Advertisement

Long-Term Functional Outcomes of Children with Hurler Syndrome Treated with Unrelated Umbilical Cord Blood Transplantation

  • Hannah Y. Coletti
  • Mieke Aldenhoven
  • Karina Yelin
  • Michele D. Poe
  • Joanne Kurtzberg
  • Maria L. EscolarEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 20)

Abstract

Objectives: Hurler syndrome is characterized by progressive multisystem deterioration leading to early death in childhood. This prospective study evaluated the long-term outcomes of patients with Hurler syndrome who underwent umbilical cord blood transplantation from unrelated donors.

Study design: Only patients with Hurler syndrome who underwent umbilical cord blood transplantation between December 1995 and March 2006 (n = 25) and who were followed for at least 5 years (n = 19) were included in the analysis. The patients were longitudinally evaluated by a multidisciplinary team of specialists following a standardized protocol.

Results: Median age at transplantation was 15.9 months (range 2.1–35), and patients were followed up until a median age of 10.1 years (range 7.2–14.9). Overall survival was 80%. All successfully transplanted patients achieved full donor chimerism and normal enzyme levels, and all children continue to make gains in development. Gross motor function was the most affected area. Vision and hearing were compromised in a minority of the patients, with some requiring corneal transplant or hearing aids. Cardiopulmonary function improved. Some children required orthopedic surgery, but severe complications were prevented in most patients. Although longitudinal growth was lower than that of unaffected children, it was considerably higher than expected from the natural course of the disease. Head circumference normalized. Hydrocephalus was not observed at longer follow-up, and cerebral atrophy decreased over time.

Conclusions: In this descriptive study of children with Hurler syndrome, unrelated umbilical cord blood transplantation was associated with improved somatic disease and neurodevelopment.

Keywords

Hematopoietic Stem Cell Transplantation Enzyme Replacement Therapy Umbilical Cord Blood Transplantation Unaffected Child Hurler Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We would like to acknowledge the families who travelled for the evaluation, some of which self-referred for follow-up, and all the clinicians at the University of North Carolina, University of Minnesota, and Duke University Medical Center who participated in the care of these patients. This study was funded by the Caterina Marcus Foundation.

References

  1. Aldenhoven M, Boelens JJ, de Koning TJ (2008) The clinical outcome of Hurler syndrome after stem cell transplantation. Biol Blood Marrow Transplant 14:485–498Google Scholar
  2. Beam D, Poe MD, Provenzale JM et al (2007) Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy. Biol Blood Marrow Transplant 13:665–674CrossRefPubMedGoogle Scholar
  3. Beesley CE, Meaney CA, Greenland G et al (2001) Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. Hum Genet 109:503–511CrossRefPubMedGoogle Scholar
  4. Braunlin EA, Harmatz PR, Scarpa M et al (2010) Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management. J Inherit Metab Dis 34:1183–1197CrossRefGoogle Scholar
  5. Dickson P, Peinovich M, McEntee M et al (2008) Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I. J Clin Invest 118:2868–2876PubMedCentralPubMedGoogle Scholar
  6. Escolar ML, Poe MD, Provenzale JM et al (2005) Transplantation of umbilical-cord blood in babies with infantile Krabbe’s disease. N Engl J Med 352:2069–2081CrossRefPubMedGoogle Scholar
  7. Guffon N, Souillet G, Maire I, Straczek J, Guibaud P (1998) Follow-up of nine patients with Hurler syndrome after bone marrow transplantation. J Pediatr 133:119–125CrossRefPubMedGoogle Scholar
  8. Hobbs JR, Hugh-Jones K, Barrett AJ et al (1981) Reversal of clinical features of Hurler’s disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet 2:709–712CrossRefPubMedGoogle Scholar
  9. Kharbanda S, Panoskaltsis-Mortari A, Haddad IY (2006) Inflammatory cytokines and the development of pulmonary complications after allogeneic hematopoietic cell transplantation in patients with inherited metabolic storage disorders. Biol Blood Marrow Transplant 12:430–437CrossRefPubMedGoogle Scholar
  10. Malm G, Gustafsson B, Berglund G et al (2008) Outcome in six children with mucopolysaccharidosis type IH, Hurler syndrome, after haematopoietic stem cell transplantation (HSCT). Acta Paediatr 97:1108–1112CrossRefPubMedGoogle Scholar
  11. Martin PL, Carter SL, Kernan NA et al (2006) Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant 12:184–194CrossRefPubMedGoogle Scholar
  12. Muenzer J, Wraith JE, Clarke LA (2009) International consensus panel on management and treatment of mucopolysaccharidosis I. Pediatrics 123:19–29CrossRefPubMedGoogle Scholar
  13. Neufeld EF, Muenzer J (2001) The mucopolysaccharidosis. In: Scriver C, Beaudet A, Sly W, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 3421–3452Google Scholar
  14. Orchard PJ, Milla C, Braunlin E, DeFor T, Bjoraker K, Blazar BR (2010) Pre-transplant risk factors affecting outcome in Hurler syndrome. Bone Marrow Transplant 45:1239–1246CrossRefPubMedGoogle Scholar
  15. Peters C, Balthazor M, Shapiro EG et al (1996) Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 87:4894–4902PubMedGoogle Scholar
  16. Peters C, Shapiro EG, Anderson J et al (1998) Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The storage disease collaborative study group. Blood 91:2601–2608PubMedGoogle Scholar
  17. Poe MD, Chagnon SL, Escolar M (2014) Early treatment is associated with improved cognition in Hurler syndrome. Ann Neurol 76(5):747–753. doi: 10.1002/ana.24246 CrossRefPubMedGoogle Scholar
  18. Prasad VK, Mendizabal A, Parikh SH et al (2008) Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes. Blood 112:2979–2989CrossRefPubMedCentralPubMedGoogle Scholar
  19. Shapiro EG, Lockman LA, Balthazor M, Krivit W (1995) Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation. J Inherit Metab Dis 18:413–429CrossRefPubMedGoogle Scholar
  20. Souillet G, Guffon N, Maire I, Pujol M et al (2003) Outcome of 27 patients with Hurler’s syndrome transplanted from either related or unrelated haematopoietic stem cell sources. Bone Marrow Transplant 31:1105–1117CrossRefPubMedGoogle Scholar
  21. Staba SL, Escolar ML, Poe M, Kim Y et al (2004) Cord-blood transplants from unrelated donors in patients with Hurler’s syndrome. N Engl J Med 350:1960–1969CrossRefPubMedGoogle Scholar
  22. Terlato NJ, Cox GF (2003) Can mucopolysaccharidosis type I disease severity be predicted based on a patient’s genotype? A comprehensive review of the literature. Genet Med 5:286–294CrossRefPubMedGoogle Scholar
  23. Thomas JA, Jacobs S, Kierstein J, Van HJ (2006) Outcome after three years of laronidase enzyme replacement therapy in a patient with Hurler syndrome. J Inherit Metab Dis 29:762CrossRefPubMedGoogle Scholar
  24. Tokic V, Barisic I, Huzjak N, Petkovic G, Fumic K, Paschke E (2007) Enzyme replacement therapy in two patients with an advanced severe (Hurler) phenotype of mucopolysaccharidosis I. Eur J Pediatr 166:727–732CrossRefPubMedGoogle Scholar
  25. Tolar J, Dickson P, Orchard PJ (2009) Intravenous and intrathecal enzyme replacement before and after hematopoietic cell transplantation for Hurler syndrome. Biol Blood Marrow Transplant 15(Suppl 2):74CrossRefGoogle Scholar
  26. Vellodi A, Young EP, Cooper A et al (1997) Bone marrow transplantation for mucopolysaccharidosis type I: experience of two British centres. Arch Dis Child 76:92–99CrossRefPubMedCentralPubMedGoogle Scholar
  27. Visigalli I, Delai S, Politi LS et al (2010) Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model. Blood 9(116):5130–5139CrossRefGoogle Scholar
  28. Weisstein JS, Delgado E, Steinbach LS, Hart K, Packman S (2004) Musculoskeletal manifestations of Hurler syndrome long-term follow-Up after bone marrow transplantation. J Pediatr Orthop 24:97–101CrossRefPubMedGoogle Scholar
  29. Whitley CB, Belani KG, Chang PN et al (1993) Long-term outcome of Hurler syndrome following bone marrow transplantation. Am J Med Genet 46:209–218CrossRefPubMedGoogle Scholar
  30. Wraith JE, Beck M, Lane R et al (2007) Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase). Pediatrics 120:e37–e46CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Hannah Y. Coletti
    • 1
  • Mieke Aldenhoven
    • 2
  • Karina Yelin
    • 1
  • Michele D. Poe
    • 3
  • Joanne Kurtzberg
    • 4
  • Maria L. Escolar
    • 3
    Email author
  1. 1.Departments of Pediatrics and Internal MedicineUniversity of North CarolinaChapel HillUSA
  2. 2.Department of Immunology/Hematology and BMTUniversity Medical Center UtrechtUtrechtThe Netherlands
  3. 3.Program for the Study of Neurodevelopment in Rare DisordersChildren’s Hospital of Pittsburgh, University of Pittsburgh Medical CenterPittsburghUSA
  4. 4.Division of Pediatric Blood and Marrow TransplantationDuke University Medical CenterDurhamUSA

Personalised recommendations