Evidence map›Paper›PMID 31113932›Full record

Trial reportBlood cancer journal2019

ABCB1 SNP predicts outcome in patients with acute myeloid leukemia treated with Gemtuzumab ozogamicin: a report from Children's Oncology Group AAML0531 Trial.

Roya Rafiee, Lata Chauhan, Todd A Alonzo, Yi-Cheng Wang, Ahlam Elmasry, Michael R Loken, Jessica Pollard, Richard Aplenc, Susana Raimondi, Betsy A Hirsch and 4 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Blood cancer journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

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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

14 authors at 11 institutions in 2 countries.

Roya RafieeDepartment of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Lata ChauhanDepartment of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Todd A AlonzoKeck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Yi-Cheng WangChildren's Oncology Group, Monrovia, CA, USA.
Ahlam ElmasryMansoura University, Mansoura, Egypt.
Michael R LokenHematologics Inc, Seattle, USA.
Jessica PollardDana-Farber/Boston Children's Cancer Center and Blood Disorders Center, Boston, MA, USA.
Richard AplencDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Susana RaimondiDepartment of Pathology, St. Jude Children's Hospital, Memphis, TN, USA.
Betsy A HirschChildren's Hospitals and Clinic of Minnesota, University of Minnesota, Minneapolis, MN, USA.
Irwin D BernsteinClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Alan S GamisDivision of Hematology/Oncology/Bone Marrow Transplantation, Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.
Soheil MeshinchiClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Jatinder K LambaDepartment of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA. jlamba@cop.ufl.edu.ORCID http://orcid.org/0000-0003-0411-0007
Fred Hutch Cancer Center · USUniversity of Florida · USAmerican Association of Colleges of Pharmacy · USChildren's Hospital of Philadelphia · USChildren's Mercy Hospital · USChildren's Oncology Group · USHarvard University · USMansoura University · EGSt. Jude Children's Research Hospital · USUniversity of Minnesota · USUniversity of Southern California · 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 DEVIDAS, MEENAKSHI · 2003 to 2013
$67.5M
Pharmacogenomics of Ara-C in AMLR01CA132946 · NCI · UNIVERSITY OF MINNESOTA · PI LAMBA, JATINDER K., POUNDS, STANLEY BARRETT · 2008 to 2025
$5.3M
Genetic Predictors of AML Treatment ResponseR01CA133881 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI APLENC, RICHARD · 2010 to 2014
$2.8M
Impact of genetic variation on response to GO therapy in COG-AML clinical trialsR21CA155524 · NCI · UNIVERSITY OF MINNESOTA · PI LAMBA, JATINDER K., WALTER, ROLAND BRUNO · 2012 to 2013
$439k
NCI NIH HHS R01 CA132946NCI NIH HHS R01 CA133881NCI NIH HHS R21 CA155524NCI NIH HHS U10 CA098413NCI NIH HHS U10 CA098543NCI NIH HHS U10 CA180886NCI NIH HHS U10 CA180899
6 · The paper itself

Abstract

Gemtuzumab-ozogamicin (GO), a humanized-anti-CD33 antibody linked with the toxin-calicheamicin-γ is a reemerging and promising drug for AML. Calicheamicin a key element of GO, induces DNA-damage and cell-death once the linked CD33-antibody facilitates its uptake. Calicheamicin efflux by the drug-transporter PgP-1 have been implicated in GO response thus in this study, we evaluated impact of ABCB1-SNPs on GO response. Genomic-DNA samples from 942 patients randomized to receive standard therapy with or without addition of GO (COG-AAML0531) were genotyped for ABCB1-SNPs. Our most interesting results show that for rs1045642, patients with minor-T-allele (CT/TT) had better outcome as compared to patients with CC genotype in GO-arm (Event-free survival-EFS: p = 0.022; and risk of relapse-RR, p = 0.007). In contrast, no difference between genotypes was observed for any of the clinical endpoints within No-GO arm (all p > 0.05). Consistent results were obtained when genotype groups were compared by GO and No-GO arms. The in vitro evaluation using HL60-cells further demonstrated consistent impact of rs1045642-T-allele on calicheamicin induced DNA-damage and cell-viability. Our results show the significance of ABCB1 SNPs on GO response in AML and warrants the need to investigate this in other cohorts. Once validated, ABCB1-SNPs in conjunction with CD33-SNPs can open up opportunities to personalize GO-therapy.

Indexed as

Biomarkers, TumorPolymorphism, Single NucleotideAdolescentAdultAllelesAntineoplastic Agents, ImmunologicalATP Binding Cassette Transporter, Subfamily BChildChild, PreschoolFemaleGemtuzumabGenotypeHumansInfantInfant, NewbornLeukemia, Myeloid, AcuteABCB1 protein, humanAntineoplastic Agents, ImmunologicalATP Binding Cassette Transporter, Subfamily BBiomarkers, TumorGemtuzumab

Identifiers

PMID31113932
PMCPMC6529443
OpenAlexW2944898939

What OpenQuestion holds

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LicenceCC BY
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.