↓ Skip to main content

A multicenter, randomized study of decitabine as epigenetic priming with induction chemotherapy in children with AML

Overview of attention for article published in Clinical Epigenetics, October 2017
Altmetric Badge

Mentioned by

twitter
1 tweeter

Citations

dimensions_citation
19 Dimensions

Readers on

mendeley
59 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
A multicenter, randomized study of decitabine as epigenetic priming with induction chemotherapy in children with AML
Published in
Clinical Epigenetics, October 2017
DOI 10.1186/s13148-017-0411-x
Pubmed ID
Authors

Lia Gore, Timothy J. Triche, Jason E. Farrar, Daniel Wai, Christophe Legendre, Gerald C. Gooden, Winnie S. Liang, John Carpten, David Lee, Frank Alvaro, Margaret E. Macy, Carola Arndt, Philip Barnette, Todd Cooper, Laura Martin, Aru Narendran, Jessica Pollard, Soheil Meshinchi, Jessica Boklan, Robert J. Arceci, Bodour Salhia

Abstract

Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases, which has been studied extensively and is approved for myelodysplastic syndrome in adults but with less focus in children. Accordingly, we conducted a phase 1 multicenter, randomized, open-label study to evaluate decitabine pre-treatment before standard induction therapy in children with newly diagnosed AML to assess safety and tolerability and explore a number of biologic endpoints. Twenty-four patients were fully assessable for all study objectives per protocol (10 in Arm A = epigenetic priming induction, 14 in Arm B = standard induction). All patients experienced neutropenia and thrombocytopenia. The most common grade 3 and 4 non-hematologic adverse events observed were gastrointestinal toxicities and hypophosphatemia. Plasma decitabine PK were similar to previously reported adult data. Overall CR/CRi was similar for the two arms. MRD negativity at end-induction was 85% in Arm A versus 67% in Arm B patients. DNA methylation measured in peripheral blood over the course of treatment tracked with blast clearance and matched marrow aspirates at day 0 and day 21. Unlike end-induction marrow analyses, promoter methylation in blood identified an apparent reversal of response in the lone treatment failure, 1 week prior to the patient's marrow aspirate confirming non-response. Decitabine-induced effects on end-induction (day 35-43 following initiation of treatment) marrows in Arm A were reflected by changes in DNA methylation in matched paired marrow diagnostic aspirates. This first-in-pediatrics trial demonstrates that decitabine prior to standard combination chemotherapy is feasible and well tolerated in children with newly diagnosed AML. Pre-treatment with decitabine may represent a newer therapeutic option for pediatric AML, especially as it appears to induce important epigenetic alterations. The novel biological correlates studied in this trial offer a clinically relevant window into disease progression and remission. Additional studies are needed to definitively assess whether decitabine can enhance durability responses in children with AML. NCT01177540.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 59 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 59 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 9 15%
Student > Master 8 14%
Researcher 6 10%
Student > Postgraduate 4 7%
Student > Doctoral Student 4 7%
Other 15 25%
Unknown 13 22%
Readers by discipline Count As %
Medicine and Dentistry 17 29%
Biochemistry, Genetics and Molecular Biology 7 12%
Nursing and Health Professions 4 7%
Pharmacology, Toxicology and Pharmaceutical Science 4 7%
Computer Science 2 3%
Other 10 17%
Unknown 15 25%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 18 December 2017.
All research outputs
#10,911,233
of 12,312,517 outputs
Outputs from Clinical Epigenetics
#514
of 565 outputs
Outputs of similar age
#286,682
of 345,827 outputs
Outputs of similar age from Clinical Epigenetics
#29
of 40 outputs
Altmetric has tracked 12,312,517 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 565 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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 345,827 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 40 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.