Nancy A Kernan1, Paul G Richardson2, Angela R Smith3, Brandon M Triplett4, Joseph H Antin5, Leslie Lehmann6, Yoav Messinger7, Wei Liang8, Robin Hume8, William Tappe8, Robert J Soiffer5, Stephan A Grupp9. 1. Pediatric Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, USA. 2. Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. 3. Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA. 4. Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. 5. Stem Cell/Bone Marrow Transplantation Program, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. 6. Center for Stem Cell Transplantation, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. 7. Cancer and Blood Disorders Program, Children's Minnesota, Minneapolis, Minnesota, USA. 8. Jazz Pharmaceuticals, Palo Alto, California, USA. 9. Pediatric Oncology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Abstract
BACKGROUND: Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) but can occur after nontransplant-associated chemotherapy. Following HSCT, VOD/SOS with multi-organ dysfunction (MOD) may be associated with >80% mortality. Defibrotide is approved to treat severe hepatic VOD/SOS post-HSCT in patients aged >1 month in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Prior to US approval, defibrotide was available to treat VOD/SOS through an expanded-access treatment (T-IND) program. A post hoc analysis of nontransplant-associated VOD/SOS patients treated with defibrotide initiated within 30 days of starting chemotherapy and followed for 70 days is presented. PROCEDURE: Patients were diagnosed by Baltimore or modified Seattle criteria or biopsy, and received defibrotide 25 mg/kg/day in four divided doses (≥21 days recommended). RESULTS: Of the 1,154 patients in the T-IND, 137 had nontransplant-associated VOD/SOS, 82 of whom developed VOD/SOS within 30 days of starting chemotherapy. Of them, 66 (80.5%) were aged ≤16 years. Across all the 82 patients, Kaplan-Meier estimated day +70 survival was 74.1%, 65.8% in patients with MOD (n = 38), and 81.3% in patients without MOD (n = 44). By age group, Kaplan-Meier estimated day +70 survival was 80.1% in pediatric patients (n = 66) and 50.0% in adults (n = 16). Treatment-related adverse events occurred in 26.8%. CONCLUSIONS: In this post hoc analysis of 82 patients initiating defibrotide within 30 days of starting chemotherapy, Kaplan-Meier estimated survival was 74.1% at 70 days after defibrotide initiation. Safety profile was consistent with prior defibrotide studies.
BACKGROUND:Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) but can occur after nontransplant-associated chemotherapy. Following HSCT, VOD/SOS with multi-organ dysfunction (MOD) may be associated with >80% mortality. Defibrotide is approved to treat severe hepatic VOD/SOS post-HSCT in patients aged >1 month in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Prior to US approval, defibrotide was available to treat VOD/SOS through an expanded-access treatment (T-IND) program. A post hoc analysis of nontransplant-associated VOD/SOSpatients treated with defibrotide initiated within 30 days of starting chemotherapy and followed for 70 days is presented. PROCEDURE: Patients were diagnosed by Baltimore or modified Seattle criteria or biopsy, and received defibrotide 25 mg/kg/day in four divided doses (≥21 days recommended). RESULTS: Of the 1,154 patients in the T-IND, 137 had nontransplant-associated VOD/SOS, 82 of whom developed VOD/SOS within 30 days of starting chemotherapy. Of them, 66 (80.5%) were aged ≤16 years. Across all the 82 patients, Kaplan-Meier estimated day +70 survival was 74.1%, 65.8% in patients with MOD (n = 38), and 81.3% in patients without MOD (n = 44). By age group, Kaplan-Meier estimated day +70 survival was 80.1% in pediatric patients (n = 66) and 50.0% in adults (n = 16). Treatment-related adverse events occurred in 26.8%. CONCLUSIONS: In this post hoc analysis of 82 patients initiating defibrotide within 30 days of starting chemotherapy, Kaplan-Meier estimated survival was 74.1% at 70 days after defibrotide initiation. Safety profile was consistent with prior defibrotide studies.
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