High-dose post-transplant cyclophosphamide impairs gammadelta T-cell reconstitution after haploidentical haematopoietic stem cell transplantation using low-dose antithymocyte globulin and peripheral blood stem cell graft (Équipe Mohty)

Clin Transl Immunology. 2020;9(9):e1171

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), gammadelta and Vdelta2(+) T-cell median counts were significantly lower in Haplo-HCT recipients and it persists at least until D360 for Vdelta2(+) T cells. PTCy induces a significant reduction in early gammadelta and Vdelta2(+) 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 gammadelta T-cell count (> 4.63 muL(-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 gammadelta 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.