Molecular pathology and clinical characteristics play a crucial role in guiding treatment selection and predicting the prognosis of diffuse large B-cell lymphoma (DLBCL). The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), have emerged as pivotal regulators of immune checkpoints in cancer. The objectives of this study are to investigate the correlation between the expression levels of PD-1 and soluble PD-L1 (sPD-L1) in the peripheral blood of DLBCL patients, analyze their clinicopathological characteristics, and identify the optimal beneficiary group for PD-1/PD-L1 blockade. Peripheral blood samples were collected from 36 DLBCL patients before their initial treatment at Shandong Cancer Hospital between December 2018 and July 2019. The expression levels of PD-1 and sPD-L1 were measured using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The clinicopathological characteristics, including age, sex, Ann Arbor stage, International Prognostic Index (IPI) score, response to treatment, etc., were recorded for each patient. The surface expression of PD-1 on peripheral blood T cells was significantly higher in DLBCL patients compared to healthy controls. There was a significant association between elevated PD-1 expression levels and the advanced Ann Arbor stage (P=0.0153) as well as the B group (P=0.0184). Higher sPD-L1 levels were associated with the GCB subtype according to Hanss classification (P=0.0435). The expression levels of PD-1 and sPD-L1 in the peripheral blood of DLBCL patients are significantly correlated with advanced disease stage, B group, and GCB subtype according to Hanss classification. This suggests that the PD-1/PD-L1 axis play a critical role in specific subgroups of DLBCL. Targeting this axis could serve as a potential therapeutic strategy to enhance the clinical outcomes of DLBCL patients. Further studies are necessary to explore the prognostic implications of PD-1 and sPD-L1 expression levels in DLBCL patients.

Objective Chemotherapy-induced thrombocytopenia (CIT) is a dose-limiting toxicity that can necessitate chemotherapy delays or dose reductions. This review examines evidence that CIT involves injury to both megakaryocytes (MKs) and the bone marrow microenvironment (BMME) and considers the implications for thrombopoietin receptor agonist (TPO-RA) therapy. Methods PubMed was searched for English-language literature without a publication-date restriction and was comprehensively updated through August 10, 2026. Evidence concerning CIT mechanisms and the mechanistic effects of TPO-RAs was integrated through a predefined narrative thematic framework, with explicit consideration of the directness of evidence for human CIT. Results Available studies suggest that TPO-RAs may have effects beyond platelet production, although evidence for vascular, metabolic, and immune microenvironmental effects derives largely from non-CIT or preclinical settings. Persistent rather than nadir CIT, lower endogenous thrombopoietin, and the absence of marrow infiltration, prior pelvic irradiation, or temozolomide exposure may enrich for response. A 2026 phase 3 trial directly demonstrated that romiplostim reduced CIT-induced chemotherapy dose modifications in persistent CIT, but biomarker-guided selection remains to be validated. Conclusion The “seed and soil” model organizes previously published evidence and should be regarded as hypothesis-generating in human CIT. Prospective studies are needed before microenvironment-directed combinations or CIT-specific biomarker thresholds can be recommended.

Objective: Richter syndrome (RS) occurs in approximately 2–10% of chronic lymphocytic leukemia (CLL) patients, more often during the disease course than at diagnosis, with a diffuse large B-cell Lymphoma (DLBCL) histology in 95% of cases. Despite great advances in the treatment of CLL in recent years, RS also develops in patients treated with novel agents, as summarized in our case report and review. Methods: We summarized 3 patients with RS treated with immunochemotherapy combined with BTK inhibitor (BTKi) or BCL2 inhibitor (BCL2i) and reviewed the literature. Results: Three RS patients were summarized. Patient 1 was transformed into DLBCL during dose reductions in ibrutinib and achieved bone marrow (BM) minimal residual disease (MRD)-negative complete response (CR) after rituximab etoposide, dexamethasone, doxorubicin, cyclophosphamide, and vincristine (R-EDOCH) combined with BTKi treatment and sustained progression-free survival (PFS) for more than 2 years. Patient 2, who transformed at the time of diagnosis, progressed after being treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), followed by PD1 antibody combined with cytosine, arabinoside, cisplatin and dexamethasone (DHAP) treatment and PD1 antibody combined with ifosfamide, carboplatin, and etoposide (ICE) treatment. Patient 2 achieved CR after treatment with rituximab, gemcitabine, and oxaliplatin (R-GemOx) combined with BTKi. Patient 3, who transformed at the time of diagnosis with CARD11, TP53, and ATM mutations, progressed after being treated with R-EDOCH combined with BTKi and achieved MRD-negative CR after treatment with R-GemOx and venetoclax, which has continued for 3 months. We summarized new protocols utilizing targeted therapy, such as BTKi acalabrutinib, and checkpoint inhibition, and the potential role of precision medicine in future trials of RS treatment. The efficacy of these protocols as single agents or in combination with immunochemotherapy is currently being evaluated. Conclusion: In our study, immunochemotherapy combined with BTKi or BCL2i achieved favorable efficacy in the treatment of RS. The treatments should be optimized by the combination of both chemotherapies and targeted therapy to develop a specific individual approach for each patient, according to previous treatment and biological characteristics.

Objective: To evaluate the prognostic value of TP53 mutations in patients with diffuse large B-cell lymphoma (DLBCL). Methods: We retrospectively analyzed the clinical data and gene sequencing results of 253 newly diagnosed DLBCL. Survival and correlation analyses were performed. Results: We further revealed significant prognostic heterogeneity among different TP53 hotspot mutations, with mutations at codons G245, R175, R273, and R282 indicating a poorer prognosis. Within the DBD, mutations in exons 5, 7, and 8 were associated with poorer PFS, while mutations in exons 5, 6, and 8 were linked to poorer OS. Additionally, mutations in the Loop-L2, Loop-L3, and LSH motifs within the DBD were all significantly associated with unfavorable PFS and OS. Notably, in the cohort treated with R-CHOP plus novel agents (R-CHOP+X), there were no significant differences in response rates or survival between TP53-mut and TP53-wt patients, suggesting this combination may overcome the adverse prognosis associated with TP53 mutations. Conclusion: TP53 mutation is a crucial adverse prognostic factor in DLBCL. Given the significant prognostic heterogeneity among different TP53 hotspot mutations, a more refined risk stratification based on the TP53 mutational profile is warranted in clinical practice. For patients with high-risk mutations, combining R-CHOP with targeted therapies and exploring novel combination strategies targeting specific pathways are recommended. In contrast, standard R-CHOP may remain an appropriate option for patients with low-risk mutations. Future prospective trials are needed to validate the efficacy of R-CHOP combined with targeted agents in TP53-mutated DLBCL to optimize treatment strategies and improve patient outcomes.