Defibrotide Effectively Prevents Veno-Occlusive Disease of the Liver (VOD) after Allogeneic Stem Cell Transplantation. An Extended Study.

VOD of the liver is reported to occur in 10–30% of patients after allogeneic HSCT, with mortality rates up to 50%. We previously reported a pilot study of defibrotide (Prociclide® Crinos, Como, Italy) VOD prophylaxis showing a significantly lower rate of VOD as compared to historical controls. We now report the results of an extended study.

Between 2000 and 2005, 157 consecutive patients were transplanted for hematological diseases. Median age was 43 y (range 5–61 y), M/F: 96/61; diagnosis was AML=42, ALL=19, CML=28, MDS/MPS=24, lymphoma=22, MM=12, AA=7, solid tumor=3. Donors were HLA-identical siblings (65%), unrelated (32%) mismatched relatives (3%). Stem cell source was peripheral blood (87%) and bone marrow (13%). The transplants were T-cell depleted by CAMPATH-1H in vitro, with (69%) or without (7%) T-cell add-back or left unmanipulated (24%). Conditioning was myeloablative with CyTBI (50%), BuCy (9%) other myeloablative (11%) or non-myeloablative (30%) using Fludara/Bu/ATG. GVHD prophylaxis was CSA with or without MTX or MMF. Nine pts received a second transplant for relapse or graft failure.

Defibrotide was given intravenously 6 hourly starting prior to conditioning up to day +20 posttransplant (dose range 20–30 mg/kg) in addition to low dose heparin. The Baltimore criteria were used to score VOD.

Results: No VOD was observed after 165 transplants. Defibrotide was well tolerated and no side effects were attributed to this medication. Median peak levels of bilirubin were 21 umol/l (range 9–286 umol/l), aPTT: 35 sec (range 24–83 sec) and fibrinogen: 7.1 g/l (range 3.1–9.5 g/l). Day 100 survival was 91±5%. With a median follow-up of 25 mths (range 3–80 mths), 1 year OS, TRM and RR were 74±7%, 13±5% and 29±8% respectively. The incidence of aGVHD >=II was 32±7 %.

Conclusion: The results of this study suggest that defibrotide is an effective prophylaxis for VOD.