Naive T cell-depleted hematopoietic stem cell transplantation to minimize immunosuppression after solid organ transplantation: case report.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Pérez-Martínez Antonio, Aguirre-Portolés Cristina, Mestre-Durán Carmen, Arreola Nidia Monserrat, Pascual-Miguel Bárbara, Stringa Pablo, López Oliva María Ovidia, Papa-Gobbi Rodrigo, González-Sacristán Rocío, Gasior Mercedes, Marcos Antonio, de Paz Raquel, Alonso José María, Al-Akioui-Sanz Karima, Pertíñez Lidia, Ferreras Cristina, Tobes Raquel, Pareja Eduardo, Balas Antonio, Vicario José Luis, Estébanez Belén, Muñoz Fernández de Legaria Marta, Ramos-Boluda Esther, Sanz Sandra, Jiménez Carlos, Camps Onys, Andrés Ane M, Hernández-Oliveros Francisco
Аннотация
METHODS: We report two patients who, post-SOT, received non-myeloablative conditioning followed by a naïve T-cell-depleted HSCT and memory T-cell (CD45RA⁻) donor lymphocyte infusions under a compassionate use program. Mixed lymphocyte reaction (MLR) experiments performed 41 (Patient #1) and 31 (Patient #2) months after SOT/HSCT and TCRβ deep Illumina sequencing, together with clonotype frequency analysis, were used to identify donor-reactive T-cell clonotypes.
RESULTS: Both patients were maintained in minimal immunosuppression with no signs of rejection more than 5 years after the SOT/HSCT. Recipient cells resulted hyporesponsive to donor and third-party cells, yet retained reactivity to CMV infection. TCRβ profiling provided an overview of the lymphocyte subpopulations before and after transplantation. Donor-reactive clonotypes potentially associated with rejection were identified pre-HSCT and monitored after this procedure.
CONCLUSIONS: Our clinical strategy is a feasible, safe approach to induce transient mixed chimerism and may support minimization of immunosuppression following SOT. Despite considerable heterogeneity between patients - affected organ, donor source (deceased/living), and HLA compatibility (fully mismatched/matched sibling) -, we consider our findings to provide a valuable foundation for development of a clinical trial recently started at our hospital: A phase I, single-center, open-label trial to assess safety and tolerability of delayed infusion of a naïve T-cell-depleted hematopoietic graft and memory T-lymphocytes in recipients of solid organ transplantation (NCT06997471).