Monoclonal gammopathy of undetermined significance (MGUS) is a common but often confusing finding on serum protein electrophoresis (SPEP) reports. In this HemeTalks episode, Drs. Rahma Warsame and Jason Chen discuss how to interpret abnormal SPEP results, evaluate patients with suspected MGUS, and differentiate between benign and concerning findings. Using real-world cases, they highlight key clinical decision points, follow-up strategies, and how to communicate results with patients effectively. Tune in for expert guidance on navigating this diagnostic gray zone in hematology.

Learning Objectives:  

1. Recognize the clinical significance of MGUS and how it is detected 
2. Understand how to interpret MGUS lab testing results in the context of monoclonal gammopathies 
3. Identify when to refer, monitor, or investigate further in patients with MGUS

Clinical Pearls:

1. MGUS is a premalignant condition that is a diagnosis of exclusion. It is defined by the presence of a serum monoclonal protein (M-protein) less than 3 g/dL, bone marrow plasma cellsl <10%, and no end organ damage (CRAB) 
2. MGUS can progress to multiple myeloma, AL amyloidosis, Waldenstrom’s macroglobulinemia 
3. Confirmatory tests for MGUS include: SPEP, FLC assay, and bone marrow (only if high risk features are present.

In this episode, Drs. Ronak Mistry and Jori May discuss the challenging decision of when to test for inherited thrombophilias and how results inform anticoagulation management. The use of thrombophilia testing has long been debated in the hematology community, due in large part to limited data and the complexity of estimating recurrent thrombotic risk. Through the case of a 36-year-old woman with a proximal deep vein thrombosis 4 weeks after an uncomplicated vaginal delivery, we explore the importance of defining provoking factors, evaluating bleeding risk, exploring previous thrombotic challenges and family history, and ultimately whether thrombophilia testing may be helpful to determine the need for long term anticoagulation.

Learning Objectives:

1. Accurately interpret the results of laboratory tests for inherited hypercoagulable disorders.
2. Identify appropriate clinical situations where testing for inherited hypercoagulable disorders can be considered.
3. Discuss how inherited thrombophilias influence decisions on the duration of anticoagulation in VTE without major transient risk factors.

Clinical Pearls:

1. Assay selection, appropriate timing of testing, and accurate interpretation of results are foundational to the use of thrombophilia testing in the care of patients with VTE.
2. The use of thrombophilia testing to guide the duration of anticoagulation in patients with VTE without major transient risk factors is debated and therefore must be individualized to every patient.

In this episode of HemeTalks, Alyssa Deffenbaugh and Dr. Toyosi Onwuemene explore the challenges of diagnosing, managing, and living with atypical hemolytic uremic syndrome (aHUS). Listeners will gain insight from a patient advocate and individual living with aHUS, as well as a physician who supports patients through diagnosis and ongoing management. Together, they highlight the importance of advocacy, community, and building a shared understanding between patients and providers. 

Learning Objectives:  

By the end of this episode, listeners will be able to: 

1. Describe at least two challenges individuals with aHUS and providers face in achieving accurate diagnosis and effective management. 
2. Identify one practical action patients or their support networks can take to advocate for better understanding, diagnosis, or management of aHUS. 
3. Describe at least one way community support helps patients, and one way it helps providers navigate aHUS more effectively through shared knowledge or encouragement.  

Clinical Pearls 

1. The aHUS Foundation offers essential patient-support resources for individuals living with aHUS, including active Facebook communities and annual conferences that help patients and families stay informed and connected. The American Society of Hematology website also provides valuable educational resources for clinicians seeking information related to rare conditions such as aHUS.
2. The annual conferences hosted by the aHUS Foundation create valuable opportunities for patients and caregivers to meet others navigating aHUS, share experiences, and build a shared understanding of life with the condition. 

The aHUS Alliance Action website provides globally sourced educational materials, patient stories, and practical tools that support understanding of aHUS. 

This podcast is part of the Rare Diseases Educational Series, developed by the American Society of Hematology and supported by Alexion.

Join us for an important conversation with Dr. Andrew Hintel and Dr. Lauren Merz as we explore how the Duffy null phenotype shapes absolute neutrophil count (ANC) and what this means for clinical care and trial design. Although common among individuals of African, Middle Eastern, and North African ancestry, the Duffy null phenotype is often misunderstood, leading to unnecessary procedures, inappropriate dose modifications, and exclusion from potentially life-saving therapies.

Through real-world examples, we discuss how standard ANC cutoffs can disadvantage Duffy null patients, the implications for chemotherapy, immunosuppressive drugs, and clozapine, and how recent updates to Common Terminology Criteria for Adverse Events grading criteria intersect with this biology. The episode also highlights ongoing efforts, supported by ASH and the Doris Duke Foundation, to establish adult and pediatric reference intervals and promote more inclusive clinical trial practices.

This discussion will equip hematologists and oncologists with practical insights to better interpret neutrophil counts, advocate for equitable trial access, and optimize treatment decisions for patients with the Duffy null phenotype.

Learning Objectives:

1. Understand the ANC by Duffy Status Project: Describe the rationale behind reconsidering absolute neutrophil count (ANC) reference ranges based on Duffy status and its implications for patient care.

2. Apply Clinical Trial Recommendations: Identify key recommendations for including patients with Duffy-null associated neutrophil counts in clinical trials and explain why these changes are important for equitable trial design.

3. Utilize Educational Resources: Recognize the educational tools and resources available to support clinicians, researchers, and institutions in adopting updated ANC reference ranges and practices.

Clinical Pearls:

1. The Duffy null phenotype is found in 10% of people United States and results in an absolute neutrophil count lower limit of normal of ~1200/uL.

2. Clinical trials do not account for this variation which results in disparities in eligibility, systemic anticancer therapy administration, and adverse event reporting.

3. The American Society of Hematology strongly recommends obtaining Duffy status in all clinical trials

Join us for a vital conversation on thalassemia in pediatric hematology with Drs. Sujit Sheth and Ashutosh Lal. Thalassemia is one of the most common inherited blood disorders in children globally, especially in populations from the Mediterranean, Middle East, South Asia, and Africa. This episode explores the different types of thalassemia, strategies for early diagnosis, the importance of transfusion and chelation therapies, and evolving curative options like stem cell transplantation and gene therapy. Using the case of a young child with beta-thalassemia major, we’ll examine both challenges and new hope on the horizon for long-term disease management.  

Learning Objectives:  

1. Understand the types and diagnostic approach to thalassemia in pediatric patients 
2. Review current standards of care including transfusions and chelation therapy 
3. Explore curative treatment options, including stem cell transplant and gene therapy 

Clinical Pearls: 

1. The thalassemias are a group of disorders of ineffective erythropoiesis, with a wide spectrum of clinical presentations, ranging from a mild anemia to transfusion dependence. 
2. The diagnosis is based on the clinical presentation, routine hematologic testing and for a more complete picture and some prognostic relevance, genetic testing of the alpha and beta globin genes. 
3. Management includes close monitoring for all patients, episodic or regular transfusions, iron chelation therapy as indicated, and assessment for stem cell transplant or gene therapy in specific cases.

Join Drs. Caimi and Sdrimas for a focused discussion on the coordination of CAR-T therapy between academic and community practices. As CAR-T use expands, ensuring seamless communication and shared responsibilities between care teams is essential. Using a real-world patient case, this episode explores how to navigate logistics, manage toxicities, and support patients in both settings—delivering collaborative, high-quality care. 

Learning Objectives:

1. Understand the shared roles and responsibilities in CAR-T patient management across care settings 

2. Identify communication strategies that support safe and effective care coordination 

3. Explore real-world barriers and solutions to bridging academic and community practice collaboration

Clinical Pearls:

1. Early and Appropriate Referral is Crucial: 
   • Community oncologists should refer patients early in the disease course. Being ineligible for transplant does not mean a patient is ineligible for CAR-T. Timely referral (i.e. before any other therapy is started unless clinically needed) allows for proper evaluation, manufacturing logistics, and bridging therapy if needed. 
2. Clear, Bidirectional Communication is Key to Safe Co-management: Successful shared care relies on:
   •  Identified point persons at both the academic and community sites (often including nurse coordinators).
   • Timely updates about treatment timelines and toxicity events. Ideally, same day if a toxicity occurs. Weekly updates for treatment timelines.
   • Use of standardized handoff templates and direct lines of communication to ensure continuity, safety, and efficiency in post-infusion      monitoring.
3. Empowering the Community Practice Enhances Access and Outcomes:
   • Academic CAR-T centers, hematologists, nursing staff, and CAR-T coordinators educating community providers on late toxicities, infection risks, and long-term monitoring enables safe local care.

Helpful resources:

• https://ashpublications.org/blood/article/141/20/2405/494965/Introduction-to-a-How-I-Treat-series-on-emergent
• https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00094-9/abstract
• https://www.astct.org/Education/Practice-Guidelines 

Join us for an insightful discussion with Drs. Natalia Neparidze and Saad Z. Usmani as we explore treatment strategies for relapsed multiple myeloma following BCMA-targeted therapy failure. With CAR T-cell therapy and bispecific antibodies revolutionizing myeloma treatment, clinicians are now faced with new challenges as patients relapse after BCMA-directed therapies. 

Through the case of a 62-year-old woman who relapsed one year post-BCMA CAR T-cell therapy, we will discuss mechanisms of resistance, treatment sequencing, and the role of novel agents like selinexor-pomalidomide-dexamethasone. This episode will provide hematologists with practical strategies to navigate post-BCMA treatment failure and optimize patient outcomes. 

 Learning Objectives 

1. Understand mechanisms of resistance and progression following BCMA-targeted therapy. 
2.  Explore non-BCMA treatment options, including alternative targets and novel agents. 
3.  Recognize key factors influencing treatment selection and patient management. 

Join us for an insightful discussion on hereditary hemorrhagic telangiectasia (HHT) with Drs. Hanny Al-Samkari and Adrienne Hammill as we explore the challenges in diagnosing and managing this genetic disorder. HHT is characterized by the development of bleeding nasal and gastrointestinal telangiectasias, as well as arteriovenous malformations (AVMs) in visceral organs and the central nervous system. Patients with HHT almost universally experience recurrent, often severe nose bleeding, and commonly develop gastrointestinal bleeding and complications of AVMs in the lung, liver, and/or brain. Through the case of a 40-year-old woman with recurrent bleeding episodes, we will explore the clinical features, diagnostic workup, and treatment options for HHT. This episode will provide valuable, evidence-based insights into how to approach the diagnosis and management of patients with HHT to improve outcomes and prevent complications. 

Learning Objectives: 

1. Identify the hallmark clinical features and diagnostic criteria for hereditary hemorrhagic telangiectasia (HHT). 
2. Explain the role of imaging and genetic testing in diagnosing HHT and assessing vascular malformations. 
3. Discuss management strategies, including proper pharmacologic management of chronic epistaxis and gastrointestinal bleeding, proper management of anemia, and management of AVMs. 

Join us for an insightful discussion on thrombotic microangiopathy (TMA) in pregnancy with Drs. Richard Burwick and Shruti Chaturvedi as we navigate the complexities of diagnosing and managing hypertensive disorders in pregnancy. These conditions often present overlapping clinical and laboratory features, making timely and accurate intervention challenging. Through the case of a 32-year-old woman at 30 weeks' gestation with severe hypertension, headache, and new-onset thrombocytopenia, we will explore key diagnostic considerations, the distinguishing features of preeclampsia with severe features, Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) syndrome, and TMA, and the best strategies for optimizing maternal and fetal outcomes in these high-risk situations. This episode offers practical, evidence-based insights to enhance the recognition and management of pregnancy-related TMA and hypertensive disorders. 

Learning Objectives: 

1. Differentiate between preeclampsia with severe features, HELLP syndrome, and TMA using clinical and laboratory findings. 
2. Identify the most appropriate diagnostic tests to confirm the underlying etiology in pregnant patients with hypertension and thrombocytopenia. 
3. Discuss immediate and long-term management strategies, including when to initiate delivery and the role of plasma exchange in suspected TMA. 

In this episode of HemeTalks, Dr. Jill Johnsen and Dr. Michelle Sholzberg explore Von Willebrand Disease (VWD), the most common inherited bleeding disorder. The discussion delves into the disease's pathophysiology, diagnostic challenges, and the latest advancements in treatment. Learn about the complexities of diagnosing VWD, and discover we are working together to improve outcomes. This episode provides valuable insights for hematologists and healthcare professionals involved in the management of bleeding disorders.  

Learning Objectives:  

1. Understand the different ways that Von Willebrand Disease can present.  
2. Identify the challenges and best practices for diagnosing Von Willebrand Disease.  
3. Understand treatment options for Von Willebrand Disease and importance of personalized care.