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Anicteric veno-occlusive disease after hematopoietic stem cell transplantation in children

Bone Marrow Transplantation volume 51, pages 135–137 (2016)Cite this article

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Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome is a potentially fatal complication following hematopoietic stem cell transplantation (HSCT) and occurs in ~30% of the children undergoing HSCT.1 Two diagnostic criteria have been used for the diagnosis of VOD, the Baltimore criteria by Jones et al.2 comprising hyperbilirubinemia of >2 mg/dL and any two of the following: weight gain of >5% from baseline, hepatomegaly or ascites. The diagnosis of VOD based on the Seattle criteria by McDonald et al.3 can be made if any two of the following are present by day +20 after HSCT: hyperbilirubinemia (>2 mg/dL), ascites or weight gain of >2% from baseline, or hepatomegaly. Prompt diagnosis and early intervention is crucial as patients with severe VOD may develop multi-organ failure, requiring intensive care and carry a high mortality of up to 84%.4 Yet there is no consensus on grading severity of VOD. Although liver biopsy is helpful for confirming the diagnosis, in the setting of coagulopathy and thrombocytopenia, it is usually avoided. Ultrasonography has been used in the diagnosis of VOD; in the study by Lassau et al. on multivariate analysis, two ultrasound criteria (splenomegaly and ascites) and one doppler criterion (flow recorded in paraumbilical vein) were correlated with the severity of VOD (P=0.0001). Demonstration of reversal of portal venous blood flow by ultrasonography can be helpful, but is often a late finding indicating advanced disease.5

The Baltimore criteria are more often used in adults and appear to be more stringent than the Seattle criteria; as patients without hyperbilirubinemia are excluded. In contrast, the Seattle criteria may lead to over diagnosis, as some patients may meet the diagnostic criteria earlier in the course of the disease. Higher serum bilirubin levels have been associated with increased severity of VOD and worse outcomes. Bearman et al.6 used total serum bilirubin level and percentage weight gain to create risk curves that would predict the likelihood of developing severe VOD. Total serum bilirubin is often used as a marker for response to treatment with defibrotide, as discussed in studies by Ho et al.7 and Richardson et al.8 However some patients with VOD may not have hyperbilirubinemia but still have all the other features consistent with VOD.9, 10 In a recent study by Myers et al.,10 five patients had a bilirubin of ⩽2 mg/dL at the time of diagnosis of VOD and reversal of portal venous flow (PVF) by ultrasonography; two of these continued to have a bilirubin of <2 mg/dL.10 There have been few studies focusing specifically on anicteric VOD. The primary aim of this study is to assess the clinical course and outcomes of patients with anicteric VOD after HSCT in children.

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References

  1. Mahadeo K, Bajwa RP . Hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation. J Pediatr Intensive Care 2014; 3: 183–193.

    Article  Google Scholar 

  2. 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  Google Scholar 

  3. 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: 116–122.

    Article  CAS  Google Scholar 

  4. 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  Google Scholar 

  5. Lassau NAA, Leclere J, Bennaceur A, Valteau-Couanet D, Hartmann O . Prognostic value of doppler-ultrasonography in hepatic veno-occlusive disease. Transplantation 2002; 74: 60–66.

    Article  Google Scholar 

  6. Bearman SI, Anderson GL, Mori M, Hinds MS, Shulman HM, McDonald GB . Venoocclusive disease of the liver: development of a model for predicting fatal outcome after marrow transplantation. J Clin Oncol 1993; 11: 1729–1736.

    Article  CAS  Google Scholar 

  7. Ho VT, Revta C, Richardson PG . Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies. Bone Marrow Transplant 2008; 41: 229–237.

    Article  CAS  Google Scholar 

  8. 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  Google Scholar 

  9. Corbacioglu S, Kernan N, Lehmann L, Brochstein J, Revta C, Grupp S et al. Defibrotide for the treatment of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation. Expert Rev Hematol 2012; 5: 291–302.

    Article  CAS  Google Scholar 

  10. Myers KC, Dandoy C, El-Bietar J, Davies SM, Jodele S . Veno-occlusive disease of the liver in the absence of elevation in bilirubin in pediatric patients after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2015; 21: 379–381.

    Article  Google Scholar 

  11. 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  Google Scholar 

  12. 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 

  13. Carreras E . How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Br J Haematol 2015; 168: 481–491.

    Article  Google Scholar 

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  1. Department Of Hematology/Oncology/BMT, Nationwide Children’s Hospital, Columbus, OH, USA

    J C Naples, M A Skeens, J Auletta, H Rangarajan, R Abu-Arja, E Horwitz, J Stanek & R S Bajwa

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  1. J C Naples
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  2. M A Skeens
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  3. J Auletta
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  8. R S Bajwa
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Correspondence to R S Bajwa.

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Naples, J., Skeens, M., Auletta, J. et al. Anicteric veno-occlusive disease after hematopoietic stem cell transplantation in children. Bone Marrow Transplant 51, 135–137 (2016). https://doi.org/10.1038/bmt.2015.208

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