Unified classification and risk-stratification in Acute Myeloid Leukemia.
Creators: name: Tazi, Yanis
name: Arango-Ossa, Juan E
name: Zhou, Yangyu
name: Bernard, Elsa
name: Thomas, Ian
name: Gilkes, Amanda
name: Freeman, Sylvie
name: Pradat, Yoann
name: Johnson, Sean J
name: Hills, Robert
name: Dillon, Richard
name: Levine, Max F
name: Leongamornlert, Daniel
name: Butler, Adam
name: Ganser, Arnold
name: Bullinger, Lars
name: Döhner, Konstanze
name: Ottmann, Oliver
name: Adams, Richard
name: Döhner, Hartmut
name: Campbell, Peter J
name: Burnett, Alan K
name: Dennis, Michael
name: Russell, Nigel H
name: Devlin, Sean M
name: Huntly, Brian JP
name: Papaemmanuil, Elli
Publisher: name: Apollo - University of Cambridge Repository
Year: 2022
Subjects: Article
/631/208/69
/631/67/69
/692/4028/67/1990/283/1897
article

description: Funder: E.P. is a Josie Robertson Investigator and is supported by the European Hematology Association, American Society of Hematology, Gabrielle’s Angels Foundation, V Foundation and The Geoffrey Beene Foundation and is a Damon Runyon Rachleff Innovator fellow. Work in the BJPH lab is funded by Cancer Research UK (C18680/A25508), the European Research Council (647685), MRC (MR-R009708-1), the Kay Kendall Leukaemia Fund (KKL1243), the Wellcome Trust (205254/Z/16/Z) and the Cancer Research UK Cambridge Major Centre (C49940/A25117). This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014), and was funded in part, by the Wellcome Trust who supported the Wellcome - MRC Cambridge Stem Cell Institute (203151/Z/16/Z). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. L.B., H.D. and B.J.P.H. are supported by the HARMONY Alliance (IMI Project No. 116026; https://www.harmony-alliance.eu/). The UK-NCRI AML working group trials were supported with research grants from the Medical Research Council (MRC), Cancer Research UK (CRUK), Blood Cancer UK and Cardiff University. We would like to thank all patients and investigators for their participation in the trials and the study.
description: Clinical recommendations for Acute Myeloid Leukemia (AML) classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis, which are present in &lt;50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize and validate 16 molecular classes describing 100% of AML patients. Each class represents diverse biological AML subgroups, and is associated with distinct clinical presentation, likelihood of response to induction chemotherapy, risk of relapse and death over time. Secondary AML-2, emerges as the second largest class (24%), associates with high-risk disease, poor prognosis irrespective of flow Minimal Residual Disease (MRD) negativity, and derives significant benefit from transplantation. Guided by class membership we derive a 3-tier risk-stratification score that re-stratifies 26% of patients as compared to standard of care. This results in a unified framework for disease classification and risk-stratification in AML that relies on information from cytogenetics and 32 genes. Last, we develop an open-access patient-tailored clinical decision support tool.