Submitted March 15, 2006
Accepted May 4, 2006
Serial transplantation of mismatched donor haematopoietic cells between HLA-identical sibling pairs with congenital immunodeficiency: in vivo tolerance permits rapid immune reconstitution following T-replete transplant without GVHD in the secondary recipient
Jonathan Marc Cohen, Valerie Rogers, H Bobby Gaspar, Alison Jones, E Graham Davies, Kanchan Rao, Daniel J McCloskey, Kimberley Gilmour, Robert Wynn, Persis J Amrolia, and Paul Veys*
Depts of Bone Marrow Transplantation, Great Ormond Street Hospital
Molecular Immunology Unit, Institute of Child Health
Clinical Immunology, Great Ormond Street Hospital
Depts of Bone Marrow Transplantation,Great Ormond Street Hospital
Clinical Transplantation Laboratory, Barts & The London NHS Trust
Department of Haematology and Bone Marrow Transplantation, Manchester Royal Infirmary
* Corresponding author; email: veysp{at}gosh.nhs.uk.
We report serial transplant procedures in two sets of brothers with X-linked primary immunodeficiency. The first boy in each family received a T-cell depleted transplant from a mismatched donor. The recipients then acted as donors for T-replete transplantation of the " tolerised" graft into their HLA-identical brothers with the same disorder. Immune reconstitution was noted to occur at a significantly faster rate in the secondary recipients, and without the occurrence of GVHD, despite the presence of donor cells mismatched for 1-3 HLA antigens. This serial transplant technique allows the primary recipient of HLA mismatched donor cells to act as a functionally " HLA matched" donor for subsequent affected siblings, and should be considered as a therapeutic option in families with congenital disorders.
