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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
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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.

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Mendeley readers

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The data shown below were compiled from readership statistics for 86 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 86 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 15 17%
Student > Master 11 13%
Researcher 8 9%
Other 6 7%
Student > Doctoral Student 5 6%
Other 14 16%
Unknown 27 31%
Readers by discipline Count As %
Medicine and Dentistry 23 27%
Nursing and Health Professions 9 10%
Biochemistry, Genetics and Molecular Biology 8 9%
Pharmacology, Toxicology and Pharmaceutical Science 5 6%
Agricultural and Biological Sciences 3 3%
Other 9 10%
Unknown 29 34%
Attention Score in Context

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
#20,456,235
of 23,012,811 outputs
Outputs from Clinical Epigenetics
#1,120
of 1,264 outputs
Outputs of similar age
#281,706
of 322,931 outputs
Outputs of similar age from Clinical Epigenetics
#20
of 28 outputs
Altmetric has tracked 23,012,811 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 1,264 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 28 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.