TY - JOUR
T1 - Association between mutation clearance after induction therapy and outcomes in acute myeloid leukemia
AU - Klco, Jeffery M.
AU - Miller, Christopher A.
AU - Griffith, Malachi
AU - Petti, Allegra
AU - Spencer, David H.
AU - Ketkar-Kulkarni, Shamika
AU - Wartman, Lukas D.
AU - Christopher, Matthew
AU - Lamprecht, Tamara L.
AU - Helton, Nicole M.
AU - Duncavage, Eric J.
AU - Payton, Jacqueline E.
AU - Baty, Jack
AU - Heath, Sharon E.
AU - Griffith, Obi L.
AU - Shen, Dong
AU - Hundal, Jasreet
AU - Chang, Gue Su
AU - Fulton, Robert
AU - O'Laughlin, Michelle
AU - Fronick, Catrina
AU - Magrini, Vincent
AU - Demeter, Ryan T.
AU - Larson, David E.
AU - Kulkarni, Shashikant
AU - Ozenberger, Bradley A.
AU - Welch, John S.
AU - Walter, Matthew J.
AU - Graubert, Timothy A.
AU - Westervelt, Peter
AU - Radich, Jerald P.
AU - Link, Daniel C.
AU - Mardis, Elaine R.
AU - DiPersio, John F.
AU - Wilson, Richard K.
AU - Ley, Timothy J.
PY - 2015/8/25
Y1 - 2015/8/25
N2 - Importance: Tests that predict outcomes for patients with acutemyeloid leukemia (AML) are imprecise, especially for those with intermediate risk AML. Objectives: To determine whether genomic approaches can provide novel prognostic information for adult patients with de novo AML. Design, Setting, and Participants: Whole-genome or exome sequencingwas performed on samples obtained at disease presentation from 71 patients with AML (mean age, 50.8 years) treated with standard induction chemotherapy at a single site starting in March 2002, with follow-up through January 2015. In addition, deep digital sequencing was performed on paired diagnosis and remission samples from 50 patients (including 32 with intermediate-risk AML), approximately 30 days after successful induction therapy. Twenty-five of the 50 were from the cohort of 71 patients, and 25 were new, additional cases. Exposures: Whole-genome or exome sequencing and targeted deep sequencing. Risk of identification based on genetic data. Main Outcomes and Measures: Mutation patterns (including clearance of leukemia-associated variants after chemotherapy) and their association with event-free survival and overall survival. Results: Analysis of comprehensive genomic data from the 71 patients did not improve outcome assessment over current standard-of-care metrics. In an analysis of 50 patients with both presentation and documented remission samples, 24 (48%) had persistent leukemia-associated mutations in at least 5%of bone marrow cells at remission. The 24 with persistent mutations had significantly reduced event-free and overall survival vs the 26 who cleared all mutations. Patients with intermediate cytogenetic risk profiles had similar findings. [Table Required]. Conclusions and Relevance: The detection of persistent leukemia-associated mutations in at least 5%of bone marrow cells in day 30 remission samples was associated with a significantly increased risk of relapse, and reduced overall survival. These data suggest that this genomic approach may improve risk stratification for patients with AML.
AB - Importance: Tests that predict outcomes for patients with acutemyeloid leukemia (AML) are imprecise, especially for those with intermediate risk AML. Objectives: To determine whether genomic approaches can provide novel prognostic information for adult patients with de novo AML. Design, Setting, and Participants: Whole-genome or exome sequencingwas performed on samples obtained at disease presentation from 71 patients with AML (mean age, 50.8 years) treated with standard induction chemotherapy at a single site starting in March 2002, with follow-up through January 2015. In addition, deep digital sequencing was performed on paired diagnosis and remission samples from 50 patients (including 32 with intermediate-risk AML), approximately 30 days after successful induction therapy. Twenty-five of the 50 were from the cohort of 71 patients, and 25 were new, additional cases. Exposures: Whole-genome or exome sequencing and targeted deep sequencing. Risk of identification based on genetic data. Main Outcomes and Measures: Mutation patterns (including clearance of leukemia-associated variants after chemotherapy) and their association with event-free survival and overall survival. Results: Analysis of comprehensive genomic data from the 71 patients did not improve outcome assessment over current standard-of-care metrics. In an analysis of 50 patients with both presentation and documented remission samples, 24 (48%) had persistent leukemia-associated mutations in at least 5%of bone marrow cells at remission. The 24 with persistent mutations had significantly reduced event-free and overall survival vs the 26 who cleared all mutations. Patients with intermediate cytogenetic risk profiles had similar findings. [Table Required]. Conclusions and Relevance: The detection of persistent leukemia-associated mutations in at least 5%of bone marrow cells in day 30 remission samples was associated with a significantly increased risk of relapse, and reduced overall survival. These data suggest that this genomic approach may improve risk stratification for patients with AML.
UR - http://www.scopus.com/inward/record.url?scp=84940545016&partnerID=8YFLogxK
U2 - 10.1001/jama.2015.9643
DO - 10.1001/jama.2015.9643
M3 - Article
C2 - 26305651
AN - SCOPUS:84940545016
SN - 0098-7484
VL - 314
SP - 811
EP - 822
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 8
ER -