Omission of in vivo T-cell depletion promotes rapid expansion of naïve CD4 + cord blood lymphocytes and restores adaptive immunity within 2months after unrelated cord blood transplant

Abstract

Umbilical cord blood transplant (UCBT) is associated with impaired early immune reconstitution. This might be explained by a lower T-cell dose infused, the naivety of cord blood T-cells and the use of in vivo T-cell depletion. We studied the pattern of early immune reconstitution and the clinical outcome of children undergoing unrelated UCBT when in vivo T-cell depletion was omitted. Thirty children affected by malignancies (46%) or immunodeficiencies (54%) underwent an unrelated UCBT. Prospective assessment of immune reconstitution and clinical outcome was performed. We observed an unprecedented CD4 + T-cell reconstitution, with a median cell count at 30 and 60d post UCBT of 0·3×10 9/l and 0·56×10 9/l, respectively. Early T-cell expansion was thymic-independent, with a rapid shift from naïve to central memory phenotype and early regulatory T-cell recovery. Viral infections were frequent (63%) but resolved rapidly in most cases and virus-specific T-lymphocytes were detected within 2months post-UCBT. Acute graft-versus-host disease (GvHD) was frequent (grade II=34%, grade III-IV=16%) but steroid responsive, and the incidence of chronic GvHD was low (14%). The omission of in vivo T-cell depletion promotes a unique thymic-independent CD4 + T-cell reconstitution after unrelated UCBT in children. We postulate that this relates to the specific immunological and ontological qualities of fetal-derived lymphocytes. © 2012 Blackwell Publishing Ltd.