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Trends in haematopoietic cell transplantation for inborn errors of metabolism

  • SSIEM SYMPOSIUM 2005
  • Published:
Journal of Inherited Metabolic Disease

Summary

For the last 25 years, haematopoietic cell transplantation (HCT) has been used as effective therapy for selected inborn errors of metabolism (IEMs), mainly lysosomal storage diseases and peroxisomal disorders. The main rational for HCT in IEMs is based on the provision of correcting enzymes by donor cells within and outside the blood compartment. The ultimate goal of HCT is to achieve a normal or near-normal life and normal neurodevelopment. HCT has been performed for more than 20 diseases. Only for Hurler syndrome, X-ALD and infantile Krabbe disease, are detailed studies available suggesting that HCT is indicated for carefully selected cases. Improvement of transplantation techniques and alternative therapies may change the recommended (contra-)indications for IEM. A recent example of emerging transplantation techniques is the fast availability of unrelated cord blood (UCB). UCB makes HCT feasible in patients with rapidly progressive neurological diseases. Because of the fast availability of UCB and therefore the ability to transplant shortly after diagnosis, there is no indication for patients in a moderate/good clinical condition to receive enzyme replacement therapy (ERT; in Hurler syndrome) prior to or during HCT and can ERT only be considered in patients with poor clinical condition. Mesenchymal stem cell infusions with HCT is an emerging technique, and might be interesting in halting the remaining defects after successful HCT. Improvement in HCT techniques and novel stem cell sources will significantly impact the safety and efficacy of this therapy as well as expand the list of candidate disorders. A good functioning worldwide registry would be necessary to measure the effects of the procedures performed in more detail.

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References

  • Aubourg P, Blanche S, Jambaque I, etal (1990) Reversal of early neurological and neuroradiological manifestations of X-linked adrenoleukodystrophy by bone-marrow transplantation. N Engl J Med 322(26): 1860–1866.

    Article  PubMed  CAS  Google Scholar 

  • Ballen KK (2005) New trends in umbilical cord blood transplantation. Blood 105(10): 3786–3792.

    Article  PubMed  CAS  Google Scholar 

  • Boelens JJ, Wynn R, O'Meara A, et al (2005a) Results of haematopoietic stem cell transplantation (HSCT) for Hurler's syndrome: european experience 1994–2004. ASH 2005 (Atlanta), abstract no. 402.

  • Boelens JJ, Wynn R, Wraith E, etal (2005b) Safety and efficacy of enzyme replacement therapy (ERT) in combination with haematopoietic stem cell transplantation (HSCT) for Hurler's syndrome: European experience 2003–2005. ASH 2005 (Atlanta) abstract no. 5307.

  • Braunlin EA, Rose AG, Hopwood JJ, Candel RD, Krivit W (2001) Coronary artery patency following long-term successful engraftment 14 years after bone marrow transplantation in the Hurler syndrome. Am J Cardiol 88(9): 1075–1077.

    Article  PubMed  CAS  Google Scholar 

  • Chao NJ, Emerson SG, Weinberg KI (2004) Stem cell transplantation (cord blood transplants). Hematology 1: 354–371.

    Article  Google Scholar 

  • Di Ferrante N, Nichols BL, Donnelly PV, etal (1971) Induced degradation of glycosaminoglycans in Hurler's and Hunter's syndromes by plasma infusion. Proc Natl Acad Sci USA 68: 303–307.

    Article  PubMed  Google Scholar 

  • Eichler FS, Barker PB, Cox C, etal (2002) Proton MR spectroscopic imaging predicts lesion progression on MRI in X-linked adrenoleukodystrophy. Neurology 58(6): 901–907.

    PubMed  CAS  Google Scholar 

  • Escolar ML, Poe MD, Provenzale JM, etal (2005) Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med 352(20): 2069–2081.

    Article  PubMed  CAS  Google Scholar 

  • Fratantoni JC, Hall CW, Neufeld EF (1969) The defect in Hurler and Hunter syndrome. II. Deficiency of specific factors involved in mucopolysaccharide degradation. Proc Natl Acad Sci USA 64: 360–366.

    Article  PubMed  CAS  Google Scholar 

  • Gluckman E, Rocha V, Arcese W, etal (2004) Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol 32(4): 397–407.

    Article  PubMed  CAS  Google Scholar 

  • Hobbs JR, Hugh-Jones K, Barrett AJ, etal (1981) Reversal of clinical features of Hurler's disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet 2: 709–712.

    Article  PubMed  CAS  Google Scholar 

  • Klein KA, Krivit W, Whitley CB (1995) Poor cognitive outcome of eleven children with Sanfilippo syndrome after bone marow transplantation and successful engraftment. Bone Marrow Transplant 15: S176.

    Google Scholar 

  • Knudson AF Jr, Di Ferrante N, Curtis JE (1971) Effect of leukocyte transfusion in a child with type II mucopolysaccharidosis. Proc Natl Acad Sci USA 68: 1738–1741.

    Article  PubMed  Google Scholar 

  • Koc ON, Peters C, Aubourg P, etal (1999) Bone marrow-derived mesenchymal stem cells remain host-derived despite successful haematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases. Exp Hematol 27(11): 1675–1681.

    Article  PubMed  CAS  Google Scholar 

  • Koc ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W (2002) Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 30(4): 215–222.

    Article  PubMed  CAS  Google Scholar 

  • Kogler G, Enczmann J, Rocha V, Gluckman E, Wernet P, etal (2005) High-resolution HLA typing by sequencing for HLA-A, -B, -C, -DR, -DQ in 122 unrelated cord blood/patient pair transplants hardly improves long-term clinical outcome. Bone Marrow Transplant 36(12): 1033–1041.

    Article  PubMed  CAS  Google Scholar 

  • Krivit W, Piermont ME, Ayaz K, etal (1984) Bone-marrow-transplantation in the Maroteaux—Lamy syndrome (mucopolysaccharidosis type VI). Biochemial and clinical status 24 months after transplantation. N Engl J Med 311: 1606–1611.

    Article  PubMed  CAS  Google Scholar 

  • Krivit W, Henslee-Downey J, Klemperer M, etal (1995a) Survival in Hurler's disease following bone marrow transplantation in 84 patients. Bone Marrow Transplant 15: S182—S185.

    Google Scholar 

  • Krivit W, Sung JH, Shapiro EG, Lockman, LA (1995b) Microglia — the effector cell for reconstitution of the central-nervous-system following bone-marrow transplantation for lysosomal and peroxisomal storage diseases. Cell Transplant 4(4): 385–392.

    Article  CAS  Google Scholar 

  • Krivit W, Shapiro EG, Peters C, etal (1998) Haematopoietic stem-cell transplantation in globoid-cell leukodystrophy. N Engl J Med 338(16): 1119–1126.

    Article  PubMed  CAS  Google Scholar 

  • Kurtzberg J, Krivit W (2004) Cord blood transplantation for lysosomal storage diseases demonstrates the potential of cord blood cells for future cellular therapies. Blood (ASH meeting), abstract no. 3602.

  • Lansky SB, List MA, Lansky LL (1987) The measurement of performance in childhood cancer patients. Cancer 60: 1651–1656.

    PubMed  CAS  Google Scholar 

  • Laughlin MJ, Eapen M, Rubinstein P, etal (2005) Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 351: 2265–2275.

    Article  Google Scholar 

  • Le Blanc K, Rasmusson I, Sundberg B, etal (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Bone Marrow Transplant 33: S185.

    Google Scholar 

  • Loes DJ, Hite S, Moser H, etal (1994a) Adrenoleukodystrophy — a scoring method for brain MR observations. Am J Neuroradiol 15(9): 1761–1766.

    CAS  Google Scholar 

  • Loes DJ, Stillman AE, Hite S, etal (1994b) Childhood cerebral form of adrenoleukodystrophy — short-term effect of bone-marrow transplantation on brain MR observations. Am J Neuroradiol 15(9): 1767–1771.

    CAS  Google Scholar 

  • Malm G, Ringden O, Winiarski J, etal (1996) Clinical outcome in four children with metachromatic leukodystrophy treated by bone marrow-transplantation. Bone Marrow Transplant 17(6): 1003–1008.

    PubMed  CAS  Google Scholar 

  • Moser HW (1997) Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain 120: 1485–1508.

    Article  PubMed  Google Scholar 

  • Moser HW (2001) X-linked adrenoleukodystrophy. In: Scriver CR, Beaudetal, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc, eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 3257–3301.

    Google Scholar 

  • Moser HW, Raymond G, Kohler W, Sokolowski P, etal (2003) Evaluation of the preventive effect of glyceryl-tri-oleates trierucate (Lorenzo's oil) therapy in X-ALD: results of two concurrent trials. In: Roels F, Baes M, de Bie S, eds. Peroxisomal Disorders and Regulation of Genes. New York: Kluwer Plenum, 369–387.

    Google Scholar 

  • Nauta AJ, Roelofs H, Fibbe WE (2004) The role of mesenchymal stem cells in immune modulation and haematopoietic engraftment. Blood Cells Mol Dis 33(3): 202–203.

    Google Scholar 

  • Neufeld EF, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR, Beaudetal, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B, eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 3421–3452.

    Google Scholar 

  • Peters C (2003) Haematopoietic cell transplantation for storage diseases. In: Forman S, Blume K, Appelbaum F, eds. Thomas'Hemotopoietic Cell Transplantation. London: Blackwell Scientific, 209–218.

    Google Scholar 

  • Peters C, Steward CG (2003) Haematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines. Bone Marrow Transplant 31(4): 229–239.

    Article  PubMed  CAS  Google Scholar 

  • Peters C, Balthazor M, Shapiro EG, etal (1996) Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 87(11): 4894–4902.

    PubMed  CAS  Google Scholar 

  • Peters C, Shapiro EG, Anderson J, etal (1998a) Hurler syndrome: II. Outcome of HLA genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. Blood 91(7): 2601–2608.

    CAS  Google Scholar 

  • Peters C, Shapiro EG, Krivit W (1998b) Hurler syndrome: past, present, and future. J Pediatr 133(1): 7–9.

    Article  CAS  Google Scholar 

  • Peters C, Charnas LR, Tan Y, etal (2004) Cerebral X-linked adrenoleukodystrophy: the international haematopoietic cell transplantation experience from 1982 to 1999. Blood 104(3): 881–888.

    Article  PubMed  CAS  Google Scholar 

  • Rocha V, Labopin M, Sanz G, etal (2005) Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 351: 2276–2285.

    Article  Google Scholar 

  • Rovelli AM, Steward CG (2005) Haematopoietic cell transplantation activity in Europe for inherited metabolic diseases: open issues and future directions. Bone Marrow Transplant 35(Supplement): S23—S26.

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Rubinstein P, Dobrila L, Rosenfield RE, etal (1995) Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. Proc Natl Acad Sci USA 92: 10119–10122.

    Article  PubMed  CAS  Google Scholar 

  • 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(4): 413–429.

    Article  PubMed  CAS  Google Scholar 

  • Shapiro E, Krivit W, Lockman L, et al (2000) Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy. Lancet 356(9231): 713–718.

    Article  PubMed  CAS  Google Scholar 

  • Souillet G, Guffon N, Maire I, etal (2003) Outcome of 27 patients with Hurler's syndrome transplanted from either related or unrelated haematopoietic stem cell sources. Bone Marrow Transplant 31(12): 1105–1117.

    Article  PubMed  CAS  Google Scholar 

  • Staba SL, Escolar ML, Poe M, etal (2004) Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med 350(19): 1960–1969.

    Article  PubMed  CAS  Google Scholar 

  • Summers CG, Purple RL, Krivit W, etal (1989) Ocular changes in the mucopolysaccharidoses after bone-marrow transplantation. Ophthalmology 96(7): 977–984.

    PubMed  CAS  Google Scholar 

  • Vellodi A, Young E, New M, etal (1992) Bone marrow transplantation for Sanfilippo disease type B. J Inherit Metab Dis 15: 911–918.

    Article  PubMed  CAS  Google Scholar 

  • Vinallonga X, Sanz N, Balaguer A, Miro L, Ortega JJ, Casaldaliga J (1992) Hypertrophic cardiomyopathy in mucopolysaccharidoses — regression after bone-marrow transplantation. Pediatr Cardiol 13(2): 107–109.

    Article  PubMed  CAS  Google Scholar 

  • Wagner JE, Davies SM, Defor TE, etal (2001) Unrelated donor umbilical cord blood transplantation (UD-UCBT) in 92 patients at the University of Minnesota: analysis of risk factors. Blood 98(11): 665A.

    Google Scholar 

  • Wall DA, Grange DK, Goulding P, Daines M, Luisiri A, Kotagel S (1998) Bone marrow transplantation for the treatment of alpha-mannosidosis. J Pediatr 133(2): 282–285.

    Article  PubMed  CAS  Google Scholar 

  • Wenger DA, Suzuki K, Suzuki Y, etal (2001) Galactosylceramide lipidosis: globoid cell leukodystrophy (Krabbe disease). In: Scriver CR, Beaudetal, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc, eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 3669–3694.

    Google Scholar 

  • Yamada Y, Kato K, Sukegawa K, etal (1998) Treatment of MPS VII (Sly disease) by allogeneic BMT in a female with homozygous A619V mutation. Bone Marrow Transplant 21(6): 629–634.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Immunology/BMT, UMC Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands

    Jaap Jan Boelens

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  1. Jaap Jan Boelens
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Correspondence to Jaap Jan Boelens.

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Communicating editor: Jean-Marie Saudubray

Competing interests: None declared

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Boelens, J.J. Trends in haematopoietic cell transplantation for inborn errors of metabolism. J Inherit Metab Dis 29, 413–420 (2006). https://doi.org/10.1007/s10545-005-0258-8

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  • DOI: https://doi.org/10.1007/s10545-005-0258-8

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