Effective T cell regeneration following high-dose chemotherapy rescued with CD34 super(+) cell enriched peripheral blood progenitor cells in children

The ex vivo enrichment for the CD34 super(+) 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 super(+) selected PBPC transplantation. The dose of CD34 super(+) cells, which were enriched to 74%, median, was 7.1 x 10 super(6)/kg, median, that of T cells was 0.071 x 10 super(6)/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 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 super(+) cells 1434/ mu l, median); (2) a normal CD4 super(+) cell count (816/ mu l, median), while CD8 super(+) 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 super(+) cells between 3 and 6 months (increase of CD4 super(+) cells 4.9-fold, median, CD8 super(+) cells 1.1-fold, median). Expansion of cells with a CD45RA super(+) phenotype (thymus-derived T cells) predominated; from 3 to 6 months the increase of CD4 super(+)/CD45RA super(+) T cells was 130-fold, that of CD4 super(+)/CD45RO super(+) cells was 1.7-fold; CD8 super(+)/CD45RA super(+) cells increased 9-fold, CD8 super(+)/CD45RO super(+) cells increased 2.1-fold, indicating effective thymopoiesis. The findings demonstrate that in paediatric patients the setting of HD-CTX rescued with autologous CD34 super(+) 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.