Early clinical course after hematopoietic stem cell transplantation in children with juvenile metachromatic leukodystrophy

Abstract

Background Long-term outcomes of hematopoietic stem cell transplantation (HSCT) in children with juvenile metachromatic leukodystrophy (MLD) have been investigated systematically, while short-term effects of HSCT on the course of the disease remain to be elucidated. Results In this study, the clinical course was evaluated over the first 24 months following HSCT, conducted at our center in 12 children with juvenile MLD (mean follow-up 6.75 years, range 3–13.5) and compared with 35 non-transplanted children with juvenile MLD. Motor function (GMFM-88 and GMFC-MLD), cognitive function (FSIQ), peripheral neuropathy (tibial nerve conduction velocity), and cerebral changes (MLD-MR severity score) were tested prospectively. Seven children remained neurologically stable over a long period, five exhibited rapid disease progression over the first 12 to 18 months after transplantation. In the latter, time from first gross motor symptoms to loss of independent walking was significantly shorter compared with non-transplanted patients at the same stage of disease (p < 0.02). Positive prognostic factors were good motor function (GMFM = 100%, GMFC-MLD = 0) and a low MR severity score (≤ 17) at the time of HSCT. Conclusions Our results show that if disease progression occurs, this happens early on after HSCT and proceeds faster than in non-transplanted children with juvenile MLD, indicating that HSCT may trigger disease progression.

Allogenic hematopoietic stem cell transplantation in two siblings with adult metachromatic leukodystrophy and a systematic literature review

“…The deterioration was very mild and without clinical symptoms. This is in line with recent description, in which NCV did not change significantly in 12 juvenile MLD patients in up to 5 years after HSCT, regardless of preexisting neuropathy 22 . It is expected that gene therapy approach might be more effective for peripheral neuropathy treatment due to achievement of higher enzyme levels, 23 as might be the case with intravenous enzyme replacement therapy 24 …”

“…Longer observation time is needed to make final conclusions, but during our observation time of 38 months, HSCT has halted the progression of MLD in both siblings, transplanted at symptomatic and presymptomatic disease stages. It has recently been observed that patients who remain stable within the first 12 to 24 months after HSCT are more likely to have a sustained stable course 22 . This supports possible sustained stable disease course in our two cases, in spite of limited observation time so far.…”

Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort

“…It can be used retrospectively, indispensably for data acquisition in rare diseases. It has been used for natural history studies, 7,16,18‐21 and studies evaluating therapy 22‐27 …”

“…It has been used for natural history studies, 7,16,[18][19][20][21] and studies evaluating therapy. [22][23][24][25][26][27] 2 | MATERIAL AND METHODS…”

Caregiver Perspective on The Initial Signs and Symptoms of Metachromatic Leukodystrophy

“…Late Infantile versus Juvenile MLD Kehrer et al (2020) found that all patients with late infantile and early juvenile onset MLD presented with motor symptoms (with or without additional cognitive symptoms). This study of 97 patients highlights that a small subset (3/35, 9%) of late infantile patients will present with both motor and cognitive symptoms, while most do present with motor symptoms only.…”