Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 156, Issue 5, Pages 656-666Publisher
WILEY
DOI: 10.1111/j.1365-2141.2011.08994.x
Keywords
immune reconstitution; CD4(+) T-cell lymphocytes; umbilical cord blood transplantation; paediatrics
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Funding
- National Institute for Health Research Biomedical Research Centres
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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 60 d post UCBT of 0.3 x 10(9)/l and 0.56 x 10(9)/l, respectively. Early T-cell expansion was thymic-independent, with a rapid shift from naive 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 2 months 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.
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