An 18-Year Review of Hemoglobinopathy Proficiency Testing: Recommendations From the College of American Pathologists Hematology and Clinical Microscopy Committee.

Context.—: The College of American Pathologists Hematology and Clinical Microscopy Committee implemented a hemoglobinopathy proficiency testing and education program to monitor and assess the performance of participating laboratories.

Objective.

Advances in Bone Marrow Evaluation.

Evaluation of bone marrow aspirate smear and trephine biopsy specimens is critical to the diagnosis of benign and malignant hematologic conditions. Digital pathology has the potential to revolutionize bone marrow assessment through implementation of artificial intelligence for assisted and automated evaluation, but there remain many barriers toward this implementation. This article reviews the current state of digital evaluation of bone marrow aspirate smears and trephine biopsies, recent research using machine learning models for automated specimen analysis, an outline of the advantages and barriers facing clinical implementation of artificial intelligence, and a potential vision of artificial intelligence-associated bone marrow evaluation.

Mast cell activation syndrome: Current understanding and research needs.

Mast cell activation syndrome (MCAS) is a term applied to several clinical entities that have gained increased attention from patients and medical providers. Although several descriptive publications about MCAS exist, there are many gaps in knowledge, resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell activation is not well understood.

Significant Variability in the Identification and Reporting of Band Neutrophils by Participants Enrolled in the College of American Pathologists Proficiency Testing Program: Time for a Change.

Context.—: Increased band neutrophils in blood smear differential counts ("bandemia") are entrenched in medicine as a flag for sepsis. However, laboratory hematology experts have long advocated for discontinuation of reporting bands separately from segmented neutrophils because of poor sensitivity and specificity, poor interobserver agreement, and availability of alternative biomarkers for sepsis.

Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis: stage I of a phase II trial.

Pentraxin 2 (PTX-2; serum amyloid P component), a circulating endogenous regulator of the inflammatory response to tissue injury and fibrosis, is reduced in patients with myelofibrosis (MF). Zinpentraxin alfa (RO7490677, PRM-151) is a recombinant form of PTX-2 that has shown preclinical antifibrotic activity and no dose-limiting toxicities in phase I trials. We report results from stage 1 of a phase II trial of zinpentraxin alfa in patients with intermediate-1/2 or high-risk MF.

CALR-mutated cells are vulnerable to combined inhibition of the proteasome and the endoplasmic reticulum stress response.

Cancer is driven by somatic mutations that provide a fitness advantage. While targeted therapies often focus on the mutated gene or its direct downstream effectors, imbalances brought on by cell-state alterations may also confer unique vulnerabilities. In myeloproliferative neoplasms (MPN), somatic mutations in the calreticulin (CALR) gene are disease-initiating through aberrant binding of mutant CALR to the thrombopoietin receptor MPL and ligand-independent activation of JAK-STAT signaling.

Clonal hematopoiesis of indeterminate potential and risk of death from COVID-19.

Two Letters to address the risks of COVID-19 in populations with precursors of hematological disease. In the first article, Miller and colleagues report on whether clonal hematopoiesis of intermediate potential (CHIP) is associated with adverse outcomes with COVID-19, finding no association between CHIP and 28-day mortality while providing data indirectly linking IL-6 signaling and patient outcomes. In the second article, Ho and colleagues investigate the outcomes of patients with monoclonal gammopathy of undetermined significance (MGUS) with COVID-19, reporting that one-fourth had a severe infection and that on multivariable analysis, adverse outcomes are more likely if immunoparesis is present.