自体造血干细胞移植治疗1型糖尿病的疗效和安全性评价

目的 对初发的新诊断1型自身免疫性糖尿病患者施行自体外周造血干细胞移植术,评估该治疗方式的安全性和有效性.方法 共有18例患者符合入选条件,获得知情同意后接受移植治疗.利用环磷酰胺和粒细胞集落刺激因子促进外周造血干细胞产生,干细胞富集后采集冷冻保存.通过环磷酰胺和抗胸腺球蛋白获取免疫抑制,于上述两种给药后即行干细胞回输.术前后监测血糖、血清C肽、HbA1C、谷氨酸脱羧酶抗体(GAD-Ab)水平和记录不良事件,对干细胞移植的疗效和安全性进行评估.结果 18例患者(6例男性,12例女性2)平均年龄(18.8±4.4)岁,平均随访天数(414±150)d.67%(12/18)患者术后停用胰岛素,最短在术后2周,最长在术后6个月.12例中有4例因上感等原因出现血糖上升而重新使用胰岛素.目前有44.4%(8/18)患者完全脱离胰岛素治疗,其余患者胰岛素用量的减量幅度平均为67.3%±22.4%.18例患者的GAD-Ab水平明显下降,转阴率33.3%(6/18).空腹C肽和餐后2 h C肽水平在术后明显上升,C肽曲线下面积(AUCC)上升更为显著,且可维持1年.在移植治疗过程中,所有患者均出现不同程度的胃肠道反应,脱发,发热,骨髓抑制等不良反应,有5例患者接受了成份血输注.未观察到明显的心、肝、肾等脏器功能受损.不良反应在干细胞回输后的2～4周逐步消失,粒细胞减少的恢复最为缓慢.结论 自体造血干细胞移植治疗有胰岛功能残存的初发1型糖尿病患者有一定的疗效,安全性较高,临床可行性强.对其治疗机制还有待进一步研究.

Efficacy and safety of autologous hematopoietic stem cell transplantation in treating type 1 diabetes mellitus

Objective To determine the safety and the therapeutic efficacy of autolagous nonmyeloablative hematopoietic stem cell transplantation (AHST) in newly-onset type 1 diabetes mellitus patients. Methods Fifteen patients with type 1 diabetes mellitus were enrolled. Hematopoietic stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were injected intravenously after conditioning with cyclophosphamide and rabbit antithymocyte globulin. Serum levels of HbA1c, C-peptide levels, and anti-glutamic acid decarboxylase antibody (GAD-Ab)titers were measured before and after AHST. Meanwhile, adverse event was recorded.Results The average age of 18 patients (6 males and 12 females)was ( 18.8±4.4 )years, the mean follow-up was ( 414± 150 ) days. 67 % ( 12/18 ) patients became insulin free, the earliest one happened at 2 weeks after AHST, and the latest one at 6 months. 4 cases resumed insulin use because of influenza and other reasons resulting in the rise of blood glucose level. Currently, 8 patients (44.4%) were completely free of insulin therapy, and the remaining cases reduced the insulin dosage by 67.3% ±22.4%. 18 cases had lowered GAD-Ab level, the negative rate was 33.3% (6/18 ). Fasting and postprandial 2 h C-peptide levels increased significantly after A HST. Area under the curve for C-peptide ( AUCC ) increased much more markedly, and it could be maintained for 1 year. Duringtransplantation,all patients had varying degrees of gastrointestinal reactions, hair loss, fever, bone marrow suppression, and other side effects. 5 patients received blood component transfusion. No damage or other severe adverse events of heart, liver, kidney, and other organs were observed. Most side effects gradually disappeared after 2-4 weeks. The recovery of neutropenia was the slowest. Conclusion Autologous hematopoietic stem cell transplantation for treatment of newly-onset type 1 diabetes with residual islet function showed a certain effect and high safety. The widened use of this new technique should be cautious until the therapeutic mechanism has been further studied.