不同大剂量环磷酰胺联合移植或不移植自体外周造血干细胞治疗重型系统性红斑狼疮23例

选择2004-10/2009-01桂林医学院附属医院风湿免疫科住院的23例重型系统性红斑狼疮患者，男3例，女20例，中位年龄(28±11)岁。分为4组：环磷酰胺10 mg/(kg•d)组12例，环磷酰胺20 mg/(kg•d)组5例，环磷酰胺30 mg/(kg•d)组4例，环磷酰胺40 mg/(kg•d)组2例。对每组患者实施不同预处理剂量的环磷酰胺，×3 d，在预处理前均采集自体外周血造血干细胞，保存细胞数为(1.7~3.8)×108/kg。所有受试者在任何时间点若白细胞低于0.5×109 L-1，血小板低于10×109 L-1即进行干细胞颈内静脉移植，回输细胞量为(2.1~3.4)×108/kg。结果显示：环磷酰胺10 mg/(kg•d)组9例血小板和白细胞无下降，3例血小板和白细胞第7~9天下降，但能自行恢复。环磷酰胺20 mg/(kg•d)组1例血小板和白细胞无下降，4例血小板和白细胞第5~9天下降，但能自行恢复，均无需自体外周造血干细胞移植支持。环磷酰胺30 mg/(kg•d)组4例血小板和白细胞第3~7天下降，其中1例于第5天回输干细胞，白细胞在移植后10，14 d 最低值分别为2.47× 109 L-1，18.8×109 L-1；移植后30 d血小板为134×109 L-1。环磷酰胺40 mg/(kg•d)组2例血小板和白细胞第3，5天下降，其中1例于第4天回输干细胞，白细胞在移植后10，14 d最低值分别为1.67×109 L-1，9.8×109 L-1；移植后30 d血小板为215×109 L-1。1例于第6天回输自体外周造血干细胞，白细胞在移植后10，14 d最低值分别为2.18×109 L-1，16.5×109 L-1；移植后30 d血小板为96×109 L-1。所有移植病例均无移植物抗宿主病、肝静脉闭塞病、出血性膀胱炎和感染的发生。与环磷酰胺10 mg/(kg•d)组比较，环磷酰胺20，30，40 mg/(kg•d)组完全的临床缓解率明显升高。提示以自体外周血干细胞移植为后盾，采用移植或不移植干细胞的方法，将很可能使重型系统性红斑狼疮达到长期的完全临床缓解。

Treating severe systemic lupus erythematosus by different high-doses of cyclophosphamide with or without autoallergic periphery hematopoietic stem cell transplantation in 23 cases

Totally 23 patients with severe systemic lupus erythematosus (SLE) admitted at the Affiliated Hospital of Guilin Medical College from October 2004 to January 2009 were selected, including 3 male and 20 female, with a median age of (28±11) years, were divided into 4 groups according to the doses of cyclophosphamide (CTX): 10 mg/(kg•d) group (n =12), 20 mg/(kg•d) group (n =5), 30 mg/(kg•d) (n=4) and 40 mg/(kg•d) (n =2). In each group, patients were treated by CTX accordingly for 3 days. The autoallergic periphery hematopoietic stem cell was collected prior to CTX treatment, and (1.7-3.8)×108/kg cells were reserved. (2.1-3.4)×108/kg cells were transplanted via internal jugular vein when the numbers of white blood cell (WBC) lower than 0.5×109/L and the platelet number lower than 10×109/L. Results demonstrated that in 10 mg/(kg•d) group, there was 9 patients had no descend of platelet and WBC, which was decreased in 3 patients at days 7-9, and recovered to normal level. In the 20 mg/(kg•d) group, 1 patients had no descend, and 4 patients descended at days 5-9, which recovered to normal level. In the 30 mg/(kg•d) group, platelet and WBC of 4 patients were descended at the days 3-7, one of which received stem cells transfusion, the minimum of WBC was 2.47×109/L and 18.8×109/L at days 10 and 14 after transplantation. The value of platelet was 134×109/L at 30 days after transplantation. In the 40 mg/(kg•d) group, platelet and WBC of 2 patients were descended at the days 3 and 5, one of which received stem cells transfusion at the days 4, and the minimum of WBC was 1.67×109/L and 9.8×109/L at days 10 and 14 after transplantation, with platelet value of 215×109/L at 30 days after transplantation; the other patient was refused autoallergic periphery hematopoietic stem cell at the days 6, and the minimum of WBC was 2.18×109/L and 16.5×109/L at days 10 and 14, with platelet value of 96×109/L at 30 days after transplantation. There was no graft-versus-host disease, hepatic venous occlusive disease, hemorrhagic cystitis and infection occurred. Compared to 10 mg/(kg•d) group, the remission rate of other 3 groups were obvious higher. Therefore, it indicates that total clinic remission may be achieved in patients with severe SLE by reinfusing autoallergic periphery hematopoietic stem cells or not on account of the technology of autoallergic periphery hematopoietic stem cell transplantation.