Current data suggests that the risk of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) is comparable to that observed in patients with solid tumours, although more robust confirmatory analyses are required. With that in mind, we investigated the occurrence of VTE in a pooled analysis of 12 "Fondazione Italiana Linfomi" (FIL) prospective clinical studies. Specifically, we wished to assess the cumulative incidence of VTE in NHL patients, evaluate the predictive value of the Khorana Score (KS), and identify other potential risk factors for VTEs. Data for VTE occurrence were retrieved from study databases and pharmacovigilance reports. Our analysis includes 1717 patients from 12 prospective phase II and III trials, including newly diagnosed NHL. We observed 53 VTEs (any grade) in 46 patients, with 20 severe VTEs in 17 patients. The cumulative incidences for "all-grade" or grade ≥3 VTEs were 2.9 % (95 % CI: 2.1-3.8) and 1.1 % (95 % CI: 0.6-1.6), respectively. KS categories were positively associated with the risk of VTE of any grade, and with severe events (i. e. grade ≥3; Gray's test p-values = 0.048 and 0.012, respectively). Among NHL patients, those with diffuse large B-cell lymphoma (DLBCL) showed a greater risk of (any grade) VTE (HR: 3.42, 95 % CI: 1.32-8.84, p-value = 0.011). Our study indicates that 1) VTE is a relevant complication for NHL patients, 2) KS is predictive of VTE events and 3) DLBCL histotype is an independent risk factor for VTE incidence, for which preventative interventions could be considered.

Bisphosphonates (BPs) are administered to Multiple Myeloma (MM) patients with bone lytic lesion. Osteonecrosis of the Jaw (ONJ) is a complication reported since 2003 in patients treated with intravenous (IV) BPs such as zoledronic acid and pamidronate, with 6%–26.3% frequency in early literature series, before some preventive measures were recommended. We evaluated the occurrence of ONJ with and without dental preventive measures in MM patients treated with BPs in our centre between 1996 and 2015. Since 2005, MM patients (already under treatment or before treatment) underwent a baseline mouth assessment (dental visit, Rx orthopantomography, and eventual tooth avulsion or dental care if necessary) and were followed by a multidisciplinary team. We reviewed the charts of 119 MM patients receiving IV BPs, classified into 3 groups: (a) “historic group” (21 patients who had started BP treatment in years before the awareness of ONJ); (b) “screening group” (20 patients starting BPs without baseline evaluation); and (c) “prevention group” (78 patients starting therapy only after baseline preventive assessment and eventual dental care measures). ONJ was observed in 3/21 patients (14.2%) from group a, in 2/20 patients (10%) from group b, and in no patients from group c (0%). Notably, the median number of IV BP administrations decreased after 2005. Our data confirmed a meaningful reduction of ONJ risk in MM patients treated with BPs if preventive measures are applied. Both implementation of prevention measures and reduction of cumulative doses of IV BPs could have contributed to a decreased incidence of ONJ.

Several infectious agents appear to provide a proliferative signal -- “antigen-drive” – that could be implicated in the pathogenesis of various type of Non-Hodgkin Lymphoma (NHL). A classical model of the infection-driven lymphoproliferative disorder is Helicobacter pylori-induced gastric MALT lymphoma, where antibiotic therapy allows the eradication of both the infectious agent and the clonal B-cell expansion. Following the footsteps of this example, several retrospective studies have found a correlation with other pathogens and B-cell Lymphomas, adding new relevant information about pathogenesis and laying the groundwork for chemotherapy-free treatments.Although no clear association has been found between infectious agents and Follicular Lymphoma (FL), a growing number of biological and clinical observations suggests the interaction of physiological and pathological microbial populations also in this subtype of lymphoma. In the last few years, epidemiological studies investigating the association of known risk factors and FL found a potential correlation with viral or bacterial infections; moreover, recent findings of the stimulation of FL clones support the importance of microbial exposure to lymphomagenesis and disease progression.In the following review we make an attempt to find tangible evidence for a role of either physiological and pathological exogenous microbial species in the pathogenesis of FL, and try to integrate the findings coming from epidemiological, biological and interventional studies to define future novel treatment and prevention strategies for FL.

Background: Expression of p190 BCR-ABL mRNA is generally considered to be confined to patients with acute lymphoid or more rarely myeloid leukemias, whereas p210 BCR-ABL mRNA is the hallmark of CML. In reality it is not uncommon the presence of p190 m-RNA in p210 CML in chronic phase, due to alternative or missplicing. Its presence seems to have no impact on prognosis in the pre-TKI era, although it may be expression of genomic instability. Aim: Primary object of this study was to investigate if the co-expression might influence the rate of early outcome surrogate endpoints such as such as optimal molecular response (EMR; BCR-ABL < 10% (IS) at 3 month and BCR-ABL < 1% or 6 month). in patients treated with TKI. Methods: Were evaluated patients with CML in chronic phase treated with TKI at our institution. We excluded cases with less than one year of treatment or treated with conventional chemotherapy. The fusion transcripts BCR-ABL were evaluated at diagnosis in peripheral blood by NESTED-PCR and the molecular response were evaluated in peripheral blood with Real-Time PCR. The patients were divided into two groups, "double transcripts" (DT) and "single transcript" (ST). Results: A total of 34 patients were analyzed. The median age was 61 years (range 22-80) and 26 (68%) were male. Ten patients (29%) were DT and twenty-fouru(71%) ST. The distribution according to Sokal score was: 2 (10%), 5 (50%) 3(30%) patients for low, intermediate and high risk in the DT, whereas 13 (54%), 10 (41%) 1 (5%) low, intermediate and high risk in ST, respectively. The optimal response at 3 month was achieved in 3 patients with DT and 20 patients with ST ( 10% vs 83), at 6-month optimal response was achieved in 3 patients with DT and 20 patients with ST (10% vs 83). No patients with BCR-ABL > 10 % at 3 months, achieved molecular response at 6 months. Summary/Conclusion: In our study the co-expression of p190 and p210 BCR-ABL transcripts influences the early molecular response to TKI and suggesting the need for a larger validation study Disclosures No relevant conflicts of interest to declare.

Background: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19–197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58–77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357–3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363–3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363–3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals. Plain language summary EPICOVIDEHA registry reports inferior outcomes of COVID-19 in patients with Philadelphia-negative chronic myeloproliferative neoplasms receiving immunosuppressive therapies. Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) incur high rates of infections during the course of their disease. The present study was aimed at assessing which patient characteristics predicted a worse outcome of SARS-COV-2 infection in individuals with MPN. To pursue this objective, the researchers analyzed the data collected by EPICOVIDEHA, an international online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. The database provided clinical data of 398 patients with MPN incurring COVID-19: Patients were mostly elderly (median age was 69 years); Forty-six percent of them were affected by myelofibrosis, which is the most severe MPN; Moreover, 32% were receiving immunosuppressive therapies (JAK inhibitors, such as ruxolitinib, steroids, or immunomodulatory IMID drugs, such as thalidomide) before COVID-19. Hospitalization was required in 54% of the patients, and the risk of being hospitalized for severe COVID-19 was independently predicted by Older age; Comorbidities; Exposure to immunosuppressive therapies. Overall, 22% of MPN patients deceased soon after COVID-19 and the risk of death was independently increased over twofold by Older age; Comorbidities; Exposure to immunosuppressive therapies before the infection. In conclusion, COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents, including JAK inhibitors, or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.