ABSTRACT
Intestinal transplantation is the most effective treatment for patients with short bowel syndrome and small bowel insufficiencies. We evaluated epithelial chimerism after infusion of autologous bone marrow mesenchymal stromal cells (BMSCs) in patients undergoing cadaveric donor isolated intestinal transplantation (I-ITx). BMSCs were isolated from patients' bone marrow via iliac puncture and expanded in vitro prior to infusion. Two out of the 3 patients were infused with autologous BMSCs, and small intestine tissue biopsies collected post-operatively were analyzed for epithelial chimerism using XY fluorescent in situ hybridization and short tandem repeat polymerase chain reaction. We observed epithelial chimeric effect in conditions both with and without BMSC infusion. Although our results suggest a higher epithelial chimerism effect with autologous BMSC infusion in I-ITx, the measurements in multiple biopsies at different time points that demonstrate the reproducibility of this finding and its stability or changes in the level over time would be beneficial. These approaches may have potential implications for improved graft survival, lower immunosuppressant doses, superior engraftment of the transplanted tissue, and higher success rates in I-ITx.
Subject(s)
Bone Marrow Transplantation/methods , Chimerism , Intestine, Small/transplantation , Mesenchymal Stem Cells/cytology , Tissue Donors , Adolescent , Adult , Child , Female , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Reproducibility of Results , Young AdultABSTRACT
PURPOSE: The combination of taxanes and anthracyclines has proven efficacy in node-positive (N+) premenopausal primary breast cancer patients. Ovarian ablation is also associated with better survival outcomes in premenopausal hormone-receptor positive (HR+) patients. Therefore, this trial aims to determine the superiority of combined hormonal treatment of ovarian ablation with tamoxifen (TMX) versus TMX alone, in premenopausal N+, HR + patients receiving adjuvant chemotherapy (AC) with taxane and anthracycline. MATERIALS AND METHODS: Premenopausal women who had surgically removed breast cancer with histologically confirmed N + and HR+ were included in the trial. The AC consisted of six cycles of taxotere, adriamycin, cytoxan or taxotere, epirubicin and cytoxan with the completion of radiation therapy. Patients were randomly assigned to receive TMX 20 mg/day for 5 years or up to menopause or TMX 20 mg/day for 5 years plus goserelin (GOS) 3.6 mg injection per month for 2 years. The primary end point was disease-free survival (DFS). RESULTS: Between 2003 and 2011, 101 consecutive patients were allocated to TMX (51 patients) and TMX/GOS (50 patients) groups. The mean follow-up period was 52.4 ± 2.8 months. DFS was 43.0 ± 3.6 months versus 49.9 ± 4.22 months (P = 0.13) and overall survival was 51.1 ± 3.8 months versus 53.1 ± 4.2 months (P = 0.50) in the TMX and TMX/GOS groups, respectively. The results showed 9% absolute risk reduction with respect to DFS in favor of the TMX/GOS group. CONCLUSION: This study group was comprised of stage II and III disease patients with high nodal status. The TMX/GOS combination reduced absolute risk of developing first locoregional or distant relapse by almost 9%. Longer follow-up is required to justify this protocol for routine use.
