<i>Prospective Symptom Burden Analysis in 784 Patients with Myeloproliferative Neoplasms: High Burden Correlates with Inflammatory/Genetic Biomarkers and Reduced Survival</i>
Notice bibliographique
Résumé
Background: Myeloproliferative neoplasms (MPN) are associated with significant symptom burden, influencing patient quality of life and management. Thorough assessment of this burden is crucial; however, data from large populational registries are limited. Our objective was to characterize symptom burden in a large MPN cohort, determining: i) age-associated differences; ii) treatment effect; iii) biologic correlatives, and iv) impact on overall survival (OS) in a large, real-world population based setting. Methods: This is a multicenter prospective study analyzing patient-reported outcomes per MPN-Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), a validated questionnaire grading (0-10) ten MPN symptoms ( JCO, 2012). Recruitment: Quebec CML-MPN Research Group registry (>20 community/academic centers). Eligibility: i) diagnosis of polycythemia vera (PV), essential thrombocytosis (ET), or myelofibrosis (MF) per WHO criteria; ii) completion of 1+ MPN-SAF TSS between 2013-2022. Conventional statistics were used (JMP® Pro 14.1.0 software; SAS Institute, NC, USA). Results: 4105 MPN-SAF TSS were completed by 784 patients (n= 285 PV, n=422 ET, n=77 MF). Median age at diagnosis was 63 years (range 19-96); female preponderance (56%). A median of 5 questionnaires were completed/patient (range 1-16). Mean symptom score was 16.7 (+/-12.3). A clinically significant total score, defined as >20, was reported by 33% of patients (n=261); most frequently women (p<0.0001) and MF cases (p=0.03). Symptom burden in the young: N=74 (9%) were age <40 years at diagnosis. At recruitment, mean aggregate and maximum MPN-SAF TSS scores were comparable across younger and older subsets (p=0.3-0.9) (Table 1), despite lower risk scores in the former (p<0.05). When scores were deconstructed, younger patients - vs older, had significantly higher levels of fatigue (p=0.03) and abdominal pain (0.007). Impact of therapy: Of those with high MPN-SAF scores, a considerable proportion were not treated (n=69/179, 39%). Higher mean scores were also reported in those having initiated therapy >36 months from diagnosis (p=0.0009). Of those with available MPN-SAF pre/post treatment, 37% showed deteriorating scores following cytoreduction, regardless of agent (p=0.4). Notably, those not on antiplatelet therapy had significantly higher mean (p=0.0006) and sub-item scores (excluding fever/night sweats). Over time, all interventions confounded, n=338 (43%) experienced worsening of MPN-SAF scores. Clinical biomarkers: Patients with anemia (hemoglobin <100 g/L) had significantly higher mean MPN-SAF scores and worse fatigue, inactivity, concentration, bone pain, and weight loss (all p<0.05). Increased C reactive protein (CRP) associated significantly with higher MPN-SAF scores (p=0.03), as well as fatigue, inactivity, early satiety, and bone pain (all p<0.05). Notably, patients with JAK2V617F variant allele frequency >50% (VAF) had higher average (p=0.03) and maximum (p=0.001) MPN-SAF, higher inactivity scores (p=0.02), and more frequent worsening scores over time (p=0.05). Survival impact: Higher mean MPN-SAF score had a significantly detrimental impact on OS (p=0.05) (Figure 1). Multivariate analysis revealed absence of antiplatelet therapy, age at diagnosis >65 years, male sex, and high-level inactivity to be independent predictors of inferior OS (HR 29, 6, 3 and 3 respectively). Conclusions: This is a large-scale study comprehensively appraising symptom burden in MPN patients, disclosing several novel findings. First, it unexpectedly exposes disproportionately severe symptoms (fatigue/abdominal pain) in younger patients. Second, it reveals deterioration of symptoms in the face of therapy in a significant number of patients, underscoring inadequacy of current therapies in symptom control. Third, it discloses anemia, elevated CRP, and JAK2 VAF>50% as putative biomarkers of symptom burden; potential adjuncts in identifying highly symptomatic subsets, particularly in situations where symptom assessment is challenging. Finally, it confirms negative survival impact of high symptom burden in a real-world setting. Overall this data exposes a critical unmet need for new therapeutic avenues aimed at alleviating symptom burden in patients with MPN. Further delineation of the inflammation-symptom relationship and future studies using novel prevention strategies are warranted.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».