Single UM171-Expanded Cord Blood Transplants Support Robust T-Cell Reconstitution with Low Rates of Severe Infections
Notice bibliographique
Résumé
Rapid T cell reconstitution following hematopoietic stem cell transplantation is essential for protection against infections and has been associated with lower incidence of chronic graft-vs-host disease (cGVHD), relapse, and transplant-related mortality (TRM). Although cord blood (CB) transplants are associated with lower rates of cGVHD and relapse, their low stem cell content results in slower immune reconstitution and higher risk of graft failure, severe infections, and TRM. Mean cumulative counts of infectious events in patients transplanted with UM171-expanded (blue) or unmanipulated (red) CB. Mean cumulative counts are shown for all infectious events (A), bacterial infections (B), and viral infections (C). Events were categorized by type and severity as per BMT CTN guidelines. Infectious events of grade 1-3 are shown in pale colors, while more severe events (grade 2-3) are shown in dark colors. Censored patients (including those who relapsed) are indicated with white circles (*p < .05, **p < .01). Recently, results of a phase I/II trial revealed that single UM171-expanded CB transplant allowed the use of smaller CB units without compromising engraftment. The present study assessed T cell reconstitution and immune function in patients transplanted with UM171-expanded CB grafts. We performed a retrospective analysis of a cohort of 20 patients treated with UM171-expanded CB and compared it to a contemporary cohort of 12 patients treated in the same institution who received unmanipulated CB transplant with similar conditioning regimens. We used flow cytometry and T cell receptor (TCR) sequencing to evaluate T cell reconstitution, and we used virus-specific ELISpot assays to evaluate T cell function in the first year post-transplantation. We also categorized infectious events according to the definitions of infection severity in the “Bone and Marrow Transplant Clinical Trials Network Technical Manual of Procedures,” Version 3.0, and report the mean cumulative count of infectious events for each cohort. While median T cell dose in graft was at least 2 to 3 times lower for the cohort of patients treated with UM171-expanded CB, numbers and phenotype of T cells at 3, 6, and 12 months post-transplant were similar between the two cohorts. TCR sequencing analyses revealed that UM171 patients had greater T cell diversity and higher numbers of clonotypes at 12 months post-transplant. This was associated with higher counts of naïve T cells and recent thymic emigrants, suggesting active thymopoiesis and correlating with the demonstration that UM171 expands common lymphoid progenitors in vitro. UM171 patients also showed rapid virus-specific T cell reactivity. Most importantly, UM171 patients showed a significantly reduced incidence of severe infections, especially for bacterial and viral infections (Figure 1). These results suggest that UM171 patients benefit from rapid T cell reconstitution, which likely contributes to the absence of moderate/severe cGVHD, infection-related mortality and late TRM observed in this cohort.
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Prédiction distillée sur la base complète
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Scores Codex et Gemma par catégorie
| 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 | 0,001 |
| 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) | 0,002 | 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.
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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
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