Defibrotide Low-Dose Continuous Infusion from Day +1 Until Day +21 after Allogeneic Stem Cell Transplantation as Prophylaxis of Veno-Occlusive Disease (VOD) of the Liver. A Single Centre Experience.
Authors: Bonini Alessandro , Avanzini Paolo , Masini Luciano , Merli Francesco , Ilariucci Fiorella , Gamberi Barbara , Tieghi Alessia , Alvarez Isabel , Immovilli Annalisa , Pilia Annalisa , Gugliotta Luigi 
Published: October 2019

Abstract
Defibrotide has been shown to be effective in the treatment and prophylaxis of the VOD,a relatively common complication after allogeneic hematopoietic stem cell transplantation(SCT).We report our experience in 41 consecutive patients(pts) for a total of 43 SCT.The analysis,closed at day +35 after BMT,is limited to 39 SCT,since 4 pts not affected by VOD died on day +3,+11,+13 and +24,respectively.The pts(mean age 42 yrs,range 16–65) were affected by acute leukemia(14), chronic myeloid leukemia(5),lymphoma(15),multiple myeloma(2),myelodisplasia(1) and solid tumor(2).Other relevant clinical characteristics were:resistant or metastatic disease 9,previous autologous BMT 6,previous allogeneic SCT 2,previous B virus hepatitis 5,liver metastases 1 and lymphoma of the liver 1.All were transplanted from their HLA-identical sibling;the conditioning regimen was defined as reduced in 15(thiotepa,fludarabine and cyclophosphamide),while it was conventional in the other 24 SCT with use of busulphan(oral 13 and iv 11) and cyclophosphamide(VP16 added in few cases;never TBI). Thirteen received bone marrow and 26 peripheral blood as source of stem cells.No T-cell depletion was done and the GVHD prophylaxis regimen was CsA+MTX for 36 pts, CsA alone for 2 pts and FK506+MTX for 1 patient.For VOD prophylaxis no Heparin was administered,while Defibrotide was given at the dosage of 10 mg/Kg in continuous iv infusion starting on day +1 until day +21 after the SCT.Defibrotide was very well tolerated,and no hemorrhagic complications were observed.Blood coagulation significant alterations were:prolonged PT(4/39),prolonged aPTT(3/39),fibrinogen elevated(23/39,never over 800 mg/dl),low level(less than 50%) of ATIII,and/or protein C,and/or protein S(2/39).By using the VOD Baltimore criteria,only 1 case of VOD was observed at day +29 in a patient who died at day +36 with VOD,aspergillosis and CMV pneumonia.The bilirubin was more than 2 times the normal value in 20/39;US scan of the liver and Doppler,performed in 15 pts with a possibile sign of VOD,was positive only in the patient who died for VOD.We documented 29 infectious complications(14 FUO,9 gram positive bacteremias,2 pneumonia and 4 invasive aspergillosis).We observed acute GVHD in 10 pts(9 grade I–II and 1 grade III).Five pts died between +36 and +100 but none for VOD(3 for progression of their disease and 2 for aspergillosis).Since in this at risk transplanted population only 1 VOD has been observed,Defibrotide low-dose continous infusion, not associated with Heparin,seems able to play a relevant role in the VOD prophylaxis.On considering the favourable results obtained by us and Others,the absence of toxicity and the low cost of Defibrotide,we intend to continue this experience with defibrotide as VOD prophylaxis,even if we foretell a large randomized study to find better indications.