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Be ready by identifying preexistingrisk factors for VOD

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

Patient icon

Patient- and disease-related risk factors1,2

  • 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
  • Resistance to activated protein C
  • Genetic factors (GSTM1 polymorphism, C282Y allele, MTHFR 677CC/1298CC haplotype)
Infant icon

Pediatric-specific patient- and disease-related risk factors

  • Low weight1
  • Age <2 years1,3
  • Lansky score <904,5
  • History of any of the following diseases1,3:
    • Osteopetrosis
    • High-dose auto-HSCT for neuroblastoma
    • Hemophagocytic lymphohistiocytosis (HLH)
    • Adrenoleukodystrophy (ALD)
    • Juvenile myelomonocytic chronic leukemia
    • Hemoglobinopathies
      • Sickle cell disease
      • Thalassemia
Overall incidence of VOD in children and infants is ~20%3,a
This is 2-fold higher than in adults6,7
Incidence can be up to 60% in high-risk pediatric patients3,a

Most hepatic-related risk factors are typically non-modifiable1

Liver icon

Hepatic-related risk factors1,2

  • 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 modifiable1

IV Bag icon

Transplant-related risk factors1,2

  • 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 can occur in any patient following HSCT
  1. 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).

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

References: 1. 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. 2. 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. 3. 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. 4. Center for International Blood & Marrow Transplant Research. Appendix L: Karnofsky/Lansky performance status. https://www.cibmtr.org/manuals/fim/1/en/topic/appendix-l-karnofsky-lansky-performance-status?q=appendix+l+karnofskylanskyperformance+status. Accessed June 13, 2019. 5. 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. 6. Nagler A, Labopin M, Berger R, et al. Allogeneic hematopoietic SCT for adults AML using i.v. BU in the conditioning regimen: outcomes and risk factors for the occurrence of hepatic sinusoidal obstructive syndrome. Bone Marrow Transplant. 2014;49(5):628-633. 7. Corbacioglu S, Cesaro E, Faraci M, et al. Lancet. 2012;379(9823):1301-1309.