Issue Archive

As B cells mature to plasma cells, they lose expression of the B-cell antigen receptor and become dependent on interactions with the microenvironment to sustain survival. In a Blood Spotlight, Ren et al review the central role of plasma cell syndecan-1 (CD138) and other stromal heparan sulfate-proteoglycans in the marrow microenvironment in supporting both normal and malignant cells, and they discuss how this pathway can be targeted for potential therapy for multiple myeloma.

Krabbe disease is a rare neurodegenerative glycogen storage disease, 80% of which presents in infancy (age 0 to 6 months). The only effective therapy is hematopoietic stem cell transplantation (HSCT), which is most effective when performed early on asymptomatic infants. Yoon et al report on HSCT for patients diagnosed at 6 to 36 months of age, showing again that asymptomatic patients have improved survival and normal or near-normal development; even symptomatic patients derive some benefit.

Dutt et al review the early real-world experience with caplacizumab for the treatment of acute immune-mediated thrombotic thrombocytopenic purpura (TTP) in a multicenter study of 85 patients.

Gray zone lymphomas (GZLs) are B-cell neoplasms with features between those of classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). Sarkozy et al compared the patterns of somatic mutations in Epstein-Barr virus–negative GZL, DLBCL, cHL, and primary mediastinal large B-cell lymphoma (PMBCL). Mediastinal GZL has a distinct profile from GZL outside the mediastinum and displays mutational overlap with cHL and PMBCL, suggesting a common cell of origin.

Langerhans cell histiocytosis (LCH) is a myeloid malignancy comprising a small percentage of malignant dendritic cells embedded in an inflammatory infiltrate. Sengal and colleagues examined the inflammatory milieu, demonstrating a prominent exhausted T-cell infiltrate with high checkpoint receptor expression. Treatment of a mouse model of LCH with a single-agent mitogen-activated protein kinase (MAPK) inhibitor or anti-PD-1 decreased myeloid cells or lymphoid cells, respectively; combined therapy was synergistic in decreasing both populations, suggesting a potential therapeutic strategy for LCH.

Ivosidenib and enasidenib are approved as single agents for relapsed/refractory acute myeloid leukemia (AML) with IDH1 and IDH2 mutations (mIDH1/2), respectively. Stein et al report a phase 1 study evaluating the efficacy and safety of these agents in combination with intensive chemotherapy for first-line therapy for mIDH AML. The therapy is well tolerated, and results are encouraging. A phase 3 trial is ongoing and will inform whether addition of targeted therapy results in superior remission rates and improved survival.

Hermansky-Pudlak syndrome (HPS) is a recessive disorder associated with loss of dense granules in several tissues, including platelets and melanosomes. Yuan and colleagues observed that a novel platelet zinc transporter, transmembrane protein 163 (TMEM163), is reduced in HPS, and that deletion of TMEM163 in mice results in abnormal zinc accumulation and loss of dense granules. These results elucidate a link between zinc homeostasis and platelet granule formation.

Rurioctocog alfa pegol is a recombinant prolonged half-life factor VIII (FVIII) product that provides safe and efficacious prophylaxis targeting a trough FVIII level exceeding 1%. Klamroth et al report that targeting a trough of 8% to 12% provides superior control of bleeding episodes without new safety signals.