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Record W4361010814 · doi:10.1016/j.jtct.2023.03.024

Effect of Autograft CD34+ Dose on Outcome in Pediatric Patients Undergoing Autologous Hematopoietic Stem Cell Transplant for Central Nervous System Tumors

2023· article· en· W4361010814 on OpenAlexafffund
Tristan Knight, Kwang Woo Ahn, Kyle Hebert, Rasha Atshan, Donna A. Wall, Kanhatai Chiengthong, Seth J. Rotz, Ellen Fraint, Hemalatha G. Rangarajan, Jeffery J. Auletta, Akshay Sharma, Carrie L. Kitko, Hasan Hashem, Kirsten M. Williams, Baldeep Wirk, Christopher C. Dvorak, Kasiani C. Myers, Michael A. Pulsipher, Anne B. Warwick, Nahal Lalefar, Kirk R. Schultz, Muna Qayed, Larisa Broglie, Mary Eapen, Gregory A. Yanik

Bibliographic record

VenueTransplantation and Cellular Therapy · 2023
Typearticle
Languageen
FieldMedicine
TopicGlioma Diagnosis and Treatment
Canadian institutionsUniversity of British ColumbiaSickKids FoundationHospital for Sick ChildrenBC Children's HospitalUniversity of Toronto
FundersCancer MoonshotNational Institute of Allergy and Infectious DiseasesOffice of Naval ResearchPharmacyclicsTakeda OncologyHealth Resources and Services AdministrationNational Institutes of HealthMorphoSysLegend BiotechSangamo TherapeuticsAstellas PharmaAdaptive BiotechnologiesKiadis Pharmabluebird bioTG TherapeuticsJazz PharmaceuticalsStemCyteBeiGeneHistoGeneticsAtara BiotherapeuticsCareDxActinium PharmaceuticalsNational Cancer InstituteGilead SciencesSwedish Orphan BiovitrumOmeros CorporationVertex PharmaceuticalsLeukemia and Lymphoma SocietyMoonshot Research and Development ProgramSanofiGlaxoSmithKlineIncytePfizerNational Heart, Lung, and Blood InstituteNovartis Pharmaceuticals CorporationCSL BehringBristol-Myers SquibbAstraZenecaAmgenMallinckrodt PharmaceuticalsAstellas Pharma US
KeywordsMedicineQuartileProportional hazards modelCD34Hematopoietic stem cell transplantationAutologous stem-cell transplantationOncologyInternal medicineTransplantationSurgeryRetrospective cohort studyClinical endpointStem cellClinical trialConfidence intervalBiology

Abstract

fetched live from OpenAlex

Consolidation with autologous hematopoietic stem cell transplantation (HSCT) has improved survival for patients with central nervous system tumors (CNSTs). The impact of the autologous graft CD34+ dose on patient outcomes is unknown. We wanted to analyze the relationship between CD34+ dose, total nucleated cell (TNC) dose, and clinical outcomes, including overall survival (OS), progression-free survival (PFS), relapse, non-relapse mortality (NRM), endothelial-injury complications (EIC), and time to neutrophil engraftment in children undergoing autologous HSCT for CNSTs. A retrospective analysis of the CIBMTR database was performed. Children aged <10 years who underwent autologous HSCT between 2008 to 2018 for an indication of CNST were included. An optimal cut point was identified for patient age, CD34+ cell dose, and TNC, using the maximum likelihood method and PFS as an endpoint. Univariable analysis for PFS, OS, and relapse was described using the Kaplan-Meier estimator. Cox models were fitted for PFS and OS outcomes. Cause-specific hazards models were fitted for relapse and NRM. One hundred fifteen patients met the inclusion criteria. A statistically significant association was identified between autograft CD34+ content and clinical outcomes. Children receiving >3.6×106/kg CD34+ cells experienced superior PFS (p = .04) and OS (p = .04) compared to children receiving ≤3.6 × 106/kg. Relapse rates were lower in patients receiving >3.6 × 106/kg CD34+ cells (p = .05). Higher CD34+ doses were not associated with increased NRM (p = .59). Stratification of CD34+ dose by quartile did not reveal any statistically significant differences between quartiles for 3-year PFS (p = .66), OS (p = .29), risk of relapse (p = .57), or EIC (p = .87). There were no significant differences in patient outcomes based on TNC, and those receiving a TNC >4.4 × 108/kg did not experience superior PFS (p = .26), superior OS (p = .14), reduced risk of relapse (p = .37), or reduced NRM (p = .25). Children with medulloblastoma had superior PFS (p < .001), OS (p = .01), and relapse rates (p = .001) compared to those with other CNS tumor types. Median time to neutrophil engraftment was 10 days versus 12 days in the highest and lowest infused CD34+ quartiles, respectively. For children undergoing autologous HSCT for CNSTs, increasing CD34+ cell dose was associated with significantly improved OS and PFS, and lower relapse rates, without increased NRM or EICs.

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)0.000
metaresearch head score (Gemma)0.001
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 score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.013
GPT teacher head0.251
Teacher spread0.238 · 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".

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Citations3
Published2023
Admission routes2
Has abstractno

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