title: 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.
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.
authors.affiliation: University Children's Hospital, Paediatric Stem Cell Transplant Program, Tuebingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Eyrich
authors.forename: P
authors.initials: P
authors.lastname: Lang
authors.forename: S
authors.initials: S
authors.lastname: Lal
authors.forename: P
authors.initials: P
authors.lastname: Bader
authors.forename: R
authors.initials: R
authors.lastname: Handgretinger
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.forename: D
authors.initials: D
authors.lastname: Niethammer
authors.forename: P G
authors.initials: PG
authors.lastname: Schlegel
mesh_terms: D000293:Adolescent; D018952:Antigens, CD34; D001402:B-Lymphocytes / Q000276:immunology; D001804:Blood Transfusion, Autologous; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D019337:Hematologic Neoplasms / Q000276:immunology / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion; D008297:Male; D010290:Parents; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014019:Tissue Donors; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34