Most frequently experienced AEs (≥2% of patients) of grades 3/4/5 severity by system organ class and MedDRA preferred term, excluding VOD/SOS and MOF in the defibrotide group
| . | Defibrotide treatment group (N = 102) . | |
|---|---|---|
| System organ class/abnormality . | Grade 3/4, n (%) . | Grade 5, n (%) . |
| Blood and lymphatic system disorders | ||
| Coagulopathy | 2 (2) | — |
| Cardiac disorders | ||
| Bradycardia | 2 (2) | — |
| Cardiac arrest | 2 (2) | — |
| GI disorders | ||
| Diarrhea | 5 (4.9) | — |
| GI hemorrhage | 5 (4.9) | — |
| Nausea | 2 (2) | — |
| General disorders and administration site conditions | ||
| Catheter site hemorrhage | 3 (2.9) | — |
| Generalized edema | 3 (2.9) | — |
| MOF* | 2 (2) | 13 (12.7) |
| Pyrexia | 2 (2) | — |
| Hepatobiliary disorders | ||
| VOD* | — | 9 (8.8) |
| Hepatic failure* | — | 2 (2) |
| Immune system disorders | ||
| GVHD* | 1 (1) | 2 (2) |
| Infections and infestations | ||
| Sepsis | 4 (3.9) | 5 (4.9) |
| Enterococcal infection | 2 (2) | — |
| Candida sepsis | — | 2 (2) |
| Pneumonia | 2 (2) | 1 (1) |
| Septic shock | 2 (2) | 1 (1) |
| Metabolism and nutrition disorders | ||
| Hyperglycemia | 2 (2) | — |
| Hypoglycemia | 2 (2) | — |
| Neoplasms, malignant and unspecified | ||
| Acute myeloid leukemia recurrent | — | 2 (2) |
| Nervous system disorders | ||
| Intracranial hemorrhage | 3 (2.9) | 1 (1) |
| Cerebral hemorrhage | 2 (2) | 1 (1) |
| Psychiatric disorders | ||
| Mental status changes | 2 (2) | — |
| Renal and urinary disorders | ||
| Hemorrhagic cystitis | 2 (2) | — |
| Renal failure* | 2 (2) | 2 (2) |
| Renal impairment | 2 (2) | — |
| Respiratory, thoracic, and mediastinal disorders | ||
| Pulmonary alveolar hemorrhage | 7 (6.9) | 5 (4.9) |
| Respiratory failure* | 3 (2.9) | 9 (8.8) |
| Lung disorder | 2 (2) | — |
| Pulmonary hemorrhage | 2 (2) | 2 (2) |
| Pleural effusion | 2 (2) | — |
| Pulmonary edema | 2 (2) | — |
| Vascular disorders | ||
| Hypotension | 26 (25.5) | — |
| Hemodynamic instability | 2 (2) | — |
| . | Defibrotide treatment group (N = 102) . | |
|---|---|---|
| System organ class/abnormality . | Grade 3/4, n (%) . | Grade 5, n (%) . |
| Blood and lymphatic system disorders | ||
| Coagulopathy | 2 (2) | — |
| Cardiac disorders | ||
| Bradycardia | 2 (2) | — |
| Cardiac arrest | 2 (2) | — |
| GI disorders | ||
| Diarrhea | 5 (4.9) | — |
| GI hemorrhage | 5 (4.9) | — |
| Nausea | 2 (2) | — |
| General disorders and administration site conditions | ||
| Catheter site hemorrhage | 3 (2.9) | — |
| Generalized edema | 3 (2.9) | — |
| MOF* | 2 (2) | 13 (12.7) |
| Pyrexia | 2 (2) | — |
| Hepatobiliary disorders | ||
| VOD* | — | 9 (8.8) |
| Hepatic failure* | — | 2 (2) |
| Immune system disorders | ||
| GVHD* | 1 (1) | 2 (2) |
| Infections and infestations | ||
| Sepsis | 4 (3.9) | 5 (4.9) |
| Enterococcal infection | 2 (2) | — |
| Candida sepsis | — | 2 (2) |
| Pneumonia | 2 (2) | 1 (1) |
| Septic shock | 2 (2) | 1 (1) |
| Metabolism and nutrition disorders | ||
| Hyperglycemia | 2 (2) | — |
| Hypoglycemia | 2 (2) | — |
| Neoplasms, malignant and unspecified | ||
| Acute myeloid leukemia recurrent | — | 2 (2) |
| Nervous system disorders | ||
| Intracranial hemorrhage | 3 (2.9) | 1 (1) |
| Cerebral hemorrhage | 2 (2) | 1 (1) |
| Psychiatric disorders | ||
| Mental status changes | 2 (2) | — |
| Renal and urinary disorders | ||
| Hemorrhagic cystitis | 2 (2) | — |
| Renal failure* | 2 (2) | 2 (2) |
| Renal impairment | 2 (2) | — |
| Respiratory, thoracic, and mediastinal disorders | ||
| Pulmonary alveolar hemorrhage | 7 (6.9) | 5 (4.9) |
| Respiratory failure* | 3 (2.9) | 9 (8.8) |
| Lung disorder | 2 (2) | — |
| Pulmonary hemorrhage | 2 (2) | 2 (2) |
| Pleural effusion | 2 (2) | — |
| Pulmonary edema | 2 (2) | — |
| Vascular disorders | ||
| Hypotension | 26 (25.5) | — |
| Hemodynamic instability | 2 (2) | — |
Severity not assessed for historical-control group.
Neither symptoms indicative of underlying disease (VOD/SOS with MOF) nor events and laboratory values expected following HSCT were recorded as AEs unless the event was considered serious. For the defibrotide group, the protocol instructed study sites to capture symptoms of VOD/SOS and/or MOF as an AE, if the event also met criteria for seriousness.