kIsabel C. Yoon, Nicholas A. Bascou, Michele D. Poe, Paul Szabolcs, Maria L. Long-term neurodevelopmental outcomes of hematopoietic stem cell transplantation for late-infantile Krabbe disease.Blood 2021; 137 (13): 1719–1730
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Although new therapies are on the horizon for patients with Krabbe disease, currently hematopoietic stem cell transplantation (HSCT) is the only effective treatment. Given the increasing number of states that are adding Krabbe disease to the newborn screening (NBS) panels, there is a need for studies investigating the outcomes of HSCT in patients with late-onset Krabbe disease. The purpose of this study was to describe the long-term transplantation outcomes of children with Krabbe disease who have onset between 6 and 36 months of age. This study is important to the Krabbe community as it supports the benefits of HCST, as well as supports a reclassification of late-infantile Krabbe disease to symptom onset at 12-36 months of age.
- In this prospective, longitudinal study, patients were evaluated at a single site according to a standardized protocol.
- This study confirmed that those patients that didn’t have symptoms (asymptomatic) at the time of transplant benefited the most and had normal to near-normal development in all domains but with some gross motor delays.
- Among symptomatic patients with Krabbe disease, those with disease onset at >12 months of age had better cognitive outcomes than untreated patients.
- Those with disease onset at ≤12 months were comparable to untreated patients.
- For those patients with late-infantile onset (19 patients in total), HSCT prolonged the lifespan and improved the functional abilities of these patients, particularly those who underwent transplantation before onset of symptoms.
- Compared with untreated patients, late-onset, asymptomatic transplant recipients had a higher probability of living longer and had improved cognitive and language function. Gross and fine motor development were most affected, with variable results.
- Traditionally, early-infantile Krabbe disease was thought to have onset from 0 to 6 months and late-infantile from 6 to 36 months. However, Bascou and colleagues found that patients with onset from 6 to 12 months had a disease presentation resembling that observed in early-infantile patients. Thus, early infantile was recently reclassified as symptom onset from 0 to 12 months and late-infantile from 12 to 36 months.
HSCT significantly alters the natural course of late-infantile Krabbe disease by improving lifespan and neurological outcomes. To the author’s knowledge, this is the first study to exclusively and longitudinally assess neurodevelopment after transplantation of late-infantile patients with Krabbe disease, by using neurophysiologic, neuroradiologic, and functional outcomes. Those patients who were asymptomatic at the time of HSCT experienced normal to near-normal development in all developmental domains. Those with disease onset at >12 months of age had better outcomes than onset ≤12 months, supporting a reclassification of late-infantile Krabbe disease as occurring at 12 to 36 months of age instead of the traditional 6 to 36 months.