ASH is spotlighting groundbreaking discoveries that are reshaping the landscape of established and emerging therapies, while providing profound insights into the biology of the hemostatic system and the pathophysiology of disease. These advances, once confined to specific conditions, now challenge researchers and clinicians to think beyond traditional boundaries. Leveraging therapies with proven efficacy can accelerate their transition from bench to bedside, yet success demands a nuanced approach — tailored to the unique disease biology, patient population, therapeutic goals, and potential complications. Striking this balance is essential to ensuring both efficacy and long-term sustainability.
Proactive Transplantation in Schwachman-Diamond Syndrome Offers Hope for Young Patients
Patients and caregivers affected by inherited bone marrow failure syndromes are faced with the dilemma of choosing potentially curative stem cell transplantation versus delaying the procedure due to the potential but significant risks associated. Outcomes data in Schwachman-Diamond Syndrome will be presented this morning (10:00 a.m. - 10:15 a.m., Convention Center, Room 11), showing that early allogeneic hematopoietic stem cell transplantation significantly improves survival for young patients with high-risk features such as TP53 mutations or bone marrow dysplasia (Abstract 441). Shifting the approach to early intervention instead of transplantation after evolution to malignancy greatly improves outcomes.
Gene Therapy Versus Stem Cell Transplantation (SCT): A Robust Argument for SCT
Yesterday’s Poster Session featured the work of Josu de la Fuente, PhD, and colleagues, presenting 10 years of real-world data from 36 countries in Europe, Asia, and Africa on allogeneic transplantation for sickle cell disease (Abstract 2184). The study’s findings indicated high cure rates with a low incidence of severe chronic graft-versus-host disease in both pediatric and adult populations, underscoring the viability of transplantation as a curative option. Senior author Emanuele Angelucci, MD, said in an interview conducted before the session that he believes the real-world data “demonstrate the increasing number of transplantations for this disease and the real-life outstanding results, clearly, hematopoietic transplantation is the benchmark for emerging gene therapy, irrespective of age.”
Reining in the Cytokine Storm Across CAR-T Therapy, COVID-19, and SLE: Is Transcriptomics the Key?
Today, researchers from China’s Zhejiang University School of Medicine will share compelling data on the single-cell transcriptomic atlas of cytokine release storm (CRS) in three diverse contexts: chimeric antigen receptor T-cell (CAR-T) therapy, COVID-19, and systemic lupus erythematosus (SLE). As a CAR-T ex-vivo gene therapist, I see CRS as the most intriguing and unpredictable presentation that could make or break a patient during the peak of disease. Join this session today (10:45 a.m. - 11:00 a.m., Manchester Grand Hyatt, Grand Hall D) to learn about the role of hyperproliferative CD8+ T cells and exhausted T cells in CRS from CAR-T therapy, the effect of myeloid cells activated by COVID-19 in the biology of the infection, and how elevated ribosomal and phagocytic activity in B cells and monocytes drive systemic inflammation in SLE (Abstract 420).
Keeping Blood Vessels Organized in Hereditary Hemorrhagic Telangiectasia
The definition of “common” depends on where and what we are looking for. Disorders of vessels, such as hereditary hemorrhagic telangiectasia (HHT), are now recognized as one of the most frequent causes of inherited bleeding, proving that if we want to effectively understand and control hemorrhage, we must look beyond the blood. Treating patients with HHT involves supporting them through their bleeding manifestations and ensuing iron deficiency anemia. But it doesn’t stop there. This afternoon’s Oral Abstract Symposia on novel treatments and outcomes in disorders of coagulation (12:00 p.m. - 1:30 p.m., Convention Center, Room 29) will showcase data on the safety of disease biology-modifying agents for HHT.
Immunomodulatory agents have long been established as an effective treatment for HHT given their angiogenic properties. The observational study conducted by Ellen Zhang, MD, and colleagues followed patients with HHT treated with pomalidomide for up to four years (Abstract 558). From a safety standpoint, there were no emergent toxicities, but the overall efficacy remains limited in patients with gastrointestinal bleeding. Who benefits from this therapy? Patients with epistaxis do! Attend this session and learn more about individualizing therapy to meets patient’s long-term goals.
New drugs are just around the corner. The AKT1/2 inhibitor VAD004, which targets the pathways that lead to vascular malformations, is the first-ever novel therapy being developed specifically for this disorder. While the drug is in the early stages of development, the proof-of-concept study that will be presented by Hanny Al-Samkari, MD, shows positive signals in terms of safety and tolerability (Abstract 553).
In its breadth and depth, #ASH24’s classical hematology program shows that advancing knowledge in hematology requires using both a microscope to zoom in on the smallest details and a telescope to grasp the vast, interconnected whole.
