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Crew et al solve a long-standing enigma in red cell biology and transfusion medicine, namely the molecular and genetic elucidation of the Er blood group antigens. Through analysis of alloantibody data and whole exome sequencing, the authors localize these antigens to the mechanosensory protein PEIZO1. Furthermore, they report that antibodies directed against 2 novel, highly prevalent Er antigens are associated with severe hemolytic disease of the fetus and newborn.


Doreille and colleagues describe 4 cases of thrombotic microangiopathy that illustrate how incorporating fast genomic explorations may transform the diagnostic workup and therapeutic approach for patients presenting with these syndromes. The authors also discuss some of the common practical issues and dilemmas which may arise when implementing such strategies.


de Botton and colleagues report on results of a randomized phase 3 study evaluating the benefit of the IDH2-targeted therapy enasidenib vs conventional therapies in relapsed IDH2-mutated acute myeloid leukemia (AML). Compared with conventional care, this open-label study demonstrates clinically important improvements in multiple secondary endpoints (event-free survival, response rates, transfusion independent) with enasidenib. However, no survival benefit is evident, likely reflecting confounding factors related to design and salvage therapies.

Dampier et al report on a large, randomized phase 3 clinical trial that compares the efficacy and safety of intravenous rivipansel, an E-Selectin antagonist, vs placebo in 345 adults and children admitted to the hospital for vaso-occlusive crises. The primary results show no significant reductions in duration of hospitalization or opioid use, while post-hoc analyses focusing on early use of rivipansel suggest some reductions in both.


The clinical picture of cutaneous T-cell lymphoma (CTCL) is characterized by erythematous, eczematous, and papulosquamous skin changes, clinically and histologically similar to other inflammatory skin diseases. Gluud et al demonstrate that malignant T cells in CTCL secrete IL-13, IL-22, and oncostatin M to induce JAK-STAT signaling in surrounding keratinocytes, downregulating filaggrin expression, and impairing skin barrier function to promote inflammation. Blockade of these cytokines reverses these changes in human skin models and supports such therapeutic approaches in these diseases.


To explore the connections between dietary iron and sickle cell disease (SCD) pathogenesis, Li and colleagues placed mice with SCD on an iron-restricted diet for 3-4 months and found a significant reduction in serum iron, tissue iron, and white blood cell iron levels without worsening anemia in these subjects. This intervention protects mice from major vascular complications and organ failure caused by vaso-occlusive disease and hemolysis and is potentially mediated by gut microbiota-host crosstalk. The restriction of dietary iron warrants investigation in iron-overloaded patients with SCD.


COVID-19 still represents a major issue for patients with lymphoid malignancies, especially those on therapy, because of immune suppression and suboptimal responses to vaccination. Davis et al report on their experience with double dose tixagevimab-cilgavimab preexposure prophylaxis in a cohort of 251 patients with chronic lymphocytic leukemia, B-cell lymphomas, multiple myeloma, or B-cell acute lymphoblastic leukemia, 63% of whom had received 3 doses of the SARS-CoV-2 vaccine. Breakthrough infections within 3 months occur despite passive immunization, affecting 11% in this series; however, hospitalization rates are low, and mortality was avoided, suggesting benefit from this strategy.


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