TY - JOUR
T1 - Improving risk stratification for 2022 European LeukemiaNet favorable-risk patients with acute myeloid leukemia
AU - Archer, Kellie J.
AU - Fu, Han
AU - Mrózek, Krzysztof
AU - Nicolet, Deedra
AU - Mims, Alice S.
AU - Uy, Geoffrey L.
AU - Stock, Wendy
AU - Byrd, John C.
AU - Hiddemann, Wolfgang
AU - Metzeler, Klaus H.
AU - Rausch, Christian
AU - Krug, Utz
AU - Sauerland, Cristina
AU - Görlich, Dennis
AU - Berdel, Wolfgang E.
AU - Woermann, Bernhard J.
AU - Braess, Jan
AU - Spiekermann, Karsten
AU - Herold, Tobias
AU - Eisfeld, Ann Kathrin
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/11/4
Y1 - 2024/11/4
N2 - Assignment of patients diagnosed with acute myeloid leukemia (AML) to the 2022 European LeukemiaNet (ELN) favorable genetic risk group has important clinical implications, as allogeneic stem cell transplantation in first complete remission (CR) is not advised due to a relatively good outcome of patients receiving chemotherapy alone and transplant-associated mortality. However, not all favorable genetic risk patients experience long-term relapse-free survival (RFS), making recognition of patients who would most likely be cured of high importance. We analyzed 297 patients aged <60 years with de novo AML classified as 2022 ELN favorable genetic risk who achieved a CR and had RNA sequencing (RNA-seq) and gene mutation data from diagnostic samples available (Alliance trial A152010). To identify prognostically relevant transcripts that can distinguish patients cured from patients susceptible to lower or higher risk of relapse or death, we fit a regularized mixture cure model (MCM) where RNA-seq expression values were our candidate covariates. To validate the identified transcripts, we analyzed 75 patients with de novo AML aged <60 years included in the 2022 ELN favorable genetic risk group who achieved a CR in an independent test set from Gene Expression Omnibus (GSE37642). Our MCM identified 145 transcripts associated with cure or long-term RFS and 149 transcripts associated with latency or shorter-term time to relapse. The area under the curve and C-statistic were, respectively, 0.946 and 0.856 for our training set and 0.877 and 0.857 for our test set. Our results suggest that the favorable risk group includes distinct transcriptionally defined subgroups with different biological properties, which may be useful for refining this genetic risk category.
AB - Assignment of patients diagnosed with acute myeloid leukemia (AML) to the 2022 European LeukemiaNet (ELN) favorable genetic risk group has important clinical implications, as allogeneic stem cell transplantation in first complete remission (CR) is not advised due to a relatively good outcome of patients receiving chemotherapy alone and transplant-associated mortality. However, not all favorable genetic risk patients experience long-term relapse-free survival (RFS), making recognition of patients who would most likely be cured of high importance. We analyzed 297 patients aged <60 years with de novo AML classified as 2022 ELN favorable genetic risk who achieved a CR and had RNA sequencing (RNA-seq) and gene mutation data from diagnostic samples available (Alliance trial A152010). To identify prognostically relevant transcripts that can distinguish patients cured from patients susceptible to lower or higher risk of relapse or death, we fit a regularized mixture cure model (MCM) where RNA-seq expression values were our candidate covariates. To validate the identified transcripts, we analyzed 75 patients with de novo AML aged <60 years included in the 2022 ELN favorable genetic risk group who achieved a CR in an independent test set from Gene Expression Omnibus (GSE37642). Our MCM identified 145 transcripts associated with cure or long-term RFS and 149 transcripts associated with latency or shorter-term time to relapse. The area under the curve and C-statistic were, respectively, 0.946 and 0.856 for our training set and 0.877 and 0.857 for our test set. Our results suggest that the favorable risk group includes distinct transcriptionally defined subgroups with different biological properties, which may be useful for refining this genetic risk category.
UR - http://www.scopus.com/inward/record.url?scp=85207691083&partnerID=8YFLogxK
U2 - 10.1016/j.xinn.2024.100719
DO - 10.1016/j.xinn.2024.100719
M3 - Article
C2 - 39529956
AN - SCOPUS:85207691083
SN - 2666-6758
VL - 5
JO - The Innovation
JF - The Innovation
IS - 6
M1 - 100719
ER -