No abstract

An association between Epstein-Barr Virus (EBV) infection and lymphoproliferative diseases has been reported with EBV + diffuse large B cell-lymphoma (DLBCL) of the elderly described as a distinct entity. In a cohort of 218 human immunodeficiency virus (HIV)-negative patients with diffuse large B-cell lymphomas, we detected EBV-DNA in 25% of whole blood (WB) samples at diagnosis. Presence and viral load in WB, mononuclear cells or plasma did not predict the presence of EBV in the tumor biopsy. Positive Hepatitis C virus (HCV) serology was associated with a higher frequency of EBV in WB. Patients with EBV-DNA in WB had a significantly shorter progression-free (p = 0.02) and overall survival (p = 0.05) after immunochemotherapy with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone). We conclude that detection of EBV in WB is not a surrogate marker for EBV-association in diffuse large B-cell lymphoma, however it associates with worse outcome.

The COVID-19 pandemic is impressively challenging the healthcare system. Several prognostic models have been validated but few of them are implemented in daily practice. The objective of the study was to validate a machine-learning risk prediction model using easy-to-obtain parameters to help to identify patients with COVID-19 who are at higher risk of death. The training cohort included all patients admitted to Fondazione Policlinico Gemelli with COVID-19 from March 5, 2020, to November 5, 2020. Afterward, the model was tested on all patients admitted to the same hospital with COVID-19 from November 6, 2020, to February 5, 2021. The primary outcome was in-hospital case-fatality risk. The out-of-sample performance of the model was estimated from the training set in terms of Area under the Receiving Operator Curve (AUROC) and classification matrix statistics by averaging the results of fivefold cross validation repeated 3-times and comparing the results with those obtained on the test set. An explanation analysis of the model, based on the SHapley Additive exPlanations (SHAP), is also presented. To assess the subsequent time evolution, the change in paO2/FiO2 (P/F) at 48 h after the baseline measurement was plotted against its baseline value. Among the 921 patients included in the training cohort, 120 died (13%). Variables selected for the model were age, platelet count, SpO2, blood urea nitrogen (BUN), hemoglobin, C-reactive protein, neutrophil count, and sodium. The results of the fivefold cross-validation repeated 3-times gave AUROC of 0.87, and statistics of the classification matrix to the Youden index as follows: sensitivity 0.840, specificity 0.774, negative predictive value 0.971. Then, the model was tested on a new population (n = 1463) in which the case-fatality rate was 22.6%. The test model showed AUROC 0.818, sensitivity 0.813, specificity 0.650, negative predictive value 0.922. Considering the first quartile of the predicted risk score (low-risk score group), the case-fatality rate was 1.6%, 17.8% in the second and third quartile (high-risk score group) and 53.5% in the fourth quartile (very high-risk score group). The three risk score groups showed good discrimination for the P/F value at admission, and a positive correlation was found for the low-risk class to P/F at 48 h after admission (adjusted R-squared = 0.48). We developed a predictive model of death for people with SARS-CoV-2 infection by including only easy-to-obtain variables (abnormal blood count, BUN, C-reactive protein, sodium and lower SpO2). It demonstrated good accuracy and high power of discrimination. The simplicity of the model makes the risk prediction applicable for patients in the Emergency Department, or during hospitalization. Although it is reasonable to assume that the model is also applicable in not-hospitalized persons, only appropriate studies can assess the accuracy of the model also for persons at home.

No abstract

of R-mini CHP therapy, in which R-mini CHOP was modified as cyclophosphamide was escalated to 500 mg/m 2 instead of vincristine omission (375 mg/m 2 /day rituximab, 25 mg/m 2 /day doxorubicin, 500 mg/m 2 /day cyclophosphamide, 40 mg/m 2 /day prednisolone). Primary endpoint was the 2-year PFS rate. Secondary endpoints were the 2-year OS, the response rate (CRR and ORR) and adverse events (AEs). Survival results were analyzed on an ITT basis. This study was registered with UMIN-CTR [www.umin.ac.jp/ctr/], identification number UMIN000011234. Results: Forty-four patients were enrolled between May 2013 and October 2016 from 13 centres of the National Hospital Organization (NHO) in Japan, and 43 patients (16 males, 27 females) were included in the ITT analysis. The median age was 84 years (range 80-92). Twenty-five patients (58%) had stage III/IV. LDH level was elevated in 27 patients (63%). Thirty-four patients (79.0%) had ECOG PS scores ≥1: 13 (30%) of score 0, 21 of (49%) of score 1, and 9 of (21%) of score 2. Eight (19%), 12 (28%), and 19 (44%) and 4 patients (9%) had low, low/intermediate, high/intermediate, and high risk according to IPI risk stratification, respectively. Among 43 patients, 35 (81%) completed 6 cycles. The reasons of discontinuation were 2 PDs, 3 AEs, 2 withdrawals of consent, and 1 sudden death. The dose intensity of all patients was maintained at 100% for both doxorubicin and cyclophosphamide throughout the cycles. Twenty-two (63%) of 35 patients who completed 6 cycles received at least one injection of G-CSF. The ORR and CRR were 95.3% and 84%, respectively. At the cut-off date (October 2018), the median follow-up time was 29 months. The 2-year PFS and OS were 64.0% [95% CI: 50.3-74.8%] and 71.1% [95% CI: 57.7-81.0%], respectively. Among 37 cases of AEs of any grade reported throughout the treatment period, 19 were Grade 3 or higher. Hematologic toxicity was the most common AE but was generally mild. Grade 3/4 neutropenia was observed in one patient besides febrile neutropenia (FN) and no cases of grade 3-4 thrombocytopenia were reported. Among 227 treatment cycles, 4 episodes of FN (1.8%) were noted in 3 patients. One died during the treatment due to sudden death. Additionally, 4 grade 3 infections, 2 grade 3 thromboembolic events, and 2 grade 3 hyperglycaemias were observed. Peripheral neuropathy was not observed in all patients. Fifteen patients (35%) died during follow-up periods due to lymphoma (n = 12) and other causes (n = 3). Summary/Conclusion: Vincristine-omitted R-mini CHP is a promising chemotherapy regimen that is not associated with peripheral neuropathy, and has a good efficacy and safety in DLBCL patients older than 80 years old.