Tandem Autologous-Nonmyeloablative (NMA) Allogeneic(Allo) Transplant (Tx) in Newly Diagnosed Multiple Myeloma (MM) Leads to Improved Survival When Compared to Conventional Allogeneic Transplant
Notice bibliographique
Résumé
Abstract Despite various strategies involving autologous Tx and use of newest drugs with anti-MM activity such as bortezomib and lenalidomide, very few patients with MM currently achieve long-term remission. Allo Tx theoretically remains an attractive option due to evidence of graft-versus-MM activity supported by small series of patients with long-term (>10 years) complete remissions (CR) following myeloablative Tx, the association between chronic graft-versus-host disease (Gvhd) and CR, and response in 20–30% of relapsed patients following donor leucocyte infusion. However, to date, the ideal strategy using Allo Tx remains uncertain. Early studies using myeloablative regimens have been associated with high (30–50%) mortality rates and late relapses have been observed despite Gvhd. Low (10–22%) reported mortality in NMA regimens is hampered by reduced CR and higher progression rates compared to ablative regimens. Additionally, long-term outcome following NMA transplant remains unclear. In this present study, we sought to compare outcomes of 2 sequential cohorts of patients with MM who underwent Allo Tx in our institution. Between 01/01 and 10/07, patients with newly diagnosed stage II–III MM were invited to participate in a phase II prospective study consisting of vincristine, adriamycine and decadron x 4 cycles followed by autologous blood stem cell Tx with melphalan 200 mg/m2. Within 3 months post autologous Tx, enrolled patients received outpatient NMA Allo Tx from a 6/6 HLA matched sibling donor with a conditioning of fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 for 5 days, followed by infusion of >4 x 106 CD34+ cells/kg. Gvhd prophylaxis was chosen to take advantage of low incidence of acute Gvhd and putative protective effect of chronic Gvhd: tacrolimus 3 mg bid was started on day (D)-8 then tapered off by D+100, with mycophenolate mofetil 1000 mg bid D+1 to D+50. Our NMA cohort was compared to MM patients who underwent full myeloablative Allo Tx between 06/90 and 01/01, mostly (N=29) with TBI; marrow was used in 54% and all received short course CSA/MTX. A total of 73 patients received NMA Tx (M/F: 43/30, median age 54 years, 73% stage III) and were compared to 39 patients with myeloablative Tx (M/F: 24/15, median age 47 years, 64% stage III). The incidence of grade II–IV acute Gvhd was significantly higher in the myeloablative group (30.7% vs 6.8%; p=0.0004); in contrast, as expected, chronic Gvhd was more frequent at 3 years following NMA Tx (90% vs 59.4%; p=0.0001). At 4 years, transplant related mortality (TRM) following myeloablative Tx was 50% compared to 17% in the NMA group (p=0.0001). Median (range) follow-up in NMA and myeloablative cohorts were 28 (3.5–82.9) and 37 (0.5–139) months, respectively. Kaplan-Meier estimates of overall survival (OS) at 2 (87% vs 59%; p=0.001) and 5 years (67% vs 44%; p=0.001) are significantly better in the NMA cohort. Similarly, disease free survival (DFS) at 2 (87% vs 48.5%; p=0.0001) and 5 years (67% vs 41%; p=0.0001) are also significantly better with the NMA Tx. In conclusion, our sequential auto-NMA Tx protocol is more effective to control MM than myeloablative Tx with significantly less TRM, better OS and DFS. These results might be explained by less advanced disease and higher incidence of chronic Gvhd in the NMA cohort. Future strategies should focus on reducing the relapse rate and incidence of extensive chronic Gvhd while preserving the graft versus MM effect.
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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 | 0,001 |
| 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 ».