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Record W3194157976 · doi:10.1016/j.jtct.2021.08.007

Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes

2021· article· en· W3194157976 on OpenAlexaff
Betül Oran, Kwang Woo Ahn, Caitrin Fretham, Amer Beitinjaneh, Asad Bashey, Attaphol Pawarode, Baldeep Wirk, Bart L. Scott, Bipin N. Savani, Christopher Bredeson, Daniel J. Weisdorf, David I. Marks, David A. Rizzieri, Edward A. Copelan, Gerhard Hildebrandt, Gregory A. Hale, Hemant S. Murthy, Hillard M. Lazarus, Jan Černý, Jane L. Liesveld, Jean A. Yared, Jean Yves-Cahn, Jeff Szer, Leo F. Verdonck, Mahmoud Aljurf, Marjolein van der Poel, Mark R. Litzow, Matt Kalaycio, Michael R. Grunwald, Miguel Ángel Díaz, Mitchell Sabloff, Mohamed A. Kharfan‐Dabaja, Navneet S. Majhail, Nosha Farhadfar, Ran Reshef, Richard F. Olsson, Robert Peter Gale, Ryotaro Nakamura, Sachiko Seo, Saurabh Chhabra, Shahrukh K. Hashmi, Shatha Farhan, Siddhartha Ganguly, Sunita Nathan, Taiga Nishihori, Tania Jain, Vaibhav Agrawal, Ulrike Bacher, Uday Popat, Wael Saber

Bibliographic record

VenueTransplantation and Cellular Therapy · 2021
Typearticle
Languageen
FieldMedicine
TopicAcute Myeloid Leukemia Research
Canadian institutionsUniversity of OttawaOttawa Hospital
FundersNational Institute of Allergy and Infectious DiseasesOffice of Naval ResearchNational Heart, Lung, and Blood InstituteU.S. Public Health ServiceHealth Resources and Services AdministrationCytoSen TherapeuticsKiadis PharmaPfizerIncyteKyowa Kirin Pharmaceutical DevelopmentJazz PharmaceuticalsMedical College of WisconsinTakeda Pharmaceuticals U.S.A.Meso Scale DiagnosticsAbbVieNational Cancer InstituteGilead SciencesKaryopharm TherapeuticsCelgeneNovartisGlaxoSmithKlineOtsuka AmericaCSL BehringBristol-Myers SquibbAstraZenecaRocheAstellas Pharma USFalk FoundationCareDxDaiichi-Sankyo
KeywordsMedicineFludarabineBusulfanMelphalanAlemtuzumabInternal medicineTransplantationRegimenHematopoietic stem cell transplantationCumulative incidenceIncidence (geometry)SurgeryGastroenterologyOncologyChemotherapyCyclophosphamide

Abstract

fetched live from OpenAlex

ABSTRACT Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m 2 . The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% ( P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [ P = .02] and 35% versus 27% at 3 years [ P = .01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P = .4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P = .03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

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: Non-randomized trial · Consensus signal: none
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 head0.011
GPT teacher head0.246
Teacher spread0.235 · 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 designNon-randomized trial
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

Citations32
Published2021
Admission routes1
Has abstractyes

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