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Myeloid clonal hematopoiesis of indeterminate potential in patients with chronic lymphocytic leukemia

2024· article· en· W4402824677 on OpenAlexaff
Abi Vijenthira, Virginia O. Volpe, Aswin Sekar, Roberta S. Azevedo, Mariia Mikhaleva, Christopher J. Gibson, Stephen P. Martindale, Rayan Fardoun, Svitlana Tyekucheva, Yue Ren, Stacey M. Fernandes, Binyamin A. Knisbacher, Cynthia K. Hahn, Gad Getz, Catherine J. Wu, Matthew S. Davids, Jennifer R. Brown

Bibliographic record

VenueBlood Advances · 2024
Typearticle
Languageen
FieldMedicine
TopicAcute Myeloid Leukemia Research
Canadian institutionsPrincess Margaret Cancer CentreUniversity of Toronto
FundersNational Cancer Institute
KeywordsChronic lymphocytic leukemiaHaematopoiesisMyeloid leukemiaImmunologyIndeterminateMyeloidMedicineLeukemiaCancer researchBiologyStem cellGenetics

Abstract

fetched live from OpenAlex

ABSTRACT: Clonal hematopoiesis of indeterminate potential (CHIP) in patients with chronic lymphocytic leukemia (CLL) has not been extensively characterized. The objective of this study was to describe the prevalence of myeloid CHIP (M-CHIP) in patients with CLL, and to determine its association with time to first treatment (TTFT) and overall survival (OS). We retrospectively analyzed data from patients participating in a prospective CLL database at the Dana-Farber Cancer Institute who had standard-of-care targeted 95-gene next-generation sequencing (NGS) performed. A schema was devised to classify mutations as M-CHIP related. M-CHIP was analyzed as a binary (present/absent) and categorical (≥2 vs 1 vs 0 mutations) predictor. We included 966 patients (median age at time of NGS, 65 years; 38% female). Overall, 747 (77%) patients had NGS performed before CLL treatment, whereas 219 (23%) had it performed after receiving treatment. Median follow-up time from NGS was 1.9 years. The prevalence of M-CHIP in untreated (12%) and treated (24%) patients with CLL was similar to that described in previous literature. M-CHIP prevalence appeared to increase with age in untreated patients, but appeared consistent across age in treated patients, suggesting that treatment (85% had prior chemotherapy) may have an impact on M-CHIP emergence even in younger patients. The presence of ≥2 M-CHIP mutations was associated with OS, even accounting for prior treatment and age, but was driven by a small subset of patients (n = 28). M-CHIP was not associated with TTFT. These findings support continued work into characterizing the effects of M-CHIP in patients with CLL.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.228
Threshold uncertainty score0.628

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.004
GPT teacher head0.247
Teacher spread0.242 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations7
Published2024
Admission routes1
Has abstractyes

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