Boffa Giacomo, Massacesi Luca, Inglese Matilde, Mariottini Alice, Capobianco Marco, Moiola Lucia, Amato Maria Pia, Cottone Salvatore, Gualandi Francesca, De Gobbi Marco, Greco Raffaella, Scimè Rosanna, Frau Jessica, Zimatore Giovanni Bosco, Bertolotto Antonio, Comi Giancarlo, Uccelli Antonio, Signori Alessio, Angelucci Emanuele, Innocenti Chiara, Ciceri Fabio, Repice Anna Maria, Sormani Maria Pia, Saccardi Riccardo, Mancardi Gianluigi
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale "F. Miulli," Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Neurology. 2021 Feb 22;96(8):e1215-e1226. doi: 10.1212/WNL.0000000000011461.
To determine whether autologous hematopoietic stem cell transplantation (aHSCT) is able to induce durable disease remission in people with multiple sclerosis (MS), we analyzed the long-term outcomes after transplantation in a large cohort of patients with MS.
To be included, a minimum dataset (consisting of age, MS phenotype, Expanded Disability Status Scale [EDSS] score at baseline, information on transplantation technology, and at least 1 follow-up visit after transplantation) was required.
Two hundred ten patients were included (relapsing-remitting [RR] MS 122 [58%]). Median baseline EDSS score was 6 (1-9); mean follow-up was 6.2 (±5.0) years. Among patients with RRMS, disability worsening-free survival (95% confidence interval [CI]) was 85.5% (76.9%-94.1%) at 5 years and 71.3% (57.8%-84.8%) at 10 years. In patients with progressive MS, disability worsening-free survival was 71.0% (59.4%-82.6%) and 57.2% (41.8%-72.7%) at 5 and 10 years, respectively. In patients with RRMS, EDSS significantly reduced after aHSCT ( = 0.001; mean EDSS change per year -0.09 [95% CI -0.15% to -0.04%]). In patients with RRMS, the use of the BCNU+Etoposide+Ara-C+Melphalan (BEAM) + anti-thymocyte globulin (ATG) conditioning protocol was independently associated with a reduced risk of no evidence of disease activity 3 failure (hazard ratio 0.27 [95% CI 0.14-0.50], < 0.001). Three patients died within 100 days from aHSCT (1.4%); no deaths occurred in patients transplanted after 2007.
aHSCT prevents disability worsening in the majority of patients and induces durable improvement in disability in patients with RRMS. The BEAM + ATG conditioning protocol is associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity.
This study provides Class IV evidence that for people with MS, aHSCT induces durable disease remission in most patients.
为了确定自体造血干细胞移植（aHSCT）是否能够诱导多发性硬化症（MS）患者实现持久的疾病缓解，我们分析了一大群MS患者移植后的长期结局。
纳入标准要求有一个最小数据集（包括年龄、MS表型、基线时的扩展残疾状态量表[EDSS]评分、移植技术信息以及移植后至少1次随访）。
纳入210例患者（复发缓解型[RR]MS 122例[58%]）。基线EDSS评分中位数为6（1 - 9）；平均随访时间为6.2（±5.0）年。在RRMS患者中，5年时无残疾恶化生存率（95%置信区间[CI]）为85.5%（76.9% - 94.1%），10年时为71.3%（57.8% - 84.8%）。在进展型MS患者中，5年和10年时无残疾恶化生存率分别为71.0%（59.4% - 82.6%）和57.2%（41.8% - 72.7%）。在RRMS患者中，aHSCT后EDSS显著降低（P = 0.001；每年平均EDSS变化为 - 0.09[95%CI - 0.15%至 - 0.04%]）。在RRMS患者中，使用卡莫司汀+依托泊苷+阿糖胞苷+美法仑（BEAM）+抗胸腺细胞球蛋白（ATG）预处理方案与无疾病活动证据3失败风险降低独立相关（风险比0.27[95%CI 0.14 - 0.50]，P < 0.001）。3例患者在aHSCT后100天内死亡（1.4%）；2007年后移植的患者未发生死亡。
aHSCT可防止大多数患者的残疾恶化，并诱导RRMS患者的残疾状况持久改善。BEAM + ATG预处理方案与更显著地抑制临床复发和MRI炎症活动相关。
本研究提供了IV类证据，即对于MS患者，aHSCT可使大多数患者实现持久的疾病缓解。
