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This article has a companion Counterpoint by Sanchorawala.

This article has a companion Point by Palladini and Merlini.

The treatment of patients with diffuse large B-cell lymphoma with double expression of MYC and BCL2 has been associated with poor outcomes. Landsburg and colleagues explore the impact of ibrutinib monotherapy with intriguing results that may spur large trials of patients with this challenging disease. 

Outcomes for children with acute lymphoblastic leukemia are generally excellent, one of the most impressive success stories in the treatment of cancer. However, identifying children with more challenging cases early in the process is of high significance. The International BFM Study Group examines and validates one such system, the United Kingdom Copy Number alteration classifier, in a manuscript with great promise to help guide future therapies. 

Patients with myeloproliferative neoplasms (MPNs) have elevated levels of proinflammatory cytokines, which result in some of the constitutional symptoms that these patients experience. Fleischman and colleagues find monocytes from patients with MPNs have defective regulation of Toll-like receptor signaling that leads to unrestrained production of inflammatory cytokines such as tumor necrosis factor that may contribute to the pathogenesis of these disorders. 

Following inflammatory responses, a series of events leads to mobilization of neutrophils that adhere to P-selectin on the apical membranes of endothelial cells. The McEver laboratory finds the neutrophil-produced oncostatin M plays a critical role in this process, establishing a paracrine signaling mechanism between neutrophils and endothelial cells that influences endothelial-cell function.

The clinical management of major bleeding episodes in patients being treated with a factor Xa inhibitor can be challenging. In a systematic review, Piran et al evaluate the role of prothrombin complex concentrates. Their comprehensive meta-analysis addresses the question of whether direct factor Xa inhibitor cessation plus prothrombin complexes or cessation alone should be the standard for the treatment of patients with major bleeding events.

The treatment of steroid refractory acute graft-versus-host disease has been a significant clinical challenge. There have been relatively few randomized clinical trials comparing different treatment options. One such approach was the use of inolimomab (an anti-CD25 monoclonal antibody that blocks interleukin-2 signaling) that was compared to antithymocyte globulin in the INO107 phase 3 trial. Socié and colleagues report on the long-term follow-up of patients treated on this trial.