Oral dysplastic complications after HSCT: Single case series of multidisciplinary evaluation of 80 patients

Oral squamous cell carcinoma (OSCC) is the most common secondary solid malignancy after hematopoietic stem‐cell transplantation (HSCT). OSCC following HSCT is frequently preceded by chronic graft‐versus‐host disease (cGVHD). The aim of this study was to describe a cohort of post‐HSCT patients and to evaluate the onset of oral epithelial dysplasia and/or OSCC over time. In this retrospective cohort study, we present a cohort of hematological patients that underwent HSCT. Demographic variables, clinical hematological data, data regarding acute graft‐versus‐host disease (aGVHD) and cGVHD, and oral clinical features were analyzed. We focused on clinicopathological features of a subgroup of 22 patients with oral cGVHD and OSCC after HSCT. Among 80 included patients, 46 patients (57,5%) developed aGVHD and 39 patients (48,7%) developed cGVHD. Oral mucosa was involved in 17 patients with aGVHD (36,9%) and in 22 patients (56,4%) with cGVHD. Out of a total of 22 oral biopsies, roughly 40% revealed mild to moderate dysplasia, and 32 % were OSCC. In the absence of international agreement on the best timing of oral follow‐up after HSCT, it is mandatory to establish a close multidisciplinary evaluation in order to prevent the onset of HSCT-related OSCC and to reduce post‐transplant mortality due to secondary tumors

Eculizumab treatment: stochastic occurrence of C3 binding to individual PNH erythrocytes

C5 blockade by eculizumab prevents complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH). However, C3-bound PNH red blood cells (RBCs), arising in almost all treated patients, may undergo extravascular hemolysis reducing clinical benefits. Despite the uniform deficiency of CD55 and of CD59, there are always two distinct populations of PNH RBCs, with (C3+) and without (C3-) C3 binding

Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae

Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3\u27 overhang inhibits 5\u27-\u3e 3\u27 resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo

Highlights from CHIMERA Collaboration

The activities performed by the CHIMERA Collaboration since the 2018 IWM-EC workshop are outlined in this paper. Experiments performed in thelast three years and results obtained through dedicated analyses of experimentaldata already acquired are summarized. A brief report on the activities conductedat GSI is also include

Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia

One of the major obstacles of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) comes from the often months-long unpredictability of bone-marrow (BM) recovery. In this prospective study in children with newly diagnosed very severe AA (n=10), who were enrolled in the therapy study SAA-BFM 94, we found a dramatically reduced diversity of both CD4+ and CD8+ BM cells, as scored by comprehensive V-beta chain T-cell receptor (TCR) analysis. Strongly skewed TCR V-beta pattern was highly predictive for good or at least partial treatment response (n=6, CD8+ complexity scoring median 35.5, range 24–73). In contrast, IST in patients with rather moderate reduction of TCR V-beta diversity (n=4, CD8+ complexity scoring median 109.5, range 82–124) always failed (P=0.0095). If confirmed in a larger series of patients, TCR V-beta repertoire in BM may help to assign children with SAA up-front either to IST or to allogeneic stem-cell transplantation

Recent results on the construction of a new correlator for neutrons and charged particles and for FARCOS

With the advent of new facilities for radioactive ion beams it is necessary to develop neutron detection systems integrated with charged-particle ones. The integration of the neutron signal, especially in the case of neutron-rich beams, becomes a mandatory requirement in order to study the property of the nuclear matter in extreme conditions. For this reason, new detectors using new materials have to be built. NArCoS (Neutron ARray for COrrelation Studies) is a project aimed at the design of a new detector based on stack of plastic scintillators, featuring both good energy and angular resolution sensitive both to neutrons and charged particles within the same detection cell. We present in this work new results on the Pulse Shape Discrimination (PSD) capabilities of two very compact detection systems: the 3 x 3 x 3 cm(3) EJ 276+SiPM and the 3 x 3 x 3 cm(3) EJ 276G +SiPM (the latter green shifted version). In addition, we compare new results about the energy calibration and resolution of the FARCOS correlator in the CHIFAR experiment performed at LNS

Multicenter Experience Using Total Lymphoid Irradiation and Antithymocyte Globulin as Conditioning for Allografting in Hematological Malignancies

A non myeloablative conditioning with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) was shown to protect against graft-versus-host disease (GVHD). To evaluate the effects of TLI-ATG in a multicenter study, 45 heavily pretreated patients, median age 51, with lymphoid (n = 38) and myeloid (n = 7) malignancies were enrolled at 9 centers. Twenty-eight patients (62%) received at least 3 lines of treatment before allografting, and 13 (29%) had refractory/relapsed disease at the time of transplantation. Peripheral blood hematopoietic cells were from HLA identical sibling (n = 30), HLA-matched (n = 9), or 1 antigen HLA-mismatched (n = 6) unrelated donors. A cumulative TLI dose of 8 Gy was administered from day -11 through -1 with ATG at the dose of 1.5 mg/kg/day (from day -11 through -7). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Donor engraftment was reached in 95% of patients. Grade II to IV acute GVHD (aGVHD) developed in 6 patients (13.3%), and in 2 of these patients, it developed beyond day 100. Incidence of chronic GVHD (cGVHD) was 35.8%. One-year nonrelapse mortality was 9.1%. After a median follow-up of 28 months (range, 3-57 months) from transplantation, median overall survival was not reached, whereas median event-free survival was 20 months. This multicenter experience confirms that TLI-ATG protects against GVHD and maintains graft-vs-tumor effects

Population and decay of C-12 states

By using the CHIMERA detector, we have measured the gamma-ray and alpha decay width of excited C-12 states important for the carbon production inastrophysical environments. For the first time, we directly observed the gamma-ray decayof the 9.64 MeV level. A gamma-ray decay width larger than previous observations wasobserved for the Hoyle state. In order to explain this enhanced yield we investigatedon the recently proposed population of an Efimov state at 7.458 MeV. The decaycharacteristics of such level are inferred

NArCoS: The new hodoscope for neutrons and charged particles

Proper detection of neutrons and charged particles is motivated by the recent efforts to construct new facilities for radioactive ion beams (RIBs) worldwide. Detection of neutrons is an important opportunity to improve our understanding of nuclear spectroscopy and reaction dynamics, with the possibility of constraining theoretical models of the nuclear equation of state (NEoS) and investigating in-medium nuclear interactions. This topic also has important implications in the study of astrophysical objects, such as neutron stars. In this work, the state-of-the-art of Neutron Array for Correlation Studies (NArCoS), a new hodoscope for neutron and charged particles under construction in Catania (INFN), is briefly reviewed