Impact of Clonal Size and High Disease Activity on Clinical Outcomes of Paroxysmal Nocturnal Hemoglobinuria: A Multicenter Registry
Notice bibliographique
Résumé
Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder that can lead to outcomes such as thrombosis, cardiovascular diseases, renal disfunction (both acute kidney injury [AKI] and chronic kidney disease [CKD]), and death (1,2). Complement inhibitors (CIs) are currently the standard of treatment, but there is no uniform consensus on whom to treat due to the rarity of the disease. The updated analysis of the International PNH Registry (2) suggests using CIs in patients with high disease activity (HDA), while the consensus of the Canadian PNH Network recommends using CIs in patients with HDA plus clonality >10% (2,3). Our aim is to determine whether HDA and clone size influence clinical outcomes in PNH in order to support either treatment recommendation. Methods This retrospective study was conducted at 4 centers in Mexico and included patients diagnosed with PNH by flow cytometry (FLAER+CD14/CD24). Characteristics at diagnosis such as symptoms, lactate dehydrogenase (LDH), thrombosis, cardiovascular events, clonality, and HDA (LDH ≥1.5 times the upper normal limit [UNL] plus PNH symptoms, hemoglobin ≤10g/dl, renal function impairment, or thrombosis) were collected. A descriptive analysis was performed, and a univariate logistic regression model was used to determine the impact of clone size and HAD on clinical outcomes. Results Information was collected from 136 patients diagnosed with PNH between 1988 and 2023, with 51.5% (n=70) being women, and a median age of 47 years (IQR;34-57). The classic PNH variant was most frequent, with 69.9% (n=95). The median follow-up was 65.99 months (IQR 14.1-106.5), with a median overall survival of 119 months (CI95% 91.6-183), and 68 patients (50.0%) deceased at the time of analysis. History of thrombosis was found in 19 patients (14%) and in 5 (3.7%) at diagnosis. Cardiovascular events (transient ischemic attack, myocardial infarction, unstable angina, and/or non-traumatic gangrene) occurred in 11 (8.08%). AKI was found in 22 (16.2%) at diagnosis and developed in 25 (18.4%) later. By last follow-up, 28 patients (20.6%) had CKD, 14 of them being on renal replacement therapy. LDH ≥1.5 times the UNL was found in 91 patients (66.9%) and 84 (61.8%) met the definition of HDA. An increase in LDH ≥1.5 times the UNL increased the probability of having hemoglobinuria (OR 11.5, CI95% 4.13-31.8, p<0.001), but not other symptoms. HDA increased the risk of thrombosis (OR 3.84, CI95% 1.06-13.9, p=0.03), cardiovascular disease (OR 14.5, CI95% 0.83-253, p=0.010), AKI (OR 7.81, CI95% 1.74-35.0, p=0.002), and CKD (OR 4.80, CI95%:1.56-14.8, p=0.003). Clonality ≥50% was found in 66.9%. Clone size was not associated with the development of thrombosis (OR 1.28, CI95% 0.46-3.57, p=0.632), AKI (OR 1.34, CI95% 0.51-3.49, p=0.55), CKD (OR 1.63, CI95% 0.63-4.18, p=0.307), or cardiovascular events (OR 2.02, CI95% 0.41-9.96, p=0.377). Discussion and Conclusions In the studied population, HDA was associated with severe outcomes such as thrombosis, AKI, CKD, and cardiovascular disease, while clone size was not associated with either of these outcomes. This suggests that the presence of HDA in PNH may justify the initiation of CI treatment regardless of clone size.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 tête enseignante, 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 ».