Multiparametric MRI Analysis of Clinical Outcome after Hematopoietic Stem Cell Transplantation in Juvenile...

Clinical outcomes after hematopoietic stem cell transplantation (HSCT) in juvenile metachromatic leukodystrophy (MLD) are variable. This study evaluated whether multiparametric MRI parameters at the time of HSCT can predict long-term clinical outcomes and assessed their longitudinal evolution over an extended follow-up.

In this retrospective, registry-based cohort study, 15 children with juvenile MLD underwent a comprehensive MRI protocol at HSCT including quantitative demyelination load, DWI, MRS, and volumetric analysis. Patients were followed clinically for a median of 5 years and retrospectively stratified into stabilized, moderately progressive, or severely progressive trajectories based on Gross Motor Function Classification-metachromatic leukodystrophy (GMFC-MLD) and cognitive performance. Baseline imaging metrics and their changes over time were compared across outcome groups.

Higher baseline demyelination load, increased ADC in the posterior limb of the internal capsule, and lower MRS metabolite ratios (NAA/Cr and NAA/Cho) were statistically significantly associated with a severely progressive clinical course. In contrast, baseline MRI severity score and brain volumes at HSCT were not predictive of outcome. Longitudinal analysis demonstrated consistent group differences in visually-assessable MRI parameters, including lesion burden, gray matter volume, total brain volume, and MRI severity score, which were most pronounced in patients with unfavorable clinical trajectories. Diffusion and spectroscopy measures showed region- and parameter-specific longitudinal effects but weaker and less consistent group separation compared with volumetric and lesion-based measures. Notably, baseline MRS metrics allowed retrospective stratification of patients with mild motor impairment (GMFC-MLD = 1) into distinct outcome groups, supporting early prognostic value.

Multiparametric MRI at the time of HSCT provides complementary prognostic and longitudinal information in juvenile MLD. Baseline microstructural and metabolic abnormalities are associated with long-term clinical trajectories, whereas longitudinal disease evolution after HSCT is more consistently captured by volumetric and lesion-based MRI markers. These findings support the use of advanced MRI biomarkers for early risk stratification and subsequent monitoring and warrant further evaluation, including in gene therapy-treated cohorts.