Haematopoietic stem cell transplantation for active systemic lupus erythematosus
Haematopoietic stem cell transplantation for active systemic lupus erythematosus
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DOI：
10.1093/rheumatology/38.8.767
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发表时间：
1999-08-01
期刊：
影响因子：
5.5
通讯作者：
Burt, RK
中科院分区：
文献类型：
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作者：
Traynor, A;Burt, RK
Objective.对于有疾病相关死亡风险的系统性红斑狼疮（SLE）患者，我们已经启动了一项强化免疫抑制和造血干细胞支持方案。入组本研究的第一例患者正处于狼疮发作期，表现为肾炎和肾功能快速下降、不受控制的高血压、免疫介导的血细胞减少和以大量心包积液和腹痛为特征的浆膜炎。抗核抗体（ANA）、抗双链DNA（ds）和补体异常。该患者干细胞移植后1年多，未服用免疫抑制药物。她的血清学检查正常，积液消退，血压正常，肾功能明显改善。本文总结了该患者的临床和血清学过程。用环磷酰胺（2.0 g/m2）和粒细胞集落刺激因子（G-CSF）（10 μ g/kg/天）动员自体造血干细胞（HSC）。使用CD 34阳性免疫选择法体外富集干细胞，并在环磷酰胺（200 mg/kg）和抗胸腺细胞球蛋白（ATG）（90 mg/kg）免疫抑制后回输。分别在第10天和第14天，中性粒细胞绝对计数（ANC）> 500/mu l（0.5 x 10（9）/l）的白色血细胞植入和非输血血小板计数>20 000/mu l（20 x 10（9）/l）的血小板植入。治疗因细胞溶解样效应而变得复杂，并伴有高磷血症、高尿酸血症、正常阴离子间隙代谢性酸中毒和肾功能不全的短暂恶化。结论。这是第一个自体T细胞耗尽造血干细胞移植治疗狼疮活动性耀斑。该患者自发病以来（13年前）首次进入完全的临床和血清学缓解，并在>1年的随访中持续存在。这种缓解的持久性是未知的。
Objective. For patients with systemic lupus erythematosus (SLE) who are at risk of disease-related mortality, we have initiated a protocol of intensive immunosuppression and haematopoietic stem cell support. The first patient enrolled in this study was in the midst of a lupus flare manifest by nephritis and rapidly declining renal function, uncontrolled hypertension, immune-mediated cytopenias, and serositis characterized by a large pericardial effusion and abdominal pain. Antinuclear antibody (ANA), anti-double-stranded (ds) DNA and complement were abnormal. This patient is now more than 1 yr post-stem cell transplant and is taking no immunosuppressive medication. Her serologies are normal, effusions have resolved, blood pressure is normal and renal function is markedly improved. The clinical and serological course of this patient is summarized here.Methods. Autologous haematopoietic stem cells (HSC) were mobilized with cyclophosphamide (2.0 g/m(2)) and granulocyte colony-stimulating factor (G-CSF) (10 mu g/kg/day). Stem cells were enriched ex vivo using CD34-positive immunoselection and reinfused after immunosuppression with cyclophosphamide (200 mg/kg) and antithymocyte globulin (ATG) (90 mg/kg).Results. White blood cell engraftment with an absolute neutrophil count (ANC) of > 500/mu l (0.5 x 10(9)/l) and platelet engraftment with a non-transfused platelet count of >20 000/mu l (20 x 10(9)/l) occurred on day 10 and 14, respectively. Therapy was complicated by a cell lysis like effect with hyperphosphataemia, hyperuricaemia, normal anion gap metabolic acidosis and transient exacerbation of renal insufficiency.Conclusion. This is the first autologous T-cell-depleted haematopoietic stem cell transplantation performed to treat lupus in an active flare. This patient has, for the first time since disease onset (13 yr ago), entered a complete clinical and serological remission which persists at >1 yr of follow-up. The durability of this remission is unknown.