去纤苷的治疗效果如何？

For some patients with leukemia and lymphoma, hematopoietic stem cell transplantation (HSCT) is the only hope to cure the disease and regain health. Hepatic veno-occlusive disease (HVOD) is one of the serious complications after hematopoietic stem cell transplantation (HSCT), and the mortality rate in patients with severe HVOD can be as high as 100%. Defibrotide (defiteli) is a single-stranded oligonucleotide mixture that has anti-thrombotic and fibrinolytic effects. In recent years, multiple clinical research results have shown that defibrotide (defiteli) is a safe and effective drug for preventing and treating HVOD.  

In vitro, defibrinoside (defiteli) enhances the enzymatic activity of plasmin that hydrolyzes fibrin clots, increases tissue plasminogen activator (t-PA) and thrombomodulin expression, and decreases von Willebrand factor (vWF) and plasminogen activation inhibitor-1 (PAI-1) expression, thereby reducing EC activation and increasing EC-mediated fibrinolysis. Defibrotide (defiteli) protects ECs from damage caused by chemotherapy, tumor necrosis factor-alpha (TNF-alpha), serum starvation, and perfusion.    

In clinical trials, heparin was used to prevent diseases such as hepatic venous occlusion while greatly increasing the risk of bleeding. However, defibrotide (defiteli) alone or in combination with heparin has a very low incidence of side effects and has achieved a good effect in preventing HVOD. In a phase III multi-center randomized clinical trial completed in Europe, a total of 356 stem cell transplant patients were recruited. The incidence of hepatic vein occlusion 30 days after transplantation was compared. It was found that 2 of 180 patients in the defibrination (defiteli) group developed hepatic vein occlusion, accounting for 12%; 35 of 176 patients in the control group developed hepatic vein occlusion, accounting for 20%.  

Defibrotide (defiteli) is the first drug approved by the FDA for the treatment of severe hepatic venule occlusion, a rare and fatal liver disease. The approval was based on a Phase 2 trial of 75 patients, a Phase 3 trial of 102 patients, and an expansion trial of an additional 351 patients. All patients in the trial were diagnosed with hepatic veno-occlusive disease and associated renal or pulmonary dysfunction after HSCT (hematopoietic stem cell transplantation). In the phase 2 trial, 44% of patients survived 100 days after transplantation, compared with 38% in the phase 3 trial and 45% in the expanded trial, and the FDA noted in a report that the expected 100-day survival rate for patients with severe hepatic veno-occlusive disease who were not treated with defiteli was 21% to 31%.