Mobilization and selection of peripheral blood hematopoietic progenitors in children with systemic sclerosis.

BACKGROUND AND OBJECTIVE: Autologous transplant of lymphocyte-depleted peripheral blood stem cells has been proposed for treatment of patients with severe autoimmune disease. However, until now, no data are available on the safety and feasibility of both stem cell collection and selection in pediatric patients with these disorders. We report on three children affected by systemic sclerosis with lung involvement, who received chemotherapy and granulocyte colony-stimulating factor (G-CSF) to mobilize autologous peripheral blood progenitors. DESIGN AND METHODS: The priming regimen consisted of cyclophosphamide (CY, 4 g/m(2)) and G-CSF (lenograstim, 10 microg/kg/day starting 2 days after cyclophosphamide administration until stem cell collection). Leukapheresis was performed when WBC and CD34+ cell count were at least 2 x 10(9)/L and 0.03 x 10(9)/L, respectively. In the first patient, positive selection of CD34+ cells was performed through the Ceprate SC stem cell concentrator (CellPro, Bothell, WA, USA). In the remaining 2 children, progenitor cells were also purged with negative selection of CD4+ and CD8+ lymphocytes performed by means of the Isolex 300i device (Baxter). RESULTS: All patients tolerated the priming regimen well and did not present any sign of autoimmune disease exacerbation. Collection was successful in all children and the number of CD34+ cells before selection ranged between 10.7 x 10(6) and 17.6 x 10(6)/kg of patient body weight. The selection of haematopoietic stem cells in the 3 patients resulted in at least 2. 6-log T-cell depletion of the cell content, with a recovery of the initial value of CD34+ cells comprised between 21 and 44%. After, a preparative regimen consisting of CY (200 mg/kg over 4 days) and Campath-1 G in vivo (10 mg/day for 2 consecutive days), patients were transplanted using cryopreserved lymphocyte-depleted progenitor cells. In all cases, a prompt hematopoietic engraftment was observed. INTERPRETATION AND CONCLUSIONS: Taken together these data suggest that mobilization, collection and selection of hematopoietic progenitors are safe and feasible in children with autoimmune disease.

Possible role of plasma neurotensin on growth hormone regulation in neonates.

OBJECTIVE: To evaluate secretion of plasma neurotensin (NT) which could be involved as a peripheral signal in growth hormone (GH) regulation, NT release was measured during early postnatal life, a period of striking changes in GH secretion. METHODS: Blood samples were collected from 19 normal full-term neonates on day 5 and at 3 months of age to evaluate plasma NT concentrations by radioimmunoassay, serum growth hormone (GH) levels using an immunofluorometric assay, and serum insulin-like growth factor-I (IGF-I) values by radioimmunoassay. RESULTS: Five day-old neonates showed significantly higher (p < 0.001) mean (+/- SEM) plasma NT levels (83.55 +/- 12.07 fmol/ml) compared with those in 11 prepubertal children and those in 14 adults who were studied as control subjects (13.30 +/- 2.90 and 9.70 +/- 1.10 fmol/ml, respectively). In 5 day-old neonates we observed significantly higher (p < 0.001) serum GH levels (29.53 +/- 3.40 ng/ml) compared with those in the prepubertal children (1.26 +/- 0.28 ng/ml). Five day-old neonates showed significantly lower (p < 0.001) serum IGF-I concentrations (27.01 +/- 0.77 ng/ml) than those in the prepubertal children (210 +/- 25 ng/ml). At 3 months of age, plasma NT levels (59.37 +/- 7.47 fmol/ml) and serum GH values (4.40 +/- 0.60 ng/ml) were significantly decreased (p < 0.001). At the 3rd month of life, serum IGF-I levels (44.88 +/- 4.30 ng/ml) were increased significantly (p < 0.001). CONCLUSIONS: The human neonate showed very high concentrations of NT and GH in comparison with those observed in control subjects. The postnatal rise in IGF-I values is presumed to determine the fall in serum GH concentrations by stimulating somatostatin secretion. Neurotensin could be involved as a peripheral signal in the inhibitory mechanisms mediated by release of somatostatin.