Allogenic hematopoietic stem cell transplantation in two siblings with adult metachromatic leukodystrophy and a systematic literature review
Cecilie Videbæk,
Jette Stokholm,
Henrik Sengeløv,
Lone U. Fjeldborg,
Vibeke Andrée Larsen,
Christian Krarup,
Jørgen E. Nielsen,
Sabine Grønborg
Affiliations
Cecilie Videbæk
Neurogenetics Clinic and Research Lab Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen Copenhagen Denmark
Jette Stokholm
Neurogenetics Clinic and Research Lab Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen Copenhagen Denmark
Henrik Sengeløv
Bone Marrow Transplant Unit Copenhagen, Department of Hematology University of Copenhagen Copenhagen Denmark
Lone U. Fjeldborg
Hjerneskadecenter Virum Den Sociale Virksomhed Denmark
Vibeke Andrée Larsen
Department of Radiology Rigshospitalet, University of Copenhagen Copenhagen Denmark
Christian Krarup
Department of Clinical Neurophysiology Rigshospitalet, University of Copenhagen Copenhagen Denmark
Jørgen E. Nielsen
Neurogenetics Clinic and Research Lab Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen Copenhagen Denmark
Sabine Grønborg
Department of Paediatrics and Adolescent Medicine, Centre for Inherited Metabolic Disease Rigshospitalet, University Hospital Copenhagen Copenhagen Denmark
Abstract Two siblings were diagnosed with adult metachromatic leukodystrophy (MLD) and treated with hematopoietic stem cell transplantation (HSCT). While the older sibling was symptomatic at the time of diagnosis, her younger brother was diagnosed and transplanted at the presymptomatic state. We describe patients' clinical, biochemical, and genetic features, as well as neuropsychological and neurophysiological test results, and brain magnetic resonance imaging from pretransplantation and posttransplantation assessments. Both patients converted to complete donor chimerism and arylsulfatase A levels normalized 3 months posttransplantation. Twelve months posttransplantation, neurological and neuropsychological assessment for both patients showed stabilization, and they remained stable for the 38 months long observation period. To assess the effect of HSCT used as treatment for the rare, adult MLD subtype on survival and stabilization, we performed a systematic literature review and included 7 studies with a total of 26 cases. Of these 26 cases, 6 patients died of HSCT‐related complications and 2 patients had graft rejection. Of the remaining 18 patients, 2 patients improved after HSCT, 13 patients stabilized, and 3 patients progressed, suggesting that HSCT potentially benefits adult MLD patients. Larger studies focusing on this subtype are needed and recommendations on criteria for HSCT in adult MLD need to be evolved.
