Issue Archive

The use of chimeric antigen receptor (CAR) T cells to treat acute myeloid leukemia (AML) has been hampered by the difficulty of identifying target antigens specific to AML that spare normal hematopoietic stem cells (HSCs), and the availability of monoclonal antibodies that increase T-cell cytotoxicity against AML. In a Plenary Paper, He and colleagues describe the use of a novel selection system to isolate heavy chain–only antibodies, also known as nanobodies, yielding bispecific CAR T cells that selectively target AML cells with limited HSC toxicity.

Klok and Huisman discuss management of bleeding risk in patients with venous thromboembolism through a discussion of 2 relevant cases.

The authors present a 3-year update of a phase 3 trial of brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (A + AVD) for frontline treatment of advanced-stage Hodgkin lymphoma. They confirm that A + AVD provides superior progression-free survival over doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without treatment intensification and avoiding the toxicity of bleomycin.

During sepsis, neutrophils release neutrophil extracellular traps (NETs) composed of DNA, histones, and antimicrobial proteins that sequester pathogens but also damage tissue through toxic degradation products. The authors demonstrate that platelet factor 4 (PF4) binds to, compacts, and prevents degradation of NETs, and that an anti-PF4 antibody modified to block immune activation through its Fc portion improves survival in a murine sepsis model.

Stored red blood cells release microvesicles (RBC-MVs) that are thought to contribute to coagulation. Noubouossie and colleagues demonstrate that RBC-MVs activate factor IX by 2 distinct pathways and may contribute to transfusion-associated complications.

The BCL2 inhibitor venetoclax has complete response rates of up to 50% in chronic lymphocytic leukemia patients, but secondary resistance reflecting acquired mutations in BCL2 can lead to treatment failure. Blombery et al report that an unexpectedly large number of patients carry multiple BCL2 mutations with subclonal variation in their occurrence.