Editor’s Note:The 66th Annual Meeting of the American Society of Hematology (ASH) took place from December 7–10, 2024, in San Diego, USA. As the largest and most comprehensive international academic conference in the field of hematology, ASH attracts leading global experts to discuss groundbreaking research and advancements. This year, Dr. He Huang’s team from the Bone Marrow Transplantation Center of The First Affiliated Hospital, Zhejiang University School of Medicine, had 20 studies selected for presentation, including eight as oral presentations. Their achievements not only highlighted their exceptional contributions but also delivered valuable research findings and innovative strategies to the global academic community.

To provide deeper insight into these impactful studies, Hematology Frontier invited  Dr. He Huang and his team members,  Dr. Yi Luo and Associate Researcher Yishan Ye, to share their research outcomes, the secrets behind their success, and their perspectives on the future of the field in a roundtable discussion.

01. Could you briefly introduce your team’s achievements at ASH this year and provide an overview of the current state of bone marrow transplantation in China, including the challenges that still need to be addressed?

Dr. He Huang: I am honored to participate in the 66th ASH Annual Meeting. This year, our team presented eight oral presentations and 12 posters, covering areas such as hematopoietic stem cell transplantation (HSCT), leukemia mechanisms, and cellular immunotherapy.

HSCT remains a critical treatment for hematological malignancies and has seen significant advancements in recent years. China has made remarkable progress in HSCT, with the number of annual transplantations exceeding 20,000, largely due to innovations such as haploidentical HSCT. At this meeting, we presented studies related to this field, including those on the prevention and treatment of graft-versus-host disease (GVHD) and relapse.

However, challenges remain:

1. Relapse: Addressing relapse post-transplantation, especially in patients with TP53 mutations or high-risk leukemia, is critical.
2. GVHD: While precision therapies have brought significant progress, better strategies are needed for resistant and chronic GVHD.
3. Donor selection: Optimizing donor selection for haploidentical transplantation to benefit more patients is a pressing issue.

Furthermore, integrating HSCT with other therapies to maximize patient outcomes at a lower cost is a goal, particularly for elderly and refractory/relapsed patients. As precision medicine advances, it is crucial to explore ways to combine HSCT with other treatments to ensure a more targeted and effective approach.

02. Your team presented a study on using the Easix score to predict survival outcomes in elderly patients undergoing haploidentical HSCT. Could you explain this dynamic prognostic tool and its implications for elderly patients?

Dr. Yi Luo: The Easix score is a simple tool based on dynamic serum biomarkers—lactate dehydrogenase (LDH), serum creatinine, and platelet count. It evaluates endothelial activation and stress indices to predict outcomes after HSCT. Historically, the Easix score has been used to predict acute GVHD. Recent prospective studies have shown its effectiveness in predicting survival and non-relapse mortality (NRM) after HSCT, but these studies primarily focused on younger patients.

Haploidentical HSCT is a major transplantation approach in China. At the same time, the incidence of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) among the elderly is rising. Many elderly patients face challenges such as reduced physical fitness and multiple comorbidities, making it critical to identify a simple and effective prognostic tool before transplantation.

Our multicenter study, involving 164 elderly patients (≥60 years) who underwent haploidentical HSCT across 12 institutions in Zhejiang Province, assessed the Easix score at key time points (pre-transplant, days 7, 14, 28, 56, and 100 post-transplant). We found that the Easix score effectively predicted NRM and survival outcomes.

Statistical analysis revealed that an Easix score ≥4.25 significantly reduced two-year survival rates. This dynamic tool can guide stratified treatment for elderly HSCT patients. For those with higher Easix scores, optimizing preconditioning regimens and managing post-transplant complications may improve outcomes.

03. Your team collaborated with the EBMT Acute Leukemia Working Group on AML transplantation strategies, presenting findings at this year’s ASH. Could you elaborate on the research and its clinical significance?

Associate Researcher Yishan Ye: Our team collaborated with the European Society for Blood and Marrow Transplantation (EBMT) on two poster presentations at this year’s ASH, continuing our long-standing research focus on AML donor selection. Selecting the optimal donor is crucial for improving survival and reducing relapse in AML, particularly in high-risk cases.

One study compared outcomes of AML patients in their second complete remission (CR2) undergoing HSCT from three donor types—haploidentical, unrelated fully matched, and related fully matched donors. Data from over 4,000 patients across 200 global centers showed:

• Outcomes of haploidentical and unrelated fully matched HSCT were similar and comparable to related fully matched HSCT.
• However, related fully matched donors had a slight advantage in reducing NRM.

While related fully matched donors remain the first choice for CR2 AML patients, improvements in post-transplant management may allow haploidentical donors to become a preferred option in the future.

The second study addressed a clinical dilemma: whether to choose younger haploidentical donors or older unrelated donors from bone marrow registries. Existing evidence suggests younger donors improve survival and reduce transplant-related mortality.

Our study, involving over 4,000 patients from more than 200 centers, compared outcomes between these donor groups. Findings showed younger haploidentical donors provided better outcomes for relatively younger and fitter patients compared to older unrelated donors. With their high availability and faster access, younger haploidentical donors may become the preferred choice for AML patients in the future.

Dr. He Huang’s team has made significant contributions to the fields of bone marrow transplantation and cellular immunotherapy, addressing key challenges such as relapse, GVHD, and donor selection. Their research continues to pave the way for innovative strategies and improved patient outcomes, with broad implications for both clinical practice and future investigations.

04. Beyond clinical studies, your team has achieved significant breakthroughs in basic research. Could you share an overall evaluation of these achievements and your insights on leading a team in exploring cutting-edge advancements?

Dr. He Huang: At this year’s ASH conference, in addition to our clinical research accomplishments, our team made notable breakthroughs in basic research. For instance, we have advanced the development of metabolically enhanced CAR-T therapy. Our earlier studies demonstrated that interleukin-10 (IL-10) can enhance the functionality of CAR-T cells.

In the field of cellular immunotherapy, we mapped the entire process of cytokine release syndrome (CRS), including its initiation, progression, cell subpopulations involved, and the interplay between cytokines. We also analyzed CRS across different diseases, distinguishing between CRS induced by cellular therapy and CRS resulting from other inflammatory or infectious causes. Particularly, we conducted insightful studies at the single-cell level, providing a detailed understanding of these processes.

In the domain of leukemia, we explored the epigenetic mechanisms underlying certain specific subtypes of leukemia, clarifying their roles in the disease’s onset and progression. Additionally, we analyzed the metabolic processes involved in the survival of red blood cells, focusing on specific factors and epigenetic mechanisms that influence erythroid differentiation and maturation. These findings were also showcased at the conference.

Our team operates with a unified philosophy: innovative clinical advancements are the driving force that enables us to better serve our patients.

However, achieving this requires addressing a range of scientific challenges. Our team has fostered close collaboration between clinical practitioners and basic science researchers, ensuring an integrated approach. This dynamic collaboration has become a hallmark of our work.

I believe this model—combining exceptional clinical practice with groundbreaking basic research—represents the future of medical progress. By synergizing these two domains, we can collectively drive advancements in hematology and ultimately improve patient care and outcomes.

Dr. He Huang

The First Affiliated Hospital, Zhejiang University School of Medicine

Professional Titles and Positions:

• Qiushi Distinguished Professor, Zhejiang University
• Special Expert of Zhejiang Province
• Chief Scientist of the 973 Program
• Chief Physician and Doctoral Supervisor
• Director, Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine
• Director, Zhejiang University Institute of Hematology
• Director, Zhejiang Provincial Engineering Center for Stem Cell and Cellular Immunotherapy
• Member, Expert Panel of the National Key Research and Development Program “Stem Cell and Translational Research”
• Deputy Director, Expert Committee of the Chinese Bone Marrow Donor Program
• Standing Committee Member, Hematology Branch of the Chinese Medical Association
• Vice Chair, Academic Committee of the Asian Cellular Therapy Organization
• Member, Executive Committee, Asia-Pacific Blood and Marrow Transplantation Group
• Member, International Academic Committee, European Society for Blood and Marrow Transplantation
• President, Zhejiang Immunology Society

Research Focus:

• Basic research on stem cells and clinical application of hematopoietic stem cell transplantation
• Cutting-edge techniques and translational research in cellular immunotherapy

Awards and Achievements:

• Twice awarded the Second Prize of the National Science and Technology Progress Award (2003 and 2015)
• Principal investigator for key projects under the 973 Program, 863 Program, National Natural Science Foundation of China, and International Cooperation and Exchange Projects, among others (27 projects)
• Published 278 SCI papers as corresponding author in top journals, including New England Journal of Medicine, Nature, Cell Research, and Lancet Haematology
• Received 15 provincial and ministerial-level science and technology awards
• Granted 21 invention patents

Academic Contributions:

• Delivered over 100 keynote speeches and oral presentations at major international conferences in the past five years
• Chief editor of the first domestic textbook on CAR-T cell therapy, “CAR-T Cellular Immunotherapy”, published by People’s Medical Publishing House
• Co-editor of the national graduate-level textbook “Hematology”, also published by People’s Medical Publishing House
• Contributed to 11 additional books and textbooks

Editorial Roles:

• Editorial board member of Bone Marrow Transplantation and Journal of Hematology and Oncology, leading journals in the field of hematopoietic stem cell transplantation.