Patients asymptomatic at the time of HSCT experienced normal to near-normal development in all developmental domains.
Patients with disease onset > 12 months had better outcomes than onset <= 12 months, supporting a reclassification of late-infantile Krabbe.
Krabbe disease is a rare neurodegenerative disorder caused by a deficiency in galactocerebrosidase. The only effective treatment is hematopoietic stem cell transplantation (HSCT). Approximately 85% of Krabbe cases are the infantile subtypes, among which ~20% are late-infantile. Prior studies demonstrated that HSCT is effective for early-infantile patients (0 - 6 months of age) transplanted while asymptomatic, compared to those transplanted while symptomatic. However, no studies evaluated the efficacy of HSCT for late-infantile patients (6 - 36 months). In this prospective, longitudinal study, patients were evaluated at a single site following a standardized protocol. Survival analysis was performed using the Kaplan-Meier method. Differences between groups were estimated using Mixed Regression models to account for within person repeated measures. Nineteen late-infantile patients underwent HSCT (1997 - 2020). Compared to untreated patients, transplanted patients had a longer survival probability and improved cognitive and language function. Gross and fine motor development were most affected with variable results. Asymptomatic patients benefitted the most from transplantation with normal to near-normal development in all domains and some gross motor delays. Among symptomatic patients, those with disease onset > 12 months of age had better cognitive outcomes than untreated patients. Those with disease onset £ 12 months were comparable to untreated patients. We found that HSCT prolongs the lifespan and improves the functional abilities of late-infantile Krabbe patients, particularly for those transplanted before symptom onset. In addition, our findings support prior literature that reclassifies late-infantile Krabbe disease to be symptom onset 12 to 36 months of age.