Dynamics of recent thymic emigrants in pediatric recipients of allogeneic hematopoetic stem cell transplantation

Abstract

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), the recurrence of recent thymic emigrants (RTE) and self-tolerant T cells indicate normalized thymic function. From 2008 to 2019, we retrospectively analyzed the RTE-reconstitution rate and the minimal time to reach normal age-specific first percentiles for CD31⁺CD45RA⁺CD4⁺T cells in 199 pediatric patients after allo-HSCT for various malignant and non-malignant diseases. The impact of clinically significant graft-versus-host disease (GvHD), age at transplantation, underlying disease and cumulative area under the curve of busulfan on RTE-reemergence was assessed in multivariable longitudinal analysis. RTE-reconstitution (coefficient -0.24, 95% CI -0.33 to -0.14, p < 0.001) was slowed down by GvHD and the time to reach P1 was significantly longer (Event Time Ratio 1.49, 95% CI 1.25 to 1.78, p < 0.001). Older age at transplantation was also associated with a slower RTE-reconstitution (coefficient -0.028, 95% CI -0.04 to -0.02, p < 0.001) and time to reach P1 was significantly longer (Event Time Ratio 1.03, 95% CI 1.02 to 1.05, p < 0.001). RTE-reconstitution velocity was not influenced by underlying disease or cumulative busulfan exposure. In summary, duration until thymic reactivation was independent of both conditioning intensity and underlying disease and was negatively influenced by older age and GvHD.