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Prognostic Impact of Monosomy 7 as a Single Anomaly In Primary MDS – Reclassification From Poor to Intermediate Prognosis

2010· article· en· W2548935397 on OpenAlexaff
Julie Schanz, Heinz Tüchler, Françesc Solé, Mar Mallo, Barbara Hildebrandt, Christian Steidl, Christa Fonatsch, Michael Pfeilstöcker, Thomas Nösslinger, Peter Valent, Aristoteles Giagounidis, Michael Lübbert, Reinhard Stauder, Otto Krieger, Michelle M. Le Beau, John M. Bennett, Peter L. Greenberg, Ulrich Germing, Detlef Haase

Bibliographic record

VenueBlood · 2010
Typearticle
Languageen
FieldMedicine
TopicAcute Myeloid Leukemia Research
Canadian institutionsBC Cancer Agency
Fundersnot available
KeywordsInternational Prognostic Scoring SystemMyelodysplastic syndromesUnivariate analysisMonosomyInternal medicineMedicineMultivariate analysisChromosome abnormalityOncologyChemotherapy regimenBone marrowPediatricsChemotherapyKaryotypeBiologyGenetics

Abstract

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Abstract Abstract 1861 Introduction: Total or partial Monosomy 7 (-7/del(7q)) is one of the most frequent cytogenetic abnormalities in MDS, occurring in about 11% of abnormal cases in patients (pts) with primary MDS. The cytogenetic module of the IPSS defines any abnormality of chromosome 7 as unfavourable and classifies them, combined with complex abnormalities, into the poor risk cytogenetic subgroup. However, in previous publications from other groups, the prognosis of isolated -7/del(7q) was described as intermediate. The aim of the present study was to re-analyze the prognostic impact of -7/del(7q) as a single anomaly based on a large, international MDS database which was previously presented at the 2009 ASH-meeting (Schanz et al. abstract #2772). Materials and Method: Patients with -7/del(7q), derived from the international MDS database were examined. The large international data collection contains 2901 patients with MDS, originating from the German-Austrian (GA)-, the International MDS Risk Analysis Workshop (IMRAW)- and the Spanish Cytogenetic Working group (GCECGH) and the International Cytogenetics Working Group of the MDS Foundation (ICWG). Inclusion criteria for the study were defined as follows: Primary MDS, age >=16, and bone marrow blasts <=30%. Regarding therapy, patients with primary MDS who received supportive care, short courses of oral chemotherapy or hemopoietic growth factors were included. Univariate and multivariate analysis were performed for overall survival (OS) and risk of AML-transformation (AML-t). In multivariate analysis, site, age, gender, bone marrow blast count, date of first diagnosis and number of peripheral cytopenias were defined as co-variables. Results: In total, 60 patients (2.1% of all pts/4.4% of abnormal cases) with an isolated -7/del(7q) were detected. The median age of these pts was 66.1 years, which is significantly lower compared to pts without monosomy 7 (70.0 years; p<0.01; t-test, 2-sided). Regarding peripheral blood count, the mean hemoglobin in -7/del(7q) pts (9.2 g/dl) as well as ANC (1.7*103/ul) did not differ significantly as compared to pts without -7/del(7q) whereas the platelet count in pts with -7/del(7q) was significantly lower (82*103/ul vs. 125*103/ul; p<0.01). The median overall survival in -7/del(7q) pts was 16.0 (95% CI 14.0–21.4) months and the Hazard ratio (HR; as compared to a normal karyotype with a median survival of 47.4 (44.0-53.4) months as the reference category) was 1.6 (1.1-2.3; <0.01). Regarding the risk of AML-transformation, the median time to AML was 42.2 (14.4-not reached) months and the HR 1.7 (0.9-3.2; p<0.01). In comparison, this differed significantly from the median survival- (p<0.0001) and time to AML-transformation (p=0.027) for complex abnormalities, which are included with -7/del(7q) in the poor risk IPSS cytogenetic subgroup and were 5.7 (4.7-6.8) and 8.2 (6.4-14.0) months, respectively. The HR for complex abnormalities was 4.3 (3.4-5.4; p<0.01) for OS and 5.2 (3.8-7.5; p<0.01) for AML-transformation. Conclusions: The re-analysis of -7/del(7q), based on the largest MDS patient cohort yet published, confirms that the prognostic impact of an isolated total or partial monosomy 7 for overall survival as well as the risk of AML-transformation is intermediate, rather than poor. This finding is anticipated to be considered in the upcoming revision of the IPSS. Acknowledgments: The authors like to thank the MDS-Foundation for its support. Disclosures: Valent: Novartis: Research Funding; Bristol-Myers Squibb: Research Funding. Bennett:Johnson & Johnson: Consultancy.

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)0.002
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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

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 head0.019
GPT teacher head0.296
Teacher spread0.277 · 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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Citations0
Published2010
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