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BLOOD COMMENTARIES

REVIEW ARTICLE

Moliterno and colleagues review the clinical burden of thrombosis in Philadelphia chromosome–negative myeloproliferative neoplasms. They focus on the contribution of clonal hematopoiesis, JAK2V617F burden, and inflammation to the risk of thrombosis, and they discuss strategies for prevention of thrombotic events.

CLINICAL TRIALS AND OBSERVATIONS

Corticosteroids have been part of the treatment backbone for multiple myeloma for decades. In a phase 2 trial, Dimopoulos et al demonstrated that in heavily treated patients with relapsed/refractory myeloma, the addition of dexamethasone to isatuximab monotherapy improves and deepens responses.

IMMUNOBIOLOGY AND IMMUNOTHERAPY

LYMPHOID NEOPLASIA

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.

MYELOID NEOPLASIA

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.

RED CELLS, IRON, AND ERYTHROPOIESIS

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.

THROMBOSIS AND HEMOSTASIS

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.

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.

TRANSPLANTATION

Endocannabinoids are arachidonic acid–containing bioactive lipids that have wide-ranging interactions with G protein–coupled receptors. The authors investigated the role of the type 2 cannabinoid receptor (CB2R) in modulating T-cell activation in the setting of murine graft-versus-host disease (GVHD). Targeting CB2R with tetrahydrocannabinol mitigates acute GVHD, suggesting that targeting this pathway may offer a novel approach to treating GVHD.

LETTERS TO BLOOD

BLOOD WORK

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