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

Hyunwoo Lee*, Kunio Nakamura, Sridar Narayanan, Robert A. Brown, Richard A. Nash, Linda M. Griffith, Kaitlyn C. Steinmiller, Steven M. Devine, George J. Hutton, Uday Popat, Michael K. Racke, George E. Georges, James D. Bowen, Douglas L. Arnold

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number103149
JournalMultiple Sclerosis and Related Disorders
Volume54
DOIs
StatePublished - Sep 2021

Keywords

  • Atrophy
  • Chemotherapy
  • Hematopoietic stem cell transplantation
  • Magnetic resonance imaging
  • Multiple sclerosis
  • Relapsing-remitting

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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