Prolonged Clinical and Molecular Remissions Following High-Dose Therapy/Autologous Stem Cell Transplantation (HDT/ASCT) and Rituximab and Interferon-alpha Maintenance for Relapsed High-Risk Follicular Lymphoma.
Notice bibliographique
Résumé
Abstract High-dose therapy and autologous stem cell transplantation (HDT/ASCT) are associated with prolonged remissions in relapsed follicular lymphoma (FL). Maintenance rituximab (R) has an accepted role in extending remissions and preclinical evidence suggests that its effects may be enhanced by the immunomodulatory capacity of interferon alpha (IFN-α). We designed a phase II study to incorporate in-vivo purging (with R) and post-transplant maintenance immunotherapy (with combined R and IFN-α) to prolong the remissions attained by HDT/ASCT. We present a planned analysis of 30 patients age ≤65 with 1–2 relapses of FL. Individuals received salvage CHOP or DHAP and proceeded with stem cell mobilization and HDT/ASCT with cyclophosphamide/carmustine/etoposide if they achieved ≥75% reduction in bulk and <15% marrow involvement. R 375 mg/m2 was given as 3 weekly doses prior to collection and as 6 weekly maintenance doses starting 12 weeks post-ASCT. IFN-α was initiated at week 10 post-ASCT with titration to a dose of 3 million units/m2 tiw for 2 years. Samples for PCR (sensitivity 0.01%) of t(14;18) or VDJ rearrangements were taken from blood/marrow to assess for molecular remission (MR). Results: Twenty-nine patients are assessable with a median follow-up for survivors of 3.1 years. Median age was 46 years (30–65) and median number of prior regimens was 2. Median response duration to prior therapy was 0.6 years and patients were enrolled 2.3 years (median) following diagnosis. The overall response rate to salvage was 93% (95% CI 83.7% to 100%) and n=23 proceeded to HDT/ASCT. Six patients did not undergo ASCT due to inadequate response (n=2), failed mobilization (n=2), cardiomyopathy (n=1), and patient withdrawal (n=1). Significant non-hematologic ASCT toxicities (grade 3/4) included: 5 episodes of interstitial pneumonitis, retinal vein occlusion (n=1), and thrombotic thrombocytopenic purpura (n=1). One patient was diagnosed with ALL 30 months following ASCT. Twenty-one individuals initiated IFN-α with 14 able to complete 2-years of maintenance (median dose of 3 × 106 units/m2 tiw). The most common reason for discontinuation was depression. At baseline, 19 patients had detectable markers by PCR. Despite in-vivo purging with R, 8 of 17 stem cell grafts had molecular disease, although graft contamination did not affect subsequent MR (p=NS). Of 16 assessable patients post-transplantation, 11/16 achieved MR prior to immunotherapy and 16/16 achieved MR during maintenance. Three patients have had a molecular relapse at 12, 18, and 36 months post-ASCT, with molecular preceding clinical relapse in 2/3 patients. Median progression-free survival for all patients is 50 months and median overall survival has not been reached. Conclusions: HDT/ASCT was feasible and well-tolerated in this high-risk population of relapsed FL. Molecular detection of lymphoma in the auto-graft did not preclude extended MR and clinical remissions post-transplant. This may be due to the enhanced clearance of minimal residual disease achieved by combination maintenance immunotherapy (R and interferon-α) post-ASCT. This is our third study in a sequential program of HDT/ASCT trials incorporating immunotherapy pre- and post-transplantation; we will present comparative evidence across the series to determine the added benefit of IFN-α in this latest approach.
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 | 0,000 | 0,000 |
| 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 | 0,001 |
| 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 ».