Objective To investigate the effect of transplantation of islet allograft with Bcl-2 gene transfection on diabetic rats. Methods Among 26 Wistar rats, 22 were built as model of diabetes, and were divided in to 3 groups. Islet cells expressing Bcl-2 by adenovirus-mediated Bcl-2 gene transfection were transplanted through the portal vein of streptozotocin-induced diabetic rats. The function and rejection of the transplanted islet allograft were evaluated by analysis of blood glucose level and histological examination after transplantation. Results 48h after transplantation, the level of blood glucose was significantly decreased in both transfected and untransfected islets transplantation groups. The euglycemia period of transfected islet cells transplantation group was longer than that of the untransfected islet cells transplantation group (16.4?4.3d vs 6.8?2.2d, P

20?109/L in 12 to 19(median 14)days after transplantation.Complete chimerism was achieved in all the patients at one month after HSCT.Two patients had acute GVHD and one had chronic GVHD.With a median follow-up of 31(19~37)months,8 of 9 patients were alive and disease-free.Conclusion The intravenous Bu/Flu conditioning regimen may reduce transplantation-related toxicities and can achieve full chimerism and high long-term disease-free survival.Allogeneic hematopoietic stem cell transplantation using intravenous Bu/Flu conditioning regimen is a safe and effective option for the patients with myeloid hematopathy.

Objective To explore the effect of hyperglycemia on the survival time, duration of disease remission and complications during induction chemotherapy for acute lymphocytic leukemia(ALL). Methods The treatment-related complications in 98 adult ALL patients with or without hyperglycemia were retrospectively analyzed. Survival time and complete remission duration(CRD) were evaluated using Kaplan-Meier method. Cox regression analysis was used to examine whether hyperglycemia was an independent predictor of disease recurrence and death. Results ALL patients with hyperglycemia were found to be older, and more likely to occur thrombocytopenia. ALL patients with hyperglycemia had a shorter CRD and survival time, and were more likely to develop infection and neuropathy. Conclusion Hyperglycemia during induction chemotherapy for ALL increased the frequency of infection and the risk of disease recurrence and death.

Objective To study the feasibility of HLA non-identical allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBHSCT) for the treatment of patients with severe aplastic anemia (SAA). Methods Four patients with SAA received non-identical allo-PBHSCT from HLA one or three loci mismatched related donors. Donors were given G-CSF 5?g/(kg?d) for 5 days, then PBSC were harvested on days 4 and 5. Prime regimen consisted of fludarbine, CTX, ATG and TBI. Combination of CsA, MTX, MMF and Simulect (CD25 monoclonal antibody) were used for GVHD prophylaxis. Results Engraft was achieved in all patients. The median days of neutrophil exceeding 0.5?109/L and platelet exceeding 20?109/L were 15.3 days (range 14~16 days) and 17.5 days (range 16~19 days), respectively. In the 14-month median follow-up duration, only one of four patients developed grade Ⅱ aGVHD, and one patient died of systemic candidiasis, the other three were alive in disease-free condition. Conclusion HLA non-identical allo-PBHSCT was well tolerated by patients with SAA, and it provided rapid and sustained engraftment without increase in incidence of GVHD.

Objective To retrospectively analyze the efficacy of a pediatric treatment protocol,BFM90,in adult patients with acute lymphobiastic leukemia (ALL) up to the age of 60 years. Methods From August 2004 to October 2007,60 adult patients (median age,40 years; range,18 to 60 years) with Philadelphia chromosome-negative ALL were treated with the BFM90 protocol. Clinical effect were historically compared with that of the 35 patients (median age,42 years; range,18 to 56 years) who were treated with Hyper-CVAD protocol. Results At 42 months,complete remission (CR) rate,event-free survival (EFS) and overall survival (OS) rates were 93 % (56 patients),60 % (36 patients) and 65 % (39 patients),respectively.Age is an important prognostic factor,with 45 years of age as best cutoff. CR (P=0.02),OS (P ＜0.001),and EFS (P ＜0.001) of BFM90 were compared superiorly with that of the previous Hyper-CVAD experience.Conclusion These results suggest that pediatric protocol superior to the outcome of adult patients with Philadelphia chromosome-negative ALL.

Objective To investigate the toxic effect of immunosuppressive drugs on apoptosis of rat pancreatic islet cells in vitro and the protective action of Bcl-2.Methods Islet cells expressing Bcl-2 and the control islet cells were cultured at different concentrations of tacrolimus and the apoptosis rate of islet cells and insulin accumulation in the culture medium were detected after 48h.Results Low and high concentrations of tacrolimus induced the apoptosis of islet cells and decreased insulin secretion.The Bcl-2 inhibited the apoptosis of islet cells induced by tacrolimus and improved the insulin secretion.Conclusion Tacrolimus may directly damage to isolated rat islet cells and the expression of Bcl-2 can protect the cells from the damage of immunosuppressive drugs.

Objective To investigate the effects of antithyroid drug(ATD) on oxidative stress in Graves disease patients with and without infiltrative ophthalmopathy.Method The levels of superoxide dismutase(SOD),glutathione peroxidase(GPx) and catalase(CAT) in erythrocytes of Graves disease patients(18 with and 20 without infiltrative ophthalmopathy) were measured before and after treatment with ATD.Results Compared with the normal control group,the levels of SOD,GPx and CAT were significantly higher in Graves disease patients with and without infiltrative ophthalmopathy.After euthyroidism was achieved with the treatment of ATD,the levels of SOD,GPx and CAT were normalized in the patients without infiltrative ophthalmopathy,but oxidative stress was still present in the patients with infiltrative ophthalmopathy.Conclusion The oxidative stress is obvious in patients with Graves ophthalmopathy,which suggests that oxidative stress is involved in orbital inflammation.

Objective To evaluate the efficacy and feasibility of Flu/ivBu/Tl" conditioning regimen for the treatment of refractory or relapsed acute non-lymphocytic leukemia in patients receiving allogeneic hematopoietie stem cell transplantation. Methods Seven patients with refractory or relapsed acute non-lymphocytic leukemia received HLA identical peripheral blood hematopoietie stem cell transplantation (PBSCT) following Flu/ivBu/TY conditioning regimen, which consisted of fludarbine, busulfex and thiotepa. All patients received cyclos-porin A (CsA) and mycophenolet mofetil (MMF) for prophylaxis of graft - versus - host disease (GVHD). Results The Flu/IVBu/TT regimen was tolerated very well, without severe regimen related toxicity. In the 31-month median follow-up duration, 5 of 7 patients were a-live in disease-free situation. Conclusion The Flu/ivBu/TT conditioning regimen reduced transplantation-related toxicities and offered high long-term disease-free survival, and was tolerated very well. Allogeneie hematopoietie stem cell transplantation using Flu/ivBu/TT condition-ing regimen is a safe and effective option for the patients with refractory/relapsed acute non-lymphocytic leukemia.

Objective To evaluate the efficacy of Flu/CTX conditioning regimen for the treatment of severe aplastic anemia in pa- tients receiving allogeneic hematopoietic stem cell transplantation. Methods Nine patients with severe aplastic anemia received HLA identi- cal peripheral blood hematopoietic stem cell transplantation (PBSCT) using Flu/CTX conditioning regimen, which consisted of fludarbine [30 mg/(m2 d) for5 days (-7 to -3) ], CTX [50mg/(kg d) for4 days(-5 to-2)]. All patients received cyclosporin A (CsA) and mycophenolet mofetil (MMF) for prophylaxis of graft-versus-host disease(GVHD). Results The Fiu/CTX regimen was very well toler- ated, with no severe regimen related toxicity. In all patients, the median days of neutrephil exceeding 0. 5×109/L and platelet exceeding 20 ×109/L were 12 days (range 10-16 days) and 16 days (range 14-19 days), respectively. Complete chimerism was achieved in all pa- tients at one month after PBSCT. Two patients had acute GVHD and one had chronic GVHD. In the 39-month median follow-up duration, all patients were alive in disease-free situation. Conclusion The Flu/CTX conditioning regimen may reduce transplantation-related toxicities and can achieve full chimerism and high long-term disease-free survival. Allogeneic hematopoietic stem cell transplantation using intravenous Fiu/CTX conditioning regimen is a safe and effective treatment method for the patients with severe aplastic anemia.

OBJECTIVETo explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.

METHODSA single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.

RESULTSAll patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.

CONCLUSIONSAA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.

Anemia, Aplastic ; drug therapy ; Benzoates ; therapeutic use ; Blood Transfusion ; China ; Ferritins ; blood ; Humans ; Iron ; blood ; Iron Chelating Agents ; therapeutic use ; Iron Overload ; drug therapy ; Liver ; Prospective Studies ; Triazoles ; therapeutic use