Omission of in vivo T-cell depletion promotes rapid expansion of naïve CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant.
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 × 10(9) /l and 0.56 × 10(9) /l, respectively. Early T-cell expansion was thymic-independent, with a rapid shift from naïve 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.
Bone Marrow Transplantation Department, Great Ormond Street Hospital, London, UK.
Robert
R
Chiesa
Kimberly
K
Gilmour
Waseem
W
Qasim
Stuart
S
Adams
Austen J J
AJ
Worth
Hong
H
Zhan
Claudia A
CA
Montiel-Equihua
Sophie
S
Derniame
Catherine
C
Cale
Kanchan
K
Rao
Prashant
P
Hiwarkar
Rachel
R
Hough
Aurore
A
Saudemont
Cristián S
CS
Fahrenkrog
Nick
N
Goulden
Persis J
PJ
Amrolia
Paul
P
Veys
D056704:Adaptive Immunity; D001402:B-Lymphocytes / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D009894:Opportunistic Infections / Q000276:immunology / Q000517:prevention & control; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome