Adding defibrotide to standard prophylaxis may help to prevent acute graft-versus-host disease

April 2023 Clinical trials Andrea Enguita
Doctor holding patient's hand and comforting him. Doctor holds the patient's hand filling out a document for discharge from the hospital.

Acute graft-versus-host disease (aGvHD) is a life-threatening complication typically occurring within 100 days after an allogeneic haematopoietic cell transplantation (allo-HCT). The results of a hypothesis-generating phase 2 study, recently published in Haematologica, suggest that adding defibrotide to standard of care prophylaxis may further reduce the risk for aGvHD after an allo-HCT. Further studies with a larger sample size are necessary to confirm these findings.

Graft-versus-host disease (GvHD) is a life-threatening complication that can occur after an allogeneic haematopoietic cell transplantation (allo-HCT). It occurs when donor T cells recognise major or minor histocompatibility mismatches or gene polymorphisms from the recipient, leading to a cytotoxic effect on healthy tissues and organs. Acute GvHD (aGvHD) typically occurs within the first 100 days after allo-HCT. The current standard of care (SOC) for prophylaxis of aGvHD suppresses the immune system to overcome the immune response from donor T-cell recognition that induces aGvHD. However, this also increases the risk of opportunistic infection and disease relapse. Defibrotide, a polydisperse mixture of predominantly single-stranded polydeoxyribonucleotide sodium salts, could potentially reduce the incidence of aGvHD without an increase in opportunistic infections and relapse. This hypothesis-generating phase 2 study evaluated the efficacy of adding defibrotide to SOC GvHD prophylaxis to prevent aGvHD post-transplant.


This phase 2 study enrolled patients with acute leukaemia or myelodysplastic syndrome who underwent myeloablative or reduced-intensity conditioning, and were scheduled to receive an allo-HCT. Patients were randomly assigned (1:1) to receive SOC plus defibrotide (n=79) or SOC alone (n=73). In both groups, 74% of patients received GvHD prophylaxis with methotrexate-based regimens and 30% with antithymocyte globulin (ATG). The primary endpoint consisted of the cumulative incidence of grade B-D aGvHD at day 100 post-transplant. Overall survival (OS) was an exploratory endpoint at day 180 post-transplant. Of note, this study was designed for hypothesis-generating and was not powered to detect minimal clinically meaningful differences between treatment arms at a significant level of 5%.

Study findings

The primary endpoint analysis revealed that the cumulative incidence of grade B-D aGvHD at day 100 post-transplant was numerically lower in the defibrotide prophylaxis arm (38.4%) compared to the SOC arm (47.1%) (difference: -8.8%, 90%CI: -22.5-4.9). This difference at day 100 was more pronounced in a subgroup of patients who received ATG (30.4% vs. 47.6% in the defibrotide and SOC arms, respectively; difference: -17.2%, 90%CI: -41.8-7.5). OS rates at day 180 post-transplant were similar between arms (86.0% vs. 86.9% in the defibrotide and SOC arms, respectively), as were the rates of serious treatment-emergent adverse events (42% vs. 44%).

While not conclusive, the results of this study suggest that adding defibrotide to SOC prophylaxis may help prevent aGvHD after allo-HCT. Further studies with larger sample sizes are necessary to confirm these findings and determine which patient subgroup might derive the most clinical benefit.


Hudspeth M, Mori S, Nachbaur D, et al. A phase II, prospective, randomized, open-label study of defibrotide added to standard-of-care prophylaxis for the prevention of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Haematologica. 2023;108(4).