Superiority of Pediatric Chemotherapy over Allogeneic Hematopoietic Cell Transplantation for Philadelphia Chromosome Negative Adult ALL in First Complete Remission: A Combined Analysis of Dana-Farber ALL Consortium and CIBMTR Cohorts
Notice bibliographique
Résumé
Abstract Introduction: In adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL), the optimal post-remission therapy remains uncertain. Although allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR1) has become a widely adopted curative strategy, the need for HCT may be supplanted by intensive, pediatric-style chemotherapy regimens. These two approaches have not previously been compared. Methods: We evaluated the outcomes of 422 related or unrelated donor HCT recipients aged 18-50 years with Ph-ALL in CR1 between 06/2002 and 12/2011 as reported to the CIBMTR. This was compared to a concurrent cohort of 108 Ph- ALL CR1 pts (18-50 years) who received a Dana Farber Cancer Institute (DFCI) ALL Consortium pediatric regimen consisting of intensive, non-HCT therapy. Primary outcome was disease-free survival (DFS). Patients in the DFCI chemotherapy cohort who received HCT in CR1 were censored at the day of HCT. Left-truncated analysis methods were used to adjust time from CR1 to transplant. Results: The HCT cohort was older (median age 34 vs. 30 years, p=0.001) and had higher diagnostic WBC counts (median 12x109/L [range <1-515) vs. 8x109/L [1-1424], p=0.001, respectively). The proportion of patients with T –ALL was lower in the HCT cohort (14% vs. 22%, p=0.03), while the incidence of t(4;11)/MLL was similar in both groups (8% vs. 10%, respectively). Of the HCT cohort 396 (94%) underwent myeloablative (MA) conditioning. Donor source was matched related donor in 176 (42%), 8/8 unrelated donors in 168 (40%), and 7/8 (18%) from 7/8 unrelated donors. In univariate analyses (Figure 1) cumulative incidence of relapse at 4 years was similar in both groups (HCT 25% [19-28] vs. chemo 23% [15-32] p=0.97). Two-year treatment-related mortality (TRM) was higher in the HCT cohort (HCT 33% [28-39] vs. chemo 4% [1-8], p<0.0001). At 4 years, DFS was superior in the chemo cohort (HCT 40% [35-45] vs. chemo 71% [60-79], p<0.0001). Four year OS also favored chemo (HCT 45% [40-50] vs. chemo 73% [63-81], p<0.0001). In multivariable analysis, independent factors predictive of treatment failure (relapse or death) were HCT (HR 3.11 [2.08 – 4.66], p<0.001) and the presence of CNS disease at diagnosis (HR 1.56 [1.03 – 2.38], p=0.04). The sole factor associated with poorer OS was the administration of HCT (HR 2.86 [1.88 – 4.34], p<0.0001). The favorable OS with chemo was maintained when restricting the HCT cohort to those recipients with related donors or fully matched (8/8) unrelated donors and those whose time from diagnosis to CR1 was <8 weeks (HR 2.14 [1.36-3.35], p=0.001). Similar outcomes were seen when restricting the HCT cohort to those who achieved CR1 < 8 weeks from diagnosis and received myeloablative conditioning. Conclusion: In this comparison of two cohorts of younger Ph- negative adults in CR1, post-remission therapy with an intensive, pediatric-inspired, chemotherapy-based regimen conferred a survival advantage when compared to allogeneic HCT. The high TRM associated with HCT is a major factor in determining outcomes after HCT. In an era of increasing adoption of pediatric regimens for adults with Ph- ALL, allogeneic HCT may no longer be required for the majority of patients who achieve CR1. These data support the need for randomized controlled studies in Ph- ALL comparing pediatric-inspired non-HCT regimens to allogeneic HCT-based therapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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 | 0,003 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 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 ».