Circulating tumor DNA (ctDNA) levels can help predict outcomes in diffuse large B-cell lymphoma (DLBCL), but its integration with DLBCL molecular clusters remains unexplored. Using the LymphGen tool in 77 DLBCL cases with both ctDNA and tissue biopsy, a 95.8% concordance rate in molecular cluster assignment was observed, showing the reproducibility of molecular clustering on ctDNA. A multicenter, prospective cohort of 166 patients with newly diagnosed DLBCL was analyzed for ctDNA levels and molecular clusters using cancer personalized profiling by deep sequencing. Patients with ctDNA levels of <2.5 log10 haploid genome equivalents (hGE)/mL had a 4-year progression-free survival (PFS) and overall survival (OS) of 71.7% and 85.7%, respectively, compared with 50.3% and 61.0% for those with higher ctDNA levels (P = .0018 and P = .0017). Recursive partitioning showed that patients with ctDNA levels of ≥2.5 log10 hGE/mL were further stratified by clusters ST2/BN2. In this group, ST2/BN2 patients associated with a favorable outcome with a 4-year PFS and OS of 87.5% and 100%, respectively, compared to 38.0% and 47.1% for other clusters (P = .003 and P = .001). Combining ctDNA levels and ST2/BN2 clusters improved outcome prediction. Low-risk patients (n = 51), characterized by ctDNA levels of <2.5 log10 hGE/mL and/or BN2/ST2 cluster, had a 4-year PFS and OS of 75.3% and 87.8%, respectively. High-risk patients (n = 115), with ctDNA levels of ≥2.5 log10 hGE/mL and no BN2/ST2 cluster, had a 4-year PFS and OS of 38.0% and 47.1%, respectively. Adding cluster assignment to ctDNA levels improved the model’s C statistics (0.63 vs 0.59 for PFS; 0.68 vs 0.63 for OS). Liquid biopsy thus provides a multilayered approach for outcome prediction in DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) worldwide. Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes. Prognosis of R/R DLBCL patients is poor, particularly for those eligible neither for chimeric antigen receptor (CAR) T-cell therapy nor autologous stem cell transplantation (ASCT), representing a significant unmet clinical need. The advent of bispecific monoclonal antibodies (BsAbs), such as bispecific T-cell engagers (BiTEs), dual affinity retargeting (DART) molecules and IgG-like bispecific antibodies, offers a novel promising therapeutic approach in the treatment of DLBCL, both as frontline treatment and in the R/R setting. BsAbs simultaneously engage two different antigens, a tumor-associated antigen and an immune cell antigen, redirecting T-cells against malignant cells and enhancing the immune response. Most BsAbs developed for the treatment of NHLs engage T-cells via CD3 and malignant B-cells via CD20, a surface antigen expressed on most lymphomatous cells. Engagement of malignant B-cells by BsAbs activates T-cells, leading to the release of multiple cytokines and potentially to two characteristic adverse events: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The most extensively studied BsAbs, in both the frontline and relapsed/refractory (R/R) settings, include epcoritamab, glofitamab, mosunetuzumab, and odronextamab. Epcoritamab and glofitamab have received FDA and EMA approval for R/R DLBCL after two or more systemic line of therapies. EMA has also approved glofitamab in combination with gemcitabine and oxaliplatin (GemOx) for patients with R/R DLBCL ineligible for ASCT, whereas this indication has not been approved by FDA. Odronextamab is approved by EMA for R/R DLBCL and FL in patients who have received at least two prior lines of therapy, but it has not been approved by FDA. Mosunetuzumab is approved by both agencies—but only for R/R follicular lymphoma (FL). BsAbs represent a breakthrough therapy in the treatment of DLBCL, especially in R/R diseases. The purpose of this article is to review the landscape of BsAbs in DLBCL.

Background: Jaundice and hyperbilirubinemia are common clinical problems characterized by the presence of bile pigments in the blood and their deposition in body tissues. This clinical condition can be associated with a broad spectrum of potential benign and malignant causes, including hepatic inflammation, biliary obstruction, impaired bilirubin conjugation and bilirubin overproduction Therefore, the hyperbilirubinemia diagnostic work-up sometimes can be highly challenging and its therapeutic management can require a multidisciplinary approach. Case Report: We report on a unique case of life-threatening jaundice and hepatic failure in a 20-year-old female who presented to the emergency room with complaints of fever, constant left abdominal pain and generalized profuse fatigue. A complete and detailed medical history, multiple tests for various infection, radiologic investigations and histological tests were performed in order to clarify the etiology of that rapidly progressive clinical condition. Based on the results, the patient jaundice was caused by an Epstein-Barr virus (EBV) infection and secondary cold agglutinin syndrome. Given the rare and complex diagnosis, multiple clinical specialists were asked to carry out the best patient management. Conclusion: This rare case highlights how challenging the differential diagnosis and treatment of hyperbilirubinemia can be, presenting a unique case of life-threatening multifactorial hepatic failure treated successfully with rituximab.

Managing immune thrombocytopenia (ITP) in HIV patients remains challenging due to refractory cases and treatment limitations. This report highlights fostamatinib as a safe, effective, and antiretroviral therapy‐compatible option, offering durable platelet stabilization in a difficult‐to‐treat population.

1. 1.1. Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, extramedullary hematopoiesis, splenomegaly, cytopenias, and debilitating system...

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