A prospective analysis of the pattern of immune reconstitution in a paediatric cohort following transplantation of positively selected human leucocyte antigen-disparate haematopoietic stem cells from parental donors

Transplantation of haematopoietic stem cells from human leucocyte antigen ( HLA)-disparate parental donors presents a promising new approach for the tr eatment of patients lacking a HLA-matched donor. Success against major obst acles such as graft-versus-host disease (GvHD) and graft rejection has rece ntly been demonstrated, so that immune reconstitution is one of the prime f actors that determines the Ion-term prognosis following transplantation. Tw enty children transplanted with megadoses of highly purified CD34(+) haemat opoietic stem cells after rigorous T-cell depletion were prospectively moni tored for their immune reconstitution during the first post-transplant yean Natural killer (NK) cells showed a marked increase on d+30. T and B cells began to reconstitute on d+72 and +68 respectively. During extended follow- up, their numbers and proliferative capacity upon mitogen stimulation conti nuaIly increased. Early reconstituting T cells were predominantly of a prim ed, activated phenotype with severely skewed T-cell receptor (TCR)-repertoi re complexity. Naive T cells emerged 6 months post transplantation, paralle led by an increase in TCR-repertoire diversity. All patients self-maintaine d sufficient immunoglobulin levels after d+200. This study demonstrates tha t paediatric. recipients of highly purified, haptoidentical stem cells are able to reconstitute functioning T-, B- and NK-cell compartments within the first post-transplant yean This, together with the absence of significant GvHD, provides a strong indication for this approach to be considered in ch ildren who lack a HLA-matched donor.