Issue Archive

Refrigerated storage is known to affect the morphology of red cells. In a Plenary Paper, Roussel et al examine the relationship between storage-induced microerythrocytes (SMEs) and transfusion recovery. Using a mouse model, they demonstrate that SMEs after long-term storage are rapidly cleared by the splenic macrophages. Abundance of SMEs is inversely correlated with red cell recovery after transfusion in human volunteers. Quantifying SMEs may allow assessment of the quality of red cell concentrates for transfusion.

While great strides have been achieved in treating hemophilia, the therapy for von Willebrand disease (VWD) has been virtually unchanged over the past 30 years. In a Perspective article, Denis and colleagues discuss the impact of VWD on health and quality of life, as well as potential innovative therapies for improving VWD care.

Le Gouill and colleagues present results of the phase 3 GAINED trial of obinutuzumab vs rituximab in untreated, high-risk, transplant-eligible patients with diffuse large B-cell lymphoma using positron emission tomography (PET)–guided consolidation therapy. Obinutuzumab is not superior to rituximab. PET-guided stratification of further therapy identifies patients who do well with completion of 6 cycles of therapy vs those who benefit from autologous transplantation and others who would benefit from novel intensification approaches.

Chaturvedi et al investigated T-cell profiles in patients with hemophagocytic lymphohistiocytosis (HLH) and sepsis, 2 contrasting cytokine storm syndromes that are often difficult to distinguish. They identified a population of CD38^high/HLA-DR⁺ activated T cells that are abundant in severe HLH and absent in sepsis. Identification of over 7% CD38^high/HLA-DR⁺ activated T cells has excellent predictive value in distinguishing HLH from sepsis and provides an important diagnostic tool.

T-cell lymphoblastic lymphoma (T-LBL) is a malignancy seen primarily in children and adolescents and is morphologically similar to T-cell acute lymphoblastic leukemia (T-ALL). As relapsed T-LBL has a dismal prognosis, Khanam and colleagues sought to define the genomic landscape of T-LBL to identify predictors of relapse. As in T-ALL, NOTCH1 is a driver for T-LBL, and mutated KMT2D is an important negative prognostic marker, providing potential targets for improved therapy.

The progression of multiple myeloma reflects a complex interaction between tumor cells and the bone marrow (BM) microenvironment. Shen and colleagues developed an elegant model of multiple myeloma progression using mouse xenografts and DNA barcoding to track myeloma interaction with the BM microenvironment. Only a subset of myeloma clones can circulate and colonize outside the BM, and RNA sequencing identifies master regulators of this process, identifying potential therapeutic targets.

Zhang et al report that canonical WNT signaling is central to the pathogenesis of sclerodermatous chronic graft-versus-host-disease (sclGVHD). Activation of WNT signaling was documented in gene expression signatures of human sclGVHD lesions, and the WNT inhibitors prevented the development of sclGVHD in mouse models. As the WNT inhibitor pyrvinium is already in clinical use and other WNT inhibitors are in clinical trials for other indications, these studies have important clinical implications.