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Table of Contents

BLOOD COMMENTARIES

REVIEW ARTICLE

Kaiser and colleagues provide a state-of-the-art review of the complex role of platelets in maintaining vascular integrity. The authors describe the processes by which platelets are recruited to the vessel wall, how they prevent hemorrhage, where they facilitate clot formation, and how the processes differ in the setting of inflammatory stresses, where platelets can function as single cells to protect vascular integrity without clot formation.

HOW I TREAT

Amengual and Pro present their approach to posttransplant lymphoproliferative disease (PTLD), complicating solid organ transplant and hematopoietic cell transplant. Using 3 illustrative cases, the authors discuss the heterogeneity of PTLD and their approach to treatment using risk-adapted strategies. These strategies include reduction of immunosuppression, immunotherapy, and chemotherapy.

CLINICAL TRIALS AND OBSERVATIONS

Gini et al report on the results of a phase 2 study of rituximab and lenalidomide in 65 frail patients over 70 years of age with diffuse large B-cell lymphoma (DLBCL). Use of this chemotherapy-free combination yielded an overall response rate of 50.8% with 27.7% of patients achieving complete remission. Median progression-free survival was 14 months, and duration of response was 64% at 2 years. Toxicity of grade ≥ 3 occurred in 34 of 65 patients. This chemotherapy-free combination has significant activity and merits further study.

HEMATOPOIESIS AND STEM CELLS

Subramanian and colleagues report on a map of genome-wide chromatin contacts of canonical transcription factor complexes that elucidates the determinants of cell-type–specific gene expression and maturation. This represents a valuable resource database for analysis of the regulatory networks of normal hematopoietic stem cell maturation and their disruption in leukemic cells.

IMMUNOBIOLOGY AND IMMUNOTHERAPY

Acute lung injury (ALI) involves a complex interaction of platelets and neutrophils to promote thrombo-inflammation. Burkard et al further elucidate the pathophysiology by examining the mechanism of neutrophil recruitment to the lung and neutrophil extracellular trap (NET) formation. Inhibition of glycoprotein VI (GPVI) through genetic knockout or antibody treatment reduced neutrophil recruitment, neutrophil activation, and NET formation, suggesting a possible strategy to reduce acute inflammation leading to ALI.

LYMPHOID NEOPLASIA

Gelebart et al report on the identification and expression of a novel AXL isoform, AXL3, that is constitutively active in mantle cell lymphoma (MCL) cells. Knockdown of AXL3 caused apoptosis in MCL cell lines, as did pharmacological inhibition in primary MCL cells in vitro and mouse xenografts in vivo, suggesting a novel therapeutic target for treating MCL.

LETTER TO BLOOD

BLOOD WORK

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