Very early recovery of T cells after alpha/beta T cell-depleted haploidentical HSCT predicts the outcome in children with leukemia.

Abstract

Functional immune reconstitution (IR) is a key factor in determining the success of hematopoietic stem cell transplantation (HSCT). IR depends on a number of factors and is typically delayed by ex vivo T cell depletion of the graft. αβ T cell depletion (αβ TCD) platform was reported to be associated with improved IR. In this retrospective study, we've focused on a homogeneous cohort of 262 children with acute leukemia first transplanted in complete remission, and investigate whether very early recovery of NK and T cells, as well as αβ and γδ T subsets, is associated with clinical outcomes. The grafts were obtained from apheresis products and processed by αβ TCD method. IR of lymphocyte subpopulations was measured in peripheral blood (PB) on day +30 after HSCT by flow cytometry. The study suggests that in the early post-HSCT period, higher absolute number of T cells, despite being far below the normal range and having a rather limited T cell receptors repertoire, is associated with radically improved non-relapse mortality (NRM). Multivariate analysis confirmed the independent effect of T-cell IR on NRM. Our results show that each 10-fold increase in T cell PB count is associated with a 2.1-fold reduction in NRM (cause-specific Hazard Ratio (csHR) 0.47), independent from other important factors such as aGVHD or serotherapy use. Based on these results we suggest that T cells recovery on day +30 after HSCT can be used in predicting NRM risk in the setting of αβ TCD HSCT. Early intervention for IR improvement can be planned.