Evidence map›Paper›PMID 36952646›Full record

ArticleJCO precision oncology2023

Polygenic Pharmacogenomic Markers as Predictors of Toxicity Phenotypes in the Treatment of Acute Lymphoblastic Leukemia: A Single-Center Study.

Trisha Larkin, Reema Kashif, Abdelrahman H Elsayed, Beate Greer, Karna Mangrola, Roya Rafiee, Nam Nguyen, Vivek Shastri, Biljana Horn, Jatinder K Lamba

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in JCO precision oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
2.9field-weighted citation impact, top 10% 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

7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Trisha LarkinDepartment of Pediatrics, University of Florida College of Medicine, Gainesville, FL.ORCID 0000-0001-5701-898X
Reema KashifDepartment of Pediatrics, University of Florida College of Medicine, Gainesville, FL.
Abdelrahman H ElsayedDepartment of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL.
Beate GreerPediatrics Division, UF Health Cancer Center, University of Florida, Gainesville, FL.
Karna MangrolaDepartment of Pediatrics, University of Florida College of Medicine, Gainesville, FL.
Roya RafieeDepartment of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL.
Nam NguyenDepartment of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL.ORCID 0000-0003-3036-4748
Vivek ShastriDepartment of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL.
Biljana HornDepartment of Pediatrics, University of Florida College of Medicine, Gainesville, FL.ORCID 0000-0002-1030-5946
Jatinder K LambaDepartment of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL.ORCID 0000-0003-0411-0007
University of Florida · USUniversity of Florida Health · US

Funding

Pharmacogenomics of Ara-C in AMLR01CA132946 · NCI · UNIVERSITY OF MINNESOTA · PI LAMBA, JATINDER K., POUNDS, STANLEY BARRETT · 2008 to 2025
$5.3M
NCI NIH HHS R01 CA132946
6 · The paper itself

Abstract

purposeAcute lymphoblastic leukemia (ALL) is the most prevalent cause of childhood cancer and requires a long course of therapy consisting of three primary phases with interval intensification blocks. Although these phases are necessary to achieve remission, the primary chemotherapeutic agents have potentially serious toxicities, which may lead to delays or discontinuations of therapy. The purpose of this study was to perform a comprehensive pharmacogenomic evaluation of common antileukemic agents and develop a polygenic toxicity risk score predictive of the most common toxicities observed during ALL treatment.

methodsThis cross-sectional study included 75 patients with pediatric ALL treated between 2012 and 2020 at the University of Florida. Toxicity data were collected within 100 days of initiation of therapy using CTCAE v4.0 for toxicity grading. For pharmacogenomic evaluation, single-nucleotide polymorphisms (SNPs) and genes were selected from previous reports or PharmGKB database. 116 unique SNPs were evaluated for incidence of various toxicities. A multivariable multi-SNP modeling for up to 3-SNP combination was performed to develop a polygenic toxicity risk score of prognostic value.

resultsWe identified several SNPs predictive of toxicity phenotypes in univariate analysis. Further multivariable SNP-SNP combination analysis suggest that susceptibility to chemotherapy-induced toxicities is likely multigenic in nature. For 3-SNPscore models, patients with high scores experienced increased risk of GI (

conclusionOur results imply that instead of a single-SNP approach, SNP-SNP combinations in multiple genes in drug pathways increases the robustness of prediction of toxicity. These results further provide promising SNP models that can help establish clinically relevant biomarkers allowing for greater individualization of cancer therapy to maximize efficacy and minimize toxicity for each patient.

Indexed as

Antineoplastic AgentsPrecursor Cell Lymphoblastic Leukemia-LymphomaCross-Sectional StudiesHumansPharmacogeneticsPhenotypeAntineoplastic Agents

Identifiers

PMID36952646
PMCPMC10309546
OpenAlexW4360608242

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.