Chronic Graft-Versus-Host Disease and Its Association with Treatment-Related Mortality, Relapse, Leukemia-Free and Overall Survival After Umbilical Cord Blood Transplantation (UCBT) In Children and Adolescents with Acute Leukemia
Notice bibliographique
Résumé
Abstract Abstract 213 Chronic graft-versus-host disease (cGVHD) is the leading cause of late transplant-related mortality (TRM) after unrelated adult donor transplantation. However, limited, mild or moderate cGVHD may be associated with higher survival in part due to an association with lower relapse risk in adults with acute and chronic leukemia. While cGVHD rates are generally lower in children, we sought to determine the impact of cGVHD after UCBT on risk of relapse, TRM, leukemia-free survival (LFS) and overall survival (OS) as well as to identify risk factors for cGVHD after UCBT. Patients <18 years with acute lymphoblastic or acute myeloblastic leukemia transplanted with a single UCB unit after myeloablative conditioning between 1995–2007 who survived without recurrent leukemia for more than 3 months were eligible for analysis. Of the 657 patients, 59% were male, 26% were >10 years of age, 24% were transplanted in third remission or beyond, 74% were conditioned with TBI, 83% had pre-transplant anti-thymocyte globulin and 11% received tacrolimus, rather than cyclosporine, for acute GVHD prophylaxis. The cumulative incidence of cGVHD was 25% at 5 years with mild, moderate and severe disease in 91, 38 and 19 patients, respectively. cGVHD rates did not vary with donor-recipient HLA disparity. We constructed Cox proportional hazard-regression models to examine the effects of cGVHD on TRM, relapse, treatment failure (relapse or death; inverse of LFS) and overall mortality adjusting for age, disease, disease status, transplantation period, GVHD prophylaxis and donor-recipient HLA match. The risks of TRM (hazard ratio [HR] 9.33, p<0.0001), treatment failure (HR 2.96, p<0.0001) and overall mortality (HR 4.79, p<0.0001) were significantly higher in patients who developed cGVHD compared to those who did not develop cGVHD. In contrast to reports in adults transplanted with bone marrow or peripheral blood, mortality risk did not vary in those with mild, moderate or severe cGVHD after UCBT. Notably, relapse risk was not altered by the development of cGVHD (HR 0.73, p=0.38). In multivariate analysis, after adjusting for age and transplantation period, cGVHD risks were higher in patients who received tacrolimus (HR 3.12, p<0.0001) and in those with a prior history of grade 2 acute GVHD (HR 2.04, p=0.0001) or grade 3–4 acute GVHD (HR 5.51, p<0.0001) with a higher risk of cGVHD in patients with grade 3–4 versus grade 2 acute GVHD (HR 2.70, p<0.0001). These data suggest cGVHD of any severity has a markedly negative impact on survival after UCBT in children with acute leukemia without the associated graft-versus-leukemia effect previously reported for other stem cell sources. This analysis compels us to reevaluate our current acute GVHD prophylaxis strategies, including how tacrolimus is typically used, in an attempt to reduce the risk of cGVHD and its deleterious effect on LFS and OS after UCBT. Disclosures: Weisdorf: Genzyme: Research Funding; Hospira:Wagner:CORD:USE: Membership on an entity's Board of Directors or advisory committees; VidaCord: 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 | 0,001 | 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 ».