DEFIBROTIDE SHOWS EFFICACY IN THE PREVENTION OF SINUSOIDAL OBSTRUCTION SYNDROME AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A RETROSPECTIVE STUDY ON 237 PATIENTS.

BACKGROUND: Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a well-known complication of allogeneic hematopoietic stem cell transplantation (HSCT) associated with a mortality rate of up to 85%.  Defibrotide has shown efficacy in treatment of SOS/VOD. Moreover, evidence exists supporting the efficacy of defibrotide as SOS/VOD prophylaxis.

OBJECTIVES: We have previously reported our single center experience on 52 HSCT recipients receiving defibrotide as SOS/VOD prophylaxis which has shown that the patients did not develop any SOS/VOD under this prophylaxis. The aim of the present study was to see if we can confirm the previous results, mainly on the decrease incidence of SOS/VOD as well as improve event-free survival (EFS) on a larger study population.

STUDY DESIGN: We extended our previous study in a single center retrospective analysis to include 237 consecutive patients (248 transplantations) transplanted between 1999 and 2009 for hematological diseases and receiving intravenous defibrotide as prophylaxis. This cohort was compared to 241 patients (248 transplantations) treated before 1999 or after 2009 when defibrotide prophylaxis was not routinely employed in our center.

RESULTS: Median follow-up for the study group was 10 (range 2-16) years and for the control group 2.7 (range 1-18) years. None of the 237 patients in the defibrotide group developed SOS/VOD. The cumulative incidence (CI) of SOS/VOD was 0% in the defibrotide group as compared to 4.8% (95%CI 2.6-8%; p=0.00046) in the control group. There was also a better one-year event-free survival (EFS) with 38% (95%CI 32%-44%) in the defibrotide group vs 28% (95%CI 22%-34%), p=0.00969 and decreased cumulative incidence of acute graft versus host disease (GVHD) in the defibrotide group 31% (95%CI 25%-37%) vs 42% (95%CI 36%-48%), p=0.026. The one-year overall survival (OS), relapse incidence (RI) and non-relapse mortality (NRM) were not statistically different. Multivariable analysis, performed taking into account clinical factors known to influence the risk of SOS/VOD, confirmed the favorable impact of defibrotide on SOS/VOD (HR 1.38e-08 [95%CI 3.28e-09-5.80e-08]; p<0.00001). Conversely, multivariable analysis failed to confirm the impact of defibrotide on 1-year EFS or acute GvHD.

CONCLUSIONS: This large retrospective study on SOS/VOD-prophylaxis with defibrotide suggests that this approach may be of benefit. These results need to be confirmed in a prospective randomized trial.