自体外周造血干细胞移植治疗继发进展型多发性硬化的疗效与安全性

目的：评价自体外周造血干细胞移植（APBSCT）治疗继发进展型多发性硬化（MS）的疗效及安全性。方法：回顾性分析2001-2010年在首都医科大学宣武医院接受APBSCT治疗的41例继发进展型MS患者的临床资料。女性31例,男性10例,年龄24～56岁,中位年龄36岁。所有患者连续5d皮下注射粒细胞集落刺激因子（G-CSF）5μg/kg动员造血干细胞。应用细胞分离机采集外周血单个核细胞（PBMC）,对28例患者应用CliniMACS免疫磁珠系统分选CD34^＋细胞,将PBMC或CD34^＋细胞置-80℃冰箱冻存。患者采用BEAMbecenum（camustine）;etoposide（teniposide）;cytosine arabinoside;melphalan]预处理方案：卡莫司汀300mg/m^2×1d;替尼泊苷150mg/m^2×4d;阿糖胞苷200mg/m^2×4d;美法仑140mg/m^2×1d。预处理后经静脉回输低温保存复苏的自体CD34^＋细胞或PBMC。应用扩充神经功能残疾量表评判患者APBSCT后神经系统功能的恢复程度,根据不良事件常用术语标准3.0版评判APBSCT的不良反应。结果：2例患者失访。39例患者治疗后随访6～100个月,平均51个月,其中16例缓解,8例稳定,15例移植后复发且病情进展。100个月累计疾病无进展生存率为55.5%。预处理后41例患者的中性粒细胞均〈0.5×10^9/L,血小板均〈25×10^9/L。经支持治疗后所有患者均获得造血重建;37例发生腹泻;3例发生替尼泊苷过敏反应;26例发生感染,其中发热性中性粒细胞减少19例,会阴肛门周围皮肤软组织脓肿2例,败血症2例,肺部真菌感染、静脉置管处皮肤感染和消化道感染各1例;6例发生植入综合征;无移植相关死亡。结论：APBSCT是治疗继发进展型MS较安全有效的方法,但使用期间应严密观察可能出现的不良反应。

Efficacy and safety of autologous peripheral blood stem cell transplantation in treatment of patients with secondary progressive multiple sclerosis

Objective： To restrospectively analyze the efficacy and safety of autologous peripheral blood stem cell transplantation （ APBSCT） in treatment of patients with secondary progressive multiple sclerosis（ MS） . Methods： Between 2001 and 2010,41 patients with secondary progressive multiple sclerosis in Xuanwu Hospital of Capital Medical University entered the study. They comprised 31 women and 10 men with mean age of 36 years. All patients received SC G-CSF 5 μg/kg for five days to mobilize hematopoietic stem cells. Peripheral blood mononuclear cells were collected by cell separator,and CD34 ＋ cells selected by CliniMACS in 28 cases. The mononucleur cell or CD34 ＋ cells were stored at-80℃ in refrigerator. The patients received a BEAM conditioning regimen comprising becenum （ camustine） 300 mg/m^2 × 1 d,etoposide （ teriposide） 150 mg/m^2 × 4 d,cytosine arabinoside 200 mg/m^2 × 4 d,and melphalan 140 mg/m^2 × 1 d. After the conditioning regimen,the CD34 ＋ cells or PBMC preserved at low temperature were restored, and were infused intravenously. The degree of recovery in the neurological function after APBSCT was evaluated with EDSS and the adverse reactions were evaluation with Common Terminology Criteria for Adverse Events V 3. 0. Results： Two patients were lost to follow-up. The follow-up duration to 39 patients after APBSCT ranged from 6 to 100 （ mean 51） months. Of them,16 patients’state was improved,8 stable,and 15 recurrence and progression. The cumulative 100-month progression-free survival rate was 55. 5% . The adverse reactions due to APBSCT were as follows： after the conditioning regimen,the neutrophils and platelet counts in 41 patients were 〈0. 5 × 10^9 /L and 〈25 × 10^9 /L,respectively,and hematopoietic reconstitution was achieved after supportive treatment in all patients,37 patients developed diarrhea; 3 patients presented with tenipeide-induced anaphylaxis; 26 patients experienced infections, including 19 cases of neutropenia with fever,2 cases of soft tissue abscess,2 cases of septicemia,1 case of pulmonary fungal infection, 1 case of skin infection,and 1 case of alimentary tract infection. Six patients developed engraftment syndrome. There was no death associated with APBSCT. Conclusion： APBSCT is a relatively effective and safe therapy for the secondary progressive multiple sclerosis; however,closely observing the possible occurrence of adverse reactions during the use of APBSCT is necessary.