大剂量免疫抑制和自体造血细胞移植治疗复发性缓解型多发性硬化后脑容量变化。

Brain volume change after high-dose immunosuppression and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis.

机构信息

McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.

出版信息

Mult Scler Relat Disord. 2021 Sep;54:103149. doi: 10.1016/j.msard.2021.103149. Epub 2021 Jul 12.

DOI:10.1016/j.msard.2021.103149

PMID:34284316

Abstract

BACKGROUND

Brain volume loss (BVL) is commonly observed after high-dose immunosuppression and autologous hematopoietic cell transplantation (HDIT/HCT) for treatment of multiple sclerosis (MS). To better understand the mechanisms of underlying BVL associated with this treatment, we characterized the time courses of whole-brain (WB), grey-matter (GM) and white-matter (WM) volume loss in relapsing-remitting MS (RRMS) patients who received BEAM-based HDIT/HCT.

METHODS

We used Jacobian integration to measure MRI-based WB, GM and WM volume changes up to 5 years after transplant in twenty-four RRMS participants who underwent BEAM-based HDIT/HCT. Using a two-piecewise mixed-effects model, we estimated the short-term (baseline to 1 year) and long-term (beyond 1 year) rates of BVL after HDIT/HCT. We also compared the rates based on the presence of gadolinium-enhancing lesions at baseline, and the maintenance of event-free survival during follow-up.

RESULTS

On average, accelerated short-term BVL of -1.37% (SE: 0.21), -0.86% (SE: 0.28) and -2.18% (SE: 0.26) occurred in WB, GM and WM, respectively. Baseline T1-weighted MRI WM lesion volume was a significant predictor in the WB (short-term) and the WM (short-term and long-term). The average rates of BVL after the initial acceleration were -0.22%/y (SE: 0.10), -0.13%/y (SE: 0.11) and -0.36%/y (SE: 0.11) in the WB, GM and WM, respectively. Participants with gadolinium-enhancing lesions at baseline had significantly higher short-term rates of GM (-1.56% vs. -0.27%, p = 0.01) and WB volume loss (-1.94% vs. -0.81%, p = 0.006) at 1 year follow-up as compared to those without gadolinium-enhancing lesions. WM volume loss was not significantly different (-2.59% vs. -1.66%, p = 0.16). Participants who maintained event-free survival had similar rates of BVL compared to those who did not.

CONCLUSIONS

BVL may accelerate for months after HDIT/HCT. However, over the long-term, adequate HDIT/HCT may reduce BVL rates to those similar to normal aging at the WB level.

摘要

背景

大剂量免疫抑制和自体造血细胞移植（HDIT/HCT）治疗多发性硬化症（MS）后，常观察到脑容量损失（BVL）。为了更好地了解与这种治疗相关的潜在 BVL 的机制，我们描述了接受 BEAM 为基础的 HDIT/HCT 的复发缓解型 MS（RRMS）患者的全脑（WB）、灰质（GM）和白质（WM）体积损失的时间过程。

方法

我们使用雅可比积分来测量 24 名接受 BEAM 为基础的 HDIT/HCT 的 RRMS 患者移植后长达 5 年的 MRI 为基础的 WB、GM 和 WM 体积变化。使用两段混合效应模型，我们估计了 HDIT/HCT 后的短期（基线至 1 年）和长期（1 年以上）BVL 率。我们还根据基线时是否存在钆增强病变以及随访期间是否保持无事件生存来比较这些率。

结果

平均而言，WB、GM 和 WM 中的短期加速性 BVL 分别为 -1.37%（SE：0.21）、-0.86%（SE：0.28）和 -2.18%（SE：0.26）。基线 T1 加权 MRI WM 病变体积是 WB（短期）和 WM（短期和长期）的显著预测因子。初始加速后的平均 BVL 率分别为 WB（0.22%/y，SE：0.10）、GM（0.13%/y，SE：0.11）和 WM（0.36%/y，SE：0.11）。与没有钆增强病变的患者相比，基线时存在钆增强病变的患者在 1 年随访时的 GM（-1.56%比-0.27%，p=0.01）和 WB 体积损失（-1.94%比-0.81%，p=0.006）的短期率明显更高。WM 体积损失无明显差异（-2.59%比-1.66%，p=0.16）。与没有发生事件的患者相比，保持无事件生存的患者的 BVL 率相似。