Issue Archive

Myelodysplastic syndromes (MDS) are heterogeneous clonal disorders with variable manifestations and outcomes. In this Special Report by Zeidan and colleagues, an international group of MDS experts propose revised criteria for the assessment of response to inform clinical investigation and practice. These updated response criteria should allow better assessment of clinical trial results in an era of emerging novel therapeutics.

Viral infection remains a serious cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Using a series of 5 illustrative cases, Dadwal and colleagues discuss preventative and preemptive therapy for the management of viral infections in patients undergoing HSCT.

Adolescents and young adults with relapsed and refractory (R/R) classical Hodgkin lymphoma (cHL) have poor outcomes. Harker-Murray and colleagues report on the results of response-adapted therapy with nivolumab and brentuximab vedotin with or without bendamustine in 43 patients with R/R cHL in the Checkmate 744 trial. With response-adapted therapy, 94% of patients achieved complete metabolic response and underwent autologous transplant. With short follow-up, 1-year progression-free survival was 91%, suggesting an approach that adjusts chemotherapy exposure to minimize toxicity with early excellent survival.

Li and colleagues report on a novel gene-therapy approach to sickle cell disease. Rather than ex vivo manipulation with lentiviral gene addition or CRISPR/Cas9-mediated fetal hemoglobin reactivation, the authors describe injection of a nonintegrating prime editor–expressing vector into a sickle mouse model with correction of over 40% of hemoglobin S alleles in vivo. Though several features need to be optimized, this technique offers a potential for gene-therapy delivery in resource-poor settings.

Gutierrez-Rodrigues et al report on the development of a machine-learning model to distinguish inherited bone marrow failure syndromes from acquired aplastic anemia. The model performed well on a well-defined cohort of patients and is confirmed in an independent cohort with 89% accuracy in predicting inherited vs immune cases. The most important clinical variable in the score is telomere length. The authors have provided a link to an online tool to make the analysis available for practitioners.

Stetka and colleagues elucidate a major role for iron trafficking in determining the red cell and platelet mass in polycythemia vera (PV). In JAK2-V617F mutant mice, PV phenotype mice were iron deficient, whereas those with essential thrombocythemia were not. PV phenotype mice increased their red cells in response to parenteral iron. Impeding iron availability with a ferroportin inhibitor or a minihepcidin normalized red cell mass, suggesting a novel therapy for controlling red cell mass in PV.

Serologically negative RhD (D^–) individuals in Asia are predominantly of the RhDEL phenotype, a polymorphism that leads to heterogeneous protein expression including a small amount of full-length RhD insufficient to agglutinate red cells in vitro. These patients have traditionally received D^– blood, stressing the blood supply. In a prospective clinical trial of D⁺ transfusion in 42 patients with RhDEL, Ji and colleagues demonstrated that none of these patients developed antibodies. In a retrospective study of over 4000 serologically D^– patients, alloanti-D was found only in true D^– individuals and in no patients with RhDEL, strongly suggesting that these individuals can be transfused with D⁺ blood.