title: Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Juvenile Metachromatic Leukodystrophy Compared With Nontransplanted Control Patients.
abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) has been the only treatment option clinically available during the last 20 years for juvenile metachromatic leukodystrophy (MLD), reported with variable outcome and without comparison with the natural course of the disease.
  
  
  
  To compare the long-term outcome of patients who underwent allogeneic HSCT with control patients who did not among a cohort with juvenile MLD.
  
  
  
  Patients with juvenile MLD born between 1975 and 2009 and who received HSCT at a median age of 7 years (age range, 1.5-18.2 years) and nontransplanted patients with juvenile MLD born between 1967 and 2007 were included in this case-control study. The median follow-up after HSCT was 7.5 years (range, 3.0-19.7 years). Patients underwent HSCT at 3 German centers between 1991 and 2012. The analysis was done between July 2014 and August 2015.
  
  
  
  Survival and transplantation-related mortality, loss of gross motor function (Gross Motor Function Classification in MLD), loss of any language function, and magnetic resonance imaging (MRI) severity score for cerebral changes. To explore prognostic factors at baseline, patients who underwent HSCT (hereafter, transplanted patients) were a priori divided into stable vs progressive disease, according to gross motor and cognitive function.
  
  
  
  Participants were 24 transplanted patients (11 boys, 13 girls) and 41 control patients (22 boys, 19 girls) who did not receive transplantation (hereafter, nontransplanted patients) with juvenile MLD. Among the transplanted patients, 4 children died of transplantation-related mortality, and 2 additional children died of rapid MLD progression 1.5 and 8.6 years after HSCT, resulting in a 5-year survival of 79% (19 of 24). Among the nontransplanted patients, 5-year survival after disease onset was 100% (41 of 41). However, 11 died of MLD progression, resulting in similar overall survival within the observation period. Nine of the long-term survivors after HSCT had disease progression, while 11 showed stable disease. Compared with the nontransplanted patients, the transplanted patients were less likely to lose their gross motor or language function and demonstrated significantly lower MRI severity scores at the latest examination. Patients after HSCT were more likely to have a stable disease course when undergoing HSCT at an early stage with no or only mild gross motor deficits (Gross Motor Function Classification in MLD level 0 or 1) and an IQ of at least 85, when age at disease onset was older than 4 years, or when MRI severity scores were low (preferably ≤17).
  
  
  
  Among patients with juvenile MLD, patients who underwent HSCT had a better gross motor and language outcome and lower MRI severity scores compared with nontransplanted patients. Transplantation at a presymptomatic or early symptomatic stage of juvenile MLD is associated with a reasonable chance for disease stabilization.
authors.affiliation: Department of Pediatric Neurology and Developmental Medicine, University Children's Hospital of Tübingen, Tübingen, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Groeschel
authors.affiliation: Department of Pediatric Oncology, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Jörn-Sven
authors.initials: JS
authors.lastname: Kühl
authors.affiliation: Department of Pediatrics, University Children's Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Annette E
authors.initials: AE
authors.lastname: Bley
authors.affiliation: Department of Pediatric Neurology and Developmental Medicine, University Children's Hospital of Tübingen, Tübingen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Kehrer
authors.affiliation: Department of Neuropediatrics, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Weschke
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital of Tübingen, Tübingen, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Döring
authors.affiliation: Department of Pediatric Neurology and Developmental Medicine, University Children's Hospital of Tübingen, Tübingen, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Böhringer
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schrum
authors.affiliation: Department of Pediatrics, University Children's Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Santer
authors.affiliation: Department of Pediatrics, University Children's Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Alfried
authors.initials: A
authors.lastname: Kohlschütter
authors.affiliation: Department of Pediatric Neurology and Developmental Medicine, University Children's Hospital of Tübingen, Tübingen, Germany.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Krägeloh-Mann
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital of Tübingen, Tübingen, Germany6Department of Pediatric Hematology and Oncology, University Children's Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000209:etiology / Q000601:surgery; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007966:Leukodystrophy, Metachromatic / Q000150:complications / Q000000981:diagnostic imaging / Q000401:mortality / Q000601:surgery*; D008279:Magnetic Resonance Imaging; D008297:Male; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult