Reduced Adverse Effects and Improved Engraftment in the Pediatric Transplant Population upon Dilution of HPC, Cord Blood Products Prior to Infusion
Notice bibliographique
Résumé
Abstract Patient specific adverse reactions are common when HPC, Cord Blood (HPC-C) units, cryopreserved in dimethylsulfoxide (DMSO) are warmed to 37°C and infused into pediatric patients. Adverse reactions, including hemodynamic instability, fever, chills, nausea, cardiomyopathy, unconsciousness, and even death have been described in the pediatric population. Additionally, hematopoietic stem cells (HSC) cryopreserved in DMSO have limited viability upon thawing due to the cellular cytotoxicity of DMSO, resulting in the potential for significant loss of cells available for transplantation and subsequent engraftment. Although DMSO is essential as a cryoprotectant for long-term preservation of hematopoeitic stem cells, standardized techniques are required to mitigate the cellular cytotoxicity and acute onset adverse events witnessed in unwashed/undiluted cord blood transplantation. Immediate mixing of thawed cord blood units with a hypertonic reconstitution solution can ameliorate many of these problems by restoring the osmolarity of the suspension, promoting colloidal-osmotic intracellular equilibrium, and reducing DMSO concentration in the infused product. In general, studies examining the benefits of dilution and/or washing of HPC-C prior to infusion have largely been confined to adult populations with varying results. Since pediatric patients often experience more significant adverse reactions, even when DMSO concentrations in the infused unit are well below the recommended maximum of 5 mL of 20% DMSO/kg body weight, examination of effective and robust techniques for minimizing these effects in the pediatric patient is crucial. The studies presented demonstrate successful utilization of diluted HPC-C products in HSC transplants in pediatric patients. HPC-C products were either infused immediately after thaw or infused after dilution with a solution of 8% Gentran-40 and 5% HSA (ReCon solution). Dilution of HPC-C products immediately after thaw appears to ensure maximal HSC recovery and viability--essential for transplant and engraftment. In experimental studies, improved HPC recovery and viability was observed in all diluted HPC-C products as compared to undiluted products. As well, the number and viability of CD34+ cells remains constant for >24 hours post thaw when HPC-C products are diluted in ReCon solution. In contrast, thawed and undiluted HPC-C units experience a significant reduction in number and viability of CD34+ cells 15–30 minutes post-thaw. Most importantly, pediatric patients displayed reduced adverse reactions when infused with diluted HPC-C products as compared to undiluted products. Dilution of HPC-C products with ReCon solution did not affect engraftment of neutrophils and/or platelets in these patients. In a specific case study, a diluted HPC-C product resulted in engraftment when a double-cord transplant with undiluted HPC-C products did not. As well, the negative adverse reaction experienced by the patient following infusion of undiluted product was not experienced when the diluted HPC-C product was infused. In the pediatric HSC transplant population it is essential not only to ensure optimal recovery and potency of HSCs in the transplant graft but also to alleviate adverse reactions. Application of HPC-C dilution protocols employing a solution of Gentran-40 and HSA provide an effective, safe, and efficient strategy for diminishing DMSO related toxicities in the pediatric HSCT patient.
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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 | 0,001 |
| 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 ».