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

Nicolas Stocker; Béatrice Gaugler; Myriam Labopin; Agathe Farge; Yishan Ye; Laure Ricard; Eolia Brissot; Remy Duléry; Simona Sestili; Giorgia Battipaglia; Clémence Médiavilla; Annalisa Paviglianiti; Anne Banet; Zoe Van De Wyngaert; Tounes Ledraa; Mohamad Mohty; Florent Malard

doi:10.1002/cti2.1171

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

Clin Transl Immunology. 2020 Sep 23;9(9):e1171. doi: 10.1002/cti2.1171. eCollection 2020.

Authors

Nicolas Stocker^{1

2}, Béatrice Gaugler¹, Myriam Labopin^{1

2

3}, Agathe Farge¹, Yishan Ye^{1

4}, Laure Ricard¹, Eolia Brissot^{1

2}, Remy Duléry^{1

2}, Simona Sestili², Giorgia Battipaglia^{1

2}, Clémence Médiavilla^{1

2}, Annalisa Paviglianiti², Anne Banet², Zoe Van De Wyngaert², Tounes Ledraa^{1

2}, Mohamad Mohty^{1

2

3}, Florent Malard^{1

2}

Affiliations

¹ INSERM, Centre de Recherche Saint-Antoine (CRSA) Sorbonne Université Paris France.
² Service d'Hématologie Clinique et Thérapie Cellulaire Hôpital Saint-Antoine, AP-HP Paris France.
³ Acute Leukemia Working Party Paris Study Office European Society for Blood and Marrow Transplantation Paris France.
⁴ Bone Marrow Transplantation Center The First Affiliated Hospital School of Medicine Zhejiang University Hangzhou China.

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.

Keywords: Epstein–Barr virus; allogeneic haematopoietic cell transplantation; haploidentical haematopoietic cell transplantation; immune reconstitution; post‐transplantation cyclophosphamide; γδ T cell.