Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia

作者：Klco, Jeffery M.; Miller, Christopher A.; Griffith, Malachi; Petti, Allegra; Spencer, David H.; Ketkar-Kulkarni, Shamika; Wartman, Lukas D.; Christopher, Matthew; Lamprecht, Tamara L.; Helton, Nicole M.; Duncavage, Eric J.; Payton, Jacqueline E.; Baty, Jack; Heath, Sharon E.; Griffith, Obi L.; Shen, Dong; Hundal, Jasreet; Chang, Gue Su; Fulton, Robert; O'Laughlin, Michelle; Fronick, Catrina; Magrini, Vincent; Demeter, Ryan T.; Larson, David E.; Kulkarni, Shashikant; Ozenberger, Bradley A.

来源：JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2015, 314(8): 811-822.

DOI：10.1001/jama.2015.9643

• MINIMAL RESIDUAL DISEASE
• COOPERATIVE-ONCOLOGY-GROUP
• COMPLETE REMISSION
• ADULT PATIENTS
• CLONAL HEMATOPOIESIS
• CYTOGENETIC ABNORMALITIES
• PROGNOSTIC IMPACT
• STEM-CELLS
• RELAPSE
• CANCER

IMPORTANCE Tests that predict outcomes for patients with acute myeloid 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 sequencing was 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. @@@ [GRAPHICS] @@@ 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.

• 出版日期2015-8-25