Issue Archive

In this Blood Spotlight, Stauber et al provide an overview of emerging concepts about clonal evolution in myeloid malignancy initiation, progression, and relapse. The authors highlight recent work proposing premalignant stem cells as a potential and clinically relevant source of clonal heterogeneity.

How long patients with chronic lymphocytic leukemia (CLL) should receive ibrutinib-based first-line therapy is unknown. Michallet and colleagues provide an update of an ongoing phase 2 trial, reporting that those patients who achieve complete remission and have no minimal residual disease (MRD) have robust benefit at 3 years after 15 months of fixed-duration therapy. These data add weight to the idea that MRD-guided therapy may assist in optimizing personalized therapy for patients with CLL.

Willier and colleagues report that the expression of target molecules for immunotherapy in pediatric acute myeloid leukemia (AML) differs from expression profiles in adult AML. On the basis of their study of 36 cases, they identify CLEC12A and CD33 as preferential immunotargets for combined targeting in pediatric AML. They also nominate the combination of CD33 and FLT3 as immunotargets specific for KMT2A-mutated infant AML.

The prothrombotic state observed in patients with COVID-19 has many dimensions. Althaus et al identify circulating procoagulant platelets in patients with severe disease and demonstrate that immunoglobulin G antibodies induced in response to SARS-CoV-2 can activate platelets by triggering apoptosis. Correlative associations suggest that this is relevant for thrombus formation in patients with severe disease.

Management of hemophilia A depends on repeated intravenous injections of factor VIII, and development of effective subcutaneous delivery is desirable but challenging. Vollack-Hesse et al describe the use of recombinant von Willebrand factor fragments to protect factor VIII from phospholipids in subcutaneous tissues, increasing bioavailability and hemostatic activity but not antigenicity in murine models. These data provide the rationale for clinical trials of this strategy.

Diagnosis of heparin-induced thrombocytopenia (HIT) can be a challenge. Pathogenic HIT antibodies selectively activate platelet factor 4 (PF4)–treated platelets. In a prospective, blinded study of more than 400 patients suspected of having HIT, Samuelson Bannow and colleagues demonstrate high accuracy of the technically simple PF4-dependent P-selectin expression assay (PEA) relative to the gold standard (serotonin release assay). Widespread use of the PEA could improve diagnosis and change clinical practice.

Ollila et al address a challenging problem: can the risk for central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma be predicted better on a molecular basis? They report that most tumors with CNS recurrence have recognizable molecular features that fall into two categories: those that resemble primary CNS lymphoma and those that resemble high-grade lymphoma. These data suggest that it is time to revisit identification of patients who may benefit from CNS prophylaxis, while highlighting how challenging that is.