Evidence map›Paper›PMID 38993741›Full record

ArticleJournal of hematology2024

Frameshift Mutations in Leukemia-Associated Genes Correlate With Superior Outcomes in Patients Undergoing Allogeneic Stem Cell Transplant for

Emma Cammann, Sindha Madhav, Lloyd Hutchinson, Jan Cerny, Muthalagu Ramanathan, Jacob R Bledsoe, Vladislav Makarenko, Shyam A Patel, Xiuling Meng, Keith Tomaszewicz and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hematology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Emma CammannUMass Medical School, Worcester, MA, USA.
Sindha MadhavDepartment of Pathology, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA, USA.
Lloyd HutchinsonDepartment of Pathology, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA, USA.
Jan CernyDepartment of Hematology-Oncology, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA, USA.
Muthalagu RamanathanDepartment of Hematology-Oncology, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA, USA.
Jacob R BledsoeDepartment of Pathology, Boston Children's Hospital, Boston, MA, USA.
Vladislav MakarenkoCommonwealth Pathology Partners, P.C., Salem, MA, USA.
Shyam A PatelDepartment of Hematology-Oncology, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA, USA.
Xiuling MengDepartment of Pathology, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA, USA.
Keith TomaszewiczDepartment of Pathology, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA, USA.
Rajneesh NathDepartment of Hematology, Medical Oncology, Banner MD Anderson Cancer Center Clinic, Gilbert, AZ, USA.
Benjamin ChenBristol Myers Squibb Company, Cambridge, MA, USA.
Bruce WodaDepartment of Pathology, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA, USA.
William SeloveUMass Medical School, Worcester, MA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Allogeneic stem cell transplant (allo-SCT) is a mainstay of treatment for acute myeloid leukemia (AML). Its success depends largely on response of donor T lymphocytes against leukemia cells, known as graft-vs-leukemia (GvL) effect. A key potential driver of GvL is immune response to mutation-derived neoantigens. Previous studies in solid tumors have demonstrated enhanced immunogenicity of frameshift (FS)-derived peptides vs. those from non-synonymous single nucleotide variants (SNVs). We therefore hypothesized that AML cases bearing FS mutations in leukemia-associated genes would be more immunogenic than those with only other types of mutations (non-FS), and thus benefit more from allo-SCT via more robust GvL. Methods: We identified AML patients who had undergone allo-SCT between 2010 and 2022 and had next-generation sequencing data available on diagnostic specimens using a 42-gene hot spot panel. We compared the impact of tumor mutations present at diagnosis on overall survival and relapse-free survival based on FS versus non-FS status. Results: Ninety-five AML allo-SCT patients were identified. We observed superior relapse-free survival (P = 0.038, hazard ratio (HR): 0.24) and borderline superior overall survival (P = 0.058, HR: 0.55) post-transplant in Conclusions: Our findings suggest that FS-mutated AML cases may benefit more from allo-SCT than those with only non-FS mutations, possibly due to increased generation of immunogenic neoepitopes. If validated in an expanded study, incorporation of somatic FS mutation status in AML could improve patient selection algorithms for bone marrow transplant and thereby lead to superior outcomes.

Indexed as

AllogeneicAMLFrameshiftNGSSurvivalTMBTransplant

Identifiers

PMID38993741
PMCPMC11236359

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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.