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PS1373 A TWENTY‐FOUR YEAR EXPERIENCE OF AUTOLOGOUS STEM CELL TRANSPLANTATION FOR LIGHT CHAIN AMYLOIDOSIS PATIENTS IN THE UNITED KINGDOM

2019· article· en· W2952260994 on OpenAlexaff
Faye Sharpley, A Petrie, Syed Mahmood, Sajitha Sachchithanantham, Helen J. Lachmann, JD Gillmore, CJ Whelan, M. Fontana, Alberto Azcona, Candida Cristina Quarta, Patricia A. Hawkins, AD Wechalekar

Bibliographic record

VenueHemaSphere · 2019
Typearticle
Languageen
FieldMedicine
TopicChronic Lymphocytic Leukemia Research
Canadian institutionsPrincess Margaret Cancer CentreUniversity Health Network
Fundersnot available
KeywordsMedicineAutologous stem-cell transplantationUnivariate analysisInternal medicineProportional hazards modelCohortAL amyloidosisAmyloidosisSurvival analysisTransplantationLog-rank testOncologyMultivariate analysisSurgeryImmunologyImmunoglobulin light chain

Abstract

fetched live from OpenAlex

Background: Autologous stem cell transplantation (ASCT) is considered to be the best method to improve long term survival outcomes in light chain amyloidosis (AL) patients, with a median survival of over 10 years. Crucially, the mortality has decreased over the decades mainly due to refinement of patient selection criteria. Aims: Our aim was to report the changing outcomes of a cohort of UK AL amyloidosis patients treated with ASCT. Methods: All patients with a proven histological diagnosis of amyloidosis and treated with an ASCT from 1994–2018 were identified from our database. Patient baseline characteristics were recorded including biomarker assessment and organ involvement, defined according to international criteria. Haematological response was assessed at six months and organ responses at 12 months, both calculated from the date of the ASCT and defined according to the international amyloidosis consensus criteria. The primary outcome was overall survival (OS), defined as time from ASCT to death. Secondary outcomes included: time to next treatment (TTNT), defined from date of ASCT to the start of next treatment, and transplant related mortality (all‐cause mortality before day +100 from return of stem cells). Survival outcomes were analysed using the Kaplan‐Meier method, with comparisons done using the log rank test. The Cox proportion hazards model was used to assess predictors of OS. All p‐values were two sided and any variable with a P value <0.10 on univariate analysis was included in the multivariate model. Results: Two hundred and sixty four patients were identified. The median age at time of ASCT was 57 years (30–70 years) and the median time from diagnosis to ASCT was 12 (0–263 months). The majority of patients were performance status 0 or 1 (84%). The median number of organs involved was two (range 1–4). The dominant organ involved was kidney (N = 180, 68.2%) with cardiac involvement in 32% (N = 85). The Mayo stage was 1: 44% (N = 63), 2: 39% (N = 56) and 3: 16% (N = 2). Eighty patients (30%) had an up‐front ASCT and 45% (N = 118) after first line treatment. Organ response was as follows: cardiac (N = 28, 60.9%), renal (N = 101, 76%) and liver (N = 7, 13.5%). The overall survival post ASCT (OS) was 87 months, (95% CI: 77–106 months) and overall treatment related mortality (TRM) was 8.7%, with a significant reduction over time: 1994–2000: 18.8%; 2001–2006: 13.6%; 2007–2012:6.2%; 2013–2018: 1.1%. A haematological response was achieved in 94.8% of patients and was a strong predictor of both survival (complete response (CR)/very good partial response (VGPR)‐139 (95% CI: 82–139 months) vs partial response (PR)/stable disease (SD)/progressive disease (PD)‐64 (95% CI: 50–92 months), P = 0.007), see figure, and TTNT (CR/ VGPR: 49 (95% CI: 24–48 months) vs. PR/SD/PD: 35 (95% CI: 9–20 months), P = <0.0001). Mayo stage (P = 0.037) and an abnormal ALP (P = <0.001) were independent predictors of OS on multivariate analysis. Summary/Conclusion: In conclusion this analysis of 264 patients with AL amyloidosis, treated with an ASCT over a 24 year period, confirms excellent long term outcomes and a marked improvement in TRM from 19% to 1% in the latest patient cohort. The median survival in patients achieving a CR response was 11.5 years. Outcomes are now comparable to large transplant centres in the United States. Given this improvement in TRM and long term survival, we confirm that ASCT still remains an important treatment modality for patients with systemic AL amyloidosis. image

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)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.375
Threshold uncertainty score0.364

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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)0.0000.000

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 head0.029
GPT teacher head0.288
Teacher spread0.259 · 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".

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Citations0
Published2019
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