In this week's episode, we'll hear about a “belt and suspenders” approach to paroxysmal nocturnal hemoglobinuria, or PNH. We’ll review long-term efficacy data for danicopan—an oral complement factor D inhibitor recently approved as an add-on to C5 inhibitor therapy.
After that: researchers show how oral pathogens may exacerbate chronic graft-versus-host disease. And they assess targeted interventions to mitigate these effects. Finally, we move from the oral to the gut microbiome. New findings suggest that intestinal dysbiosis, induced by antibiotics, may adversely affect outcomes among patients who are receiving CAR-T cell therapy.

Featured Articles:

• Long-term efficacy and safety of danicopan as add-on therapy to ravulizumab or eculizumab in PNH with significant EVH
• Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease
• Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy

In this week's episode we’ll find out about longer term results from a pivotal trial of mosunetuzumab in relapsed/refractory follicular lymphoma, potential use of CD70 CAR T-cells that secrete an anti-CD33/anti-CD3 bispecific antibody as a therapy for acute myeloid leukemia, and how ferroptosis regulates hemolysis in stored red blood cells.

Featured Articles:

• Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥2 prior therapies
• CD70 CAR T cells secreting an anti-CD33/anti-CD3 dual-targeting antibody overcome antigen heterogeneity in AML
• Ferroptosis regulates hemolysis in stored murine and human red blood cells

In this Review Series episode on Basic/Translational Science of Factor VIII, Factor IX, and von Willebrand Factor introduced by Dr. Thomas Ortel, we’ll hear from contributing authors Drs. Ben Samuelson Jones, Mac Monroe and Peter Lenting as they discuss how the functional roles of these 3 proteins are interconnected.

Click here to view the complete Review Series featured in Volume 144 Issue 21 of Blood.

In this week's episode we'll learn about asciminib plus dasatinib in Philadelphia chromosome-positive acute leukemia. In a phase 1 study, combining two tyrosine kinase inhibitors with distinct mechanisms of action had encouraging activity in patients with de novo disease. After that: new research demonstrates that the iron exporter ferroportin contributes to the iron-sensing properties of liver endothelial cells. But is it the primary mediator of systemic iron homeostasis? Finally: anemia in pregnant patients with beta-thalassemia minor. In the third trimester, about one-third of patients have hemoglobin levels of 9 grams per deciliter or lower. This report may help to guide the appropriate diagnosis of anemia while limiting unnecessary testing and interventions. 

Featured Articles:

• Asciminib plus dasatinib and prednisone for Philadelphia chromosome–positive acute leukemia
• The hepcidin-ferroportin axis modulates liver endothelial cell BMP expression to influence iron homeostasis in mice
• β-Thalassemia minor is associated with high rates of worsening anemia in pregnancy

In this week's episode we’ll learn more about a phase 2 trial of first-line zanubrutinib, obinutuzumab, and venetoclax in TP53-mutated mantle cell lymphoma; early development of hyperdiploidy in multiple myeloma; and a phase 1 trial of the asparaginase pegcrisantaspase plus venetoclax in relapsed/refractory acute myeloid leukemia.

Featured Articles:

• Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation
• Development of hyperdiploidy starts at an early age and takes a decade to complete
• A phase 1 study of the amino acid modulator pegcrisantaspase and venetoclax for relapsed or refractory acute myeloid leukemia

In this week's episode we'll learn about C3-targeted therapy in autoimmune hemolytic anemias. Based on results of an open-label, phase 2 study, pegcetacoplan was well-tolerated, with encouraging efficacy, particularly in patients with cold agglutinin disease. After that: Venetoclax sensitivity testing to predict AML response. In a significant step toward precision medicine, researchers have validated an assay capable of predicting response to the venetoclax-azacitidine regimen. Finally, an improved basic understanding of human coagulation factor XIII. Investigators present the cryo-electron microscopy structure of Factor XIII complex, providing new insights into etiology and the deleterious effects of certain specific mutations.

Featured Articles:

• Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia
• Ex vivo venetoclax sensitivity predicts clinical response in acute myeloid leukemia in the prospective VenEx trial
• Cryo-EM structure of the human native plasma coagulation factor XIII complex

In this Review Series episode on Globin Disorders introduced by Drs. Thomas Coates and Irene Roberts, we’ll hear from Dr. Douglas Higgs and Dr. Mitchell Weiss as they address advances in our understanding of globin gene biology.

Click here to view the complete Review Series featured in Volume 144 Issue 8 of Blood.

In this week's episode we’ll learn more about an experimental regimen for classical Hodgkin lymphoma that combines brentuximab vedotin, nivolumab, and chemotherapy; a possible role for type 1 interferon signaling in developing autoantibodies to red blood cells in sickle cell disease; and how genomic alterations affecting class I human leukocyte antigen molecules may affect patients with cutaneous T-cell lymphoma. 

Featured Articles:

• Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma
• IFN-I promotes T-cell–independent immunity and RBC autoantibodies via modulation of B-1 cell subsets in murine SCD
• Genetic alteration of class I HLA in cutaneous T-cell lymphoma

In this week's episode we'll learn about the role of iron in myelodysplastic syndromes, or MDS. After that: long-term treatment outcomes in immune thrombocytopenia from the STOPAGO study.  Finally, new insights into APL treatment outcomes and prognostic factors from the large-scale Harmony APL project which used ATRA-Arsenic combination therapy.

Featured Articles:

• Genetic iron overload aggravates, and pharmacological iron restriction improves, MDS pathophysiology in a preclinical study
• Long-term follow-up of the STOPAGO study
• Acute promyelocytic leukemia: long-term outcomes from the HARMONY project

In this week's episode, we’ll learn about the prevalence and impact of dexamethasone dose reductions during triple or quadruple therapy for newly diagnosed multiple myeloma, a conditional knockout mouse model for testing gene therapy in X-linked sideroblastic anemia, and real-world efficacy and safety of ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma.

Featured Articles:

• Dexamethasone dose intensity does not impact outcomes in newly diagnosed multiple myeloma: a secondary SWOG analysis
• An erythroid-specific lentiviral vector improves anemia and iron metabolism in a new model of XLSA
• Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma