Results Of The Large Prospective Study On The Use Of Defibrotide (DF) In The Treatment Of Hepatic Veno-Occlusive Disease (VOD) In Hematopoietic Stem Cell Transplant (HSCT). Early Intervention Improves Outcome - Updated Results Of a Treatment IND (T-IND) Expanded Access Protocol

• Published in: Blood 2013-11, Vol.122 (21), p.700-700
• Main Authors: Richardson, Paul G., Smith, Angela R., Triplett, Brandon M., Kernan, Nancy A., Grupp, Stephan A, Arai, Sally, Haut, Paul R., Martin, Paul L., Symons, Heather J., Lehmann, Leslie E., Simms-Waldrip, Tiffany, Gillio, Alfred P., Horn, Biljana N., Shore, Tsiporah B., Krishnan, Amrita Y., Petrovic, Aleksandra, Kirov, Ivan I., Woolfrey, Ann E., Greiner, Robert J., Mineishi, Shin, Boyer, Michael, Hannah, Alison L., Antin, Joseph H., Hume, Robin, Bandiera, Valeria, Heringa, Carin, Soiffer, Robert J.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.700.700

Given the life-threatening nature of severe VOD (sVOD) and associated multi-organ failure (MOF), the absence of other approved therapies for this complication in the USA, and the promising results to date with DF in this setting, DF has been made available since 2007 through a prospective T-IND. The aim of the T-IND is to gather additional data on safety and response to DF in a broader patient (pt) population, including those with sVOD/MOF and those with non-severe VOD. Thus far, this is the largest prospective evaluation of DF for the treatment of sVOD/MOF in pts undergoing HSCT, and in pts who developed VOD following chemotherapy (non-HSCT pts). Here we provide an update on the efficacy and safety of DF in HSCT and non-HSCT pts, together with analysis of other clinical features of interest, including GvHD. The original T-IND protocol required pts to have a diagnosis of VOD by Baltimore criteria (total bilirubin ≥2.0 mg/dL with ≥2 of the following: hepatomegaly, ascites or 5% weight gain) with MOF (either renal and/or pulmonary failure) following HSCT, and was amended to allow inclusion of pts with non-severe VOD (defined as no MOF) occurring either post-HSCT and post-chemotherapy. Key exclusion criteria included clinically significant bleeding or the need for >1 vasopressor. Complete response (CR) was defined as bilirubin 1 HSCT); 284 pts had severe disease at study entry. The most common diagnosis was leukemia (29% AML; 22% ALL; 6% other). Conditioning regimen included CY (66%), BU (50%) and TBI (36%). Median onset of VOD was 15 d post-HSCT. Of HSCT pts, 35% (147/425) achieved CR and 55% (Kaplan-Meier estimate) survived to D+100. In pts with sVOD, CR was 29% and D+100 survival was 48%. For pts with non-severe VOD, CR and D+100 survival was 47% and 69%, respectively. In all HSCT pts, delay of >2 d (vs ≤2 d) in the start of DF after VOD diagnosis resulted in reduced CR (25% vs 39%, p=0.0052) and survival (Kaplan-Meier estim