Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy.
Abstract
Metachromatic leukodystrophy (MLD) is an inherited demyelinating disease that causes
progressive neurologic deterioration, leading to severe motor disability, developmental
regression, seizures, blindness, deafness, and death. The disease presents as a late-infantile,
juvenile, or adult form. Hematopoietic stem cell transplantation has been shown to
slow disease progression. The purpose of this longitudinal study was to evaluate long-term
treatment outcomes after unrelated donor umbilical cord blood (UCB) transplantation
in pediatric patients according to disease burden and age at onset (ie, late-infantile
versus juvenile). Engraftment, survival, treatment-related toxicity, graft-versus-host
disease, neurophysiologic measures, and neurodevelopmental function were assessed.
To evaluate whether signal intensity abnormalities on magnetic resonance imaging (ie,
modified Loes scores) predict post-transplant cognitive and gross motor development,
a general linear mixed model was fit to the data. Twenty-seven patients underwent
transplantation after myeloablative chemotherapy; 24 patients engrafted after the
initial transplantation. Seven patients died of infection, regimen-related toxicity,
or disease progression. Twenty patients (6 with late-infantile onset and 14 with juvenile
onset) were followed for a median of 5.1 years (range, 2.4 to 14.7). We found that
patients with motor function symptoms at the time of transplant did not improve after
transplantation. Brainstem auditory evoked responses, visual evoked potentials, electroencephalogram,
and/or peripheral nerve conduction velocities stabilized or improved in juvenile patients
but continued to worsen in most patients with the late-infantile presentation. Pretransplant
modified Loes scores were highly correlated with developmental outcomes and predictive
of cognitive and motor function. Children who were asymptomatic at the time of transplantation
benefited most from the procedure. Children with juvenile onset and minimal symptoms
showed stabilization or deterioration of motor skills but maintained cognitive skills.
Overall, children with juvenile onset had better outcomes than those with late-infantile
onset. As in other leukodystrophies, early intervention correlated with optimal outcomes.
We conclude that UCB transplantation benefits children with presymptomatic late-infantile
MLD or minimally symptomatic juvenile MLD.
Type
Journal articleSubject
HumansLeukodystrophy, Metachromatic
Graft vs Host Disease
Disease Progression
Myeloablative Agonists
Magnetic Resonance Imaging
Electroencephalography
Treatment Outcome
Cord Blood Stem Cell Transplantation
Survival Analysis
Longitudinal Studies
Motor Skills
Age of Onset
Neural Conduction
Adolescent
Child
Child, Preschool
Infant
Female
Male
Unrelated Donors
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https://hdl.handle.net/10161/24689Published Version (Please cite this version)
10.1016/j.bbmt.2013.01.010Publication Info
Martin, Holly R; Poe, Michele D; Provenzale, James M; Kurtzberg, Joanne; Mendizabal,
Adam; & Escolar, Maria L (2013). Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic
leukodystrophy. Biology of blood and marrow transplantation : journal of the American Society for
Blood and Marrow Transplantation, 19(4). pp. 616-624. 10.1016/j.bbmt.2013.01.010. Retrieved from https://hdl.handle.net/10161/24689.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Joanne Kurtzberg
Jerome S. Harris Distinguished Professor of Pediatrics
Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology,
pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation,
and novel applications of cord blood and birthing tissues in the emerging fields of
cellular therapies and regenerative medicine. Dr. Kurtzberg serves as the Director
of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant
and Cellular Therapy Program, Director of the Carolina
James Michael Provenzale
Professor of Radiology
I have the following major research areas:I. Diffusion tensor imaging (an MR technique
that measures rate and direction of microscopic water motion) to examine white matter
pathways in the brain. This technique is used by many investigators in an attempt
to understand white matter microstructure. My recent work has centered on the histological
correlation of DTI metrics. In addition, because DTI metrics can vary substantially
within a single scanner at multiple time points as well as be
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