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Incidence and management of hepatic venoocclusive disease in 237 patients undergoing reduced-intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT)

Bone Marrow Transplantation volume 38, pages 823–824 (2006)Cite this article

Hepatic venoocclusive disease (VOD) is a clinical syndrome comprising of hyperbilirubinaemia, painful enlargement of the liver, ascites and weight gain with a typical onset by day 30 following haematopoietic stem cell transplantation (HSCT). Diagnosis is confirmed by liver histology and differential diagnoses such as hepatic graft-versus-host disease (GVHD), drug-induced cholestasis and sepsis have to be excluded. The dose intensity of conditioning regimens has an important effect on the subsequent development of VOD. A 6-month prospective European Group for Blood and Marrow Transplantation study reported an incidence of VOD post autologous and allogeneic bone marrow transplantation at 3.1 and 8.9%, respectively.1 Indeed, following myeloablative conditioning with high-dose cytoreductive therapy±total body irradiation (TBI), the incidence of VOD has been reported to be as high as 54%.2 In contrast, using a non-myeloablative conditioning regimen with 2 Gy TBI±fludarabine, the MD Anderson group reported hyperbilirubinaemia in 84% of patients receiving allogeneic transplants, but with no reports of VOD.3 VOD is a significant cause of morbidity and mortality following allogeneic HSCT, with limited treatment options. Anticoagulants and antifibrinolytic agents such as heparin, and tissue plasminogen activator, which prevent microvascular thrombosis and may reduce hepatic sinusoidal injury, have been used with limited success. Defibrotide (DF) is the sodium salt of a single-stranded polydeoxyribonucleotide with anti-ischaemic, anti-inflammatory and thrombolytic without significant anticoagulant property. Recently, DF has shown promise in prophylaxis and treatment of VOD following allogeneic transplantation. We have retrospectively reviewed the incidence of VOD among patients treated with reduced-intensity conditioning (RIC) HSCT at our centre, and evaluated the use of DF to treat patients with VOD (Table 1).

Table 1 Patient characteristics and treatment details
Full size table

Two hundred and thirty-seven non-myeloablative allografts were performed from January 1999 to December 2004. The median recipient age was 51 years (range: 19–72 years). Patients were conditioned with BCNU/etoposide/cytarabine/alemtuzumab (n=37), fludarabine/melphalan/alemtuzumab (n=26) for lymphoid disorders (non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukaemia, myeloma) and fludarabine/busulphan/alemtuzumab (chronic myelogenous leukaemia, myelodysplastic syndrome, acute myelogenous leukaemia) (n=174) for myeloid disorders. Forty-five patients had a previous HSCT (21 autografts, 24 allografts). During pre-transplantation assessment, 10 patients were noted to have impaired baseline liver function tests (LFTs) and an additional eight patients had serological evidence of past hepatitis B infection. All patients had LFTs and body weight monitored daily until discharge and twice weekly thereafter for the first 3 months. Cyclosporine levels were performed daily as inpatient and twice weekly as outpatient. All suspected patients had liver imaging and comorbid events such as sepsis, GVHD and hepatotoxic drug exposure were excluded wherever possible. Clinical diagnosis of VOD was determined based on previously described criteria.4

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References

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  1. Department of Haematological Medicine, Kings College London and Kings College Hospital, London, UK

    K Ramasamy, Z Y Lim, A Pagliuca, R Grundy, S Devereux, A Y L Ho & G J Mufti

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  1. K Ramasamy
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  2. Z Y Lim
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Correspondence to G J Mufti.

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Ramasamy, K., Lim, Z., Pagliuca, A. et al. Incidence and management of hepatic venoocclusive disease in 237 patients undergoing reduced-intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT). Bone Marrow Transplant 38, 823–824 (2006). https://doi.org/10.1038/sj.bmt.1705528

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