The following information is preliminary and subject to change.
Sessions on Malignant Hematology
Acute lymphoblastic leukemia (ALL) is an aggressive hematologic malignancy that affects both children and adults. The majority of children diagnosed with ALL are cured and the outcome of adult ALL has significantly improved over the past decade with the use of intensive pediatric-style regimens. ALL in adults, particularly older patients, remains a challenging disease to treat due to more frequent disease resistance and inability of adults to tolerate intensive chemotherapy. Novel therapeutic approaches for adults with ALL, including CAR-T cell and antibody-based therapies, as well as improvements in the measurement and management of minimal residual disease (MRD) offers new hope for adults with ALL.
Dr. Noelle Frey will discuss outcomes of CAR-T cell therapy with a focus on both clinical responses and toxicity. She will highlight unique challenges applying CAR-T to children, young adults, and older adults. Dr. Frey will discuss when to consider CAR-T cell therapy versus other approaches (chemotherapy, novel agents, transplant) in clinical practice.
Dr. Marlise Luskin will discuss the specific challenges of treating older adults with ALL with conventional chemotherapy. She will then review encouraging emerging data regarding treatment of older adults with novel approaches less reliant on conventional chemotherapy. Dr. Luskin will offer recommendations for management.
Dr. Nicola Goekbuget will discuss approaches for assessing and interpreting MRD in ALL including pros and cons of various strategies. She will discuss when to assess MRD and how to manage persistent and/or recurrent MRD with a focus on the use of novel targeted therapies and the role of transplant.
Marlise R. Luskin, MD
Dana-Farber Cancer Institute
The landscape of advances in AML therapy has rapidly expanded over the last few year. New options for treating patients who are older or frail as well as those fit and candidates for transplant are now available and are being utilized within their approved indications as well as in ongoing clinical trials. This education session will describe these new agents and combinations as well as provide insight into areas of investigation and upcoming novel agents. Specific aims include reviewing indications for inclusion of novel agents in initial therapy versus in the relapse/salvage setting. We will address the area of maintenance therapy after induction and consolidation with or without transplant including duration of therapy and response monitoring. And finally we will address which patient populations are most appropriate for each agent and review particularly challenging scenarios such as elderly / unfit patients, secondary AML, recurrence after prior targeted therapy and other high risk subgroups.
Dr Felicitas Thol will outline recent developments in the treatment of newly diagnosed AML. She will discuss initial diagnostic approaches and give details about indications and efficacy of newly approved treatment options. In this talk a treatment algorithm for newly diagnosed and relapsed AML patients will be outlined.
Dr. Christian Thiede will focus his discussion on the use of maintenance therapies following induction and consolidation therapy. This will include both transplanted and transplant-ineligible patient populations. He will include a discussion of MRD (measureable residual disease) and its application to maintenance surveillance in AML patients.
Dr. Margaret Kasner will address which patient populations are likely to benefit from the recently approved and novel investigational agents. She will address particularly challenging scenarios including elderly / unfit patients and secondary AML subgroups. The talk will include a discussion of recurrence after prior targeted therapy including how to sequence therapies and resistance mechanisms. Finally there will be a discussion of novel agents under investigation for addressing difficult to treat patient populations.
Margaret Kasner, MD
Sidney Kimmel School of Medicine, Thomas Jefferson Hospital
Multiple Myeloma (MM) is the second most frequent malignant hematological disease with a variable incidence worldwide but accounting for 1% of all cancers and 15% of blood cancers. Over the last century, the introduction of novel therapeutic classes produced a significant improvement of both progression-free (PFS) and overall survival (OS). However, in spite of all these advances there are some special subgroups of patients with poorer outcomes than expected and considered with high-risk features: their identification and management will be addressed in this session. On the other hand, MM usually affects to older adults and the incorporation of frailty assessments is necessary and will be also discussed in order to individualize and optimize the management. Finally, the incorporation of minimal residual disease for the response evaluation as a relevant prognostic factor will contribute to optimize the management and could drive not only the type of treatment but its optimal duration.
Dr, Maria-Victoria Mateos will discuss how to identify and manage high-risk Myeloma patients. Patient, disease and outcome-based factors identify this subgroup of patients. Their management should be response-adapted and based on the use of the best available therapeutic options with the goal of achieving the deepest and sustained response over time.
Dr. Ashley Rosko will outline how to incorporate frailty assessments in the evaluation of older adults with Multiple Myeloma in the clinical setting with consideration of other factors such as patient preferences, treatment risks/benefits, life expectancy, and disease biology. Disease and patient factors at diagnosis, transplant and relapse will be discussed and how frailty/fitness assessments influence treatment decisions.
Dr. Noopur Raje will address the improvements in multiple myeloma therapy through the achievement of deep responses that are beyond the limit of detection of historical immunohistochemistry and conventional flow cytometry, such as next generation flow cytometry and sequencing for assessing minimal residual disease (MRD). Dr Raje will review the data supporting MRD testing as well as its limitations and how it may fit in with current and future clinical practice.
Universidad de Salamanca, IBSAL, Centro de Investigación del Cáncer, IBMCC-CSIC
The availability of small molecule therapy +/- antibodies for the treatment of CLL has dramatically prolonged survival compared to that expected when the only available options were chemoimmunotherapy-based. However, whether continuous therapy regimens or finite therapy regimens are optimal is unclear. In addition, ideal sequencing of small molecule therapy is unclear; there may not be one best strategy that fits all patients.
Professor Constantin Tam will discuss the benefits and limitations of continuous therapy in patients with CLL. Both B-cell receptor (BCR) inhibitors and venetoclax have been utilized in continuous therapy regimens. Recent results of long term followup with such regimens will be described, both in terms of efficacy as well as long term safety. He will also discuss how the durability of responses are differentially influenced by adverse biological risk factors including TP53 mutation/deletion, unmutated IgHV status, and karyotypic complexity. Finally he will describe practical considerations such as treatment location and accessibility to real time laboratory testing that may impact choice of therapy.
Professor Florence Cymbalista will discuss the opportunities and challenges of time limited frontline treatment in CLL. This talk will review the current approved options and the results of the recent phase II and phase III trials in particular exploring Venetoclax-based regimens, and will outline the on-going trials with pending results. She will discuss the impact of comorbidities, comedications and patient/physician preferences on treatment decisions. Using a case based approach, she will suggest how time limited treatment may benefit fit as well as unfit patients.
Dr. Deborah Stephans will cover the use of anti-CD20 monoclonal antibody combination therapies in patients with CLL. She will discuss using antibodies in combination with chemotherapy as well as with BCR inhibitors or venetoclax. She will analyze their possible contribution to deeper remissions as well as the effect on durability of responses, whether the regimen is continuous or time limited.
Susan M. O'Brien, MD
UCI Cancer Center
The development of BCR-ABL tyrosine kinase inhibitors revolutionized therapy for chronic myeloid leukemia, causing those who treat CML to shift much of their focus to management of long-term toxicities and the possibility of TKI cessation. In spite of this success, there remain a minority of patients who still progress to advanced phases of CML.
Dr. Andreas Hochhaus will discuss TKI discontinuation and strategies to increase the number of eligible patients.
Dr. Michael Mauro will discuss life-long TKI therapy, including management of cardiovascular risk factors and other toxicities.
Dr. Gabriela Hobbs will discuss advanced phase CML and the management of accelerated and blast phase disease.
Kendra Sweet, MD
Moffitt Cancer Center
Although the outcome for many patients with newly diagnosed aggressive B-cell lymphoma is excellent, several subtypes are therapeutically challenging with sub-optimal outcomes following standard therapy. The session aims to discuss emerging understanding of the biology of difficult to treat aggressive B-cell lymphomas in the context of new and emerging therapies. A spate of new approaches and agents are in development for these diseases and latest results of pertinent trials will be discussed and analyzed.
Dr. Kieron Dunleavy will discuss the challenges and controversies of up-front and later therapy selection in ‘double-hit’ and other high-grade B-cell lymphomas. Significant strides have been made recently in improved understanding of the biology of these disease and this is reflected in more refined categorizations, which he will discuss. Many recently developed and approved novel therapies including cellular therapies and bi-specific antibodies have demonstrated good efficacy in these diseases and he will discuss latest results and implications for up-front investigation.
Dr. Bjorn Chapuy will focus on recent advances in the understanding of the molecular heterogeneity of diffuse large B-cell lymphoma. Recent work has refined the molecular definition of DLBCL and this is interesting to consider in the context of new therapies for the disease. He will discuss molecular heterogeneity in the context of R-CHOP therapy and purported mechanisms behind resistance, including understanding additional molecularly defined clusters within molecular sub-groups.
Dr. Reem Karmali will outline the strengths and limitations of CD19 CARTs as customized engineered products vs off-the-shelf immunotherapies such as bispecific CD20-CD3 antibodies as therapeutic options for relapsed/refractory aggressive B-cell non-Hodgkin lymphomas. Clinical efficacy and safety data for CD19 CARTs and bispecific CD20-CD3 antibodies will be reviewed for general and vulnerable populations. Guidance will be provided on the optimization of therapeutic algorithms for relapsed/refractory aggressive B-cell lymphoma with the availability of CARTs and the emergence of off-the-shelf immunotherapies.
Kieron Dunleavy, MD
This session on Hodgkin lymphoma: Cure and Optimal Survivorship will review current therapeutic options for newly diagnosed patients with stage I-II Hodgkin lymphoma as well as options for patients with relapsed and refractory HL, focusing on treatments options at first relapse prior to stem cell transplantation as well as options for multiply relapsed patients. Each speaker will discuss the current therapeutic landscape as well as novel therapeutic options currently under investigation.
Dr. Kristie Blum will review several of the ongoing controversies regarding the use of chemotherapy, radiation, and PET-directed therapy in patients with previously untreated early stage Hodgkin lymphoma. These controversies include definitions of response, when to incorporate radiotherapy, the number of cycles of chemotherapy and type of regimen utilized, and the treatment of bulky disease. In addition, the session will review the latest data addressing long term risks with these therapeutic approaches and will also review recent clinical trials examining the incorporation of brentuximab and checkpoint inhibitors into front-line regimens for early stage Hodgkin lymphoma.
Dr. Marie Jose Kersten will discuss salvage therapy options for patients who relapse after front-line therapy for Hodgkin lymphoma. The discussion will review traditional combination chemotherapy salvage regimens as well as newer approaches incorporating brentuximab, checkpoint inhibitors, or combinations of these agents with conventional cytotoxics.
Dr. Mehdi Hamadani will discuss the challenging subset of classical Hodgkin lymphoma patients with disease refractory to both brentuximab vedotin and checkpoint inhibitors (double refractory patients). The presentation aims to identify patients likely to benefit from conventional cytotoxic and targeted therapies, and review modern outcomes of allogeneic transplantation as a curative modality. Finally the presentation will cover state of experimental cellular therapies including CAR T-cells, EBV-directed cytotoxic T-cells and NK cell based approaches.
Kristie A. Blum, MD
Emory Winship Cancer Institute
Allogeneic hematopoietic cell transplantation (alloHCT) remains one of the most potent therapies to eradicate high-risk hematologic malignancies and hematologic/immune disorders. Access to alloHCT is constrained at the patient level due to concerns of procedure-related morbidity and mortality. At the system level, seen and invisible factors conspire to further limit access. Expanding alloHCT to older patients, wider donor availability, and socio-economic development has sparked utilization to nearly double in the past decade. Further adaptions will be necessary to ensure all patients who need a transplant have the option to receive one.
Dr. Andrew Artz will discuss emerging data on the use and outcomes of alloHCT among older patients. An updated approach on how to consider and optimize older candidates for alloHCT-from diagnosis to transplant-will be presented, with special attention on tools to characterize heterogeneity of aging.
Dr. Vanderson Rocha will describe an international perspective on global growth of allotransplant related to demographics, socioeconomic factors, and providers and health care systems. He will detail the expanding eligibility of patients (elderly with or without comorbidities) and donors (unrelated and haploidentical). Finally, Dr Rocha will explore how new technologies may further increase access and improve outcomes of allotransplants.
Dr. Navneet Majhail will outline a United States perspective on alloHCT access. How race, geography, socio-economics and other factors present both barriers and opportunities will be explained.
Andrew S. Artz, MD,MS
City of Hope
Our knowledge of the immune system and its role in various hematologic disorders has grown exponentially over the past several decades. In this session, we discuss the fundamentals of the immune system, as well as how immunodeficiencies can lead to malignancies and how T cells can be utilized as therapeutic agents in cancer and viral infections.
Dr. Shannon Carty will give a general overview of the immune system and the complex interplay between its cellular components, as well as what constitutes a typical immune response. She will highlight how immune dysfunction can lead to hematologic disorders and discuss therapeutic approaches to enhancing the immune response to hematologic malignancies.
Dr. Sung-Yun Pai will highlight how immunodeficiencies, both inherited and acquired, can lead to malignancy. She will discuss the immunologic defects in people living with HIV infection and how these are related to the development of cancer. Additionally, she will detail clinical disorders involving inborn errors of immunity that affect lymphocytes and/or DNA repair with a focus on how these can increase malignancy risk.
Dr. Nathan Singh will detail the use of modified T cells as therapeutic agents in cancer and viral infections. The specific clinical products approved for the treatment of hematologic malignancies will also be discussed, as well as concepts around patient selection and toxicity management
Shannon A. Carty, MD
email@example.com, Ann Arbor, MI
Patients with indolent lymphoma share a long disease course, and similar treatment paradigms meant to lengthen life quality and duration of treatment response. The ability to provide personalized care for patients with indolent lymphoma requires a careful approach that balances individual patient clinical, biologic and genetic considerations towards the understanding of assessing patient risk. The plethora of therapeutic options available and in development for indolent lymphoma requires a precision approach to optimize therapeutic outcomes.
In this series, Dr. Carla Casulo will discuss patient and tumor-specific factors associated with risk of disease progression, histologic transformation, and premature death from follicular lymphoma. She will review established prognostic models, discuss their strengths and weaknesses when applied in clinical practice, and review approaches to incorporate the clinical and mutational data into novel prognostic tools at different points in the patient’s lifetime.
Dr. Youn Kim will review the disease heterogeneity and the unique quality of life issues in patients with mycosis fungoides (MF) and Sézary syndrome (SS), the major subtypes of cutaneous T-cell lymphoma. She will discuss the complexity and challenges in managing MF and SS which exhibit variable and dynamic disease activity across skin and non-skin compartments. Dr. Kim will present the framework in addressing treatment selection and will discuss the approach for optimal integration and utilization of available clinical, pathologic, and biomarker data for prioritizing therapies and personalizing management.
Dr. Robin Foà will cover the possible role of MRD in the management of patients with indolent NHL, focusing in particular on follicular lymphoma (FL). The data in support of MRD monitoring for both advanced and localized disease will be discussed. How MRD monitoring may be used in the clinical management of FL patients will be presented. The talk will also address current limitations of MRD monitoring and how new technologies may overcome them in order to more widely apply MRD to FL patients, as well to other indolent NHLs.
Carla Casulo, MD
University of Rochester Medical Center
It Takes a Village: Maximizing Supportive Care and Minimizing Toxicity During Childhood Leukemia Therapy - Live Q&A
Risk adapted chemotherapy and enhanced supportive care have contributed to improved cure rates for childhood leukemia. However, the delivery of optimal therapy continues to be hampered by acute toxicities, resulting in interruption and omission of essential chemotherapy. Minimizing the morbidity and mortality from treatment-related toxicities requires vigilant supportive care by multidisciplinary teams. In addition, novel immunotherapies have brought with them unique toxicities that can also be life-threatening. This education session will review guidelines for assessment, prophylaxis and management of common toxicities of childhood leukemia therapy.
Dr. Brian Fisher will discuss an evidence-based approach to antifungal prophylaxis and empirical therapy during periods of neutropenia in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Additionally, he will discuss the utility of fungal biomarkers for diagnosing invasive fungal disease at specific clinical time points during neutropenic periods. He will present data from recently completed large prospective observational and randomized studies in these patient populations while also highlighting gaps in knowledge that need to be addressed in future investigations.
Dr. Kasey Leger will review the impact of cardiotoxicity in children with AML and highlight opportunities for cardioprotection during AML therapy. Strategies for primary cardioprotection, including dexrazoxane and liposomal anthracyclines, will be reviewed. The role of various imaging modalities for cardiotoxicity monitoring will be described, along with their potential to inform toxicity-responsive cardioprotection efforts. Finally, Dr. Leger will propose a practical approach to clinical decision making in cases of cardiac dysfunction during pediatric AML therapy, balancing the competing risks of optimizing cancer cure and preserving short and long-term cardiac function.
Dr. Deepa Bhojwani will focus on common central nervous system toxicities during chemotherapy and immunotherapy for childhood ALL. She will review the manifestations of subacute methotrexate neurotoxicity, its management and the importance of methotrexate re-challenge after recovery from the neurotoxic episode. She will then discuss immune effector cell associated neurotoxicity syndrome (ICANS), a frequent toxicity of blinatumomab and CAR T-cell therapy. Algorithms for management based on severity, and novel strategies based on the pathophysiology of ICANS will be reviewed.
Deepa Bhojwani, MD
Children's Hospital of Los Angeles
Los Angeles, CA
For many years, the clinical management of patients with myelodysplastic syndrome was stagnant. Recent advances in molecular profiling have begun to lift the lid on optimal prognostication. Moreover, some of the identified molecular lesions have helped to demystify the mechanisms responsible for MDS, driving novel drug development. Incorporation of molecular profiles into established prognostic tools will soon help to better identify appropriate treatments for patients with higher and lower risk disease. While novel therapies show real potential, the recent approval of oral hypomethylating agents have the potential to optimize the existing therapeutic armamentarium.
Dr. Maria Teresa Voso will update on the role of molecular profiling in the diagnosis of myelodysplastic syndromes. She will outline the role of next generation sequencing techniques to guide the diagnostic algorithm in patients with an unclear clinical picture. This presentation will also show the value of molecular methods to accurately stratify the disease, indicate closer patients' follow-up or treatment intensification, including allogenic stem cell transplantation in younger patients with an unfavorable profile.
Dr. Elizabeth Griffith will discuss the importance of dose, schedule and adherence for optimal efficacy of hypomethylating agents in the management of patients with the myelodysplastic syndrome. Recent approval of two oral hypomethylating agents has the potential to address some, but not all, of these challenges. Appreciation for the differential pharmacokinetic (PK) profiles for these approved agents will help to inform toxicity management for the treating clinician.
In this talk, Dr. Amy DeZern discusses that current scoring systems may not address all prognostic factors relevant in clinical practice, especially for patients with lower risk MDS. Dr. DeZern emphasizes the emerging role of t-MDS and challenges in their general management. She then reviews the role of stem cell transplantation in lower risk MDS.
Elizabeth A. Griffiths, MD
Roswell Park Comprehensive Cancer Center
In the last 15 years, the knowledge about the pathogenesis of myeloproliferative neoplasms (MPN) has greatly increased, both on disease evolution and on arterial and venous thrombotic complications. Despite the improvements the clinical management of patients with MPN presents several unmet needs, including optimization of primary and secondary thromboprophylaxis to reduce the still high rate of thrombotic events; the identification of personalized approaches to define the optimal timing for transplant vs non-transplant treatment in primary myelofibrosis; and the use of disease modifying treatments in patients at low vascular risk belonging to special categories, such as the younger population whose life is threatened by a chronic uncurable disease.
Dr. Anna Falanga will discuss the evidence and mechanisms of high risk of thrombosis in patients with MPN and COVID-19. She will outline the roles of individual- and disease-specific thrombotic risk factors, as well as of bleeding risk factors and concomitant treatments, in defining the patient risk level and identifying the best measures to prevent thrombosis in both MPN and COVID-19. Using a case-based approach, this talk will also focus on venous thromboembolism and will address the challenge of choosing the best anticoagulant treatment and its duration in a patient with PV, pulmonary embolism, and COVID-19.
Dr. Vikas Gupta will outline a risk-adapted approach for selection of upfront hematopoietic cell transplantation (HCT) versus non-transplant therapies for myelofibrosis in chronic phase. He will also overview the progress of symptom directed JAK inhibitor (JAKi) therapy towards disease modifying novel therapies for MF.
Dr. Elizabeth Hexner will discuss how our molecular and mechanistic understanding of the pathobiology of myeloproliferative neoplasms intersect with clinical treatment outcomes with interferons. She addresses the central paradox of treating MPN, a pro-inflammatory state, with a pro-inflammatory cytokine. As well as how might interferons help to address notable gaps in treatment for patients considered to have low vascular risk but high morbidity, such as younger and pregnant patients.
Anna Falanga, MD
University of Milan Bicocca/Hospital Papa Giovanni XXIII, Bergamo
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for several diseases. Advances in treatment practices have helped improved survival after allo-HCT, though life expectancy after allogeneic HCT remains lower than that of the general population. There is an increasing recognition of medical and psychosocial complications after HCT that can lead to significant patient and health care burden. Through a case-based approach, this educational session will focus on updates in the area of psychosocial and two main medical complications after allogeneic HCT: infectious and pulmonary issues. Strategies to optimally recognize, prevent and treat these sequelae of allo-HCT will be discussed.
Dr Nandita Khera will outline the burden of psychosocial complications to emphasize the need for proactively collecting and intervening on patient reported outcomes after allo-HCT. She will describe the current approach to screening and management of these complications and identify opportunities for future practice and research to fulfill the unmet needs in this area. Her talk will highlight the barriers in delivery of psychosocial care and how innovative care models can help overcome them to provide comprehensive, coordinated, and patient centered care.
Dr Kirsten Williams will discuss the impact of noninfectious lung complications on long term outcomes. She will discuss the current approaches to diagnose and treat these complications, as well as risk factors for their development. She will also highlight the gaps in knowledge such as lack of specific clinical diagnostic criteria for many of these conditions, and the few available noninvasive tools for evaluation. Her talk will also describe the current understanding of the pathogenesis of these noninfectious lung conditions which may one day inform prevention.
Dr Per Ljungman will discuss important infections, which can occur late after an allogeneic stem cell transplantation and these infections’ impact on morbidity and mortality especially in patients with chronic GVHD. He will also discuss the impact of the COVID-19 pandemic on survivors after allo-HCT. His talk will also highlight the need for vaccinations both to classic pathogens such as pneumococci and influenza but also address the current knowledge about vaccinations against COVID-19.
Nandita Khera, MD
Graft-versus-host disease (GVHD) remains a major cause of transplant-related morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), which continues to limit its therapeutic potential. For several decades, little progress was made in the prevention and treatment of GVHD. In addition, there has been limited understanding of the impact and significance of GVHD and its treatment on patients’ health-related quality of life. Recent insights into the pathophysiology of GVHD have led to several successful clinical trials investigating biologically-based, novel therapeutic approaches. This educational session will review updates in new risk-adapted approaches to the treatment of acute GVHD and biologically-based novel prevention and treatment strategies in chronic GVHD. Further, the session will review the significant impact of GVHD on patient-reported quality of life and strategies to maximize multi-disciplinary supportive care to optimize the care of GVHD patients.
Dr Sherman Holtan will review evidence surrounding recent risk-adapted approaches to treating acute GVHD. This evidence will be discussed in the context of 3 patient scenarios: (1) new acute GVHD diagnosis, (2) steroid-refractory acute GVHD, and (3) steroid-dependent acute GVHD.
Dr. Betty Hamilton will provide an outline of the advances in the understanding of the biology of chronic graft-versus-host disease (GVHD). Using this as a framework, she will review the current novel approaches to chronic GVHD prevention and treatment; and provide examples of the successful implementation of clinical trials with clinical endpoints relevant to GVHD and transplant outcomes. This talk will address goals of GVHD treatment and future approaches to better understand the biologic targets in chronic GVHD.
Dr. Areei El-Jawahri will discuss the impact of chronic GVHD on patient-reported quality of life, physical functioning, and psychological wellbeing. She will then discuss critical strategies to manage the supportive care needs of patients living with chronic GVHD including monitoring of patient-reported symptoms, routine screening for psychological distress, systematic review of care needs, multidisciplinary care expertise for management of organ-specific symptoms, and maximizing supportive care measured targeted to address organ-specific GVHD symptoms.
Betty K. Hamilton, MD
Ola Landgren, MD
Sylvester Comprehensive Cancer Center, University of Miami
Sessions on Non-Malignant Hematology
Hematologists face frequent challenges in the evaluation and treatment of patients with unusual or unexplained thrombotic and bleeding disorders. Common questions include how to approach unexplained arterial thrombosis, venous thrombosis in unusual locations, and bleeding disorders that remain undiagnosed after frontline testing. This educational session aims to provide a diagnostic framework and evidence-based treatment approaches for these common clotting and bleeding conundrums. A case-based approach will highlight important concepts.
Dr. Jori May will provide an overview of the common and uncommon causes of arterial thrombosis. She will highlight areas of management that have recently evolved such as dual pathway inhibition in atherosclerotic disease, antithrombotic therapy selection in embolic stroke of undetermined source and left ventricular thrombus, the role of patent foramen ovale closure for secondary stroke prevention, and the thrombotic potential of COVID-19 infection and vaccination.
Dr. Kristi Smock will outline an approach to diagnosing bleeding disorders that present with normal conventional coagulation tests. She will highlight specific disorders of hemostasis that may present diagnostic challenges and will explore the reasons for these challenges using a case-based approach. This talk will outline appropriate testing strategies and provide practical information on test interpretation and limitations to assist hematologists in evaluating patients with undiagnosed bleeding disorders.
Dr. Marc Zumberg will provide a case-based presentation focused on the diagnosis and treatment of clots in the splanchnic and cerebral circulation, including discussion of controversies. Existing evidence, including findings from recent systematic reviews and meta-analyses, will be summarized and recommendations given. Discussion of data concerning the efficacy of direct oral anticoagulants in treating clots in unusual locations will be included.
Kristi J Smock, MD
University of Utah and ARUP Laboratories
Salt Lake City, UT
Coagulation testing for the accurate diagnosis of bleeding or thrombotic patients requires multiple laboratory assays with complex methodologies according to diagnostic algorithm and comprehensive interpretation by experts for the appropriate management of the patients. Challenges include assay Interference, particularly in clot based assays, by commonly used anticoagulants leading to erroneous results, emergence of new useful coagulation tests that lack familiarity, and technical aspects that are relevant to individual results and widely utilized clinical decision rules. This session will cover a “potpourri” of challenging and practical topics by a case based approach to improve attendee’s selection and interpretation of coagulation tests and to increase their awareness of limitations and pitfalls of coagulation testing.
Dr. Karen Moser will discuss about DOAG interference in specialized coagulation testing. Direct oral anticoagulants may interfere in a variety of routine and specialized hemostasis assays. Understanding the potential for interferences is essential to avoid erroneous interpretation of results. This session will provide a brief overview of expected patterns of DOAC interference in hemostasis assays and will discuss strategies that physicians and clinical laboratories can use to minimize DOAC interference.
Dr. Jay Raval will discuss about expanded menu of tests for the diagnosis of thrombotic thrombocytopenic purpura (TTP).
Dr. Andrew Goodwin will provide an overview of d-dimer test. D-dimer assays were frequently ordered during the COVID-19 global pandemic as part of the diagnostic work-up for COVID-associated coagulopathy. The D-dimer assay, which is sensitive to detecting fibrinolysis associated with thrombus formation, is useful in the evaluation of patients with VTE and, for certain assays, it is approved for the exclusion of VTE in patients with a low to intermediate pre-test probability. Ordering medical providers should recognize some key differences in D-dimer assays when used to diagnose patients with a potential thrombotic event. Additionally, recognizing the difference between a D-dimer assay unit of measure is important when utilizing pre-test probability models or management algorithms.
Heesun J. Rogers, MD
Treatment options for sickle cell disease (SCD) have increased substantially over the last five years. Added to new potentially disease modifying therapies are the promise of curative therapies in development. As a result, it is important that affected individuals have discussions with sickle cell experts when considering therapeutic options.
Dr. Krishanmurti will review outcomes in hematopoetic stem cell transplant (HCT) from HLA identical siblings, improvements in conditioning regimen and novel methods of GVHD prophylaxis. He will also discuss improvements in the use of alternative donors for HCT for SCD. He will also explore exciting upcoming options including antibody-based conditioning regimens and ex-vivo umbilical cord blood expansion.
Dr. Kanter will discuss the current gene therapies undergoing clinical trials in SCD. She will expand on the different types of gene therapies in use, the differences in measuring efficacy across these therapies and the risks and safety concerns associated with gene therapy. She will also discuss some potential risk mitigation strategies moving forward.
Dr. Badaway will discuss the importance of improving participation and conduct of clinical trials for people with SCD. He will review several current partnerships to improve patient engagement. Dr. Badaway will also discuss the importance of patient reported outcomes in all SCD trials and the need for a patient-centered approach to clinical trials in SCD.
Julie Kanter, MD
University of Alabama Birmingham
Dameshek's Riddle in Practice: Is this Aplastic Anemia, Paroxysmal Nocturnal Hemoglobinuria, or Hypoplastic Leukemia? - Live Q&A
The overlap in clinical presentation and bone marrow features of acquired and inherited causes of hypocellular marrow failure pose a significant diagnostic challenge in real case scenarios, particularly in patients with moderate cytopenia(s). The accurate distinction among acquired and inherited causes of hypocellular marrow failure is critical to inform appropriate therapy. In this session, we will review current approaches to the evaluation of these patients and highlight select therapeutic decisions and surveillance cares.
Dr. Sio?án Keel will review the diagnostic work-up of patients presenting with hypocellular bone marrow failure. She will present a case-based discussion on how to establish a timely and accurate diagnosis to expediate appropriate treatment. Her talk will include clinical and laboratory pearls in the diagnostic distinction between acquired aplastic anemia, hypocellular MDS, and classical inherited bone marrow failure syndrome or inherited myeloid malignancy predisposition syndromes among adolescent and adult patients.
Dr. Daria Babushok will discuss the evaluation of positive paroxysmal nocturnal hemoglobinuria (PNH) flow cytometry results. Although PNH cells can be readily identified by flow cytometry, assessing the clinical significance of a PNH clone requires an understanding of PNH pathogenesis and its relationship to immune-mediated bone marrow failure. Dr. Babushok will review considerations for interpreting the validity and clinical relevance of PNH flow cytometry, including the diagnostic significance of a PNH clone in bone marrow failure disorders and indications for starting complement inhibitor therapy for PNH.
Dr. Anupama Narla will briefly review congenital and acquired bone marrow failure syndromes and highlight the wide phenotypic spectrum in these diseases which must be considered in the differential diagnosis of both children and adults with unexplained defects in hematopoiesis and evidence of aplastic anemia. Her talk will highlight the importance of establishing the correct diagnosis for these rare disorders as it has implications for treatment, medical management, cancer screening, and family planning.
Sioban B. Keel, MD
University of Washington
Prophylaxis factor replacement therapy is now considered standard of care in both pediatric and adult patients with hemophilia with a severe phenotype to protect musculoskeletal health and improve quality of life.
Dr. Ming Lim will focus on current practical points on choosing the type of factor concentrate, dose, and interval while considering the appropriate target trough factor levels and bleeding triggers such as level of physical activity and joint status. Pharmacokinetics assessment and its incorporation in the clinic for an individualized approach are also discussed. The adoption of an individualized prophylaxis regimen leads to optimal utilization of factor concentrates with maximum efficacy and minimum waste.
Dr. Alice Ma will discuss novel non-factor therapies in use and in development for hemophilia A and B. Products discussed will include emicizumab and the rebalancing therapies fitusiran, the anti TFPI agents, as well as other novel therapeutics and position their current and projected use in hemophilia care.
Dr. George will discuss the current status of hemophilia gene therapy, including basic principles, current clinical trials, outstanding questions that have emerged from clinical trials and anticipated licensure of hemophilia gene therapy vectors.
Alice Ma, MD
University of North Carolina At Chapel Hill
Chapel Hill, NC
Although hemoglobinopathies are the most common hereditary anemias, the other inherited red cell disorders still apply a significant disease burden worldwide, from fetal life to older adulthood. The significant heterogeneity of these disorders, posing challenges to their diagnosis and clinical management, will be considered in this educational session, with focus on the red cell membrane disorders, enzymopathies, and the Diamond-Blackfan anemia. The speakers will present representative patient cases in order to discuss the implementation of classic and newer diagnostic technologies, including genetic evaluation, and provide updates in clinical management and treatment approaches.
Dr. Theodosia Kalfa will expand on comprehensive evaluation of the red cell membrane disorders, including phenotypic and genetic testing, and discuss relevant clinical management considerations tailored to the diagnosis and pathophysiology.
Dr. Lucio Luzzato will present on red cell enzymopathies of the classic glycolytic pathway, the pentose phosphate pathway, and disorders of enzymes involved in nucleotide metabolism, as they are now understood at the biochemical and molecular level. He will also discuss advances in molecular diagnosis for red cell enzymopathies and ongoing research for targeted treatment.
Dr. Lydie Da Costa will discuss the intricacies and heterogeneity in presentation of Diamond-Blackfan anemia (DBA) and elaborate on the progress in understanding the molecular basis and the pathophysiology for DBA and DBA-like diseases, aiding to developing and pursuing new therapeutic options.
Theodosia A. Kalfa, MD, PhD
Cincinnati Children's Hospital Medical Center
Let the CHIP(s) Fall Where They May? Burdens and Benefits of Diagnosing Clonal Hematopoiesis - Live Q&A
The accumulation of somatic mutations is inevitable in virtually all tissues, particularly in highly proliferative tissues such as hematopoietic system. Such mutations result in somatic mosaicism. Occasionally, this mostly stochastic process may result in functional changes of key hematopoietic genes leading to relative increase in stem cell fitness and clonal expansion, the phenomenon called clonal hematopoiesis (CH). CH represents an acquired, context-dependent advantage of mutated hematopoietic stem cell over unmutated counterparts. Thus, CH is a common-age related condition and may provide an enhanced hematopoietic cell fitness via evasion of intra- or extracellular stress. This educational session will address the etiology and mechanisms behind CH in various biological and clinical conditions and explain the mechanism underlying “improved” stem cell fitness in various contexts. The session will also discuss malignant and non-malignant consequences of CH and provide a guide for using molecular testing in diagnostic work-up of cytopenias. Lastly, we will discuss the prevalence and characteristics of CH in inherited bone marrow failure syndromes and its propensity for leukemic transformation.
Dr. Lukasz Gondek will address the nomenclature of clinical entities associated with CH such as age-related clonal hematopoiesis (ARCH), clonal hematopoiesis of indeterminant potential (CHIP) and clonal cytopenia of unknown significance (CCUS). He will also discuss the etiology of CH in various clinical and biological settings. Moreover, he will outline the impact of acquired somatic mutations on hematopoietic stem cell fitness in the context of various cell-intrinsic and cell-extrinsic factors.
Dr. Afaf Osman will discuss the clinical consequences of emerging myeloid precursor states including CHIP and CCUS. She will present a diagnostic approach to the workup of unexplained cytopenias focusing on the role of molecular diagnostics in this setting. Using a case-based approach she will review the interpretation of next generation sequencing (NGS) panels in the context of cytopenias.
Dr. Moonjung Jung will describe recent advances in our understanding of clonal hematopoiesis and somatic transformation in IBMFS, with a focus on Shwachman-Diamond syndrome, Fanconi anemia, severe congenital neutropenia, short telomere syndrome and SAMD9/SAMD9L disorders. This talk will address differences between clonal hematopoiesis observed in IBMFS and age-related clonal hematopoiesis, and potential ways to incorporate the biological insights of CH into clinical practice.
Lukasz P. Gondek, MD,PhD
Johns Hopkins University
The management of Sickle Cell Disease (SCD) has rapidly changed over the past few years. With the approval of new medications, however, we now have new questions in addition to old ones. Although there are significant benefits documented with the use of hydroxyurea, we are still learning how to integrate the use of the newly approved medications into care. Specifically, four drugs are now approved for management of SCD and need careful consideration as to which patient will benefit from each of these. In addition, patients with SCD who are undergoing surgery are at high risk for complications and require strategies to improve outcomes. Finally, complications such as priapism, leg ulcers, and pulmonary hypertension have significant associated morbidity and mortality, also requiring treatment considerations. This session will address the approach to incorporating treatment of patients with SCD with these new medications as well as the approach to these significant complications. Dr. Leila Jerome Clay will outline the history and presentation and complications of sickle cell disease. She will discuss the historical perspective of the disease and an overview of the recent treatment modalities and management of sickle cell disease. Dr. Charity Oyedeji will outline optimization strategies for individuals with sickle cell disease undergoing surgery. She will describe strategies to minimize risks of postoperative complications in individuals with sickle cell disease, summarize the evidence for preoperative transfusion, postoperative venous thromboembolism prophylaxis, and postoperative pain management. Dr Payal Desai will discuss the current data on leg ulcers, priapism, and pulmonary HTN in sickle cell disease. She will note the current limited data on effective therapies and also review the current ongoing trials in the field.
Nirmish Shah, MD
Duke University School of Medicine
The management of patients with hematologic disorders often involves multi-disciplinary care, both for primary hematologic diseases that affect multiple organ systems, as well as for diseases with secondary hematologic complications. This educational session will explore the role of the hematologist in three diseases that necessarily involve multiple subspecialists: HHT, CTEPH, and cirrhosis. Using a case-based approach, this program will highlight the role of hematology within a broader context of disease management.
Dr. Adrienne Hammill will discuss the challenges of making a diagnosis of HHT given widely variable clinical presentations using a case-based approach. She will review the pathophysiology of this disease and present screening strategies and therapeutic options in accordance with the Second International Guidelines for the Diagnosis and Management of HHT published in 2020. Focusing on ways these patients can present to hematologists, she will discuss the multidisciplinary team approach and coordination required for optimal care of patients with HHT.
Dr. Karlyn Martin will outline the evaluation for and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Using a case-based approach, she will review criteria for CTEPH and CTED, and discuss how to approach the diagnostic evaluation of CTEPH. Finally, she will present an approach to treatment, including medical, surgical, and interventional therapies that require multi-disciplinary care.
Dr Lara Roberts will discuss the evidence for rebalanced hemostasis in advanced chronic liver disease and the dual propensity to bleeding and thrombosis. Using a case-based approach, the implications and management of abnormal coagulation and/or thrombocytopenia in the periprocedural setting will be outlined. Finally, she will address the challenges of anticoagulation for portal vein thrombosis.
Karlyn A. Martin, MD
Our understanding of myelopoiesis and the interplay between genetics, the innate and adaptive immune system, and the environment has changed the way we evaluate, monitor, and treat neutropenia disorders. It is now recognized that neutropenia can be a common presentation of both hematopoietic and immune congenital disorders and recognition and differentiation from benign causes is essential for patient management. Development of malignancy remains an immense obstacle for patient survival, but improved understanding of clonal hematopoiesis in congenital neutropenia disorders may lead to earlier recognition and improved outcomes. This educational session will review the modern evaluation of the neutropenic patient and common management decisions to optimize patient health. It will explore the mechanisms of clonal hematopoiesis in congenital neutropenia and how advances in this field are influencing our decisions on screening and treatment with hematopoietic cell transplant. Finally, it will highlight the role of the neutrophil in a broader context of the immune system and how immune dysregulation through genetic mutation or iatrogenic treatment can influence the production and function of the neutrophil.
Dr. Connelly will outline the diagnostic evaluation of neutropenia in both pediatric and adult patients. Based on the diagnosis and presence or absence of a mature neutrophil pool, he will provide a framework to guide treatment decisions including management of fever and use of G-CSF. Finally, he will review outcomes of hematopoietic cell transplant in congenital neutropenia and discuss a general transplant approach for patients with and without malignancy.
Dr. Link will present recent data regarding the development of clonal hematopoiesis and progression to leukemia in congenital neutropenia with specific focus on Severe Congenital Neutropenia and Shwachman Diamond Syndrome. He will discuss how our growing understanding of clonal hematopoiesis is advancing our clinical management of neutrophil patients, including how we monitor for leukemia and the role of hematopoietic cell transplant before malignant development in the era of enhanced molecular testing.
Dr. Walkovich will discuss the consequences of immune dysregulation on myelopoiesis and how to recognize immune disorders in neutropenic patients. She will review the pathophysiology driving neutropenia in inborn errors of immunity and draw connections to possible similar mechanisms of neutropenia resulting from immune related oncology therapies. By understanding the role of the immune system in myelopoiesis, she will discuss the use of targeted therapies in the context of immune dysregulation to improve myelopoiesis.
Kelly J. Walkovich, MD
University of Michigan, Ann Arbor, MI
Ann Arbor, MI
Hematologists are often asked to risk stratify and optimize hematologic disorders in patients preparing for surgery. Common issues include the perioperative management of anticoagulant and antiplatelet agents as well as assessment and management of thrombocytopenia, particularly heparin-induced thrombocytopenia. Given an aging population of patients with inherited bleeding disorders such as hemophilia and von Willebrand disease, the need for cardiac and orthopedic procedures is also increasing, along with need for hematologic expertise in the perioperative management of these conditions.
Dr. Allison Burnett will be discussing key aspects of anticoagulation management around surgical procedures. She will describe important differences between DOAC and warfarin management in this population, and rationale for those differences. She will also outline approaches for assessing thromboembolic and bleeding risk to aid in developing a patient-centered perioperative plan. Through cased-based discussion, she will demonstrate application of evidence-based, standardized approaches to promote safe, effective patient care.
Dr. Nathan Connell will discuss an approach to managing inherited bleeding disorders in aging patients needing surgery. Evidence-based guidelines for management of aging patients with bleeding disorders are lacking, largely due to underrepresentation of elderly patients in clinical trials, as well as the rarity of many bleeding disorders. He will discuss the current guidelines and recommendations in the perioperative hemostatic management of elderly patients with hemophilia, von Willebrand disease, as well as other rare bleeding disorders.
Dr. Allyson Pishko will outline an approach to evaluating a patient with HIT prior to cardiac interventions or surgery. She will review the "phases of HIT" and implications for heparin re-exposure during cardiac surgery. She will discuss alternative (non-heparin) anticoagulants in this setting. She will use a case-based approach to highlight situations where cardiac surgery should be delayed and strategies to minimize the risk if delays are not possible.
Nathan T. Connell, MD
Brigham and Women's Hospital
Dr. Rezan Abdul-Kadir will include a case presentation and discussion on the management of pregnancy in women with different types of von Willebrand Disease.
Marie Scully, MD
University College London
London, ENG, United Kingdom
This session will provide a comprehensive update on the thalassemia syndromes.
Dr. Sujit Sheth will briefly discuss the burden of thalassemia worldwide, and present a rationale for screening for carriers and potentially affected individuals. He will focus on thalassemia testing at various time points, including at prenatal, newborn, and postnatal visits. With immigration changing the prevalence of thalassemia in many western countries including the US, many individuals at risk may not have been identified appropriately. An algorithm of a suggested testing schema will be presented for adults whose diagnosis may have been missed in childhood. These strategies will identify individuals who would benefit for counseling, particularly when considering having a family.
Dr. Tippi MacKenzie will discuss novel approaches to the management of alpha thalassemia. She will briefly review the pathophysiology of alpha thalassemia, with particular focus on alpha thalassemia major which has the most severe clinical presentation. She will then discuss how intrauterine transfusion therapy has changed the clinical landscape by leading to long term survival in a disease that was otherwise considered fatal either in utero or shortly after birth. Finally, she will review the existing literature on allogeneic hematopoietic cell transplant as definitive therapy for alpha thalassemia major, and briefly review a novel strategy of intrauterine hematopoietic cell transplant followed by postnatal booster transplant for alpha thalassemia.
Dr. Erica Esrick will discuss novel therapies for beta thalassemia patients, beyond transfusions and chelation. She will discuss medications that are either recently approved or currently under investigation, as well as curative approaches including gene therapy and gene editing. Sample patient cases will be presented to highlight the risks and potential benefits of these therapies that patients and providers will need to consider in their clinical decision-making.
Sujit Sheth, MD
Weill Cornell Medicine
New York, NY
The COVID-19 pandemic has caused immense morbidity and mortality and, despite unprecedented public health measures, continues to rage across the United States and the world. Though COVID-19 is a primarily a respiratory illness, coagulation abnormalities are common in patients with COVID-19 and patients are at increased risk of venous and arterial thrombotic events. Immunothrombosis is recognized as central to the pathogenesis of COVID-19 organ dysfunction and anticoagulation has emerged as an attractive therapeutic intervention. This education session will explore the pathophysiology of COVID-19 associated coagulopathy and thrombosis and evidence supporting best practices in management including anticoagulation strategies depending on disease severity and clinical setting. The session will also discuss the role of passive immune therapies including convalescent plasma and monoclonal antibodies in COVID-19.
Dr. Shruti Chaturvedi will discuss the COVID-19-associated coagulopathy and bleeding in hospitalized patients including epidemiology, pathogenesis and evidence supporting current management recommendations. She will also discuss cytopenias as well as thrombotic and hemostastic complications associated with COVID-19 vaccination.
Dr. Scott Kaatz will primarily discuss the use of anticoagulation prophylaxis in COVID-19. He will briefly discuss the pathophysiology of immune micro thrombosis and the epidemiology of VTE. Vaccine-induced Thrombotic Thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome also be discussed.
Dr. Lise Estcourt will discuss the use of passive antibody therapies within the COVID-19 pandemic, including polyclonal and monoclonal antibody therapies that have been used within clinical trials. She will summarize the current evidence base for their use and how they should be used.
Shruti Chaturvedi, MBBS
Johns Hopkins University School of Medicine
Transfusion support remains a key intervention in the management of patients with SCD. Red cell transfusions are used in the acute and chronic management of many complications related to SCD, but are not without adverse effects, including alloimmunization and iron overload. This educational session will focus on the specific indications for transfusion, and the management and avoidance of two major transfusion-related complications, red cell alloimmunization and hemolytic transfusion reactions which continue to pose significant challenges both for patients, clinical teams, blood banks and immunohematological reference centers. Updates will be provided on the indications for transfusion in SCD and what international guidelines have in common with and their differences to the ASH guidelines, the advances in genotype red cell matching to minimize red cell alloimmunization, and new approaches for managing hemolytic transfusion reactions.
Dr France Pirenne, will review the different situations of blood group polymorphism that are involved in allo immunization in sickle cell disease. The most important and consensual preventive measure is prophylactic red cell antigen matching for Rh (D,C,E,c,e) and K antigens. The prevention of allo immunization by extension of matching to other blood groups, including variant antigens of the RH blood group, the use of genotyping rather than serology to characterize significant blood groups, and the prophylactic administration of immunosuppressive treatments remain a matter of debate. These strategies will be discussed, based on recent ASH recommendations, experience and literature.
Dr. Jeanne Hendrickson will discuss the management of delayed hemolytic transfusion reactions in patients with SCD. She will review the pathophysiology of antibody positive and antibody negative hemolytic transfusion reactions, including the roles that antibody evanescence and complement activation may play. She will discuss bystander hemolysis and potential therapeutic options for ongoing reactions, as well as strategies to prevent future reactions.
Michael Murphy, MD
University of Oxford
Oxford, ENG, United Kingdom