Evidence map›Paper›PMID 38890297›Full record

ArticleBlood cancer journal2024

Real world predictors of response and 24-month survival in high-grade TP53-mutated myeloid neoplasms.

Amandeep Kaur, Alexandra E Rojek, Emily Symes, Mariam T Nawas, Anand A Patel, Jay L Patel, Payal Sojitra, Barina Aqil, Madina Sukhanova, Megan E McNerney and 22 more

Abstract read
In one paragraph

Article in Blood cancer journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–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.

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

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Guideline
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  5. Molecular and Clinical Insights intoInternational journal of molecular sciences · 2025
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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

32 authors.

Amandeep Kaur *Department of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Alexandra E Rojek *Hematology/Oncology Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
Emily SymesDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Mariam T NawasHematology/Oncology Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
Anand A PatelHematology/Oncology Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
Jay L PatelDepartments of Pathology and Hematology/Oncology, University of Utah/ARUP, Salt Lake City, UT, USA.
Payal SojitraDepartment of Pathology, Rutgers Robert Wood Johnson Medical School New Brunswick NJ, New Brunswick, NJ, USA.
Barina AqilDepartment of Pathology, Northwestern Memorial Hospital, Chicago, IL, USA.
Madina SukhanovaDepartment of Pathology, Northwestern Memorial Hospital, Chicago, IL, USA.ORCID 0000-0002-1843-7038
Megan E McNerneyDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Leo P WuDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Aibek AkmatbekovDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Jeremy SegalDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Melissa Y TjotaDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Sandeep GurbuxaniDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.ORCID 0000-0003-0716-8730
Jason X ChengDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Su-Yeon YeonDepartment of Pathology, University of Illinois, Chicago, IL, USA.ORCID 0000-0003-2600-4133
Harini V RavisankarDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Carrie FitzpatrickDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Angela LagerHematology/Oncology Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
Michael W DrazerHematology/Oncology Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
Caner SayginHematology/Oncology Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
Pankhuri WanjariDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Panagiotis KatsonisMolecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-7172-1644
Olivier LichtargeMolecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Jane E ChurpekDivision of Hematology, Department of Medicine, University of Wisconsin, Madison, WI, USA.
Sharmila B GhoshDepartment of Pathology, Henry Ford Health Systems, Detroit, MI, USA.
Ami B PatelDepartments of Pathology and Hematology/Oncology, University of Utah/ARUP, Salt Lake City, UT, USA.
Madhu P MenonDepartments of Pathology and Hematology/Oncology, University of Utah/ARUP, Salt Lake City, UT, USA.
Daniel A ArberDepartment of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.ORCID 0000-0002-2160-9689
Peng Wang *Department of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA.
Girish Venkataraman *Department of Pathology, Sections of Hematopathology and Genomic Pathology, University of Chicago Medicine, Chicago, IL, USA. girish.venkataraman@uchospitals.edu.ORCID 0000-0002-8674-2608

Funding

BASIC RESEARCH TRAINING IN MEDICAL ONCOLOGYT32CA009566 · NCI · UNIVERSITY OF CHICAGO · PI OLUFUNMILAYO F. OLOPADE · 1987 to 2026
$10.5M
NCI NIH HHS T32 CA009566
6 · The paper itself

Abstract

Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 rate was 25.6% (50/195). We additionally identified several pre-therapy factors predictive of inferior CR1 including male gender (P = 0.026), ≥2 autosomal monosomies (P < 0.001), -17/17p (P = 0.011), multi-hit TP53 allelic state (P < 0.001) and CUX1 co-alterations (P = 0.010). In univariable analysis of the entire cohort, inferior OS24 was predicated by ≥2 monosomies (P = 0.004), TP53 VAF > 25% (P = 0.002), TP53 splice junction mutations (P = 0.007) and antecedent treated myeloid neoplasm (P = 0.001). In addition, mutations/deletions in CUX1, U2AF1, EZH2, TET2, CBL, or KRAS ('EPI6' signature) predicted inferior OS24 (HR = 2.0 [1.5-2.8]; P < 0.0001). In a subgroup analysis of HMA +/-Ven treated individuals (N = 144), TP53 VAF and monosomies did not impact OS24. A risk score for HMA +/-Ven treated individuals incorporating three pre-therapy predictors including TP53 splice junction mutations, EPI6 and antecedent treated myeloid neoplasm stratified 3 prognostic distinct groups: intermediate, intermediate-poor, and poor with significantly different median (12.8, 6.0, 4.3 months) and 24-month (20.9%, 5.7%, 0.5%) survival (P < 0.0001). For the first time, in a seemingly monolithic high-risk cohort, our data identifies several baseline factors that predict response and 24-month survival.

Indexed as

MutationTumor Suppressor Protein p53AdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedPrognosisTreatment OutcomeTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID38890297
PMCPMC11189545

What OpenQuestion holds

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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.