Education Spotlight Sessions

Debate: PCC or Andexanet alfa for Managing Bleeding in Patients in Oral Xa Inhibitors?

Chair:

David Garcia
University of Washington
Seattle, WA

Speakers:

Sam Schulman, MD, PhD
McMaster University
Hamilton, ON, Canada
PCC Should Be Used to Reverse Xai Anticoagulants

Deborah Siegal, MD,MSc
University of Ottawa
Ottawa, ON, Canada
Andexanet Should Be Used to Reverse Xai Anticoagulants

Managing Previvorship in Hematology: Clinical Approaches to CCUS and MBL

Methodological advances in laboratory hematology have led to a new type of patient: the "previvor.” These are patients with abnormal laboratory tests of unclear significance. Such results give patients a label but do not classify them as having a disease which requires specific therapy. Data on risk of progression to overt disease is emerging, but many patients live in a state of risk, neither progressing nor being assured of normal hematologic function long-term. Recently, great efforts have been undertaken to better clarify these entities, the risk of progression to clinically significant disease, optimal follow-up, and finally, if there is a subset of patients who may benefit from specific therapy. The speakers will emphasis what we know, what is hypothesized for the future, and the ethical and practical issues of caring for patients with two of these entities: CCUS and MBL. Dr. Xie will review the definitions and prevalence of clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). She will discuss strategies to estimate risk for progression, outline clinical management, and review current clinical trial opportunities. Dr. Ghia will discuss the different entities the comprise monoclonal B cell lymphocytosis (MBL) and how they may precede the development of chronic lymphocytic leukemia (CLL). He will describe how biological and clinical features can help distinguish those at risk of clinical consequences and review strategies to manage affected individuals.

Chair:

Gregory A Abel, MD, MPH
Dana-Farber Cancer Institute
Boston, MA

Speakers:

Zhuoer Xie, MD,MS
Moffitt Cancer Center
Lutz, FL
CCUS is Increasingly Significant in Clinical Practice

Paolo Ghia, MD,PhD
Università Vita-Salute and IRCCS Ospedale San Raffaele
Milan, Italy
Monoclonal B-cell Lymphocytosis: at a Crossroad Between Disease and Senescence

What is a “Normal” Neutrophil Count? The Duffy Red Cell Antigen, Ancestry, Genetics and Evolution

It is well-established that the absolute neutrophil count (ANC) in many individuals of African and Middle Eastern ancestry is lower than that in White individuals. This lower ANC is associated with homozygosity for a single nucleotide polymorphism (rs2814778) in the promoter region of the Duffy antigen receptor of chemokines (DARC) gene (also called ACKR1, atypical chemokine receptor 1) which confers the Duffy null phenotype [Fy(a-b-)]. This was historically called ‘benign ethnic neutropenia’, but the preferred term is Duffy-null associated neutrophil count, DANC. Several studies indicate that the Duffy-null genotype causes a change in the morphology of neutrophils, facilitating their migration into tissues, thus reducing the number of circulating neutrophils and causing an ‘apparent neutropenia’. Indeed, individuals who have DANC have circulating neutrophil counts that are approximately 2000/uL lower than Duffy non-null individuals, normal bone marrow cellularity and maturation, and a robust response to infections. The Duffy-null genotype is not associated with an increased risk of infection, yet individuals with DANC may experience iatrogenic adverse health outcomes due to their Duffy-null status. This session will be based on cases derived from clinical practice that will highlight the issues that arise from misinterpretation of the ANC in an individual with DANC. With knowledge of this genetic association, normal neutrophil count limits should not be defined by race or ethnicity, but by genetics. Dr. Lauren Merz will discuss the distribution and prevalence of the Duffy null phenotype as well as the selective pressures that likely led to the evolution of this variant. She will describe the physiological impact of this variant on neutrophil behavior and localization. Furthermore, Dr. Merz will review the assessment, development, and implementation of a Duffy null specific ANC reference range. Dr. Mark Sloan will provide an overview of the expected neutrophil count in persons with the Fy(a-b-) phenotype and suggest potential changes to avoid pathologizing healthy individuals. Dr. Sloan will also discuss the clinical implications of the Duffy null phenotype, including its impact on clinical research.

Chair:

Maureen Okam Achebe, MD,MPH
Brigham and Women's Hospital
Boston, MA

Speakers:

Lauren E. Merz, MD,MSc
Dana-Farber Cancer Institute
Boston, MA
Duffy-null Associated Neutrophil Counts--What is Normal

John Mark Sloan, MD
Boston University School of Medicine
Boston, MA
Clinical Implications of the Duffy Antigen

Where the Bench Meets the Bedside: Laboratory Correlates in Clinical Trials

Correlative studies are essential to improve our understanding of the bioactivity and/or potential resistance mechanisms of candidate therapeutics in clinical trials. We know that the design of clinical trials through a translational research lens requires true bench to bedside thought. Some trials do this better than others. Here the speakers will rationally discuss the role of laboratory correlates in clinical trials and how they are viewed by those with clinical and laboratory expertise. They will also emphasize the impact to the patient in terms of burden of added testing and where burden could outweigh benefit. The titles are intentionally provocation with some satire as obviously both sides "Care" we just need to emphasize each point of view of why to care.

Chair:

Justin Taylor, MD
University of Miami
Miami, FL

Speakers:

Valeria Santini
AOU Careggi-University of Florence
Firenze, Italy
Laboratory Scientists Don't Care

Who are the Alternatives for Cellular Therapies? Engineering and Retargeting Other Effector Lymphocytes

Autologous CD19-specific CAR-T cells have demonstrated remarkable activity against several B-cell malignancies, facilitating the explosion of an entirely new field of therapeutics. However, surprising failures in their development have refocused the field on solving product manufacture delays and failures, and recognizing that the biologic properties of autologous products derived from heavily-treated patients may not be optimal. Moreover, the field continues to evolve in its understanding that the ideal phenotypes and effector functions may vary among disease indications. In parallel, our understanding of the biology and progress in manufacturing has progressed rapidly for alternative effector cell types to the classic aß T cells. These alternative types - namely ?d T cells, NKT cells, and NK cells - possess similar effector function but with distinct cytokine profiles, metabolic pathways, and homing receptor repertoires, along with low GvHD potential when administered across HLA barriers. These properties may make them ideal candidates for specific indications and make them more amenable to implementation as off-the-shelf allogeneic cellular therapeutics. Here, we will compare and contrast these alternative cell types, describe the features that make them amenable to specific indications, and present new advances in the manufacturing, genetic modification, and clinical testing for hematologic cancers.

Chair:

Dean Anthony Lee, MD, PhD
Nationwide Children’s Hospital
Columbus, OH

Speakers:

Carlos A. Ramos, MD
Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital
Houston, TX
Are ab T cells the Best Source for Cancer Cell Therapy?

Jonathan P H Fisher
UCL Great Ormond Street Institute of Child Health
London, ENG, United Kingdom
Engineering T cells: A New Tool for Cancer Immunotherapy