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Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and <i>KMT2A</i>-rearranged AML

2021· article· en· W3201071899 on OpenAlexaff
Kamal Menghrajani, Alexandra Gomez-Arteaga, Rafael Madero‐Marroquin, Mei‐Jie Zhang, Khalid Bo-Subait, J. Ortiz Sánchez, Hailin Wang, Mahmoud Aljurf, Amer Assal, Ulrike Bacher, Sherif M. Badawy, Nelli Bejanyan, Vijaya Raj Bhatt, Christopher Bredeson, Michael Byrne, Paul Castillo, Jan Černý, Saurabh Chhabra, Stefan O. Ciurea, Zachariah DeFilipp, Nosha Farhadfar, Shahinaz M. Gadalla, Robert Peter Gale, Siddhartha Ganguly, Lohith Gowda, Michael R. Grunwald, Shahrukh K. Hashmi, Gerhard Hildebrandt, Christopher G. Kanakry, Ankit Kansagra, Farhad Khimani, Maxwell M. Krem, Hillard M. Lazarus, Hongtao Liu, Rodrigo Martino, Fotios V. Michelis, Sunita Nathan, Taiga Nishihori, Richard F. Olsson, Ran Reshef, David A. Rizzieri, Jacob M. Rowe, Bipin N. Savani, Sachiko Seo, Akshay Sharma, Melhem Solh, Celalettin Üstün, Leo F. Verdonck, Christopher S. Hourigan, Brenda M. Sandmaier, Mark R. Litzow, Partow Kebriaei, Daniel J. Weisdorf, Yanming Zhang, Martin S. Tallman, Wael Saber

Bibliographic record

VenueBlood Advances · 2021
Typearticle
Languageen
FieldMedicine
TopicAcute Myeloid Leukemia Research
Canadian institutionsPrincess Margaret Cancer CentreOttawa Hospital
FundersOffice of Naval ResearchPharmacyclicsSanofi GenzymeTakeda OncologyGenentechHealth Resources and Services AdministrationNational Institutes of HealthOmeros CorporationAstellas PharmaAdaptive BiotechnologiesPfizerIncyteKiadis Pharmabluebird bioNational Institute of Allergy and Infectious DiseasesAngiocrine BioscienceKaryopharm TherapeuticsActinium PharmaceuticalsDaiichi Sankyo EuropeNational Cancer InstituteGilead SciencesMoonshot Research and Development ProgramSanofiCancer MoonshotMedical College of WisconsinStemCyteMemorial Sloan-Kettering Cancer CenterWeill Cornell Medical CollegeCSL BehringBristol-Myers SquibbLegend BiotechAmerican Society of Clinical OncologyGlaxoSmithKlineBe The Match FoundationSeagenAstellas Pharma USClinical and Translational Science Center, Weill Cornell Medical CollegeAmgenNational Heart, Lung, and Blood InstituteNovartis Pharmaceuticals CorporationMedacJazz Pharmaceuticals
KeywordsInternal medicineMedicineAdverse effectMyeloid leukemiaOncologyDiseaseTransplantationLeukemiaRisk stratificationHematopoietic stem cell transplantation

Abstract

fetched live from OpenAlex

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

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)0.003
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 score0.024
Threshold uncertainty score0.865

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.014
GPT teacher head0.286
Teacher spread0.272 · 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

Citations13
Published2021
Admission routes1
Has abstractyes

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