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 blo t/polymerase chain reaction analysis of variable number tandem repeats on g enomic DNA from peripheral blood. Early haemopoiesis was fully donor in ori gin in 24 out of 35 cases and remained so throughout the post-transplant co urse in all but one patient, who evolved to stable mixed chimaerism. The re maining 11 cases (31%) initially showed mixed chimaerism: four of these rej ected, one eventually eradicated host haemopoiesis to become fully donor ha emopoietic, and the remaining six had persistent mixed chimaerism, with 5-3 8% 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 pa tients with full donor chimaerism. These studies confirm that the mixed chi maeric state is common following SCT for thalassaemia, often persists (with up to 4 years follow-up) and is compatible with long-term cure. Analysis o f chimaerism in patients undergoing SCT for beta -thalassaemia enables moni toring 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.