Comparison of first-line treatment with bendamustine plus rituximab versus R-CHOP for patients with follicular lymphoma grade 3A: Results of a retrospective study from the Fondazione Italiana Linfomi.

In the setting of follicular lymphoma (FL), frontline therapy with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) has represented for many years the standard of care for patients with symptomatic advanced disease. More recently, the combination of bendamustine plus rituximab (R-B) has emerged as an alternative therapeutic option. We present a retrospective, multicenter, observational study aimed at comparing outcomes and toxicities observed in 145 patients diagnosed with grade 3A FL treated with a first line therapy in 15 Italian Fondazione Italiana Linfomi centers between the 1st of January 2014 and the 30th of May 2018. Seventy patients were treated with R-B and 75 with R-CHOP. In the R-B group, the median age at the time of diagnosis was 67 years compared with 59 years in the R-CHOP group. Patients in R-B group achieved a similar overall response rate (96% vs. 99%) and a better complete remission rate (87% vs. 80%, p=0.035) compared with patients in R-CHOP group. Progression free survival (PFS) was similar between individual treated with R-CHOP and R-B (48- month PFS 77.7% vs. 76.6% respectively, p=0.745). The overall survival was significantly longer with R-CHOP treatment (HR=0.16; 95% IC, 0.04-0.74; p=0.007); however, no statistical significant difference was observed after adjustment for age. With the limitations of the study design, our results suggest that both R-B and R-CHOP seem to be valid first-line treatment options in FL3A.

Ecological transition and sustainable development: integrated statistical indicators to support public policies.

The evolution of the concept of sustainability and the availability of new statistical information requires constant checks on the set of indicators so that they accurately perform the task of representing well-being in our society. The Sustainable Development Goals refer to various development domains relating to environmental, social, economic, and institutional issues that have been placed at the basis of the Missions envisaged by the National Recovery and Resilience Plan (NRRP). Specifically, the subject of ecological transition and the related statistical indicators and the evaluations of the effectiveness of the programming implemented by the NRRP to pursue it in practice are of significant interest. The numerous data available were analyzed at a regional level through multivariate statistical methodologies (Totally Fuzzy and Relative method) capable of synthesizing the various information to evaluate the territorial adequacy of the economic planning of its various components. Through the representation on a GIS basis of the geographical distribution of the synthesis values of the fuzzy indices, the paper highlights the different starting point existing between Italian regions. So, these integrated statistical indicators can help public policies to be oriented in a more coherent way with their environmental declared objectives. Starting from the availability of multiple data, it is developed an integrated approach to the evaluation of the local government policies in place and to monitor the progress of subsequent interventions by the Italian government.

In chronic lymphocytic leukaemia, SLAMF1 deregulation is associated with genomic complexity and independently predicts a worse outcome.

In a series of 349 patients with chronic lymphocytic leukaemia (CLL), we found lower levels of signalling lymphocytic activation molecule family member 1 (SLAMF1) expression in cases with highly complex karyotypes, as defined by the presence of five or more chromosomal abnormalities (CK5; P < 0·001) and with major chromosomal structural abnormalities (P < 0·001). SLAMF1 downregulation was significantly associated with advanced Binet Stage (P = 0·001), CD38 positivity (P < 0·001), high ß2 -microglobulin levels (P < 0·001), immunoglobulin heavy chain variable region gene (IGHV) unmutated status (P < 0·001), 11q deletion (P < 0·001), tumour protein p53 (TP53) disruption (P = 0·011) and higher risk CLL International Prognostic Index categories (P < 0·001). Multivariate analysis showed that downregulated SLAMF1 levels had independent negative prognostic impact on time-to-first treatment (P < 0·001) and overall survival (P < 0·001).

Relapsed/refractory diffuse large B-cell lymphoma patients. A multicenter retrospective analysis of eligibility criteria for car-T cell therapy.

Anti-CD19 chimeric antigen receptor (CAR) T cells represent the first approved third-line therapy associated with long-term remissions in patients with refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL). Eligibility criteria to identify patients who can successfully receive CAR-T are still debated. For this reason, the aim of this study was to identify factors influencing eligibility and define a realistic patient estimate. Of 1100 DLBCL patients, 137 were included. Based on the Juliet trial inclusion criteria, only 64 patients (46.7%) would be eligible. Median overall survival (OS) was 8.04 months in eligible vs 3.23 in non-eligible patients (p < 0.001). Multivariate analysis identified stage III-IV (p = 0.017) and ECOG ≥2 (p < 0.001) as significant independent prognostic factors for OS. Moreover, only 64/1100 (5.8%) DLBCL patients would be truly eligible for CAR-T. Our real-life data confirm that with a  longer waiting time patients with advanced stage and poor ECOG are less likely to be eligible for CAR-T cell infusion.

Management of elderly patients with immune thrombocytopenia: Real-world evidence from 451 patients older than 60 years.

INTRODUCTION: Primary Immune thrombocytopenia (ITP) in the elderly is a major clinical challenge which is increasingly frequent due to global ageing population. MATERIALS AND METHODS: To describe baseline ITP features, management, and outcome, a centralized electronic database was established, including data of 451 patients aged ≥60 years that were treated from 2000 onwards and were observed for ≥1 year (total observation of 2704 patient-years). RESULTS: At ITP diagnosis, median age was 71.1 years (age ≥ 75: 42.8%); 237 (53.9%) patients presented with haemorrhages (grade ≥ 3: 7.5%). First-line therapy included prednisone (82.9%), dexamethasone (14.6%), thrombopoietin-receptor agonists (TRAs, 1.3%), and oral immunosuppressive agents (1.1%). Prednisone starting dose ≥1 mg/kg/d (p = .01) and dexamethasone 40 mg/d (p < .001) were mainly reserved to patients aged 60-74, who were more treated with rituximab (RTX, p = .02) and splenectomy (p = .03) second-line. Overall response rates to first and second-line therapies were 83.8% and 84.5%, respectively, regardless of age and treatment type/dose. A total of 178 haemorrhages in 101 patients (grade ≥ 3: n. 52, 29.2%; intracranial in 6 patients), 49 thromboses in 43 patients (grade ≥ 3: n. 26, 53.1%) and 115 infections in 94 patients (grade ≥ 3: n. 23, 20%) were observed during follow-up. Incidence rates of complications per 100 patient-years were: 4.5 (haemorrhages, grade ≥ 3: 1.7), 1.7 (thromboses, grade ≥ 3: 0.9), and 3.9 (infections, grade ≥ 3: 0.7). TRAs use were associated with reduced risk of bleeding and infections, while cardiovascular risk factors (particularly, diabetes) significantly predicted thromboses and infections. CONCLUSIONS: Age-adapted treatment strategies are required in elderly and very elderly patients.

Real-world experience with decitabine as a first-line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy.

Despite widespread use of decitabine to treat acute myeloid leukaemia (AML), data on its effectiveness and safety in the real-world setting are scanty. Thus, to analyze the performance of decitabine in clinical practice, we pooled together patient-level data of three multicentric observational studies conducted since 2013 throughout Italy, including 306 elderly AML patients (median age 75 years), unfit for intensive chemotherapy, treated with first-line decitabine therapy at the registered schedule of 20 mg/m2 /iv daily for 5 days every 4 weeks. Overall response rate (ORR), overall survival (OS) curves, and multivariate hazard ratios (HRs) of all-cause mortality were computed. Overall, 1940 cycles of therapy were administered (median, 5 cycles/patient). A total of 148 subjects were responders and, therefore, ORR was 48.4%. Seventy-one patients (23.2%) had complete remission, 32 (10.5%) had partial remission, and 45 (14.7%) had haematologic improvement. Median OS was 11.6 months for patients with favourable-intermediate cytogenetic risk and 7.9 months for those with adverse cytogenetic risk. Median relapse-free survival after CR was 10.9 months (95% confidence interval [CI]: 8.7-16.0). In multivariate analysis, mortality was higher in patients with adverse cytogenetic risk (HR=1.58; 95% CI: 1.13-2.21) and increased continuously with white blood cell (WBC) count (HR=1.12; 95% CI: 1.06-1.18). A total of 183 infectious adverse events occurred in 136 patients mainly (>90%) within the first five cycles of therapy. This pooled analysis of clinical care studies confirmed, outside of clinical trials, the effectiveness of decitabine as first-line therapy for AML in elderly patients unfit for intensive chemotherapy. An adverse cytogenetic profile and a higher WBC count at diagnosis were, in this real life setting, unfavourable predictors of survival.

Vitamin D Status in Rheumatoid Arthritis: Inflammation, Arterial Stiffness and Circulating Progenitor Cell Number.

BACKGROUND AND AIMS: Suboptimal vitamin D status was recently acknowledged as an independent predictor of cardiovascular diseases and all-cause mortality in several clinical settings, and its serum levels are commonly reduced in Rheumatoid Arthritis (RA). Patients affected by RA present accelerated atherosclerosis and increased cardiovascular morbidity and mortality with respect to the general population. In RA, it has been reported an impairment of the number and the activity of circulating proangiogenic haematopoietic cells (PHCs), including CD34+, that may play a role in endothelial homeostasis. The purpose of the study is to investigate the association between vitamin D levels and PHCs, inflammatory markers, and arterial stiffening in patients with RA. METHODS AND RESULTS: CD34+ cells were isolated from 27 RA patients and 41 controls. Vitamin D levels, C-reactive protein (CRP), fibrinogen, pulse wave velocity (PWV), and carotid intima-media thickness (cIMT) were also evaluated. CD34+ count and vitamin D levels were lower in RA patients as compared to controls, while fibrinogen, CRP, PWV and cIMT were higher in RA patients. CD34+ cell number appeared to be associated with vitamin D levels, and negatively correlated to fibrinogen and early atherosclerosis markers (PWV and cIMT); vitamin D levels appear also to be inversely associated to fibrinogen. CONCLUSIONS: RA patients with moderate disease activity presented with low vitamin D levels, low CD34+ cell count, increased PWV and cIMT; we found that vitamin D deficiency is associated to CD34+ cell reduction in peripheral blood, and with fibrinogen levels. This suggests that vitamin D might contribute to endothelial homeostasis in patients with RA.

The cancer stem cell hypothesis: a guide to potential molecular targets.

Common cancer theories hold that tumor is an uncontrolled somatic cell proliferation caused by the progressive addition of random mutations in critical genes that control cell growth. Nevertheless, various contradictions related to the mutation theory have been reported previously. These events may be elucidated by the persistence of residual tumor cells, called Cancer Stem Cells (CSCs) responsible for tumorigenesis, tumor maintenance, tumor spread, and tumor relapse. Herein, we summarize the current understanding of CSCs, with a focus on the possibility to identify specific markers of CSCs, and discuss the clinical application of targeting CSCs for cancer treatment.