Constitutively active NOTCH2 signaling is a hallmark in chronic lymphocytic leukemia (CLL). The precise underlying defect remains obscure. Here we show that the mRNA sequence coding for the NOTCH2 negative regulatory region (NRR) is consistently deleted in CLL cells.
View Article and Find Full Text PDFBackground: Chimeric antigen receptor T (CART) cell therapy targeting the B cell specific differentiation antigen CD19 has shown clinical efficacy in a subset of relapsed/refractory (r/r) diffuse large B cell lymphoma (DLBCL) patients. Despite this heterogeneous response, blood pre-infusion biomarkers predicting responsiveness to CART cell therapy are currently understudied.
Methods: Blood cell and serum markers, along with clinical data of DLBCL patients who were scheduled for CART cell therapy were evaluated to search for biomarkers predicting CART cell responsiveness.
Here we analyzed SARS-CoV-2-specific antibodies and T-cell responses after two coronavirus disease 2019 vaccinations over a six-month period in patients with hematological malignancies and assessed the effect of a third vaccination in a subgroup. Sixty-six patients and 66 healthy controls were included. After two vaccinations seroconversion was seen in 52% and a T-cell-specific response in 59% of patients compared with 100% in controls (p = 0.
View Article and Find Full Text PDFBackground: Cancer patients infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have an increased risk of mortality. Here, we investigated predictive factors for coronavirus disease 2019 (COVID-19) associated mortality in patients with neoplastic diseases treated throughout Austria.
Methods: In this multicentric nationwide cohort study, data on patients with active or previous malignant diseases and SARS-CoV‑2 infections diagnosed between 13 March 2020 and 06 April 2021 were collected.
Autoimmune conditions can occur in a temporary relationship with any malignant lymphoma. In many instances, treatment at diagnosis is not required, but symptomatic autoimmune conditions represent an indication for treatment, particularly in chronic lymphoproliferative diseases. Treatment is selected depending on the predominant condition: autoimmune disease (immunosuppression) or lymphoma (antilymphoma therapy).
View Article and Find Full Text PDFThe Bruton tyrosine kinase (BTK) inhibitor ibrutinib has substantially improved therapeutic options for chronic lymphocytic leukemia (CLL). Although ibrutinib is not curative, it has a profound effect on CLL cells and may create new pharmacologically exploitable vulnerabilities. To identify such vulnerabilities, we developed a systematic approach that combines epigenome profiling (charting the gene-regulatory basis of cell state) with single-cell chemosensitivity profiling (quantifying cell-type-specific drug response) and bioinformatic data integration.
View Article and Find Full Text PDFPurpose: To determine whether, in patients with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL), [F]FDG PET/MR can capture treatment effects within the first week after treatment initiation, and whether changes in glucose metabolism and cell density occur simultaneously.
Methods: Patients with histologically proven HL or NHL were included in this prospective IRB-approved study. Patients underwent [F]FDG PET/MR before, and then 48-72 h after (follow-up 1, FU-1) and 1 week after (FU-2) initiation of the first cycle of their respective standard chemotherapy (for HL) or immunochemotherapy (for NHL).
Objective: Limited data exist on gender-specific aspects in hematologic malignancies and have been obtained mostly in non-Hodgkin lymphomas. The objective of this study was to investigate gender-specific aspects in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT).
Methods: A retrospective data analysis of 191 patients with MM who underwent ASCT was performed.
Rare disorders often represent a challenge for clinicians and require close collaboration of an interdisciplinary team.We present the complex case of a 22-year-old male with Danon disease and late-onset of posttransplant lymphoproliferative disorder after heart transplantation. The critical aspects of his condition were: pre-existing rhabdomyolysis; infiltration of muscle and gut with lymphoma; advanced clinical stage with bulky disease; nonresponsiveness to the reduction of immunosuppression and rituximab monotherapy; expected cardiotoxicity of anthracyclines.
View Article and Find Full Text PDFObjective: The aims of the study were to examine a) patients' knowledge of palliative care, b) patients' expectations and needs when being admitted to a palliative care unit, and c) patient's concept of a good palliative care physician.
Methods: The study was based on a qualitative methodology, comprising 32 semistructured interviews with advanced cancer patients admitted to the palliative care unit of the Medical University of Vienna. Interviews were conducted with 20 patients during the first three days after admission to the unit and after one week, recorded digitally, and transcribed verbatim.
The cannabinoid receptors 1 and 2 (CNR1&2) are overexpressed in a variety of malignant diseases and cannabinoids can have noteworthy impact on tumor cell viability and tumor growth. Patients diagnosed with chronic lymphocytic leukemia (CLL) present with very heterogeneous disease characteristics translating into highly differential risk properties. To meet the urgent need for refinement in risk stratification at diagnosis and the search for novel therapies we studied CNR expression and response to cannabinoid treatment in CLL.
View Article and Find Full Text PDFSome patients with diffuse large B-cell lymphoma (DLBCL) require intensive care unit (ICU) admission prior to or during chemotherapy. We analyzed all unscheduled ICU admissions in 331 consecutive patients (18-93 years) with newly diagnosed DLBCL. Thirty-seven patients (11.
View Article and Find Full Text PDFMedicine (Baltimore)
December 2015
Clin Cancer Res
June 2015
Purpose: To determine the value of diffusion-weighted MRI (DWI-MRI) for treatment response assessment in 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-avid lymphoma.
Experimental Design: Patients with FDG-avid Hodgkin (HL) or non-Hodgkin lymphoma (NHL) at pretherapeutic 18F-FDG-PET/CT, who had also undergone pretherapeutic whole-body DWI-MRI, were included in this prospective study. Depending on the histologic lymphoma subtype, patients received different systemic treatment regimens, and follow-up DWI-MRI and 18F-FDG-PET/CT were performed at one or more time points, depending on the clinical course.
In chronic lymphocytic leukaemia (CLL), lipoprotein lipase (LPL) mRNA overexpression is an established poor prognostic marker, its function, however, is poorly understood. Measuring extracellular LPL enzymatic activity and protein, we found no difference between levels in CLL patients and those of controls, both before and after heparin treatment in vivo and in vitro. Investigating LPL knock down effects, we determined five potential downstream targets, of which one gene, STXBP3, reportedly is involved in fatty acid metabolism.
View Article and Find Full Text PDFUridine diphospho glucuronosyltransferase 2B17 (UGT2B17) glucuronidates androgens and xenobiotics including certain drugs. The UGT2B17 gene shows a remarkable copy number variation (CNV), which predisposes for solid tumors and influences drug response. Here, we identify a yet undescribed UGT2B17 mRNA overexpression in poor-risk chronic lymphocytic leukemia (CLL).
View Article and Find Full Text PDFBackground: G protein-coupled receptor 5D (GPRC5D) is a novel surface receptor. As this new subtype of G protein-coupled receptors was discovered, little is known about the role of this gene.
Materials And Methods: In this retrospective study, we investigated GPRC5D mRNA expression by real-time polymerase chain reaction (RT-PCR) in bone marrow (BM) of 48 patients with multiple myeloma (MM).
Background: Treatment of follicular lymphoma with rituximab is currently recommended at a dose of 375 mg/m(2). We aimed to provide a rationale for optimal dosing and scheduling of this anti-CD20 antibody based on pharmacokinetics.
Design And Methods: Clinical efficacy of immunochemotherapy with rituximab, fludarabine and mitoxantrone followed by 2-monthly rituximab maintenance was evaluated in 29 patients with previously untreated follicular lymphoma in a prospective phase II trial (AGMT-NHL9).