Traynor A, Burt R K
Northwestern University School of Medicine, Division of Hematology Oncology and the Robert H. Lurie Cancer Center, Chicago, IL 60611, USA.
Rheumatology (Oxford). 1999 Aug;38(8):767-72. doi: 10.1093/rheumatology/38.8.767.
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.
Autologous haematopoietic stem cells (HSC) were mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (G-CSF) (10 microg/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).
White blood cell engraftment with an absolute neutrophil count (ANC) of >500/microl (0.5 x 10(9)/l) and platelet engraftment with a non-transfused platelet count of >20000/microl (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.
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 discase 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.
对于有疾病相关死亡风险的系统性红斑狼疮（SLE）患者，我们启动了一项强化免疫抑制和造血干细胞支持方案。本研究纳入的首例患者正处于狼疮活动期，表现为肾炎、肾功能迅速下降、高血压控制不佳、免疫介导的血细胞减少以及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（ds）DNA和补体均异常。该患者目前已接受干细胞移植超过1年，未服用任何免疫抑制药物。她的血清学指标正常，积液已消退，血压正常，肾功能明显改善。现将该患者的临床和血清学病程总结如下。
采用环磷酰胺（2.0 g/m²）和粒细胞集落刺激因子（G-CSF）（10 μg/kg/天）动员自体造血干细胞（HSC）。使用CD34阳性免疫选择法在体外富集干细胞，并在给予环磷酰胺（200 mg/kg）和抗胸腺细胞球蛋白（ATG）（90 mg/kg）进行免疫抑制后回输。
白细胞于第10天植入，绝对中性粒细胞计数（ANC）>500/μl（0.5×10⁹/l），血小板于第14天植入，未输注血小板计数>20000/μl（20×10⁹/l）。治疗过程中出现了类似细胞溶解的效应，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加重。
这是首例为治疗狼疮活动期而进行的自体T细胞清除造血干细胞移植。该患者自疾病发作（13年前）以来首次进入完全临床和血清学缓解期，随访超过1年仍持续缓解。这种缓解的持久性尚不清楚。
