Issue Archive

In this Blood Spotlight, Sykes et al describe the clinical features and therapy of this rare monoclonal gammopathy and discuss what is known and unknown about its pathophysiology.

Byrd and colleagues report follow-up (median, 41 months) results for a phase 1/2 trial of acalabrutinib treatment for patients with relapsed chronic lymphocytic leukemia. Their data on pharmacodynamics and immune reconstitution complement updated summaries of persistence, safety, and efficacy.

For patients with follicular lymphoma being staged with positron-emission scanning before first-line therapy, the finding of lesions with high avidity often triggers concerns about the presence of transformed disease. This study reports that high avidity is not associated with a high risk of transformation during or following standard therapy.

Six and colleagues report their analyses of long-term hematopoesis in 2 gene therapy trials, enumerating repopulating stem and progenitor cell numbers and deducing their differentiation potential based on clone tracking and novel bioinformatic approaches.

Pillarisetti and colleagues report preclinical validation of the orphan surface receptor GPRC5D as a potential target for T-cell mediated therapy in myeloma. Using cell lines and primary cells, they also provide a comprehensive in vitro and in vivo evaluation of a novel bispecific antibody designed to achieve this.

CD49d positivity in >30% of cells by flow cytometry is a recognized negative prognostic marker in patients with chronic lymphocytic leukemia (CLL). Tissino and colleagues report that in patients with CD49b-negative CLL, the presence of small subclones of CD49b highly expressing cells is sufficient to accord a similarly adverse prognosis with either chemo-immunotherapy or ibrutinib therapy.

Secondary acute myeloid leukemia in patients with myeloproliferative neoplasms is a fraught clinical scenario, requiring new therapeutic options. Saenz et al report mechanisms of adaptive and innate resistance to BET inhibition and how rational combination with a disruptor of β-catenin signaling can avert this, generating encouraging in vivo activity in preclinical models.

Johnston and colleagues demonstrated assembly of heparin-induced thrombocytopenia (HIT) immune complexes along von Willebrand factor (VWF) strings released by injured endothelium. This helps explain arterial thrombosis in HIT and suggests that disruption of platelet factor 4–von Willebrand factor (PF4-VWF) complex formation may provide a new therapeutic approach.

Carestia and colleagues report that mice treated with aspirin have significantly reduced platelet aggregation and neutrophil extracellular trap release during Staphylococcus aureus infection. Furthermore, aspirin reduces intravascular thrombin activity, microvascular occlusion, and organ damage.

Distinguishing between late acute graft-versus-host-disease (GVHD) and chronic GVHD is challenging. Schultz et al report comprehensive immune profiling at day 100 posttransplant and demonstrate how this can distinguish the two, opening avenues for further investigations into their respective biologies.