自体外周造血干细胞移植治疗进展型多发性硬化初步研究

Preliminary result on effects of autologous peripheral blood stem cell transplantation on progressive multiple sclerosis

目的 评价自体外周造血干细胞移植术 (APBSCT)治疗进展型多发性硬化的疗效及其安全性和毒性。方法 移植组进展型多发性硬化患者 10例 ,造血干细胞动员应用惠尔血 ,预处理应用卡氮芥、依托泊苷、阿糖胞苷、马法兰 (BEAM方案 ) ,移植前采用CD+ 3 4 纯化和未纯化两种方法处理。对照组进展型多发性硬化患者 10例 ,应用糖皮质激素或免疫抑制剂治疗。中位随访时间 10个月 (范围 4～ 2 2个月 )。应用扩充神经功能残疾量表 (EDSS)、年平均发作次数和MRI进行疗效评价。结果移植组患者移植后 12个月EDSS评分较对照组降低 (分别为 3 4 1± 0 2 3和 6 31± 1 2 1,P <0 0 1) ,平均年发作次数降低 (分别为 0 37± 0 0 7和 1 83± 0 4 2 ,P <0 0 1)。移植组患者移植后MRI强化病灶数较移植前均减少 (P <0 0 1) ;移植前CD+ 3 4 纯化者较未纯化者治疗更有效 (P <0 0 1)。动员、预处理和移植期间无一例死亡 ,常见的不良反应为胃肠道反应和感染 ;在移植后 2例患者有一过性轻度神经功能损害 ,1例在 10个月时复发。结论 APBSCT治疗进展型MS患者近期治疗效果是明显的 ,安全性是可靠的 ,长期疗效仍需进一步随访观察。

Objective To assess the effects of autologous peripheral blood stem cell transplantation (APBSCT) on progressive multiple sclerosis and to obtain information on its toxicity and safety. Methods Total 10 patients with progressive multiple sclerosis (MS) were transplanted with APBSCT, after BEAM conditioning regimen (carmustine, etoposide, cytosine-arabinoside, and melphalan). Granulocyte-colony-stimulating factor (G-CSF) was used for stem cell mobilization. 10 patients with progressive MS were received routine medical therapy as controls. The median follow-up time was 10 months (4-22). Results The results showed that the mean EDSS rating scores of 10 patients in one year after APBSCT was significantly decreased (3.41±0.23 and 6.31±1.21,respectively, P <0.01) in the transplantation group than the control group, so was the median numbers of attacks per year (0.37±0.07 and 1.83±0.42,respectively, P <0.01). The gadolinium-enhancing lesions on MRI were improved significantly after APBSCT for number of the lesion sites and enhancement. The regimen with CD + 34 selection was more effective than CD + 34 non-selection.Vomiting and nausea and infections were the principal toxic complications. Mild and transient worsening of neurological signs were observed in 3 patients in the post-transplant period. Two patients worsened at 3 months and one patient relapsed at 10 months. Conclusion APBSCT appears feasible in treating progessive MS and can be accomplished with minimal toxicity. Early evaluation at 18 months post transplant indicates clinical benefits. However, these observations still need long-term follow-up.