Remission of severe myasthenia gravis after autologous stem cell transplantation.
Remission of severe myasthenia gravis after autologous stem cell transplantation.
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DOI：
10.1002/acn3.51898
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发表时间：
2023-11
影响因子：
5.3
通讯作者：
Georges, George E.
中科院分区：
文献类型：
--
作者：
Schlatter, Monica I.;Yandamuri, Soumya S.;O'Connor, Kevin C.;Nowak, Richard J.;Pham, Minh C.;Obaid, Abeer H.;Redman, Callee;Provost, Marie;Mcsweeney, Peter A.;Pearlman, Michael L.;Tees, Michael T.;Bowen, James D.;Nash, Richard A.;Georges, George E.
重症肌无力(MG)是一种自身抗体介导的神经肌肉接头疾病，涉及运动终板上的乙酰胆碱受体。对1例难治性重症肌无力患者进行大剂量化疗(HDIT)和自体造血细胞移植(HCT)的安全性和反应性评价。作为HDIT/HCT治疗难治性自身免疫性神经疾病患者的试点研究的一部分，一名患有严重难治性MG的患者接受了治疗。在用利妥昔单抗、泼尼松和G-CSF动员造血干细胞后，患者接受了由卡莫司汀、依托泊苷、阿糖胞苷、马法兰和兔抗胸腺细胞球蛋白组成的HDIT，随后进行了自体红细胞移植。观察治疗前后抗乙酰胆碱受体自身抗体的变化。这位患者在进行胸腺移植/红细胞移植前14年 被诊断为乙酰胆碱受体抗体阳性MG，并未行胸腺切除术、治疗性血浆置换和多种免疫调节剂治疗。重症肌无力美国基金会(MGFA)临床分级在HDIT/HCT前为IVb。她对HDIT/HCT耐受性良好，在治疗后几天内临床症状开始改善。术后1年和2年 ，患者仍无症状。HDIT/HCT后，与AChR结合的自身抗体持续存在，免疫细胞亚型的相对频率发生变化。HDIT/HCT在1例重症难治性MG患者中诱导疾病活动性完全缓解。这一反应可能表明细胞介导的病因学可能是难治性MG病例的一个重要因素。有必要进行二期临床试验，以确定HDIT/HCT是否能有效治疗重症难治性MG，并进一步了解疾病的发病机制。
Myasthenia gravis (MG) is an autoantibody‐mediated neuromuscular junction disorder involving the acetylcholine receptors on the motor endplate. The safety and response to high‐dose chemotherapy (HDIT) and autologous hematopoietic cell transplantation (HCT) were assessed in a patient with severe refractory MG. As part of a pilot study of HDIT/HCT for patients with treatment‐resistant autoimmune neurological disorders, a patient with severe refractory MG underwent treatment. After mobilization of hematopoietic stem cells with rituximab, prednisone, and G‐CSF, the patient had HDIT consisting of carmustine, etoposide, cytarabine, melphalan, and rabbit antithymocyte globulin, followed by autologous HCT. The effect of treatment on the autoantibody to the acetylcholine receptor (AChR) was assessed. The patient had been diagnosed with AChR antibody‐positive MG 14 years before HDIT/HCT and had failed thymectomy, therapeutic plasma exchange, and multiple immunomodulatory agents. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was IVb before HDIT/HCT. She tolerated HDIT/HCT well and started to improve clinically within days of treatment. At both 1 and 2 years after HDIT/HCT, patients remained symptom‐free. After HDIT/HCT, AChR‐binding autoantibodies persisted, and the relative frequency of immune cell subtypes shifted. HDIT/HCT induced a complete response of disease activity in a patient with severe refractory MG. This response may suggest that a cell‐mediated etiology may be a significant contributing factor in refractory MG cases. A phase 2 clinical trial is warranted to establish if HDIT/HCT can be an effective therapy for severe refractory MG and to gain a further understanding of disease pathogenesis.
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