Combination of ATG and Post-Transplant Cyclophosphamide for Gvhd Prophylaxis in Matched and Mismatched Donor Peripheral Blood Stem Cell Transplants for Myeloid Malignancies
Notice bibliographique
Résumé
Introduction ATG and post-transplant cyclophosphamide (PTCy) have been individually shown to be efficacious in reducing rates of GVHD in HLA matched and mismatched transplants. We adopted a combination regimen of ATG and PTCy for GVHD prophylaxis in HLA matched and mismatched transplants for myeloid malignancies in our centre, to decrease the rates of acute and chronic GVHD. Objectives We assessed the overall and progression free survival, incidence of acute and chronic GVHD, relapse rates and non-relapse mortality with this protocol. Patients and Methods Reduced intensity conditioning protocol consisted of iv Fludarabine, iv Busulphan, and low dose TBI. GVHD prophylaxis was with Thymoglobulin total dose 4.5mg/kg, PTCy total dose 100 mg/kg and cyclosporine. The stem cell source was G-CSF stimulated PBSCs. Results 169 patients (median age 58 y, range 19-74y) with high-risk myeloid malignancies (AML-64.5%, MDS-19%, MPN-12%) were treated with this protocol after obtaining institutional approval. The donor types were as follows-10/10 matched unrelated donor (MUD) in 67, 9/10 mismatched unrelated (MMUD) in 24, 10/10 matched related donor(MRD) in 35 and haplo-identical (HI) donors in 43 patients. The median follow-up in the entire cohort was 12 months. The 1year OS in the MUD, MMUD, MRD and HI groups were 73%, 54%, 74% and 56% respectively and the corresponding 1 year PFS were 66%, 38%, 49% and 51% respectively. The percentage of graft failure (primary and/or secondary) in the 4 groups were 1.5%, 12.5%, 0% and 16.3% respectively. The relapse rates were 21% in MUD, 42% in MMUD, 29% in MRD and 14% in HI groups. The MMUD patients had significantly inferior OS (p=0.03), and PFS (p=0.003), and significantly higher risk of relapse(p=0.009), compared to MUD patients. The overall incidence of grade 3-4 acute GVHD in our patients was 10 % and of moderate/severe NIH stage chronic GVHD was 11.6% which is low compared to conventional GVHD prophylaxis regimes. The percentages for grade 3-4 acute GVHD according to donor type were 16.4% in MUD, 4.2% in MMUD, 5.8% in MRD and 9.3% in HI groups and that of moderate/severe NIH stage chronic GVHD were 7.5%, 8.4%, 11.4% and 16.3% respectively. There were high rates of viral reactivation observed with this dual T lymphocyte suppression strategy. The overall incidences of CMV, and EBV reactivation and BK cystitis were 48%, 33% and 17% respectively. In addition, there were 12 pathologically confirmed cases of post-transplant lympho-proliferative disorder. Conclusion Our experience shows that PT-Cy and ATG can be combined for GVHD prophylaxis in PBSCTs for high risk myeloid malignancies and results in low rates of Gr3-4 acute GVHD and moderate/severe chronic GVHD across different donor types with acceptable relapse rates. High rates of viral re-activation are a concern and need close monitoring.
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 | 0,000 |
| 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 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 ».