Serial transplantation of mismatched donor hematopoietic cells between HLA-identical sibling pairs with congenital immunodeficiency: in vivo tolerance permits rapid immune reconstitution following T-replete transplantation without GVHD in the secondary recipient.
We report serial transplantation procedures in 2 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 "tolerized" 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 graft-versus-host disease (GVHD), despite the presence of donor cells mismatched for 1 to 3 HLA antigens. This serial transplantation 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.
Cohen
Jonathan M
JM
Department of Bone Marrow Transplantation, Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, United Kingdom.
Rogers
Valerie
V
Gaspar
H Bobby
HB
Jones
Alison
A
Davies
E Graham
EG
Rao
Kanchan
K
McCloskey
Daniel J
DJ
Gilmour
Kimberley
K
Wynn
Robert
R
Amrolia
Persis J
PJ
Veys
Paul
P
D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics / Q000276:immunology / Q000628:therapy; D005260:Female; D006680:HLA Antigens; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D035781:Siblings; D014184:Transplantation, Homologous; D014430:Twins, Monozygotic; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000276:immunology / Q000628:therapy*
D006680:HLA Antigens