Evidence map›Paper›PMID 24970842›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014

Detection of minimal residual disease in B lymphoblastic leukemia by high-throughput sequencing of IGH.

David Wu, Ryan O Emerson, Anna Sherwood, Mignon L Loh, Anne Angiolillo, Bryan Howie, Jennifer Vogt, Mark Rieder, Ilan Kirsch, Christopher Carlson and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 1 pooled it
16.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.

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  9. Next-Generation Sequencing in Adult B Cell Acute Lymphoblastic Leukemia Patients.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2017
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27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

David WuDepartment of Laboratory Medicine, University of Washington, Seattle, Washington.
Ryan O EmersonAdaptive Biotechnologies, Seattle, Washington.
Anna SherwoodAdaptive Biotechnologies, Seattle, Washington.
Mignon L LohPediatric Hematology/Oncology, University of California, San Francisco, San Francisco, California.
Anne AngiolilloChildren's National Medical Center, The George Washington University of Medicine, Washington, DC.
Bryan HowieAdaptive Biotechnologies, Seattle, Washington.
Jennifer VogtAdaptive Biotechnologies, Seattle, Washington.
Mark RiederAdaptive Biotechnologies, Seattle, Washington.
Ilan KirschAdaptive Biotechnologies, Seattle, Washington.
Christopher CarlsonAdaptive Biotechnologies, Seattle, Washington.
David WilliamsonAdaptive Biotechnologies, Seattle, Washington.
Brent L WoodDepartment of Laboratory Medicine, University of Washington, Seattle, Washington.
Harlan RobinsFred Hutchinson Cancer Research Center, Seattle, Washington. hrobins@fhcrc.org.
University of Washington · USFred Hutch Cancer Center · US

Funding

NCTN BIQSFP ANBL1531 (NRT)U10CA180886 · NCI · PUBLIC HEALTH INSTITUTE · PI Douglas S. Hawkins · 2014 to 2026
$390.6M
COG FOREIGN ACCRUALU10CA098543 · NCI · NATIONAL CHILDHOOD CANCER FOUNDATION · PI ADAMSON, PETER C. · 2003 to 2013
$335.5M
COG SDMC - Statistics CoreU10CA180899 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TODD A ALONZO · 2014 to 2026
$132.8M
Children's Oncology Group Statistics &Data Center GrantU10CA098413 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ANDERSON, JAMES R · 2003 to 2013
$67.5M
Support for Human Specimen Banking in NCI-Supported Cancer Clinical TrialsU24CA114766 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI RAMIREZ MILAN, NILSA DEL CARMEN · 2005 to 2014
$14.5M
NCI NIH HHS CA98543-09NCI NIH HHS U10 CA098413NCI NIH HHS U10 CA098543NCI NIH HHS U10 CA180886NCI NIH HHS U10 CA180899NCI NIH HHS U10 CA98543NCI NIH HHS U24 CA114766
6 · The paper itself

Abstract

purposeHigh-throughput sequencing (HTS) of immunoglobulin heavy-chain genes (IGH) in unselected clinical samples for minimal residual disease (MRD) in B lymphoblastic leukemia (B-ALL) has not been tested. As current MRD-detecting methods such as flow cytometry or patient-specific qPCR are complex or difficult to standardize in the clinical laboratory, sequencing may enhance clinical prognostication. EXPERIMENTAL

designWe sequenced IGH in paired pretreatment and day 29 post-treatment samples using residual material from consecutive, unselected samples from the Children's Oncology Group AALL0932 trial to measure MRD as compared with flow cytometry. We assessed the impact of ongoing recombination at IGH on MRD detection in post-treatment samples. Finally, we evaluated a subset of cases with discordant MRD results between flow cytometry and sequencing.

resultsWe found clonal IGH rearrangements in 92 of 98 pretreatment patient samples. Furthermore, while ongoing recombination of IGH was evident, index clones typically prevailed in MRD-positive post-treatment samples, suggesting that clonal evolution at IGH does not contribute substantively to tumor fitness. MRD was detected by sequencing in all flow cytometry-positive cases with no false-negative results. In addition, in a subset of patients, MRD was detected by sequencing, but not by flow cytometry, including a fraction with MRD levels within the sensitivity of flow cytometry. We provide data that suggest that this discordance in some patients may be due to the phenotypic maturation of the transformed cell.

conclusionOur results provide strong support for HTS of IGH to enhance clinical prognostication in B-ALL.

Indexed as

High-Throughput Nucleotide SequencingDisease-Free SurvivalFlow CytometryGene Rearrangement, B-Lymphocyte, Heavy ChainHumansImmunoglobulin Heavy ChainsLeukemia, B-CellNeoplasm, ResidualPrognosisImmunoglobulin Heavy Chains

Identifiers

PMID24970842
PMCPMC5142743
OpenAlexW2045807214

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.