Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Underdiagnosed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) as a major cause of multi-organ failure in acute leukemia transplant patients: an analysis from the EBMT Acute Leukemia Working Party

Bone Marrow Transplantation volume 56, pages 917–927 (2021)Cite this article

Subjects

Abstract

Allogeneic hematopoietic cell transplantation (alloHCT) is a complex, potentially fatal therapy featuring a myriad of complications. Triggering event(s) of such complications vary significantly, but often a so-called “multi-organ failure” (MOF) is reported as the leading cause of death. The identification of the exact trigger of MOF is critical towards early and disease-specific intervention to improve outcome. We examined data from 202 alloHCT patients reported to have died of MOF from the EBMT registry aiming to determine their exact cause of death focusing on veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) due to its life-threatening, often difficult to capture yet preventable nature. We identified a total of 70 patients (35%) for whom VOD/SOS could be considered as trigger for MOF and leading cause of death, among which 48 (69%) were previously undiagnosed. Multivariate analysis highlighted history of hepatic comorbidity or gentuzumab use and disease status beyond CR1 as the only significant factors predictive of VOD/SOS incidence (OR = 6.6; p = 0.001 and OR = 3.3; p = 0.004 respectively). VOD/SOS-related MOF was widely under-reported, accounting for 27% of deaths attributed to MOF of unknown origin without a previous VOD/SOS diagnosis. Our results suggest most missed cases developed late VOD/SOS beyond 21 days post-alloHCT, highlighting the importance of the newly revised EBMT criteria.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: VOD diagnosis per scoring system.

Similar content being viewed by others

References

  1. 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 Transpl. 2015;50:781–9.

    Article  CAS  Google Scholar 

  2. Marta P, Maribel D-R, Enric C. Endothelial dysfunction in hematopoietic cell transplantation. Clin Hematol Int. 2019;1:45–51.

    Article  Google Scholar 

  3. 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 Transpl. 2016;51:906–12.

    Article  CAS  Google Scholar 

  4. 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;44:778–83.

    Article  CAS  Google Scholar 

  5. McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED. Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors. Hepatology. 1984;4:116–22.

    Article  CAS  Google Scholar 

  6. Cao Z, Villa KF, Lipkin CB, Robinson SB, Nejadnik B, Dvorak CC. Burden of illness associated with sinusoidal obstruction syndrome/veno-occlusive disease in patients with hematopoietic stem cell transplantation. J Med Econ. 2017;20:871–83.

    Article  Google Scholar 

  7. Kernan NA, Grupp S, Smith AR, Arai S, Triplett B, Antin JH, et al. Final results from a defibrotide treatment-IND study for patients with hepatic veno-occlusive disease/sinusoidal obstruction syndrome. Br J Haematol. 2018;181:816–27.

    Article  CAS  Google Scholar 

  8. Richardson P, Aggarwal S, Topaloglu O, Villa KF, Corbacioglu S. Systematic review of defibrotide studies in the treatment of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS). Bone Marrow Transpl. 2019;54:1951–62.

    Article  CAS  Google Scholar 

  9. 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;379:1301–9.

    Article  CAS  Google Scholar 

  10. Picod A, Bonnin A, Battipaglia G, Giannotti F, Ruggeri A, Brissot E, et al. Defibrotide for sinusoidal obstruction syndrome/veno-occlusive disease prophylaxis in high-risk adult patients: a single-center experience study. Biol Blood Marrow Transpl. 2018;24:1471–5.

    Article  CAS  Google Scholar 

  11. Corbacioglu S, Kernan NA, Pagliuca A, Ryan RJ, Tappe W, Richardson PG. Incidence of anicteric veno-occlusive disease/sinusoidal obstruction syndrome and outcomes with defibrotide following hematopoietic cell transplantation in adult and pediatric patients. Biol Blood Marrow Transpl. 2020;26:1342–9.

    Article  CAS  Google Scholar 

  12. Roeker LE, Kim HT, Glotzbecker B, Nageshwar P, Nikiforow S, Koreth J, et al. Early clinical predictors of hepatic veno-occlusive disease/sinusoidal obstruction syndrome after myeloablative stem cell transplantation. Biol Blood Marrow Transpl. 2018;25:137–44.

    Article  Google Scholar 

  13. Hahn T, Sucheston-Campbell LE, Preus L, Zhu X, Hansen JA, Martin PJ, et al. Establishment of definitions and review process for consistent adjudication of cause-specific mortality after allogeneic unrelated-donor hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2015;21:1679–86.

    Article  Google Scholar 

  14. Kanate AS, Nagler A, Savani B. Summary of scientific and statistical methods, study endpoints and definitions for observational and registry-based studies in hematopoietic cell transplantation. Clin Hematol Int. 2019;2:2–4.

    Article  Google Scholar 

  15. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transpl. 2009;15:1628–33.

    Article  Google Scholar 

  16. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.

    Article  CAS  Google Scholar 

  17. Terwey TH, Vega-Ruiz A, Hemmati PG, Martus P, Dietz E, le Coutre P, et al. NIH-defined graft-versus-host disease after reduced intensity or myeloablative conditioning in patients with acute myeloid leukemia. Leukemia. 2012;26:536–42.

    Article  CAS  Google Scholar 

  18. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.

    Article  CAS  Google Scholar 

  19. Cosmin T, Jun C, Maher A-H, Frank C, Kelli C, Al-Homsi AS. Current status and future directions in graft-versus-host disease prevention following allogeneic blood and marrow transplantation in adults. Clin Hematol Int. 2020;2:5–12.

    Article  Google Scholar 

  20. Maria Queralt S, Arjun Datt L, Wilson L, Zeyad A-S, David L, Dennis K, et al. Safety and efficacy of haploidentical peripheral blood stem cell transplantation for myeloid malignancies using post-transplantation cyclophosphamide and anti-thymocyte globulin as graft-versus-host disease prophylaxis. Clin Hematol Int. 2019;1:105–13.

    Google Scholar 

  21. Rashmika RP, Sorab G, Sebastian G, Bipin NS, Gabor V, Arnon N, et al. Current status and perspectives of irradiation-based conditioning regimens for patients with acute leukemia undergoing hematopoietic stem cell transplantation. Clin Hematol Int. 2019;1:19–27.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sorbonne University, Department of Clinical Hematology and Cellular Therapy, Saint Antoine Hospital, INSERM UMR 938, Paris, France

    Abdul Hamid Bazarbachi, Rama Al Hamed, Myriam Labopin & Mohamad Mohty

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Abdul Hamid Bazarbachi & Rama Al Hamed

  3. Division of Infectious Diseases, Brigham & Women’s, Harvard Medical School, Boston, MA, USA

    Rama Al Hamed

  4. Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland

    Kazimierz Halaburda

  5. Département d’Hématologie, Hospices Civils de Lyon, Pierre-Bénite, France

    Helene Labussiere

  6. HSCT Unit, SC Ematologia, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

    Paolo Bernasconi

  7. University Hospital Antwerp, Edegem, Belgium

    Wilfried Schroyens

  8. Department of Pediatric Oncology and Haematology, University Hospital of Rennes, Rennes, France

    Virginie Gandemer

  9. Radboud University Medical Centre, Nijmegen, The Netherlands

    Nicolaas P. M. Schaap

  10. Service d’hématologie, Centre Hospitalier Universitaire, 06000, Nice, France

    Michael Loschi

  11. Department of Haematology and Oncology, University Hospital Pilsen, Pilsen, Czech Republic

    Pavel Jindra

  12. Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    John Snowden

  13. Department of Hematology, The Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China

    Depei Wu

  14. Department of Hematology, Hopitaux Universitaires Strasbourg, Strasbourg, France

    Blandine Guffroy

  15. BMT Unit, Department of Hematology, IDIBAPS, Hospital Clinic, Institut Josep Carreras, Barcelona, Spain

    Montserrat Rovira

  16. Caen University Hospital, Hematology Institute, Caen, France

    Sylvain P. Chantepie

  17. Department of Hematology, Saint-Luc University Hospital, Brussels, Belgium

    Xavier Poiré

  18. Hematology Department, Complejo Asistencial Universitario de Salamanca-IBSAL; Centro de Investigación del Cáncer-IBMCC, Salamanca, Spain

    Lucia Lopez-Corral

  19. Heartlands Hospital, Birmingham, UK

    Manos Nikolousis

  20. Hematology Division, University of Pisa, Pisa, Italy

    Matteo Pelosini

  21. Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

    Fabio Ciceri

  22. Department of Hematology, University and CHU of Liège, 4000, Liège, Belgium

    Frederic Baron

  23. Department of Internal Medicine, American University of Beirut, Beirut, 1107 2020, Lebanon

    Ali Bazarbachi

  24. Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Franz-Josef-Strauss-Allee 11, University Hospital of Regensburg, Regensburg, Germany

    Selim Corbacioglu

  25. Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    Bipin N. Savani

  26. Department of Hematology, School of Medicine, University of Zagreb, Zagreb, Croatia

    Zinaida Peric

  27. Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel-HaShomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Arnon Nagler

  28. Josep Carreras Foundation and Research Institute, Hospital Clinic/University of Barcelona Campus, Barcelona, Spain

    Enric Carreras

Authors
  1. Abdul Hamid Bazarbachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rama Al Hamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Myriam Labopin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazimierz Halaburda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helene Labussiere
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paolo Bernasconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wilfried Schroyens
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Virginie Gandemer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nicolaas P. M. Schaap
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael Loschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Pavel Jindra
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. John Snowden
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Depei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Blandine Guffroy
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Montserrat Rovira
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Sylvain P. Chantepie
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Xavier Poiré
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Lucia Lopez-Corral
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Manos Nikolousis
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Matteo Pelosini
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Fabio Ciceri
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Frederic Baron
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Ali Bazarbachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Selim Corbacioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Bipin N. Savani
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Zinaida Peric
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Arnon Nagler
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Enric Carreras
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Mohamad Mohty
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohamad Mohty.

Ethics declarations

Conflict of interest

MM reports grants and lecture honoraria from Janssen, Sanofi, and Jazz Pharmaceuticals; lecture honoraria from Celgene, Amgen, Bristol-Myers Squibb, Takeda, and Pfizer; and grants from Roche, all outside the submitted work. JAS reports lecture honoraria from Jazz, Janssen, Sanofi, Gilead and Mallinckrodt, and chairing NHS England Specialised Commissioning Clinical Reference Group for Blood and Marrow Transplantation, all outside the submitted work. FB has received travel grants and/or speaker honoraria from Celgene, AbbVie, Novartis, Pfizer and Sanofi. PJ has received travel grants and/or lecture honoraria from Novartis, Bristol-Myers Squib and Janssen, all outside the submitted work

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bazarbachi, A.H., Al Hamed, R., Labopin, M. et al. Underdiagnosed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) as a major cause of multi-organ failure in acute leukemia transplant patients: an analysis from the EBMT Acute Leukemia Working Party. Bone Marrow Transplant 56, 917–927 (2021). https://doi.org/10.1038/s41409-020-01135-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-01135-3

This article is cited by

Search

Advanced search

Quick links