Background: Indolent non follicular B-Cell Lymphomas (INFL) are a heterogeneous group of lymphomas and include small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphomas (LPL) and marginal zone ...lymphomas of splenic (SMZL), nodal (NMZL) and extranodal (ENMZL) subtypes. In 2010 the NF10 study was started by the Fondazione Italiana Linfomi as a prospective registry specifically devised for investigating the prognosis of this group of lymphomas. We provide a preliminary report describing registered cases with an emphasis on initial therapy.
Methods: The registration of consecutive adult patients with newly diagnosed INFL and no exclusion criteria is ongoing at a dedicated website via secure HTTP protocols. For the purposes of the study in addition to the conventional INFL subtype, the category of disseminated MZL and CD5- low grade lymphoma were also considered. So far the study has been activated in 65 centers in Europe and South America.
Results: Between July 2010 and July 2015, 665 cases have been registered. The current report is based on 395 cases that have been validated. Forty-seven (12%) cases were registered as SLL, 76 (19%) as LPL, 59 (15%) as CD5-low grade and 213 (54%) as MZL, including 73 (18%) SMZL, 18 (5%) NMZL, 81 (21%) ENMZL or 41 (10%) disseminated subtypes.
Median age was 67 years (range 29-94), 53% of patients were males; Ann Arbor stage was III-IV in 79%; 14% had B symptoms, 7% had ECOG performance status > 1, lactate dehydrogenase and b2-microglobulin were elevated in 70% and 54% of cases, respectively. Six percent of cases were HCV positive (HCV+ rate was 7.5% among MZL cases). Regarding HBV infection, 21% of patients were HBcAb-positive and 3% of patients were HBsAg-positive.
Immediate systemic therapy was planned in 50% of patients. SMZL, SLL and CD5-low grade were the subtypes with the lower rates of immediate therapy (44%, 46% and 24% respectively) whereas ENMZL were addressed to systemic therapy in 67% of cases. When systemic therapy was prescribed rituximab (R) was used in 88%. In 81% of patients R was combined to cytotoxic therapy including alkylating agents in 40%, CHOP-like in 18%, bendamustine in 17% and fludarabine in 6%.
ENMZL and CD5-low grade had the highest rates of R-alkylating use (61% and 64%); SMZL and MZL were frequently treated with R-CHOP like regimens (35% and 40%).
Young age at diagnosis (less than 60 years) and increased b2-microglobulin were more frequently associated with patients requiring immediate systemic therapy. With 22 months of median follow up, 2-year progression free survival and overall survival (OS) were 88% (95CI: 83-92) and 95% (95CI: 91-97) respectively; the initial choice of deferring immediate therapy did not impact on OS.
Conclusions: We provide a complete report on the initial approach to patients with INFL showing that immediate therapy is required in half of the cases with a heterogeneous approach among INFL subtypes. The majority of patients requiring therapy was treated with the combination of R and alkylating agents. The NF10 study confirms that a web-based world-wide cooperation allows the collection of a relevant and complete data set, providing a platform for future prognostic and pathobiological studies in order to identify novel and more efficient therapeutic targets.
Luminari:Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Ferrero:Mundipharma: Other: Speakers Honoraria; Celgene: Other: Speakers Honoraria. Gaidano:Celgene: Research Funding; Morphosys, Roche, Novartis, GlaxoSmith Kline, Amgen, Janssen, Karyopharm: Honoraria, Other: Advisory boards.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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The discovery of the NPM mutation in acute myeloid leukemia (AML) allowed to identify a distinct entity with intermediate-good prognosis particularly when the FLT3/ITD mutation is absent. The most ...appropriate consolidation treatment of these patients upon the achievement of the first complete remission has not been established yet and the role of allogeneic stem cell transplantation (SCT) is still debated.
to assess long-term outcome of adult patients with NPM positive acute myeloid leukemia according to type and intensity of consolidation therapy.
Between May 2000 and February 2012, 1155 patients were enrolled into two consecutive, prospective Northern Italy Leukemia Group (NILG) trials (00/01 and 02/06). Six-hundred sixty nine were studied for NPM mutation and 218 (33%) proved positive (by immunohistochemistry or by molecular analysis) (Falini et al, Haematologica. 2007 Apr;92(4):519-32). Median age of NPM+ patients was 50 years (range 16-72) and 134 (61%) were female. Median WBC was 33.3 x 10^9/L (range 0.9-313.9), 71 (33%) had myelomonocytic leukemia (FAB M4), and 211 (96%) had de novo AML. According to the European Leukemia Net (ELN) classification, cytogenetic risk groups were: normal 178 (82%), intermediate 26 (12%), unfavorable 2 (1%) and unknown 12 (5%). Eighty-two (38%) patients had a concurrent FLT3/ITD mutation and 31 (14%) a FLT3/TKD mutation. According to cytogenetics and additional risk factors (late response, WBC count >50x10^9/L, FAB class M0/6/7, hepato/splenomegaly, MDS-related/secondary AML, FLT3/ITD mutation), patients were stratified in standard (SR) and high (HR) risk groups.
In both studies the remission induction was based on combination of cytarabine with idarubicin. Post-remission therapy was allogeneic SCT in HR while high-dose cytarabine or busulfan/cyclophosphamide with autologous SCT was given to SR patients. The molecular evaluation of minimal residual disease (MRD) was planned after induction, before the post-remission consolidation and the follow-up.
Complete remission (CR) was achieved in 196/218 (90%) NPM+ patients. One hundred sixty-eight out of 196 remitters (86%) received post-remission consolidation therapy: allogeneic SCT 72 (37%), high dose Ara-C 74 (38%), autologous SCT 14 (7%), other therapy 8 (4%); 28 patients did not receive consolidation due to early relapse (n=24), CR death (n=3), and loss to follow-up (n=1). With a median follow-up of 1.8 years (range 0.008-12.66), 99 CR patients (50.5%) were alive in 1st CR, 13 (6.5%) died of complications, and 84 (43%) had recurrent AML. In a cumulative analysis, 5-year overall and disease-free survival were 46% (OS) and 43% (DFS), respectively. In univariate analysis FLT3/ITD mutation (n=82) affected negatively 5-year OS (29% vs. 49%, P < .0001) and DFS (27% vs. 46%, P < .0001), whereas FLT3/TDK mutation did not. In patients with FLT3/ITD mutation able to receive consolidation therapy (n=49), the application of allogeneic SCT improved DFS significantly (55% vs. 18%, P = .03) and reduced the cumulative incidence of relapse (CIR) (39% vs. 81%, P = .026). In patients with NPM+ and FLT3/ITD- AML, the risk of relapse after high dose cytarabine or autologous SCT (n=68) was more than doubled compared to that observed after allogeneic SCT (n=42) (50% vs. 23%, P= .08) (Figure). However, DFS (48% vs. 69.5%, p= .17), and OS (60% vs. 72%, p= .80) were not significantly different since allogeneic SCT was associated with higher treatment related mortality, albeit effective in the salvage of some relapsed patients. In multivariate analysis, FLT3/ITD mutation was the most powerful factor that unfavorably affected OS, DFS and CIR, while age > 55 years negatively affected OS and DFS. No other clinical factor was predictive for relapse in FLT3- patients. The relationship between MRD and clinical outcome is currently being studied and will be presented.
Our data indicate that allogeneic SCT is the most active post-remission treatment for NPM+ AML, but its benefit over chemotherapy may be limited in patients without FLT3/ITD. For this reason the evaluation of MRD could help identify the patients for whom an allogeneic SCT should be preferable.
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No relevant conflicts of interest to declare.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In a energy scenario moving fast towards the deployment of renewable energy technologies and the need of reducing CO2 emissions, hybrid energy systems for rural electrification are a feasible ...alternative solution to the utilization of conventional Diesel generators. The project focuses on the design and optimization of an off-grid hybrid energy system for a village of around 250 inhabitants in Gujarat, India. The energy system is part of a bigger project, “G.I.V.E. Center of Excellence”, which has an innovative concept on a more sustainable rural lifestyle. The system, which has to depend mainly on locally available resources, intends to serve three main services: electrical demand, water purification and thermal energy for cooking. Two system configurations were designed and optimized to supply the estimated demand. The main outcome is a techno-economic analysis of the different system performances, which leads to a conclusion: dealing with the services individually has lower costs of implementation, less than half if compared to the implementation of a conventional Diesel generator. Furthermore, CO2 emissions are drastically reduced. A sensitivity analysis was performed to address the different uncertainties such as the cost of the fuel. The result shows that if enough biomass resource would be available, a system based only on renewable energy technologies is economically profitable.
G.I.V.E. Scandinavia
Objectives
Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the ...major neurological complications in a large cohort of COVID-19 patients.
Methods
Retrospective, observational analysis on all COVID-19 patients admitted from February 23rd to April 30th, 2020 to ASST Papa Giovanni XXIII, Bergamo, Italy for whom a neurological consultation/neurophysiological assessment/neuroradiologic investigation was requested. Each identified neurologic complication was then classified into main neurologic categories.
Results
Of 1760 COVID-19 patients, 137 presented neurologic manifestations that manifested after COVID-19 symptoms in 98 pts and was the presenting symptom in 39. Neurological manifestations were classified as: (a) cerebrovascular disease 53 pts (38.7%) including 37 ischemic and 11 haemorrhagic strokes, 4 transient ischemic attacks, 1 cerebral venous thrombosis; (b) peripheral nervous system diseases 31 (22.6%) including 17 Guillain–Barrè syndromes; (c) altered mental status 49 (35.8%) including one necrotizing encephalitis and 2 cases with RT-PCR detection of SARS-Cov-2 RNA in CSF; (d) miscellaneous disorders, among whom 2 patients with myelopathy associated with Ab anti-SARS-CoV-2 in CSF. Patients with peripheral nervous system involvement had more frequently severe ARDS compared to patients with cerebrovascular disease (87.1% vs 42%; difference = 45.1% 95% CI 42.0–48.2;
χ
2
= 14.306;
p
< 0.0002) and with altered mental status (87.1% vs 55.6%; difference = 31.5% 95% CI 27.5–37.5%;
χ
2
= 7.055;
p
< 0.01).
Conclusion
This study confirms that involvement of nervous system is common in SARS-CoV-2 infection and offers clinicians useful information for prevention and prompt identification in order to set the adequate therapeutic strategies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications, we compared glomerular filtration rate ...(GFR; primary outcome), cardiovascular events, retinopathy, and neuropathy in 380 hypertensive type 2 diabetics with albuminuria <200 mg/min included in a multicenter, double-blind, placebo-controlled trial (DEMAND Delapril and Manidipine for Nephroprotection in Diabetes) and randomized to 3-year treatment with manidipine/delapril combination (10/30 mg/d; n=126), delapril (30 mg/d; n=127), or placebo (n=127). GFR was centrally measured by iohexol plasma clearance. Median monthly GFR decline (interquartile range IQR) was 0.32 mL/min per 1.73 m (IQR0.16–0.50 mL/min per 1.73 m) on combined therapy, 0.36 mL/min per 1.73 m (IQR0.18–0.53 mL/min per 1.73 m) on delapril, and 0.30 mL/min per 1.73 m (IQR0.12–0.50 mL/min per 1.73 m) on placebo (P=0.87 and P=0.53 versus combined therapy or delapril, respectively). Similar findings were observed when baseline GFR values were not considered for slope analyses. Albuminuria was stable in the 3 treatment groups. The hazard ratio (95% CI) for major cardiovascular events between combined therapy and placebo was 0.17 (0.04–0.78; P=0.023). Among 192 subjects without retinopathy at inclusion, the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 (0.07–0.99; P=0.048). Among 200 subjects with centralized neurological evaluation, the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 (0.24–0.87; P=0.017) and 0.52 (0.27–0.99; P=0.048), respectively. Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo (P=0.03) but did not change on combined or delapril therapy. Treatment was well tolerated. In hypertensive type 2 diabetic patients, combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease, retinopathy, and neuropathy and stabilized insulin sensitivity.
Objective
To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the first pandemic wave, ...Lombardia.
Methods
Adult patients admitted to 20 Neurological Units between 1/3–30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO).
Results
Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for
SARS-CoV-2
was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia.
Conclusions
We detected an increased incidence of GBS in COVID-19 patients which can reflect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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