Defitelio (defibrotide) / Medison, IRCCS San Raffaele Hospital, Jazz, SOBI - LARVOL DELTA

Thiotepa-busulfan-fludarabine conditioning in allogeneic hematopoietic stem cell transplantation for blast-phase myeloproliferative neoplasm (PubMed, Rinsho Ketsueki) - "This case suggests that a multidisciplinary treatment strategy incorporating TBF conditioning may improve relapse-free survival in patients with BP-MPN."

Journal • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Essential Thrombocythemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Otorhinolaryngology • Thrombocytosis • Transplantation

A phase 2 trial of defibrotide for the prevention of chimeric antigen receptor T-cell-associated neurotoxicity syndrome. (PubMed, Blood Adv) - P2 | "This open-label, single-arm, phase 2 study evaluated safety and efficacy of defibrotide for prevention of CAR-T-associated neurotoxicity in patients with relapsed/refractory large B-cell lymphoma receiving axicabtagene ciloleucel. Nevertheless, results contribute valuable data for potential therapeutic insight on the management of CAR-T-associated neurotoxicity. Trial registration: ClinicalTrials.gov identifier: NCT03954106."

CAR T-Cell Therapy • Journal • P2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hepatology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases

Impact of defibrotide on survival in sinusoidal obstruction syndrome / veno-occlusive disease: a retrospective cohort study comparing two sequential treatment eras. (PubMed, Hematology) - "Defibrotide treatment was associated with improved outcome in SOS/VOD. Inflammatory status appeared to be related to disease onset and resolution."

Clinical • Journal • Retrospective data • Bone Marrow Transplantation • Transplantation

INOTUZUMAB OZOGAMICIN IN PEDIATRIC CD22-POSITIVE VERY HIGH RISK FIRST RELAPSE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA: PRELIMINARY RESULTS OF THE ITCC-059 STUDY (EHA 2025) - "Two cases of SOS gr3 were reported, both occurred in transplanted pts and resolved after treatment with defibrotide. InO showed high efficacy as reinduction treatment in pediatric VHR 1st rel BCP-ALL. New combination strategies to further improve outcomes are needed in pts with HR genetics (in particular TP53 mut/del), which may include bcl2 or menin inhibitors."

Clinical • Acute Lymphocytic Leukemia • Pediatrics • BCL2 • CD22 • KMT2A • PBX1 • TP53

Sinusoidal Obstruction Syndrome in Children with CD22+ B-Cell Precursors Acute Lymphoblastic Leukemia (BCP-ALL) Treated with Inotuzumab Ozogamicin in Trial ITCC-059: Risk Factors and Outcomes (ASH 2024) - P2 | "In phase IA, phase II and stratum III, patients received single agent InO; while in phase IB InO was combined with vincristine and dexamethasone...Overall, 14 (13%) patients developed SOS, 2 during treatment, 10 after HSCT, and 2 after subsequent chemotherapy including high-dose methotrexate and cyclophosphamide...All SOS cases received treatment with defibrotide, except one patient in which SOS resolved with supportive management...The time between last InO and HSCT seems a significant risk factor for developing SOS, as in previous studies in adults treated with gemtuzumab ozogamicin. Taking into account also the longer median half-life of InO in pediatrics (T1/2 423 h,17.6 days; Trial NCT02981628), a minimum interval of 35 days after last InO dose and HSCT could be considered based on these data."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Hepatology • Leukemia • Oncology • Pediatrics • Septic Shock • CD22

Inotuzumab ozogamicin in paediatric very high risk first B-cell acute lymphoblastic leukaemia relapse (ITCC-059): a multicentre, single-arm, phase 2 trial. (PubMed, Lancet Haematol) - P1/2 | "Inotuzumab ozogamicin showed high activity as reinduction treatment in paediatric very high risk first B-cell acute lymphoblastic leukaemia relapse and a favourable toxicity profile with no treatment-related deaths."

Journal • P2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Neutropenia • Oncology • Pediatrics • Respiratory Diseases • Thrombocytopenia • Transplantation • AFF1 • CD22 • PBX1 • TCF3

Defibrotide plus best standard of care compared with best standard of care alone for the prevention of sinusoidal obstruction syndrome (HARMONY): a randomised, multicentre, phase 3 trial. (PubMed, Lancet Haematol) - P3 | "Defibrotide did not show a benefit in the prophylaxis of sinusoidal obstruction syndrome. Additional studies of carefully selected patients at high risk of sinusoidal obstruction syndrome after HSCT are warranted."

Journal • P3 data • Bone Marrow Transplantation • Cerebral Hemorrhage • Dental Disorders • Febrile Neutropenia • Hepatology • Neutropenia • Pediatrics • Stomatitis • Transplantation

Proteomics in the discovery of biomarkers of major complications after allogeneic hematopoietic cell transplantation. (PubMed, Curr Opin Hematol) - "Most proteomic biomarker studies in allo-HCT derive from small single-center discovery cohorts. Multicenter validation, harmonized biobanking, and integration with clinical risk models are required before these biomarkers can enter transplant practice."

Biomarker • IO biomarker • Journal • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • BTN3A2 • IL1R1 • REG3A • SLAMF7

Defibrotide Therapy for Hepatic Veno-Occlusive Disease Following Liver Transplantation: A Case Series (ACG 2026) - "However, bleeding risk requires careful consideration, as seen in the second case. Further research is needed to determine the safety and efficacy of defibrotide for VOD in liver transplant patients."

Clinical • Bone Marrow Transplantation • Fibrosis • Hematological Disorders • Hepatology • Immunology • Primary Biliary Cholangitis • Transplant Rejection • Transplantation

A Double-Edged Sphere: When Yttrium-90 Leads to Radioembolization-Induced Liver Disease (ACG 2026) - "Two months prior, he underwent two sessions of Y-90 radioembolization spaced two months apart, followed by approximately one month of fruquintinib therapy...The patient received vitamin K and N-acetylcysteine, but bilirubin did not improve...Defibrotide was considered for the overlapping REILD and VOD/SOS picture but was deferred due to limited evidence outside stem cell transplant populations and a high bleeding potential, with risks outweighing benefits...Serial changes in liver function tests reflecting progressive hepatic synthetic dysfunction following Y-90 radioembolization Figure: Graph 2. Progressive changes in hepatic biochemical markers during inpatient management"

CNS Disorders • Colorectal Cancer • Hepatic Encephalopathy • Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Liver Cancer • Liver Failure • Nephrology • Renal Disease • Solid Tumor

Diagnostic and Predictive Accuracy of Liver Elastography for Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease After Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis (ACG 2026) - "Earlier defibrotide initiation after diagnosis improves Day +100 survival, but clinical criteria and Doppler ultrasound have limited sensitivity for early hepatic congestion... Twelve studies (n = 1,545; 9 prospective) met inclusion criteria. Diagnostic synthesis (10 analyses from 9 studies) yielded sensitivity 0.71 (95% CI 0.61-0.79), specificity 0.93 (95% CI 0.78-0.98), and SROC AUC 0.773 (moderate certainty; Figure 1). Predictive synthesis (6 studies) yielded sensitivity 0.85 (95% CI 0.69-0.93), specificity 0.88 (95% CI 0.66-0.97), and SROC AUC 0.907 (high certainty; Figure 2A-B)."

Retrospective data • Review • Bone Marrow Transplantation • Hepatology • Transplantation

Diagnostic delay of veno-occlusive disease in a myelofibrosis patient with pre-transplant transjugular intrahepatic portosystemic shunt: a case report. (PubMed, Front Oncol) - "Early after transplantation, the patient developed rapidly progressive hyperbilirubinemia without the typical manifestations of VOD, leading initially to an alternative diagnostic hypothesis and delayed initiation of defibrotide therapy...This case highlights a previously underrecognized diagnostic pitfall: standard diagnostic criteria for VOD may be unreliable in patients with altered portal circulation. Clinicians should maintain a high index of suspicion in this setting and consider early treatment when biochemical abnormalities emerge, as prompt recognition remains critical for improving outcomes."

Journal • Bone Marrow Transplantation • Cardiovascular • Hepatology • Hypertension • Liver Failure • Myelofibrosis • Pain • Portal Hypertension • Transplantation

Long-term outcome of sinusoidal obstruction syndrome secondary to hematopoietic stem cell transplantation. (PubMed, JHEP Rep) - "Development of signs of portal hypertension and liver-related complications are common in the long-term after SOS following HSCT, especially when patients did not receive defibrotide, and this affects patients' survival. Features consistent with a porto-sinusoidal vascular disorder may be seen in liver histology in a subset of patients at the long-term follow-up after SOS."

Journal • Bone Marrow Transplantation • Cardiovascular • CNS Disorders • Hepatic Encephalopathy • Hepatology • Hypertension • Portal Hypertension • Transplantation

Early-onset severe sinusoidal obstruction syndrome following adjuvant CAPOX: clinicoradiological diagnosis and favourable outcome after treatment with defibrotide. (PubMed, Rev Esp Enferm Dig) - "Sinusoidal obstruction syndrome (SOS) is an uncommon hepatic vascular complication classically associated with haematopoietic stem cell transplantation, although it may also occur following oxaliplatin-based chemotherapy. This case highlights that SOS may occur early, even after limited exposure to oxaliplatin in the adjuvant setting. Early recognition and assessment with hepatic Doppler ultrasound are essential to establish the diagnosis and initiate prompt treatment."

Journal • Cardiovascular • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Hematological Disorders • Hepatology • Hypertension • Liver Failure • Oncology • Portal Hypertension • Thrombocytopenia • Transplantation

Evaluation of Prophylactic Defibrotide Use in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Multicenter Retrospective Cohort Study. (PubMed, J Pers Med) - "These findings represent associations, not causation, and likely reflect residual confounding by indication-as defibrotide prophylaxis was preferentially administered to patients perceived to be at highest clinical risk. Prospective studies with appropriate confounding adjustment are needed to clarify the role of defibrotide in SOS prevention."

Journal • Retrospective data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Pediatrics • Transplantation

Defibrotide for the Treatment of Severe COVID-19 (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: Brigham and Women's Hospital | Trial primary completion date: Jun 2026 ➔ Dec 2026

Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Allogeneic HSCT outcomes and impact of defibrotide prophylaxis on SOS after inotuzumab in pediatric B-ALL. (PubMed, Blood Adv) - "Defibrotide prophylaxis was well tolerated with low rates of adverse events and discontinuation. These results support the use of InO for children with relapsed or refractory B-ALL and suggest that defibrotide prophylaxis may reduce the incidence of SOS during HSCT after InO."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Otorhinolaryngology • Pediatrics • Transplantation

Incidence, clinical risk factors, and biomarkers of SOS/VOD following allogeneic HSCT in adults. A real-life study by the Spanish group of HSCT and cell therapy (GETH-TC). (PubMed, Bone Marrow Transplant) - "Defibrotide was used in 44 patients (56%) who developed SOS/VOD...Multivariate analysis confirmed the prognostic value for SOS/VOD incidence of second or subsequent HSCT, use of parenteral nutrition, high tacrolimus/sirolimus levels, INR > 1.5 before SOS, as well as day 0 EASIX ≥ 2 (sHR 1.67; p = 0.036), d + 7 EASIX ≥ 6 (sHR 2.86; p < 0.001), and d + 14 EASIX ≥ 6 (sHR 2.87; p = 0.003). In conclusion, SOS/VOD incidence is similar to previous series and significantly impacts NRM. EASIX score was validated as a risk factor of SOS/VOD."

Biomarker • Journal • Bone Marrow Transplantation

Late-onset Anicteric Veno-occlusive Disease after Haploidentical HSCT: Diagnostic Challenges in the Setting of CMV Reactivation. (PubMed, Mediterr J Hematol Infect Dis) - No abstract available

Journal • Bone Marrow Transplantation • Cytomegalovirus Infection

Tracking complement overactivation on the endothelium and isohemagglutinin dynamics in ABO-incompatible living donor kidney transplantation (ISTH 2026) - "Aims To evaluate complement injury and ISO rebound kinetics in ABOi-LDKT, and the effect of a complement inhibitory drug (eculizumab) and an endothelial protective agent (defibrotide) as treatment strategies. C5b9 deposition in ABOi ‑ LDKT. DOI*10.1016/j.rpth.2026.106291"

Nephrology • Renal Disease • Transplantation

EASIX independently predicts VOD after allo-HCT with PTCy and outperforms soluble endothelial biomarkers (ISTH 2026) - "Methods We analyzed 112 adult allo-HCT recipients receiving post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis...All VOD cases received defibrotide, and 3 (75%) achieved complete response...Table or Figure Upload (2) Figure 1. Biomarker trends according to VOD diagnosis Page 3 DOI*10.1016/j.rpth.2026.106318"

Biomarker • Graft versus Host Disease • Hepatology • Immunology • Myeloproliferative Neoplasm • VCAM1

Complement-targeted therapies for transplant-associated thrombotic microangiopathy: recent advances. (PubMed, Front Pharmacol) - "Earlier non-complement-directed therapies, including calcineurin inhibitor modification, plasma exchange, defibrotide, and rituximab, showed limited and inconsistent benefit...Prospective and large cohort data support the clinical activity of eculizumab (C5 inhibitor), with meaningful improvements in survival and organ recovery. Ravulizumab (long-acting C5 inhibitor) has shown encouraging phase 3 results, and narsoplimab (MASP-2 inhibitor), which became the first approved treatment for TA-TMA, has demonstrated promising outcomes, including activity in some patients previously exposed to C5 inhibition. In addition, newer agents targeting C5, C3, or factor B are expanding the therapeutic horizon for TA-TMA, although efficacy data are still limited for some of these therapies. Overall, complement-targeted therapies represent a therapeutic advance in TA-TMA, and ongoing prospective studies will be crucial to define optimal agent selection, sequencing, and integration into..."

Journal • Review • Bone Marrow Transplantation • Hematological Disorders • Thrombocytopenia • Transplantation • Transplantation Associated Thrombotic Microangiopathy

Time to resolution of veno-occlusive disease/sinusoidal obstruction syndrome post-HCT in defibrotide-treated adults from two European registries. (PubMed, Bone Marrow Transplant) - "Serious treatment-emergent adverse events of interest occurred in 31% of patients with VOD/SOS resolution. This pooled analysis supports the utility of defibrotide treatment for VOD/SOS and highlights that treatment may often need to be continued beyond 21 days to achieve resolution."

Journal • Otorhinolaryngology • Transplantation

RETROSPECTIVE STUDY OF SINUSOIDAL OBSTRUCTION SYNDROME IN PEDIATRIC PATIENTS WITH PRE-TRANSPLANT INOTUZUMAB OZOGAMICIN :A SINGLE CENTER STUDY FROM CHINA (EHA 2026) - "RIC regimen includes two categories, the one is TBI 2-3Gy plus fludarabine,melphalan,cetirizine and cyclophosphamide ,the other one is busulfan plus fludarabine,melphalan and cyclophosphamide...SOS prophylaxis and treatment Ursodiol and alprostadil were routinely administered for SOS prophylaxis for all patients undergoing HSCT at our center. Defibrotide was used for patients diagnosis of severe SOS, and for the mild SOS supportive treatment was the most important...Interval time < 40days is the only significant facor both in univariate analysis( P =0.015) and multivariate analysis( P =0.002). Summary/Conclusion Inotuzumab has proven to effective in R/R ALL but SOS may require more attention in patients with prior use of Inoand increasing the interval time (preferably more than 40 days) from the last administration of Ino to HSCT may reduce the occurrence of this fatal complications."

Pre-transplantation • Retrospective data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Leukemia • Pediatrics • Transplantation

HOSPITAL BASED OUTPATIENT DAILY DOSING MYELOABLATIVE INTRAVENOUS AND PHARMACOKINETICALLY GUIDED BUSULFAN BASED CONDITIONING FOR ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT – SINGLE CENTER EXPERIENCE (EHA 2026) - "Results A total of 36 consecutive patients received MAC OD BU; 25 (69.4%) received BU with Fludarabine and 10 (27.8%) received BU with Cyclophosphamide...SOS occurred in 2 patients (5.6%) and was treated successfully with Defibrotide; there were no major adverse cardiopulmonary events, otherwise thrombotic microangiopathy occurred in 1 patient (2.8%)...Summary/Conclusion Hospital-based outpatient once daily PK-guided Busulfan dosing is a safe, feasible, and effective myeloablative conditioning. This is a practical strategy limiting inpatient utilization in large volume transplant centers."

Clinical • PK/PD data • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation • CD33