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Effective and tolerable treatments are needed for older patients with classical Hodgkin lymphoma. We report results for older patients with classical Hodgkin lymphoma treated in the large phase III ECHELON-1 study of frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Modified progression-free survival per independent review facility for older versus younger patients (aged ≥60 vs.

The tumor microenvironment is the cellular and molecular environment in which the tumor exists and with which it continuously interacts. In B-cell lymphomas, this microenvironment is intriguing in that it plays critical roles in the regulation of tumor cell survival and proliferation, fostering immune escape as well as the development of treatment resistance. The purpose of this review is to summarize the proceedings of the Second Annual Summit on the Immune Microenvironment in Hematologic Malignancies that took place on September 11–12, 2014 in Dublin, Ireland. We provide a timely overview of the composition and biological relevance of the cellular and molecular microenvironment interface and discuss the role of interactions between the microenvironment and neoplastic cells in a variety of B-cell lymphomas. In addition, we focus on various novel therapeutic strategies that target the tumor microenvironment, including agents that modulate B-cell receptor pathways and immune-checkpoints, chimeric antigen receptor T cells and immunomodulatory agents.

High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit lymphoma) have an aggressive clinical course. We investigated the prognostic value of transformation from low-grade lymphoma, cytological features (high grade versus large cell), MYC rearrangement partners (immunoglobulin versus nonimmunoglobulin gene), and treatment. We evaluated 100 adults with double-/triple-hit lymphoma, reviewing cytological features; cell of origin; and rearrangements of MYC, BCL2, and BCL6 using MYC, BCL2, and BCL6 break-apart and IGH/MYC, IGL/MYC, IGK/MYC, and IGH/BCL2 dual-fusion interphase fluorescence in situ hybridization probes. Outcome analysis was restricted to patients with lymphoma, de novo or at transformation, who received anthracycline-based chemotherapy. Among them, 60% had high-grade cytological features; 91% had a germinal center B-cell phenotype, and 60% had a MYC/IG rearrangement. Germinal center B-cell phenotype was associated with BCL2 rearrangements (P

The prevalence, presenting clinical and pathological characteristics, and outcomes for patients with diffuse large B-cell lymphoma that is Epstein-Barr virus positive remain uncertain as does the impact of congenital or iatrogenic immunosuppression. Patients with newly diagnosed diffuse large B-cell lymphoma with available tissue arrays were identified from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource. Patients infected with human immunodeficiency virus or who had undergone a prior organ transplant were excluded. Epstein-Barr virus-associated ribonucleic acid testing was performed on all tissue arrays. A history of significant congenital or iatrogenic immunosuppression was determined for all patients. At enrollment, 16 of the 362 (4.4%) biopsies were positive for Epstein-Barr virus. Thirty-nine (10.8%) patients had a significant history of immunosuppression. Patients with Epstein-Barr-positive diffuse large B-cell lymphoma had no unique clinical characteristics but on pathology exhibited a higher frequency of CD30 positivity (25.0% versus 8.1%, respectively; P

Waldenström’s macroglobulinemia is an indolent, lymphoproliferative disease, characterized by a heterogeneous lymphoplasmacytic bone marrow infiltrate and high immunoglobulin M production. While technological advances over the past several decades have dramatically improved the possibilities of studying the molecular basis of Waldenström’s macroglobulinemia, the pathogenesis of the disease remains fragmented. Undoubtedly, research has been successful in uncovering underlying aberrations and deregulated mechanisms in this disease, providing useful information for identifying biomarkers for disease diagnosis, risk stratification and therapeutic intervention, but there is still a long way to go before the pathogenesis of Waldenström’s macroglobulinemia is fully revealed. In addition, the low number of in vitro or in vivo models significantly challenges extensive analysis. In this manuscript, we review the molecular basis of this disease.

Background Lymphopenia and tumor-associated macrophages are negative prognostic factors for survival in classical Hodgkin’s lymphoma. We, therefore, studied whether the peripheral blood absolute lymphocyte count/absolute monocyte count ratio at diagnosis affects survival in classical Hodgkin’s lymphoma.Design and Methods We studied 476 consecutive patients with classical Hodgkin’s lymphoma followed at the Mayo Clinic from 1974 to 2010. Receiver operating characteristic curves and area under the curve were used to determine cut-off values for the absolute lymphocyte count/absolute monocyte count ratio at diagnosis, while proportional hazards models were used to compare survival based on the absolute lymphocyte count/absolute monocyte count ratio at diagnosis.Results The median follow-up period was 5.6 years (range, 0.1–33.7 years). An absolute lymphocyte count/absolute monocyte count ratio at diagnosis of 1.1 or more was the best cut-off value for survival with an area under the curve of 0.91 (95% confidence interval, 0.86 to 0.96), a sensitivity of 90% (95% confidence interval, 85% to 96%) and specificity of 79% (95% confidence interval, 73% to 88%). Absolute lymphocyte count/absolute monocyte count ratio at diagnosis was an independent prognostic factor for overall survival (hazard ratio, 0.18; 95% confidence interval, 0.08 to 0.38, P