In this week's episode, Blood editor Dr. James Griffin interviews Drs. George Goshua, Gerd Blobel, and Paul Kaminski on their latest articles published in Blood. Dr. Goshua elaborates on the background and then insights from "Haploidentical transplant, gene therapy, and standard care in sickle cell disease: a cost-effectiveness analysis". This analysis provides valuable guidance for clinicians, patients, and health systems as they consider treatment choices. However, as concluded in the accompanying Blood Commentary, the true measure of success is not which therapy “wins” the economic argument, but whether each patient receives the therapy best suited to their clinical needs and values. Then, Drs. Gerd Blobel and Paul Kaminski share "Dissecting polycomb complexes for enhanced fetal hemoglobin production", which utilizes a comprehensive CRISPR-based screen to interrogate the components of these repressive complexes and identified a single protein domain in EZH2, a subunit of PRC2, as a potential therapeutic target. They demonstrate that inhibition of the domain encoded by exon 14 of EZH2 selectively derepresses fetal hemoglobin expression, raising the possibility of developing drugs that specifically target this domain to treat hemoglobinopathies.

In this week's episode, Blood editor Dr. Laura Michaelis interviews Drs. Matthew Frank and Jieqing Zhu on their latest articles published in volume 147 issue 22 of Blood. Dr. Frank discusses "How I treat HLH-like toxicities after immune effector cell therapy", in which the two cases presented emphasize the need for early identification, the use of anticytokine therapy with either emapalumab or ruxolitinib when organ toxicities worsen despite conventional CRS-directed treatment, and the need for ancillary supportive care as central to success. Dr. Zhu shares insights from "Structural Basis of HPA-1 a Alloimmunization in FNAIT and Allosteric Regulation of Integrin Conformation" where they probed the structure-function relationships underpinning interactions of alloantibodies against the most common target, human platelet antigen 1a (HPA-1a). Their data can help explain why some alloantibodies cause severe hemorrhagic FNAIT while others result in milder, asymptomatic thrombocytopenia.

In this week's episode, Blood editor Dr. Laura Michaelis interviews Drs. Pierre-Yves Dumas and Samik Basu on their latest articles published in Blood. Dr. Dumas talks about "Prognostic impact of FLT3-ITD microclones in young adults with acute myeloid leukemia treated with intensive chemotherapy" where the team was able to identify that ultra-low-burden FLT3-ITD microclones are associated with higher relapse risk and inferior relapse-free survival. Their work encourages the evaluation of FLT3 inhibitor strategies. Dr. Basu discusses "CD19 CAR T-cell therapy is feasible for patients with pemphigus vulgaris treated without lymphodepletion in the RESET-PV trial". In four patients, the treatment was well tolerated and supported CAR T-cell expansion and persistence, challenging the need for lymphodepletion and supporting chemotherapy-free approaches in autoimmune disease.