Issue Archive

Prognostication is an important part of everyday practice in allogeneic stem cell transplantation (HSCT). In this Perspective, Mohamed L. Sorror reviews the currently available disease-related and nonrelapse mortality indices, identifying their strengths and weaknesses while providing practical recommendations for current decision-making in HSCT and future refinements to prognostic modeling.

In this Blood Spotlight review, Carbone and colleagues summarize the current knowledge about immunological aspects of the tumor microenvironment (TME) in Hodgkin lymphoma and other B-cell lymphomas, which vary considerably. Despite an increasingly sophisticated understanding of the immune microenvironment, composition of the TME does not distinguish between those lymphomas that will respond and those that will not. The authors call for ongoing research to better decipher this conundrum.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group that generally has disappointing response rates and short-lived response to cytotoxic chemotherapy. Ruan and colleagues report that epigenetic priming with the oral hypomethylating agent azacitidine in combination with first-line standard cytotoxic chemotherapy achieves a 75% complete remission rate and 66% 2-year progression-free survival in a phase 2 study, with efficacy greater in the nodal T-follicular helper cell lymphoma subtype. This combination is being explored in a randomized phase 2 trial.

Recently, caplacizumab has become part of standard initial therapy with plasma exchange (PEX) and immunosuppression for immune thrombotic thrombocytopenic purpura. Prasannan et al investigated time to achieve ADAMTS13 activity >30% in patients receiving caplacizumab therapy compared to historical controls. The authors report longer median times to recovery with caplacizumab, with significantly more patients (28%) requiring >58 days after PEX to reach this activity threshold. As yet, this difference is unexplained, and further research is required to guide management when there is delayed recovery of ADAMTS13 activity.

Yoon and colleagues reveal that patients with diffuse large B-cell lymphoma at diagnosis exhibit a profound intestinal dysbiosis. In a study of over 100 patients, relative overrepresentation of Enterobacteriaceae family members in the stool robustly and independently correlated with subsequent febrile neutropenia and relapse with first-line R-CHOP chemotherapy. These provocative results require further corroboration but suggest future studies to evaluate interventions for intestinal dysbiosis are needed.

Intrinsic and treatment-induced immune dysfunction makes infections the major cause of death for patients with chronic lymphocytic leukemia (CLL) requiring therapy. In a retrospective study, Tadmor et al report on the positive impact of antiviral treatment for patients with CLL testing positive for SARS-CoV-2 infection, with lower risks of death and hospitalization, particularly in patients over 65 years of age. The authors identify those patients who appear to benefit most from this simple intervention.

Pure erythroid leukemia (PEL) is a rare and aggressive subtype of acute myeloid leukemia, and driver NFIA-ETO2 fusions have only been seen in pediatric patients with PEL. Piqué-Borràs et al utilized multiple model systems to show that NFIA-ETO2 impairs erythroid differentiation and drives proliferation but is insufficient to induce full leukemic transformation. Concomitant TP53 mutation enables penetrance of full blown PEL, providing a valuable murine model of this rare disease for further study.

Patients with mutations in the endoribonuclease SLFN14 have a dominantly inherited moderate bleeding diathesis with thrombocytopenia and mild platelet dysfunction. Using patient platelets and megakaryocytes, as well as CRISPR/Cas9 engineered cell lines with megakaryocytic differentiation potential, Ver Donck et al identify excessive rRNA degradation in platelets and megakaryocytes and defective megakaryopoiesis. The authors’ work implicates ribosomal biogenesis as an important regulator of platelet production.