Issue Archive

Platelets are critical for hemostasis and thrombosis, but recent research highlights their role in many other processes, including inflammation, wound healing, and lymphangiogenesis. Edited by José López, this series focuses on the emerging role of platelets in cancer, influencing tumor growth and metastasis, immune evasion, and tumor angiogenesis. The reviews present the current understanding of mutual cross talk between platelets and tumors, communication mediated by RNA transfer and extracellular vesicles, and the potential of antiplatelet agents for cancer treatment.

Patients with chronic lymphocytic leukemia (CLL) have been previously shown to have poor responses to antibacterial and antiviral vaccines. In a Plenary Paper that is also this month’s CME article, Herishanu and colleagues discuss the outcome of vaccination against COVID-19 in 167 patients with CLL, again demonstrating a significantly impaired vaccine response. The lowest response rates were seen in patients undergoing active treatment, while the highest responses were seen in patients who were in complete remission after therapy; however, even treatment-naïve patients had lower responses than healthy controls. In this series, no responses were achieved in patients treated with anti-CD20 antibodies within 12 months of vaccination.

Relapsed acute myeloid leukemia (AML) after hematopoietic stem cell transplantation has a very poor prognosis. Previous studies have demonstrated that immune checkpoint blockade can increase the graft-versus-leukemia response. Using parallel transcriptomic analysis of bone marrow and immunophenotyping of peripheral blood, Penter et al show that clinical response to ipilimumab is associated with increased CD8⁺ T-cell infiltration and activation associated with increased expression of proinflammatory cytokines.

Large granular lymphocyte (LGL) leukemia arises in either T cells or natural killer (NK) cells. Distinguishing chronic lymphoproliferative disease of NK cells (CLPD-NK) from reactive NK cell expansion is hampered by the absence of a readily identified clonal marker. Pastoret et al used NK receptor phenotyping and next-generation sequencing to divide CLPD-NK from reactive NK expansion, demonstrating that STAT3 and TET2 mutations represent clonal markers in 2 subsets of CLPD-NK. Furthermore, TET2 mutations were found in both NK and myeloid cells, linking CLPD-NK and other myeloid malignancies.

Low-density lipoprotein receptor-related protein–associated protein 1 (LRPAP1) was previously identified by B-cell receptor expression cloning as a frequent autoantigen of mantle cell lymphoma (MCL). Thurner and colleagues analyzed 312 patients from 2 European MCL Network trials. They found that 13% of patients had LRPAP1 autoantibodies and that the presence of these autoantibodies is associated with superior failure-free and overall survival.

Corticosteroids are used to treat the acute complications of chimeric antigen receptor (CAR) T-cell therapy. Strati et al examine the impact of corticosteroids on patient outcomes following CAR T-cell therapy for large B-cell lymphoma. Use of higher doses of steroids is associated with shorter progression-free survival at 10 months and decreased overall survival.

von Willebrand disease (VWD) is phenotypically heterogeneous, and 35% of patients with type 1 VWD have no known pathogenic von Willebrand factor (VWF) gene variant. Sadler et al sequenced the entire genomic VWF locus of 737 patients with type 1 VWD or low VWF levels. They report that an accumulation of rare nonsynonymous variants, both pathogenic and nonpathogenic, contributes to the level of VWF and accounts for 31% of the variance in VWF antigen levels.

The calf muscle pump contributes to venous return from the legs, and reduced calf pump function (rCPF) is linked to chronic venous insufficiency, poor wound healing, and all-cause mortality. Since venous stasis is an established risk factor for venous thromboembolism (VTE), Houghton et al examined the impact of rCPF on thrombotic risk. In a cohort study of 1532 patients, rCPF appears to be a risk factor for VTE and is associated with higher mortality.

Posttransplant cyclophosphamide (PTCy) has supported engraftment and control of graft-versus-host disease (GVHD) in haploidentical transplantation, making haplo-transplantation a viable therapeutic option with an increased donor pool. In an analysis of the CIBMTR database, Goldsmith and colleagues report that PTCy is associated with increased CMV infection that in turn is associated with increased non-relapse mortality.