Prominin-1 Mobilisation, Collection and Immunoselection in Cancer Patients for Liver Regeneration.

Abstract

Abstract 2141Poster Board II-118 Background:CD133+ (Prominin-1 positive) is a 5-transmembrane glycoprotein that identifies immature progenitor stem cells.Immature hematopoietic stem cells retain the possibility to give origin to tissues different from hematopoietic cell lines (transdifferentiation). Material and methods:In this preliminary study we investigated the possibility to mobilize, collect, immunoselect and reinfuse autologous CD133+ immature stem cells in liver cancer patients. This approach was adopted to obtain, in a short time, an adequate volume increase of the disease free liver thus extending the resectability criteria of the liver, with the final goal to prolong survival.We enrolled 4 patients with a large liver cancer and no chance of resection. The mobilization protocol consisted in: G-CSF administration (10 μg/kg/day ) for 3-5 days, peripheral blood stem cell (PBSC) monitoring starting from the 3rd day, leukapheresis (LKF) collection processing 3 blood volumes when CD133+ cells>15 μL. Patients were monitored during mobilization, collection and post collection phase for clinical status, blood pressure and bleeding. Positive CD133+ immunoselection (Miltenyi Clinimacs) was performed on LKF product after overnight storage. Quality controls on positive fraction consisted in viability and purity of CD133+ cells by cytofluorimetric analysis and clonogenic assays. Microbial tests were performed on the negative fraction.After LKF, patients underwent right portal embolization and infusion of CD133+ cells into the opposite portal vein by a percutaneous access. Evaluation of liver regeneration was performed 30 days after stem cell infusion by spiral CT and galactose clearance. Liver resection was carried out if liver regeneration reached 30-40%. Results:Stem cell mobilization, LKF content and immunoselected cells are detailed in tab 1. No relevant side effects were observed. We obtained an efficient stem cell mobilization in all patients enrolled. No bacterial or fungal contamination was observed in cells infused. Results about liver regeneration and patients' follow up are detailed in table 2.Table 1Mobilization, leukapheresis content and characteristics of cells infused.Median pts' weight (range): 79.7 kg (63 -120) Median days for mobilization (range) 4 (3-4) Median WBC count at the time of collection (range) 37.3×106/ml (26-48) Median PBSC at the time of collection (range) CD133+: 21/mL (16-47.7)>CD34+: 41.5/ mL (22-82)Leukapheresis content mean (range) WBC: 113.2×109 (20.4-200.3) CD133+: 172.7×106 (40.1-372.5) CD34+: 265.3×106 (60-592.6)Characteristics of cells infused mean (range) CD133+: 65.7×106 (41-83) CD133+/kg 0.85×106 (0.29-1.35) CD133+ recovery: 38% (26-55) Viability % (7AAD): 98% (96-99) Purity: 94% (91-95)Table 2Liver regeneration after portal vein infusion of CD133+ cells. FLRV(Future Liver Remnant Volume) expressed as volume (cc) and percentage of total liver mass.Case 1Case 2Case 3Case 4Total volume (cc)1745168913082816Basal FLRV (%)441 (25)611/36290/22723/2630 Days post-treatment FLRV (%)920 (48)772/45568/401080/38TumorCholangiocarcinomaHCC multifocal, PV invasionMetastases of rectal cancerMetastases of colon cancerSurgeryResectedProgression of diseaseResectedResectedStatusAlive free from disease (15 months follow-up)Dead (8 months from diagnosis)Alive, residual disease (12 months follow-up )Alive (6 months follow -up), disease progression Conclusions:Our approach to liver regeneration was feasible and safe with no relevant side effects. We observed an efficient stem cell mobilization comparable to healthy donors also in liver cancer patients. The infusion of CD133+ cells allowed a significant hepatic tissue regeneration in all patients. Controlled clinical trials are needed to confirm our preliminary results. Disclosures:No relevant conflicts of interest to declare.