Editor's Note: Intravascular large B-cell lymphoma (IVLBCL) is a rare form of non-Hodgkin lymphoma with atypical clinical presentations, leading to high rates of misdiagnosis and missed diagnosis in clinical practice. There is an urgent need to improve the current status of diagnosis and treatment. Recently, the "2024 Northern Hematology and Oncology Immunotherapy Conference," hosted by the Tianjin Society of Hematology and Regenerative Medicine, was held grandly in the northern coastal city of Tianjin. The conference brought together renowned hematology experts from across the country, focusing on the immunotherapy of hematologic malignancies. They explored the latest advances in the diagnosis and treatment of various hematologic sub-specialties, the pathogenesis of hematologic tumors, and progress in immunotherapy. At the conference, Dr. Bing Xu from The First Affiliated Hospital of Xiamen University delivered an outstanding report titled "Advances in the Diagnosis and Treatment of Intravascular Large B-Cell Lymphoma—Interpretation of the 2023 Chinese Expert Consensus," providing crucial guidance for comprehensively understanding and recognizing this disease. Hematology Frontier invited Dr. Bing Xu to share further insights on this topic.Current Status and Challenges in the Diagnosis and Treatment of IVLBCL in China
Dr. Bing Xu: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. Due to its low incidence, it is considered a rare disease. The hallmark of IVLBCL is the accumulation of tumor cells within the blood vessels, which leads to atypical clinical manifestations, making diagnosis extremely challenging. Many patients are only diagnosed with IVLBCL posthumously. The delay in diagnosis often results in missed treatment opportunities and non-standardized treatment processes, contributing to high mortality rates. This is currently one of the major challenges in the field of IVLBCL.
Two Diagnostic Techniques to Improve IVLBCL Diagnosis
Dr. Bing Xu: IVLBCL primarily manifests as unexplained fever, with other symptoms including neurological manifestations, skin changes, and lung abnormalities, though none of these are specific enough for a definitive diagnosis through imaging alone. However, recent years have seen significant progress in the field of IVLBCL in China. First, the discovery of significantly elevated interleukin-10 (IL-10) levels has been found to assist in guiding pathological examination and improving early diagnosis. Secondly, deep skin biopsy has now been recommended by both international and domestic experts as a primary diagnostic method for IVLBCL. By performing random deep skin biopsies on areas such as the abdomen and lower limbs, the diagnosis of IVLBCL can be made more easily.
Immunochemotherapy as a Foundation: New Treatment Methods Show Initial Efficacy
Dr. Bing Xu: Once IVLBCL is diagnosed, treatment is recommended to be based on immunochemotherapy, which has been shown to be more effective than chemotherapy alone. When the central nervous system is involved, standard immunochemotherapy cannot cross the blood-brain barrier, so a combination of immunochemotherapy and high-dose methotrexate is recommended. For younger patients who are responsive to chemotherapy, autologous hematopoietic stem cell transplantation may further improve outcomes.
In recent years, a study conducted by Peking Union Medical College Hospital made significant progress, demonstrating that the combination of zanubrutinib and R-CHOP in treating IVLBCL showed promising efficacy. However, the number of cases in this study was relatively small, so further research with larger sample sizes is needed to validate these findings. Since most IVLBCL cases belong to the MCD subtype, Bruton’s tyrosine kinase (BTK) inhibitors are likely to be effective. Combining BTK inhibitors with immunochemotherapy could potentially improve treatment outcomes for this disease.
Overall, while IVLBCL is a relatively rare disease with atypical clinical presentations that can easily lead to missed diagnoses, timely and accurate diagnosis followed by standardized treatment can yield favorable outcomes. The purpose of the “Chinese Expert Consensus on the Diagnosis and Treatment of Intravascular Large B-Cell Lymphoma” is to enhance clinicians’ awareness of the disease, including the use of diagnostic tests or biopsies to confirm the diagnosis, and to guide standardized treatment according to consensus standards, thereby significantly improving patient prognosis.
Dr. Bing Xu
- Chief Physician, Professor, and PhD Supervisor
- Recipient of the State Council Special Allowance
- National Distinguished Physician
- Prominent Young and Middle-Aged Expert with Outstanding Contributions in Fujian Province
- Director of the Hematology Department at Xiamen University and Director of the Hematology Research Institute at Xiamen University
- Director of the Hematology Department and the Internal Medicine Training Base at The First Affiliated Hospital of Xiamen University
- Standing Member of the Hematology Physician Branch of the Chinese Medical Doctor Association
- Vice President of the Hematology Branch of the Chinese Society of Geriatric Medicine and Chair of the Leukemia Working Committee
- Head of the Follicular Lymphoma Working Group in China
- Standing Member of three professional committees under the Chinese Anti-Cancer Association, including Hematologic Tumors and Lymphoma
Professor Xu has received eight provincial and ministerial-level Science and Technology Progress Awards as the first completer, and has led six key and general projects under the National Natural Science Foundation of China. He has published over 200 papers as the first or corresponding author in journals such as BLOOD and JHO, with more than 100 SCI papers and a total impact factor exceeding 600. He is also the first inventor on six national invention patents.
