Strength to Endure: Superiority of MAC over RIC in Patients <65 Years Undergoing Stem Cell Transplantation Using ATG-Ptcy-CSA for Gvhd Prophylaxis
Notice bibliographique
Résumé
Background: Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) is a curative treatment for many hematological diseases. Reduced-intensity conditioning (RIC) regimens were developed to decrease the toxicities associated with myeloablative conditioning (MAC) regimens, especially in older or less fit patients. RIC and MAC have been compared previously; RIC is known to have a higher risk of relapse, but this is usually counterbalanced by the higher rate of non-relapse mortality (NRM) with MAC, making overall survival (OS) between the two options comparable. However, it remains unclear how younger patients perform with RIC in terms of toxicity and overall survival compared to MAC. This study aims to compare the outcomes of RIC and MAC in patients younger than 65 years, all receiving a unified graft-versus-host disease (GVHD) prophylaxis regimen. Methods: A retrospective analysis was conducted for 640 patients who underwent Allo-HCT for different hematological diseases at Princess Margaret Cancer Centre between October 2015 and October 2023. All patients were under the age of 65 years and received a unified GVHD prophylaxis with a combination of ATG, PTCy, and cyclosporine. Outcomes compared included overall survival (OS), relapse-free survival (RFS), GVHD-free/RFS (GRFS), acute and chronic GVHD, post-transplant bloodstream infections, and graft failure. Results: A total of 640 patients were reviewed, with 434 receiving RIC and 206 receiving MAC. AML was the most common diagnosis (50.3%), with similar distributions in both RIC (47.7%) and MAC (55.8%) groups (p=0.07). Significant differences were noted in ALL (RIC 6.9% vs. MAC 17.0%, p<0.001) and MF (RIC 11.1% vs. MAC 2.9%, p<0.001). Lymphoma was more prevalent in the RIC group (5.8% vs. 1.9%, p<0.05). The RIC group was older on average (57 vs. 45 years, p<0.001). More RIC patients had KPS <90 (20.3% vs. 8.7%, p<0.001) and HCT-CI ≥3 (41.7% vs. 20.9%, p<0.001). Significant differences were seen in the use of matched related donors (16.6% RIC vs. 2.9% MAC, p=0.004) and frozen grafts (29.5% RIC vs. 20.4% MAC, p=0.02). The MAC group showed significantly higher 2-year OS (70.8% vs. 61.1%, p=0.02), RFS (66.4% vs. 54.7%, p=0.014), and GRFS (55.2% vs. 43.2%, p=0.012) compared to the RIC group. The 2-year cumulative incidence of relapse was higher in the RIC group (26.7% vs. 17.5%, p=0.018), while NRM rates were similar (13.9% vs. 16.8%, p=0.54). Although the overall incidence of acute GVHD was higher in the MAC group (44.2% vs. 32.7%, p=0.013), there was no significant difference in acute GVHD grades II-IV or chronic GVHD between the groups. The overall rate of BSI by day 30 was similar between the MAC and RIC groups (49.5% vs. 46.8%, p=0.90). Graft failure at one year was significantly higher in the RIC group compared to the MAC group (7.4% vs. 2.9%, p=0.02). Conclusion: In patients younger than 65 years undergoing Allo-HCT with ATG and PTCy for GVHD prophylaxis, MAC is associated with superior OS, RFS, and GRFS compared to RIC. The RIC group had higher relapse rates, with NRM rates being comparable, suggesting that MAC should be considered for patients who can tolerate it, especially those at higher risk of relapse. The study's limitations include its retrospective nature and unbalanced cohorts. Future prospective trials are warranted to validate these findings in the context of combining ATG and PTCy for GVHD 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 | 0,005 | 0,010 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 ».