Defibrotide for GVHD Prevention in HSCT

The disease stage at HSCT for hematological malignancies was defined according to the European Group for Blood and Marrow Transplantation (EBMT) risk score (31 (link)). The disease stage for nonmalignancies was defined as the hematopoietic cell transplant comorbidity index (HCT-CI) (32 (link)). The myeloablative conditioning regimen was defined as total body irradiation ≥ 8 Gy, busulfan 16 mg/kg, or melphalan 140 mg/m² (53 (link)). All patients were treated according to the standard myeloablative protocols based on chemotherapy and radiation dosing, as previously described (46 (link), 54 (link)). GVHD prophylaxis was performed with tacrolimus. Additional GVHD prophylaxis included mycophenolate mofetil for the matched unrelated donor (MUD), with the addition of posttransplant cyclophosphamide from 2013 in the case of a haploidentical donor. Serotherapy with anti-thymocyte globulin was also assessed as an independent variable. Prevention and treatment of infection and other elements of transplant-specific supportive care were performed according to institutional standard practices. Duration of follow-up was defined as the time from HSCT to last contact or death. Acute and cGVHD were diagnosed and graded using standard criteria (55 , 56 (link), 57 (link)).
The study’s primary endpoints were comparing the incidence of aGVHD and chronic GVHD-free survival between the defibrotide group and the control group. The incidence of GVHD was defined as any GVHD requiring systemic immune suppressive therapy. The secondary endpoints evaluated the influence of defibrotide prophylaxis on the incidence of early and late transplant-related complications. Early transplant-related complications were defined as events occurring within 100 d after HSCT unrelated to primary disease recurrence.