Tandem Autologous-Allogeneic Nonmyeloablative Sibling Transplant in Relapsed Follicular Lymphoma Leads to Impressive Progression Free Survival with Minimal Toxicity.
Notice bibliographique
Résumé
Abstract Abstract 50 High dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been shown to prolong progression free survival (PFS) as well as overall survival (OS) in patients (pts) with relapsed follicular lymphoma (FL). However, ASCT is usually not considered curative. Myeloablative allogeneic transplant has produced long term PFS in a subgroup of pts but is hampered by significant transplant related mortality (TRM). Reduced intensity transplant has less TRM but reports suggest a higher relapse rate. We therefore hypothesized that a tandem strategy consisting of ASCT followed by nonmyeloablative allogeneic transplant (NMT) would mimic a myeloablative allogeneic transplant without the associated early toxicity. We initiated such a prospective protocol for pts with relapsed FL in 2003. Patients underwent ASCT with a chemotherapy based conditioning regimen; 3 months post ASCT, pts with a 6/6 related donor received an outpatient NMT with 5 days of fludarabine 30 mg/m2/d and cyclophosphamide 300 mg/m2/d followed by infusion of ≥4×106 donor CD34+ cells/kg. GVHD prophylaxis, selected to take advantage of the low incidence of acute and the putative protective effect of chronic GVHD (as we have previously published in BBMT 2009 Aug;15(8):919), consisted of tacrolimus 3 mg bid started on day (D)-8 to achieve levels of 10–15 nmol/L then tapered off by D+100 and mycophenolate mofetil 1 g bid from D+2 to D+50. Between 4/2003 and 10/2008, 27 pts (M/F: 19/8) underwent tandem transplant, including 25 with FL and 2 with histology compatible with either FL or marginal zone lymphoma; 6/27 had histological progression towards an aggressive lymphoma. Median age was 49 years (range 34–65). The pts had previously been treated with a median of 3 lines of therapy (range 2–6). Median time from diagnosis to transplant was 34 months (range 14–131); 8 patients had never been exposed to rituximab. Disease status prior to ASCT was: 8 CR, 14 PR and 5 refractory. Conditioning chemotherapy for ASCT was: BEAC (n=14) and BEAM (n=13). 23 pts received peripheral blood stem cells and 4 received bone marrow for their ASCT. 2 pts received radiotherapy after ASCT to sites of previously bulky disease. Median time between ASCT and NMT was 133 days (range: 75–285). Pre NMT disease status was: 14 CR, 8 PR, 3 refractory, and 2 unknown. Median number of CD34+ cells/kg infused for NMT was 8.2 ×106 (range 3.2–29.2). Engraftment was prompt in all pts. 5 pts (18%) developed acute GVHD: 1 grade II and 4 grade III (2 classic acute and 3 delayed onset). Overall, 18 (67%) pts developed extensive chronic GVHD requiring treatment. Disease status at last follow up was: 22 CR and 5 unconfirmed CR. To date, there has been no disease progression and only 1 patient has died from GVHD at +11 months. With a median follow-up of 34 months (range 11–70) OS and PFS are both 96% at 3 and 5 years. In conclusion: 1) ASCT followed by sibling NMT for relapsed FL appears to be safe and well tolerated. 2) Disease response and PFS are excellent even in refractory and transformed cases of FL. 3) This novel approach warrants further investigation in larger prospective studies. Disclosures: No relevant conflicts of interest to declare.
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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 | 0,000 |
| 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 | 0,000 |
| 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 ».