Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease : Final Results From the International Compassionate Use Program

Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable and potentially fatal complication of hematopoietic cell transplantation (HCT) or nontransplantation-associated chemotherapy/radiotherapy. In cases of severe hepatic VOD/SOS, typically defined by associated multiorgan failure (MOF, also known as multiorgan dysfunction), mortality exceeds 80%. Preclinical and early clinical data have provided a rationale for defibrotide treatment in hepatic VOD/SOS. Based on this evidence and in recognition of the dismal prognosis for these patients, defibrotide was made available through an international multicenter compassionate-use program conducted from December 1998 to March 2009. Physicians participating in the program voluntarily provided demographic and outcome data for patients given defibrotide. Efficacy and safety analyses were performed using the data received for 710 treated patients. Defibrotide was given at 10, 25, 40, 60, or 80 mg/kg/day for a median of 15 days (range, 1 to 119 days). By Kaplan-Meier analysis, the estimated overall day +100 survival was 54% (58% in the 25 mg/kg/day dose group). Adverse events (AEs) were reported in 53% of patients. The most common AEs were MOF, progression of hepatic VOD/SOS, sepsis, and graft-versus-host disease, which were consistent with the AEs expected for this patient population. No clinically meaningful trends in AEs were identified by gender, age, or dose group. Safety and efficacy results were consistent with prior studies of defibrotide in hepatic VOD/SOS, and subgroup analyses lend support to the use of the 25 mg/kg/day dose. (C) 2016 American Society for Blood and Marrow Transplantation.Peer reviewe

Single breath diffusing capacity for carbon monoxide in stable asthma

Background: Single breath diffusing capacity for carbon monoxide (Dco) is commonly used as a simple method of assessing overall pulmonary gas exchange properties. Studies of Dco in bronchial asthma have yielded conflicting results. Objective: To study Dco and to determine the factors influencing Dco in patients with asthma. Methods: Dco was prospectively measured in 80 consecutive never-smoker patients with uncomplicated stable asthma. The topographic distribution of lung perfusion was determined in 10 asthmatics and 10 controls, with a Xe-133 radionuclide scan. Results: The mean (SD) value of Dco was increased to 117 (17) percent of predicted values; individual values were either within or above normal limits; diffusion was also elevated at 116 (19) percent after correction for alveolar volume (transfer coefficient, D/VA). The Dco was not correlated with atopic status, duration of asthma, or results of spirometric tests; there was a weak negative correlation between D/VA and FEV(1) or residual volume. There was a better perfusion of the upper zones of the lungs in asthmatics as compared with controls. Among the asthmatics, there was a strong positive correlation between Dco and the apex to base perfusion ratio (r=0.975). Conclusions: Dco is normal or high among never smoker patients with uncomplicated asthma; elevated Dco may be attributed to a better perfusion of the apices of the lungs; the latter could result from two mutually nonexclusive mechanisms: an increase in pulmonary arterial pressure and/or a more negative pleural pressure generated during inspiration as a consequence of bronchial narrowing. The unexpected finding of high Dco should raise the possibility of bronchial asthma in patients with otherwise undiagnosed conditions