title: Evidence for improved survival in postsymptomatic stem cell-transplanted patients with Krabbe's disease.
abstract: 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.
authors.affiliation: Hunter James Kelly Research Institute, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York. tjlangan@buffalo.edu.|Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York. tjlangan@buffalo.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Langan
authors.affiliation: Hunter James Kelly Research Institute, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York.|Department of Biostatistics, Population Health Observatory, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Barcykowski
authors.affiliation: Department of Biostatistics, Population Health Observatory, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dare
authors.affiliation: Hunter James Kelly Research Institute, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Pannullo
authors.affiliation: Hunter James Kelly Research Institute, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York.|Department of Biostatistics, Population Health Observatory, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York.
authors.forename: Leah
authors.initials: L
authors.lastname: Muscarella
authors.affiliation: Hunter James Kelly Research Institute, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York.|Department of Biostatistics, Population Health Observatory, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Carter
mesh_terms: D017668:Age of Onset; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007965:Leukodystrophy, Globoid Cell / Q000401:mortality* / Q000601:surgery*; D008297:Male; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: early diagnosis; leukodystrophies; neurodegenerative diseases; newborn screening