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EDITORIAL

Edited by Christian Steidl and Associate Editor Freda K. Stevenson, this Review Series provides state-of-the-art summaries on 4 integrated topics highlighting the importance of understanding the interactions between lymphoma cells and their tumor microenvironment. The emphasis is on follicular and diffuse large B-cell lymphomas, but the paradigms are relevant across the spectrum of B-cell lymphomas.

BLOOD COMMENTARIES

REVIEW SERIES

Edited by Christian Steidl and Associate Editor Freda K. Stevenson, this Review Series provides state-of-the-art summaries on 4 integrated topics highlighting the importance of understanding the interactions between lymphoma cells and their tumor microenvironment. The emphasis is on follicular and diffuse large B-cell lymphomas, but the paradigms are relevant across the spectrum of B-cell lymphomas.

Edited by Christian Steidl and Associate Editor Freda K. Stevenson, this Review Series provides state-of-the-art summaries on 4 integrated topics highlighting the importance of understanding the interactions between lymphoma cells and their tumor microenvironment. The emphasis is on follicular and diffuse large B-cell lymphomas, but the paradigms are relevant across the spectrum of B-cell lymphomas.

Edited by Christian Steidl and Associate Editor Freda K. Stevenson, this Review Series provides state-of-the-art summaries on 4 integrated topics highlighting the importance of understanding the interactions between lymphoma cells and their tumor microenvironment. The emphasis is on follicular and diffuse large B-cell lymphomas, but the paradigms are relevant across the spectrum of B-cell lymphomas.

Edited by Christian Steidl and Associate Editor Freda K. Stevenson, this Review Series provides state-of-the-art summaries on 4 integrated topics highlighting the importance of understanding the interactions between lymphoma cells and their tumor microenvironment. The emphasis is on follicular and diffuse large B-cell lymphomas, but the paradigms are relevant across the spectrum of B-cell lymphomas.

CLINICAL TRIALS AND OBSERVATIONS

In the first prospective multicenter clinical trial to examine the role of anticomplement therapy with eculizumab in hematopoietic stem cell transplant–associated thrombotic microangiopathy (TMA), Jodele and colleagues demonstrate that high survival rates, 71% at 6 months, are achievable in children and young adults presenting with multiorgan dysfunction. These results are promising given prospectively collected historical control survival rates of 18% at the same time point. Further studies building on this biomarker-informed regimen are required to better understand how to utilize eculizumab, including before major organ dysfunction is manifest.

IMMUNOBIOLOGY AND IMMUNOTHERAPY

Alvarez Calderon and colleagues report on developing a fully human monoclonal antibody that disrupts the interaction between the inhibitory receptor CD161 on blood cancer cells and its ligand, CLEC2D. CD161 blockade enhances natural killer cell and T-cell effector function against malignant B cells, highlighting the potential for targeting CD161 as a novel future immunotherapeutic strategy in hematological malignancies.

MYELOID NEOPLASIA

Baumgartner and colleagues retrospectively analyzed a cohort of 5541 patients with monocytosis using the 2022 revised criteria for the definition of chronic myelomonocytic leukemia (CMML), which now allow diagnosis if the monocyte count exceeds 0.5 x 109/L. The authors demonstrate that patients with monocyte counts between 0.5 and 1.0 x 109/L and newly classified as CMML indeed have survival rates similar to those of patients with monocytosis >1.0 x 109/L but that genomic features suggest different disease trajectories. This work helps clinicians negotiate the new classifications and suggests that genomic patterns may prove more informative than arbitrary cell-count cutoffs.

RED CELLS, IRON, AND ERYTHROPOIESIS

The first- and second-generation C5 inhibitors eculizumab and ravulizumab have revolutionized care for patients with paroxysmal nocturnal hemoglobinuria (PNH). In this month’s CME article, Kelly et al report on the outcomes with C5 inhibition over 20 years, providing a benchmark for advice to patients about the effectiveness and safety of this treatment. Patients with PNH without bone marrow failure (BMF) had near-normal life expectancy, whereas those with BMF had significantly inferior survival to age- and sex-matched controls, highlighting a key subgroup of patients with high unmet needs in 2024.

THROMBOSIS AND HEMOSTASIS

Circulating antiphospholipid antibodies (aPLs) are an important risk factor for the development of thrombosis and pregnancy complications, and while we understand how they cause these clinical diseases, their etiology has been unknown. Müller-Calleja and colleagues reveal that tissue factor (TF) is vital for the development of autoantibodies against phospholipids in murine models. The authors show that pharmacologic inhibition of TF prevents aPL formation, suggesting a potential clinical strategy.

TRANSPLANTATION

Low levels of vitamin A have been associated with the development of gastrointestinal graft-versus-host disease (GVHD). Khandelwal et al report on the results of a randomized, placebo-controlled phase 2 trial in which a single dose of oral vitamin A given to children prior to conditioning resulted in no improvement in the incidence of acute GVHD compared to placebo but was associated with lower rates of chronic GVHD.

LETTER TO BLOOD

BLOOD WORK

CONTINUING MEDICAL EDUCATION (CME) QUESTIONS

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