Impact of immunoablation and autologous hematopoietic stem cell transplantation on gray and white matter atrophy in multiple sclerosis

Mult Scler. 2018 Jul;24(8):1055-1066. doi: 10.1177/1352458517715811. Epub 2017 Jun 15.

Abstract

Background: Immunoablation and autologous hematopoietic stem cell transplantation (IA/aHSCT) halts relapses, white matter (WM) lesion formation, and pathological whole-brain (WB) atrophy in multiple sclerosis (MS) patients. Whether the latter was due to effects on gray matter (GM) or WM warranted further exploration.

Objective: To model GM and WM volume changes after IA/aHSCT to further understand the effects seen on WB atrophy.

Methods: GM and WM volume changes were calculated from serial baseline and follow-up magnetic resonance imaging (MRI) ranging from 1.5 to 10.5 years in 19 MS patients treated with IA/aHSCT. A mixed-effects model with two predictors (total busulfan dose and baseline T1-weighted WM lesion volume "T1LV") characterized the time-courses after IA/aHSCT.

Results: Accelerated short-term atrophy of 2.1% and 3.2% occurred in GM and WM, respectively, on average. Both busulfan dose and T1LV were significant predictors of WM atrophy, whereas only busulfan was a significant predictor of GM atrophy. Compared to baseline, a significant reduction in GM atrophy, not WM atrophy, was found. The average rates of long-term GM and WM atrophy were -0.18%/year (standard error (SE): 0.083) and -0.07%/year (SE: 0.14), respectively.

Conclusion: Chemotherapy-related toxicity affected both GM and WM. WM was further affected by focal T1-weighted lesion-related pathologies. Long-term rates of GM and WM atrophy were comparable to those of normal-aging.

Keywords: Multiple sclerosis; atrophy; axonal loss; magnetic resonance imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrophy / pathology
  • Brain / drug effects
  • Brain / pathology*
  • Female
  • Gray Matter / drug effects
  • Gray Matter / pathology*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis / therapy*
  • Transplantation Conditioning / adverse effects
  • White Matter / drug effects
  • White Matter / pathology*
  • Young Adult