Prognostic Factors for Outcome of Nonmyeloablative Allogeneic Stem Cell Transplantation (NST) in Poor-Risk Chronic Lymphocytic Leukemia (CLL): Final Results from a Prospective Multicenter Trial (GCLLSG CLL3X study)
Notice bibliographique
Résumé
Abstract In order to refine the indications for NST in CLL, we analyzed prognostic factors for various endpoints of the CLL3X trial. CLL3X was a phase-2 trial investigating in a multicenter setting feasibility, toxicity and efficacy of NST in patients with poor-risk CLL. Patients <65 years were eligible if they had progressive disease in the presence of an unfavorable VH status, were fludarabine refractory, or had failed autoSCT. Central genetic work-up including FISH karyotyping was mandatory. Conditioning was based on fludarabine and cyclophosphamide. Centers could opt for routine addition of in-vivo T-cell depletion with alemtuzumab (TCD). Donors were HLA-matched (6/6) siblings or unrelated volunteers. Prospective longitudinal monitoring of minimal residual disease (MRD) was done centrally by MRD-flow or RQ-PCR. MRD results were communicated to the investigators for preemptive immunomodulation (restriction of immunosuppression or donor lymphocyte infusions). Results: Between June 2001 and March 2007, 113 patients were accrued in 16 centers. Thirteen patients had to be excluded due to ineligibility, and 10 patients did not proceed to NST because they lacked a donor, died or developed Richter’s transformation prior to NST, or refused NST. The 90 patients remaining had received 4 (1–11) pre-transplant regimens. 39/71 (55%) had an unfavorable FISH karyotype (del 11q- (37%) or del 17p- (18%)). 42/90 (47%) were fludarabine refractory, but only 24% had uncontrolled disease at NST. Allografts were obtained from related (39%) or unrelated donors (61%). TCD was performed in 12 patients. Due to logistical reasons, continuous sampling for prospective MRD monitoring was possible in only 4 centers representing 58% of the patients. With a median follow-up of 28 (6–80) months, 3-year non-relapse mortality, relapse incidence (REL), event-free survival (EFS) and overall survival (OS) from NST was 23% (95%CI 12%–34%), 42% (29%–56%), 42% (30%–54%), and 66% (55%–78%), respectively. Univariate log rank comparisons identified refractory disease at NST and TCD; but not age, fludarabine resistance, donor, and del 17p- as adverse factors for EFS. Three-year EFS was 43% (95%CI 14%–71%) with del 17p- vs 41% (27%–55%) without del 17p-. Cox regression models (adjusting for age, del 17p-, fludarabine resistance, remission status at NST, TCD, and donor) confirmed younger age (hazard ratio (HR)/year 0.94 (95%CI 0.89–0.99) and TCD (HR 3.68 (1.36–9.92)) as significant prognostic variables for REL; refractory disease at NST (HR 4.08 (1.9–8.74)) and TCD (HR 3.26 (1.53–6.94)) for EFS; and refractory disease at NST (HR 3.87 (1.62–9.25)) for OS. Three-year EFS was 57% (43%–72%) in patients who had sensitive disease at NST and no TCD employed, with no relapse occurring after the 3-year landmark. Only one relapse was observed in 25 patients (5 with del 17p-) who were MRD negative at month +12; and 15 out of 16 patients event-free more than 3 years after NST with MRD values available were MRD negative at last assessment. Conclusions: T-replete NST from related or unrelated donors results in sustained MRD-negative EFS in a significant proportion of patients with poor-risk CLL including those with del 17p-. NST should be performed before disease has become refractory. The potential benefit of preemptive post-transplant immunomodulation guided by real-time MRD monitoring remains to be settled.
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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| 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 | 0,001 | 0,001 |
| 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 ».