Mycophenolate Compared to Methotrexate As Part of Cyclosporine Based-GVHD Prophylaxis Does Not Affect Transplant Outcomes, Reduces Organ Specific Acute And Chronic GVHD, but Increases The Risk of CMV Viremia In Matched Related Donor Peripheral Blood Stem Cell Transplantation
Notice bibliographique
Résumé
Abstract Introduction Graft versus host disease (GVHD) remains the most frequent and serious complication following allogeneic hematopoietic stem cell transplantation (HSCT). There is marked variability in GVHD prophylaxis regimens but the most commonly used is methotrexate (MTX) in combination with cyclosporine (CSA). However MTX toxicity can mandate dose reductions resulting in an increased risk of acute GVHD (aGVHD). There is limited and conflicting data on the efficacy of mycophenolate (MMF) in comparison to MTX. Methods and patients We retrospectively reviewed 242 consecutive patients who received related donor myeloablative peripheral blood stem cell transplantation between 2002 and 2012 at the Princess Margaret Cancer Centre, Toronto Canada. We compared patients who received MMF/CSA (n=71) (institutional standard of care since 2009), to a historical control who received MTX/CSA (n=171). MTX was given IV as 15 mg/m2 on day +1, and 10 mg/m2 on days +3, +6, and +11 post HSCT with adjustments made for mucositis, renal and liver dysfunction and effusions. MMF was given as 45mg/kg/day in 3 divided doses orally from day 0 to +30 post HSCT. In both GVHD prophylaxis regimens the CSA strategy was the same (5 mg/kg/day IV q12h starting day -1 aiming for therapeutic trough levels between 200-400 mcg/L). Routine surveillance of CMV viremia was performed using pp65 antigenemia (>1 positive cell) until 2011 and thereafter this was performed using PCR (>200 copies). There were no differences in patient characteristics except for age and conditioning regimens due to period effect and institutional changes in practice. Results There was no difference between the MTX/CSA and MMF/CSA groups in 3-year overall survival (66.1% vs 56.9%, p=0.09), 3-year non-relapse mortality (19.0% vs 27.4%, p=0.13) and relapse (15.5% vs 16.0%, p=0.56). Patients in the MMF/CSA group had significantly faster neutrophil and platelet engraftments: medians of 13 vs 18 days and 10 vs 14 days respectively (p<0.001). The cumulative incidence of aGVHD (grades 2-4) was significantly higher in the MTX/CSA group 74.4% vs 45.1% (p<0.001). There was no difference in the incidence of gut aGVHD but there was a higher incidence of skin (71.5% vs 51.5% p<0.001) and liver (53.0% vs 11.3% p<0.001) aGVHD in the MTX/CSA vs MMF/CSA groups. There was no difference between the two groups in the 5-year cumulative incidence of chronic GVHD (cGVHD) or gastrointestinal, liver or skin cGVHD. There was however, a significantly lower incidence of lung, eye and mouth cGVHD in the MTX/CSA group: 29% vs 46.8% (p=0.04) for lung cGVHD, 37.7% vs 71.5% (p<0.001) for eye cGVHD and 59.6% vs 72.8% (p=0.001) for mouth cGVHD. The incidence of CMV reactivation was significantly lower in the MTX/CSA group, 40.9% vs 58.1% (p<0.001) in the MMF/CSA group. In multivariate analysis MMF/CSA was identified as an independent favorable factor for aGVHD (p=0.001, HR 0.62) but as a significant risk factor for CMV reactivation (p=0.005, HR 1.94). Conclusion The use of MMF/CSA in MRD PBSC transplant is not inferior as GVHD prophylaxis in comparison with MTX/CSA. MMF/CSA is associated with faster engraftment but a higher risk of CMV reactivation. Disclosures: Off Label Use: Mycophenoplate compared to methotrexate as part of cyclosporine based graft versus host disease prophylaxis.
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 | 0,000 | 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) | 0,002 | 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 ».