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目的探索用联合大剂量免疫抑制剂进行强免疫清除,但保留骨髓造血功能而无需造血干细胞移植(SCT)的方法,治疗儿童难治性系统性红斑狼疮(SLE)的疗效。方法2004-08—2005-04对中山大学附属第一医院儿科收治的难治性SLE5例进行二种方案的疗效分析。5例均有肾损害,其中4例肾病理WHO-Ⅳ型和大量蛋白尿,2例免疫性溶血性贫血,1例免疫性血小板减少,均曾用包括环磷酰胺(CTX)和甲基泼尼松龙双冲击等治疗无效或病情反复无法控制。4例给予方案1治疗,另1例因严重水肿和尿少不宜用大剂量CTX,给予方案2治疗。疗效用SLE疾病活动性指数记分(SLEDAI)评估。结果方案1从CTX结束算起,中性粒细胞恢复到0.5×109/L平均需10d,方案2从Ara-C结束起,中性粒细胞恢复到0.5×109/L需16d;治疗3周时SLEDAI平均从9.2降至4.4,尿蛋白从(++++)降至(0～+),合并有重度难治性贫血或血小板减少者,治疗后血红蛋白或血小板分别恢复正常或接近正常;方案2治疗的1例由于肾血管血栓形成未能控制,病情短暂好转后再度恶化,1个月后死于DIC和肾功能衰竭;另4例随访5～16个月,病情基本控制。结论控制在一定范围内的大剂量免疫抑制剂治疗SLE,无需SCT而能恢复自身造血,同时能相当大程度清除病态免疫系统,使常规治疗无效者病情缓解,值得进一步探索。

Intense immunoablative therapy for childhood refractory systemic lupus erythematosus: observation of 5 cases

?? AbstractObjectiveIn this trial we investigated the safety and efficacy of nonmyeloablative but intense immunoablative chemotherapy without SCT in the treatment of childhood refractory SLE. MethodsFive refractory SLE patients were female aged 10~16 at the study??4 with WHO class ?? nephritis??2 with immune hemolytic anemia and 1 with immune thrombocytopenia.Previous therapy including monthly I.V.cyclophasphamide (CTX) and high -dose methylprednisolone failed for the 5 cases.Among these cases,4 received regimen A and 1 received regimen B.The disease activity was measured by SLEDAI before and after the treatment. ResultsThere was no treatment-related death.The median time to achieve a neutrophile count of 0.5??109/L was 10 days after the last dose of chemotherapy in regimen A,and the time was 16 days in regimen B.The average SLEDAI decreased from 9.2 to 4.4,and the proteinuria decreased from (++++) to (0~+) in 3 weeks after the treatment.Two cases with complication of hemolytic anemia and 1 with thrombocytopenia before the treatment recovered to normal or nearly normal hemogram respectively.Among these 5 cases,1 patient had a short time improvement during the therapy,but died 50 days later because of refractory thrombosis of renal vein; 4 other patients achieved complete or partial remission within 5~16 months follow-up. ConclusionDose-controlled high-dose chemotherapy leads to hemotopoietic reconstitution without SCT and has significantly clinical benefit in children with refractory SLE by immunoablation.Therefore this approach deserves further study.