TY - JOUR
T1 - Risk Stratification in Older Intensively Treated Patients With AML
AU - Versluis, Jurjen
AU - Metzner, Marlen
AU - Wang, Ariel
AU - Gradowska, Patrycja
AU - Thomas, Abin
AU - Jakobsen, Niels Asger
AU - Kennedy, Alison
AU - Moore, Rachel
AU - Boertjes, Emma
AU - Vonk, Christian M.
AU - Kavelaars, Francois G.
AU - Rijken, Melissa
AU - Gilkes, Amanda
AU - Schwab, Claire
AU - Beverloo, H. Berna
AU - Manz, Markus
AU - Visser, Otto
AU - Van Elssen, Catharina H. M. J.
AU - de Weerdt, Okke
AU - Tick, Lidwine W.
AU - Biemond, Bart J.
AU - Vekemans, Marie-Christiane
AU - Freeman, Sylvie D.
AU - Harrison, Christine J.
AU - Cook, Jonathan A.
AU - Dennis, Mike
AU - Knapper, Steven
AU - Thomas, Ian
AU - Craddock, Charles
AU - Ossenkoppele, Gert J.
AU - Löwenberg, Bob
AU - Russell, Nigel
AU - Valk, Peter J. M.
AU - Vyas, Paresh
N1 - Publisher Copyright:
© 2024 by American Society of Clinical Oncology.
PY - 2024/12/1
Y1 - 2024/12/1
N2 - PURPOSE AML is a genetically heterogeneous disease, particularly in older patients. In patients older than 60 years, survival rates are variable after the most important curative approach, intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT). Thus, there is an urgent need in clinical practice for a prognostic model to identify older patients with AML who benefit from curative treatment. METHODS We studied 1,910 intensively treated patients older than 60 years with AML and high-risk myelodysplastic syndrome (HR-MDS) from two cohorts (NCRIAML18 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 5 1,204) for association with overall survival (OS). Relative weights of selected variables determined the prognostic model, which was validated in AML (n 5 491) and HR-MDS cohorts (n 5 215). 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% 6 4%, intermediate: 38% 6 2%, poor: 21% 6 2%, very poor: 4% 6 1%; [2] 54% 6 9%, 43% 6 4%, 27% 6 4%, 4% 6 3%; and [3] 54% 6 10%, 33% 6 6%, 14% 6 5%, 0% 6 3%, respectively). This new AML601 classification improves current prognostic classifications. Importantly, patients within the AML601 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 AML601 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.
AB - PURPOSE AML is a genetically heterogeneous disease, particularly in older patients. In patients older than 60 years, survival rates are variable after the most important curative approach, intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT). Thus, there is an urgent need in clinical practice for a prognostic model to identify older patients with AML who benefit from curative treatment. METHODS We studied 1,910 intensively treated patients older than 60 years with AML and high-risk myelodysplastic syndrome (HR-MDS) from two cohorts (NCRIAML18 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 5 1,204) for association with overall survival (OS). Relative weights of selected variables determined the prognostic model, which was validated in AML (n 5 491) and HR-MDS cohorts (n 5 215). 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% 6 4%, intermediate: 38% 6 2%, poor: 21% 6 2%, very poor: 4% 6 1%; [2] 54% 6 9%, 43% 6 4%, 27% 6 4%, 4% 6 3%; and [3] 54% 6 10%, 33% 6 6%, 14% 6 5%, 0% 6 3%, respectively). This new AML601 classification improves current prognostic classifications. Importantly, patients within the AML601 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 AML601 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.
UR - http://www.scopus.com/inward/record.url?scp=85203663430&partnerID=8YFLogxK
U2 - 10.1200/JCO.23.02631
DO - 10.1200/JCO.23.02631
M3 - Article
C2 - 39231389
SN - 0732-183X
VL - 42
SP - 4084
EP - 4094
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 34
ER -