Mariottini Alice, Marchi Leonardo, Innocenti Chiara, Di Cristinzi Maria, Pasca Matteo, Filippini Stefano, Barilaro Alessandro, Mechi Claudia, Fani Arianna, Mazzanti Benedetta, Biagioli Tiziana, Materozzi Francesca, Saccardi Riccardo, Massacesi Luca, Repice Anna Maria
Department of Neurosciences, Drug and Child Health, University of Florence, Florence, Italy.
Department of Neurology 2 and Tuscan Region Multiple Sclerosis Referral Centre, Careggi University Hospital, Florence, Italy.
Front Neurol. 2022 Feb 24;13:820256. doi: 10.3389/fneur.2022.820256. eCollection 2022.
Autologous haematopoietic stem cell transplantation (AHSCT) is highly effective in reducing new inflammatory activity in aggressive multiple sclerosis (MS). A remarkable decrease of serum neurofilament light chains (sNfL) concentration, a marker of axonal damage, was reported in MS following high-intensity regimen AHSCT, but hints for potential neurotoxicity had emerged. sNfL and brain atrophy were therefore analysed in a cohort of patients with aggressive MS treated with intermediate-intensity AHSCT, exploring whether sNfL might be a reliable marker of disability progression independent from new inflammation (i.e. relapses and/or new/gadolinium-enhancing MRI focal lesions).
sNfL concentrations were measured using SIMOA methodology in peripheral blood from relapsing-remitting (RR-) or secondary-progressive (SP-) MS patients undergoing AHSCT (MS AHSCT), collected before transplant and at months 6 and 24 following the procedure. sNfL measured at a single timepoint in SP-MS patients not treated with AHSCT without recent inflammatory activity (SP-MS CTRL) and healthy subjects (HD) were used as controls. The rate of brain volume loss (AR-BVL) was also evaluated by MRI in MS AHSCT cases.
Thirty-eight MS AHSCT (28 RR-MS; 10 SP-MS), 22 SP-MS CTRL and 19 HD were included. Baseline median sNfL concentrations were remarkably higher in the MS AHSCT than in the SP-MS CTRL and HD groups ( = 0.005 and <0.0001, respectively), and levels correlated with recent inflammatory activity. After a marginal (not significant) median increase observed at month 6, at month 24 following AHSCT sNfL concentrations decreased compared to baseline by median 42.8 pg/mL (range 2.4-217.3; = 0.039), reducing by at least 50% in 13 cases, and did not differ from SP-MS CTRL ( = 0.110) but were still higher than in HD ( < 0.0001). Post-AHSCT AR-BVL normalised in 55% of RR-MS and in 30% of SP-MS. The effectiveness and safety of AHSCT were aligned with the literature.
sNfL concentrations correlated with recent inflammatory activity and were massively and persistently reduced by intermediate-intensity AHSCT. Association with response to treatment assessed by clinical or MRI outcomes was not observed, suggesting a good sensitivity of sNfL for recent inflammatory activity but low sensitivity in detecting ongoing axonal damage independent from new focal inflammation.
自体造血干细胞移植（AHSCT）在降低侵袭性多发性硬化症（MS）的新炎症活动方面非常有效。据报道，在接受高强度方案AHSCT的MS患者中，轴突损伤标志物血清神经丝轻链（sNfL）浓度显著降低，但已出现潜在神经毒性的迹象。因此，在一组接受中等强度AHSCT治疗的侵袭性MS患者中分析了sNfL和脑萎缩情况，探讨sNfL是否可能是独立于新炎症（即复发和/或新的/钆增强MRI局灶性病变）的残疾进展的可靠标志物。
使用SIMOA方法测量接受AHSCT（MS AHSCT）的复发缓解型（RR-）或继发进展型（SP-）MS患者外周血中的sNfL浓度，在移植前以及术后6个月和24个月采集样本。在未接受AHSCT且近期无炎症活动的SP-MS患者（SP-MS CTRL）和健康受试者（HD）中单次测量的sNfL用作对照。还通过MRI评估了MS AHSCT病例的脑体积损失率（AR-BVL）。
纳入了38例MS AHSCT患者（28例RR-MS；10例SP-MS）、22例SP-MS CTRL和19例HD。MS AHSCT组的基线sNfL浓度中位数显著高于SP-MS CTRL组和HD组（分别为 = 0.005和<0.0001），且水平与近期炎症活动相关。在术后6个月观察到中位数有轻微（不显著）升高后，AHSCT术后24个月时，sNfL浓度与基线相比中位数降低了42.8 pg/mL（范围2.4 - 217.3； = 0.039），13例患者降低了至少50%，与SP-MS CTRL组无差异（ = 0.110），但仍高于HD组（<0.0001）。AHSCT术后，55%的RR-MS患者和30%的SP-MS患者的AR-BVL恢复正常。AHSCT的有效性和安全性与文献一致。
sNfL浓度与近期炎症活动相关，中等强度AHSCT可使其大幅且持续降低。未观察到与通过临床或MRI结果评估的治疗反应之间的关联，这表明sNfL对近期炎症活动具有良好的敏感性，但在检测独立于新局灶性炎症的持续性轴突损伤方面敏感性较低。
