Effectiveness of Defibrotide in the Prevention of VOD Among Patients Receiving Allogeneic Hematopoetic Cell Transplantation: A Retrospective Single Center Experience

Hepatic venooclusive disease (VOD), is one of the major regimen related early complications of hematopoietic cell transplantation (HCT). The incidence of VOD ranges between 3% to 54% in different series. Mortality rates also differ according to severity of the disease and defibrotide treatment. We aimed to assess the impact of defibrotide prophylaxis on the incidence of VOD in our center by day 30 after allogeneic HST (allo-HCT).

We retrospectively analyzed 87 consecutive patients who had received allo-HCT with different diagnosis of hematological diseases in our transplantation unit between January 2009 and August 2012 in two groups acoording two VOD prophylaxis they received. The first (standard group; n: 59) and second (defibrotide group; n: 28) groups of patients were treated with allo-HST during January 2009-October 2011 and November 2011-August 2012 (n:28), respectively. Patient characteristics are summarized in Table 1. All of the patients had enoxaparin (as long as Plt ≥ 30000/mm³ and absence of bleeding), ursodeoxycolic acid and N-acetylsistein prophylaxis. Twenty eight of the patients in the second group received upfront defibrotide 10 mg/kg/day i.v between posttransplantation days 1 and 14 in addition to standard VOD prophylaxis approach. If the patients were diagnosed as VOD, defibrotide dose was increased to 25 mg/kg/day i.v in the prophylaxsis group. Fifty nine of the patients belonging to standard group did not have the opportunity to get defibrotide for prophylaxis or treatment due to drug supply. Diagnosis and classification of severity was defined according to Seattle criteria. None of the patients had hepatic biopsy for histopathological diagnosis mainly because of the thrombocytopenia/coagulopaty associated bleeding risk.

Nine of eighty seven (10%) patients diagnosed as VOD; only one of these patients was in the defibrotide group. Less patients were diagnosed as VOD in the defibrotide (8/59; 3.5%) compared to standard prophlaxis (1/28;13%) group (p=0,153). Number of patients who were diagnosed with mild/moderate/severe VOD were 2/3/4,respectively. The median day of VOD diagnosis was posttransplantation day 9(2–19). The median of maximum bilirubin level was 5 (2,1–24). Seven of nine (77%) patients died during the follow up. Eight patients in standard who were diagnosed with VOD could not be treated with the defibrotide as the drug was unavailable during this time period in our country. The only patient with VOD in second group received primary defibrotide prophylaxis and the dose of the drug was increased to treatment dosage when VOD was diagnosed. Venooclusive disease of the two alive patients resolved completely without defibrotide treatment. Hypoxemia and O₂ requirement was observed in four patients. The median diuretic (furosemide; IV) requirement for weight gain of the patients was found to be lower for patients in defibrotide arm (160 mg; (0–4280 mg)) compared to standard prophylaxis arm (280 mg; (20–6500 mg)) (p=0,196).

There are several factors that can effect VOD incidence during allogeneic stem cell transplantation. Myeloablative conditioning, previous liver disease, poor performance status, and alternative donors are the variables with higher impact on VOD development. Our patient groups were not statistically different according to the conditioning regimen, number of transplantations and previous hepatic disease status. Zheng et al reported the incidence of VOD with or without defibrotide prophylaxis as 13,7% and 4.4%, respectively. Although our results are similar to this report we did not observed a significant difference in terms of VOD between the two groups. The majority of our patients had either moderate or severe disease and mortality was very high in the group without defibrotide prophylaxis; as a consequence of inability to reach to defibrotide. In conclusion, defibrotide seems to be a very promising agent to reduce VOD incidence by prophylactic usage.

No relevant conflicts of interest to declare.