Issue Archive

Edited by Associate Editor Michael Hallek and Podcast Editor Laurie H. Sehn, this Review Series highlights the biologic features of, clinical phenotype of, and therapeutic approaches to high-risk lymphoid malignancies, namely, lymphomas that exhibit rapid growth, present acutely, and require timely therapy. Although many patients are cured with chemotherapy, a subset of patients have treatment resistance and inferior outcomes. This timely set of state-of-the-art reviews addresses the challenges of defining and treating high-risk patients with lymphoma.

Edited by Associate Editor Michael Hallek and Podcast Editor Laurie H. Sehn, this Review Series highlights the biologic features of, clinical phenotype of, and therapeutic approaches to high-risk lymphoid malignancies, namely, lymphomas that exhibit rapid growth, present acutely, and require timely therapy. Although many patients are cured with chemotherapy, a subset of patients have treatment resistance and inferior outcomes. This timely set of state-of-the-art reviews addresses the challenges of defining and treating high-risk patients with lymphoma.

Edited by Associate Editor Michael Hallek and Podcast Editor Laurie H. Sehn, this Review Series highlights the biologic features of, clinical phenotype of, and therapeutic approaches to high-risk lymphoid malignancies, namely, lymphomas that exhibit rapid growth, present acutely, and require timely therapy. Although many patients are cured with chemotherapy, a subset of patients have treatment resistance and inferior outcomes. This timely set of state-of-the-art reviews addresses the challenges of defining and treating high-risk patients with lymphoma.

Edited by Associate Editor Michael Hallek and Podcast Editor Laurie H. Sehn, this Review Series highlights the biologic features of, clinical phenotype of, and therapeutic approaches to high-risk lymphoid malignancies, namely, lymphomas that exhibit rapid growth, present acutely, and require timely therapy. Although many patients are cured with chemotherapy, a subset of patients have treatment resistance and inferior outcomes. This timely set of state-of-the-art reviews addresses the challenges of defining and treating high-risk patients with lymphoma.

Edited by Associate Editor Michael Hallek and Podcast Editor Laurie H. Sehn, this Review Series highlights the biologic features of, clinical phenotype of, and therapeutic approaches to high-risk lymphoid malignancies, namely, lymphomas that exhibit rapid growth, present acutely, and require timely therapy. Although many patients are cured with chemotherapy, a subset of patients have treatment resistance and inferior outcomes. This timely set of state-of-the-art reviews addresses the challenges of defining and treating high-risk patients with lymphoma.

Chakraborty and colleagues report on a retrospective study on 283 patients treated with daratumumab-containing regimens for light chain amyloidosis to determine the prognostic impact of cytogenetic abnormalities. The only cytogenetic abnormality with significant negative prognostic value was gain/amplification of chromosome 1q (+1q), which had inferior response rate, event-free survival, and overall survival. As previously reported, the authors confirm that t(11;14), present in over half of patients, has no negative prognostic impact in the setting of daratumumab-containing therapy.

Primary hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder that can only be cured by hematopoietic stem cell transplantation (HSCT). Reduced-intensity conditioning has improved transplant survival by reducing toxicity-related mortality but with increased mixed chimerism and graft failure. Verkamp and colleagues report that the interferon-gamma antibody emapalumab, approved for treatment of primary HLH, also has a positive impact on HSCT: overall survival is not increased, but mixed chimerism is markedly reduced as is need for intervention, including donor lymphocyte infusion and second transplants.

Anti–B-cell maturation antigen (BCMA) T-cell engagers (TCEs) are effective agents in multiple myeloma, but 33% of patients show primary refractoriness, and others become refractory with time. In this month’s CME article, Lee and colleagues used whole genome sequencing and in vitro studies to assess the basis for TCE resistance. The authors demonstrate that soluble BCMA shed from tumor cells is an important predictor of primary refractoriness that can be abrogated by increased TCE dose, alternative targets, or gamma secretase inhibitors.

Patients undergoing chemotherapy are at an increased risk of thrombosis, but the mechanism for thrombotic risk is unknown. Xue and colleagues report that gasdermin E (GSDME) is expressed in platelets and induces pyroptosis, contributing to platelet hyperactivity and cisplatin- and etoposide-related thrombosis. Both agents activate caspase-3 to cleave GSDME, releasing a fragment that leads to membrane pore formation and platelet granule release. Loss of GSDME protects mice from cisplatin-induced hyperactivity and thrombosis, suggesting a potential entry point for therapy to protect against this complication.

Human saliva contains extracellular vesicles (EVs) that expose extrinsic complexes of tissue factor and activated factor VII (FVIIa), triggering coagulation. Thaler et al demonstrate that these EVs are present in patients with severe hemophilia A and are capable of activating factor X. This may explain why patients with hemophilia do not generally have oropharyngeal mucosal bleeding while patients with FVII deficiency do.