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Haploidentical stem cell transplantation with CD3+-/CD19+- depleted peripheral stem cells for patients with advanced stage sickle cell disease and no alternative donor: results of a pilot study

Bone Marrow Transplantation volume 52, pages 938–940 (2017)Cite this article

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Sickle cell disease (SCD) is one of the most frequent inherited diseases and the most prevalent hemoglobinopathy worldwide.1 The very divergent clinical manifestations seem to be based on interactions between sickle cells, endothelium and immune cells promoting the systemic vasculopathy with consecutive ubiquitous end organ damage.2 Despite significant improvements in preventive and therapeutic modalities, SCD is a progressively debilitating and chronic multiorgan disease with a persistently high risk of morbidity and mortality.1, 3 Children with SCD can develop a progressive neurocognitive deficit without overt strokes. Their quality of life is significantly impaired with a high incidence of disability and unemployment.4

To date allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative option and currently only offered to patients with serious SCD-related complications like strokes and acute chest syndromes and only if an HLA-matched related sibling donor (MSD) or matched unrelated donor (MUD)5 is available. Myeloablative alloHSCT with bone marrow (BM) or cord blood from MSD and a busulfan (Bu)- based conditioning regimen combined with cyclophosphamide (Cy) or with thiotepa (TT) and fludarabine (Flu) are the standard of care.5, 6 One of the major improvements was the addition of anti-thymocyte globulin (ATG) to the conditioning regimen, which decreased the rejection rate from 22.6 to 3% and increased overall survival (OS) to 95%.7

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References

  1. Gluckman E . Allogeneic transplantation strategies including haploidentical transplantation in sickle cell disease. Hematology Am Soc Hematol Educ Program 2013; 2013: 370–376.

    Article  PubMed  Google Scholar 

  2. Kaul DK, Finnegan E, Barabino GA . Sickle red cell-endothelium interactions. Microcirculation 2009; 16: 97–111.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bolanos-Meade J, Brodsky RA . Blood and marrow transplantation for sickle cell disease: is less more? Blood Rev 2014; 28: 243–248.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Verduzco LA, Nathan DG . Sickle cell disease and stroke. Blood 2009; 114: 5117–5125.

    Article  CAS  PubMed  Google Scholar 

  5. Bernaudin F, Socie G, Kuentz M, Chevret S, Duval M, Bertrand Y et al. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood 2007; 110: 2749–2756.

    Article  CAS  PubMed  Google Scholar 

  6. Locatelli F, Kabbara N, Ruggeri A, Ghavamzadeh A, Roberts I, Li CK et al. Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling. Blood 2013; 122: 1072–1078.

    Article  CAS  PubMed  Google Scholar 

  7. Panepinto JA, Walters MC, Carreras J, Marsh J, Bredeson CN, Gale RP et al. Matched-related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research. Br J Haematol 2007; 137: 479–485.

    Article  PubMed  Google Scholar 

  8. Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med 2014; 371: 339–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Stahl T, Bohme MU, Kroger N, Fehse B . Digital PCR to assess hematopoietic chimerism after allogeneic stem cell transplantation. Exp Hematol 2015; 43: 462–468 e461.

    Article  CAS  PubMed  Google Scholar 

  10. Luznik L, Fuchs EJ . High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation. Immunol Res 2010; 47: 65–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bolanos-Meade J, Fuchs EJ, Luznik L, Lanzkron SM, Gamper CJ, Jones RJ et al. HLA-haploidentical bone marrow transplantation with post-transplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood 2012; 120: 4285–4291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R et al. HLA-haploidentical stem cell transplantation after removal of alphabeta+ T and B cells in children with nonmalignant disorders. Blood 2014; 124: 822–826.

    Article  CAS  PubMed  Google Scholar 

  13. Booth C, Lawson S, Veys P . The current role of T cell depletion in paediatric stem cell transplantation. Br J Haematol 2013; 162: 177–190.

    Article  CAS  PubMed  Google Scholar 

  14. Handgretinger R . Negative depletion of CD3(+) and TcR alphabeta(+) T cells. Curr Opin Hematol 2012; 19: 434–439.

    Article  CAS  PubMed  Google Scholar 

  15. Oevermann L, Lang P, Feuchtinger T, Schumm M, Teltschik HM, Schlegel P et al. Immune reconstitution and strategies for rebuilding the immune system after haploidentical stem cell transplantation. Ann NY Acad Sci 2012; 1266: 161–170.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Author contributions

JF, BP and SC reviewed the literature, analyzed the data and wrote the manuscript. JF, BP, KR, DW, EH and SC were involved in the clinical management of the patients. All authors contributed to the intellectual content of this paper and approved the final manuscript.

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  1. J Foell and B Pfirstinger: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Regensburg, Germany

    J Foell, B Pfirstinger, K Rehe & S Corbacioglu

  2. Department of Internal Medicine III, Hematology and Oncology, University Hospital of Regensburg, Regensburg, Germany

    D Wolff & E Holler

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  1. J Foell
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Correspondence to S Corbacioglu.

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Foell, J., Pfirstinger, B., Rehe, K. et al. Haploidentical stem cell transplantation with CD3+-/CD19+- depleted peripheral stem cells for patients with advanced stage sickle cell disease and no alternative donor: results of a pilot study. Bone Marrow Transplant 52, 938–940 (2017). https://doi.org/10.1038/bmt.2017.49

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