Potential clinical impact of T-cell lymphocyte kinetics monitoring in patients with B cell precursors acute lymphoblastic leukemia treated with blinatumomab: a single-center experience

Blinatumomab is a bispecific anti-CD3 and anti-CD19 antibody that acts as a T-cell engager: by binding CD19+ lymphoblasts, blinatumomab recruits cytotoxic CD3+ T-lymphocytes to target the cancer cells. Here we describe seven different patients affected by B-cell precursor acute lymphoblastic leukemia (Bcp-ALL) and treated with blinatumomab, on which we evaluated the potential association between the amount of different T-cells subsets and deep molecular response after the first cycle, identified as a complete remission in the absence of minimal residual disease (CR/MRD). The immune-system effector cells studied were CD3+, CD4+ effector memory (T4-EM), CD8+ effector memory (T8-EM), and T-regulatory (T-reg) lymphocytes, and myeloid-derived suppressor cells (MDSC). Measurements were performed in the peripheral blood using flow cytometry of the peripheral blood at baseline and after the first cycle of blinatumomab. The first results show that patients with a higher proportion of baseline T-lymphocytes achieved MRD negativity more frequently with no statistically significant difference (p=0.06) and without differences in the subpopulation count following the first treatment. These extremely preliminary data could potentially pave the way for future studies, including larger and less heterogeneous cohorts, in order to assess the T-cell kinetics in a specific set of patients with potential synergy effects in targeting myeloid-derived suppressor cells (MDSC), commonly known to have an immune evasion mechanism in Bcp-ALL

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Target Therapy for Extramedullary Relapse of <i>FLT3</i>-ITD Acute Myeloid Leukemia: Emerging Data from the Field

FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase family member. Mutations in FLT3, as well known, represent the most common genomic alteration in acute myeloid leukemia (AML), identified in approximately one-third of newly diagnosed adult patients. In recent years, this has represented an important therapeutic target. Drugs such as midostaurin, gilteritinib, and sorafenib, either alone in association with conventional chemotherapy, play a pivotal role in AML therapy with the mutated FLT3 gene. A current challenge lies in treating forms of AML with extramedullary localization. Here, we describe the general features of myeloid sarcoma and the ability of a targeted drug, i.e., gilteritinib, approved for relapsed or refractory disease, to induce remission of these extramedullary leukemic localizations in AML patients with FLT3 mutation, analyzing how in the literature, there is an important development of cases describing this promising potential for care

Unruptured Aneurysms Italian Study (UAIS) background and method

Treatment of unruptured cerebral aneurysms still represents an unsettled question in neurosurgical and neuroradiological communities. Although nowadays the indication for treatment have become relatively clear, indeed uncertainity remains for what concerns the proper treatment modality (surgical or endovascular) in terms of both the risk and the mid and long-term efficacy of the two procedures. The "Unruptured Aneurysms Italian Study" is a cooperative prospective study which aims to delineate the "State of the Art" in a nation based population. It has been designed: 1) to depict the nationwide modality of treatment of Unruptured Aneurysms, 2) to assess in the most objective way the overall treatment-related mortality and morbidity as well as the surgical and endovascular risk in the respective patient populations (it is not a surgical versus endovascular study) and 3) to asses the efficacy of the different procedures in the mid and long term periods. The study started on June 2003 and to June 2006, 637 patients have been enrolled. The study will end when the 1000th patient is enrolled

Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020