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 106/kg, median. The patients were homogenous with respect to features with a potential to effect T cell reconstitution (low median age, (3.5 years); stage TV malignant tumours in first CR, uncomplicated post-treatment course). The results of sequential FAGS analyses showed that by 9 months after treatment all four patients had recovered (1) a normal T cell count (CD3(+) cells 1434/mu l, median); (2) a normal CD4(+) cell count (816/mu l, median), while CD8(+) cells were recovered (>330/mu l) 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 WO-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.