Analysis of allogeneic hematopoietic stem cell transplantation with high-dose cyclophosphamide-induced immune tolerance for severe aplastic anemia.

The study was aimed to explore the efficacy and safety of allo-HSCT with high-dose cyclophosphamide-induced immune tolerance for SAA. In the present study, 20 cases (12 male, 8 female; average age = 17.8 years) received reduced-intensity conditioning allo-HSCT from August 2012 to August 2014 in the Beijing Military Region General Hospital. All were HLA mismatched and received CSA; 11 received ATG-intensive immune therapy. Donors underwent mobilization with cell colony-stimulating factor. The modified preconditioning regimen included reduced-strength fludarabine combined with Busulfex and cytarabine, cyclophosphamide. Cyclophosphamide (50 mg/kg/d) induced immune tolerance 3 days after transplantation and was combined with immunosuppressive agents, including CSA, MTX, and FK506, for GVHD prophylaxis and the management of observed toxicity, GVHD and DFS. Hematopoietic reconstitution was achieved in 17 cases and engraftment after a second transplantation in an additional three cases. The average times to engraftment were 17.4 and 21.3 days, respectively, with neutrophils ≥0.5 × 109/L and platelets ≥20 × 109/L. Engraftment was confirmed by the evidence of 100 % donor hematopoiesis; T lymphocyte subset counts also increased significantly after transplantation. During follow-up monitoring to April 2015 (median duration = 17.7 months), three patients died of complications, while the other 17 showed disease-free survival (DFS rate = 85 %; longest DFS period = 32 months). Reduced-intensity allo-HSCT with high-dose cyclophosphamide-induced immune tolerance treatment is effective for SAA and can be the key technology extensively used in clinic, but its efficacy needs to be confirmed further with prospective randomized study with increased sample size.

Effect of overexpression of hypoxia-inducible factor-1α induced by hyperoxia in vivo in LNCaP tumors on tumor growth rate.

OBJECTIVE: To study effect of overexpression of hypoxia-inducible factor-1α induced by hyperoxia in vivo in LNCaP tumors on tumor growth rate. METHODS: The prostate cancer LNCaP cells were inoculated in the abdomen of mice. All the mice were randomly placed in the gas chamber with different oxygen content. The groups were divided as follows: twelve mice in hypoxia group, sixteen mice in normoxia group, ten mice in hyperoxia group. After 28 d of treatment, the mice were weighed, the blood samples were taken from the left ventricle, and the tumor was isolated and weighed. Tumor growth, angiogenesis and vascularization, HIF-1α expression and intracellular signal transduction molecules expression in each group of xenografts were detected and analyzed by using Western blotting and immunofluorescence and determination of hemoglobin. RESULTS: Comparison of the growth of xenografts in each group showed that, the xenografts growth of hypoxia group was more quickly than that of normoxia group. The difference was statistically significant (P = 0.004). The difference in xenografts growth between hyperoxia group compared and normoxia group was not statistically significant (P > 0.05). The expressions of HIF-1α, VEGF and VEGF-R of xenografts in hyperoxia group were significantly higher than those of normoxia group (P < 0.05). The expression of HIF-1α of xenografts in hypoxia group and normoxia group were similar. The blood growth rate of xenografts in hypoxia group (170%) was significantly higher than that of normoxia group (40%) (P < 0.05). The expression of Nrf2 of xenografts in hyperoxia group was significantly higher than that of normoxia group (P < 0.05). CONCLUSIONS: When hyperoxia induces the overexpression of HIF-1α in LNCaP tumor, it will not affect tumor growth. It provides a new ideas and theoretical basis for the clinical treatment of prostate cancer.