In vitro and in vivo T-cell depletion with myeloablative or reduced-intensity conditioning in pediatric hematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Anti-thymocyte globulin (ATG) is given in various conditioning regimens for children and young adults undergoing hematopoietic stem cell transplantation (HSCT) from HLA non-identical donors in order to reduce the risks of graft-versus-host disease (GvHD) and rejection after the transplant. The aim of this study was to define the effect of in vitro T-cell depletion in addition to ATG on the reconstitution of T-cell-mediated immunity. DESIGN AND METHODS: We retrospectively analyzed the engraftment kinetics and clinical performance of 134 patients (median age 5.80 years) who received ATG during myeloablative or reduced intensity conditioning, and either in vitro T-cell-depleted or unmanipulated grafts.
RESULTS: T-cell reconstitution was significantly delayed after T-cell-depleted grafts, irrespectively of the conditioning intensity (p<0.001). The incidence of fatal viral and fungal infections was higher in recipients of T-cell-depleted grafts than in those receiving unmanipulated grafts (26.6-29% versus <or=13%). The rejection rate was likewise higher in recipients of T-cell-depleted grafts whether following myeloablative or reduced intensity conditioning (37% and 18%, associated with recipient chimerism or non-engraftment, respectively) versus <or=4% without graft T-cell depletion. Grades 3 and 4 acute GvHD (CI+/-SE <or=0.11+/-0.03) and severe Epstein-Barr virus lymphoproliferative disease (1.49% fatal) were rare. INTERPRETATION AND
CONCLUSIONS: A combination of ex vivo and in vivo T-cell depletion, although inhibiting GvHD, prolongs the interval of T cell deficiency after HSCT and favors rejection and infections, implying that the requirement for this type of extensive T-cell depletion should be carefully re-evaluated.