Krabbe's disease (KD) is a severe neurodegenerative disorder affecting white matter in the brain and peripheral nerves. Transplantation of hematopoietic stem cells (HSCT), although not curative, has been shown to extend survival and alleviate neurodevelopmental symptoms when treatment precedes the onset of symptoms. Existing evidence, although not tested statistically, seems clearly to show that postsymptomatic transplantation does not improve neurodevelopmental outcomes. The impact of postsymptomatic HSCT treatment on survival, however, is an open question. This study uses a KD registry to examine the effect of HSCT on survival of symptomatic KD patients. Sixteen transplanted patients were matched by age of onset to 68 nontransplanted patients. The potential confounding effect of age of onset was, therefore, avoided. To quantify the effect of HSCT over time, we used Cox regression analysis, and we observed a sustained and nearly 2.2-fold risk of death from KD in patients who were not transplanted relative to those who were transplanted (one-tailed P = 0.0365; 95% lower bound = 1.07). The improvement of survival resulting from HSCT did not appear to depend on the age of symptom onset. Thus, these results establish a long-term, quantitative benefit of HSCT even in patients who are already experiencing symptoms. They also provide a benchmark for improved survival that can be used for potential new treatments for KD. © 2016 Wiley Periodicals, Inc.
Keywords: early diagnosis; leukodystrophies; neurodegenerative diseases; newborn screening.
© 2016 Wiley Periodicals, Inc.