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

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Abstract
Transplantation of haematopoietic stem cells from human leucocyte antigen (HLA)‐disparate parental donors presents a promising new approach for the treatment of patients lacking a HLA‐matched donor. Success against major obstacles such as graft‐versus‐host disease (GvHD) and graft rejection has recently been demonstrated, so that immune reconstitution is one of the prime factors that determines the long‐term prognosis following transplantation. Twenty children transplanted with megadoses of highly purified CD34+ haematopoietic stem cells after rigorous T‐cell depletion were prospectively monitored for their immune reconstitution during the first post‐transplant year. 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 continually increased. Early reconstituting T cells were predominantly of a primed, activated phenotype with severely skewed T‐cell receptor (TCR)‐repertoire complexity. Naive T cells emerged 6 months post transplantation, paralleled by an increase in TCR‐repertoire diversity. All patients self‐maintained sufficient immunoglobulin levels after d +200. This study demonstrates that paediatric recipients of highly purified, haploidentical stem cells are able to reconstitute functioning T‐, B‐ and NK‐cell compartments within the first post‐transplant year. This, together with the absence of significant GvHD, provides a strong indication for this approach to be considered in children who lack a HLA‐matched donor.