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Transplant Toxicities

Veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic stem cell transplantation: Middle East/North Africa regional consensus on prevention, diagnosis and management

Abstract

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) of the liver is a serious, early complication of haematopoietic stem cell transplantation (HSCT), severe and very severe forms of which are associated with a high mortality rate. A wide variety of patient, disease and treatment-related risk factors for VOD/SOS have been identified. Several bodies have published recommendations for the diagnosis, prevention and management of VOD/SOS following HSCT. A group of regional experts have developed a consensus statement on the diagnosis, prevention and management of VOD/SOS in the Middle East and North Africa region to help in the management of HSCT patients in the region. Risk factors of particular relevance in the region include iron overload in thalassaemia patients, some hereditary metabolic disorders due to consanguinity and infection with hepatitis virus B or C. Recommendations include diagnosis of VOD/SOS based on established clinical criteria, prophylaxis with defibrotide and/or ursodeoxycholic acid in patients at increased risk of VOD/SOS, and treatment with defibrotide for patients with severe/very severe VOD/SOS (and, if clinically indicated, in those with moderate or rapidly progressing VOD/SOS, as per the new European Society for Blood and Marrow Transplantation classification).

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References

  1. Tuncer HH, Rana N, Milani C, Darko A, Al-Homsi SA . Gastrointestinal and hepatic complications of hematopoietic stem cell transplantation. World J Gastroenterol 2012; 18: 1851–1860.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant 2010; 16: 157–168.

    Article  PubMed  Google Scholar 

  3. Carreras E, Díaz-Beyá M, Rosiñol L, Martínez C, Fernández-Avilés F, Rovira M . The incidence of veno-occlusive disease following allogeneic hematopoietic stem cell transplantation has diminished and the outcome improved over the last decade. Biol Blood Marrow Transplant 2011; 17: 1713–1720.

    Article  PubMed  Google Scholar 

  4. Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A et al. BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. Br J Haematol 2013; 163: 444–457.

    Article  CAS  PubMed  Google Scholar 

  5. Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M et al. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 2015; 50: 781–789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Apperley J, Carreras E, Gluckman E, Masszi T (eds). The EBMT Handbook: Haematopoietic Stem Cell Transplantation, 6th edn. European School of Haematology: Paris, France, 2012.

    Google Scholar 

  7. Jones RJ, Lee KS, Beschorner WE, Vogel VG, Grochow LB, Braine HG et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation 1987; 44: 778–783.

    Article  CAS  PubMed  Google Scholar 

  8. Shulman HM, Hinterberger W . Hepatic veno-occlusive disease–liver toxicity syndrome after bone marrow transplantation. Bone Marrow Transplant 1992; 10: 197–214.

    CAS  PubMed  Google Scholar 

  9. Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M et al. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant 2016; 51: 906–912.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cheuk DK. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: Prophylaxis and treatment controversies. World J Transplant 2012; 2: 27–34.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 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  PubMed  Google Scholar 

  12. Chalandon Y, Roosnek E, Mermillod B, Newton A, Ozsahin H, Wacker P et al. Prevention of veno-occlusive disease with defibrotide after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2004; 10: 347–354.

    Article  CAS  PubMed  Google Scholar 

  13. Dignan F, Gujral D, Ethell M, Evans S, Treleaven J, Morgan G et al. Prophylactic defibrotide in allogeneic stem cell transplantation: minimal morbidity and zero mortality from veno-occlusive disease. Bone Marrow Transplant 2007; 40: 79–82.

    Article  CAS  PubMed  Google Scholar 

  14. Cheuk DK, Chiang AK, Ha SY, Chan GCF . Interventions for prophylaxis of hepatic veno-occlusive disease in people undergoing haematopoietic stem cell transplantation. Cochrane Database Syst Rev 2015; 5: CD009311.

    Google Scholar 

  15. Richardson PG, Elias AD, Krishnan A, Wheeler C, Nath R, Hoppensteadt D et al. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population. Blood 1998; 92: 737–744.

    CAS  PubMed  Google Scholar 

  16. Richardson PG, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D et al. Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome. Blood 2002; 100: 4337–4343.

    Article  CAS  PubMed  Google Scholar 

  17. Richardson PG, Soiffer RJ, Antin JH, Uno H, Jin Z, Kurtzberg J et al. Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial. Biol Blood Marrow Transplant 2010; 16: 1005–1017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Richardson PG, Riches ML, Kernan NA, Brochstein JA, Mineishi S, Termuhlen AM et al. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood 2016; 127: 1656–1665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Richardson PG, Smith AR, Triplett BM, Kernan NA, Grupp SA, Antin JH et al. Defibrotide for pediatric and adult patients with hepatic veno-occlusive disease: interim age subgroup survival analysis from an ongoing expanded access program in the US. Bone Marrow Transplant 2015; 50: S74 (Abstract O127).

    Article  Google Scholar 

  20. Dalle JH, Giralt SA . Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: risk factors and stratification, prophylaxis, and treatment. Biol Blood Marrow Transplant 2016; 22: 400–409.

    Article  PubMed  Google Scholar 

  21. Corbacioglu S, Carreras E, Mohty M, Pagliuca A, Ballabbio M, Hume R et al. Defibrotide for the treatment of hepatic veno-occlusive disease: an update from the international compassionate use program in 710 patients. Biol Blood Marrow Transplant 2015; 21: S108.

    Article  Google Scholar 

  22. Al Beihany A, Al Omar H, Sahovic E, Chaudhri N, Al Mohareb F, Al Sharif F et al. Successful treatment of hepatic veno-occlusive disease after myeloablative allogeneic hematopoietic stem cell transplantation by early administration of a short course of methylprednisolone. Bone Marrow Transplantation 2008; 41: 287–291.

    Article  CAS  PubMed  Google Scholar 

  23. Myers KC, Lawrence J, Marsh RA, Davies SM, Jodele S . High-dose methylprednisolone for veno-occlusive disease of the liver in pediatric hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant 2013; 19: 500–503.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors’ face-to-face meetings were supported financially by Biologix and Jazz Pharmaceuticals. Their discussions were facilitated by Mohamad Mohty (Université Pierre & Marie Curie, Hôpital Saint-Antoine, Paris, France), Josu de La Fuente (St Mary’s Hospital and Imperial College London, UK) and Fiona Dignan (Manchester Royal Infirmary, UK). Editorial support was provided by Synergy Medical Communications Ltd.

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Correspondence to A Bazarbachi.

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All authors received honoraria from Biologix for attending expert panel meetings.

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Al Jefri, A., Abujazar, H., Al-Ahmari, A. et al. Veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic stem cell transplantation: Middle East/North Africa regional consensus on prevention, diagnosis and management. Bone Marrow Transplant 52, 588–591 (2017). https://doi.org/10.1038/bmt.2016.300

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