外周血单个核细胞与纯化CD34^(+)细胞移植在治疗血栓闭塞性脉管炎导致重度肢体缺血的长期疗效比较

Comparison of long-term outcomes between autologous peripheral blood mononuclear cell and purified CD34^(+)cell transplantation in treating thromboangiitis obliterans-induced critical limb ischemia

目的比较自体外周血单个核细胞(PBMNC)与纯化CD34^(+)细胞(PCC)移植治疗血栓闭塞性脉管炎(TAO)导致的重度肢体缺血(CLI)的长期疗效。方法选择自2014年8月—2016年12月于复旦大学附属中山医院血管外科确诊为TAO并接受干细胞移植治疗的患者43例,均为男性;年龄范围20~58岁,年龄为(41.7±10.6)岁。根据移植的细胞产物将患者分为PBMNC组(23例)和PCC组(20例),于全身麻醉下将PBMNC或PCC于缺血侧下肢行均匀肌内注射,每点注射PBMNC或PCC 0.5 mL。记录并比较两组移植细胞产物的体积和移植CD34^(+)细胞数量、移植后注射点疼痛情况。记录移植前和移植后1、3、5年的无大截肢生存率(MAFS)、无痛步行时间(PFWT)、Wong-Baker面部疼痛评分(WBFPS)、踝肱指数(ABI)、趾肱指数(TBI)、经皮氧分压(TcPO_(2)),以及移植前、移植后1、6个月和移植后1、3、5年非CLI状态的患者比例。结果PBMNC组移植的细胞体积为(80.2±12.4)mL,显著大于PCC组的(40.1±2.6)mL(P<0.001)。PBMNC组、PCC组患者移植CD34^(+)细胞数量分别为(4.2±1.6)×10^(5)、(3.6±1.2)×10^(5)个/kg,两组间的差异无统计学意义(P=0.177)。PBMNC组注射点疼痛发生率为43.5%(10/23),显著高于PCC组的2/20(P=0.015);PBMNC组移植后第5年的MAFS为91.3%,PCC组为94.7%,两组间的差异无统计学意义(P=0.651)。与同组移植前比较,两组移植后1、3、5年的PFMT均显著延长(P值均<0.001),WBFPS均显著降低(P值均<0.001),ABI、TBI、TcPO_(2)均显著增高(P值均<0.001)。移植前所有患者卢瑟福分级均为5级。PBMNC组移植后1、6个月和1、3、5年非CLI状态的患者比例均显著高于同组移植前(P值均<0.05),PCC组移植后6个月和1、3、5年非CLI状态的患者比例均显著高于同组移植前(P值均<0.05);PBMNC组移植后1、6个月非CLI状态的患者比例均显著高于PCC组同时间点(P值均<0.05)。结论TAO患者经PBMNC或PCC移植治疗后均获得令人满意的长期疗效;PBMNC移植后早期即可改善卢瑟福分级,而PCC移植后注射点疼痛发生较少。

Objective To compare long-term clinical outcomes between autologous peripheral blood mononuclear cell(PBMNC)and purified CD34^(+) cell(PCC)transplantation in the treatment of critical limb ischemia(CLI)caused by thromboangiitis obliterans(TAO).Methods Forty-three TAO patients who received PBMNC(23 patients)or PCC(20 patients)transplantation at our center from August 2014 to December 2016 were enrolled in this retrospective study.The patients were all male with a mean age of(41.7±10.6)years(range,20-58 years).Under general anesthesia,patients received intramuscular injection of PBMNC or PCC(0.5 mL per site)in their ischemic limbs.The volume of autoimplant,number of CD34^(+) cells transplanted and pain of injection site were recorded.Follow-up outcomes included major amputation-free survival rate(MAFS),pain-free walking time(PFWT),Wong-Baker FACES Pain Rating Scale(WBFPS),ankle-brachial index(ABI),toe-brachial index(TBI),percutaneous oxygen partial pressure(TcPO_(2))and non-CLI ratio.Results The transplanted volume in PBMNC group was significantly larger than that in PCC group([80.2±12.4]mL vs.[40.1±2.6]mL,P<0.001).The number of transplanted CD34^(+) cells was(4.2±1.6)×10^(5)/kg in PBMNC group and(3.6±1.2)×10^(5)/kg in PCC group(P=0.177).The patients in PBMNC group seemed more likely to suffer from pain at injection site as compared with PCC group(43.5%[10/23]vs.2/20,P=0.015).In terms of limb salvage,there was no statistic difference in 5-year MAFS(91.3%in PBMNC group and 94.7%in PCC group,P=0.651).PFWT,ABI,TBI and TcPO_(2) all showed significant increases while decrease was observed in WBFPS 1,3 and 5 years after treatment(all P<0.001).All patients were in Rutherford class 5 at admission.Significant improvement of Rutherford class had been observed in PBMNC group since 1 month after transplantation while observed since 6 months in PCC group(all P<0.05).And the non-CLI ratio was significantly higher in PMBNC group than that in PCC group 1 and 6 months after transplantation(both P<0.05).Conclusion Both PBMNC and PCC transplantation can achieve satisfactory long-term outcomes in the treatment of TAO-induced CLI.PBMNC transplantation can achieve earlier Rutherford class improvement and patients receiving PCC transplantation are less likely to suffer from postoperative pain at injection site.