Issue Archive

Molecular analysis has modified the view of complete remission in acute myeloid leukemia (AML) to include consideration of measurable residual disease. In this Perspective, the authors highlight the complexity of interpreting clonal hematopoiesis to distinguish residual AML from ancestral clones of uncertain significance, new or emerging clones, or donor-derived clones in patients undergoing stem cell transplantation.

Steroid-resistant graft-versus-host disease (GVHD) has a dismal prognosis. Jagasia et al report that, in a phase 2 study of the JAK1/2 inhibitor ruxolitinib to treat 71 patients with steroid-resistant GVHD, over half of patients responded (including 27% of patients with a complete response), leading to markedly improved survival.

POEMS syndrome is a rare plasma cell dyscrasia with variable manifestations. Bender and colleagues used a novel high-throughput sequencing technique to demonstrate that monoclonal λ light-chain clones are detectable in the vast majority of patients with POEMS syndrome and that they show highly restricted VJ region usage that can help define and diagnose the disease.

Using sequencing of over 900 patients with diffuse large B-cell lymphoma (DLBCL), the authors used model clustering of mutations to define DLBCL subtypes that provide important prognostic information.

RAS gene mutations are challenging to target therapeutically. Zambetti et al investigated the role of posttranslational modification in the pathogenesis of N-Ras–mediated transformation. “Knock-in” of a mutation to block palmitoylation of mutant N-Ras abolishes its transforming ability, identifying a potential therapeutic target for NRAS-mutant cancers.

Sparkenbaugh and colleagues demonstrate that inhibition of tissue factor or inhibition of protease-activated receptor 1 (PAR-1), the major receptor for thrombin, reduces microvascular stasis in mouse models of sickle cell disease (SCD). These results suggest that activation of coagulation is a direct contributor to vaso-occlusive crisis in SCD and support a potential trial of anticoagulation to reduce SCD-related crises.

Numerous studies have elucidated risk factors for venous thromboembolism (VTE) and bleeding in hospitalized medical patients, leading to complex algorithms to assess risks and benefits of anticoagulation. From these studies, this systematic review identifies 23 risk factors for VTE and 15 for bleeding that can help inform future, and perhaps better, algorithms for risk assessment.

Baron et al report excellent responses to temozolomide in 21 patients (19 relapsed/refractory) with primary vitreoretinal lymphoma. Treatment is well tolerated, even in elderly patients.