Unrelated umbilical cord blood transplant for juvenile metachromatic leukodystrophy: a 5-year follow-up in three affected siblings

Abstract

Unrelated umbilical cord blood transplantation (UCBT) was used to treat three siblings with juvenile metachromatic leukodystrophy (jMLD). The efficacy of this therapy was measured over a 5-year period with serial neurological examinations, neuroimaging, nerve conduction studies (NCS), and neuropsychological evaluations (NPE). Outcomes were a function of disease stage at time of UCBT with alteration of disease course occurring in the first 2 years after UCBT and then subsequent halting of progression and stabilization of symptoms and disease.

Figure 1

Brain magnetic resonance images in the middle sibling (A, B, C), and youngest sibling (D, E, F, G) before and after UCBT. The middle sibling had moderate white matter changes on initial MRI (A), which showed improvement with re-imaging at two (B) and five years (C) post-transplant. There was associated enlargement of the lateral ventricles, which may represent atrophy of previously affected white matter. The youngest sibling had no initial white matter changes (D); however, 6 months after transplant she had minor WMSAs near the occipital horns of the lateral ventricles (E). These WMSAs resolved within the next 6 months (data not shown) and there has been no significant change in her neuroimaging at two (F) and five years post-transplant. Scoring with a modified Loes scoring system for MLD [21] gave estimated scores for the middle sibling (pre-transplant: 11; two-years post-transplant: 8; and five-years post-transplant: 8) and for the youngest sibling (pre-transplant: 0; two-years post-transplant: 2; and five-years post-transplant: 2). All images are FLAIR sequences and were performed on a 1.5-Tesla machine, except for the five year follow-up studies which were performed with a 3-Tesla machine (this may enhance the previously noted WMSAs, however there was no change in the size of the WMSAs from two to five years post-UBCT).