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Record W4394009899 · doi:10.1016/j.jtct.2024.03.030

The Adverse Event Landscape of Stem Cell Transplant: Evidence for AGVHD Driving Early Transplant Associated Toxicities

2024· article· en· W4394009899 on OpenAlexaff
Takuto Takahashi, Benjamin Watkins, Brandi Bratrude, Donna Neuberg, Kyle Hebert, Kayla Betz, Alison Yu, Sung Won Choi, Jeffrey Davis, Christine Duncan, Roger Giller, Michael Grimley, Andrew C. Harris, David A. Jacobsohn, Nahal Lalefar, Nosha Farhadfar, Michael A. Pulsipher, Shalini Shenoy, Aleksandra Petrović, Kirk R. Schultz, Gregory A. Yanik, Bruce R. Blazar, John Horan, Amelia Langston, Leslie S. Kean, Muna Qayed

Bibliographic record

VenueTransplantation and Cellular Therapy · 2024
Typearticle
Languageen
FieldMedicine
TopicHematopoietic Stem Cell Transplantation
Canadian institutionsBC Children's HospitalUniversity of British Columbia
FundersNational Institute of Allergy and Infectious DiseasesNational Heart, Lung, and Blood InstituteU.S. Food and Drug AdministrationNational Institutes of HealthHarvard Medical SchoolLeukemia and Lymphoma Society
KeywordsAdverse effectMedicineStem cellEvent (particle physics)OncologyInternal medicineBiologyGenetics

Abstract

fetched live from OpenAlex

Although unrelated-donor (URD) hematopoietic cell transplantation (HCT) is associated with many toxicities, a detailed analysis of adverse events, as defined by the Common Terminology Criteria for Adverse Events (CTCAE), has not previously been curated. This represents a major unmet need, especially as it relates to assessing the safety of novel agents. We analyzed a detailed AE database from the "ABA2" randomized, double-blind, placebo-controlled clinical trial of abatacept for acute graft-versus-host disease (AGVHD) prevention, for which the FDA mandated a detailed AE assessment through Day +180, and weekly neutrophil and platelet counts through Day +100. These were analyzed for their relationship to key transplant outcomes, with a major focus on the impact of AGVHD on the development/severity of AEs. A total of 2102 AEs and 1816 neutrophil/platelet counts were analyzed from 142 8/8-HLA-matched URD HCT recipients on ABA2 (placebo cohort, n = 69, abatacept cohort, n = 73). This analysis resulted in 2 major observations. (1) Among graft source, conditioning intensity, age, and Grade 2 to 4 AGVHD, only AGVHD impacted Grade 3 to 5 AE acquisition after the first month post-transplant. (2) The development of Grade 3 to 4 AGVHD was associated with thrombocytopenia. We have created a detailed resource for the transplant community by which to contextualize clinical toxicities after transplant. It has identified AGVHD as a major driver of post-HCT Grade 3 to 5 AEs, and underscored a link between AGVHD and thrombocytopenia. This establishes a critical safety framework upon which the impact of novel post-transplant AGVHD therapeutics should be evaluated. This trial was registered at www.clinicaltrials.gov (#NCT01743131).

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.005
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0050.000

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 head0.030
GPT teacher head0.276
Teacher spread0.246 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2024
Admission routes1
Has abstractno

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