Lisukov I A, Sizikova S A, Kulagin A D, Kruchkova I V, Gilevich A V, Konenkova L P, Zonova E V, Chernykh E R, Leplina O Y, Sentyakova T N, Demin A A, Kozlov V A
Novosibirsk State Medical Academy, Novosibirsk, Russia.
Lupus. 2004;13(2):89-94. doi: 10.1191/0961203304lu491oa.
Systemic lupus erythematosus (SLE) is an immune-mediated disease that is responsive to suppression or modulation of the immune system. Patients with SLE who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide (Cy), represent a subset of patients at high risk of early death. We investigated the efficacy and toxicity of high-dose immunosuppression and autologous hematopoietic stem cell transplantation (SCT) to treat such patients. Six patients (all female, age 15-29 years) with severe refractory SLE were enrolled in the clinic of our institution from 1998 to 2003. All patients were seriously ill, with SLE disease activity indices (SLEDAI) of 6-30, including two cases with central nervous system lupus, one case with lung vasculitis, and three cases with nephritis and nephrotic syndrome. All patients were registered in the European Group for Blood and Marrow Transplantation (EBMT)/European League Against Rheumatism (EULAR) database. Previous immunosuppression included pulse Cy intravenous, prednisolone (standard doses and pulse therapy), oral Cy and azathioprine, with little or no effect on disease progression. Autologous hemopoietic stem cells were collected from bone marrow (n = 4) or mobilized from peripheral blood with Cy and granulocyte colony-stimulating factor (G-CSF) (n = 2). Pre-transplant conditioning regimens included BEAM +/- ATG (n = 2), melphalan 140 mg/m2 + etoposid 1600 mg/m2 (n = 2) and Cy 200 mg/kg +/- ATG (n = 2). Median time to an absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L and platelet count greater than 50 x 10(9)/L was 13 and 15 days, respectively. Three patients died on days 11, 22 and 63 due to transplant-related complications. The follow-up is now 60 and six months for two patients (complete remission), and 42 months for one other patient (partial response). All patients had experienced multiple and severe episodes of infections pre-SCT and long-term history of corticosteroid therapy (3-14 years). We conclude that achievement of prolonged, corticosteroid-free remissions is a reality. Judicious selection of patients earlier in disease or in remission, but with a high risk of relapse or further progression, will diminish transplantation-related mortality.
系统性红斑狼疮（SLE）是一种免疫介导的疾病，对免疫系统的抑制或调节有反应。尽管使用了标准剂量的静脉注射环磷酰胺（Cy），但仍经历持续性多器官功能障碍的SLE患者是早期死亡高风险的患者亚群。我们研究了大剂量免疫抑制和自体造血干细胞移植（SCT）治疗此类患者的疗效和毒性。1998年至2003年，6例（均为女性，年龄15 - 29岁）严重难治性SLE患者在我们机构的诊所入组。所有患者病情严重，系统性红斑狼疮疾病活动指数（SLEDAI）为6 - 30，其中2例患有中枢神经系统狼疮，1例患有肺血管炎，3例患有肾炎和肾病综合征。所有患者均登记在欧洲血液和骨髓移植组（EBMT）/欧洲抗风湿病联盟（EULAR）数据库中。先前的免疫抑制包括静脉脉冲Cy、泼尼松龙（标准剂量和脉冲疗法）、口服Cy和硫唑嘌呤，对疾病进展几乎没有影响。自体造血干细胞从骨髓采集（n = 4）或通过Cy和粒细胞集落刺激因子（G - CSF）从外周血动员采集（n = 2）。移植前预处理方案包括BEAM +/- 抗胸腺细胞球蛋白（ATG）（n = 2）、美法仑140 mg/m² + 依托泊苷1600 mg/m²（n = 2）和Cy 200 mg/kg +/- ATG（n = 2）。绝对中性粒细胞计数（ANC）大于0.5×10⁹/L和血小板计数大于50×10⁹/L的中位时间分别为13天和15天。3例患者因移植相关并发症分别在第11天、22天和63天死亡。两名患者的随访时间现在分别为60个月和6个月（完全缓解），另一名患者为42个月（部分缓解）。所有患者在SCT前都经历过多次严重感染发作和长期皮质类固醇治疗史（3 - 14年）。我们得出结论，实现长期无皮质类固醇缓解是现实的。在疾病早期或缓解期但复发或进一步进展风险高的患者中进行明智选择，将降低移植相关死亡率。
