Fassas A, Anagnostopoulos A, Kazis A, Kapinas K, Sakellari I, Kimiskidis V, Smias C, Eleftheriadis N, Tsimourtou V
Department of Hematology, The George Papanicolaou General Hospital, Thessaloniki, Greece.
J Clin Immunol. 2000 Jan;20(1):24-30. doi: 10.1023/a:1006686426090.
Based on the good results of experimental transplantation in animal models of multiple sclerosis and of other autoimmune diseases, we have treated 24 patients suffering from chronic progressive multiple sclerosis with high-dose chemotherapy (BEAM regimen) followed by autologous blood stem cell rescue and antithymocyte globulin. Blood stem cells were mobilised with cyclophosphamide at 4g/m2 and G- (or GM-) CSF. In 9 cases, additional CD34+ cell-selection of the graft was performed. Here we update previously published results of this novel treatment, mainly with regard to clinical efficacy, as the median follow-up time has reached 40 months (range, 21-51). Infections were the principal toxicity early after the procedure, with death of a patient from aspergillosis 65 days post stem cell infusion. No serious late events occurred apart from a case of autoimmune thyroiditis that developed 11 months after transplant in a patient who had received a CD34+ cell-depleted graft. Mild and transient neurotoxicity was observed in 10 patients (42%), most probably associated with fever and infections. Eighteen patients (18/23; 78%) responded to the treatment, i.e., they were improved or stabilized, while five patients progressed, of which 4 had primary progressive disease. Of those improved or stabilised (18), 9 patients have maintained stable condition whereas 9 developed relapses or they slowly resumed progression, although their disability scores have not gotten worse than they were before transplantation. The probability of progression-free survival (compared to entry status) at 3 years is 92% for patients with secondary progressive disease and 39% for the primary progressive type. CD34+ cell-selection did not seem to yield better results except for a delay in progression or in relapse after transplantation. These results appear better than those achieved by any other treatment of progressive multiple sclerosis, including beta-interferon, but they need to be confirmed by other open or controlled studies in view of the well-known difficulty of judging objectively the effect of a treatment in patients with this disease.
基于在多发性硬化症及其他自身免疫性疾病动物模型中的实验性移植取得的良好结果，我们对24例慢性进展性多发性硬化症患者进行了大剂量化疗（BEAM方案），随后进行自体血干细胞挽救及抗胸腺细胞球蛋白治疗。使用环磷酰胺4g/m²及G-（或GM-）集落刺激因子动员血干细胞。9例患者对移植物进行了额外的CD34⁺细胞分选。在此，我们更新此前发表的关于这种新疗法的结果，主要涉及临床疗效，因为中位随访时间已达40个月（范围21 - 51个月）。感染是术后早期的主要毒性反应，1例患者在干细胞输注后65天死于曲霉病。除1例接受CD34⁺细胞去除移植物的患者在移植后11个月发生自身免疫性甲状腺炎外未出现严重晚期事件。10例患者（42%）出现轻度和短暂的神经毒性，很可能与发热及感染有关。18例患者（18/23；78%）对治疗有反应，即病情改善或稳定，而5例患者病情进展，其中4例为原发性进展性疾病。在病情改善或稳定的18例患者中，9例病情维持稳定，9例出现复发或缓慢恢复进展，尽管其残疾评分未比移植前恶化。继发进展性疾病患者3年无进展生存概率（与入组时状态相比）为92%，原发性进展性类型为39%。除了移植后进展或复发延迟外，CD34⁺细胞分选似乎未产生更好的结果。这些结果似乎优于包括β-干扰素在内的其他进展性多发性硬化症治疗方法所取得的结果，但鉴于客观判断该疾病患者治疗效果存在众所周知的困难，需要其他开放或对照研究予以证实。
