Efficacy and safety of haemopoietic stem cell transplant (HSCT) for mucopolysaccharidosis type I-Hurler syndrome (MPS-IH): a systematic review

Background Mucopolysaccharidosis type I-Hurler’s (MPS-IH) is the most severe form of MPS-I, with onset in infancy, followed by rapid neurodegeneration, and death typically within the first decade in untreated patients. A previous systematic review (SR) concluded that treatment with allogeneic haematopoietic stem-cell transplant (allo-HSCT) offers a clear survival and neurocognitive advantage, but does not prevent residual somatic disease. That review was published 15 years ago, which implies a need for a new SR to capture long-term efficacy, as well as safety outcomes reported since. Methods We conducted a SR following guidelines of the Cochrane Collaboration and the Centre for Reviews and Dissemination. The search strategy had no date limits and was applied to multiple databases including MEDLINE and EMBASE. Searches were completed on 17.12.24. Reference checking ensured inclusion of all papers. All studies of allo-HSCT in MPS-IH were included if there were any efficacy outcomes with at least 5-years of follow-up, or any safety outcomes. Results Thirty-five studies were included, none of which were comparative, 28 were retrospective and three included enzyme replacement therapy. Twenty-seven reported > 5-year efficacy, which showed survival was at least 80% in many studies (median follow-up between 3.8 and 9 years), including up to 62% at 10 years in one study, and 73.7% at 20 years in another. Neurocognitive and ambulatory preservation was observed in some patients, but in others there was progressive decline. Skeletal disease, poor ophthalmological outcomes with corneal opacity, cardiovascular disease, particularly affecting the heart valves, and pulmonary disease were also common. Nineteen studies reported safety, showing that graft versus host disease and pulmonary infections were common. Conclusion Allo-HSCT appears to be an effective intervention for MPS-IH that can extend survival and preserve long-term neurological and physical function, particularly when administered early. However, although it remains the standard of care in modifying the disease course, skeletal, cardiovascular and sensory deficits often persist. The procedure also carries measurable risks, particularly related to mortality, GvHD and infection. Consequently, continued research and innovation are essential to improve long-term outcomes and quality of life for individuals with MPS‑IH.