defibrotide and Ascites

Veno-occlusive disease (VOD) is the most common regimen-related toxicity accompanying stem cell transplantation (SCT). Severe VOD complicated by multisystem organ failure (MOF) remains almost uniformly fatal. Preliminary experience with defibrotide (DF), a single-stranded polydeoxyribonucleotide with fibrinolytic, antithrombotic, and anti-ischemic properties, in the treatment for severe VOD has suggested safety and activity. Eighty-eight patients who developed severe VOD after SCT were treated with DF under a defined treatment plan. At diagnosis, median bilirubin was 76.95 microM (4.5 mg/dL), median weight gain was 7%, ascites was present in 84%, and abnormal hepatic portal venous flow was present in 35%. At DF initiation, median bilirubin had increased to 215.46 microM (12.6 mg/dL), and MOF was present in 97%. DF was administered intravenously in doses ranging from 5 to 60 mg/kg per day for a median of 15 days. No severe hemorrhage or other serious toxicity related to DF was reported. Complete resolution of VOD was seen in 36%, with 35% survival at day +100. Predictors of survival included younger age, autologous SCT, and abnormal portal flow, whereas busulfan-based conditioning and encephalopathy predicted worse outcome. Decreases in mean creatinine and plasminogen activator inhibitor 1(PAI-1) levels during DF therapy predicted better survival. The complete response rate, survival to day +100, and absence of significant DF-associated toxicity in this largest patient cohort reported to date confirm the results of earlier studies. Certain features associated with successful outcome may correlate with DF-related treatment effects, and prospective evaluation of DF therapy for severe VOD should allow better definition of predictors of response or failure.

Topics: Adolescent; Adult; Ascites; Bilirubin; Biopsy; Child; Child, Preschool; Female; Fibrinolytic Agents; Graft vs Host Disease; Hepatic Veno-Occlusive Disease; Humans; Infant; Infusions, Intravenous; Liver; Male; Middle Aged; Multiple Organ Failure; Neoplasms; Peripheral Blood Stem Cell Transplantation; Polydeoxyribonucleotides; Prospective Studies; Transplantation Conditioning; Treatment Outcome

Pulmonary venoocclusive disease (PVOD) is a rare form of pulmonary vascular disease with pulmonary hypertension characterized by preferential involvement of the pulmonary venous system. Hepatic venoocclusive disease (HVOD), also known as sinusoidal obstruction syndrome, is a condition that occurs in 13% to 15% of patients after hematopoietic stem cell transplantation (HSCT). Although hepatic and pulmonary venoocclusive diseases may share some pathologic features as well as some etiologies such as HSCT, these two disorders have never been described together in a single adult patient. We report the case of a patient who received HSCT and developed HVOD and PVOD within 9 months. Despite their differences, PVOD and HVOD share common risk factors and associated conditions, suggesting that in the context of HSCT, the two diseases share common pathophysiological mechanisms. Optimal treatment for HSCT-related PVOD remains to be determined.

Topics: Ascites; Cardiac Catheterization; Endothelin Receptor Antagonists; Female; Fibrinolytic Agents; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Hyperbilirubinemia; Leukemia, Myeloid, Acute; Middle Aged; Phenylpropionates; Polydeoxyribonucleotides; Pulmonary Arterial Hypertension; Pulmonary Veno-Occlusive Disease; Pyridazines; Transplantation, Homologous; Treatment Outcome; Ultrasonography