title: Haemopoietic stem cell transplantation induces tolerance to donor antigens but not to foreign FVIII peptides.
abstract: A 22-year-old male with severe haemophilia A and high responding factor VIII (FVIII) inhibitor underwent sibling haematopoietic stem cell transplantation in an attempt to eradicate the inhibitor. A reduced intensity conditioning regimen was followed by bone marrow infusion and continuous FVIII administration during immune reconstitution. Although substantial levels of FVIII:C (>100 IU dL(-1)) were maintained initially, at day +23 inhibitor titres rose, indicating boosting of recipient memory repertoire, despite complete donor chimerism. On day +46, he developed Klebsiella pneumoniae septicaemia and died. This case shows that, despite very successful transplantation tolerance, the procedure failed to control long-term memory effector immune cells.
authors.affiliation: Department of Haematology, Imperial College, Du Cane Road, London, UK. j.uprichard@imperial.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Uprichard
authors.forename: F
authors.initials: F
authors.lastname: Dazzi
authors.forename: J F
authors.initials: JF
authors.lastname: Apperley
authors.forename: M A
authors.initials: MA
authors.lastname: Laffan
mesh_terms: D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000032:analysis; D005169:Factor VIII / Q000276:immunology*; D017809:Fatal Outcome; D018380:Hematopoietic Stem Cell Transplantation; D006467:Hemophilia A / Q000150:complications / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007710:Klebsiella Infections / Q000175:diagnosis; D007711:Klebsiella pneumoniae / Q000302:isolation & purification; D008297:Male; D018805:Sepsis / Q000209:etiology; D055815:Young Adult
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII