Superior Survival of Myeloablative over Reduced-Intensity Conditioning in MDS Patients below 65 Years Using a Combination of Antithymocyte Globulin and Post-Transplantation Cyclophosphamide As Gvhd Prophylaxis
Notice bibliographique
Résumé
Background: Allogeneic hematopoietic cell transplantation (Allo-HCT) is a potentially curative treatment for patients with myelodysplastic syndrome (MDS), particularly those classified as high-risk. The choice of conditioning regimen remains contentious, with previous studies indicating that overall survival (OS) is similar between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC), although RIC is associated with lower transplant-related mortality (TRM) and higher relapse rates. This study aims to evaluate the outcomes of MAC versus RIC in patients undergoing Allo-HCT for MDS, with a unified graft-versus-host disease (GVHD) prophylaxis regimen comprising a combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy). Methods: We performed a retrospective analysis of 80 MDS patients who underwent Allo-HCT at Princess Margaret Cancer Centre between October 2015 and October 2023. Patients were under the age of 65 years and received the same GVHD prophylaxis with a combination of ATG, PTCy, and cyclosporine. Outcomes assessed included overall survival (OS), relapse-free survival (RFS), GVHD-free/RFS (GRFS), acute and chronic GVHD, and graft failure. Results: Among our cohort, 59 patients received RIC (Fludarabine 35 mg/m²/day for 4 days + Busulfan 3.2 mg/kg/day for 2 days + TBI 200, Fludarabine 35 mg/m²/day for 4 days + Treosulfan 10 or 14 g/m² for 3 days) and 21 patients received MAC (Fludarabine 35 mg/m²/day for 4 days + Busulfan 3.2 mg/kg/day for 4 days). The median age was significantly lower in the MAC group than in the RIC group (52 years vs. 60 years) (p<0.001). Matched unrelated donors (MUD) constituted the majority of the donor pool (52.5%), with no significant difference between the RIC and MAC groups (p=0.25). The RIC group had a higher proportion of patients with a hematopoietic cell transplant comorbidity index (HCT-CI) ≥3 (44.1% vs. 14.3%, p=0.02). The 1-year OS was significantly higher in the MAC group than in the RIC group (85.7% vs. 52.0%, p=0.03). The 1-year non-relapse mortality (NRM) did not significantly differ between the RIC and MAC groups (20.4% vs. 14.3%, p=0.47). The 1-year relapse rate was higher in the RIC group than in the MAC group (28.9% vs. 9.5%, p=0.05). The incidence of acute GVHD grade I-IV at day 100 was higher in the MAC group but did not reach statistical significance (52.4% vs. 39.0%, p=0.19). There were no significant differences observed between MAC and RIC in the incidence of acute GVHD grade II-IV (23.8% vs. 27.1%, p=0.85) or grade III-IV (9.5% vs. 6.8%, p=0.61), respectively. However, the incidence of chronic GVHD at 1 year was significantly higher in the MAC group compared to the RIC group (36.8% vs. 5.7%, p<0.001). Our analysis also indicated a trend of superiority in the 1-year GRFS in the MAC group compared to the RIC group (61.9% vs. 43.9%, p=0.17). Regarding the risk of graft failure, there was no significant difference in the incidence of graft failure between the comparative groups (p=0.22). Looking at infectious complications post-HCT, there was no significant difference in the incidence of bloodstream infection (BSI) between the MAC group and the RIC group (61.9% vs. 50.8%, p=0.52). Additionally, the risk of CMV reactivation did not statistically differ between the groups (p=0.12). Conclusion: Our findings suggest that MAC may offer better overall survival and relapse-free survival in patients under 65 years undergoing stem cell transplantation with ATG-PTCy-CSA, despite a higher incidence of chronic GVHD. The lack of significant differences in non-relapse mortality between conditioning regimens highlights the need for individualized patient assessment when selecting the appropriate conditioning regimen.
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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) | 0,001 | 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 ».