Effective T cell regeneration following high-dose chemotherapy rescued with CD34+ cell enriched peripheral blood progenitor cells in children.
The ex vivo enrichment for the CD34+ cell fraction of PBPC, while it retains the capacity to restore haematopoiesis and potentially reduces a contamination by tumour cells, implements a depletion of T cells. To test whether such a setting adversely affects T cell reconstitution, we monitored T cells in four paediatric patients after CD34+ selected PBPC transplantation. The dose of CD34+ cells, which were enriched to 74%, median, was 7.1 x 10(6)/kg, median, that of T cells was 0.071 x 10(6)/kg, median. The patients were homogenous with respect to features with a potential to effect T cell reconstitution (low median age, (35 years); stage IV malignant tumours in first CR, uncomplicated post-treatment course). The results of sequential FACS analyses showed that by 9 months after treatment all four patients had recovered (1) a normal T cell count (CD3+ cells 1434/microl, median); (2) a normal CD4+ cell count (816/microl, median), while CD8+ cells were recovered (>330/microl) already by 3 months; (3) a normal CD4/CD8 ratio (1.8, median), as a result of an augmented growth of CD4+ cells between 3 and 6 months (increase of CD4+ cells 4.9-fold, median, CD8+ cells 1.1-fold, median). Expansion of cells with a CD45RA+ phenotype (thymus-derived T cells) predominated; from 3 to 6 months the increase of CD4+/CD45RA+ T cells was 130-fold, that of CD4+/CD45RO+ cells was 1.7-fold; CD8+/CD45RA+ cells increased 9-fold, CD8+/CD45RO+ cells increased 2.1-fold, indicating effective thymopoiesis. The findings demonstrate that in paediatric patients the setting of HD-CTX rescued with autologous CD34+ selected PBPC per se is not predictive of an impaired T cell recovery. High thymic activity may be a key factor for the rapid restoration of T cells.
Heitger
A
A
University Children's Hospital Innsbruck, Austria.
Kern
H
H
Mayerl
D
D
Maurer
K
K
Nachbaur
D
D
Frühwirth
M
M
Fink
F M
FM
Niederwieser
D
D
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000276:immunology* / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D009447:Neuroblastoma / Q000276:immunology* / Q000628:therapy*; D012208:Rhabdomyosarcoma / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology