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

Overview of attention for article published in JAMA: Journal of the American Medical Association, August 2015
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (83rd percentile)

Mentioned by

news
7 news outlets
blogs
2 blogs
twitter
122 tweeters
facebook
4 Facebook pages

Readers on

mendeley
93 Mendeley
citeulike
2 CiteULike
Title
Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia
Published in
JAMA: Journal of the American Medical Association, August 2015
DOI 10.1001/jama.2015.9643
Pubmed ID
Authors

Jeffery M. Klco, Christopher A. Miller, Malachi Griffith, Allegra Petti, David H. Spencer, Shamika Ketkar-Kulkarni, Lukas D. Wartman, Matthew Christopher, Tamara L. Lamprecht, Nicole M. Helton, Eric J. Duncavage, Jacqueline E. Payton, Jack Baty, Sharon E. Heath, Obi L. Griffith, Dong Shen, Jasreet Hundal, Gue Su Chang, Robert Fulton, Michelle O'Laughlin, Catrina Fronick, Vincent Magrini, Ryan T. Demeter, David E. Larson, Shashikant Kulkarni, Bradley A. Ozenberger, John S. Welch, Matthew J. Walter, Timothy A. Graubert, Peter Westervelt, Jerald P. Radich, Daniel C. Link, Elaine R. Mardis, John F. DiPersio, Richard K. Wilson, Timothy J. Ley, 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, Welch, John S, Walter, Matthew J, Graubert, Timothy A, Westervelt, Peter, Radich, Jerald P, Link, Daniel C, Mardis, Elaine R, DiPersio, John F, Wilson, Richard K, Ley, Timothy J, Jerald P. Radich

Abstract

Tests that predict outcomes for patients with acute myeloid leukemia (AML) are imprecise, especially for those with intermediate risk AML. To determine whether genomic approaches can provide novel prognostic information for adult patients with de novo AML. 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. Whole-genome or exome sequencing and targeted deep sequencing. Risk of identification based on genetic data. Mutation patterns (including clearance of leukemia-associated variants after chemotherapy) and their association with event-free survival and overall survival. 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 survival vs the 26 who cleared all mutations (median [95% CI]: 6.0 months [95% CI, 3.7-9.6] for persistent mutations vs 17.9 months [95% CI, 11.3-40.4] for cleared mutations, log-rank P < .001; hazard ratio [HR], 3.67 [95% CI, 1.93-7.11], P < .001) and reduced overall survival (median [95% CI]: 10.5 months [95% CI, 7.5-22.2] for persistent mutations vs 42.2 months [95% CI, 20.6-not estimable] for cleared mutations, log-rank P = .003; HR, 2.86 [95% CI, 1.39-5.88], P = .004). Among the 32 patients with intermediate cytogenetic risk, the 14 patients with persistent mutations had reduced event-free survival compared with the 18 patients who cleared all mutations (median [95% CI]: 8.8 months [95% CI, 3.7-14.6] for persistent mutations vs 25.6 months [95% CI, 11.4-not estimable] for cleared mutations, log-rank P = .003; HR, 3.32 [95% CI, 1.44-7.67], P = .005) and reduced overall survival (median [95% CI]: 19.3 months [95% CI, 7.5-42.3] for persistent mutations vs 46.8 months [95% CI, 22.6-not estimable] for cleared mutations, log-rank P = .02; HR, 2.88 [95% CI, 1.11-7.45], P = .03). 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.

Twitter Demographics

The data shown below were collected from the profiles of 122 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 93 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 2 2%
Italy 2 2%
United States 2 2%
Australia 1 1%
Japan 1 1%
Sweden 1 1%
Unknown 84 90%

Demographic breakdown

Readers by professional status Count As %
Researcher 20 22%
Student > Ph. D. Student 16 17%
Student > Master 14 15%
Other 11 12%
Professor > Associate Professor 8 9%
Other 24 26%
Readers by discipline Count As %
Medicine and Dentistry 36 39%
Agricultural and Biological Sciences 26 28%
Biochemistry, Genetics and Molecular Biology 16 17%
Unspecified 4 4%
Mathematics 3 3%
Other 8 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 134. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 September 2017.
All research outputs
#66,035
of 8,747,744 outputs
Outputs from JAMA: Journal of the American Medical Association
#1,374
of 20,884 outputs
Outputs of similar age
#2,549
of 233,392 outputs
Outputs of similar age from JAMA: Journal of the American Medical Association
#73
of 437 outputs
Altmetric has tracked 8,747,744 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 20,884 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 38.7. This one has done particularly well, scoring higher than 93% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 233,392 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 437 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 83% of its contemporaries.