Development of third party grafts from pooled CD34- selected cryopreserved cord blood units for stem cell transplantation
Notice bibliographique
Résumé
Umbilical cord blood (CB) is a valuable alternative source of stem cells for patients who do not have a compatible donor for allogeneic stem cell transplantation. Unfortunately, few banked cord blood units contain sufficient hematopoietic stem cells to transplant adult patients. Different approaches have been used to increase the number of infused HSC including the use of two or three HLA compatible CBUs, co-transplantation with related HLA haploidentical grafts to provide "third party" support, and cell expansion. These alternative approaches have the disadvantage of increasing the cost of graft procurement or relying on a related haploidentical donor that may not be available. I developed a method that aimed to increase the number of HSC available for transplantation by creating a third-party graft from pooled HLA-blind cryopreserved CBUs enriched for CD34+ cells. By using only CBUs rejected by the public cord blood bank, the cost of developing this mixed CBUs graft has been minimized. Over 60% of all collected CBUs do not qualify for public banking and could potentially be salvaged to create third-party grafts for clinical use. To pursue this project, it was necessary to establish a clinical grade research cord blood bank to ensure the availability of CBUs for experimental graft development. This project covered all aspects of cord blood banking from screening potential mothers, to CBU collection, processing, cryopreservation, and release of CBUs for transplantation. From October 2007 to December 2012, 2313 CBUs have been collected. Approximately 38% of the collected CBUs qualified for the Québec public cord blood bank and 1418 CBUs were retained. A small volume of CBUs did not qualified for any banking mainly due to a volume of less than 20 mL, CBUs being more than 96 hours post collection or positive bacteriology/serology testing. Some of the key accomplishments that permitted the successful creation of mixed cord blood grafts were the development of pooling methods to minimize the toxicity of the cryopreservative DMSO while simultaneously thawing and combining multiple CBUs. I also observed that passive transfer of anti-A and anti-B immunoglobulin-gamma could bind ABO-incompatible fetal leukocytes and potentially interfere with cell yields and function. The quality of mixed cord blood grafts was optimized by dilution of thawed CBUs to reduce DMSO concentration from 10% to 1% and selecting CBUs that had maternal-fetal ABO compatibility. Mixed cord blood grafts using from 12 to 45 CBUs were pooled with a mean nucleated cell recovery of 87% post-thawing and 73% post-centrifugation with a yield of CD34+ cells, sufficient for third party support in allogeneic cord blood transplantation. The safety and utility of using mixed cord blood grafts for allogeneic stem cell transplantation has been demonstrated in a clinical trial developed and conducted at the MUHC. Seven recipients with hematological cancers received, after myeloablative conditioning, a ≥ 4/6 HLA compatible CBU, followed by infusion of the third-party graft containing on average 2.5 x 105 CD34+ cell/kg. The median neutrophil engraftment time was 19.5 days. One patient had primary graft failure. All engrafted patients showed a 100% HLA-matched donor chimerism at first assessment on day +14. Six patients were alive at day +100 while one patient died at day +28 of disease relapse. All engrafted recipients developed grade I-III acute graft-versus-host-disease that responded promptly to treatment and no patients developed chronic GVHD.These results demonstrate that increasing the number of HSCs by using third-party cells from pooled HLA-blind CBUs to support a ≥ 4/6 HLA compatible CBU is safe, feasible, and results in rapid engraftment. Future studies are warranted to better understand the role of pooled third party units and factors involved in the homing of stem cells to their natural niche to facilitate the selection of units for engraftment.
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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 ».