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Introduction: Despite well-established clinical criteria for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) following allogeneic hematopoietic cell transplantation (HCT), there is a lack of established diagnostic protein biomarkers. Methods: Prospective samples were collected from patients with very severe SOS/VOD at diagnosis and days +3, +7, +14, and +30 post-initiation of defibrotide. Samples from age-matched controls with no VOD were collected at days +14, +30, +60, +90, and +180 following allogeneic HCT. Serum samples were analyzed for 2,925 protein levels by antibody-based proximity extension assay (PEA). Mean differences in the log-transformed abundance values were compared using t tests in a volcano plot. Results: Five patients with very severe SOS/VOD and 5 control patients were compared. Ten proteins were identified that showed a statistically significant and log-transformed 3-fold increase in concentration. They were CALCA, CCL20, GPR37, IGFBP4, IL1RL1, SLC39A14, SPINK4, FABP3, MYL3, and CHCHD10. Four different proteins, namely, CD83, leukocyte associated immunoglobulin-like receptor 2 (LAIR2), CD7, and HEM6 showed a significant decrease with defibrotide treatment. SOS/VOD resolved in 80% (n = 4) of patients, while 1 patient deceased due to SOS/VOD. Conclusion: PEA technology identified 10 proteins that were significantly elevated in patients with very severe SOS/VOD. Prospective studies in a larger cohort using this technology may be able to conclusively identify diagnostic protein biomarkers for SOS/VOD. [ABSTRACT FROM AUTHOR]

Abstract Introduction To diagnose sinusoidal obstruction syndrome/veno‐occlusive disease (SOS/VOD), transabdominal ultrasonography is usually used to detect hemodynamic changes, but we tried to detect the changes using four‐dimensional computed tomography (4D‐CT). A 42‐year‐old Japanese woman was diagnosed with late‐onset SOS/VOD with transabdominal ultrasonography and was also assessed using 4D‐CT. Method We analyzed the portal vein (PV) contrast effect every 1.5 seconds and plotted the values of the contrast effect. With this graph, we analyzed three hemodynamic parameters. Result We found that these parameters correlated with the patient's status and indicated stasis due to sinusoid constriction. Conclusion 4D‐CT may become a helpful tool to diagnose and follow up with SOS/VOD.

Inotuzumab ozogamicin (InO) is an antibody‐drug conjugate approved for the treatment of relapsed/refractory B‐cell acute lymphoblastic leukemia (ALL). Several clinical trials are investigating InO in combination with low‐intensity chemotherapy or other anti‐ALL–targeted therapies in the salvage and frontline settings, notably in older adults who often cannot tolerate intensive chemotherapy and tend to have higher‐risk disease. InO is also increasingly used to bridge patients to hematopoietic stem cell transplantation (HSCT), in sequence with chimeric antigen receptor T‐cell therapy, to eliminate measurable residual disease and to prevent post‐HSCT relapse. Veno‐occlusive disease/sinusoidal obstruction syndrome is a potential complication of InO treatment, particularly when followed by HSCT. Herein, the authors review the historical development and current status of InO, strategies for mitigating the risk of InO‐related veno‐occlusive disease/sinusoidal obstruction syndrome, and future directions for InO research and clinical use. Inotuzumab ozogamicin is approved to treat relapsed/refractory B‐cell acute lymphoblastic leukemia but is increasingly used in other treatment settings. The authors review the historical development and current status of inotuzumab ozogamicin in adult B‐cell acute lymphoblastic leukemia. [ABSTRACT FROM AUTHOR]

Hippocampal neurogenesis (HN) occurs throughout the life course and is important for memory and mood. Declining with age, HN plays a pivotal role in cognitive decline (CD), dementia, and late-life depression, such that altered HN could represent a neurobiological susceptibility to these conditions. Pertinently, dietary patterns (e.g. Mediterranean diet) and/or individual nutrients (e.g. vitamin D, omega 3) can modify HN, but also modify risk for CD, dementia, and depression. Therefore, the interaction between diet/nutrition and HN may alter risk trajectories for these ageing-related brain conditions. Using a subsample (n  = 371) of the Three-City cohort—where older adults provided information on diet and blood biobanking at baseline and were assessed for CD, dementia, and depressive symptomatology across 12 years—we tested for interactions between food consumption, nutrient intake, and nutritional biomarker concentrations and neurogenesis-centred susceptibility status (defined by baseline readouts of hippocampal progenitor cell integrity, cell death, and differentiation) on CD, Alzheimer's disease (AD), vascular and other dementias (VoD), and depressive symptomatology, using multivariable-adjusted logistic regression models. Increased plasma lycopene concentrations (OR [95% CI]  =  1.07 [1.01, 1.14]), higher red meat (OR [95% CI]  =  1.10 [1.03, 1.19]), and lower poultry consumption (OR [95% CI]  =  0.93 [0.87, 0.99]) were associated with an increased risk for AD in individuals with a neurogenesis-centred susceptibility. Increased vitamin D consumption (OR [95% CI]  =  1.05 [1.01, 1.11]) and plasma γ-tocopherol concentrations (OR [95% CI]  =  1.08 [1.01, 1.18]) were associated with increased risk for VoD and depressive symptomatology, respectively, but only in susceptible individuals. This research highlights an important role for diet/nutrition in modifying dementia and depression risk in individuals with a neurogenesis-centred susceptibility. [ABSTRACT FROM AUTHOR]

Gallbladder diseases are very common, and their diagnosis is based on clinical–laboratory evaluation and imaging techniques. Considering the different imaging diagnostic tools, ultrasound (US) has the advantage of high accuracy combined with easy availability. Therefore, when a gallbladder disease is suspected, US can readily assist the clinician in the medical office or the emergency department. The high performance of US in the diagnosis of gallbladder diseases is mainly related to its anatomic location. The most frequent gallbladder pathological condition is gallstones disease, easily diagnosed via US examination. Acute cholecystitis (AC), a possible complication of gallstone disease, can be readily recognized due to its specific sonographic features. Additionally, a number of benign, borderline or malignant gallbladder lesions may be detected via US evaluation. The combined use of standard B-mode US and additional sonographic techniques, such as contrast-enhanced ultrasonography (CEUS), may provide a more detailed study of gallbladder lesions. Multiparametric US (combination of multiple sonographic tools) can improve the diagnostic yield during gallbladder examination. [ABSTRACT FROM AUTHOR]

Summary: Background: Sinusoidal obstruction syndrome is a potentially fatal complication following hematopoietic cell transplantation, high-intensity chemotherapies and increasingly seen with calicheamicin based leukemia therapies. Paediatric specific European Society for Blood and Marrow Transplantation (pEBMT) diagnostic criteria have demonstrated benefit in single center studies compared to historic criteria. Yet, the extent to which they have been universally implemented remains unclear. Methods: We conducted a retrospective multi-centre study to examine the potential impact of the Baltimore, modified Seattle and pEBMT criteria on the incidence, severity, and outcomes of sinusoidal obstruction syndrome among paediatric hematopoietic cell transplantation patients. Findings: The incidence of sinusoidal obstruction syndrome in this cohort (n = 488) was higher by pEBMT (21.5%) vs historic modified Seattle (15.6%) and Baltimore (7.0%) criteria (p

Two Northern cheetahs (Acinonyx jubatus soemmeringii) were euthanased at the Zoological Society of London's Whipsnade Zoo due to old age and degenerative joint disease. Both animals were found to have mild to moderate fibrosis of the space of Disse (veno‐occlusive disease) and multiple congested, tortuous vessels running from the hepatic portal vein to the caudal vena cava (acquired portosystemic shunt). We hypothesise that the shunts result from portal hypertension caused by the veno‐occlusive disease, and that this helps relieve pressure on the sinusoidal endothelium, limiting progression of the disease. As acquired portosystemic shunt is a known sequel to portal hypertension, we believe that acquired portosystemic shunt may be more common in cheetahs with veno‐occlusive disease than is currently reported, and provide a practical protocol and gross images as diagnostic tools to aid in the postmortem diagnosis of this condition. [ABSTRACT FROM AUTHOR]

Pulmonary veno-occlusive disease (PVOD) is an extremely rare condition in oncology practice. Although PVOD is clinically similar to pulmonary arterial hypertension, the conditions differ in terms of pathophysiology, management, and prognosis. This report discusses the case of a 47-year-old woman who developed dyspnea and fatigue after high-dose cyclophosphamide chemotherapy and autologous hematopoietic stem cell transplantation for relapsed lymphoma. The patient exhibited tachycardia, tachypnea, and hypotension, but other findings in the physical examination were unremarkable. The imaging studies showed no evidence of pulmonary embolism, but multiple ground-glass opacities and bilateral pleural effusions were observed on chest high-resolution computed tomography scans. In the right heart catheterization study, the mean pulmonary artery pressure and pulmonary vascular resistance were 35 mm Hg and 5.93 Wood units, respectively, with a normal pulmonary capillary wedge pressure of 10 mm Hg. Pulmonary function tests revealed a remarkable reduction in the percentage predicted value of diffusing capacity of the lungs for carbon monoxide to 31%. Lymphoma progression, collagen diseases, infectious diseases such as human immunodeficiency virus or parasitic infections, portal hypertension, and congenital heart disease were carefully excluded as these are also capable of causing pulmonary arterial hypertension. Thereafter, we reached a final diagnosis of PVOD. The patient was treated with supplemental oxygen and a diuretic during 1 month of hospitalization, which relieved her right heart overload symptoms. Herein, we present the patient’s clinical course and diagnostic workup because misdiagnosis or inappropriate treatment can lead to unfavorable outcomes in patients with PVOD.

Purpose: Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplantation (HSCT) with a high incidence in pediatric patients. This study aimed to detect signs of hypofibrinolysis using thrombelastography. Methods: In this prospective single-center study, thrombelastographic measurements (EX and TPA tests) were taken during HSCT to detect signs of impaired coagulation, clot formation, or hypofibrinolysis. Results: Of 51 patients undergoing allogeneic and autologous HSCT, five (9.8%) developed VOD and received defibrotide treatment. Thrombelastography measurements were also obtained from 55 healthy children as a control group. The results show that clot lysis was prolonged in VOD patients compared to other HSCT patients and control group (lysis time, TPA test: day + 14 to + 21: VOD: 330 ± 67 s vs. HSCT: 246 ± 53 s; p = 0.0106; control: 234 ± 50 s; control vs. VOD: p = 0.0299). The maximum lysis was reduced in HSCT patients compared to controls (EX test: control: 8.3 ± 3.2%; HSCT: day 0 to + 6: 5.3 ± 2.6%, p < 0.0001; day + 7 to + 13: 3.9 ± 2.1%, p < 0.0001; day + 14 to d + 21: 4.1 ± 2.3%, p < 0.0001). Conclusion: These results suggest that HSCT patients exhibit reduced fibrinolytic capacities and patients diagnosed with VOD show signs of hypofibrinolysis. This prospective study shows that fibrinolysis can be assessed in a rapid and accessible way via thrombelastography. Thrombelastography might be a parameter to support the diagnosis of a VOD and to serve as a follow-up parameter after the diagnosis of a VOD. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound is a valuable tool to evaluate liver lesions in a pediatric patient cohort. Unusual progressive hepatic echogenicity (UPHE) is a self-limiting phenomenon noted in a cohort of children after administration of ultrasonographic contrast agents (UCAs). UPHE appears initially as heterogeneous branching similar to portal venous gas, culminating in a diffuse globular appearance. The etiology of UPHE is unclear and may be from underlying hepatic microvascular disease or altered gut permeability. This case series describes pediatric patients with UPHE following UCA bolus and discusses its potential mechanisms in children. [ABSTRACT FROM AUTHOR]

Abstract Veno‐occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a rare, serious complication following haematopoietic cell transplantation (HCT). This systematic literature review evaluated differences in clinical manifestations of VOD/SOS post‐HCT in adults and children. Medline and Embase were searched up to 4 March 2021 for reports of VOD/SOS post‐HCT; VOD/SOS diagnostic guidelines were included. Publications were evaluated based on inclusion of five cardinal clinical features of VOD/SOS (ascites, hepatomegaly, hyperbilirubinaemia, right upper quadrant [RUQ] pain and weight gain ≥5%). Overall, 204 publications were included. At diagnosis, hyperbilirubinaemia was more common in adults (93%) versus children (82%), weight gain ≥5% and hepatomegaly were more common in children (86%, 89%) versus adults (73%, 76%) and ascites and RUQ pain were similar between age groups. While 40% of cases had all five cardinal features, age was not a substantial determinant of the likelihood of missing any single specific feature. The proportion of cases, where hyperbilirubinaemia was the first recorded feature, was higher in children versus adults; weight gain and RUQ pain appeared first in a greater proportion of adults versus children. VOD/SOS diagnosis can be challenging; features may not present in a distinct sequence. This necessitates continuous vigilance by those involved in patient monitoring post‐HCT.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in SARS-CoV-2 positive candidates is usually delayed until the clinical resolution of the infection's symptoms and a negative nasopharyngeal molecular test. However, prolonged SARS-CoV-2 positivity has been frequently observed in haematological malignancies, thus representing a challenge for the timing of transplant procedures. Here, we report on the case of a 34-year-old patient with recent pauci-symptomatic COVID-19 undergoing transplant for high-risk acute Blymphoblastic leukemia before achieving viral clearance. Shortly before their scheduled allogeneic HSCT from a matched unrelated donor, the patient developed mild Omicron BA.5 infection receiving nirmatrelvir/ritonavir with fever resolution within 72 hours. Twenty-three days after COVID-19 diagnosis, because of increasing minimal residual disease values in the context of high-risk refractory leukemia and clinical resolution of SARS-2-CoV infection with reduction of viral load at surveillance nasopharyngeal swabs, it was decided not to delay further allo-HSCT. During myelo-ablative conditioning, the nasopharyngeal SARS-CoV-2 viral load increased while the patient remained asymptomatic. Consequently, two days before the transplant, intra-muscular tixagevimab/cilgavimab 300/300 mg and a 3-day course of intravenous remdesivir were administered. During the pre-engraftment phase, venoocclusive disease (VOD) occurred at day +13, requiring defibrotide treatment to obtain a slow but complete recovery. The post-engraftment phase was characterized by mild COVID-19 at day +23 (cough, rhino-conjunctivitis, fever) that spontaneously resolved, achieving viral clearance at day +28. At day +32, she experienced grade I acute graft-versus host disease (a-GVHD, skin grade II) treated with steroids and photo-apheresis, without further complications during follow-up until day +180. Addressing the issue of allo-HSCT timing in patients recovering from SARS-CoV-2 infection with high-risk malignant diseases is challenging because of 1] the high risk of COVID-19 clinical progression, 2] the impact of transplant delay on leukemia prognosis and 3] the occurrence of endothelial complications such as VOD, a-GVHD, and transplant associated thrombotic micro-angiopathy. Our report describes the favourable outcome of allo-HSCT in a recipient with active SARS-CoV2 infection and high-risk leukemia thanks to timely anti-SARS-CoV-2 preventive therapies and prompt management of transplant-related complications. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in SARS-CoV-2 positive candidates is usually delayed until the clinical resolution of the infection’s symptoms and a negative nasopharyngeal molecular test. However, prolonged SARS-CoV-2 positivity has been frequently observed in haematological malignancies, thus representing a challenge for the timing of transplant procedures. Here, we report on the case of a 34-year-old patient with recent pauci-symptomatic COVID-19 undergoing transplant for high-risk acute B-lymphoblastic leukemia before achieving viral clearance. Shortly before their scheduled allogeneic HSCT from a matched unrelated donor, the patient developed mild Omicron BA.5 infection receiving nirmatrelvir/ritonavir with fever resolution within 72 hours. Twenty-three days after COVID-19 diagnosis, because of increasing minimal residual disease values in the context of high-risk refractory leukemia and clinical resolution of SARS-2-CoV infection with reduction of viral load at surveillance nasopharyngeal swabs, it was decided not to delay further allo-HSCT. During myelo-ablative conditioning, the nasopharyngeal SARS-CoV-2 viral load increased while the patient remained asymptomatic. Consequently, two days before the transplant, intra-muscular tixagevimab/cilgavimab 300/300 mg and a 3-day course of intravenous remdesivir were administered. During the pre-engraftment phase, veno-occlusive disease (VOD) occurred at day +13, requiring defibrotide treatment to obtain a slow but complete recovery. The post-engraftment phase was characterized by mild COVID-19 at day +23 (cough, rhino-conjunctivitis, fever) that spontaneously resolved, achieving viral clearance at day +28. At day +32, she experienced grade I acute graft-versus host disease (a-GVHD, skin grade II) treated with steroids and photo-apheresis, without further complications during follow-up until day +180. Addressing the issue of allo-HSCT timing in patients recovering from SARS-CoV-2 infection with high-risk malignant diseases is challenging because of 1] the high risk of COVID-19 clinical progression, 2] the impact of transplant delay on leukemia prognosis and 3] the occurrence of endothelial complications such as VOD, a-GVHD, and transplant associated thrombotic micro-angiopathy. Our report describes the favourable outcome of allo-HSCT in a recipient with active SARS-CoV2 infection and high-risk leukemia thanks to timely anti-SARS-CoV-2 preventive therapies and prompt management of transplant-related complications.

Pulmonary veno-occlusive disease (PVOD) is an extremely rare condition in oncology practice. Although PVOD is clinically similar to pulmonary arterial hypertension, the conditions differ in terms of pathophysiology, management, and prognosis. This report discusses the case of a 47-year-old woman who developed dyspnea and fatigue after high-dose cyclophosphamide chemotherapy and autologous hematopoietic stem cell transplantation for relapsed lymphoma. The patient exhibited tachycardia, tachypnea, and hypotension, but other findings in the physical examination were unremarkable. The imaging studies showed no evidence of pulmonary embolism, but multiple ground-glass opacities and bilateral pleural effusions were observed on chest high-resolution computed tomography scans. In the right heart catheterization study, the mean pulmonary artery pressure and pulmonary vascular resistance were 35 mm Hg and 5.93 Wood units, respectively, with a normal pulmonary capillary wedge pressure of 10 mm Hg. Pulmonary function tests revealed a remarkable reduction in the percentage predicted value of diffusing capacity of the lungs for carbon monoxide to 31%. Lymphoma progression, collagen diseases, infectious diseases such as human immunodeficiency virus or parasitic infections, portal hypertension, and congenital heart disease were carefully excluded as these are also capable of causing pulmonary arterial hypertension. Thereafter, we reached a final diagnosis of PVOD. The patient was treated with supplemental oxygen and a diuretic during 1 month of hospitalization, which relieved her right heart overload symptoms. Herein, we present the patient's clinical course and diagnostic workup because misdiagnosis or inappropriate treatment can lead to unfavorable outcomes in patients with PVOD. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced veno-occlusive disease (VOD) is a rare liver dysfunction seen among pediatric cancer patients which could lead to severe morbidity and mortality. Defibrotide is the commonly used antidote in the management of both stem cell transplant and chemotherapy-associated VOD along with liver supportive measures. Defibrotide is costly and generally not accessible to majority of patients treated at resource poor settings. In this report, we describe the successful management of chemotherapy-induced VOD with timely administration of N-acetyl cysteine. [ABSTRACT FROM AUTHOR]

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT), especially in severe cases. Patient outcomes are improved with prompt treatment; however, diagnosing this disease is challenging as many clinical symptoms of VOD/SOS overlap with other post-HCT complications. A biomarker-based prognostic test for the assessment of VOD/SOS risk, termed "VODCheck" was developed in a previous study but has not yet been validated. This study aimed to validate the accuracy of VODCheck as a prognostic test for VOD/SOS in an independent cohort of patients. VODCheck incorporates hyaluronan (HA), angiopoietin-2 (ANG-2), and thrombomodulin (TM) based on their association with VOD/SOS, their analytical characteristics, and their ability to complement each other in a multivariate prognostic model. To validate VODCheck we measured plasma biomarker levels from a subset of patients enrolled in the control arm of a phase 3 study that tested VOD/SOS prophylaxis. We used a hierarchical design with prespecified primary (day 7), secondary A (day 15), and secondary B (day 1) hypotheses to verify the prognostic accuracy of VODCheck post-HCT. The cases of VOD/SOS (n = 22) were age-matched ∼1:3 with controls (n = 65). VODCheck was prognostic of VOD/SOS risk at all 3 time points with an area under the curve (AUC) of .815 (P < .001) for day 7, .836 (P < .001) for day 15, and .706 (P = .002) for day 1 post-HCT. A multivariate analysis confirmed the prognostic accuracy of VODCheck after adjustment for confounders such as age, VOD/SOS risk status, primary disease, and ozogamicin treatment. VODCheck was validated as an independent predictor of risk for VOD/SOS within 15 days post-HCT and appears to provide clinicians with actionable information to improve patient care., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Abstract Background Vasculitis and phlebitis with vascular occlusion within appendix specimen is rare. Several authors have reported COVID-19 related veno-occlusive disease in hepatic pathology, but lymphoid aggregation with phlebitis is unusual in appendix specimen. We present a case with medium size venule phlebitis in an appendix of a patient recovered from COVID-19 infection. Case presentation A 27-year-old who recently recovered from COVID-19 infection 12 weeks prior, presented with acute appendicitis, confirmed on computed tomography and operative findings. He underwent an uneventful laparoscopic appendicectomy. Histopathology showed veno-occlusive vasculitis within the appendix specimen. Conclusions Veno-occlusive disease within the appendix is uncommon. Emerging data suggest COVID-19 infection can cause systemic vascular complications. We herein report a case of healthy patient with no past medical history with an unusual findings of medium vessels phlebitis within the appendix post COVID-19 infection.

We present the case of a young adult, who developed several hepatic post-HCT complications, which made differential diagnosis extremely difficult. [ABSTRACT FROM AUTHOR]

Sinusoidal obstruction syndrome (SOS) is a unique form of liver injury that occurs after exposure to chemotherapeutic drugs and toxins. The diagnosis of SOS in humans remains a challenge as the clinical criteria have low specificity and there are no reliable noninvasive biomarkers. The mechanism of injury is believed to be damage to liver endothelial cells, primarily sinusoidal endothelial cells (SECs), which leads to sinusoidal dilation, central venous fibrosis, and/or nodular regeneration. Nonclinical data suggest that this uncommon liver toxicity can be recapitulated in cynomolgus monkeys, and it is critical that pathologists are familiar with its characteristic clinicopathologic features. Elevations in liver enzymes, in particular aspartate aminotransferase, associated with isolated thrombocytopenia, should raise the suspicion of SEC injury for specific drug classes. Characterization of liver microscopic findings in monkeys benefits from the use of appropriate stains, such as reticulin stain, and VEGFR2 and CD34 immunohistochemical (IHC) stains. CD41 IHC demonstrates platelet accumulation in injured sinusoids, the likely cause of thrombocytopenia commonly reported in SOS. In conclusion, this report provides a comprehensive characterization of the pathology findings of drug-induced SOS in monkeys with the objectives of ensuring appropriate nonclinical recognition of the liability and informing clinical development strategy and monitoring. [ABSTRACT FROM AUTHOR]

Hepatic sinusoidal obstruction syndrome, also known as veno-occlusive disease, can occur as a complication of myeloablative chemotherapy, as a result of low-intensity chemotherapy-related liver toxicity or radiotherapy of the liver. Symptoms of sinusoidal obstruction syndrome can range from asymptomatic to liver dysfunction or severe disease with life-threatening acute multi-organ failure. Imaging features can suggest or support this clinical diagnosis. Familiarity with the imaging spectrum of sinusoidal obstruction syndrome is therefore important for both radiologists and clinical oncologists. Here, multi-modality radiologic appearances of sinusoidal obstruction syndrome in pediatric patients are illustrated, including outcome after follow-up. [ABSTRACT FROM AUTHOR]

Aims: This study evaluated cost-effectiveness of defibrotide vs best supportive care (BSC) for the treatment of hepatic veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS) with multiorgan dysfunction (MOD) post-hematopoietic cell transplantation (HCT) in Spain. Materials and methods: A two-phase Markov model, comprising a 1-year acute phase with daily cycles and a lifetime long-term phase with annual cycles, was adapted to the Spanish setting. The model included a cohort of patients with severe VOD/SOS (defined as VOD/SOS with MOD) post-HCT. For the acute phase, efficacy and VOD/SOS-related length of stay were obtained from a phase 3 defibrotide study (NCT00358501). VOD/SOS-related hospital stays were 7.5 and 23.2 days in defibrotidetreated and BSC patients, respectively. Defibrotide-treated patients spent 30% of their stay in the intensive care unit vs 60% in BSC patients. Assumptions for the long-term phase and utility values were obtained from the literature. Costs were from the Spanish Health System perspective (e2019). Defibrotide cost was based on 25 mg/kg/day over 17.5 days, using local expert opinion. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were estimated over a lifetime horizon, applying a 3% discount rate for costs and outcomes. Sensitivity analyses assessed the robustness of the results. Results: Defibrotide produced an additional 1.214 QALYs and 1.348 LYs vs BSC, with a total cost of e33,708 more than BSC alone. However, defibrotide resulted in savings up to e16,644/patient for cost of hospital stay. Difference between costs and effective measures led to ratios of e27,757/QALY and e25,007/LY gained. Additional hospital stays had the greatest influence on base-case results. Probabilistic analysis confirmed the robustness of the deterministic results. Limitations: Limitations include use of historical controls and assumptions extrapolated from the literature. Conclusions: This cost-effectiveness model, adapted to the Spanish setting, showed that defibrotide is a cost-effective alternative to BSC alone in patients with severe VOD/SOS post-HCT. [ABSTRACT FROM AUTHOR]

Abstract Background Busulfan (Bu) is a key component of several conditioning regimens used before hematopoietic stem cell transplantation (HSCT). However, the optimum systemic exposure (expressed as the area under the concentration-time curve [AUC]) of Bu for clinical outcome in children is controversial. Methods Research on pertinent literature was carried out at PubMed, EMBASE, Web of science, the Cochrane Library and ClinicalTrials.gov . Observational studies were included, which compared clinical outcomes above and below the area under the concentration-time curve (AUC) cut-off value, which we set as 800, 900, 1000, 1125, 1350, and 1500 μM × min. The primary efficacy outcome was notable in the rate of graft failure. In the safety outcomes, incidents of veno-occlusive disease (VOD) were recorded, as well as other adverse events. Results Thirteen studies involving 548 pediatric patients (aged 0.3–18 years) were included. Pooled results showed that, compared with the mean Bu AUC (i.e., the average value of AUC measured multiple times for each patient) of > 900 μM × min, the mean AUC value of

Budd-Chiari syndrome (BCS) results from an occlusion of the hepatic venous flow which in turn leads to portal hypertension causing ascites and other signs of liver dysfunction. Here, we present the case of a 43-year-old woman with recurrent ascites who was found to have BCS secondary to an inferior vena cava thrombosis extending into the hepatic veins. Although she had a normal platelet count on admission, additional laboratory investigations revealed an MPL mutation. She was discharged on anticoagulation with apixaban and later found to have thrombocytosis on repeat blood work, confirming the diagnosis of essential thrombocytosis, following which she was started on myelosuppressive therapy with hydroxyurea.

Introduction: To diagnose sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), transabdominal ultrasonography is usually used to detect hemodynamic changes, but we tried to detect the changes using four-dimensional computed tomography (4D-CT). A 42-year-old Japanese woman was diagnosed with late-onset SOS/VOD with transabdominal ultrasonography and was also assessed using 4D-CT. Method We analyzed the portal vein (PV) contrast effect every 1.5 seconds and plotted the values of the contrast effect. With this graph, we analyzed three hemodynamic parameters., Result: We found that these parameters correlated with the patient's status and indicated stasis due to sinusoid constriction., Conclusion: 4D-CT may become a helpful tool to diagnose and follow up with SOS/VOD., Competing Interests: Satoshi Iyama: Alexion Pharmaceuticals: Honoraria, Research Funding; MSD: Research Funding; Otsuka Pharmaceutical: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; SymBio Pharmaceuticals: Honoraria, Research Funding; Astellas: Honoraria; CSL Behring: Honoraria; Daiichi Sankyo: Honoraria; Meiji Pharma: Honoraria; Nippon Shinyaku: Honoraria; Novartis Honoraria; Hiroto Horiguchi: Otsuka Pharmaceutical: Honoraria, Kyowa Kirin: Honoraria, Chugai pharmaceutical: Honoraria, Janssen pharmaceutical; Kyowa Kirin.: Honoraria, Abbvie pharmaceutical: Honoraria. Kohichi Takada: Daiichi Sankyo: Honoraria. The rest of the authors declare no conflict of interest., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

We herein report a rare case of idiopathic portal hypertension (IPH)-like disease that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A 53-year-old woman who underwent allo-HSCT for acute myeloid leukemia showed portal hypertension with radiological and histopathological findings consistent with IPH, distinct from veno-occlusive disease (VOD) and graft-versus-host disease (GVHD) of the liver. This case highlights the importance of considering IPH-like disease as a potential cause of portal hypertension after allo-HSCT. Awareness of this complication can aid in the early diagnosis and appropriate management of patients post allo-HSCT.

Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). We previously reported the efficacy of the Hokkaido Ultrasonography (US)-based scoring system (HokUS-10) for US findings. To establish easier-to-use criteria, we retrospectively evaluated US findings from 441 patients, including 30 patients with SOS using the HokUS-10 scoring system. Using logistic regression analysis, we established the novel diagnostic criteria HokUS-6. In the presence of ascites, US diagnosis was made in the presence of two of the following 6 parameters: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase. The AUC, sensitivity, and specificity of HokUS-6 were 0.974 (95% confidence interval 0.962-0.990), 95.2%, and 96.9%, respectively. The scores were significantly higher in patients with severe SOS than in those with non-severe SOS (p = 0.013). Furthermore, the scores before HSCT were significantly higher in patients who developed SOS than in controls (p = 0.001). The HokUS-6 is an easy and useful way to diagnose and identify the risk of SOS. [ABSTRACT FROM AUTHOR]

Introduction. Sinusoidal obstruction syndrome (SOS), previously known as venoocclusive disease, is a rare life-threatening complication of chemotherapy, mostly associated with hematopoietic stem cell transplantation. SOS occurs in approximately 22% of children and 30% of infants undergoing treatment for oncological diseases, which is 2-3 times more often than in adults. Defibrotide (DF) is currently the only drug that is approved for the treatment of SOS, but due to the rarity of the disease and lack of prospective studies, the evidence of DF efficiency remains uncertain. Several studies suggest the benefit of SOS prophylaxis with DF. Objective. Systematically assess the effectiveness of the use of DF in children for prophylaxis and treatment of SOS in clinical trials, published within the last 10 years. Methods. Literature search in PubMed and Google Scholar was performed between the 1st of November 2023 and the 1st of December 2023. We used "defibrotide", "sinusoidal obstruction syndrome, "veno-occlusive disease", "pediatric" and "children" as keywords. The systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Case reports, reviews, metaanalyses, studies published more than 10 years ago and studies with no children were excluded. Results. 15 publications -- 10 retrospective studies, 3 prospective studies, one randomized clinical trial, and one controlled clinical trial - met the inclusion criteria and were analyzed in this review. In total, 7655 patients were included into the studies, with 3121 (40,7%) children <18 y. Eight studies evaluated only SOS treatment with DF, four studies described only SOS prophylaxis with DF, and three studies - both prophylaxis and treatment. The DF dose range was between 12,5 and 60,0 mg/kg/day, with the mean dosage of 25 mg/kg/day. Three studies showed the benefit of SOS prophylaxis with DF while three studies concluded that the prophylaxis is not useful. The studies evaluating DF treatment reported overall survival rates ranging from 25% to 90.4%. All studies supported the benefit of DF for the treatment of SOS. Conclusions. This systematic review suggests that the treatment of SOS with DF in children is effective and should be applied in clinical practice. However, the most recent studies do not show enough evidence that SOS prophylaxis with DF has significant benefits. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and effectiveness of the Protégé nitinol self-expanding stent for the treatment of iliofemoral veno-occlusive disease. Materials and Methods: A retrospective review was performed of 376 (284 left, 92 right) Protégé stents in 212 limbs of 183 patients (mean age: 53 ± 17 years, 52% female) treated for iliofemoral veno-occlusive disease between 2011 and 2018. Binary patency was assessed with duplex ultrasound and calculated by Kaplan Meier analysis. Clinical outcomes were evaluated by clinical-etiology-anatomy-pathophysiology (CEAP) classification and Villalta scores. Adverse events were recorded and categorized per Society of Interventional Radiology reporting standards. Results: Of the 212 limbs, 125 presented with acute thrombosis and 28 with chronic thrombosis requiring thrombectomy (n = 44), catheter directed thrombolysis (n = 32), or both (n = 77). Fifty-nine limbs were non-thrombotic. Mean follow-up time was 11.44 ± 11.37 months. Kaplan Meier analysis revealed a primary limb-level patency of 92.3%, 88.6%, 86.9% and 86.9% at 6, 12, 24 and 36 months, respectively. CEAP and Villalta scores improved from a median of C3 (range: 0–6) to C1 (0–5) (p < 0.001) and from a mean of 13.4 ± 7.5 to 5.3 ± 4.9 (p < 0.001), respectively. Nine minor and 2 major adverse events were recorded. Conclusions: Endovascular treatment of iliofemoral veno-occlusive disease with the Protégé self-expanding stent appears to have good mid-term patency. Level of Evidence: Level 4, Case Series [ABSTRACT FROM AUTHOR]

Hepatic veno-occlusive disease (VOD/sinusoidal obstructive syndrome) represents a constellation of clinical findings including right upper quadrant pain, jaundice, hepatomegaly, and ascites. In the post-hematopoietic stem cell transplant (SCT) setting, the reported incidence has been 10–15%, with severe VOD historically resulting in high mortality rates. Novel agents including calicheamicin conjugated with CD33 (gemtuzumab ozogamicin; GO) and CD22 (inotuzumab ozogamicin; InO) are increasingly used for the treatment of acute myeloid leukemia and acute lymphoblastic leukemia, respectively. Both GO and InO are highly active, but also have unique hepatotoxicity profiles, including a higher risk of VOD in recipients of SCT. Introduction of GO and InO into pre-SCT leukemia management adds additional complexity to SCT patient selection and toxicity monitoring. In this article, we describe and review the risks and management associated with VOD in SCT recipients exposed to GO and InO. [ABSTRACT FROM AUTHOR]