Donor bone marrow from a sibling with inborn error of metabolism for treatment of acute leukaemia - clinical and biochemical consequences in the non-affected recipient

Bone Marrow Transplant. 2000 Apr;25(8):909-11. doi: 10.1038/sj.bmt.1702333.

Abstract

Bone marrow transplantation (BMT) is increasingly used in an attempt to correct inborn errors of metabolism (IEM). However, little is known about effects of BMT from patients with IEM donating for non-affected recipients. We present data from a 8.5-year-old girl who underwent BMT in second remission for relapsed acute lymphoblastic leukaemia (ALL) at the age of 7 years from her HLA-identical brother who was severely affected by Hunter syndrome (Mucopolysaccharidosis type II, iduronate-2-sulphatase (IDS) deficiency). After BMT not only leukocyte but also plasma activity of IDS was absent. Mixing experiments and immunoadsorption suggest antibody-mediated enzyme inhibition. However, her urinary glycosaminoglycan excretion has not increased post BMT and clinical signs of mucopolysaccharidosis are absent 20 months after BMT. We conclude that patients with white cell enzyme deficiencies and other IEMs do not have to be excluded from bone marrow donation. Antibody production by the graft may occur and be reflected by a marked reduction in plasma enzyme levels but not tissue activity. Similar antibody responses resulting in enzyme inactivation might also affect other enzyme replacement strategies for individuals with IEM.

Publication types

  • Case Reports

MeSH terms

  • Acute Disease
  • Bone Marrow Transplantation*
  • Child
  • Female
  • Glycosaminoglycans / urine
  • Graft Survival
  • Humans
  • Iduronate Sulfatase / blood
  • Iduronate Sulfatase / immunology
  • Isoantibodies / blood
  • Leukemia / therapy*
  • Metabolism, Inborn Errors / blood*
  • Mucopolysaccharidosis II / blood
  • Nuclear Family
  • Tissue Donors

Substances

  • Glycosaminoglycans
  • Isoantibodies
  • Iduronate Sulfatase