Evidence map›Paper›PMID 39078289›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2024

Pharmacogenomic Score Effectively Personalizes Treatment of Acute Myeloid Leukemia.

Richard J Marrero, Huiyun Wu, Xueyuan Cao, Phani Krishna Parcha, Abdelrahman H Elsayed, Hiroto Inaba, Dennis John Kuo, Barbara A Degar, Kenneth Heym, Jeffrey W Taub and 6 more

2 registry-linked trialsAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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.

NCT00136084 phase3completednot on this map

A Collaborative Trial for the Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia

TypeinterventionalSponsorSt. Jude Children's Research HospitalRan2002 to 2012Enrolled238ConditionsLeukemia, Myelocytic, AcuteArmsCladribine, Cyclophosphamide, Cytarabine, Daunorubicin, Dexamethasone, Etoposide, Cytarabine, Gemtuzumab, L-asparaginase, Mercaptopurine, methotrexate, Mitoxantrone, Prednisone, Vincristine
NCT00703820 phase3completednot on this map

AML08: A Phase II Randomized Trial of Clofarabine Plus Cytarabine Versus Conventional Induction Therapy And A Phase II Study Of Natural Killer Cell Transplantation In Patients With Newly Diagnosed Acute Myeloid Leukemia

TypeinterventionalSponsorSt. Jude Children's Research HospitalRan2008 to 2020Enrolled324ConditionsAcute Myeloid LeukemiaArmsCytarabine, Daunorubicin, Etoposide, Clofarabine, CliniMACS
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Review
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

16 authors.

Richard J MarreroDepartment of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida.ORCID 0000-0002-0789-1075
Huiyun WuDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0003-2728-4608
Xueyuan CaoDepartment of Health Promotion and Disease Prevention, University of Tennessee Health Science Center, Memphis, Tennessee.ORCID 0000-0002-4396-7460
Phani Krishna ParchaDepartment of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida.ORCID 0000-0003-4326-4463
Abdelrahman H ElsayedDepartment of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida.ORCID 0000-0002-8150-6825
Hiroto InabaDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0003-0605-7342
Dennis John KuoDivision of Pediatric Hematology-Oncology, Rady Children's Hospital San Diego/University of California, San Diego, California.ORCID 0000-0003-4154-0057
Barbara A DegarDana-Farber Cancer Institute, Boston Children's Hospital, Boston, Massachusetts.ORCID 0000-0002-1295-6021
Kenneth HeymCook Children's Medical Center, Fort Worth, Texas.ORCID 0000-0002-6635-435X
Jeffrey W TaubChildren's Hospital of Michigan, Detroit, Michigan.ORCID 0000-0003-2228-3235
Norman LacayoLucile Packard Children's Hospital and Stanford Cancer Institute, Palo Alto, California.ORCID 0000-0003-4573-5118
Ching-Hon PuiDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0003-0303-5658
Raul C RibeiroDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9956-5647
Jeffrey E RubnitzDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0001-9885-3527
Stanley B PoundsDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9167-2114
Jatinder K LambaDepartment of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida.ORCID 0000-0003-0411-0007

Funding

University of Florida Health Cancer Center Support GrantP30CA247796 · NCI · UNIVERSITY OF FLORIDA · PI Alison Ivey · 2023 to 2026
$10.9M
Pharmacogenomics of Ara-C in AMLR01CA132946 · NCI · UNIVERSITY OF MINNESOTA · PI LAMBA, JATINDER K., POUNDS, STANLEY BARRETT · 2008 to 2025
$5.3M
American Cancer Society (ACS) SAP 21-061-01National Cancer Institute (NCI) P30CA247796National Cancer Institute (NCI) R01CA132946NCI NIH HHS P30 CA247796NCI NIH HHS R01 CA132946
6 · The paper itself

Abstract

purposeCytarabine (also known as ara-C) has been the backbone of acute myeloid leukemia (AML) chemotherapy for more than five decades. Recent pharmacogenomics-based 10-SNP ara-C (ACS10) scores showed low ACS10 (≤0) to be associated with poor outcomes in patients with AML treated with standard chemotherapy. Here, we evaluated the ACS10 score in the context of three different induction I regimens in patients with pediatric AML. EXPERIMENTAL

designACS10 score groups (low, ≤0, or high, >0) were evaluated for association with event-free survival (EFS) and overall survival (OS) by three randomized treatment arms in patients treated on the AML02 (NCT00136084) and AML08 (NCT00703820) clinical trials: AML02 low-dose ara-C (LDAC arm, n = 91), AML02 + AML08 high-dose ara-C (HDAC arm, n = 194), and AML08 clofarabine + ara-C (Clo/ara-C arm, n = 105) induction I regimens.

resultsWithin the low-ACS10 score (≤0) group, significantly improved EFS and OS were observed among patients treated with Clo/ara-C as compared with LDAC (EFS, HR = 0.45; 95% CI, 0.23-0.88; P = 0.020; OS, HR = 0.44; 95% CI, 0.19-0.99; P = 0.048). In contrast, within the high-ACS10 score group (score >0), augmentation with Clo/ara-C was not favorable as compared with LDAC (Clo/ara-C vs. LDAC, EFS, HR = 1.95; 95% CI, 1.05-3.63; P = 0.035; OS, HR = 2.10; 95% CI, 0.96-4.59; P = 0.063). Personalization models predicted 9% improvement in the outcome in ACS10 score-based tailored induction (Clo/ara-C for low and LDAC for high-ACS10 score groups) as compared with nonpersonalized approaches (P < 0.002).

conclusionsOur findings suggest that tailoring induction regimens using ACS10 scores can significantly improve outcomes in patients with AML. Given the SNPs are germline, preemptive genotyping can accelerate matching the most effective remission induction regimen.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCytarabineLeukemia, Myeloid, AcutePrecision MedicineAdolescentChildChild, PreschoolFemaleHumansInfantMalePharmacogeneticsPolymorphism, Single NucleotidePrognosisCytarabine

Identifiers

PMID39078289
PMCPMC11444877

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Registered trials

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.