自体外周血造血干细胞移植治疗1型糖尿病的临床观察

目的 探讨自体外周血造血干细胞移植治疗1型糖尿病的有效性及安全性.方法 2009年11月至2010年8月于解放军第三○九医院细胞治疗科诊治的16例1型糖尿病患者经环磷酰胺+粒细胞集落刺激因子动员造血干细胞至外周血,血细胞分离机采集外周血造血干细胞并予以冻存;患者采用环磷酰胺+猪抗人淋巴细胞球蛋白方案预处理后,经静脉回输造血干细胞.观察所有患者移植前后胰岛素注射剂量、糖化血红蛋白(HbA1c)水平、C肽水平、血糖水平,同时记录治疗过程中的不良反应.结果 自体外周血造血干细胞移植后12例患者脱离胰岛素,脱离胰岛素时间在移植后3～20 d,中位时间为9 d.中位随访28周(8～44周).12例中最长已脱离胰岛素10个月余,无患者再重新依赖胰岛素.4例患者未脱离胰岛素,此4例患者移植前均C肽水平低且病程较长,但胰岛素用量均较移植前下降,所有患者胰岛功能较前明显改善.所有患者未出现骨髓抑制等严重不良反应.结论 自体外周血造血干细胞移植治疗1 型糖尿病,初步结果显示出一定的临床有效性及安全性,远期疗效有待进一步验证.

Abstract：

Objective To explore the efficacy and safety of autologous peripherial blood hematopoietic stem cell transplantation (APBHST) in patients with type 1 diabetes mellitus. Methods Hematopoietic stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor for 16 patients with type 1 diabetes mellitus who admitted to our department during November 2009 to August 2010. And then stem cells were collected from peripheral blood by leukapheresis and cryopreservation. The cells were infused intravenously after conditioning with cyclophosphamide and antithymocyte globulin. To compare the daily dose of exogenous insulin requirements, the serum levels of hemoglobin A1c (HbA1c), C-peptide, islet cell function during the mixed meal tolerance test were measured before and at different times after APBHST. Blood glucose was monitored 7 times a day before and after APBHST. And the adverse effects were recorded during and after APBHST. Results The median follow-up was 28 weeks (range: 8-44 weeks). Twelve of 16 patients stayed free from insulin at 3-20 days post APBHST. And islet cell function greatly improved after APBHST. Four of 16 patients required exogenous insulin but the dosage decreased. And all 4 patients had a poor level of C-peptide before APBHSCT. There were no such severe adverse effects as myelosuppression. Conclusion Very encouraging results have been obtained in the patients treated with APBHST. There is definite therapeutic effects and safety in a short term. But further follow-up is necessary to confirm the duration of insulin independence and the mechanisms of action.     

急性髓系白血病患者异基因骨髓移植后复发行同一供者二次移植一例

Objective To evaluate the efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of leukemia relapsed after first allo-HSCT from one sibling donor.Methods One patient with acute myeloid leukemia (AML-M4) underwent sibling donor bone marrow transplant (conditioning regimens was Bu/Cy) and relapsed after 18 months. The patient received the same donor's peripheral blood stem cell (PBSC) for second transplantation after receiving CY-TBI regimens,and reduced intension of prophylaxis of GVHD. Results The patient achieved stable engraftment after second HSCT. The patients suffered acute GVHD (intestinal Ⅳ and cutaneous Ⅲ) and had been complete remission to +8 months. Conclusion Second related HSCT is feasible in relapsed patient who had undergone related allo-BMT.     

急性髓系白血病患者异基因骨髓移植后复发行同一供者二次移植一例

Objective To evaluate the efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of leukemia relapsed after first allo-HSCT from one sibling donor.Methods One patient with acute myeloid leukemia (AML-M4) underwent sibling donor bone marrow transplant (conditioning regimens was Bu/Cy) and relapsed after 18 months. The patient received the same donor's peripheral blood stem cell (PBSC) for second transplantation after receiving CY-TBI regimens,and reduced intension of prophylaxis of GVHD. Results The patient achieved stable engraftment after second HSCT. The patients suffered acute GVHD (intestinal Ⅳ and cutaneous Ⅲ) and had been complete remission to +8 months. Conclusion Second related HSCT is feasible in relapsed patient who had undergone related allo-BMT.     

血液病合并糖尿病行异基因造血干细胞移植后的血糖变化

背景：最近研究表明,使用大剂量正规的胰岛素治疗控制血糖水平,仍有50%的患者会出现血管、眼神经及肾脏的并发症。而作者在利用异基因造血干细胞移植治疗白血病过程中发现患者合并的糖尿病症状消失,这是否提示异基因造血干细胞移植可以作为治疗糖尿病的有效方法呢？
　　目的：探讨造血干细胞移植治疗糖尿病的可能性。
　　方法：回顾分析既往做过的异基因造血干细胞移植的血液病患者,其中合并糖尿病4例。4例患者基础疾病分别为急性淋巴细胞白血病、慢性粒细胞白血病、再生障碍性贫血及骨髓增生异常综合征。异基因造血干细胞移植预处理方案均为环磷酰胺/全身照射,移植物抗宿主病预防均采用环孢菌素A+短程氨甲喋呤,移植前口服降糖药物或注射胰岛素进行血糖控制。
　　结果与结论：4例患者均造血恢复,移植物证据检测为供者植入,在移植后4-6个月患者血糖均恢复了正常(脱离降糖药物及胰岛素治疗),1例患者1年后死于白血病复发,其余3例患者随访至今血糖稳定。     

急性髓系白血病患者异基因骨髓移植后复发行同一供者二次移植一例

 目的　探索血缘HLA全相合骨髓造血干细胞移植（HSCT）后复发病例进行同一供者外周血造血干细胞二次移植（HSCT2）的可行性。方法　1例急性髓系白血病（M4）患者接受血缘HLA全相合供者骨髓移植后18个月复发,染色体检查提示为受者复发型。给予CY-TBI预处理后输注同一供者外周血HSCT2,同时降低预防移植物抗宿主病（GVHD）强度。结果　患者HSCT2后获得稳定植入,患者并发急性GVHD（肠道Ⅳ级,皮肤Ⅲ级）,完全缓解至+8月。结论　对于血缘造血干细胞供者移植后复发的患者,HSCT2同一供者HSCT是可行的。     

自体骨髓移植治疗儿童1型糖尿病

目的 探讨自体骨髓移植治疗1型糖尿病的有效性及安全性.方法 16例1型糖尿病患者采集自体骨髓并予以冻存;采用环磷酰胺+兔抗人胸腺细胞球蛋白方案预处理后经静脉回输骨髓.观察移植前后胰岛素注射剂量、糖化血红蛋白(HbA1c)水平、C肽水平、血糖水平及不良反应.结果 随访(62-365)d,中位随访时间265d,68.8％(11/16)患者术后停用胰岛素,开始停用胰岛素时间在骨髓移植后(5-114)d,中位时间为21d,最长停用胰岛素360d.11例停用胰岛素患者中2例于移植后2个月左右重新使用胰岛素,5例未停用者胰岛素用量均较移植前减少(P＜0.05).移植后患者C肽水平较移植前明显上升(P＜0.05),所有患者未出现长期骨髓抑制等严重不良反应.结论 自体骨髓移植治疗1型糖尿病,初步结果显示临床有效性及安全性,远期疗效有待进一步验证.     

单剂G-CSF动员自体骨髓有核细胞移植治疗糖尿病足

目的探讨经单剂粒细胞集落刺激因子（G-CSF）动员后的骨髓有核细胞移植治疗糖尿病足的效果。方法自2004年5月-2008年2月对解放军总医院第309临床部、徐州市中心医院、河北医科大学第一附属医院、北京市中医医院、河北唐山工人医院的69例糖尿病足患者（69条患肢）随机分组,骨髓组直接采集自体骨髓200mL,单剂G-CSF动员组在采集骨髓前1d给予G-CSF 2μg/kg,采集骨髓100mL,骨髓组采集200mL,分离骨髓有核细胞,检测骨髓有核细胞总数,流式细胞仪检测CD34＋细胞百分比,将分离的骨髓有核细胞移植于患者患肢腓肠肌。结果足部疼痛改善率动员组为89.7%（35/39）,骨髓组为90.0%（27/30）;两组所有患者在治疗后腿部疼痛均有不同程度改善,动员组1-3d所有患肢（39/39）冷感均有不同程度改善,骨髓组26/30条患肢在1-10d有不同程度改善,两组患者的患肢经皮氧分压均有不同升高。结论利用单剂G-CSF动员患者骨髓可有效提高骨髓采集物中的有核细胞数量,可减少患者骨髓采集量,不影响糖尿病足疗效。     

干细胞在再生医学领域的临床应用现状及其前景

干细胞在一定条件下，可以定向分化成机体内的功能细胞，形成任何类型的组织和器官，文章叙述了干细胞与再生医学的概念与分类，探讨了干细胞在糖尿病、心肌细胞损伤性疾病、神经损伤性疾病治疗方面的应用，分析并总结了干细胞与再生医学所面临的问题。分析处理资料显示，干细胞已经广泛应用于心血管系统疾病、神经系统疾病、骨骼肌肉相关疾病，糖尿病等多种疾病的临床试验中，并且取得初步疗效，展示了广泛的临床应用前景。     

肝脏多发局灶性脂肪变性误诊一例

目的 探讨肝脏多发局灶性脂肪变性的误诊原因,以提高临床诊断率.方法 报告1例肝脏多发局灶性脂肪变性,分析误诊原因.结果 患者因间断性右下腹部胀痛伴便血1个月入院.B超检查示肝内多发强回声结节,CT诊断考虑局灶性脂肪肝,全身PET-CT检查示肝脏转移瘤,经超声引导下肝结节穿刺病理活检确诊为肝脏多发局灶性脂肪变性.予重组人干扰素α1b治疗后病情稳定,半年后复查肝脏B超恢复正常.结论 当影像学发现肝脏多发占位时应考虑到肝脏多发局灶性脂肪变性的可能,及时行肝组织病理活检以确诊.