evans Foundation, the Projects of National Relevance of the Italian Ministry of University and Research, Associazione Italiana per la Ricerca sul Cancro, the Japan Agency for Medical Research and Development, Cancer Research UK, the Austrian Science Fund, the MEXT [Japanese Ministry of Education, Culture, Sports, Science and Technology] Program for Promoting Research on the Supercomputer Fugaku, the Japan Society for the Promotion of Science, the Taiwan Department of Health, and Celgene Corporation through the MDS Foundation.)
Databáze: MEDLINE