Allogeneic haematopoietic stem cell transplantation in late-onset metachromatic leukodystrophy.
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Schoenmakers Daphne H, Datema Mareen R, Beerepoot Shanice, Asbreuk Marije A B C, Bergner Caroline G, Awißus Carolin, Bley Annette, Sigel Helen, Bredow Janna, Calbi Valeria, Fumagalli Francesca, Inverso Emilia, Eklund Erik A, Grønborg Sabine W, Grol Wietske H M, Videbæk Cecilie, Kehrer Christiane, van der Knaap Marjo S, Schnermann Nick, Rosewich Hendrik, Lang Peter, van Hasselt Peter M, Lindemans Caroline A, de Witte Moniek, Langeveld Mirjam, Schöls Ludger, Boelens Jaap Jan, Vieira Päivi, Uusimaa Johanna, Mochel Fanny, Sevin Caroline, Hollak Carla E M, Groeschel Samuel, Wolf Nicole I
Аннотация
Metachromatic leukodystrophy (MLD) is a progressive neurometabolic disease which can be treated with hematopoietic stem cell transplantation (HSCT). With emerging therapies like gene therapy, understanding the effectiveness of HSCT in late-onset forms has become increasingly important. Late-onset forms are rare, and the limited evidence on eligibility and outcomes complicates treatment decisions. The aim was to compare the long-term outcomes of the largest European cohort of HSCT-treated and untreated late-juvenile and adult MLD patients. In this observational multi-center registry-based study, retrospective and prospective data from the MLD initiative registry were used. Late-onset patients with a confirmed diagnosis from nine European centers were included. We analysed clinical and patient-reported outcomes. Patients were grouped by symptom status at diagnosis, and we performed visual outcome assessment and regression analysis. Fifteen pre-symptomatic HSCT-treated patients were compared with 37 early or advanced symptomatic HSCT-treated, and 79 untreated late-onset MLD patients. Patients were followed for up to 25 years after diagnosis, with median follow-ups of 14.5 (5.1-17.9), 5.6 (2.8-12.5) and 9.0 (3.3-17.1) years and median ages at follow-up of 30.0 (23.6-35.0), 23.5 (18.0-30.8), and 27.8 (17.7-40.0) for pre-symptomatic HSCT, symptomatic HSCT, and untreated patients, respectively. Advanced disease stage (ADS) was observed in 4/15 (27%) of pre-symptomatic HSCT, 29/37 (78%) symptomatic HSCT, and 57/79 (72%) of untreated patients (p=0.004). HSCT appears to delay ADS (HR 1.49 95%CI 0.96-2.30) and improves quality-of-life and daily life functioning measures. HSCT has a positive effect on the course of the disease, especially in pre-symptomatic patients, but cannot always prevent the progression of symptoms. Quality-of-life improves across all stages of the disease, with pre-symptomatic treatment yielding the greatest benefits. These findings emphasize the importance of early diagnosis and intervention. This study may inform treatment decisions and provides an evidence base for future comparison with innovative therapies.