Stem Cell Dose and Time To Engraftment Does Not Predict Outcome After Autologous Stem Cell Transplantation For Relapsed Aggressive NHL
Notice bibliographique
Résumé
Abstract Introduction Autologous stem cell transplantation (ASCT) is the standard of care for relapsed aggressive lymphomas. Time to neutrophil and platelet engraftment is strongly correlated with CD34+ cell number infused but data are conflicting as to whether patients who receive greater numbers of CD34+ stem cells have improved outcomes. We sought to determine whether short term engraftment predicts progression-free survival (PFS) independent of other disease-specific prognostic factors. Methods From the Princess Margaret Cancer Centre transplant database, we identified patients undergoing ASCT for relapsed aggressive lymphoma between 2007-2011. Data were extracted on prognostic features at relapse/progression, stem cell collection, engraftment, and time to progression and death. All patients received platinum-based salvage chemotherapy and those with chemosensitivity were mobilised with cyclophosphamide, etoposide and filgrastim (minimum threshold 2x106 CD34 cells/kg) and proceeded to ASCT. Patients who failed initial mobilisation were remobilised using plerixafor. High-dose therapy consisted of etoposide 60mg/kg Day -4 and melphalan 180mg/m2 Day -3 with stem cells infused on Day 0. Filgrastim 300µg daily was started from Day +7 until neutrophil recovery to >1.0 x106/uL. Platelet engraftment was defined as an unsupported platelet count >20 x 109/L. Results 97 patients with DLBCL (n=66), transformed (n=24) and T-cell lymphoma (n=7) were reviewed. Median age was 54 (range 20-67), 61% were male and median IPI score on relapse was 2. Fifty one percent relapsed within 12 months of last therapy, and of the patients with B-cell lymphoma, 81% received rituximab prior to salvage chemotherapy. Median stem cell dose was 5.7x106 CD34+ cells/kg (range 1.69-17.82) with a median number of apheresis sessions to achieve this of 2 (range 1-4). Median time to neutrophils >0.5x106/uL was 11 days (range 9-14) and platelets >20x106/uL was 14 days (range 10-23). The Spearman correlation test confirmed a higher stem cell dose was significantly associated with shorter time to neutrophil (p=0.0014) and platelet engraftment (p=0.0003). From date of ASCT, median follow-up was 3.1 years in progression-free patients. For the entire cohort, PFS was 50% and overall survival (OS) was 74% at 3 years. On univariable analysis, patients with B-cell lymphoma with IPI score of 0-2 had a 3-year PFS of 59%, v 28% for those with IPI of 3-4 (p=0.03) (n=90). Patients with early relapse within 12 months of last therapy had inferior 3-year PFS, 42% v 59% for those with initial PFS > 1 year (p=0.08). Patients with B-cell lymphoma who received rituximab with primary chemotherapy had worse 3-year PFS: 47% v 69% (p=0.11). There were no associations of PFS with lymphoma subtype, dose of stem cells infused, number of apheresis sessions and neutrophil or platelet engraftment. Similarly, on univariable analysis of OS for the entire cohort, only secondary IPI (0-2 v 3-4) was significant, with 3-year OS 82% v 48%, respectively (p=0.01). Multivariable Cox regression analysis of outcomes for patients with B-cell lymphoma in a model including IPI score, time to relapse, prior rituximab, CD34+ cell dose and neutrophil and platelet engraftment times confirmed IPI was the only significant variable predicting PFS (HR 1.99, p=0.03) and OS (HR 3.2, p=0.006). Conclusions In this cohort of patients with aggressive lymphomas, CD34+ cell dose was correlated with time to neutrophil and platelet engraftment but was not predictive of PFS or OS. Secondary IPI score, relapse within 12 months, and for B-cell lymphomas previous use of rituximab were predictive of outcomes post ASCT. Disclosures: Kuruvilla: Roche: Honoraria. Kukreti:Millennium Pharmaceuticals: Research Funding; Onyx: Research Funding. Keating:Roche: Honoraria. Crump:Roche: Honoraria; Jansen-Ortho: Honoraria; Celgene: Honoraria; Lundbeck: Honoraria; Novartis: Research Funding; Seattle Genetics: Honoraria.
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 | 0,001 |
| 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 | 0,001 | 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 ».