Contribution of Chemotherapy Mobilization to Disease Control in Multiple Myeloma Treated with Autologous Transplantation
Notice bibliographique
Résumé
Abstract Background: Autologous hematopoietic progenitor cells (auto-HC) can be mobilized either by hematopoietic growth factors (GF) alone or cytotoxic chemotherapy + GF (CC+GF). The latter is associated with higher CD34+ yields, but is associated with increased costs and risks of infection and hospitalization. In patients with multiple myeloma (MM) undergoing Auto-HCT, it is uncertain whether mobilization with CC+GF affects post transplant outcomes. Methods: We conducted a retrospective analysis of patients with MM undergoing their first AHPCT following high dose melphalan (≥140 mg/m2) between 2007 and 2012 in US and Canada and registered with the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients who had a planned subsequent allogeneic transplant, received VAD or similar induction therapy, had disease progression prior to transplant, or were mobilized with plerixafor were excluded from the analysis. The primary endpoint was progression-free survival (PFS) and the main secondary end-points were transplant-related mortality (TRM), relapse and overall survival (OS). Results: There were 519 patients in GF and 449 in CC+GF with median follow-up of 42 and 46 months respectively. The most common mobilizing CC regimen was single agent cyclophosphamide (71%). GF and CC+GF groups were similar but there were more patients in GF with only one prior line of therapy, lenalidomide exposure and CR at the time of transplant and more patients in CC+GF with low HCT co-morbidity index, prior thalidomide exposure and planed second autologous transplant (Table 1). Median number of days for auto-HC collection was 2 (IQR 1-3) in GF and 1 (IQR 1-3) in CC+GF (P<0.001). There were fewer days between collection and transplant (median 16 vs. 18, P<0.001) and fewer CD34+ cells (x 106/kg) infused at transplant (median 3.9, IQR=3.1-4.8, vs. 5.1, IQR 3.5-6.9, P<0.001) in GF than in CC+GF. Kinetics of neutrophil engraftment (> 0.5 x 109/L) was similar between groups (13 vs. 13 days, P=0.69) while platelet engraftment (> 20 x 109/L) was faster in CC+GF (median 19 vs. 18 days, P=0.006). There was no difference between groups in number of hospitalization days (14 vs. 14, P=0.7). In univariate analysis, there was no significant difference between the two groups in OS, PFS, or TRM. In multivariate analysis, stage III at diagnosis and Karnofsky status <90 but not modality of mobilization were associated with worse PFS. Similarly HCT-CI >2, Stage III at diagnosis and immunoglobulin isotype (IgG/IgA/Others), but not mobilization were associated with OS. Adjusted 3-years PFS was 43% (95% C.I. 38-48) in GF and 40% (95% C.I. 35-45) in CC+GF, P=0.33 (Figure). Adjusted 3-years OS was 82% (95% C.I. 78-86) vs 80% (95% C.I. 75-84), P=0.43 and adjusted 5-year OS was 62% (95C.I. 54-68) vs. 60% (95% C.I. 52-67), P=0.76, for GF and CC+GF respectively (Figure). Conclusions: MM patients undergoing AHPCT have similar outcomes irrespective of the use of cytotoxic chemotherapy mobilization. We found no evidence that chemotherapy mobilization contributes to disease control in MM. Table Characteristics of patients and treatments GF CC+GF P N=519 N=449 Lines of therapy <0.001 1 382 (74) 265 (59) 2 113 (22) 136 (30) >2 24 (5) 48 (11) Prior therapy <0.001 Thalidomide+Bortezomb+-Steroid 74 (14) 92 (20) Lenalidomide+Bortezomb+-Steroid 121 (23) 48 (11) Thaildomide+-Steroid 85 (16) 106 (24) Bortezomib+-Steroid 132 (25) 136 (30) Lenalidomide+-Steroid 107 (21) 67 (15) Disease status at HCT 0.05 CR 84 (16) 48 (11) PR 407 (78) 378 (84) MR/NR/SD 28 (5) 23 (4) HCT-CI 0.006 0 227 (44) 227 (51) 1-2 147 (29) 134 (30) >2 145 (28) 88(20) Time from diagnosis to HCT <0.001 <6 mo 221 (43) 140 (31) 6-12 mo 298 (57) 309 (69) Year of HCT 0.03 2007-2008 289 (56) 272 (61) 2009-2010 105 (20) 100 (22) 2011-2012 125 (24) 77 (17) Melphalan dose 0.40 140-180 mg/m2 71 (14) 70 (16) >180 mg/m2 448 (86) 379 (84) Transplant type 0.02 Single transplant 417 (80) 331 (74) Multiple Transplants Planned 2ndAuto (0-6 mo) 42 (8) 63 (14) Planned 2ndAuto (>6 mo) 5 (1) 6 (1) Use of maintenance agent 198 (38) 176 (39) 0.29 Figure 1 Figure 1. Disclosures Costa: Sanofi: 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 | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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 ».