In BCR-ABL1 Positive B-Cell Acute Lymphoblastic Leukemia, Steroid Therapy Induces Hypofibrinogenemia

Hypofibrinogenemia (HF) in adult acute lymphoblastic leukemia (ALL) of B lineage is uncommon and mostly associated with asparaginase (ASP) delivery. Since we noticed a significant reduction in fibrinogen (FBG) plasma levels even before the first ASP dose, we aim to assess the levels of FBG during induction treatment and explore if the FBG fall correlated with therapies other than asparaginase and/or specific leukemia biological features. We retrospectively analyzed FBG levels in 115 patients with B-ALL. In 74 (64%) out of 115 patients FBG decline occurred during the steroid prephase. In univariate analysis, such a steroid-related HF was significantly associated with BCR-ABL1 rearrangement (p = 0.00158). None of those experiencing HF had significant modifications of liver function tests during induction treatment. Our retrospective study suggests that in B-ALL, steroid therapy can also induce HF and that such an event is preferentially observed in patients carrying BCR-ABL1 rearrangements. The pathogenesis of this phenomenon is still unclear. We attempt to explain it by applying the International Society of Thrombosis and Hemostasis-Disseminated Intravascular Coagulation score (ISTH-DIC score); nonetheless additional studies are needed to clarify further the mechanisms of HF in this subset of patients

Moral Decision-Making, Stress, and Social Cognition in Frontline Workers vs. Population Groups During the COVID-19 Pandemic: An Explorative Study

On March 9, 2020, Italy has gone into “lockdown” because of COVID-19 pandemic, with a national quarantine. All non-essential working activities and schools of all levels have been temporarily closed: consequently, the entire population have been forced to dramatically change their daily habits. The pandemic raised important psychological, moral, social, and economic issues. Our research focused on the moral decision-making of people during an emergency. This paper reports two studies. The aim of Study 1 was to evaluate moral decision-making, level of perceived stress, ability of mentalizing and empathy in university students and Italian workers. 224 front-line workers (FLW), 413 second-line workers (SLW), and 663 university students (US), during Italian Phase 1 of lockdown, completed an online questionnaire. The results of Study 1 showed that participants in the FLW group are more likely to choose utilitarian solutions and judge as morally acceptable actions finalized to saving lives of more people if this requires sacrificing a low number of individuals. At the same time, decision-making was experienced as less unpleasant and less arousing with respect to the other two groups, demonstrating a greater ability to keep emotional control under pressure. In Study 2, we compared the same variables used in Study 1, selecting two professional categories from the FLW group engaged in emergency during COVID-19, namely healthcare providers (n = 82) and public safety personnel (n = 117). Our results showed that healthcare providers were more stressed and emotionally involved than public safety personnel, with higher empathic concern and arousal in moral decision-making. We suggest it is essential providing immediate psychological support and monitoring physical and emotional well-being for workers in the front-line during emergencies like the COVID-19 pandemic, in order to prevent experiences of moral distress or mental health problems

Clinical features of prognostic significance in myelodysplastic patients with normal karyotype at high risk of transformation

The International Prognostic Scoring System (IPSS) for myelodysplastic syndromes (MDS) has defined patients with a normal karyotype as a good risk cytogenetic subgroup, but nevertheless a fraction of these patients has a poor outcome similar to that of high risk patients. We retrospectively analysed our series of myelodysplastic patients with normal karyotype observed in a period of 11 years, with the aim of identifying clinical features of possible prognostic significance within this subgroup of patients. Multivariate analysis showed that among clinical scoring systems, the Bournemouth score appears the best prognostic indicator for risk of leukemic transformation, and platelet count <100 × 10 9/l -1, presence of haemorrhagic symptoms at time of diagnosis and morphologic FAB classification are the main prognostic factors for prediction of survival. In the absence of genetic abnormalities as detected by conventional cytogenetics or even the more sensitive molecular techniques in MDS, clinical variables could be of help in identifying patients with different prognosis, suitable for risk adapted therapeutic strategies. © 2004 Elsevier Ltd. All rights reserved

Rituximab as Single Agent in Primary MALT Lymphoma of the Ocular Adnexa

Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic immunotherapy with anti-CD20 monoclonal antibody has been investigated as first-line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas is still unknown. The present study evaluated retrospectively the outcome of seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom six were treated with single agent Rituximab. All patients received 6 cycles of Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was 100%; four patients (67%) achieved a Complete Remission, and two (33%) achieved a partial response. In four patients an additional Rituximab maintenance every 2-3 months was given for two years. After a median follow-up of 29 months (range 8–34), no recurrences were observed, without of therapy- or disease-related severe adverse events. None of the patients needed additional radiotherapy or other treatments. Rituximab as a single agent is highly effective and tolerable in first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore, durable responses are achievable with the same-agent maintenance. Rituximab can be considered the agent of choice in the management of an indolent disease in whom the “quality of life” matter is of primary importance

Refining of vegetable oils and fats; formation pathway and mitigation of 3-MCPDe and Glycidyl esters

Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation

LIN28B increases neural crest cell migration and leads to transformation of trunk sympathoadrenal precursors

The RNA-binding protein LIN28B regulates developmental timing and determines stem cell identity by suppressing the let-7 family of microRNAs. Postembryonic reactivation of LIN28B impairs cell commitment to differentiation, prompting their transformation. In this study, we assessed the extent to which ectopic lin28b expression modulates the physiological behavior of neural crest cells (NCC) and governs their transformation in the trunk region of developing embryos. We provide evidence that the overexpression of lin28b inhibits sympathoadrenal cell differentiation and accelerates NCC migration in two vertebrate models, Xenopus leavis and Danio rerio. Our results highlight the relevance of ITGA5 and ITGA6 in the LIN28B-dependent regulation of the invasive motility of tumor cells. The results also establish that LIN28B overexpression supports neuroblastoma onset and the metastatic potential of malignant cells through let-7a-dependent and let-7a-independent mechanisms

Elderly patients with Ph+ chronic myelogenous leukemia (CML): Results of imatinib mesylate treatment

Thirty-five patients with Ph+ CML aged more than 60 years were treated with imatinib. Twenty-four patients (group A) were in late chronic phase (CP) and eleven patients (group B) were in accelerated/blastic phase (AP/BP). In group A, complete haematological response (CHR) was achieved by all patients; seventeen patients (70.8%) attained a complete cytogenetic response (CCR), one (4.1%) attained a partial CR, one (4.1%) a minor CR (Ph+ 70%) and five (21%) were resistant (Ph+ 100%), toxicity was mild: seven patients had a transient cytopenia, three a skin reaction, one a moderate oedema and one muscular pain. After a median follow-up of 15 months, 1 patient died in progression and 23 patients are alive (2 in BP and 21 in persisting response). In group B, one patient died after 3 months in aplastic phase from sepsis, three patients were resistant and seven patients (63.7%) achieved CHR; of these, four obtained CCR. After a median follow-up of 17 months, 4 patients have died from progressive disease, 6 are alive; 1 in AP and 5 in CHR (4 of them being in CCR). Present data indicate that imatinib is safe also in elderly with clinical results as good as in younger patients. © 2004 Elsevier Ltd. All rights reserved