Risk Stratification in Older Intensively Treated Patients With AML.
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Versluis Jurjen, Metzner Marlen, Wang Ariel, Gradowska Patrycja, Thomas Abin, Jakobsen Niels Asger, Kennedy Alison, Moore Rachel, Boertjes Emma, Vonk Christian M, Kavelaars Francois G, Rijken Melissa, Gilkes Amanda, Schwab Claire, Beverloo H Berna, Manz Markus, Visser Otto, Van Elssen Catharina H M J, de Weerdt Okke, Tick Lidwine W, Biemond Bart J, Vekemans Marie-Christiane, Freeman Sylvie D, Harrison Christine J, Cook Jonathan A, Dennis Mike, Knapper Steven, Thomas Ian, Craddock Charles, Ossenkoppele Gert J, Löwenberg Bob, Russell Nigel, Valk Peter J M, Vyas Paresh
Аннотация
METHODS: We studied 1,910 intensively treated patients older than 60 years with AML and high-risk myelodysplastic syndrome (HR-MDS) from two cohorts (NCRI-AML18 and HOVON-SAKK). The median patient age was 67 years. Using a random survival forest, clinical, molecular, and cytogenetic variables were evaluated in an AML development cohort (n = 1,204) for association with overall survival (OS). Relative weights of selected variables determined the prognostic model, which was validated in AML (n = 491) and HR-MDS cohorts (n = 215).
RESULTS: The complete cohort had a high frequency of poor-risk features, including 2022 European LeukemiaNet adverse-risk (57.3%), mutated TP53 (14.4%), and myelodysplasia-related genetic features (65.1%). Nine variables were used to construct four groups with highly distinct 4-year OS in the (1) AML development, (2) AML validation, and (3) HR-MDS test cohorts ([1] favorable: 54% ± 4%, intermediate: 38% ± 2%, poor: 21% ± 2%, very poor: 4% ± 1%; [2] 54% ± 9%, 43% ± 4%, 27% ± 4%, 4% ± 3%; and [3] 54% ± 10%, 33% ± 6%, 14% ± 5%, 0% ± 3%, respectively). This new AML60+ classification improves current prognostic classifications. Importantly, patients within the AML60+ intermediate- and very poor-risk group significantly benefited from allo-HCT, whereas the poor-risk patients showed an indication, albeit nonsignificant, for improved outcome after allo-HCT.
CONCLUSION: The new AML60+ classification provides prognostic information for intensively treated patients 60 years and older with AML and HR-MDS and identifies patients who benefit from intensive chemotherapy and allo-HCT.