title: Relationship between mixed chimerism and rejection after bone marrow transplantation in thalassaemia.
abstract: BACKGROUND
  Thalassaemia is a genetic disease that requires a hypertransfusion regimen to treat the anaemia caused by enhanced red blood cell destruction. The only radical cure for thalassaemia is to correct the genetic defect by bone marrow transplantation from an HLA-identical donor capable of producing and maintaining a normal haemoglobin level in the recipient. Complete donor haematopoiesis is not essential for sustained engraftment and the simultaneous presence of haematopoietic cells of both donor and recipient origin is not a rare event after a transplant.
  
  
  METHODS
  The evolution of marrow engraftment of 93 transplanted thalassaemic patients, all from Middle East or Asian countries, was monitored by analysis of short tandem repeats.
  
  
  RESULTS
  Forty-three of 93 (46%) patients experienced a status of mixed chimerism early after bone marrow transplantation. Results of further engraftment analysis in these patients showed in 27 complete donor engraftment; rejection occurred in seven, while eight maintained the presence of both host and donor-derived cells. Interestingly, five out of the seven patients who rejected their transplant showed more than 25% residual host cells early after transplantation.
  
  
  CONCLUSIONS
  Our study confirmed that the presence of large amounts of residual host cells within the first 2 months after a transplant is a risk factor for graft rejection also in a group of patients with wide ethnic heterogeneity, irregular transfusion regimens and/or poor chelation treatment. Ten percent of the transplanted thalassaemic patients maintained coexistence of donor and recipient cells, showing a stable functional graft, characterized by normal production of beta globin chains and high levels of haemoglobin. A mechanism responsible for peripheral tolerance induction, such as the production of specific regulatory T-cell clones, seems to play a key role in the induction of long-term tolerance after the transplant.
authors.affiliation: Laboratorio di Immunogenetica e Biologia dei Trapianti, Fondazione IME, Roma, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Andreani
authors.forename: Manuela
authors.initials: M
authors.lastname: Testi
authors.forename: Mariarosa
authors.initials: M
authors.lastname: Battarra
authors.forename: Paola
authors.initials: P
authors.lastname: Indigeno
authors.forename: Annalisa
authors.initials: A
authors.lastname: Guagnano
authors.forename: Paola
authors.initials: P
authors.lastname: Polchi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Guido
authors.initials: G
authors.lastname: Lucarelli
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D008297:Male; D013789:Thalassemia / Q000628:therapy*; D018183:Transplantation Chimera