Hereditary Spherocytosis: Can Next-Generation Sequencing of the Five Most Frequently Affected Genes Replace Time-Consuming Functional Investigations?

Congenital defects of the erythrocyte membrane are common in northern Europe and all over the world. The resulting diseases, for example, hereditary spherocytosis (HS), are often underdiagnosed, partly due to their sometimes mild and asymptomatic courses. In addition to a broad clinical spectrum, this is also due to the occasionally complex diagnostics that are not available to every patient.

Glucosylceramide Synthase Inhibitors Induce Ceramide Accumulation and Sensitize H3K27 Mutant Diffuse Midline Glioma to Irradiation.

H3K27M mutant (mut) diffuse midline glioma (DMG) is a lethal cancer with no effective cure. The glycosphingolipids (GSL) metabolism is altered in these tumors and could be exploited to develop new therapies. We tested the effect of the glucosylceramide synthase inhibitors (GSI) miglustat and eliglustat on cell proliferation, alone or in combination with temozolomide or ionizing radiation.

Analysis of RBP expression and binding sites identifies PTBP1 as a regulator of CD19 expression in B-ALL.

Despite massive improvements in the treatment of B-ALL through CART-19 immunotherapy, a large number of patients suffer a relapse due to loss of the targeted epitope. Mutations in the locus and aberrant splicing events are known to account for the absence of surface antigen. However, early molecular determinants suggesting therapy resistance as well as the time point when first signs of epitope loss appear to be detectable are not enlightened so far.

Monitoring of Circulating CAR T Cells: Validation of a Flow Cytometric Assay, Cellular Kinetics, and Phenotype Analysis Following Tisagenlecleucel.

Chimeric antigen receptor (CAR) T cell therapy is a potent new treatment option for relapsed or refractory hematologic malignancies. As the monitoring of CAR T cell kinetics can provide insights into the activity of the therapy, appropriate CAR T cell detection methods are essential. Here, we report on the comprehensive validation of a flow cytometric assay for peripheral blood CD19 CAR T cell detection.

Clinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK).

Introduction: Extracranial rhabdoid tumours are rare, highly aggressive malignancies primarily affecting young children. The EU-RHAB registry was initiated in 2009 to prospectively collect data of rhabdoid tumour patients treated according to the EU-RHAB therapeutic framework.

Methods: We evaluated 100 patients recruited within EU-RHAB (2009-2018).

Safety and Activity of the Combination of Ceritinib and Dasatinib in Osteosarcoma.

Osteosarcoma (OS) is the second most common cause of cancer-related death in pediatric patients. The insulin-like growth factor (IGF) pathway plays a relevant role in the biology of OS but no IGF targeted therapies have been successful as monotherapy so far. Here, we tested the effect of three IGF specific inhibitors and tested ceritinib as an off-target inhibitor, alone or in combination with dasatinib, on the proliferation of seven primary OS cells.

Multivariate analysis on complications of central venous access devices in children with cancer and severe disease influenced by catheter tip position and vessel insertion site (A STROBE-compliant study).

Context: Reliable long-term central venous access device (CVAD) is essential for the management of pediatric patients with cancer or chronic diseases. However, there is no general consensus for optimal catheter tip location and vessel insertion site in children.

Objective: This single center study analyzes the risk of complications associated with long-term upper body CVAD and evaluates them with respect to catheter tip location as well as vessel insertion site.

Central Venous Access Devices (CVAD) in Pediatric Oncology Patients-A Single-Center Retrospective Study Over More Than 9 Years.

Central venous access devices (CVAD) provide important benefits in the management of oncological pediatric patients. However, these catheters are responsible for severe complications. In this context, we aimed to analyze all patients receiving a CVAD in the Department of Pediatric Hematology and Oncology of the University hospital of Mainz over a period of 9 years, focused on CVAD related complications.

Personalized therapy: CNS HGNET-BCOR responsiveness to arsenic trioxide combined with radiotherapy.

High-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a rare, highly malignant tumor. At the time of this publication, no standard protocol exists to treat this tumor entity. In this work, we tested the responsiveness of the primary culture PhKh1 derived from tumor tissue from a pediatric HGNET-BCOR patient (P1) to inhibitors of the Sonic hedgehog pathway combined with radiation.

Processing of two latent membrane protein 1 MHC class I epitopes requires tripeptidyl peptidase II involvement.

The EBV Ag latent membrane protein 1 (LMP1) has been described as a potential target for T cell immunotherapy in EBV-related malignancies. However, only a few CD8(+) T cell epitopes are known, and the benefit of LMP1-specific T cell immunotherapy has not yet been proven. In this work, we studied the processing of the two LMP1 HLA-A02-restricted epitopes, YLLEMLRWL and YLQQNWWTL.

Cultivated anti-Aspergillus T(H)1 cells.

Invasive aspergillosis remains a serious complication in patients undergoing allogeneic stem cell transplantation. Since it became clear that lymphocytes provide a critical secondary defense against fungi, adoptive transfer of functionally active anti-Aspergillus T cells might be an option to restore adaptive immune effector mechanisms. Using the interferon (IFN)-gamma secretion assay, we isolated human activated T cells upon stimulation with a cellular extract of Aspergillus fumigatus.

Enumeration of functionally active anti-Aspergillus T-cells in human peripheral blood.

Invasive aspergillosis remains a life-threatening complication in patients undergoing allogeneic stem cell transplantation (SCT). Since CD4(+) T-cells provide a critical secondary defense against Aspergillus spp., the quantification of "functional" anti-Aspergillus T-cells might be important in the clinical care of allogeneic transplant patients.

Generation and characterization of anti-Candida T cells as potential immunotherapy in patients with Candida infection after allogeneic hematopoietic stem-cell transplant.

Because lymphocytes play a major role in the host response to Candida infection, adoptive transfer of anti-Candida T cells might be a therapeutic option in patients undergoing allogeneic hematopoietic stem-cell transplant (alloHSCT) who have invasive Candida infection. Using the interferon (IFN)- gamma secretion assay, we isolated human anti-Candida T cells after stimulation with a cellular extract of C. albicans.

Flow cytometric analysis of virus-specific T lymphocytes: practicability of detection of HCMV-specific T lymphocytes in whole blood in patients after stem cell transplantation.

The detection and quantification of specific T lymphocytes against human cytomegalovirus (HCMV) has proven an important laboratory marker in the monitoring of patients after stem cell transplantation (SCT). In these patients HCMV infections may cause severe disease and death. However, the determination of HCMV-specific T lymphocytes may be limited by lymphopenia occurring after transplantation.

Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus.

Invasive aspergillosis remains a serious complication in patients undergoing allogeneic stem cell transplantation (SCT). Since it became clear that lymphocytes provide a critical secondary defense against fungi, adoptive transfer of functionally active anti-Aspergillus T cells might be an option to restore adaptive immune effector mechanisms. Using the interferon (IFN)-gamma secretion assay, we isolated human activated T cells upon stimulation with a cellular extract of Aspergillus fumigatus.