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Risk Factors for VOD/SOS

Be ready by identifying preexistingrisk factors for VOD/SOS

Most patient- and disease-related risk factors are typically non-modifiable1,2

Patient icon

Patient- and disease-related risk factors include1-3,a

  • Advanced disease (beyond second CR or relapse/refractory)
  • Female receiving norethindrone
  • Older age (in adult patients)
  • Karnofsky score <90%
  • Adult metabolic syndrome
  • Thalassemia
  • Deficit of AT III or t-PA

With a higher incidence of VOD/SOS in children, it is critical to recognize risk factors specific to this vulnerable patient population2,5

Infant icon

Pediatric-specific patient- and disease-related risk factors include2,3,5,6

  • Low weight
  • Age <2 years
  • Lansky score <90
  • History of any of the following diseases:
    • Osteopetrosis
    • High-dose auto-HSCT for neuroblastoma
    • Hemophagocytic lymphohistiocytosis (HLH)
    • Adrenoleukodystrophy (ALD)
    • Juvenile myelomonocytic leukemia (JMML)
    • Hemoglobinopathies
      • Sickle cell disease
      • Thalassemia
Overall incidence of VOD/SOS in children and infants is ~20%5,b
This is 2-fold higher than in adults5 

Incidence can be up to 60% in high-risk pediatric patients5,b

Most hepatic-related risk factors are typically non-modifiable1,2

Liver icon

Hepatic-related risk factors include1-3

  • Previous use of:
    • Gemtuzumab ozogamicin
    • Inotuzumab ozogamicin
  • Transaminase levels >2.5 x ULN
  • Serum bilirubin >1.5 x ULN
  • Cirrhosis
  • Hepatic fibrosis
  • Active viral hepatitis
  • Abdominal or hepatic irradiation
  • Use of hepatotoxic drugs
  • Iron overload

Transplant-related risk factors are modifiable2

IV Bag icon

Transplant-related risk factors include1-3

  • Allogeneic HSCT
  • Second HSCT
  • Myeloablative conditioning regimen
  • Non–T-cell-depleted graft
  • Unrelated donor/HLA mismatch
  • Oral or high-dose BU-based conditioning regimen
  • High-dose TBI-based conditioning regimen
Vigilant monitoring is important regardless of risk factors, as VOD/SOS can occur in any patient following HSCT2,3,5,7,8
Know the various diagnostic criteria to be ready to act on VOD/SOS 
  1. Does not include liver disease, which is categorized as a hepatic-related risk factor.
  2. Based on a position paper proposing diagnostic and severity criteria for SOS/VOD in pediatric patients on behalf of the European Society for Blood and Marrow Transplantation (EBMT).5

AT III=antithrombin III; BU=busulfan; CR=complete remission; HLA=human leukocyte antigen; HSCT=hematopoietic stem-cell transplantation; SOS=sinusoidal obstruction syndrome; TBI=total body irradiation; t-PA=tissue plasminogen activator; ULN=upper limit of normal; VOD=veno-occlusive disease.

References: 1. Cairo MS, Cooke KR, Lazarus HM, Chao N. Modified diagnostic criteria, grading classification and newly elucidated pathophysiology of hepatic SOS/VOD after haematopoietic cell transplantation. Br J Haematol. 2020;190(6):822-836. 2. Mohty M, Malard F, Abecassis 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(6):781-789. 3. Mohty M, Malard F, Abecassis 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(7):906-912. 4. Corbacioglu S, Jabbour EJ, Mohty M. Risk factors for development of and progression of hepatic veno-occlusive disease/sinusoidal obstruction syndrome. Biol Blood Marrow Transplant. 2019;25(7):1271-1280. 5. Corbacioglu S, Carreras E, Ansari M, et al. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2018;53(2):138-145. 6. Center for International Blood & Marrow Transplant Research. Appendix L. Accessed January 20, 2022. Karnofsky/Lansky performance status. https://www.cibmtr.org/manuals/fim/1/en/topic/appendix-l-karnofsky-lansky-performance-status 7. Carreras E, Díaz-Beyá M, Rosiñol L, et al. 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(11):1713-1720. 8. Carreras E. How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Br J Haematol. 2015;168(4):481-491.