Blood Podcast: Season 2, Episode 23
In this week’s episode, we will review a study demonstrating low rates of response to the Pfizer-BioNTech COVID-19 vaccine among patients with chronic lymphocytic leukemia, review a study looking at associations between post-transplantation cyclophosphamide and cytomegalovirus infection according to donor source, and look at new research indicating that abnormal venous calf muscle pump function in the legs is a risk factor for venous thromboembolism (VTE) and predictor of all-cause mortality.
Aspirin and antiplatelet treatments in cancer
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.
Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia
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.
Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation
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.
Linking the KIR phenotype with STAT3 and TET2 mutations to identify chronic lymphoproliferative disorders of NK cells
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.
von Willebrand factor antigen levels are associated with burden of rare nonsynonymous variants in the VWF gene
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.
