The classic prognostic factors in advanced Hodgkin\u2019s lymphoma patients are losing their meaning at the time of Pet-guided treatments

The International Prognostic Score (IPS) is the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma (HL). It incorporates seven clinical parameters independently associated with a poorer outcome: male sex, age, stage IV, hemoglobin level, white blood cell and lymphocyte counts, and albumin level. Since the development of the IPS, there have been significant advances in therapy and supportive care. Recent studies suggest that the IPS is less discriminating due to improved outcomes with ABVD therapy. The aim of the present study was to asses if classic prognostic factors maintain their prognostic meaning at the time of response-adapted treatment based on interim PET scans. We evaluated the prognostic significance of IPS in the 520 advanced stage HL patients enrolled in the PET-guided, HD0801 trial in which PET2-positive patients underwent a more intense treatment with an early stem-cell transplantation after 2 cycles of ABVD. We observed that in these patients, the IPS completely loses its prognostic value together with all the single parameters that contribute to the IPS. Furthermore, neutrophils, monocytes, lymphocytes, and the ratio among them also no longer had any predictive value. We believe that the substantial improvement in survival outcomes in PET2-positive patients treated with early autologous transplantation could explain the complete disappearance of the residual prognostic significance of the IPS

Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy:a population-based study in six European regions

ObjectiveTo explore the prescribing patterns of selective serotonin reuptake inhibitors (SSRIs) before, during and after pregnancy in six European population-based databases.DesignDescriptive drug utilisation study.SettingSix electronic healthcare databases in Denmark, the Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK.PopulationAll women with a pregnancy ending in a live or stillbirth starting and ending between 2004 and 2010.MethodsA common protocol was implemented across databases to identify SSRI prescriptions issued (UK) or dispensed (non-UK) in the year before, during or in the year following pregnancy.Main outcome measuresThe percentage of deliveries in which the woman received an SSRI prescription in the year before, during or in the year following pregnancy. We also compared the choice of SSRIs and changes in prescribing over the study period.ResultsIn total, 721 632 women and 862943 deliveries were identified. In the year preceding pregnancy, the prevalence of SSRI prescribing was highest in Wales [9.6%; 95% confidence interval (CI95), 9.4-9.8%] and lowest in Emilia Romagna (3.3%; CI95, 3.2-3.4%). During pregnancy, SSRI prescribing had dropped to between 1.2% (CI95, 1.1-1.3%) in Emilia Romagna and 4.5% (CI95, 4.3-4.6%) in Wales. The higher UK pre-pregnancy prescribing rates resulted in higher first trimester exposures. After pregnancy, SSRI prescribing increased most rapidly in the UK. Paroxetine was more commonly prescribed in the Netherlands and Italian regions than in Denmark and the UK.ConclusionsThe higher SSRI prescribing rates in the UK, compared with other European regions, raise questions about differences in the prevalence and severity of depression and its management in pregnancy across Europe.</p

Performance Of A Liquid Argon Time Projection Chamber Exposed To The WANF Neutrino Beam

We present the results of the first exposure of a Liquid Argon TPC to a multi-GeV neutrino beam. The data have been collected with a 50 liters ICARUS-like chamber located between the CHORUS and NOMAD experiments at the CERN West Area Neutrino Facility (WANF). We discuss both the instrumental performance of the detector and its capability to identify and reconstruct low multiplicity neutrino interactions.Comment: 14 pages, 12 figures. Submitted for publication to Physical Review

Caspase-2-mediated cell death is required for deleting aneuploid cells

Caspase-2, one of the most evolutionarily conserved of the caspase family, has been implicated in maintenance of chromosomal stability and tumour suppression. Caspase-2 deficient (Casp2-/-) mice develop normally but show premature ageing-related traits and when challenged by certain stressors, succumb to enhanced tumour development and aneuploidy. To test how caspase-2 protects against chromosomal instability, we utilized an ex vivo system for aneuploidy where primary splenocytes from Casp2-/- mice were exposed to anti-mitotic drugs and followed up by live cell imaging. Our data show that caspase-2 is required for deleting mitotically aberrant cells. Acute silencing of caspase-2 in cultured human cells recapitulated these results. We further generated Casp2C320S mutant mice to demonstrate that caspase-2 catalytic activity is essential for its function in limiting aneuploidy. Our results provide direct evidence that the apoptotic activity of caspase-2 is necessary for deleting cells with mitotic aberrations to limit aneuploidy.S Dawar, Y Lim, J Puccini, M White, P Thomas, L Bouchier-Hayes, D R Green, L Dorstyn and S Kuma

Diffuse large B-cell lymphoma in octogenarians aged 85 and older can benefit from treatment with curative intent: a report on 129 patients prospectively registered in the Elderly Project of the Fondazione Italiana Linfomi (FIL)

Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged &gt;85 (late octogenarians [LO]) were underrepresented, and selection criteria were poorly defined. We analyzed the clinical characteristics and outcomes of LO enrolled in the FIL Elderly Project in terms of the treatment received (palliative vs. curative) and of their simplified geriatric assessment (sGA), then compared them with early octogenarians (EO) aged 80-84 and with those aged 65-79 classified as UNFIT or FRAIL according to sGA enrolled in the same study. Of the 1,163 patients, 370 were &gt;80 and 129 LO. Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs. 23%; P=0.001) and had worse 2-year overall survival (OS) (48% vs. 63%; P=0.001) and 2-year progression-free survival (PFS) (43% vs. 56%; P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P&lt;0.001), without any difference between full or reduced doses. Rituximab within palliation improved outcome (2-yr OS with or without rituximab 42% vs. 22%; P=0.008). Elderly Prognostic Index (EPI) performed better than sGA in identifying different risk categories, and high-risk EPI retained an independent unfavorable effect on OS and PFS, together with treatment without anthracycline. In conclusion, late octogenarians can benefit from a curative approach with reduced-dose anthracycline and from rituximab within palliation. EPI may help in patient selection more than sGA can

Real-world Outcomes of Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated With Polatuzumab Vedotin-based Therapy.

After FDA and EMA approval of the regimen containing polatuzumab vedotin plus rituximab and bendamustine (PolaBR), eligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients in Italy were granted early access through a Named Patient Program. A multicentric observational retrospective study was conducted focusing on the effectiveness and safety of PolaBR in everyday clinical practice. Fifty-five patients were enrolled. There were 26 females (47.3%), 32 patients were primary refractory and 45 (81.8%) resulted refractory to their last therapy. The decision to add or not bendamustine was at physician's discretion. Thirty-six patients underwent PolaBR, and 19 PolaR. The 2 groups did not differ in most of baseline characteristics. The final overall response rate was 32.7% (18.2% complete response rate), with a best response rate of 49.1%. Median disease-free survival was reached at 12 months, median progression-free survival at 4.9 months and median overall survival at 9 months, respectively. Overall, 88 adverse events (AEs) were registered during treatment in 31 patients, 22 of grade ≥3. Eight cases of neuropathy occurred, all of grades 1-2 and all related to polatuzumab. The two groups of treatment did not differ for effectiveness endpoints but presented statistically significant difference in AEs occurrence, especially in hematological AEs, in AEs of grade equal or greater than 3 and in incidence of neuropathy. Our data add useful information on the effectiveness of Pola(B)R in the setting of heavily pretreated DLBCL and may also suggest a better tolerability in absence of bendamustine without compromise of efficacy

Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study

Abstract Introduction Research on associations between medication use during pregnancy and congenital anomalies is significative for assessing the safe use of a medicine in pregnancy. Congenital anomaly (CA) registries do not have optimal information on medicine exposure, in contrast to prescription databases. Linkage of prescription databases to the CA registries is a potentially effective method of obtaining accurate information on medicine use in pregnancies and the risk of congenital anomalies. Methods We linked data from primary care and prescription databases to five European Surveillance of Congenital Anomalies (EUROCAT) CA registries. The linkage was evaluated by looking at linkage rate, characteristics of linked and non-linked cases, first trimester exposure rates for six groups of medicines according to the prescription data and information on medication use registered in the CA databases, and agreement of exposure. Results Of the 52,619 cases registered in the CA databases, 26,552 could be linked. The linkage rate varied between registries over time and by type of birth. The first trimester exposure rates and the agreements between the databases varied for the different medicine groups. Information on anti-epileptic drugs and insulins and analogue medicine use recorded by CA registries was of good quality. For selective serotonin reuptake inhibitors, antiasthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants, the recorded information was less complete. A presentation was given at the 54th Annual Meeting of the Teratology Society in Washington, USA, 28 June-2 July 2014. Key Points Linkage of primary care or prescription databases to congenital anomaly (CA) registries improved the quality of information on maternal use of medicines in pregnancy. The quality of information improved particularly for medicine groups that are less fully registered in CA registries, such as selective serotonin reuptake inhibitors, anti-asthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants

THE ELDERLY PROGNOSTIC INDEX (EPI) PREDICTS EARLY MORTALITY IN OLDER PATIENTS WITH DLBCL. A SUBSTUDY OF THE ELDERLY PROJECT BY THE FONDAZIONE ITALIANA LINFOMI (FIL)

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