Plerixafor Successfully Rescues Poor Mobilizers Resulting in Adequate CD34 Cell Numbers However Stem Cell Products Yield Lower Numbers of CFU/CD34 and Delayed Neutrophil Engraftment
Notice bibliographique
Résumé
Abstract Background: The CXCR4 inhibitor plerixafor was studied as a rescue agent in the setting of poor chemotherapy/filgrastim mobilization in a phase II trial of adults with lymphoma and myeloma who underwent a peripheral hematopoietic stem cell (HSC) mobilization prior to autologous transplant (ASCT) (NCT01037517). Given the wide range of expression of CD34 in myeloid precursors we were interested in the quality of the CD34 positive cells that were collected to proceed to transplant in poor mobilizers. Amongst a population of poor mobilizers would the CD34+ population contain cells of a more differentiated phenotype or express different proportions of homing receptors as CD34 cells collected from patients who mobilized easily? Methods: From 2009 to 2012 sequential adult patients with a diagnosis of lymphoma or multiple myeloma undergoing chemo-mobilization in preparation for autologous stem cell collection were enrolled on a phase II study to examine a strategy of plerixafor rescue in the setting of poor mobilization. Plerixafor (240 mcg/kg sc X 1) was administered on the evening prior to planned apheresis in subjects with a post nadir white blood cell count >1 X109/L and a peripheral blood [CD34] ≤ 10x106/L on the day prior to planned collection. Participants proceeded to stem cell apheresis the next day if their peripheral blood CD34 > 10x106/L. An aliquot from the mobilized product was analyzed for CD34+ cell subsets using markers of stemness ( CD33-, CD90, CD133 , CD166) and homing (CD26, CD49F, CD184) Differences between the groups are reported as means ±standard deviation and compared by two tailed t-tests. Results: 46/48 subjects were successfully mobilized in one day (HSC collection of >2 x 106 CD34+ cells/kg): 38 pts were not administered plerixafor (good mobilizer) and 8 pts were administered plerixafor (plerixafor rescue). The two participants not able to mobilize with plerixafor had evidence of progression of underlying disease within 2 weeks of attempted mobilization. Forty four participants (6/8 plerixafor and 38/38 good mobilizers) underwent ASCT. Median time to platelet engraftment was similar between good mobilizers (12 d, range 9-22d) and the plerixafor rescue group (13 d, range 12-13 d). The median time to neutrophil engraftment was prolonged in the plerixafor rescue group (23 d, range 17-67d) compared to good mobilizers (17 d, range 10-31d). CD34 content/kg of the apheresis product collected was similar between groups (good mobilizer 11.6±7.9 versus the plerixafor rescue group 6.4±4.6 p = 0.1). Subset analysis of CD34 positive cells in the products showed comparable expression of markers associated with more immature HSC progenitors but fewer CFU per CD34 positive cell plated. Homing receptors on the CD34 positive cells were similar despite the use of a CXCR4 inhibitor in the poor mobilizers. (See table) TableGood mobilizer N= 38 (Mean % ± SD)Plerixafor rescue N= 8 (Mean % ± SD)P valueStemmness MarkersCD90+ (Thy-1)24.4±12.730.6±19.30.3CD133+ (prominin1)59.1 ± 12.959.1 ± 16.80.9CD166+ (ALCAM)5.7±3.36.6±5.10.5CD33- (Siglec-3)80.6±3.369.8±13.10.01CFU/105 CD34+ cells1015±799276±3160.02Homing MarkersCD26 (dipeptidyl peptidase-4)5.4±410.4±13.30.05CD49F (VLA4)8.5±7.96.8±9.70.6CD184 (CXCR4)16.2±20.517.7±9.70.8 Discussion: Plerixafor used to rescue patients at risk of poor mobilization resulted in collection of adequate numbers of CD34+ cells for transplantation and allowed ASCT in a majority of poor mobilizers in our series. Delayed neutrophil recovery, was seen in the poor mobilizer cohort. We did not see a skewing of the CD34+ cells in the products from poor mobilizers to a more mature phenotype but did find lower clonogenic potency with fewer CFU generated/CD34 cells plated. Disclosures Off Label Use: Plerixafor used as initial mobilization strategy in autologous stem cell mobilization.
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 | 0,000 | 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) | 0,002 | 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 ».