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Pediatric Transplants

Haematopoietic cell transplantation (HCT) in combination with enzyme replacement therapy (ERT) in patients with Hurler syndrome

Abstract

Hurler syndrome (MPS 1H) is the severe form of mucopolysaccharidosis type 1 (MPS 1). Haematopoietic cell transplantation (HCT) is the treatment of choice, but carries a high incidence of graft failure and morbidity. The use of enzyme replacement therapy (ERT) might improve the clinical signs and symptoms before HCT, resulting in less transplantation-related complications. Moreover, clearance of glycosaminoglycans (GAG's) from the bone marrow might improve engraftment. Twenty-two patients with MPS 1H received one or more HCT procedures in combination with ERT. One patient with severe cardiomyopathy improved significantly after ERT. All children were in a relatively good clinical condition before HCT. Of patients 59, 82 and 86% were alive and engrafted after one, two and three HCT procedures, respectively. Two patients died after repetitive HCT. No serious ERT-infusion-related toxicity occurred. ERT with HCT was well tolerated. Neither a positive nor a negative effect on the number of patients who are alive and engrafted after receiving ERT before HCT as compared to a historic cohort was noted. However, patients in a poor clinical condition before HCT might benefit from ERT.

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References

  1. Neufeld EF, Muenzer J . The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds). The metabolic & molecular bases of inherited disease. McGraw-Hill: New York, 2001, pp 3421–3452.

    Google Scholar 

  2. Hobbs JR, Hugh-Jones K, Barrett AJ, Byrom N, Chambers D, Henry K et al. Reversal of clinical features of Hurler's disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet 1981; 2: 709–712.

    Article  CAS  PubMed  Google Scholar 

  3. Braunlin EA, Stauffer NR, Peters CH, Bass JL, Berry JM, Hopwood JJ et al. Usefulness of bone marrow transplantation in the Hurler syndrome. Am J Cardiol 2003; 92: 882–886.

    Article  PubMed  Google Scholar 

  4. Souillet G, Guffon N, Maire I, Pujol M, Taylor P, Sevin F et al. Outcome of 27 patients with Hurler's syndrome transplanted from either related or unrelated haematopoietic stem cell sources. Bone Marrow Transplant 2003; 31: 1105–1117.

    Article  CAS  PubMed  Google Scholar 

  5. Vellodi A, Young EP, Cooper A, Wraith JE, Winchester B, Meaney C et al. Bone marrow transplantation for mucopolysaccharidosis type I: Experience of two British centres. Arch Dis Childhood 1997; 76: 92–99.

    Article  CAS  Google Scholar 

  6. Peters C, Balthazor M, Shapiro EG, King RJ, Kollman C, Hegland JD et al. Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 1996; 87: 4894–4902.

    CAS  PubMed  Google Scholar 

  7. Peters C, Shapiro EG, Anderson J, Henslee-Downey PJ, Klemperer MR, Cowan MJ et al. Hurler syndrome: II. Outcome of HLA genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. Blood 1998; 91: 2601–2608.

    CAS  PubMed  Google Scholar 

  8. Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P et al. Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med 2004; 350: 1960–1969.

    Article  CAS  PubMed  Google Scholar 

  9. Kakkis ED, Muenzer J, Tiller GE, Waber L, Belmont J, Passage M et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med 2001; 344: 182–188.

    Article  CAS  PubMed  Google Scholar 

  10. Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (Laronidase). J Pediatr 2004; 144: 581–588.

    Article  CAS  PubMed  Google Scholar 

  11. Shull RM, Kakkis ED, McEntee MF, Kania SA, Jonas AJ, Neufeld EF . Enzyme replacement in a canine model of Hurler-syndrome. Proc Natl Acad Sci USA 1994; 91: 12937–12941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Baxter MA, Wynn RF, Schyma L, Holmes DK, Wraith JE, Fairbairn LJ et al. Marrow stromal cells from patients affected by MPS I differentially support haematopoietic progenitor cell development. J Inherit Metab Dis 2005; 28: 1045–1053.

    Article  CAS  PubMed  Google Scholar 

  13. Lansky SB, List MA, Lansky LL, Ritter-Sterr C, Miller DR . The measurement of performance in childhood cancer patients. Cancer 1987; 60: 1651–1656.

    Article  CAS  PubMed  Google Scholar 

  14. Boelens JJ, Wynn R, O’Mearra A, Veys P, Cavazzana-Calzo M, Wulffraat N . Results of haematopoietic stem cell transplantation (HSCT) for Hurler's syndrome: European experience 1994–2004. Blood 2005; 106: 121a (abstr. 402).

    Google Scholar 

  15. Rubinstein P, Rosenfield RE, Adamson JW, Stevens CE . Stored placental blood for unrelated bone marrow reconstitution. Blood 1993; 81: 1679–1690.

    CAS  PubMed  Google Scholar 

  16. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  17. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  18. Reiss U, Cowan M, McMillan A, Horn B . Hepatic venoocclusive disease in blood and bone marrow transplantation in children and young adults: incidence, risk factors, and outcome in a cohort of 241 patients. J Pediatr Hematol Oncol 2002; 24: 746–750.

    Article  PubMed  Google Scholar 

  19. Grewal SS, Wynn R, Abdenur JE, Burton BK, Gharib M, Haase C et al. Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome. Genet Med 2005; 7: 143–146.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank our collaborators for sharing their patient information: Drs Pierre Bordigoni and Alexandra Salmon (Nancy, France), Mary Coussons (Data manager Manchester, UK), Dr Claudia Haase (Jena, Germany) and Dr Gunilla Malm (Karolinska, Huddinge, Sweden). The Dutch Health Care Insurance Board (CVZ) is acknowledged for partial funding of the study.

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Correspondence to J-J Boelens.

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Cox-Brinkman, J., Boelens, JJ., Wraith, J. et al. Haematopoietic cell transplantation (HCT) in combination with enzyme replacement therapy (ERT) in patients with Hurler syndrome. Bone Marrow Transplant 38, 17–21 (2006). https://doi.org/10.1038/sj.bmt.1705401

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