Lymphoma is an expanding health burden across China, driven by an annual incidence of 6.03 per 100,000. A 2026 special issue of the American Journal of Hematology consolidates nine recent studies addressing diverse lymphoma subtypes, highlighting advances in molecular diagnostics, targeted therapy, immunotherapy, CAR-T-cell therapy, and transplantation practices.
The landscape of lymphoma care is undergoing a profound shift. Researchers and clinicians are moving beyond conventional chemotherapy regimens, incorporating precision tools to track minimal residual disease, refine risk stratification, and sequence novel biologic agents. These developments arrive as public health registries document an escalating trend in lymphoma diagnoses over the past two decades.
The Expanding Diagnostic Utility of Circulating Tumor DNA
Molecular monitoring via circulating tumor DNA (ctDNA) is redefining how clinicians evaluate treatment response. A prospective multicenter study focusing on peripheral T-cell lymphoma demonstrated that ctDNA achieved a 75.2% sensitivity for mutations originally detected in tumor tissue.
Shifts in ctDNA concentration and variant allele frequency closely mirrored patient treatment response and progression-free survival. However, the diagnostic performance of ctDNA varied substantially across distinct disease subtypes. Sensitivity peaked at 82.1% in angioimmunoblastic T-cell lymphoma, yet dropped to 37.1% in extranodal natural killer/T-cell lymphoma.
In cases of primary central nervous system lymphoma, patients receiving a therapeutic combination of rituximab, high-dose methotrexate, and orelabrutinib showed encouraging patterns. The clearance of cerebrospinal fluid ctDNA during treatment correlated strongly with achieving a complete response and prolonged progression-free survival. This molecular clearance frequently demonstrated superior predictive accuracy compared to interim PET/CT imaging, while the clearance of MYD88 mutations similarly signaled favorable clinical outcomes.
Novel Regimens and Stem Cell Strategies in T-Cell and NK/T-Cell Lymphomas
For lymphomas where standard therapeutic options remain scarce, clinical trials are testing chemotherapy-free combinations and aggressive transplantation pathways. The phase II RCLARITY trial evaluated a regimen comprising rituximab, lenalidomide, and chidamide in patients with relapsed or refractory angioimmunoblastic T-cell lymphoma. The combination yielded an overall response rate of 71.4%, with a median overall survival of 17.6 months.
Extranodal natural killer/T-cell lymphoma, a subtype with heightened prevalence in East Asia, received distinct focus. A retrospective analysis of 107 patients with advanced disease who achieved complete remission found that upfront autologous stem cell transplantation was associated with a higher three-year progression-free survival rate of 78.2%, compared to 54.6% for patients who did not undergo upfront transplantation. The overall survival benefit, however, lacked statistical significance after adjusting for other clinical treatment factors.
Addressing procedural hurdles in transplant delivery, a prospective evaluation examined stem cell mobilization in patients categorized as poor mobilizers. Among 140 Chinese patients, the addition of plerixafor to granulocyte colony-stimulating factor allowed 80.7% of participants to reach the target threshold of at least 2 × 10^6 CD34+ cells per kilogram within four or fewer apheresis days.
Bispecific Antibodies as a Bridge to CAR-T Therapy
Real-world data regarding bispecific antibody treatment offer clarity on sequential immunotherapy strategies. Among 64 Chinese patients with relapsed or refractory aggressive B-cell lymphoma, glofitamab-based salvage therapy achieved an overall response rate of 78.7% and a complete response rate of 41.1%.
Estimated one-year progression-free and overall survival rates stood at 61.3% and 67.7%, respectively. Crucially, prior exposure to bispecific antibodies did not compromise subsequent CAR-T-cell manufacturing success or clinical efficacy in this cohort.
Investigators observed that patients who responded to glofitamab possessed higher baseline CD4+ effector T-cell counts and greater early CD8+ T-cell expansion. These immunological markers indicate that a patient’s functional T-cell state heavily influences their response to CD20×CD3 bispecific therapy, reinforcing glofitamab’s viability as a bridging strategy to CAR-T cell infusion.
Refining Risk Assessment Through Multi-Omics and Long-Term Survival Data
Beyond individual therapeutics, researchers are combining multiple layers of biological and clinical data to sharpen risk stratification. In primary central nervous system lymphoma, investigators utilized whole-genome sequencing and multiplex immunofluorescence to isolate distinct genomic and tumor microenvironment subgroups.
This integrated approach identified a small high-risk population constituting 9.8% of the cohort, characterized by a median overall survival of only three months, a vulnerability traditional clinical risk factors frequently fail to capture.
These modern diagnostic and therapeutic expansions occur against a backdrop of known long-term treatment risks. Across broad clinical cohorts, long-term survivors of Hodgkin lymphoma face elevated cumulative mortality risks decades post-therapy, driven largely by second malignancies, cardiovascular disease, and pulmonary complications. Historical data from multicenter cohorts of patients treated between 1965 and 2000 documented an absolute excess mortality of 123 excess deaths per 10,000 person-years, with standardized mortality ratios persisting in 40-year survivors.
Subsequent analyses of patients treated between 2000 and 2016—the era where ABVD became the preferred frontline regimen—similarly identified heart disease and infection as leading causes of non-lymphoma mortality, particularly among older adults. Contemporary protocols increasingly integrate risk-adapted and PET-adapted strategies to curtail cumulative toxicity without sacrificing disease control.
