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Record W4377195778 · doi:10.1111/bjh.18863

Granulocyte transfusion during cord blood transplant for relapsed, refractory <scp>AML</scp> is associated with massive <scp>CD8</scp><sup>+</sup> T‐cell expansion, significant cytokine release syndrome and induction of disease remission

2023· article· en· W4377195778 on OpenAlexaff
Roisin Borrill, Kay Poulton, Laura Kusyk, Amy Routledge, Denise Bonney, Ramya Hanasoge‐Nataraj, Madeleine Powys, Omima Mustafa, Helen Campbell, Srividhya Senthil, Richard Dillon, Jelena Jovanović, Suzy Morton, Beki James, Kanchan Rao, Simon Stanworth, Joanne E. Konkel, Robert Wynn

Bibliographic record

VenueBritish Journal of Haematology · 2023
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsInstitute of Infection and Immunity
FundersChildren's Cancer and Leukaemia Group
KeywordsMedicineCytokine release syndromeInternal medicineImmunologyHematopoietic stem cell transplantationGastroenterologyTransplantationT cellImmune system

Abstract

fetched live from OpenAlex

Summary In high‐risk myeloid malignancy, relapse is reduced using cord blood transplant (CBT) but remains the principal cause of treatment failure. We previously described T‐cell expansion in CBT recipients receiving granulocyte transfusions. We now report the safety and tolerability of such transfusions, T‐cell expansion data, immunophenotype, cytokine profiles and clinical response in children with post‐transplant relapsed acute leukaemia who received T‐replete, HLA‐mismatched CBT and pooled granulocytes within a phase I/II trial (ClinicalTrials.Gov NCT05425043). All patients received the transfusion schedule without significant clinical toxicity. Nine of ten patients treated had detectable measurable residual disease (MRD) pre‐transplant. Nine patients achieved haematological remission, and eight became MRD negative. There were five deaths: transplant complications (n = 2), disease (n = 3), including two late relapses. Five patients are alive and in remission with 12.7 months median follow up. Significant T‐cell expansion occurred in nine patients with a greater median lymphocyte count than a historical cohort between days 7–13 (median 1.73 × 109/L vs. 0.1 × 109/L; p < 0.0001). Expanded T‐cells were predominantly CD8+ and effector memory or TEMRA phenotype. They exhibited markers of activation and cytotoxicity with interferon‐gamma production. All patients developed grade 1–3 cytokine release syndrome (CRS) with elevated serum IL‐6 and interferon‐gamma.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Case report · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
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 integrity0.0000.001
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 head0.015
GPT teacher head0.250
Teacher spread0.234 · 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 designCase report
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

Citations10
Published2023
Admission routes1
Has abstractyes

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