Defibrotide prophylaxis for prevention of sinusoidal obstruction syndrome

Stephan A Grupp and colleagues 1 Grupp SA Corbacioglu S Kang HJ et al. Defibrotide plus best standard of care compared with best standard of care alone for the prevention of sinusoidal obstruction syndrome (HARMONY): a randomised, multicentre, phase 3 trial. Lancet Haematol. 2023; 10: e333-e345 Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar did a randomised study comparing intravenous defibrotide plus best standard care with best standard care alone among 372 patients at high risk of developing sinusoidal obstruction syndrome after haematopoietic stem-cell transplantation (HSCT), including 145 allogeneic and 32 autologous HSCTs. However, it should be noted that the mean serum ferritin levels before HSCT were associated with the incidence of sinusoidal obstruction syndrome in previous reports. 2 Corbacioglu S Jabbour EJ Mohty M Risk factors for development of and progression of hepatic veno-occlusive disease/sinusoidal obstruction syndrome. Biol Blood Marrow Transplant. 2019; 25: 1271-1280 Summary Full Text Full Text PDF PubMed Google Scholar , 3 Hwang DY Kim S-J Cheong J-W et al. High pre-transplant serum ferritin and busulfan-thiotepa conditioning regimen as risk factors for hepatic sinusoidal obstructive syndrome after autologous stem cell transplantation in patients with malignant lymphoma. Leuk Lymphoma. 2016; 57: 51-57 Crossref PubMed Scopus (13) Google Scholar , 4 Kloehn J Brodt G Ernst J Gruhn B Analysis of risk factors for hepatic sinusoidal obstruction syndrome following allogeneic hematopoietic stem cell transplantation in pediatric patients. J Cancer Res Clin Oncol. 2022; 148: 1447-1455 Crossref PubMed Scopus (5) Google Scholar A previous study reported their analysis involving 132 patients with malignant lymphoma who received autologous HSCT including 108 (82%) patients who received busulfan-based conditioning regimens. Among 83 (63%) patients with elevated pre-HSCT serum ferritin levels, the mean serum ferritin level in patients who developed sinusoidal obstruction syndrome was higher than in those who did not (3046·2 vs 885·2, p=0·002). Furthermore, multivariate analysis of this study showed that the use of busulfan-thiotepa conditioning regimen (odds ratio 13·69, 95% CI 2·50–74·99; p=0·003) and high mean serum ferritin levels before HSCT (≥950 ng/mL; odds ratio 13·69; 95% CI 2·50–74·99; p=0·003) were risk factors for the development of hepatic sinusoidal obstruction syndrome. 3 Hwang DY Kim S-J Cheong J-W et al. High pre-transplant serum ferritin and busulfan-thiotepa conditioning regimen as risk factors for hepatic sinusoidal obstructive syndrome after autologous stem cell transplantation in patients with malignant lymphoma. Leuk Lymphoma. 2016; 57: 51-57 Crossref PubMed Scopus (13) Google Scholar Thus, we wondered whether the mean serum ferritin levels before HSCT of the two groups were well balanced in this study. Defibrotide plus best standard of care compared with best standard of care alone for the prevention of sinusoidal obstruction syndrome (HARMONY): a randomised, multicentre, phase 3 trialDefibrotide did not show a benefit in the prophylaxis of sinusoidal obstruction syndrome. Additional studies of carefully selected patients at high risk of sinusoidal obstruction syndrome after HSCT are warranted. Full-Text PDF Defibrotide prophylaxis for prevention of sinusoidal obstruction syndrome – Authors' replyWe appreciate the comments by Motoharu Shibusawa and Tetsuya Tanimoto regarding ferritin levels in the context of the HARMONY trial comparing intravenous defibrotide and best standard care or best standard care alone after haematopoietic stem-cell transplantation (HSCT).1 As they point out, there are studies that suggest an association between sinusoidal obstruction syndrome (also known as veno-oclusive disease) risk and pre-HSCT ferritin levels.2–4 As a result, they question whether serum ferritin levels were balanced across the treatment groups on this study. Full-Text PDF