Incidence, Risk Factors for Early Hepatotoxicity and Its Impact on Survival in Patients with Myelofibrosis Undergoing Allogeneic Hematopoietic Cell Transplantation
Notice bibliographique
Résumé
Abstract Abstract 1951 Allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment for myelofibrosis (MF), but it is associated with significant morbidity and mortality. Hepatotoxicity is an important regimen-related toxicity of HCT. MF is a myeloproliferative disorder with several features that may impair hepatic function and predispose to liver injury. These include extramedullary hematopoiesis, increased hepatic iron overload from blood transfusions, portal hypertension, and splanchnic vein thrombosis (SVT). It is hypothesized that patients with MF are at high risk of acute hepatocellular injury after allogeneic HCT due to existing hepatic impairment and/or underlying risk factors for hepatotoxicity. We conducted a retrospective chart review of consecutive patients (pts) with MF who underwent HCT from 1981 to 2011 to assess the incidence of liver toxicity, risk factors and its impact on survival. 53 pts were identified: idiopathic MF, 39; post-polycythemia vera (PV) MF, 4; post-essential thrombocytopenia (ET) MF, 10. 94% of the transplants were performed after 1995. The International Prognostic Scoring System (IPSS) at the time of HCT included intermediate 2 risk (34%) and high risk (55%). Pre-HCT transfusion dependency according to Gale criteria was observed in 60% pts. 11 pts (21%) had a significant history of hepatoportal disease (i.e. SVT, biopsy proven hepatic iron overload, evidence of portal hypertension). Conditioning intensity was myeloablative in 66% and reduced in 34%. Mean baseline values of bilirubin, AST and serum albumin were 14uM (4–38), 24U/L (8–90) and 39g/L (30–49), respectively. The incidence of mild (34.2mM to 102.6mM), moderate (102.6mM to 342mM) and severe (greater than 342mM) hyperbilirubinemia in the first 6 weeks post-HCT was 32%, 40% and 4%, respectively. The frequency of transaminitis (AST >2x ULN) was 29%. On average, albumin decreased by 9 +/− 4g/L, where a reduction of 10g/L or greater was observed in 44% of patients. There were 18 cases (35%) of hepatic veno-occlusive disease. In a bivariate analysis, older age at HCT, female gender and longer disease duration were significantly associated with AST elevation, while a history of hepatoportal disease predicted hyperbilirubinemia. The etiology of MF (i.e. idiopathic, post-PV, post-ET), IPSS, transfusion dependency, degree of hepatosplenomegaly, donor match and conditioning intensity had no impact on hepatocellular injury. Significantly lower overall survival was associated with moderate/severe hyperbilirubinemia (p 0.02) and severe AST elevation (p 0.02). The hazard ratios for non-relapse mortality (NRM) for moderate/severe rises in bilirubin and AST were 4.36 and 7.24, respectively. Our study shows a high risk of early hepatotoxicity in MF patients undergoing HCT. Early hepatotoxicity is an important cause of NRM and inferior survival in this population. These findings are useful in patient counseling and improving the selection of patients with MF for HCT, as well as in monitoring those at risk for acute hepatocellular injury in the post-HCT setting. Disclosures: Gupta: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.
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 | 0,000 | 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 | 0,000 |
| 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 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 ».