Blood Podcast: Season 2, Episode 9
In this week’s episode, a study that provides further evidence of poor prognosis in patients with multiple myeloma who have “double hit” mutations targeting TP53, examine the early use of BCR-ABL1 kinetics to predict the likelihood of treatment free remission in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors, and learn more about a direct causative link between IL-18 with arrythmias and myocardial fibrosis in sickle cell cardiomyopathy.
IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias
Patients with sickle cell disease (SCD) are predisposed to cardiomyopathy, and previous reports suggest that interleukin-18 (IL-18) may play a role in cardiac dysfunction. In a mouse model of SCD, the authors demonstrate that IL-18 causes ventricular tachycardia and altered cardiac relaxation; conversely, IL-18 inhibition decreases fibrosis and improves diastolic function. They further demonstrate that in patients with SCD, plasma IL-18 levels correlate with myocardial fibrosis and prolonged QTc, suggesting IL-18 as a novel therapeutic target to protect against SCD-related cardiac disease.
Early BCR-ABL1 kinetics are predictive of subsequent achievement of treatment-free remission in chronic myeloid leukemia
About half of patients with chronic myeloid leukemia with a major molecular response to tyrosine kinase inhibitors (TKIs) can come off therapy with sustained response, but determining who is likely to stay in remission is still not established. Shanmuganathan et al report that the kinetics of response to TKIs are predictive of treatment-free response (TFR). Patients with a halving time of ,9.35 days have an 80% chance of sustained TFR, while a halving time of .21.85 days predicts only 4% long-term TFR.
del(17p) without TP53 mutation confers a poor prognosis in intensively treated newly diagnosed patients with multiple myeloma
Deletion of the short arm of chromosome 17 [del(17p)] is associated with poor prognosis in multiple myeloma, but there is a controversy whether poor outcome is restricted to those with del(17p) who also have a somatic mutation in their residual TP53 gene (“double hit”). In a study of 121 patients with del(17p) compared with 2505 patients without del(17)p, the authors report that although the outcome in the setting of the p53 double hit is the worst, del(17p) alone also confers a negative prognosis.
Local blood coagulation drives cancer cell arrest and brain metastasis in a mouse model
Feinauer et al used in vivo laser scanning microscopy to examine brain microvessels to determine how circulating tumor cells can colonize the brain and cause brain metastases. They demonstrate that tumor cells in the brain microvasculature are immobilized by microthrombi dependent on thrombin generation and recruitment of von Willebrand factor (VWF) and platelets. Further, they show that thrombin inhibition or VWF antibody, but not antiplatelet agents, reduces brain metastasis formation.
Anticoagulant therapy for splanchnic vein thrombosis: a systematic review and meta-analysis
There are no well-established standards for the treatment of splanchnic vein thrombosis (SVT), including whether anticoagulation improves outcomes. The authors performed a meta-analysis of nearly 8000 reported cases of SVT to assess the benefits and complications of anticoagulation. Although confounded by the heterogeneity of the assessed populations, the data suggest that anticoagulation improves recanalization and reduces clot extension without increasing bleeding.
