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Accounting for 15% of all lymphomas, Hodgkin lymphoma (HL) is a relatively rare disease but the most common malignancies among young adults. Over the last decades prognosis markedly improved with the refinement of evidence based therapies. Current riskadapted therapies usually consist of polychemotherapies such as ABVD or BEACOPPesc and up to 90% of all patients may be considered cured after adequate first-line treatment. Due to this favorable development recent research focused on reduction of therapeutic intensity and more individualized approaches. Prognosis is worse in relapsed or refractory HL (rrHL), where high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is associated with progression-free survival (PFS) of only 50%. Outcomes tend to be inferior in elderly patients or those ineligible for intensified therapies due to comorbidities. This review delineates the development of current standard approaches in first-line and rrHL treatment and summarizes key findings of recent large scale clinical trials. Innovative approaches including response-guided therapy or implementation of novel agents are covered in a separate article. [ABSTRACT FROM AUTHOR]

Purpose of Review: Hodgkin lymphoma (HL) occurs at two age peaks around 25 and 60 years of age. Due to varying fitness and co-morbidities older patients are a heterogeneous group that has relatively poor treatment outcomes. The evolving therapeutic landscape for older HL is summarized herein., Recent Findings: Due to lack of data from larger trials and approval of novel drugs, first-line treatment of limited-stage HL (i.e. early-stage favourable and unfavourable) remains largely A(B)VD and radiotherapy based. For patients with advanced-stage HL, the anti-CD30 antibody-drug conjugate brentuximab vedotin is approved in combination with AVD chemotherapy (BV-AVD). Due to toxicities such as febrile neutropenia or polyneuropathy and lack of improvement in progression-free and overall survival in the older subgroup, fully concomitant BV-AVD is however not used widely. More recently, promising early data was reported with the combination of nivolumab and AVD (N-AVD) in patients >60 years with advanced-stage HL. Second-line treatment depends on fitness and might include high-dose chemotherapy and autologous stem-cell transplantation for selected patients. For unfit or multiply relapsed patients, anti-PD1 antibodies are the preferred treatment option., Summary: The increasing number of older HL patients constitutes a therapeutic challenge despite recent advances and the increased usage of targeted agents., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Microenvironmental bystander cells are essential for the progression of chronic lymphocytic leukemia (CLL). We have discovered previously that LYN kinase promotes the formation of a microenvironmental niche for CLL. Here we provide mechanistic evidence that LYN regulates the polarization of stromal fibroblasts to support leukemic progression. LYN is overexpressed in fibroblasts of lymph nodes of CLL patients. LYN-deficient stromal cells reduce CLL growth in vivo. LYN-deficient fibroblasts show markedly reduced leukemia feeding capacity in vitro. Multi-omics profiling reveals that LYN regulates the polarization of fibroblasts towards an inflammatory cancer-associated phenotype through modulation of cytokine secretion and extracellular matrix composition. Mechanistically, LYN deletion reduces inflammatory signaling including reduction of c-JUN expression, which in turn augments the expression of Thrombospondin-1, which binds to CD47 thereby impairing CLL viability. Together, our findings suggest that LYN is essential for rewiring fibroblasts towards a leukemia-supportive phenotype., (© 2023. The Author(s).)

History and Clinical Findings: A 53-year-old male presented with massive pruritus, whole-body exanthema, generalized muscle pain, and exercise dyspnoea NYHA II., Findings and Diagnosis: Further hematologic examination lead to diagnosis of myeloid and lymphoid neoplasia with eosinophilia (MLN-EO) with FIPL1L1-PDGFRA fusion gene. An echocardiographic examination revealed a thrombus in the right ventricle. Magnetic resonance imaging (MRI) showed an extensive intracavitary thrombus extending from the apex to the right ventricular outflow tract., Therapy and Course: Oral anticoagulation with phenprocoumon and a targeted therapy with imatinib were initiated. Follow-up at 11- and 23-months revealed diminishing of the thrombus. Further follow-up did not show any complications., Conclusions: In summary, Loeffler's endocarditis caused by a myeloid and lymphoid neoplasm associated with eosinophilia and abnormalities of FIP1L1-PDGFRA rearrangement could be treated successfully with oral anticoagulation therapy and the tyrosine-kinase inhibitor imatinib., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

To evade elimination by the host immune system, tumor cells commonly exploit physiological immune checkpoint pathways, restraining efficient anti-tumor immune cell function. Growing understanding of the complex dialog between tumor cells and their microenvironment contributed to the development of immune checkpoint inhibitors. This innovative strategy has demonstrated paradigm-shifting clinical activity in various malignancies. Antibodies targeting programmed death 1 and cytotoxic T-lymphocyte-associated protein-4 are also being investigated in lymphoid malignancies with varying levels of activity and a favorable toxicity profile. To date, evaluated only in the setting of relapsed or refractory disease, anti-programmed death 1 antibodies such as nivolumab and pembrolizumab show encouraging response rates particularly in classical Hodgkin lymphoma but also in follicular lymphoma and diffuse-large B-cell lymphoma. As the first immune checkpoint inhibitor in lymphoma, nivolumab was approved for the treatment of relapsed or refractory classical Hodgkin lymphoma by the Food and Drug Administration in May 2016. In this review, we assess the role of the pathways involved and potential rationale of checkpoint inhibition in various lymphoid malignancies. In addition to data from current clinical trials, immune-related side effects, potential limitations and future perspectives including promising combinatory approaches with immune checkpoint inhibition are discussed., (Copyright© Ferrata Storti Foundation.)