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. Click here to view publication
Hematopoietic stem cell transplantation (Hematopoietic stem cell transplantation (HSCT), a type of transplantation using multipotent hematopoietic stem cells typically derived from bone marrow, peripheral blood, or that from umbilical cord b...) 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.
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 Hematopoietic stem cell transplantation (HSCT), a type of transplantation using multipotent hematopoietic stem cells typically derived from bone marrow, peripheral blood, or that from umbilical cord b.... The long-term results show that early Hematopoietic stem cell transplantation (HSCT), a type of transplantation using multipotent hematopoietic stem cells typically derived from bone marrow, peripheral blood, or that from umbilical cord b... changes the natural history of Krabbe disease by improving both lifespan and functional abilities.
- 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.
- 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.