Molecular Quantification of Pre-Treatment Bone Marrow Clonal Cells in Multiple Myeloma Is a Novel Predictive Indicator of Remission Length.
Notice bibliographique
Résumé
Abstract Multiple myeloma (MM) is a clonal B-cell malignancy with an accumulation of plasma cells in the bone marrow (BM). Newer treatments continue to increase remission occurrence and decrease side effects, however, relapse invariably occurs. Current diagnostic and monitoring criteria such as bone marrow plasmacytosis (BMPC) and serum M-protein levels (Mpr) fail to predict the length of remission for a given patient. The clonal IgH VDJ gene rearrangement provides a molecular method of measuring the MM disease burden. This unique biomarker can identify and quantify the number of malignant cells through analysis of genomic DNA with quantitative PCR. Here we use SYBR Green real-time quantitative PCR (rqPCR) to measure the level of clonal cells, termed VDJ%, in 91 previously untreated and 51 relapsed pre-treatment BM aspirates from MM patients. Kaplan-Meier analysis showed that VDJ%s lower than the median were associated with longer event free survivals (EFSs) (p=0.0077, HR=0.57). These patients were treated with a variety of different regimens (including VAD, ASCT, Melphalan, Prednisone, Thalidomide, Dexamethasone, Velcade or Revlimid). A modest correlation between the VDJ% and the BMPC was observed (p=0.0003, r2=0.099) but, the BMPC was not able to stratify these patients into groups with significantly different EFSs (p=0.1153, HR=0.6521) as was the VDJ%. This result confirms the BMPC’s poor association with outcome. The Mpr was not significantly correlated with VDJ% (p=2312, r2=0.012). The IMWG response subcategories correlated well with EFS where the poorer the response the shorter the EFS. However, there was no significant correlation between the pre-treatment VDJ% and the response subcategories. In addition to the pre-treatment BM samples, the tumor burden in 30 remission BM samples was quantified. To date, neither the remission VDJ% nor the reduction in VDJ% relative to the pre-treatment VDJ% was associated with EFS in a Kaplan-Meier analysis. The remission VDJ% had a significant yet modest correlation with the remission BMPC (p=0.014, r2=0.27) and nadir Mpr (p=0.0001, r2=0.61). Additionally, the IMWG response subcategory correlated with the proportionate reduction of the remission BM (p=0.036). Taken together these results indicate that VDJ% in pre-treatment BMs, but not the matched BMPC or Mpr, is a significant measure of outcome. The percent of clonal cells as measured in BM aspirates with rqPCR could be developed as a novel tool for predicting outcome by placing patients into a high risk or low risk category for EFS. Patients with a higher than median VDJ% have a shorter EFS than patients with a VDJ% below the median. RqPCR enumerates all cells containing the clonal sequence and thus may include relevant cells types not counted in the BMPC or reflected in the protein electrophoresis and not proportionally represented in remission BMs. The predictive value of pre-treatment VDJ% occurred despite varying types of therapy and tumor response, suggesting that these factors might provide independent prognostic information.
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 | 0,001 | 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) | 0,002 | 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 ».