纯化自体外周血CD34^+细胞移植治疗肢体重度缺血的中期疗效

Mid-term outcomes of transplantation of purified CD34+ cells from peripheral blood in treatment of critical limb ischemia

目的探讨纯化CD34+细胞移植治疗肢体重度缺血的中期疗效。方法自2009年5月至2011年12月录入30例肢体重度缺血患者,男性29例,女性1例,平均年龄43 ± 12岁(23 ~ 75岁),均不具备外科血管重建条件,共治疗31条下肢和4条上肢。G-CSF(5~10μg/kg)动员,第5天采集外周血单个核细胞,分选获得纯化CD34+细胞,肢体肌肉局部注射。根据移植细胞数分为3组:低剂量组(105/kg)、中剂量组(5 × 105/kg)和高剂量组(106/kg)。结果随访16 ~ 48个月,1个月和2个月时Wong-Baker FACES疼痛评分由术前7 ± 2降到3 ± 3(P< 0.001)和1 ± 2(P< 0.001)。术后3个月和6个月:最长无痛步行时间由术前的(5 ± 3)min分别延长至(12 ± 6)min(P< 0.001)和(19 ± 5)min(P< 0.001);踝肱指数由术前的0.44 ± 0.20提高至0.62 ± 0.18(P= 0.04)和0.66 ± 0.14(P< 0.001);经皮氧分压由术前(26 ± 11)mmHg分别上升至(42 ± 11)mmHg(P < 0.001)和(56 ± 12)mmHg(P< 0.001)。16例溃疡患者愈合11例。Kaplan Meier生存分析法计算16个月保肢率为84﹪(95﹪可信区间为0.63 ~ 0.94)。3个不同剂量组之间的比较,治疗效果差异无统计学意义,除了1个月时WFPRSC检测结果显示:高剂量组明显优于低、中剂量组。结论纯化自体外周血CD34+细胞移植治疗肢体重度缺血性疾病安全、可行,能够较为持久地缓解缺血,挽救肢体,改善患者生活质量。

Objective To evaluate the mid-term outcomes of transplantation of purified peripheral blood CD34^＋ cells in treatment of critical limb ischemia. Methods From May 2009 to November 2011, 30 patients with critical limb ischemia underwent transplantation of purified peripheral blood CD34^＋ cells. Mean age was 43 ±12 years （23-75）, and all patients were not suitable for surgical or endovascular revascularization. G-CSF was subcutaneously injected for 5 days before apheresis for peripheral blood mononuclear cells. Then CliniMACS system was used to isolate CD34^＋ cells. The patients were divided into 3 groups： low-dose （105/kg）; medium-dose （5×10^5）/kg; and high-dose （106/kg）. The outcomes were compared among 3 groups. Results The follow-up was accomplished in 27 cases, ranging from 16 - 48 months （ 30 ± 8 ）. One month after transplantation, the rest pain was obviously relieved in all cases, and the Wong-Baker FACES pain rating score significantly decreased from 7 ± 2 to 3 ± 3 （0-2）, P 〈 0.001. The peak pain-flee walking time was significantly improved from （5 ^＋ 3） min to （ 12 ± 6） min at 3 month and （ 19 ± 5） min at 6 month respectively. The ankle- brachial index increased from 0.44 ^＋ 0.20 to 0.62 ± 0.18 at 3 month and 0.66 ^＋ 0.14 at 6 month, respectively. Of 14 cases with ulcer, 11 healed. Transcutaneous partial oxygen pressure rose from （26 ± 11 ） mmHg to （42 ± 11 ） mmHg at 3 month and （56 ± 12） mmHg at 6 month, respectively. No serious complications were observed either per^＋operatively or postoperatively. Conclusions Transplantation of purified peripheral blood CD34^＋ cells appeared to be effective and safe for critical limb ischemia.