Carreras Enric, Saiz Albert, Marín Pedro, Martínez Carmen, Rovira Montserrat, Villamor Neus, Aymerich Marta, Lozano Miquel, Fernández-Avilés Francesc, Urbano-Izpizua Alvaro, Montserrat Emili, Graus Francesc
BMT Unit, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain.
Haematologica. 2003 Mar;88(3):306-14.
Autologous stem cell transplantation (ASCT) is currently being evaluated as a therapy for patients with multiple sclerosis (MS). We report the results of a phase II trial to evaluate feasibility and toxicity of CD34+ selected ASCT (CD34+/ASCT) and treatment results at one year of follow-up.
Patients with advanced secondary progressive (SP) or relapsing-remitting (RR) MS and confirmed worsening of the extended disability status scale (EDSS) in the previous year despite interferon or other immunotherapies were included. Peripheral blood stem cells were obtained by leukaphereses after mobilization with cyclophosphamide (Cy) and granulocyte colony-stimulating factor (G-CSF). CD34+ selection was performed by means of an Isolex 300 or CliniMACS device. BCNU, Cy and antithymocyte globulin (ATG) were administered as conditioning regimen.
Fifteen patients (9 SPMS and 6 RRMS) with a median EDSS of 6.0 (4.5-6.5) and a median of 3 (1-7) relapses in the previous year were included. Mobilization was unsuccessful in one patient. During mobilization, one patient had a transient neurologic deterioration. The main complication during ASCT were engraftment syndrome, which developed in three patients, CMV reactivation in one, and neurologic deterioration in two patients coinciding with high-fever related to ATG. Hematologic recovery was fast and complete in all cases. At 12 months, the EDSS had improved in three patients, worsened in two and remained stable in nine. Despite withdrawal of all immunosuppressive therapy only two patients had relapses. Magnetic resonance imaging showed disappearance of enhanced T1 lesions but oligoclonal bands persisted in the cerebrospinal fluid of all evaluated cases.
CD34+/ASCT using BCNU, Cy and ATG as conditioning regimen has an acceptable toxicity and clearly reduces the progression of MS. Further follow-up is necessary to establish the real impact of this procedure on the long-term evolution of the disease.
自体干细胞移植（ASCT）目前正作为一种治疗多发性硬化症（MS）患者的方法进行评估。我们报告了一项II期试验的结果，以评估CD34 +选择的ASCT（CD34 + / ASCT）的可行性和毒性以及一年随访时的治疗结果。
纳入患有晚期继发进展型（SP）或复发缓解型（RR）MS且尽管接受了干扰素或其他免疫疗法但在前一年扩展残疾状态量表（EDSS）仍证实恶化的患者。用环磷酰胺（Cy）和粒细胞集落刺激因子（G - CSF）动员后，通过白细胞分离术获取外周血干细胞。通过Isolex 300或CliniMACS装置进行CD34 +选择。以卡莫司汀（BCNU）、Cy和抗胸腺细胞球蛋白（ATG）作为预处理方案。
纳入了15例患者（9例继发进展型MS和6例复发缓解型MS），EDSS中位数为6.0（4.5 - 6.5），前一年复发中位数为3次（1 - 7次）。1例患者动员失败。动员期间，1例患者出现短暂性神经功能恶化。ASCT期间的主要并发症为植入综合征，3例患者发生，1例患者出现巨细胞病毒（CMV）重新激活，2例患者出现神经功能恶化且与ATG相关的高热同时发生。所有病例血液学恢复迅速且完全。12个月时，3例患者EDSS改善，2例患者恶化，9例患者保持稳定。尽管停用了所有免疫抑制治疗，但仅2例患者复发。磁共振成像显示增强T1病变消失，但所有评估病例的脑脊液中寡克隆带持续存在。
以BCNU、Cy和ATG作为预处理方案的CD +34 / ASCT具有可接受的毒性，且明显降低了MS的进展。需要进一步随访以确定该程序对疾病长期演变的实际影响。
