High-dose post-transplant cyclophosphamide impairs γδ T-cell reconstitution after haploidentical haematopoietic stem cell transplantation using low-dose antithymocyte globulin and peripheral blood stem cell graft

高剂量移植后环磷酰胺会损害采用低剂量抗胸腺细胞球蛋白和外周血干细胞移植的单倍体相合造血干细胞移植后γδ T细胞的重建。

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Abstract

OBJECTIVES: Haploidentical haematopoietic cell transplantation (Haplo-HCT) using peripheral blood stem cell (PBSC) grafts and post-transplant cyclophosphamide (PTCy) is being increasingly used; however, data on immunological reconstitution (IR) are still scarce. METHODS: This retrospective study evaluated T-cell immunological reconstitution in 106 adult patients who underwent allogeneic haematopoietic cell transplantation for haematologic malignancies between 2013 and 2016. RESULTS: At D30, while conventional T cells reached similar median counts in Haplo-HCT recipients (n = 19) and controls (n = 87), γδ and Vδ2(+) T-cell median counts were significantly lower in Haplo-HCT recipients and it persists at least until D360 for Vδ2(+) T cells. PTCy induces a significant reduction in early γδ and Vδ2(+) T-cell proliferation at D  7. At one year, the rate of increase in Epstein-Barr virus (EBV) viral load was significantly higher in Haplo-HCT recipients as compared to controls (61% versus 34%, P = 0.02). In multivariate analysis, a higher γδ T-cell count (> 4.63 μL(-1)) at D30 was the only independent parameter significantly associated with a reduced risk of increase in EBV viral load (RR 0.34; 95% CI, 0.15-0.76, P = 0.009). CONCLUSION: Immunological reconstitution of γδ T cells is significantly delayed after Haplo-HCT using PTCy and low-dose ATG and is associated with an increased risk of increase in EBV viral load.

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