Search Results (8)

Background/Objectives: The anti-GD2 monoclonal antibody dinutuximab beta has become standard of care maintenance therapy for high-risk neuroblastoma (HR-NB) in the first-line setting and is also approved in the relapsed/refractory setting. We present a retrospective review of 37 children with HR-NB included in the Hungarian Childhood Cancer Registry who received dinutuximab beta (first-line maintenance therapy, n = 31; relapsed/refractory, n = 6). Methods: All patients received dinutuximab beta continuously over the first 10 days of each 35-day cycle, with dosing based on body surface area/weight. Five cycles were planned, with further cycles administered at the treating physician’s discretion. Results: At data cutoff, the overall disease control rate was 54.1% (20/37) (complete response, 51.4% (19/37); partial response, 0.0% (0/37), stable disease, 2.7% [1/37]); two patients (5.4%) had progressive disease, and 15 patients (40.5%) had died. The 5-year overall survival (OS) and event-free survival (EFS) rates in the overall population were 63.3% (95% confidence interval, 49.1−81.7) and 56.2% (95% confidence interval, 42.1−75.0), respectively. Grade 3 or 4 adverse events (including blood and lymphatic system disorders, hypoxia, hypotension, and capillary leak syndrome) were generally consistent with dinutuximab beta’s known safety profile. Conclusions: Dinutuximab beta was an effective immunotherapy for patients with HR-NB in routine clinical practice, with a generally manageable side effect profile. Full article

Systemic Capillary Leak Syndrome (SCLS) and Cytokine Release Syndrome (CRS) have both been described as rare but severe adverse reactions induced by Programmed cell death protein 1 (PD-1) inhibitors such as pembrolizumab. We report the case of a 40-year-old woman undergoing treatment with pembrolizumab for a stage 4 cervical squamous cell carcinoma who presented with anasarca, hypotension, hemoconcentration and signs of multisystemic inflammation. After elimination of alternative causes such as nephrotic syndrome, cardiac dysfunction and cirrhosis, she was diagnosed with both pembrolizumab-induced SCLS and CRS. She was successfully treated with a multimodal treatment approach including intravenous immunoglobulins, steroids, diuretics and axitinib for SCLS as well as ruxolitinib for CRS. After several months of hospitalization, her symptoms finally improved with this treatment regimen, and she was able to attain euvolemic state and be discharged from the hospital. This case highlights certain rare and severe adverse effects of treatment with PD-1 inhibitors. Furthermore, it proposes a novel therapeutic approach for similar cases based upon probable underlying physiopathological mechanisms in SCLS and CRS. Full article

Capillary leak syndrome (CLS) is a rare, potentially life-threatening systemic disease with a mortality rate of more than 30%. Its major clinical manifestation and diagnostic basis are systemic hyperedema. However, we lack knowledge about the presence of severe myocardial edema in patients with CLS. If myocardial edema cannot be detected, it will become a dangerous hidden condition that threatens the safety of patient lives. With the routine application of point-of-care critical ultrasound (POC-CUS) in clinical practice, we found that 2 of 37 (5.41%) CLS patients had severe myocardial edema as the main manifestation. It is also necessary to distinguish it from myocardial noncompaction in newborn infants with severe myocardial edema. This paper will help us to have a deeper understanding and correct management of CLS and, thus, help us to improve the prognosis of patients. This article also suggests the necessity of routine implementation of POC-CUS in the neonatal intensive care unit. Full article

At present, the management of patients with acute respiratory distress syndrome (ARDS) largely focuses on ventilator settings to limit intrathoracic pressures by using low tidal volumes and on FiO₂/PEEP relationships to maintain optimal gas exchange. Acute respiratory distress syndrome is a complex medical disorder that can develop in several primary acute disorders, has a rapid time course, and has several classifications that can reflect either the degree of hypoxemia, the extent of radiographic involvement, or the underlying pathogenesis. The identification of subtypes of patients with ARDS would potentially make precision medicine possible in these patients. This is a very difficult challenge given the heterogeneity in the clinical presentation, pathogenesis, and treatment responses in these patients. The analysis of large databases of patients with acute respiratory failure using statistical methods such as cluster analysis could identify phenotypes that have different outcomes or treatment strategies. However, clinical information available on presentation is unlikely to separate patients into groups that allow for secure treatment decisions or outcome predictions. In some patients, non-invasive positive pressure ventilation provides adequate support through episodes of acute respiratory failure, and the development of specialized units to manage patients with this support might lead to the better use of hospital resources. Patients with ARDS have capillary leak, which results in interstitial and alveolar edema. Early attention to fluid balance in these patients might improve gas exchange and alter the pathophysiology underlying the development of severe ARDS. Finally, more attention to the interaction of patients with ventilators through complex monitoring systems has the potential to identify ventilator dyssynchrony, leading to ventilator adjustments and potentially better outcomes. Recent studies with COVID-19 patients provide tentative answers to some of these questions. In addition, expert clinical investigators have analyzed the promise and difficulties associated with the development of precision medicine in patients with ARDS. Full article

Systemic capillary leak syndrome (SCLS) is a rare and potentially life-threatening disorder characterized by reversible plasma extravasation and vascular collapse. This study aimed to investigate the association between different types of COVID-19 vaccine and SCLS in a real-world setting. We used individual case safety reports of SCLS after COVID-19 vaccination from the WHO pharmacovigilance database, VigiBase. A disproportionality analysis of ChAdOx1 nCoV-19 and mRNA-based vaccines was performed. The information component (IC) and reporting odds ratio (ROR) were calculated from the entire database and viral vaccines data subset. A positive 95% lower end of the IC (IC₀₂₅) value (>0) using Bayesian neural network analysis and lower end of the ROR 95% confidence interval (ROR₀₂₅) ≥1 were defined as the ADR signal detection threshold. A total of 101 (0.004%) events of SCLS were identified. A significant potential signal of disproportionality of SCLS was noted in ChAdOx1 nCoV-19 when applied as the denominator for entire database (IC₀₂₅ = 0.24, ROR₀₂₅ = 1.23) and all viral vaccines (IC₀₂₅ = 0.41, ROR₀₂₅ = 1.59). No significant potential signal was noted for two mRNA-based vaccines as denominators for the entire database (IC₀₂₅ = −0.49, ROR₀₂₅ = 0.71) and all viral vaccines (IC₀₂₅ = −0.32, ROR₀₂₅ = 0.77). Contrary to ChAdOx1 nCoV-1, no safety signal for developing SCLS was identified for mRNA-based vaccines. Full article

Capillary leak syndrome (CLS) is a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT) characterized by weight gain, generalized edema, hypotension, and hypoalbuminemia. The primary pathogenesis is injury of the capillary endothelium resulting in a loss of intravascular fluid into the interstitial space. Treatment is limited to vascular endothelial growth factor withdrawal and systemic corticosteroids. We report two cases with CLS where weight gain, ascites, and hypotension developed after neutrophil engraftment following allogeneic HSCT. We obtained serial electrolytes, blood urea nitrogen, creatinine, and albumin from these patients. Ultrasound with Doppler tracing performed on both patients showed no reversal of portal venous flow. Issues addressed were the restoration of regular hydration by hydroxyethyl starch (HES) solutions, together with systemic corticosteroids and forced diuresis. Tetrastarch was administered 10 and 20 days, respectively. Both patients recovered without sequelae. CLS is a frequent complication after allogeneic HSCT. The effects of HES on CLS merit further consideration and prospective study. Full article

Capillary leak syndrome (CLS) is a rare disease with profound vascular leakage, which can be associated with a high mortality. There have been several reports on CLS as an adverse effect of anti-cancer agents and therapy, but the incidence of CLS according to the kinds of anti-cancer drugs has not been systemically evaluated. Thus, the aim of our study was to comprehensively meta-analyze the incidence of CLS by different types of cancer treatment or after bone marrow transplantation (BMT). We searched the literatures (inception to July 2018) and among 4612 articles, 62 clinical trials (studies) were eligible. We extracted the number of patients with CLS, total cancer patients, name of therapeutic agent and dose, and type of cancer. We performed a meta-analysis to estimate the summary effects with 95% confidence interval and between-study heterogeneity. The reported incidence of CLS was categorized by causative drugs and BMT. The largest number of studies reported on CLS incidence during interleukin-2 (IL-2) treatment (n = 18), which yielded a pooled incidence of 34.7% by overall estimation and 43.9% by meta-analysis. The second largest number of studies reported on anti-cluster of differentiation (anti-CD) agents (n = 13) (incidence of 33.9% by overall estimation and 35.6% by meta-analysis) or undergoing BMT (n = 7 (21.1% by overall estimation and 21.7% by meta-analysis). Also, anti-cancer agents, including IL-2 + imatinib mesylate (three studies) and anti-CD22 monoclinal antibodies (mAb) (four studies), showed a dose-dependent increase in the incidence of CLS. Our study is the first to provide an informative overview on the incidence rate of reported CLS patients as an adverse event of anti-cancer treatment. This meta-analysis can lead to a better understanding of CLS and assist physicians in identifying the presence of CLS early in the disease course to improve the outcome and optimize management. Full article

Systemic capillary leak syndrome (SCLS) is a rare disease characterized by shock caused by capillary hyperpermeability. The disease can occur in cancer patients and effective therapeutic strategies have not been established yet. The aim of the study was to analyze the clinical and laboratory data, treatment modalities, and mortality rate of patients and to identify contributing factors leading to mortality of SCLS in cancer. We searched MEDLINE (inception to July 2018) and of 4612 articles, we identified 62 case reports on SCLS associated with cancer or cancer-related drugs in a total of 53 articles. SCLS was associated with cancer itself in 43.6%, with anti-cancer agents in 51.6% and bone marrow transplantation (BMT) in 4.8%. Among anti-cancer agents, granulocyte-colony stimulating factor (G-CSF) was the most frequently associated drug (14.6%), followed by interleukin (IL)-2 (11.4%). The most common associated malignancies were hematologic (61.3%) with non-Hodgkin lymphoma (22.7%) and multiple myeloma (12.9%) being the leading causes. Common symptoms and signs included dyspnea (27.4%), edema (67.7%), hypotension (32.2%), pleural effusion (29.0%), ascites (22.7%), oliguria (22.7%), and weight gain (21.0%). Patients with SCLS were treated with steroids (59.7%), volume replacement (33.8%), diuretics (24.2%), inotropes (9.6%), methylxanthines (12.8%), β2 agonists (4.8%), while intravenous immunoglobulins (IVIG) were administered in 2 patients (3.2%) only. Among sixteen deaths during follow-up, four were directly attributed to SCLS. Hematologic malignancies were associated with an increased risk for mortality (hazard ratio (HR) 8.820, 95% confidence interval (CI) 1.126–69.063, p = 0.038). Taken together, SCLS can be one important adverse event in cancer patients and careful monitoring of fluid volume is required in the management of SCLS. Full article