Impact of Extramedullary Disease on the Outcomes after Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults with Acute Myeloid Leukemia - a CIBMTR Analysis
Notice bibliographique
Résumé
Background: In patients with AML, EMD can occur in the central nervous system (CNS) or other sites, in addition to bone marrow (BM) disease. Only a few retrospective studies have evaluated the impact of EMD on outcomes after alloHCT for children with AML. We hypothesized that the presence of EMD at AML diagnosis would be associated with inferior outcomes after alloHCT. Methods: The Center for International Blood and Marrow Transplant Research (CIBMTR) database was used to compare the effect of EMD in patients with AML. Based on EMD at diagnosis, patients were grouped as BM involvement (Group I), BM+CNS involvement (Group II), and BM+other EMD±CNS (Group III). The primary outcome was 1year (y) progression-free survival (PFS) with 1y overall survival (OS), non-relapse mortality (NRM), cumulative incidence (CI) of acute and chronic graft versus host disease (GVHD), and CI of relapse as secondary endpoints. Kaplan Meier estimates were used to assess survival outcomes and groups compared using log-rank test; Cox regression was used to identify covariates associated with survival. Results: Our cohort includes 938 children (<21y; 52% male) who received first alloHCT for AML between 2008-2019. All patients were in a morphologic complete remission (CR) and confirmed to have no evidence of EMD at the time of alloHCT. Our study cohort included 630 Group I, 212 Group II and 96 Group III patients. Group III patients were younger at HCT (median age 2.9y vs 10.8y Group I, 10y Group II;), had poor-risk cytogenetics (50% vs 37% Group I, 39% Group II) and a higher pediatric disease risk index (52.1% vs 21.9% Group I, 25% Group II) and poor risk cytogenetics (50% vs 39% Group I, 37% Group II). The majority (63%) of patients had low comorbidity burden by expanded youth malignant HCT comorbidity index (score of 0-1, no difference between groups). While 67.5% of patients received chemotherapy-only conditioning, 32.1% received total body irradiation (TBI) based, and the remaining chemotherapy with low-dose TBI (4.5%) conditioning regimens. Radiation to other sites, including CNS, was reported in 6.7% of the study cohort. Donors were mostly unrelated cords (42.4%), matched unrelated (20.5%), and matched siblings (18%), with the remainder being haploidentical (6.4%) and mismatched unrelated (6.9%)Graft sources included bone marrow (39.8%), umbilical cord blood (46.4%), and peripheral blood (14.8%). GVHD prophylaxis was commonly calcineurin inhibitor-based (89%), with the remainder receiving post-transplant cyclophosphamide-based prophylaxis (6.1%) or ex vivo T cell-depleted grafts (3.2%). At a median follow of 69.8 months (range 3.4-155 months), the 1y PFS of the entire group was 67.4%. The day +100 acute GVHD, 1y NRM, relapse incidence, OS, and chronic GVHD of the entire group was 31.7%, 10.3%, 22.6%, 77%, and 29.6% respectively. Multivariable analysis of factors associated with relapse, after adjusting for disease status (includes MRD), age, and TBI use, EMD was associated with improved survival: Group II: hazard ratio (HR) of 0.697 (95% CI 0.515-0.944; p=0.012) and Group III HR of 0.695 (95% CI 0.459-1.053; p=0.087) compared to Group I cohort. There was no difference in PFS (p=0.21), NRM (p= 0.27), and OS (p=0.90) among the groups. Conclusion: Our results suggest that the presence of EMD with BM at diagnosis did not impact clinical outcomes post-alloHCT. Although this cohort describes a subset of patients with EMD - those who were able to clear EMD prior to HCT and proceed to HCT - we observed that EMD at diagnosis among those who are otherwise able to proceed to HCT does not portend worse HCT outcomes or more relapse. It is possible that, in this setting, the ability to clear EMD prior to HCT was suggestive of chemotherapy-sensitive disease.
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 | 0,002 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,002 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| 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 ».