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Use of defibrotide to treat transplant-associated thrombotic microangiopathy: a retrospective study of the Paediatric Diseases and Inborn Errors Working Parties of the European Society of Blood and Marrow Transplantation

Bone Marrow Transplantation volume 52, pages 762–764 (2017)Cite this article

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Endothelial cell activation syndromes, including capillary leak syndrome, engraftment syndrome, sinusoidal obstruction syndrome and transplant-associated thrombotic microangiopathy, collectively are common complications following haematopoietic stem cell transplantation (HSCT), can lead to a complicated post-transplant clinical course and are associated with significant morbidity and mortality. Transplant-associated thrombotic microangiopathy (TA-TMA) is caused by widespread endothelial dysfunction, predominantly in the kidneys and brain, but also lung, liver and gut, and can lead to multiorgan failure for many patients. The disease is within the spectrum of microangiopathic haemolytic anaemia and thrombocytopenia and is associated with intravascular platelet activation and formation of platelet-dense thrombi within the microcirculation.1 Given the overlap of symptoms with other post-HSCT endothelial activation symptoms, the disease is not always recognised, with a variably reported prevalence of around 12–39%.2, 3

Associated factors for the development of TA-TMA include viral infections, GvHD, chemotherapy and stem cell inoculums from unrelated donors,2, 3 which cause endothelial damage, and likely each potentiate any initial endothelial insult.

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References

  1. Elsallabi O, Bhatt VR, Dhakal P, Foster KW, Tendulkar KK . Hematopoietic stem cell transplant-associated thrombotic microangiopathy. Clin Appl Thromb Hemost 2016; 22: 12–20.

    Article  CAS  Google Scholar 

  2. Jodele S, Laskin BL, Dandoy CE, Myers KC, El-Bietar J, Davies SM et al. A new paradigm: diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev 2015; 29: 191–204.

    Article  Google Scholar 

  3. Uderzo C, Bonanomi S, Busca A, Renoldi M, Ferrari P, Iacobelli M et al. Risk factors and severe outcome in thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation. Transplantation 2006; 82: 638–644.

    Article  Google Scholar 

  4. Daly AS, Xenocostas A, Lipton JH . Transplantation-associated thrombotic microangiopathy: twenty-two years later. Bone Marrow Transplant 2002; 30: 709–715.

    Article  CAS  Google Scholar 

  5. Kim SS, Patel M, Yum K, Keyzner A . Hematopoietic stem cell transplant- associated thrombotic microangiopathy: review of pharmacologic treatment options. Transfusion 2015; 55: 452–458.

    Article  CAS  Google Scholar 

  6. Kornblum N, Ayyanar K, Benimetskaya L, Richardson P, Iacobelli M, Stein CA . Defibrotide, a polydisperse mixture of single-stranded phosphodiester oligonucleotides with lifesaving activity in severe hepatic veno-occlusive disease: clinical outcomes and potential mechanisms of action. Oligonucleotides 2006; 16: 105–114.

    Article  CAS  Google Scholar 

  7. Corbacioglu S, Greil J, Peters C, Wulffraat N, Laws HJ, Dilloo D et al. Defibrotide in the treatment of children with veno-occlusive disease (VOD): a retrospective multicentre study demonstrates therapeutic efficacy upon early intervention. Bone Marrow Transplant 2004; 33: 189–195.

    Article  CAS  Google Scholar 

  8. Corbacioglu S, Cesaro S, Faraci M, Valteau-Couanet D, Gruhn B, Rovelli A et al. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial. Lancet 2012; 379: 1301–1309.

    Article  CAS  Google Scholar 

  9. Strouse C, Richardson P, Prentice G, Korman S, Hume R, Nejadnik B et al. Defibrotide for treatment of severe veno-occlusive disease in pediatrics and adults: an exploratory analysis using data from the center for international blood and marrow transplant research. Biol Blood Marrow Transplant 2016; 22: 1306–1312.

    Article  CAS  Google Scholar 

  10. Cho BS, Yahng SA, Lee SE, Eom KS, Kim YJ, Kim HJ et al. Validation of recently proposed consensus criteria for thrombotic microangiopathy after allogeneic hematopoietic stem-cell transplantation. Transplantation 2010; 90: 918–926.

    Article  CAS  Google Scholar 

  11. Corti P, Uderzo C, Tagliabue A, Della Volpe A, Annaloro C, Tagliaferri E et al. Defibrotide as a promising treatment for thrombotic thrombocytopenic purpura in patients undergoing bone marrow transplantation. Bone Marrow Transplant 2002; 29: 542–543.

    Article  CAS  Google Scholar 

  12. Vasu S, Wu H, Satoskar A, Puto M, Roddy J, Blum W et al. Eculizumab therapy in adults with allogeneic hematopoietic cell transplant-associated thrombotic microangiopathy. Bone Marrow Transplant 2016; 51: 1241–1244.

    Article  CAS  Google Scholar 

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Acknowledgements

LY has received an unrestricted travel grant from JAZZ Pharmaceuticals.

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Authors and Affiliations

  1. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK

    L Yeates, M A Slatter & A R Gennery

  2. Department of Pediatrics, BMT Unit, University of Milan, Milan, Italy

    S Bonanomi & C Uderzo

  3. Department of Haematology, Singapore General Hospital, Singapore, Singapore

    F L W I Lim, S Y Ong & W H Y Hwang

  4. EBMT Data and Study Office, Saint-Antoine Teaching Hospital, Paris, France

    A Dalissier

  5. Department of Hematology, Allogeneic HSCT Unit, Azienda Policlinico Umberto I, Sapienza University of Rome, Rome, Italy

    W Barberi

  6. Department of Pediatrics, University Medical Center Ulm, Ulm, Germany

    A Shulz

  7. Centre de Cancérologie Charles Bruneau, CHU Sainte-Justine, Montréal, Canada

    M Duval

  8. Paediatric Haematopoietic Cell Transplantation, Rigshospitalet, University Hospital, Copenhagen, Denmark

    C Heilmann

  9. Haematology Intensive Care, Brussels University Hospital, Brussels, Belgium

    A Willekens

  10. Division of Stem Cell Transplantation and Immunology, University Hospital Frankfurt, Frankfurt, Germany

    P Bader

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  1. L Yeates
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Correspondence to A R Gennery.

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Yeates, L., Slatter, M., Bonanomi, S. et al. Use of defibrotide to treat transplant-associated thrombotic microangiopathy: a retrospective study of the Paediatric Diseases and Inborn Errors Working Parties of the European Society of Blood and Marrow Transplantation. Bone Marrow Transplant 52, 762–764 (2017). https://doi.org/10.1038/bmt.2016.351

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