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3527 Resolution of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) with Defibrotide Following HCT in Adult and Pediatric Patients: Pooled Analysis of Defifrance and EBMT PASS Registries

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster II
Hematology Disease Topics & Pathways:
clinical trials, Research, Clinical Research, real-world evidence, registries
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Mohamad Mohty, MD, PhD1, Franco Locatelli, MD, PhD2, Didier Blaise3*, Regis Peffault De Latour4*, Hélène Labussière-Wallet5*, Vian Amber6*, Virginie Gandemer7*, Deborah Gutierrez8*, Nalina Dronamraju9*, Jean-Hugues Dalle10* and Micha Srour11*

1Saint-Antoine Hospital, Sorbonne University, Paris, France
2IRCCS Bambino Gesù Children’s Hospital, Catholic University of the Sacred Heart, Rome, Italy
3Institut Paoli-Calmettes, Aix Marseille Université, Management Sport Cancer Laboratoire (MSC), Marseille, France
4Hôpital Saint-Louis, Université Paris Cité, Paris, France
5Hôpital Lyon Sud, Pierre Bénite, France
6Jazz Pharmaceuticals, Oxford, United Kingdom
7University Hospital of Rennes, Rennes, France
8Jazz Pharmaceuticals, Lyon, France
9Jazz Pharmaceuticals, Philadelphia, PA
10Hôpital Robert-Debré, GHU APHP Nord et Université de Paris Cité, Paris, France
11CHU de Lille, Université de Lille, INSERM U1286, Infinite, Lille, France


Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT). Defibrotide is approved for the treatment of severe VOD/SOS post-HCT in patients aged >1 month in the European Union and for VOD/SOS with renal or pulmonary dysfunction post-HCT in the United States. Outcomes from two real-world observational studies were pooled for analysis of treatment duration and time to resolution of VOD/SOS in patients given defibrotide for the treatment of severe or nonsevere VOD/SOS post-HCT.


DEFIFrance was an observational study that collected retrospective and prospective data on patients receiving defibrotide at 53 French transplant centers from July 2014 to March 2020. VOD/SOS severity was categorized retrospectively/prospectively using adult European Group for Blood and Marrow Transplantation (EBMT) criteria in patients aged ≥18 years, and in patients aged <18 years using pediatric EBMT criteria. EBMT PASS was a multinational, prospective, observational study that enrolled defibrotide-treated patients from April 2015 to July 2018. VOD/SOS severity was graded based on investigators’ clinical expertise. For this pooled analysis, mild/moderate and severe/very severe cases in DEFIFrance were combined with nonsevere and severe cases in EBMT PASS, respectively. Investigators in both registries diagnosed VOD/SOS using classical/standard criteria.


Overall, 414 defibrotide-treated patients with VOD/SOS post-HCT were included (336 from DEFIFrance and 78 from EBMT PASS). The median (interquartile range [IQR]) time from HCT to VOD/SOS diagnosis was 13 (IQR: 8, 21) and 14 (IQR: 8, 22) days in patients with severe and nonsevere VOD/SOS, respectively. Overall, 299/410 patients (73%) had resolution of VOD/SOS. Disease severity data was missing from 4 patients. Among 275 adult patients, VOD/SOS resolution was achieved in 44/60 (73.3%) with nonsevere and 128/215 (59.5%) with severe VOD/SOS. Median treatment duration was 15.5 days (IQR: 13, 22) for nonsevere and 18.5 days (IQR: 13.5, 22) for severe VOD/SOS. Of 135 pediatric patients, VOD/SOS resolution occurred in 47/48 (98%) with nonsevere and 80/87 (92%) with severe VOD/SOS. Median treatment duration was 16 days (IQR: 13, 21) in nonsevere and 21 days (IQR: 12.5, 29) in severe VOD/SOS. Among adult patients with resolution of VOD/SOS, symptoms resolved after day 21 in 32% of patients with nonsevere and 31% of patients with severe VOD/SOS. A higher proportion of pediatric patients with severe (44%) compared with nonsevere VOD/SOS (15%) required >21 days of treatment for resolution of symptoms; correspondingly, 85% of pediatric patients with nonsevere and 56% with severe VOD/SOS had resolution with ≤21 days of defibrotide treatment. Kaplan-Meier (KM)–estimated survival at day 100 post-HCT among patients with severe VOD/SOS was 84% (95% confidence interval [CI]: 78%, 88%) in those who achieved VOD/SOS resolution and 14% (95% CI: 8%, 22%) in those who did not; among patients with nonsevere VOD/SOS, this was 94% (95% CI: 87%, 98%) and 35% (95% CI: 15%, 57%), respectively.

Serious treatment-emergent adverse events (TEAEs) of interest occurred in 25% of patients with VOD/SOS resolution. In patients treated for ≤21 days and >21 days, respectively, the most common serious TEAEs of interest by category were infection (14% and 15%) and hemorrhage (12% and 13%). Among patients with VOD/SOS resolution, the most common causes of death were infection (severe: 11%; nonsevere: 2%) and graft-versus-host disease (severe: 6%; nonsevere: 2%).


Time to resolution of VOD/SOS tended to be longer in patients with severe versus nonsevere VOD/SOS, with many patients requiring >21 days of therapy to achieve resolution. A higher proportion of adult vs pediatric patients attained a CR >21 days after initiation of defibrotide treatment. Day 100 survival was higher in patients with VOD/SOS resolution versus without, regardless of severity, highlighting the importance of VOD/SOS resolution. The safety profile of defibrotide in the real-world setting was consistent with reports from previous studies, supporting the utility of defibrotide treatment per the prescribing information.

Disclosures: Mohty: JAZZ PHARMACEUTICALS: Honoraria, Research Funding. Blaise: Jazz Pharmaceuticals: Honoraria. Peffault De Latour: Jazz Pharmaceuticals: Honoraria. Amber: Jazz Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Gutierrez: Jazz Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Dronamraju: Jazz Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Dalle: Jazz Pharmaceuticals: Honoraria.

*signifies non-member of ASH