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. PATIENTS AND 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. DISCUSSION AND CONCLUSION: 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.
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. PATIENTS AND 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. DISCUSSION AND CONCLUSION: 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: M C Walters; M Patience; W Leisenring; Z R Rogers; V M Aquino; G R Buchanan; I A Roberts; A M Yeager; L Hsu; T Adamkiewicz; J Kurtzberg; E Vichinsky; B Storer; R Storb; K M Sullivan Journal: Biol Blood Marrow Transplant Date: 2001 Impact factor: 5.742
Authors: M Andreani; S Nesci; G Lucarelli; P Tonucci; S Rapa; E Angelucci; B Persini; F Agostinelli; M Donati; M Manna Journal: Bone Marrow Transplant Date: 2000-02 Impact factor: 5.483
Authors: G Lucarelli; M Galimberti; P Polchi; E Angelucci; D Baronciani; C Giardini; M Andreani; F Agostinelli; F Albertini; R A Clift Journal: N Engl J Med Date: 1993-09-16 Impact factor: 91.245
Authors: A Lawitschka; M Faraci; I Yaniv; P Veys; P Bader; J Wachowiak; G Socie; M D Aljurf; M Arat; J J Boelens; R Duarte; A Tichelli; C Peters Journal: Bone Marrow Transplant Date: 2015-01-26 Impact factor: 5.483
Authors: N A Fouzia; E S Edison; K M Lakshmi; A Korula; S R Velayudhan; P Balasubramanian; A Abraham; A Viswabandya; B George; V Mathews; A Srivastava Journal: Bone Marrow Transplant Date: 2017-10-16 Impact factor: 5.483
Authors: H B Zheng; B Watkins; V Tkachev; S Yu; D Tran; S Furlan; K Zeleski; K Singh; K Hamby; C Hotchkiss; J Lane; S Gumber; A B Adams; L Cendales; A D Kirk; A Kaur; B R Blazar; C P Larsen; L S Kean Journal: Am J Transplant Date: 2016-09-19 Impact factor: 8.086
Authors: Emanuela Anna Roselli; Riccardo Mezzadra; Marta Claudia Frittoli; Giulietta Maruggi; Erika Biral; Fulvio Mavilio; Fabrizio Mastropietro; Antonio Amato; Giovanni Tonon; Chiara Refaldi; Maria Domenica Cappellini; Marco Andreani; Guido Lucarelli; Maria Grazia Roncarolo; Sarah Marktel; Giuliana Ferrari Journal: EMBO Mol Med Date: 2010-08 Impact factor: 12.137