期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 114, 期 2, 页码 422-432出版社
WILEY
DOI: 10.1046/j.1365-2141.2001.02934.x
关键词
immune reconstitution; haploidentical; CD34(+) stem cell transplantation; T-cell repertoire diversity; CDR3 size spectratyping
类别
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 Ion-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 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 continuaIly 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, 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 children who lack a HLA-matched donor.
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