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

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.

The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia

“…Recent works provide a promising option by optimizing ATG dosing (2.5 mg/kg daily for 3 days) to reduce viral activation while maintaining sufficient GvHD prophylaxis in haplo-HSCT ( 45 , 46 ). Similar phenomena were observed in haplo-HSCT using a combination of post-transplantation cyclophosphamide and low-dose ATG ( 47 , 48 ). A lower dose of ATG (2.5 mg/kg) successfully reduces CMV reactivation without compromising the favorable effect of preventing GvHD ( 49 ).…”

An Unconventional View of T Cell Reconstitution After Allogeneic Hematopoietic Cell Transplantation

“…Of note, their reconstitution does not appear to be dependent on conditioning intensity ( 118 ), however, γδ T cells appear extremely sensitive to PTCy in the setting of haploidentical transplantation. In this setting, γδ, and especially the Vδ2 + T‐cell counts were significantly lower in the early post-transplantation period ( 131 , 132 ). This effect on the Vδ2 + cell population persisted for up to one year post-transplantation and correlated with more frequent EBV reactivation ( 131 ).…”

“…In this setting, γδ, and especially the Vδ2 + T‐cell counts were significantly lower in the early post-transplantation period ( 131 , 132 ). This effect on the Vδ2 + cell population persisted for up to one year post-transplantation and correlated with more frequent EBV reactivation ( 131 ).…”

Human herpesvirus type 6 reactivation after haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide and antithymocyte globulin: risk factors and clinical impact

“… 36,37 Combining ATG with PT-Cy can induce a significant reduction in early gamma-delta (γδ) T-cell proliferation, and is associated with a higher risk of increase in EBV viral loads. 38 However, the impact of such a delayed lymphocyte reconstitution on HHV6 reactivation has scarcely been studied. Two previous studies have reported a protective effect of higher lymphocyte counts (CD3+ lymphocytes ≥ 200/µL) against HHV6 reactivation.…”