As vibrant blossoms filled the streets of Shanghai and the Huangpu River shimmered beneath the morning sun, the 2025 Hematology Translational and Innovation Conference, held in parallel with the 10th Shanghai Lymphoid Disease Symposium, was convened from June 27 to 29. This prominent academic event brought together leading experts from China and abroad to share research achievements and foster the translation of basic science into clinical advances. With a focus on innovative therapies, professional education, and scientific communication, the conference provided a dynamic platform for collaboration and progress.At the meeting, Professor Wenyu Shi—Vice Chair of the Lymphoma Committee of the Jiangsu Medical Doctor Association and faculty member at the Affiliated Hospital of Nantong University—shared a series of important research findings from the Jiangsu Collaborative Lymphoma Group (JCLG). Her presentation highlighted advances in the understanding of lymphoma-associated hemophagocytic lymphohistiocytosis (HLH), with emphasis on clinical characteristics, prognostic factors, and treatment strategies. The aim was to offer practical insights to support evidence-based clinical practice.
Oncology Frontier – Hematology Frontier is pleased to present this detailed summary for our readers.
Lymphoma-Associated HLH: Unique Challenges in the Elderly Population and a Novel Prognostic Model
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome triggered by a range of underlying conditions. It is characterized by excessive activation of cytotoxic T cells and natural killer (NK) cells, which in turn stimulate macrophage activation and the release of large quantities of inflammatory cytokines, ultimately leading to multi-organ and multi-system dysfunction. Among its subtypes, lymphoma-associated HLH (LA-HLH) is a severe immune-related complication triggered by lymphoma. It is particularly distinct in elderly patients, who exhibit unique clinical patterns and prognostic outcomes.
The Jiangsu Collaborative Lymphoma Group (JCLG) has conducted a series of in-depth investigations focusing on elderly patients with LA-HLH, aiming to better characterize their clinical features, prognostic factors, and treatment outcomes.
Prognostic Modeling for Elderly LA-HLH Patients
In elderly LA-HLH patients, B-cell non-Hodgkin lymphomas (NHL) accounted for 61.3% of cases, while T/NK-cell lymphomas made up 35.3%—a distribution pattern that differs notably from younger patients. The most common subtype was diffuse large B-cell lymphoma (DLBCL), comprising 56.7% of cases, followed by angioimmunoblastic T-cell lymphoma (AITL) at 9.3%. DLBCL was more prevalent among older patients, whereas aggressive NK-cell leukemia (ANKL) and extranodal NK/T-cell lymphoma (ENKL) were more frequently observed in younger populations.
Survival analysis revealed a median overall survival (OS) of 92 days for elderly LA-HLH patients. Interestingly, OS and 60-day survival probabilities were comparable between elderly and younger patients, with no significant statistical difference. However, patients with T/NK-cell lymphomas had dramatically shorter survival than those with B-cell lymphomas or Hodgkin lymphoma (39 days vs. 418 days). Furthermore, receiving HLH-directed therapy prior to lymphoma treatment or using etoposide-containing regimens was not associated with improved OS.
Further investigation identified three independent adverse prognostic factors for OS: the T/NK-cell subtype, low platelet count (< 37×10⁹/L), and elevated serum creatinine (> 62.05 μmol/L). Based on these variables, the research team developed a prognostic scoring model that stratifies elderly LA-HLH patients into low-, intermediate-, and high-risk groups. Each group demonstrated distinctly different survival durations and 60-day survival probabilities. This model provides clinicians with a powerful quantitative tool for personalized treatment planning and more accurate prognostic evaluation.
Clinical and Prognostic Significance of Serum β2-Microglobulin in Lymphoma-Associated HLH
β2-microglobulin (B2M), a component of the light chain of major histocompatibility complex (MHC) class I molecules, plays an important role in immune regulation. However, its clinical significance and prognostic value in lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) have not been fully elucidated.
In a recent study, the median B2M level in LA-HLH patients was reported at 5.19 mg/L, with the majority of patients exhibiting elevated levels significantly higher than those observed in general lymphoma populations. Using a cutoff value of 8.73 mg/L, the study found that patients with high B2M levels had a markedly shorter median overall survival—just 21 days—compared to 236 days in the low B2M group. The 6-month survival rates also showed a striking difference: 22% in the high-level group versus 54% in the low-level group. Additionally, B2M levels were found to correlate with serum creatinine, platelet count, and albumin levels.
Further analysis identified several risk factors associated with poor prognosis: elevated B2M, increased creatinine, neutropenia, severe thrombocytopenia, low fibrinogen levels, and high Epstein-Barr virus (EBV) DNA copy numbers. These variables were integrated into a prognostic model that stratified patients into low-, intermediate-, and high-risk groups. The median overall survival for each group was 428 days, 102 days, and 18 days, respectively. The corresponding 6-month survival rates were 67%, 46%, and 14%, showing significant differences across risk strata.
The findings suggest that B2M is an independent prognostic factor in LA-HLH and is positively correlated with creatinine levels. This highlights its potential utility in risk stratification and treatment planning for patients with this aggressive and often fatal complication of lymphoma.
Application of the EASIX Score in T/NK-Cell Lymphoma-Associated HLH
Focusing on the distinct subtype of T/NK-cell lymphoma-associated HLH (T/NK-LAHLH), the study explored the prognostic utility of the Endothelial Activation and Stress Index (EASIX), a marker originally developed to reflect endothelial dysfunction. EASIX is calculated using the formula: EASIX = LDH (U/L) × Creatinine (mg/dL) / Platelet count (10⁹/L).
In this analysis, 212 patients who met the HLH-2004 diagnostic criteria and were diagnosed with T/NK-LAHLH were included. Using X-tile software, the optimal EASIX cutoff value was determined to be 40.1. Patients with EASIX scores above this threshold had significantly worse prognoses.
Building on this, researchers developed a prognostic index incorporating three key variables: EASIX (2 points), age (1 point), and fibrinogen level (1 point). This model allowed precise stratification of patients into distinct risk categories, demonstrating strong predictive power for survival outcomes. As a simple and practical tool, this prognostic index offers valuable clinical utility in managing T/NK-LAHLH, a highly complex and aggressive disease.
Conclusion
Taken together, the Jiangsu Collaborative Lymphoma Group’s series of studies have made significant progress in characterizing the clinical features and constructing prognostic models for lymphoma-associated HLH. These findings deepen understanding of the disease and offer robust, evidence-based guidance for clinical decision-making. Future prospective validation and expanded clinical research will be essential to confirm and refine these insights, with the ultimate goal of improving outcomes and quality of life for patients affected by this challenging condition.
Expert Profile
Professor Wenyu Shi holds an MD degree and serves as Chief Physician, Professor, and Doctoral Supervisor. She is the Director of the Department of Oncology and the Oncology Teaching and Research Office at the Affiliated Hospital of Nantong University. She also serves as Deputy Director of the Department of Hematology and Deputy Director of the Institute of Hematological Diseases.
Professor Shi has held visiting academic positions at the University of Texas MD Anderson Cancer Center and Duke University in the United States, as well as at Queen Mary Hospital of the University of Hong Kong.
She currently serves in multiple key academic and professional leadership roles: – Member, Lymphoid Disease Group, 11th Committee of the Hematology Branch, Chinese Medical Association – Deputy Director, Jiangsu Branch of the China HLH Alliance; Chair, Lymphoma-Associated HLH Group, Jiangsu Branch – Member, Anti-Lymphoma Alliance, Chinese Society of Clinical Oncology (CSCO); Vice Chair, Jiangsu Anti-Lymphoma Alliance – Chair, Lymphoma Branch, Jiangsu Association of Geriatric Medicine – Vice Chair, Lymphoma Committee, Jiangsu Medical Doctor Association – Standing Committee Member and Secretary General, Hematology Branch, Jiangsu Medical Doctor Association – Deputy Head, Lymphoma Group, Jiangsu Medical Association – Vice Chair, Lymphoma Committee, Jiangsu Society of Research Hospitals – Chair, 2nd Lymphoma Committee, Jiangsu Anti-Cancer Association – Selected Talent in Jiangsu’s “Six Talent Peaks” Program – Key Medical Talent in Nantong’s “226 Talent Program”
She has led two projects funded by the National Natural Science Foundation of China and is primarily engaged in both clinical and basic research on lymphoma.
Jiangsu Province Hospital
Attending Physician and Postdoctoral Fellow, Department of Hematology, Jiangsu Province Hospital Secretary, Hematology Branch and Lymphoma Committee, Jiangsu Medical Doctor Association Secretary, Jiangsu Branch of the China HLH Alliance
First or corresponding author of multiple SCI-indexed publications in top international journals, including Nature Reviews Clinical Oncology, Journal of Hematology & Oncology, Modern Pathology, Blood Cancer Journal, and British Journal of Haematology
Recipient of the Jiangsu Anti-Cancer Association Science and Technology Award (2022) Principal investigator of research projects funded by the National Natural Science Foundation of China and others Holder of four authorized national invention patents
