Publications by authors named "Luigi Marcheselli"

102 Publications

The Prognostic and Predictive Role of Somatic Mutations in Ovarian Cancer: Results from a Multicenter Cohort Study.

Diagnostics (Basel) 2021 Mar 21;11(3). Epub 2021 Mar 21.

Department of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41124 Modena, Italy.

Previous research involving epithelial ovarian cancer patients showed that, compared to germline (gBRCA) mutations, somatic (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs. Among the 158 patients included in the study, 17.09% of patients carried a pathogenic or likely pathogenic gBRCA variant and 15.19% of patients presented pathogenetic or likely pathogenic sBRCA variants and/or CNVs. Overall, 81.6% of the patients included in this study were diagnosed with a serous histotype, and 77.2% were in advanced stages. Among women diagnosed in advanced stages, gBRCA patients showed better progression-free survival and OS as compared to sBRCA and wild-type patients, whereas sBRCA patients did not show any advantage in outcome as compared to wild-type patients. In this study, the introduction of CNV analyses increased the detection rate of sBRCA mutations, and the resulting classification among gBRCA, sBRCA and wild-type patients was able to properly stratify the prognosis of OC patients. Particularly, sBRCA mutation patients failed to show any outcome advantage as compared to wild-type patients.
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http://dx.doi.org/10.3390/diagnostics11030565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003908PMC
March 2021

mutation rate and characteristics of prostate tumor in breast and ovarian cancer families: analysis of 6,591 Italian pedigrees.

Cancer Biol Med 2021 Mar 12. Epub 2021 Mar 12.

Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena 41124, Italy.

Objective: As prostate cancer (PrC) shows a mutation rate as high as 30%, it becomes crucial to find the optimal selection criteria for genetic testing. The primary objective of this study was to evaluate the mutation rate in families with PrC associated with breast and/or ovarian cancers; secondary aims were to compare the characteristics of families and BRCA-related PrC outcome among and carriers.

Methods: Following the Modena criteria for the test, we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score ≥7 PrCs, by testing breast or ovarian cases and inferring the mutation in the prostate cases. The characteristics of families and BRCA-related PrC outcomes were measured using the chi-square (χ) test and Kaplan-Meier methods, respectively.

Results: Among 6,591 families, 580 (8.8%) with a Gleason score ≥ 7 PrCs were identified, of which 332 (57.2%) met the Modena selection criteria for BRCA testing. Overall, 215 breast or ovarian cancer probands (64.8%) were tested, of which 41 resulted positive for and one for genes (19.5%). No statistically significant differences were found in BRCA-related PrC prognosis and in the characteristics of families among BRCA1, BRCA2 and non-tested patients. Ten of 23 (44%) mutations in the gene fell in the prostate cancer cluster region (PCCR) at the 3´ terminal of the 7914 codon.

Conclusions: It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and PrC. A trend toward a worse prognosis has been found in carriers.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0481DOI Listing
March 2021

Simplified Geriatric Assessment in Older Patients With Diffuse Large B-Cell Lymphoma: The Prospective Elderly Project of the Fondazione Italiana Linfomi.

J Clin Oncol 2021 Apr 12;39(11):1214-1222. Epub 2021 Feb 12.

Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy.

Purpose: To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL).

Methods: We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050).

Results: We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases.

Conclusion: The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.
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http://dx.doi.org/10.1200/JCO.20.02465DOI Listing
April 2021

All-oral metronomic DEVEC schedule in elderly patients with peripheral T cell lymphoma.

Cancer Chemother Pharmacol 2020 Dec 18;86(6):841-846. Epub 2020 Oct 18.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Purpose: Peripheral T cell lymphomas (PTCLs) have an overall poor prognosis. Indeed, registry data in elderly patients show that the median progression-free survival (mPFS) following first- and second-line therapies are only 6.7 and 3.1 months, respectively. The aim of the study is to show the activity of metronomic chemotherapy, a regular administration of low chemotherapeutic drug doses allowing a favourable toxicity profile, on elderly PTCL patients.

Methods: We report a series of 17 PTCL patients, treated with the all-oral metronomic schedule DEVEC (prednisolone-etoposide-vinorelbine-cyclophosphamide) in four Italian centres. Patients 5/17 (29.4%) were treatment-naïve (naïve) and 12/17 (70.6%) were relapsed-refractory (RR), respectively. The median age was 83 years (range 71-87) and 71.5 years (range 56-85) for naïve and RR, respectively. In vitro activity of metronomic vinorelbine (VNR), etoposide (ETO) and their concomitant combination on HH, a PTCL cell line, was also assessed.

Results: Histology: PTCL-not-otherwise-specified = 12; angioimmunoblastic = 2; NK/T nasal type = 1; adult-type leukaemia lymphoma = 1, transformed Mycosis Fungoides = 1. The overall response rate was 80 and 58% in naïve and RR, respectively; whereas the PFS was 20 in naïve (95% CI 0-43) and 11 months (95% CI 4.2-17.8) in RR. The occurrence of relevant adverse events was 23.5%, which was managed with ETO dose reduction. In vitro experiments showed that both metronomic VNR and ETO caused a significant inhibitory activity on HH cells and a strong synergism when administered concomitantly.

Conclusion: All-oral DEVEC showed an encouraging activity and acceptable toxicity. This schedule deserves further studies in elderly PTCL also for assessing combinations with targeted drugs.
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http://dx.doi.org/10.1007/s00280-020-04172-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568761PMC
December 2020

Lifestyle Intervention on Body Weight and Physical Activity in Patients with Breast Cancer can reduce the Risk of Death in Obese Women: The EMILI Study.

Cancers (Basel) 2020 Jun 27;12(7). Epub 2020 Jun 27.

Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, 41124 Modena, Italy.

Background obesity and sedentary lifestyle have been shown to negatively affect survival in breast cancer (BC). The purpose of this study was to test the efficacy of a lifestyle intervention on body mass index (BMI) and physical activity (PA) levels among BC survivors in Modena, Italy, in order to show an outcome improvement in obese and overweight patients.

Methods: This study is a single-arm experimental design, conducted between November 2009 and May 2016 on 430 women affected by BC. Weight, BMI, and PA were assessed at baseline, at 12 months, and at the end of the study. Survival curves were estimated among normal, overweight, and obese patients.

Results: Mean BMI decreased from baseline to the end of the study was equal to 2.9% ( = 0.065) in overweight patients and 3.3% in obese patients ( = 0.048). Mean PA increase from baseline to the end of the study was equal to 125% ( < 0.001) in normal patients, 200% ( < 0.001) in overweight patients and 100% ( < 0.001) in obese patients. After 70 months of follow-up, the 5-year overall survival (OS) rate was 96%, 96%, and 93%, respectively in normal, obese, and overweight patients. Overweight patients had significantly worse OS than normal ones (HR = 3.69, 95%CI = 1.82-4.53 = 0.027) whereas no statistically significant differences were seen between obese and normal patients (HR 2.45, 95%CI = 0.68-8.78, = 0.169).

Conclusions: A lifestyle intervention can lead to clinically meaningful weight loss and increase PA in patients with BC. These results could contribute to improving the OS in obese patients compared to overweight ones.
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http://dx.doi.org/10.3390/cancers12071709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407899PMC
June 2020

Improving the international prognostic index score using peripheral blood counts: Results of a large multicenter study involving 520 patients with diffuse large B cell lymphoma.

Hematol Oncol 2020 Oct 17;38(4):439-445. Epub 2020 Jun 17.

Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy.

The main purpose of this study was to assess whether it is possible to improve the prognostic impact of international prognostic index (IPI) score by combining it with peripheral blood counts. Thus, we evaluated the prognostic power of lymphocyte, neutrophil, and monocyte counts in 520 patients with diffuse large B cell lymphoma treated with R-CHOP, confirming that these parameters have a strong impact on overall survival (OS). Using revised IPI (R-IPI), 44% of patients were categorized as poor-risk and showed an OS at 5 years of 46%. As OS at 5 years of the 520 patients is 67%, it is clearly evident that R-IPI tends to overestimate the proportion of patients with poor prognosis. Accordingly, in an attempt to improve the discriminating power of R-IPI, we evaluated and compared three different scores by combining the neutrophil lymphocyte ratio (NLR) and absolute monocyte count (AMC) with the following values: (a) IPI score 3-5, (b) age > 60 years and performance status, (c) age  ≥ 65 years and LDH > ULN. The three indexes studied, had a similar 5 years OS for the high-risk group (46%-52%), but the proportion of patients classified as poor-risk were 37%, 20%, and 32%, respectively, which are lower than 44% identified with R-IPI. Thus, while R-IPI overestimates the number of high-risk patients, after applying our models, it is possible to recognize patients who are truly at high-risk. Of the three scores, the most accurate appears to be that based on NLR, AMC, LDH > ULN and age ≥ 65 years, which identifies 32% of high-risk patients, correlating well with what is seen in clinical practice.
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http://dx.doi.org/10.1002/hon.2757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687198PMC
October 2020

BRCA Detection Rate in an Italian Cohort of Luminal Early-Onset and Triple-Negative Breast Cancer Patients without Family History: When Biology Overcomes Genealogy.

Cancers (Basel) 2020 May 15;12(5). Epub 2020 May 15.

Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, 41124 Modena, Italy.

NCCN Guidelines recommend BRCA genetic testing in individuals with a probability >5% of being a carrier. Nonetheless, the cost-effectiveness of testing individuals with no tumor family history is still debated, especially when BRCA testing is offered by the national health service. Our analysis evaluated the rate of BRCA pathogenic or likely-pathogenic variants in 159 triple-negative breast cancer (TNBC) patients diagnosed ≤60 years, and 109 luminal-like breast cancer (BC) patients diagnosed ≤35 without breast and/or ovarian family histories. In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1). Mutation prevalence was 64.2% ≤30 years, 31.8% in patients aged 31-40, 16.1% for those aged 41-50 and 7.9% in 51-60s. A total of 40% of patients with estrogen receptors (ER) 1-9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (4.6% ). Mutation prevalence was 0% between 0-25 years, 9% between 26-30 years and 6% between 31-35 years. In conclusion, BRCA testing is recommended in TNBC patients diagnosed ≤60 years, regardless of family cancer history or histotype, and by using immunohistochemical staining <10% for both ER and/PR. In luminal-like early-onset BC, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes along with BRCA genetic testing.
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http://dx.doi.org/10.3390/cancers12051252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281631PMC
May 2020

Long-term results of the MCL01 phase II trial of rituximab plus HyperCVAD alternating with high-dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma.

Br J Haematol 2021 Mar 14;192(6):1011-1014. Epub 2020 May 14.

CHIMOMO Department, University of Modena and Reggio Emilia, Modena, Italy.

Mantle cell lymphoma is a rare and incurable lymphoproliferative disorder. In the MCL01 trial, patients were treated with the R-HCVAD regimen [rituximab plus HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone; R-CVAD) alternating with high-dose methotrexate and cytarabine (AM)] for four cycles followed by autologous stem cell transplantation (ASCT) for those who reached only a partial response. After a median follow-up of 10·5 years, we reported 10-year progression-free and overall survival rates of 35% and 61% respectively, with a 10-years cumulative incidence rate of second malignancies of 10·6%. Mature results of the MCL01 trial confirmed the efficacy of HyperCVAD-AM as a frontline regimen for younger patients (≤65 years).
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http://dx.doi.org/10.1111/bjh.16714DOI Listing
March 2021

Citarinostat and Momelotinib co-target HDAC6 and JAK2/STAT3 in lymphoid malignant cell lines: a potential new therapeutic combination.

Apoptosis 2020 06;25(5-6):370-387

Unit of Oncohematology and Osteoncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Histone deacetylase (HDAC) inhibitors represent an encouraging class of antitumor drugs. HDAC inhibitors induce a series of molecular and biological responses and minimal toxicity to normal cells. Citarinostat (Acy-241) is a second generation, orally administered, HDAC6-selective inhibitor. Momelotinib (CYT387) is an orally administered inhibitor of Janus kinase/signal transducer of transcription-3 (JAK/STAT3) signaling. Momelotinib showed efficacy in patients with myelofibrosis. We hypothesized that both HDAC and JAK/STAT pathways were important in lymphoproliferative disorders, and that inhibiting JAK/STAT3 and HDAC simultaneously might enhance the efficacy of momelotinib and citarinostat without increasing toxicity. Accordingly, we tested the citarinostat + momelotinib combination in lymphoid cell lines. Citarinostat + momelotinib showed strong cytotoxicity; it significantly reduced mitochondrial membrane potential, down-regulated Bcl-2 and Bcl-xL, and activated caspases 9 and 3. Caspase-8 was upregulated in only two lymphoid cell lines, which indicated activation of the extrinsic apoptotic pathway. We identified a lymphoid cell line that was only slightly sensitive to the combination treatment. We knocked down thioredoxin expression by transfecting with small interfering RNA that targeted thioredoxin. This knockdown increased cell sensitivity to the combination-induced cell death. The combination treatment reduced Bcl-2 expression, activated caspase 3, and significantly inhibited cell viability and clonogenic survival.
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http://dx.doi.org/10.1007/s10495-020-01607-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244621PMC
June 2020

Positron-emission tomography-based staging reduces the prognostic impact of early disease progression in patients with follicular lymphoma.

Eur J Cancer 2020 02 8;126:78-90. Epub 2020 Jan 8.

Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Previous studies reported that early progression of disease (POD) after initial therapy predicted poor overall survival (OS) in patients with follicular lymphoma (FL). Here, we investigated whether pre-treatment imaging modality had an impact on prognostic significance of POD.

Methods: In this retrospective study, we identified 1088 patients with grade I-IIIA FL; of whom, 238 patients with stage II-IV disease were initially treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), and 346 patients were treated with rituximab-based chemotherapy. Patients (N = 484) from the FOLL05 study served as an independent validation cohort. We risk-stratified patients based on pre-treatment radiographic imaging (positron-emission tomography [PET] versus computed tomography [CT]) and early POD status using event-defining and landmark analyses. A competing risk analysis evaluated the association between early POD and histologic transformation.

Results: In the discovery cohort, patients with POD within 24 months (PFS24) of initiating R-CHOP therapy had a 5-year OS of 57.6% for CT-staged patients compared with 70.6% for PET-staged patients. In the validation cohort, the 5-year OS for patients with early POD was 53.9% and 100% in CT- and PET-staged patients, respectively. The risk of histologic transformation in patients whose disease progressed within one year of initiating therapy was higher in CT-staged patients than in PET-staged patients (16.7% versus 6.3%, respectively), which was associated with a 9.7-fold higher risk of death.

Conclusion: In FL, pre-treatment PET staging reduced the prognostic impact of early POD compared with CT staging. Patients with early POD and no histologic transformation have an extended OS with standard therapy.
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http://dx.doi.org/10.1016/j.ejca.2019.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331469PMC
February 2020

Influence of Thoracic Endovascular Repair on Aortic Morphology in Patients Treated for Blunt Traumatic Aortic Injuries: Long Term Outcomes in a Multicentre Study.

Eur J Vasc Endovasc Surg 2020 Mar 3;59(3):428-436. Epub 2020 Jan 3.

Department of Vascular Surgery, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia, Modena, Italy.

Objective: The aim of this study was to evaluate aortic remodelling and associated complications in patients treated by thoracic endovascular aneurysm repair (TEVAR) for blunt traumatic aortic injuries (BTAI).

Methods: This was a retrospective, observational, multicentre study. Remodelling was considered as aortic diameter variations of >2 mm and distal graft and aortic axis angle modification measured by computed tomography angiography (CTA). The predefined levels of measurement were the proximal end of the graft (D1: landing in zone [LZ] 2; D2: LZ 3); distal end (D3); and control measurement (D4) 15 mm beyond D3. Survival, procedure, graft, and/or radiation exposure related complications were registered. CTA was required within three months and at one, six, and 10 years post-operatively.

Results: Between 2004 and 2017 52 patients were treated; 47 were included for remodelling analysis (five immediate deaths were excluded); median age was 47 years (range 20-80 years). Mean TEVAR oversizing was 19.6% ± 9.7% (range 5%-35%). Following a median follow up of 67.4 ± 56.1 months (range 14-153 months) survival at one, three, six, and 10 years was 90.4% (standard error [SE] 4.1%), 88.3% (SE 4.5%) 84.8% (SE 5.5%), and 84.8% (SE 5.5%), respectively. There were no procedure/graft related complications except for one late intramural haematoma that required re-intervention. Freedom from aortic remodelling at one, six, and 10 years was 85.1% (SE 5.2%), 30.9% (SE 8.6%), and 24.7% (SE 8.8%), respectively. The increase in D1/D2 and D3 diameters were influenced by time from intervention (both p < .001), age (p < .001 and p = .002, respectively) and sealing in zone 2 (p = .027 and p = .042, respectively). For every 10% increase in oversizing, proximal neck diameter remodelling was 3.4% (p = .05). The distal axis decreased over time (p < .001; significant between three and six years).

Conclusion: TEVAR is safe for BTAI in the mid to long term. This study reports a correlation between time, oversizing, and remodelling, but the level of adverse events was low.
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http://dx.doi.org/10.1016/j.ejvs.2019.05.008DOI Listing
March 2020

Incidence and outcomes of rare T cell lymphomas from the T Cell Project: hepatosplenic, enteropathy associated and peripheral gamma delta T cell lymphomas.

Am J Hematol 2020 02 25;95(2):151-155. Epub 2019 Nov 25.

CHIMOMO Department University of Modena and Reggio Emilia, Modena, Italy.

The T Cell Project was the largest prospective trial to explore the incidence, treatment patterns, and outcomes for T cell lymphomas. The rare subtypes of T cell lymphomas, including hepatosplenic T cell lymphoma (HSTCL), enteropathy associated T cell lymphoma (EATL), and peripheral gamma delta T cell lymphomas (PGDTCLs) are poorly represented in most studies and there is little data regarding treatment patterns. We report results from 115 patients with hepatosplenic (n = 31), enteropathy associated (n = 65), and PGDTCLs (n = 19). While anthracycline regimens were most commonly used as first line therapy, response rates ranged from 20%-40% and were suboptimal for all groups. Autologous stem cell transplantation was performed as a consolidation in first remission in a small number of patients (33% of HSTCL, 7% of EATL, and 12% of PGDTCL), and four patients with HSTCL underwent allogeneic stem cell transplantation in first remission. The progression free survival at 3 years ranged from 28%-40% for these rare subtypes, and the overall survival at 3 years was most favorable for PGDTCL (70%). These data highlight the need for novel treatment approaches for rare subtypes of T cell lymphomas and for their inclusion in clinical trials.
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http://dx.doi.org/10.1002/ajh.25674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025136PMC
February 2020

Early progression as a predictor of survival in marginal zone lymphomas: an analysis from the FIL-NF10 study.

Blood 2019 09 10;134(10):798-801. Epub 2019 Jul 10.

Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Marginal zone lymphomas (MZLs) are indolent nonfollicular B-cell lymphomas (INFLs) and have heterogeneous clinical behavior. Recently, time to progression of disease at 24 months (POD24) was identified to stratify overall survival (OS) in follicular non-Hodgkin lymphoma and in INFL. Here, we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry headed by Fondazione Italiana Linfomi (FIL). POD24 was only calculated for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis. Among the 1325 patients enrolled in the NF10 study, we identified 321 patients with MZL for whom immediate therapy was planned right after lymphoma diagnosis. Overall, POD24 was confirmed in 59 patients (18%). Three-year OS for patients with POD24 was 53% with a hazard ratio of 19.5 (95% confidence interval, 8.4-45) compared with patients without POD24 (3-year OS, 95%). Association of POD24 with OS was confirmed for the subgroup of splenic and extranodal MZLs. Assessment of POD24 stratifies subsequent outcome in MZL and identifies a high-risk population. This trial was registered at www.clinicaltrials.gov as #NCT02904577.
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http://dx.doi.org/10.1182/blood.2019001088DOI Listing
September 2019

The A.L.A.N. score identifies prognostic classes in advanced biliary cancer patients receiving first-line chemotherapy.

Eur J Cancer 2019 08 2;117:84-90. Epub 2019 Jul 2.

Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK; Gastrointestinal Unit, The Royal Marsden NHS Trust, London and Surrey, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. Electronic address:

Background: Chemotherapy is the mainstay treatment for advanced biliary cancer (ABC). Best supportive care and clinical trials are currently alternative options. The identification of a prognostic score that can be widely applied to daily practice has the potential to better inform clinical management of ABC patients.

Methods: A cohort of 123 ABC patients undergoing first-line chemotherapy was used as an exploratory cohort to define the prognostic value of laboratory tests routinely performed in clinical practice. Kaplan-Meier analysis was used to investigate the association between the variables and overall survival (OS). Those variables that were statistically significant at the multivariate analysis were combined in a multiplex score. Performance of the novel prognostic score was confirmed in a validation cohort of 60 ABC patients.

Results: Baseline actual neutrophil count, lymphocytes-monocytes ratio, neutrophil-lymphocytes ratio and albumin (A.L.A.N.) correlated with OS at the multivariate analysis in the exploratory cohort. When combined in the multiplex, A.L.A.N. score was able to identify three classes of ABC patients with significantly different OS (high-risk: median OS, 5 months; intermediate-risk: median OS, 12 months and low-risk: median OS, 22 months; p:<0.001). The score performed well in the different subtypes of ABC and was independent of stage, performance status and chemotherapy regimen. The performance of the A.L.A.N. score was confirmed in a validation cohort of cholangiocarcinoma patients (high-risk: median OS, 4.3 months; intermediate-risk: median OS 9.3 months, low-risk: median OS 13 months; p:0.005).

Conclusions: The A.L.A.N score can be derived by variables routinely recorded in clinical practice and can provide prognostic assessment of ABC patients considered for first-line treatment.
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http://dx.doi.org/10.1016/j.ejca.2019.05.030DOI Listing
August 2019

The metronomic all-oral DEVEC is an effective schedule in elderly patients with diffuse large b-cell lymphoma.

Invest New Drugs 2019 06 26;37(3):548-558. Epub 2019 Apr 26.

Hematology Unit, IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy.

Metronomic-chemotherapy (M-CHT) has been rarely assessed in non-Hodgkin-lymphoma (NHL). Therefore, in 2011 we started experimenting a new all-oral M-CHT schedule termed DEVEC (Deltacortene®, etoposide, vinorelbine, cyclophosphamide, +/-Rituximab) in diffuse-large-B-cell lymphoma (DLBCL) patients. Methods Patients with stage Ib-IV were enrolled as follows: 1) treatment-naïve, frail ≥65y, or unfit ≥85y; and 2) relapsed/refractory (R/R) ≥55y. Data were prospectively collected from six Italian centres and compared for efficacy to two reference groups, treated with established iv Rituximab-CHT in 1 and 2 line respectively. Results from April-2011 to March-2018, 17/51(33%) naïve, 21/51(41%) refractory and 13/51(25.5%) relapsed patients started DEVEC; 39/51(76.5%) were de-novo DLBCL; 10/51(19.6%) transformed-DLBCL and 2/51(3.9%) unclassifiable-DLBCL/classical-Hodgkin-lymphoma. The median age was 85y (range=77-93) and 78y (range=57-91) in naïve and R/R respectively and overall the DEVEC patients had very poor features compared to the reference. The rate of grade≥3 haematological-AEs was 43%(95CI=29-58%): G3-neutropenia was the most frequent; grade≥3 extra-haematological-AEs was 13.7% (95%CI=5.4-25.9%), the most frequent was infection. One-year OS and PFS were 67% and 61% for naive, 60% and 50% for reference-naïve respectively; Cox proportional hazard ratio (Cox-PH-ratio) for OS and PFS were 0.69 (95%CI=0.27-1.76;p=.441) and 0.68 (95%CI=0.28-1.62;p=.381) respectively. One-year OS and PFS were 48% and 39% in the R/R, 36% and 17% in the reference-R/R respectively; Cox-PH-ratio for OS and PFS, were 0.76 (95%CI=0.42-1.40; p=.386) and 0.48 (95%CI=0.28-0.82; p=.007) respectively. Conclusion The favourable activity of DEVEC compared to a real-life series and the convenience of an oral administration, may possibly lay the groundwork for a paradigm-shift in the treatment of elderly DLBCL.
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http://dx.doi.org/10.1007/s10637-019-00769-5DOI Listing
June 2019

Outcome of transformed follicular lymphoma worsens according to the timing of transformation and to the number of previous therapies. A retrospective multicenter study on behalf of Fondazione Italiana Linfomi (FIL).

Br J Haematol 2019 05 21;185(4):713-717. Epub 2019 Feb 21.

Haematology, ASST Spedali Civili di Brescia, Brescia, Italy.

Optimal treatment for transformed follicular lymphoma (tFL) is not fully defined. Clinical characteristics and treatments that impact on post-transformation outcome of 176 biopsy-proven tFL were analysed. Transformation occurred at initial diagnosis in 52% (Group 1) and after a FL diagnosis in 48% (Group 2). Five-year overall survival was 84% for Group 1 and 51% for Group 2 (P < 0·001). In Group 1, 5-year progression-free survival was superior after rituximab maintenance compared to observation only (94% vs. 53%, P = 0·024). In Group 2, an inverse trend was found between survival and both a higher number of pre-transformation treatment lines and a short time-to-transformation.
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http://dx.doi.org/10.1111/bjh.15816DOI Listing
May 2019

The prognostic role of end of treatment FDG-PET-CT in patients with diffuse large B cell lymphoma can be improved by considering it with absolute monocyte count at diagnosis.

Leuk Lymphoma 2019 08 28;60(8):1958-1964. Epub 2019 Jan 28.

e Sant'Andrea Hospital , Rome , Italy.

It is well established that some patients with diffuse large B-cell lymphoma (DLBCL) and the negative end of treatment PET-CT (EOT-PET-CT) will relapse, while a proportion with positive uptake can still obtain long-term EFS. We reviewed data of 200 consecutive, previously untreated patients with DLBCL recorded in Italy and Israel between 2007 and 2015. We found that patients with negative EOT-PET-CT with AMC > 630/mmc have a 3-years EFS of 72%, compared to those with AMC ≤ 630/mmc that have an EFS of 84%. Furthermore, considering patients with positive EOT-PET-CT, those with AMC > 630/mmc have a 3-years EFS of 8%, while those with AMC ≤ 630/mmc have an EFS of 38%. Thus, it appears that combining the gold standard for response evaluation EOT-PET-CT with a simple and inexpensive parameter like AMC at diagnosis, further improves prognostication in DLBCL. Applying this simple method can be useful for all doctors working in lymphoma clinical practice.
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http://dx.doi.org/10.1080/10428194.2018.1564049DOI Listing
August 2019

Influence of Type of Fixation and Other Characteristics on Outcome after Endovascular Repair of Ruptured Abdominal Aortic Aneurysms.

Ann Vasc Surg 2019 May 28;57:83-90. Epub 2018 Nov 28.

Department of Vascular Surgery, Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara, Modena, Italy.

Background: Endovascular treatment nowadays represents a valuable option in the treatment of ruptured abdominal aortic aneurysms (rAAAs). The aim of this study is to evaluate a 15-year, single-center experience with endovascular treatment of rAAAs and the role of the type of fixation in outcome.

Methods: Retrospective analysis of all consecutive hemodynamically stable and unstable patients with a diagnosed rAAA treated at this hospital with an endovascular procedure between December 1999 and January 2015 was conducted. Patients with symptomatic aneurysms and impending ruptures were excluded. Predictive factors of immediate and overall major complications and survival were investigated. Study end points included technical and clinical success, mortality, and major adverse events.

Results: This study included 142 patients. Technical success was 97.1% within 30 days, 60 major adverse events were reported in 43 patients (30.3%), including 40 deaths (28.2%). Clinical success at 30 days was 59.9%. Predictive factors of 30-day mortality were chronic renal disease (odds ratio [OR] 3.44, P = 0.006), chronic obstructive pulmonary disease (OR 2.42, P = 0.032), hemodynamic instability at presentation (OR 4.57, P = 0.001), and the use of an aortic balloon (OR 23.4, P < 0.001). The use of local anesthesia (OR 0.38, P = 0.017) had a protective influence. One-year survival was 52%. At a median follow-up of 44 months (range 0.5-152), overall survival was 39% (95% CI 30-48), with a median overall survival of 13 month (95% CI 6-36). Five-year survival was 23%. Predictive factors of long-term mortality were advanced age (>85 years) (hazard ratio [HR] 2.0, P = 0.002), hemodynamic instability at admission (HR 1.90, P = 0.005), and the use of an aortic balloon (HR 4.56, P < 0.001). The implantation of an anatomically fixated (AFIX) device was found to be protective against mortality (OR 0.41, P = 0.011).

Conclusions: In this series, satisfactory rates of complications and survival were observed after endovascular repair of rAAAs. In addition to the well-known predictors of outcome, the type of fixation also seems to play a significant role, and the AFIX device was associated with improved longer term survival when its use was deemed feasible.
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http://dx.doi.org/10.1016/j.avsg.2018.09.022DOI Listing
May 2019

Efficacy of bendamustine and rituximab in splenic marginal zone lymphoma: results from the phase II BRISMA/IELSG36 study.

Br J Haematol 2018 12 8;183(5):755-765. Epub 2018 Nov 8.

APHP, Saint-Louis Hospital, Haemato-oncology- Paris Diderot University, Paris, France.

Splenectomy in addition to immunotherapy with rituximab can provide quick and sometimes durable disease control in patients with splenic marginal zone lymphoma (SMZL). However, systemic chemotherapy is ultimately required in many cases. The BRISMA (Bendamustine-rituximab as first-line treatment of splenic marginal zone lymphoma)/IELSG (International Extranodal Lymphoma Study Group)36 trial is an open-label, single arm phase II study designed by the IELSG in cooperation with the Fondazione Italiana Linfomi and the lymphoma Study Association according to Simon's two-stage method. The primary endpoint was complete response rate. Fifty-six patients with SMZL diagnosis confirmed on central revision were treated with bendamustine (90 mg/m  days 1, 2) and rituximab (375 mg/m  day 1) every 28 days for six cycles (B-R). The overall response and CR rates were 91% and 73%, respectively. Duration of response, progression-free survival and overall survival at 3 years were 93% (95% confidence interval [CI] 81-98), 90% (95% CI 77-96) and 96% (95% CI 84-98), respectively. Toxicity was mostly haematological. Neutropenia grade ≥3 was recorded in 43% of patients; infections and febrile neutropenia in 5·4% and 3·6%. Overall, 14 patients (25%) experienced serious adverse events. Five patients (9%) went off-study because of toxicity and one patient died from infection. In conclusion, B-R resulted in a very effective first-line regimen for SMZL. Based on the results achieved in the BRISMA trial, B-R should be considered when a chemotherapy combination with rituximab is deemed necessary for symptomatic SMZL patients.
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http://dx.doi.org/10.1111/bjh.15641DOI Listing
December 2018

Rituximab and the risk of transformation of follicular lymphoma: a retrospective pooled analysis.

Lancet Haematol 2018 Aug 4;5(8):e359-e367. Epub 2018 Jul 4.

Hospices Civils de Lyon, Universite Claude Bernard Lyon 1, Department of Haematology, Pierre Benite, France.

Background: Histological transformation of follicular lymphoma to aggressive lymphoma is a serious event with a substantial effect on patient outcome. The aim of the Aristotle study was to assess the effect of rituximab on the risk of histological transformation and its outcome.

Methods: 11 cooperative groups or institutions across Europe contributed data to this study. Eligible patients (≥18 years) had histologically confirmed follicular lymphoma grade 1, 2, or 3a, diagnosed between Jan 2, 1997, and Dec 20, 2013. Histological transformation was defined as a biopsy-proven aggressive lymphoma that occurred as a first event after first-line therapy. The primary endpoints were the cumulative hazard of histological transformation and survival after transformation.

Findings: Information was available for 10 001 patients with follicular lymphoma, 8116 of whom were eligible for analysis. 509 histological transformations were reported. After a median follow-up of 87 months (range 1-221; 2·5-97·5th percentile 5-160), the 10-year cumulative hazard of histological transformation was 7·7% (95% CI 6·9-8·5). The 10-year cumulative hazard of histological transformation was 5·2% (95% CI 4·5-6·2) in patients who received rituximab and 8·7% (7·2-10·6) in those who did not (hazard ratio [HR] 0·73, 95% CI 0·58-0·90; p=0·004). The 10-year cumulative hazard of histological transformation was 5·9% (95% CI 5·0-7·0) for patients who received induction rituximab only and 3·6% (95% CI 2·3-5·5) for those treated with induction and maintenance rituximab (HR 0·55, 95% CI 0·37-0·81; p=0·003). This finding was confirmed in a multivariate analysis (p=0·016). 287 deaths were recorded in 509 patients with histological transformation, resulting in a 10-year survival after transformation of 32% (95% CI 26-38). Survival after transformation did not differ between patients not exposed to rituximab and those who received rituximab in induction only (HR 0·94, 95% CI 0·69-1·28; p=0·70), and those who received rituximab in induction and maintenance (0·96, 0·58-1·61; p=0·88).

Interpretation: The risk of histological transformation as a first event can be significantly reduced by the use of rituximab. These findings support the need to inform patients using rituximab nowadays that the risk of transformation is lower than it was before the introduction of rituxumab.

Funding: Associazione Angela Serra per la Ricerca sul Cancro, European Lymphoma Institute, European Hematology Association Lymphoma Group, Fondazione Italiana Linfomi, Spanish Group of Lymphoma and Bone Marrow Transplantation.
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http://dx.doi.org/10.1016/S2352-3026(18)30090-5DOI Listing
August 2018

Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS). A new prognostic model developed by the International T cell Project Network.

Br J Haematol 2018 06 19;181(6):760-769. Epub 2018 Apr 19.

Stanford University Medical Center, Stanford, CA, USA.

Different models to investigate the prognosis of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) have been developed by means of retrospective analyses. Here we report on a new model designed on data from the prospective T Cell Project. Twelve covariates collected by the T Cell Project were analysed and a new model (T cell score), based on four covariates (serum albumin, performance status, stage and absolute neutrophil count) that maintained their prognostic value in multiple Cox proportional hazards regression analysis was proposed. Among patients registered in the T Cell Project, 311 PTCL-NOS were retained for study. At a median follow-up of 46 months, the median overall survival (OS) and progression-free survival (PFS) was 20 and 10 months, respectively. Three groups were identified at low risk (LR, 48 patients, 15%, score 0), intermediate risk (IR, 189 patients, 61%, score 1-2), and high risk (HiR, 74 patients, 24%, score 3-4), having a 3-year OS of 76% [95% confidence interval 61-88], 43% [35-51], and 11% [4-21], respectively (P < 0·001). Comparing the performance of the T cell score on OS to that of each of the previously developed models, it emerged that the new score had the best discriminant power. The new T cell score, based on clinical variables, identifies a group with very unfavourable outcomes.
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http://dx.doi.org/10.1111/bjh.15258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033106PMC
June 2018

The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a report from the prospective, International T-Cell Project.

Haematologica 2018 07 29;103(7):1191-1197. Epub 2018 Mar 29.

Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.

This analysis explored factors influencing survival of patients with primary refractory and relapsed peripheral T-cell lymphomas enrolled in the prospective International T-cell Project. We analyzed data from 1020 patients with newly diagnosed disease, enrolled between September 2006 and December 2015. Out of 937 patients who received first-line treatment, 436 (47%) were identified as refractory and 197 (21%) as relapsed. Median time from the end of treatment to relapse was 8 months (range 2-73). Overall, 75 patients (8%) were consolidated with bone marrow transplantation, including 12 refractory and 22 relapsed patients. After a median follow up of 38 months (range 1-96 months) from documentation of refractory/relapsed disease, 440 patients had died. The median overall survival (OS) was 5.8 months; 3-year overall survival rates were 21% and 28% for refractory and relapsed patients, respectively (<0.001). Patients receiving or not salvage bone marrow transplantation had a 3-year survival of 48% and 18%, respectively (<0.001). In a univariate Cox regression analysis, refractory disease was associated with a higher risk of death (HR=1.43, =0.001), whereas late relapse (>12 months, HR 0.57, =0.001) and salvage therapy with transplantation (HR=0.36, <0.001) were associated with a better OS. No difference was found in OS with respect to histology. This study accurately reflects outcomes for patients treated according to standards of care worldwide. Results confirm that peripheral T-cell lymphomas patients had dismal outcome after relapse or progression. Patients with chemotherapy sensitive disease who relapsed after more than 12 months might benefit from consolidation bone marrow transplantation.
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http://dx.doi.org/10.3324/haematol.2017.186577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029527PMC
July 2018

Combined Hormonal Contraceptive Use and Risk of Breast Cancer in a Population of Women With a Family History.

Clin Breast Cancer 2018 02 14;18(1):e15-e24. Epub 2017 Nov 14.

Department of Oncology, Haematology and Respiratory Disease, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.

Background: We estimated the association between combined hormonal contraceptive (CHC) use and breast cancer (BC) incidence in a well-selected population of women at familial risk of BC at the Modena Family Cancer Clinic.

Materials And Methods: We performed a retrospective cohort study by reviewing the data from 2527 women (4.5% BRCA mutation carriers, 72.2% high risk, and 23.3% intermediate risk using the Modena criteria and the Tyrer-Cuzick model).

Results: We did not find any specific feature of breast cancer (infiltration, hormone receptor and HER2 status, onset before age 35 years, multiple diagnoses) in the CHC users (P > .05). Only 2.0% of women used a preparation with ≥ 50 μg of ethinylestradiol (EE). The use of CHCs was not associated with an increased risk of breast cancer (cumulative hazard: never used, 0.17; CHC users, 0.20; P = .998), regardless of the duration of use (cumulative hazard: never used, 0.17, used < 5 years, 0.20; used 5-10 years, 0.14; used > 10 years, 0.25; P = .414). This was confirmed for the different risk groups when interacted in a Cox proportional hazard regression model. The EE dose did not influence the risk of BC (cumulative hazard, 2.37; 95% confidence interval, 0.53-10.1; never used, 0.18; EE < 20 μg used, 0.04; EE ≥ 20 μg used, 0.16; P = .259). The types of progestins used might influence the risk, with some, such as gestodene (P = .028) and cyproterone acetate (P = .031), associated with an even greater reduced risk.

Conclusions: CHC use does not increase the risk of BC in a population of women with a family history, encouraging CHC use in this group of women.
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http://dx.doi.org/10.1016/j.clbc.2017.10.016DOI Listing
February 2018

Standard "off-the-shelf" multibranched thoracoabdominal endograft in urgent and elective patients with single and staged procedures in a multicenter experience.

J Vasc Surg 2018 04 31;67(4):1005-1016. Epub 2017 Oct 31.

Centro Oncologico Modenese, Policlinico di Modena, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia, Modena, Italy.

Objective: The objective of this study was to assess immediate and midterm outcomes for urgent/emergent and elective patients with thoracoabdominal aortic aneurysms (TAAAs) treated with the first commercially available "off-the-shelf" multibranched endograft for endovascular aneurysm repair, with a single-step or a staged surgical approach.

Methods: A multicenter, nonrandomized, retrospective study was conducted of TAAA patients grouped by urgent/emergent and elective treatment with multibranched endograft for endovascular aneurysm repair at 13 Italian centers from November 2012 to August 2016. Urgent/emergent repair was classified as rupture in 16%, impending rupture in 9%, pain in 53%, or a maximum TAAA diameter ≥80 mm in 22%. Study end points were technical success, mortality, spinal cord ischemia, target visceral vessel (TVV) patency, and procedure-related reinterventions at 30 days and at follow-up.

Results: Seventy-three patients (274 TVVs) were enrolled. Treatment was performed in elective (n = 41 [56%]) or urgent/emergent (n = 32 [44%]) settings, according to a single-step (n = 30 [41%]) or staged (n = 43 [59%]) approach. Technical success was 92%. Mortality within 30 days was 4% (n = 3 urgent/emergent patients) due to myocardial infarction. Spinal cord ischemia was recorded in two patients (3%; elective group). The primary patency of TVVs was 99% (three renal branch occlusions). Procedure-related reinterventions were required in five cases (7%). At least one adverse event from any cause ≤30 days was registered in 42% (n = 31). At a median follow-up of 18 months (range, 1-43 months), eight (11%) deaths (elective vs urgent/emergent, 2% vs 22%; P = .018), three (1%) cases of branch occlusion or stenosis, and five (7%) reinterventions were recorded. A survival of 88% (standard error [SE], 4%), 86% (SE, 4%), and 82% (SE, 5%) was evidenced at 12, 24, and 36 months, respectively. Urgent/emergent repair and female gender were identified as independent risk factors for all-cause mortality (P < .001 and P = .015, respectively), and the staged approach was identified as protective (P = .026). Freedom from reintervention was 86% (SE, 4%) and 83% (SE, 5%) at 12 and 24 months.

Conclusions: The first off-the-shelf multibranched endograft seems safe in both urgent/emergent and elective settings. The staged surgical approach appears to positively influence overall survival. This unique device and its operators will usher in a new treatment paradigm for TAAA repair.
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http://dx.doi.org/10.1016/j.jvs.2017.08.068DOI Listing
April 2018

Long-Term Results of the FOLL05 Trial Comparing R-CVP Versus R-CHOP Versus R-FM for the Initial Treatment of Patients With Advanced-Stage Symptomatic Follicular Lymphoma.

J Clin Oncol 2018 03 2;36(7):689-696. Epub 2017 Nov 2.

Stefano Luminari, Angela Ferrari, and Francesco Merli, Azienda Ospedaliera Arcispedale Santa Maria Nuova-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Reggio Emilia; Stefano Luminari, Martina Manni, Alessandra Dondi, Vittoria Tarantino, Luigi Marcheselli, and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; Annalisa Chiarenza, Azienda Ospedaliera Universitaria Policlinico-Vittorio Emanuele, University of Catania, Catania; Chiara Rusconi, Azienda Socio Sanitaria Territoriale (ASST) -Grande Ospedale Metropolitano Niguarda; Andrés J.M. Ferreri, IRCCS San Raffaele Scientific Institute, Milano; Alessandra Tucci, ASST-Spedali Civili di Brescia, Brescia; Umberto Vitolo, Città della Salute e della Scienza University and Hospital, Torino; Sofia Kovalchuk, University of Florence, Florence; Emanuele Angelucci, Ospedale Policlinico San Martino, Genova; Alessandro Pulsoni, Sapienza University of Rome, Rome; Luca Arcaini, Fondazione IRCCS Policlinico San Matteo, Pavia; Francesco Angrilli, Spirito Santo Hospital, Pescara; Gianluca Gaidano, University of Eastern Piedmont, Novara; Caterina Stelitano, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria; Giovanni Bertoldero, Ospedale di Mirano, Mirano; Nicola Cascavilla, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo; Flavia Salvi, Ospedale SS Antonio e Biagio, Alessandria; and Daniele Vallisa, Guglielmo da Saliceto Hospital, Piacenza, Italy.

Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone) with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-FM (rituximab plus fludarabine and mitoxantrone) regimens without rituximab maintenance as initial therapy for patients with advanced-stage follicular lymphoma (FL). A previous analysis with a median follow-up of 34 months showed a superior 3-year time to treatment failure, the primary study end point, with R-CHOP and R-FM versus R-CVP and showed R-CHOP to have a better risk-benefit ratio in terms of toxicity than R-FM. We report a post hoc analysis of this trial after a median follow-up of 7 years. Patients and Methods Of the 534 enrolled patients, 504 were evaluable. At the time of analysis, the median follow-up was 84 months (range, 1 to 119 months). Results The 8-year time to treatment failure and progression-free survival rates were 44% (95% CI, 39% to 49%) and 48% (95% CI, 43% to 53%), respectively. The hazard ratio for progression-free survival adjusted by FL International Prognostic Index 2 versus R-CVP was 0.73 for R-CHOP (95% CI, 0.54 to 0.98; P = .037) and 0.67 for R-FM (95% CI, 0.50 to 0.91; P = .009). The 8-year overall survival (OS) rate was 83% (95% CI, 79% to 87%), with no significant differences among study arms. Overall, we observed a higher risk of dying as a result of causes unrelated to lymphoma progression with R-FM versus R-CVP. Conclusion With an 83% 8-year OS rate, long-term follow-up of the FOLL05 trial confirms the favorable outcome of patients with advanced-stage FL treated with immunochemotherapy. The three study arms had similar OS but different activity and toxicity profiles. Patients initially treated with R-CVP had a higher risk of lymphoma progression compared with those receiving R-CHOP, as well as a higher risk of requiring additional therapy.
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http://dx.doi.org/10.1200/JCO.2017.74.1652DOI Listing
March 2018

Empathic attitudes among nursing students: a preliminary study.

Acta Biomed 2017 07 18;88(3S):22-30. Epub 2017 Jul 18.

Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia.

Background And Aim: An empathic approach is fundamental for therapeutic relationship between nurse and patient. According to some researchers, female nursing students show higher empathic attitude in comparison with males, but both show a decline in empathy level as their studies progress. This preliminary study evaluated the self-reported emotional empathy level among undergraduate students at first and second year of nursing 3-year course.

Method: To assess empathy level, the Balanced Emotional Empathy Scale (BEES) was administered to all students enrolled in the 2015/16 academic year (N=142), at the beginning of first year (T0) and at mid-point of second year (T1) of nursing course. Data were statistically analyzed.

Results: 118 nursing students participated in the first and 99 in the second survey. The BEES global mean score for the longitudinal group (n=99) slightly decreased  from T0 (mean=37.1±19.5 SD) to T1 (mean=33.5±22.6 SD) (t=1.20, p=0.23; t-test for paired data). Female students reported a statistically significant higher mean BEES score compared to male students in both surveys.

Conclusions: Our preliminary data suggest a slight decline in empathy level among nursing students with the progress of study course, in accordance with  previous studies. In particular, our study shows higher levels of empathy in female students and lower levels in male students, compared to other studies.  Further surveys aimed at investigating the empathy attitude at the end of nursing course could confirm the decline tendency reported by this preliminary study. Other research focusing on the causes of empathy decline are necessary to explain this phenomenon.
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http://dx.doi.org/10.23750/abm.v88i3 -S.6610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357591PMC
July 2017

New insights into sinusoidal obstruction syndrome.

Intern Med J 2017 Oct;47(10):1173-1183

Paediatric Hematology-Oncology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.

Background: Entry criteria included patients who developed sinusoidal obstruction syndrome (SOS) at a single centre from January 2000 to December 2011. Patients who underwent haemopoietic stem cell transplantation or actinomicyn-based chemotherapy for nephroblastoma were selected. The study group comprised five patients with SOS who were compared with a control group of seven patients without SOS.

Aim: To study the relationships between endothelial extracellular vesicles (EV) and plasminogen-activator inhibitor type 1(PAI-1) to assess their modification in the early phase of SOS.

Methods: Consecutive blood samples were tested for cell-derived EV, PAI-1 and coagulation parameters. Any statistically significant correlation between all datasets was searched.

Results: Antithrombin level and platelet count were statistically significantly reduced in SOS patients, suggesting a consumption status. PAI-1:Ag and PAI-1:act showed an inverse relationship with platelet counts (coef. -0.034, SE = 0.016; P = 0.041 and -0.052, SE = 0.019; P = 0.011 respectively). During follow up, PAI-1:Ag was inversely related to EV CD144+ (coef. -0.261, SE = 0.094; P = 0.007) and antithrombin (coef -0.509, SE = 0.175; P = 0.005). PAI-1:act showed an inverse association with EV CD144+ (coef.-0.251, SE = 0.121; P = 0.043), EV CD31+/CD41+ (coef. -0.004, SE = 0.002; P = 0.026) and antithrombin (coef. -0.470, SE = 0.220; P = 0.038). EV generated by rupture of gap junctions (EV CD144+) were increased in SOS patients and also showed a change over time.

Conclusion: This study demonstrates the existence of an ongoing procoagulant and hypofibrinolytic status in SOS, indicating a possible role for anticoagulant therapy. Moreover, these findings suggest a role for EV CD 144+, either alone or in combination with PAI-1, as a new biomarker for SOS.
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http://dx.doi.org/10.1111/imj.13550DOI Listing
October 2017

Ricolinostat, a selective HDAC6 inhibitor, shows anti-lymphoma cell activity alone and in combination with bendamustine.

Apoptosis 2017 06;22(6):827-840

Program of Innovative Therapies in Oncology and Haematology, Department of Diagnostic Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Via del Pozzo, 71, 41124, Modena, Italy.

Histone deacetylase inhibitors (HDACis) have emerged as a new class of anticancer agents, targeting the biological process including cell cycle and apoptosis. We investigated and explained the anticancer effects of an HDAC6 inhibitor, ricolinostat alone and in combination with bendamustine in lymphoma cell lines. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) generation, Bcl-2 protein expression, cell cycle progression and tubuline expression were determined by flow cytometry. The effects of ricolinostat alone and in combination on the caspases, PI3K/Akt, Bcl-2 pathways, ER stress and UPR were assessed by immunoblotting. Ricolinostat shows anti lymphoma activity when used as single agent and its capability to induce apoptosis is synergistically potentiated by the bendamustine in lymphoma cell lines. Drug combination reduced the proportion of cells in the G/G and S phases and caused an increase of "sub-G/G" peak. The synergistic effect accompanied with the increased ROS, activation of caspase-8, -9, and -3, the cleavage of PARP and modulated by Bcl-2 proteins family. In addition, the exposure of ricolinostat induced the acetylation level of α-tubulin, the extend of which was not further modified by bendamustine. Finally, the apoptosis effect of ricolinostat/bendamustine may be mediated by a corresponding effect on microtubule stabilization. Our data suggest that ricolinostat in combination with bendamustine may be a novel combination with potential for use as an antitumor agent in lymphoma.
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http://dx.doi.org/10.1007/s10495-017-1364-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5401712PMC
June 2017