Matthew D. Wright, Michele D. Poe, Anthony DeRenzo, Shilpa Haldal, Maria L. Escolar. Developmental outcomes of cord blood transplantation for Krabbe disease; a 15-year study
Neurology Aug 2017, 10.1212/WNL.0000000000004418; DOI:10.1212/WNL.0000000000004418.
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Background
Hematopoietic stem cell transplantation (HSCT) is the standard of care for infantile-onset Krabbe disease and has been shown to significantly improve neurological outcomes in newborns who are transplanted before symptoms of Krabbe disease are apparent.
Summary
This article summarizes the long-term neurodevelopmental outcomes of 18 children (11 girls and 7 boys) diagnosed with early-infantile Krabbe disease who were transplanted in the first 7 weeks of life. Mean follow-up for these children was 9.5 years ( range 4-15 years). The surviving patients function at a much higher level than untreated children or children with symptoms who underwent HSCT. The long-term results show that early HSCT changes the natural history of Krabbe disease by improving both lifespan and functional abilities.
Results
- The prospective study evaluated 18 patients from December 1999 to October 2015.
- 15 of the 18 patients were identified prenatally/neonatally through family history and 3 patients were identified as a result of newborn screening programs (NBS).
- 13 patients are currently surviving. Three patients died of complications during the peritransplant period, 1 died of a surgical complication unrelated to Krabbe disease 6 years post-transplant and 1 patient died of disease progression 15 years post-transplant.
- Evaluating cognitive function in these infants is challenging because motor difficulties affect test performance. All but one patients received special education services.
- Most patients continue to have a wide range of motor disability, from slightly abnormal gait to severely impaired ambulation. All patients received physical therapy at one time.
- FIne motor skills are generally preserved; however, some patients developed weakness in the trunk area and a tendency to turn their arms, which affects the ends of the fingers and the ability to manipulate objects.
Key Points
- The surviving children function at a much higher level than untreated patients or any of the symptomatic children who underwent HCST.
- The school-aged children continue to learn and improve cognitive skills when given the right support for their motor disabilities.
- Motor disease in treated children varies according to the degree of brain and peripheral nerve involvement at the time of transplantation.
- When considering those patients who responded best, it is evident that treatment with HCST has allowed children to live relatively normal lives up to the early teen years.
- Patients at risk for high or moderate risk for infantile Krabbe disease should be referred to a specialized center for evaluation to achieve the best possible outcomes.