title: Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease.
abstract: BACKGROUND
  Infantile Krabbe's disease produces progressive neurologic deterioration and death in early childhood. We hypothesized that transplantation of umbilical-cord blood from unrelated donors before the development of symptoms would favorably alter the natural history of the disease among newborns in whom the disease was diagnosed because of a family history. We compared the outcomes among these newborns with the outcomes among infants who underwent transplantation after the development of symptoms and with the outcomes in an untreated cohort of affected children.
  
  
  METHODS
  Eleven asymptomatic newborns (age range, 12 to 44 days) and 14 symptomatic infants (age range, 142 to 352 days) with infantile Krabbe's disease underwent transplantation of umbilical-cord blood from unrelated donors after myeloablative chemotherapy. Engraftment, survival, and neurodevelopmental function were evaluated longitudinally for four months to six years.
  
  
  RESULTS
  The rates of donor-cell engraftment and survival were 100 percent and 100 percent, respectively, among the asymptomatic newborns (median follow-up, 3.0 years) and 100 percent and 43 percent, respectively, among the symptomatic infants (median follow-up, 3.4 years). Surviving patients showed durable engraftment of donor-derived hematopoietic cells with restoration of normal blood galactocerebrosidase levels. Infants who underwent transplantation before the development of symptoms showed progressive central myelination and continued gains in developmental skills, and most had age-appropriate cognitive function and receptive language skills, but a few had mild-to-moderate delays in expressive language and mild-to-severe delays in gross motor function. Children who underwent transplantation after the onset of symptoms had minimal neurologic improvement.
  
  
  CONCLUSIONS
  Transplantation of umbilical-cord blood from unrelated donors in newborns with infantile Krabbe's disease favorably altered the natural history of the disease. Transplantation in babies after symptoms had developed did not result in substantive neurologic improvement.
authors.affiliation: Program for Neurodevelopmental Function in Rare Disorders, Clinical Center for the Study of Development and Learning, University of North Carolina at Chapel Hill, Chapel Hill 27599-7255, USA. maria.escolar@cdl.unc.edu
authors.forename: Maria L
authors.initials: ML
authors.lastname: Escolar
authors.forename: Michele D
authors.initials: MD
authors.lastname: Poe
authors.forename: James M
authors.initials: JM
authors.lastname: Provenzale
authors.forename: Karen C
authors.initials: KC
authors.lastname: Richards
authors.forename: June
authors.initials: J
authors.lastname: Allison
authors.forename: Susan
authors.initials: S
authors.lastname: Wood
authors.forename: David A
authors.initials: DA
authors.lastname: Wenger
authors.forename: Daniel
authors.initials: D
authors.lastname: Pietryga
authors.forename: Donna
authors.initials: D
authors.lastname: Wall
authors.forename: Martin
authors.initials: M
authors.lastname: Champagne
authors.forename: Richard
authors.initials: R
authors.lastname: Morse
authors.forename: William
authors.initials: W
authors.lastname: Krivit
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
mesh_terms: D001921:Brain / Q000033:anatomy & histology; D002657:Child Development; D036101:Cord Blood Stem Cell Transplantation; D018450:Disease Progression; D004569:Electroencephalography; D005071:Evoked Potentials; D005260:Female; D005312:Fetal Blood / Q000637:transplantation*; D005698:Galactosylceramidase / Q000134:cerebrospinal fluid / Q000378:metabolism; D006085:Graft Survival; D006128:Growth; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D018730:Infant Behavior; D007231:Infant, Newborn / Q000254:growth & development; D007965:Leukodystrophy, Globoid Cell / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D008137:Longitudinal Studies; D008297:Male; D009048:Motor Skills; D019957:Motor Skills Disorders / Q000209:etiology; D009431:Neural Conduction; D016019:Survival Analysis; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: D005698:Galactosylceramidase