Defibrotide in Treating Patients With Liver Damage Following Peripheral Stem Cell Transplantation

Inclusion Criteria

• •Clinical diagnosis of VOD defined by:
• •* Jaundice (bilirubin ≥ 2 mg/dL) and 2 or more of the following: ascites, weight gain \> 5% above baseline weight (see Section 5.2), hepatomegaly, RUQ pain
• •* Patients with jaundice and reversal of flow on Doppler examination of the portal vein will be eligible with one of the following: ascites, weight gain \> 5% above baseline weight, hepatomegaly, RUQ pain
• •* Patients with pre-existing hepatomegaly must have documentation by physical exam or imaging that liver size is increased over baseline at admission
• •* Patients who do not meet the criteria in Section 3.1.1 (ie. have two of the major criteria but not three) and have biopsy proven VOD are eligible in the presence of characteristics consistent with severe disease (see below).
• •* Patients with concurrent, confounding causes of liver dysfunction clinically evident or evident on ultrasound or other radiographic imaging (such as evidence of biliary ductal dilatation or focal tissue defects) may require biopsy-proven VOD and/or elevated wedged trans-hepatic venous pressure gradient measurement ( ≥10 mm mercury) to be considered eligible. Best medical judgment and further imaging studies can be used to clarify the diagnosis and determine confounding causes of liver dysfunction.
• •Severity of VOD defined by:
• •* For patients addressed by the Bearman model (i.e. within 16 days of SCT and conditioned with either BU/CY, CY/TBI or CBV), there must be a 30% or greater risk of severe VOD (see Appendix B).
• •* For all other patients who are not addressed by the Bearman model (ie. beyond 16 days of SCT and/or not conditioned with either BU/CY,
• •* CY/TBI or CBV), there must be concomitant multi-organ failure defined as presence of one or more of the following :
• •* renal dysfunction: a) creatinine ≥2x value on the date of admission day to the BMT unit for conditioning or ≥2x lowest value during conditioning (use the lowest value for calculation), or b) creatinine clearance or GFR ≤50% of admission value, or c) dialysis dependence"
• •* pulmonary dysfunction: documentation of oxygenation saturation ≤ 90% on room air; requirement for positive pressure/ventilator dependence
• •----pulmonary dysfunction must not be attributable to another cause (e.g. documented infectious pneumonia)
• •* central nervous dysfunction: documentation of confusion, lethargy, and/or delirium ---- central nervous dysfunction must not be attributable to another cause (e.g. documented cyclosporin toxicity)
• •* Patients or their parents/guardians or designated proxy must have the ability to give voluntary informed consent to the protocol. Where possible, patient assent will also be obtained
• •* Patients must be ≥ 12 hours after cessation of heparin
• •* Patient must have an eligible diagnosis of VOD by Day 35 post transplant