Single-centre prospective clinical and procedural analysis identifying causes of delay to haematopoietic stem cell transplant in MPS I (Hurler syndrome) patients

ABSTRACT

The international standard treatment for mucopolysaccharidosis type I - Hurler syndrome (MPS1H) is haemopoietic stem cell transplant (HSCT) preceded by intravenous enzyme replacement therapy (ERT), with HSCT ideally undertaken before 18 months age to achieve best outcome. The invasive nature and high risk of morbidity and mortality associated with HSCT, in addition to a complex patient cohort, demands an extensive pre-transplant work-up to minimise risks where avoidable. This is achieved by collaboration between transplant and specialist paediatric LD-metabolic services. Transplant may be delayed due to clinical complications pre-transplant, but non-clinical disruptions have also been encountered in practice causing delays from time of diagnosis to transplantation. This work aimed to identify clinical complications and non-clinical disruptions in this process, and to identify areas of improvement for clinical practice, ultimately to achieve timely intervention and optimise clinical outcomes. A single-centre prospective clinical and procedural analysis of 7 MPS1H patients undergoing HSCT between April 2020 - January 2021 was completed. Age at diagnosis (median(range)) was 10 (1.5–25) months. Time from diagnosis to starting ERT (median(range)) was 10 (3–26) days. Time from diagnosis to transplant (median(range)) was 158 (101–189) days, with age at transplant 14 (6.5–30) months. Multiple reasons causing delay were identified. Clinical factors included presence of dilated cardiomyopathy, requirement for adenotonsillectomy to treat obstructive sleep apnoea, Covid-19 infection, vascular device infection, and acute neurosurgical issues including hydrocephalus requiring ventriculoperitoneal shunt and cervical spine stenosis requiring decompression. Non-clinical factors identified included late cancellation of required investigations, missed clinic appointments, and issues with accessing HSCT donors due to UK/European political situation and Covid-19 restrictions. Clear communication between teams was found to be a key identifying factor in ensuring timely completion of the pre-HSCT.