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目的探讨自体外周血干细胞移植(auto-PBHSCT)治疗难治性学龄前儿童风湿病的可行性、安全性和有效性。方法幼年皮肌炎(JDM)、幼年系统性红斑狼疮(JSLE)、幼年类风湿关节炎(JRA)各1例,均为男性患儿,年龄分别为3、6、6岁,病程分别为14、3.6、22个月,常规治疗中病情进展,库欣征明显,患病后患儿身高均无增长。JDM 患儿肌力Ⅱ级,吞咽肌和呼吸肌受损,明显 Gottron’s征和向阳性皮疹;JSLE 患儿表现为蝶形红斑、蛋白尿、贫血,脑 MRI 显示脱髓鞘病变,系统性红斑狼疮疾病活动性指数(SLEDAI)≥12分;JRA 患儿双膝、踝、腕、肘严重多关节炎。以环磷酰胺(CTX)+粒细胞集落刺激因子(G-CSF)进行外周造血干细胞动员,经 CliniMACS 细胞分选仪分选 CD34~+细胞。预处理方案:JSLE 和 JRA 为卡氮芥(BCNU)+足叶乙甙(VP16)+阿糖胞苷(Ara-C)+马法兰(MEL)及抗胸腺球蛋白(ATG);JDM 为 CTX+Mel 及 ATG。回输 CD34~+细胞数分别为9.45×10~6/kg、5.46×10~6/kg 和9.60×10~6/kg。观察移植治疗前后风湿病状态和免疫学指标的变化。结果 3例患儿移植后分别于+9 d、+13 d、+11 d 粒细胞≥0.5×10~9/L,+14 d、+18 d 和+13 d 血小板≥20×10~9/L。CD4处于低水平,CD4/CD8倒置。JDM 移植后1个月皮疹消失,肌力Ⅴ级,移植后2个月血清肌酶、肌电图恢复正常。JSLE 移植后3个月皮疹消退,无蛋白尿,脑 MRI 病变吸收,移植后8个月自身抗体转阴性,SLEDAI 为2～3分。JRA 移植后3周关节炎好转,移植后3个月无关节肿胀及活动受限。均停用激素和免疫抑制药物,库欣征消退,18个月身高增长10～15 cm,均已上小学或学前班,随访25～27个月无复发。结论 auto-PBHSCT 治疗难治性学龄前儿童风湿病近期疗效显著,安全性及远期疗效有待进一步观察。
Objective To investigate the feasibility, safety and efficacy of auto-PBHSCT in the treatment of rheumatic diseases in refractory preschool-age children. Methods One case of juvenile dermatomyositis (JDM), juvenile systemic lupus erythematosus (JSLE) and juvenile rheumatoid arthritis (JRA) were all male males with the ages of 3, 6 and 6 years old, respectively, and their durations were 14 , 3.6,22 months, the progress of routine treatment progress, Cushing syndrome significantly, no increase in children’s height after illness. JDM children muscle strength Ⅱ, swallowing muscle and respiratory muscle damage, obviously Gottron’s sign and positive rash; JSLE children showed butterfly erythema, proteinuria, anemia, brain MRI showed demyelinating lesions, systemic lupus erythematosus Disease activity index (SLEDAI) ≥ 12 points; JRA children knees, ankles, wrists, elbows severe polyarthritis. Peripheral blood stem cells were mobilized with cyclophosphamide (CTX) + granulocyte colony-stimulating factor (G-CSF), and CD34 + cells were sorted by CliniMACS cell sorter. Pretreatment protocol: JSLE and JRA were BCNU + VP16 + MEL and ATG; JDM was CTX + Mel and ATG. The number of CD34 ~ + cells transfused was 9.45 × 10 ~ 6 / kg, 5.46 × 10 ~ 6 / kg and 9.60 × 10 ~ 6 / kg, respectively. To observe the changes of rheumatism status and immunological indexes before and after transplantation. Results The results showed that the number of granulocytes≥0.5 × 10 ~ 9 / L at +9 d, +13 d, +11 d, +20 d, +18 d and +13 d at platelet ≥20 × 10 ~ 9 / L. CD4 is low, CD4 / CD8 upside down. One month after JDM transplantation, the rash disappeared and the muscle strength was V level. Serum muscle enzymes and EMG returned to normal after 2 months of transplantation. 3 months after JSLE rash subsided, no proteinuria, brain MRI lesions absorbed, autoantibodies negative 8 months after transplantation, SLEDAI 2 to 3 points. Arthritis improved 3 weeks after JRA transplantation, and there was no joint swelling and limited activity 3 months after transplantation. Both steroid and immunosuppressive drugs were discontinued. The Cushing syndrome subsided and the height increased by 10-15 cm at 18 months. Both of them had reached primary school or preschool and had no recurrence after 25-27 months of follow-up. Conclusion Auto-PBHSCT treatment of refractory preschool children with rheumatic short-term significant effect, safety and long-term efficacy remains to be further observed.