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What is the minimum level of donor chimerism necessary to sustain transfusion independence in thalassaemia?

Bone Marrow Transplantation volume 46, pages 769–770 (2011)Cite this article

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Allogeneic haemopoietic SCT is an established procedure for achieving transfusion independence in patients with β-thalassaemia major.1 Transfusion independence is not contingent on achieving or sustaining full donor chimerism (DC). Up to one-third of patients have mixed chimerism (MC) at 2 months, with the number decreasing to around 10% at 2 years post transplant.2 Patients with persistent MC can become transfusion independent, suggesting that a low level of engrafted donor cells can maintain this clinical state.2, 3 However, the minimum level of stable DC necessary for transfusion independence is uncertain. We report a 5-year-old girl with β-thalassaemia major who remains transfusion independent with a stable marrow DC of 10% at 3 years following a matched sibling allogeneic BMT.

In contrast to the malignant disease setting, the presence of transient MC does not inevitably lead to graft failure in thalassaemics.2, 4 In a study of 295 patients undergoing BMT with a minimum of 2 years follow-up, about one-third of patients were observed to have MC at 2 months after BMT and over time this decreased to 9% at 2 years after the transplant.2 In an analysis of 27 consecutive cord blood transplants from related donors, all cord blood recipients engrafted and displayed MC early after transplantation, 13 patients converted to full DC over time, whereas 14 maintained stable MC after a median follow-up of 42 (range 15–76) months with all patients being alive and transfusion independent.4 In these studies, the lowest reported DC was 10% in two patients who remained transfusion independent at 1 year post transplant. Although patients with stable MC can sustain long-term transfusion independence, the level of MC within the first 2 months after BMT is highly predictive of secondary graft failure. Patients with >25% MC have a 96% risk of becoming transfusion dependent and those with an MC between 10 and 25% have a 41% risk of doing so.2 It would appear, therefore, that the outcome for patients with MC is related to achieving a state of stable long-term MC. About 10% of patients achieve this state wherein the number of donor marrow cells is sufficient to sustain erythroid cell production and maintain transfusion independence.5 However, graft failure has been known to occur after a long period of stable MC.6 The reasons as to why patients with persistent MC remain transfusion independent are uncertain. A possible explanation could be the presence of high proportions of IL-10-producing type 1 regulatory cells (Tr1) in such patients, possibly as a result of MC providing chronic allogenic stimulus.7 Endogenous IL-10 inhibits alloreactivity against both host and donor cells and may be responsible for the induction and maintenance of long-term tolerance. Such patients are reported to have a lower incidence of GVHD.8 It has also been reported that transfusion independency can be maintained by an increase in autologous HbF production post transplant in the event of graft failure.9 This explanation may partly apply to our case as HbF production was increased when the DC reached its nadir, although, in the absence of erythroid chimerism, we do not know whether it was produced by donor or autologous erythropoiesis.

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References

  1. Lucarelli G, Gaziev J . Advances in the allogeneic transplantation for thalassemia. Blood Rev 2008; 22: 53–63.

    Article  Google Scholar 

  2. Andreani M, Nesci S, Lucarelli G, Tonucci P, Rapa S, Angelucci E et al. Long-term survival of ex-thalassemic patients with persistent mixed chimerism after bone marrow transplantation. Bone Marrow Transplant 2000; 25: 401–404.

    Article  CAS  Google Scholar 

  3. Andreani M, Manna M, Lucarelli G, Tonucci P, Agostinelli F, Ripalti M et al. Persistence of mixed chimerism in patients transplanted for the treatment of thalassemia. Blood 1996; 87: 3494–3499.

    CAS  Google Scholar 

  4. Lisini D, Zecca M, Giorgiani G, Montagna D, Cristantielli R, Labirio M et al. Donor/recipient mixed chimerism does not predict graft failure in children with b-thalassemia given an allogeneic cord blood transplant from an HLA-identical sibling. Haematologica 2008; 93: 1859–1867.

    Article  PubMed  Google Scholar 

  5. Andreani M, Testi M, Battarra M, Indigeno P, Guagnano A, Polchi P et al. Relationship between mixed chimerism and rejection after bone marrow transplantation in thalassaemia. Blood Transfus 2008; 6: 143–149.

    PubMed  PubMed Central  Google Scholar 

  6. Giardini C, Visani G, Lucesole M, Leopardi G, Sparaventi G, D’Adamo F et al. Unusual late rejection of the first graft seven years after allogeneic transplant for thalassemia successfully treated with second BMT. Bone Marrow Transplant 2007; 39 (Suppl. 1): S191 (Poster 781).

    Google Scholar 

  7. Serafini G, Andreani M, Testi M, Battarra M, Bontadini A, Biral E et al. Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia. Haematologica 2009; 94: 1415–1426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Svenberg P, Mattsson J, Ringden O, Uzunel M . Allogeneic hematopoietic SCT in patients with non-malignant diseases, and importance of chimerism. Bone Marrow Transplant 2009; 44: 757–763.

    Article  CAS  PubMed  Google Scholar 

  9. Paciaroni K, Gallucci C, De Angelis G, Alfieri C, Roveda A, Lucarelli G . Sustained and full fetal hemoglobin production after failure of bone marrow transplant in a patient homozygous for beta 0-thalassemia: a clinical remission despite genetic disease and transplant rejection. Am J Hematol 2009; 84: 372–373.

    Article  PubMed  Google Scholar 

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  1. Department of Paediatric Haematology, Sheffield Children's Hospital, Sheffield, UK

    A Alfred & A J Vora

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  1. A Alfred
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  2. A J Vora
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Correspondence to A J Vora.

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Alfred, A., Vora, A. What is the minimum level of donor chimerism necessary to sustain transfusion independence in thalassaemia?. Bone Marrow Transplant 46, 769–770 (2011). https://doi.org/10.1038/bmt.2010.186

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