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BLOOD COMMENTARIES

PLENARY PAPER

HOW I TREAT

A very common challenge in managing patients with primary immune thrombocytopenia (ITP) is what to do after initial corticosteroid therapy has not fully resolved the clinical problem and further therapy is indicated. Ghanima et al outline their approaches to this problem in a practical companion to recently published guidelines.

CLINICAL TRIALS AND OBSERVATIONS

The prothrombin time–based international normalized ratio (PT-INR) is the benchmark for warfarin therapy monitoring, but is it the best way to monitor anticoagulation with this drug? Oskarsdottir and colleagues propose a new test that is insensitive to changes in factor VII but also reflective of the changes in factors II and X, which determine the antithrombotic effect. In a retrospective observational study, use of the Fiix-normalized ratio test appears to offer advantages over the PT-INR, with reductions in thromboembolic events, frequency of testing, and dose adjustments, without an increase in major bleeding.

HEMATOPOIESIS AND STEM CELLS

IMMUNOBIOLOGY AND IMMUNOTHERAPY

Gallego et al analyzed in detail the impact of a gain-of-function mutation of CXCR4 responsible for the WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis) on dendritic cells (DCs) in humans and mice. They show that patients with WHIM syndrome exhibit quantitative defects in circulating plasmacytoid DCs but not conventional DCs and that this is due to reduced plasmacytoid DC egress from the marrow rather than related to defects in differentiation or function.

LYMPHOID NEOPLASIA

Mato et al report the results of an open-label multicenter phase 2 study of the phosphoinositide 3-kinase (PI3K) inhibitor umbralisib in patients with chronic lymphocytic leukemia (CLL) intolerant of prior Bruton tyrosine kinase or other PI3K inhibitors. They note a median progression-free survival of approximately 2 years and a tolerable toxicity profile, suggesting that this is an effective strategy for this subgroup of patients.

MYELOID NEOPLASIA

While isocitrate dehydrogenase (IDH) mutations are not considered to define a distinct subclass of acute myeloid leukemia (AML), selective IDH inhibitors are now in phase 3 trials in combination with intensive chemotherapy (IC). Using a large prospectively studied cohort of newly diagnosed patients with IDH-mutated AML treated with IC, Duchmann and colleagues investigated associations between other concurrent mutations and prognosis. Their data, presented in this month's CME article, suggest that concurrent NPM1 mutation is a favorable prognostic factor and that allogeneic transplantation improves disease-free and overall survival for patients with accepted unfavorable genetic characteristics.

THROMBOSIS AND HEMOSTASIS

Dimitrios Giannis,Steven L. Allen,James Tsang,Sarah Flint,Tamir Pinhasov,Stephanie Williams,Gary Tan,Richa Thakur,Christian Leung,Matthew Snyder,Chirag Bhatia,David Garrett,Christina Cotte,Shelby Isaacs,Emma Gugerty,Anne Davidson,Galina S. Marder,Austin Schnitzer,Bradley Goldberg,Thomas McGinn,Karina W. Davidson,Matthew A. Barish,Michael Qiu,Meng Zhang,Mark Goldin,Miltiadis Matsagkas,Eleni Arnaoutoglou,Alex C. Spyropoulos,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium,on behalf of the Northwell COVID-19 Research Consortium

In this prospective registry study of approximately 5000 patients, Giannis et al investigated associations between a range of comorbid conditions and postdischarge thrombotic events in patients hospitalized with COVID-19. They report that prophylactic-dose anticoagulation following discharge may be beneficial, with 46% fewer major thrombotic events or deaths observed in the cohort selected to receive this therapy.

LETTER TO BLOOD

BLOOD WORK

ERRATA

CONTINUING MEDICAL EDUCATION (CME) QUESTIONS

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