Analysis of chimaerism in thalassaemic children undergoing stem cell transplantation.
We have prospectively assessed the relative contribution of host and donor to haemopoiesis following stem cell transplantation (SCT) in children with beta-thalassaemia major (n = 35), using karyotype analysis or Southern blot/polymerase chain reaction analysis of variable number tandem repeats on genomic DNA from peripheral blood. Early haemopoiesis was fully donor in origin in 24 out of 35 cases and remained so throughout the post-transplant course in all but one patient, who evolved to stable mixed chimaerism. The remaining 11 cases (31%) initially showed mixed chimaerism: four of these rejected, one eventually eradicated host haemopoiesis to become fully donor haemopoietic, and the remaining six had persistent mixed chimaerism, with 5--38% host haemopoiesis. The risk of graft rejection was high when > 15% host haemopoiesis was present at 3 months post transplant: four out of six such patients rejected their grafts; conversely, zero out of 29 patients with < 15% host haemopoiesis at 3 months rejected (P < 0.0001). There was a higher incidence of significant acute and chronic graft-versus-host disease in patients with full donor chimaerism. These studies confirm that the mixed chimaeric state is common following SCT for thalassaemia, often persists (with up to 4 years follow-up) and is compatible with long-term cure. Analysis of chimaerism in patients undergoing SCT for beta-thalassaemia enables monitoring of engraftment in the early post-transplant period, provides insight into the biology of engraftment and may be useful in identifying patients at high risk of rejection.
Amrolia
P J
PJ
Department of Haematology, Hammersmith Hospital, London, UK.
Vulliamy
T
T
Vassiliou
G
G
Lawson
S
S
Bryon
J
J
Kaeda
J
J
Dokal
I
I
Johnston
R
R
Veys
P
P
Darbyshire
P
P
Roberts
I A
IA
D000017:ABO Blood-Group System; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002678:Chimera; D006084:Graft Rejection / Q000235:genetics*; D006086:Graft vs Host Disease / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018598:Minisatellite Repeats; D011446:Prospective Studies; D019172:Transplantation Conditioning; D017086:beta-Thalassemia / Q000235:genetics / Q000628:therapy*
D000017:ABO Blood-Group System