Haemopoietic stem cell transplantation induces tolerance to donor antigens but not to foreign FVIII peptides


James Uprichard, Department of Haematology, Imperial College, 5th Floor Commonwealth Building, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK. Tel.: +44 20 8383 2298; fax: +44 20 8742 9335; e-mail: j.uprichard@imperial.ac.uk


Summary.  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.