Abstract：
BACKGROUND: Biomarkers predictive of disability outcomes in individual multiple sclerosis (MS) patients undergoing autologous haematopoietic stem cell transplantation (AHSCT) are currently lacking. As correlations between spinal cord atrophy and clinical disability in MS were previously described, in this study spinal cord size was investigated in MS patients treated with AHSCT, exploring whether baseline spinal cord volume may predict disability progression after AHSCT.
METHODS: relapsing-remitting (RR-) and secondary-progressive (SP-) MS patients treated with AHSCT (BEAM/ATG regimen) at a single academic centre in Florence, who performed at least two standardized brain magnetic resonance imaging (MRIs) scans (acquired between one-year pre-AHSCT to 5 years after AHSCT) were included. Cervical spinal cord atrophy was estimated as upper cervical spinal cord cross-sectional area (SCCSA). Brain volume loss (BVL) was analysed at the same timepoints.
RESULTS: Eleven (8 RR-; 3 SP-) MS patients were included. Over a median follow-up of 66 (range 37 - 100) months, no relapses nor brain MRI activity were observed; disability progressed in 2 cases (both SP-MS). Baseline SCCSA was associated with EDSS change between pre- and one-year post-AHSCT. Compared to patients who stabilized, patients who progressed after AHSCT tended to have lower SCCSA at C4 level at baseline and year 1 after AHSCT. Longitudinal changes in SCCSA or BVL did not correlate with EDSS change.
CONCLUSIONS: Baseline pre-AHSCT SCCSA, but not its longitudinal changes nor BVL, predicted EDSS change within the two years following AHSCT. SCCSA may represent a biomarker of treatment response and a promising screening tool for assessing patient eligibility for high-impact treatments such as AHSCT.
METHODS: relapsing-remitting (RR-) and secondary-progressive (SP-) MS patients treated with AHSCT (BEAM/ATG regimen) at a single academic centre in Florence, who performed at least two standardized brain magnetic resonance imaging (MRIs) scans (acquired between one-year pre-AHSCT to 5 years after AHSCT) were included. Cervical spinal cord atrophy was estimated as upper cervical spinal cord cross-sectional area (SCCSA). Brain volume loss (BVL) was analysed at the same timepoints.
RESULTS: Eleven (8 RR-; 3 SP-) MS patients were included. Over a median follow-up of 66 (range 37 - 100) months, no relapses nor brain MRI activity were observed; disability progressed in 2 cases (both SP-MS). Baseline SCCSA was associated with EDSS change between pre- and one-year post-AHSCT. Compared to patients who stabilized, patients who progressed after AHSCT tended to have lower SCCSA at C4 level at baseline and year 1 after AHSCT. Longitudinal changes in SCCSA or BVL did not correlate with EDSS change.
CONCLUSIONS: Baseline pre-AHSCT SCCSA, but not its longitudinal changes nor BVL, predicted EDSS change within the two years following AHSCT. SCCSA may represent a biomarker of treatment response and a promising screening tool for assessing patient eligibility for high-impact treatments such as AHSCT.
摘要：
背景：目前缺乏预测接受自体造血干细胞移植（AHSCT）的多发性硬化（MS）患者残疾结局的生物标志物。由于脊髓萎缩和MS临床残疾之间的相关性先前被描述，在这项研究中，研究了接受AHSCT治疗的MS患者的脊髓大小，探讨基线脊髓体积是否可以预测AHSCT后的残疾进展。
方法：在佛罗伦萨的一个学术中心接受AHSCT（BEAM/ATG方案）治疗的复发缓解（RR-）和继发性进展（SP-）MS患者，纳入了至少两次标准化脑磁共振成像（MRI）扫描（在AHSCT前一年至AHSCT后5年之间获得）。颈脊髓萎缩估计为上颈脊髓横截面积（SCCSA）。在相同的时间点分析脑体积损失(BVL)。
结果：包括11例（8例RR-；3例SP-）MS患者。中位随访时间为66个月（范围37-100个月），未观察到复发或脑MRI活动；2例（均为SP-MS）残疾进展。基线SCCSA与AHSCT前后一年的EDSS变化相关。与稳定的患者相比，AHSCT后进展的患者在基线和AHSCT后第1年时的C4水平倾向于降低SCCSA.SCCSA或BVL的纵向变化与EDSS变化无关。
结论：AHSCTSCCSA之前的基线，但不是它的纵向变化也不是BVL，预测AHSCT后两年内EDSS的变化。SCCSA可以代表治疗反应的生物标志物和用于评估患者对高影响治疗如AHSCT的资格的有希望的筛选工具。
方法：在佛罗伦萨的一个学术中心接受AHSCT（BEAM/ATG方案）治疗的复发缓解（RR-）和继发性进展（SP-）MS患者，纳入了至少两次标准化脑磁共振成像（MRI）扫描（在AHSCT前一年至AHSCT后5年之间获得）。颈脊髓萎缩估计为上颈脊髓横截面积（SCCSA）。在相同的时间点分析脑体积损失(BVL)。
结果：包括11例（8例RR-；3例SP-）MS患者。中位随访时间为66个月（范围37-100个月），未观察到复发或脑MRI活动；2例（均为SP-MS）残疾进展。基线SCCSA与AHSCT前后一年的EDSS变化相关。与稳定的患者相比，AHSCT后进展的患者在基线和AHSCT后第1年时的C4水平倾向于降低SCCSA.SCCSA或BVL的纵向变化与EDSS变化无关。
结论：AHSCTSCCSA之前的基线，但不是它的纵向变化也不是BVL，预测AHSCT后两年内EDSS的变化。SCCSA可以代表治疗反应的生物标志物和用于评估患者对高影响治疗如AHSCT的资格的有希望的筛选工具。
