High-Grade B-Cell Lymphoma (HGBCL) with gene rearrangements in MYC and BCL2 and/or BCL6 is an aggressive malignancy usually presenting in advanced stages. Current recommendations suggest the use of regimens more intensive than R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), which are based on retrospective studies and single-arm prospective trials that included patients who are mostly in the advanced stage, and did not receive consolidation radiotherapy.

The optimal approach and treatment of HGBCL, whether limited-stage (LS) or advanced-stage, remains to be determined. Here we describe the promising outcomes of three patients with LS and low IPI HGBCL with the use of R-CHOP as induction chemotherapy regimen, which was followed by consolidation radiotherapy.

Three women, 54-, 60-, and 64-years of age diagnosed to have HGBCL with MYC, and BCL2 and/or BCL6 rearrangements, with Ann Arbor stages I-IIE were included in this case series. All three patients had complete metabolic response to 6 cycles of R-CHOP and was subsequently treated with consolidation involved site radiotherapy (ISRT; total dose 30-36 Gy). Chemotherapy and radiotherapy were tolerated very well. All patients remain to be in remission, with the longest being at 23 months.

Outcomes of patients with HGBCL generally remain to be poor, but this may not be the case for patients with limited-stage disease and favorable clinicopathologic risk profile. Nevertheless, the treatment of HGBCL is currently evolving and more studies are needed to determine the ideal approach and preferred chemotherapy regimen. Also, more studies are needed to elucidate the potential role of consolidation radiotherapy in patients with limited-stage HGBCL to improve survival outcomes. Findings of this case series suggest that patients with LS HGBCL may still derive benefit from R-CHOP followed by consolidation ISRT, but prospective trials are needed to confirm this.

Copy number alteration (CNA) is a significant genetic change in pediatric B-cell acute lymphoblastic leukemia (B-ALL), with CDKN2A/B deletions, PAX5 deletions, and IKZF1 deletions being the most common. Recent studies have increasingly highlighted the potential prognostic significance of these gene deletions and multiple co-deletions in pediatric B-ALL. This paper reviews the main detection methods for CNA, as well as the prognostic characteristics and treatment approaches for common CNA in pediatric B-ALL.
Humans ; DNA Copy Number Variations ; Child ; PAX5 Transcription Factor/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Cyclin-Dependent Kinase Inhibitor p15/genetics* ; Ikaros Transcription Factor/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Gene Deletion ; Cyclin-Dependent Kinase Inhibitor p16/genetics* ; Prognosis

OBJECTIVE: To explore the effect of simvastatin monotherapy or in combination with doxorubicin on diffuse large B-cell lymphoma (DLBCL) cells and its possible molecular mechanisms. METHODS: The differences in the expression levels of genes and proteins related to the mevalonate (MVA) pathway between DLBCL tissues and reactive lymph node hyperplasia tissues were compared via database analysis, as well as their effects on the prognosis. CCK-8 assay was used to detect the effect of simvastatin and doxorubicin on the viability of different subtypes of DLBCL cells, EdU was used to detect cell proliferation, flow cytometry was used to detect apoptosis, and Western blot was used to detect related protein and signaling pathway proteins. RESULTS: The expression levels of MVA pathway-related genes were increased in tumor tissues of DLBCL patients through the TCGA database, and the median overall survival time of DLBCL patients in HMGCR high expression group was shorter (all P < 0.05). Meanwhile, according to The Human Protein Atlas database, HMGCR protein was significantly high expressed in DLBCL tumor tissue compared with normal tissue. The viability of DLBCL cell lines treated with simvastatin or doxorubicin monotherapy was decreased in time- and concentration-dependent manner, and could be further inhibited by simvastatin combined with doxorubicin especially in GCB subtype cell lines. Both simvastatin and doxorubicin could inhibit the proliferation of DLBCL cell lines, and their combination further suppressed dramatically. Both the two drugs promoted apoptosis in DLBCL cell lines, and the apoptosis was further increased after their combination. Compared with monotherapy, the expression of HMGCR protein and apoptosis-related protein Bcl-2 was further decreased but cleaved-caspase3 and Bax increased after combination therapy. Meanwhile, the expression level of phosphorylated proteins in PI3K-Akt pro-survival signaling pathway were decreased especially in GCB subtype cell lines. CONCLUSION HMGCR, the protein associated with cholesterol synthesis pathway, is highly expressed in DLBCL tumor tissues and indicates poor prognosis. Simvastatin, a lipid-lowering drug, combined with doxorubicin can further affect the survival of DLBCL tumor cells at the cellular level.
Humans ; Lymphoma, Large B-Cell, Diffuse/metabolism* ; Doxorubicin/pharmacology* ; Simvastatin/pharmacology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Signal Transduction ; Cell Line, Tumor ; Hydroxymethylglutaryl CoA Reductases/metabolism*

OBJECTIVE: To assess the prognostic significance of plasma fibrinogen（FIB） levels in patients of diffuse large B-cell lymphoma(DLBCL). METHODS: We retrospectively analyzed 203 newly diagnosed with DLBCL patients who met the study requirements from November 2016 to May 2024. Based on the receiver operating characteristic (ROC) curve analysis of plasma FIB levels during diagnosis, the critical value of FIB was determined, and patients were divided into high FIB and low FIB groups. The clinical characteristics and relevant laboratory indicators of two groups were compared. The impact of plasma FIB levels on overall survival (OS) were evaluated using Kaplan-Meier curves as well as univariate and multivariate Cox regression analysis. The differences in FIB and other laboratory indicators under different disease states were compared. RESULTS: According to the ROC curve, the optimal cut-off value of FIB was 3.49 g/L. Compared with the high FIB group (>3.49 g/L), the low FIB group (≤3.49 g/L) had a significant decrease in neutrophil count (ANC) (P =0.001) and platelet count (PLT) (P =0.027), and a significant increase in prealbumin (PA) (P =0.001). A high FIB level was associated with decreased OS (P =0.005). Univariate analysis results showed that FIB had an impact on survival of patients(HR＝2.031，95%CI : 1.221-3.375, P =0.006). Multivariate analysis showed that higher FIB level was an independent adverse prognostic factor affecting patients survival （HR＝2.684， 95%CI :1.478-4.875, P =0.001）. Compared with patients with newly diagnosed or recurrent DLBCL, patients with complete remission showed a significant decrease in FIB (P _ND < 0.001, P _R=0.001) and ANC (P _ND < 0.001, P _R=0.021), as well as an increase in albumin (ALB) (P _ND < 0.001, P _R=0.018) and PA (P _ND < 0.001, P _R < 0.001). CONCLUSION Elevated FIB is a poor prognostic factor for DLBCL patients. The plasma FIB level is correlated with laboratory indicators such as ANC, PLT, PA, and disease status in DLBCL patients. Dynamic monitoring can assist in the early detection of changes in the condition.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Fibrinogen/metabolism* ; Prognosis ; Retrospective Studies ; Male ; Female ; ROC Curve ; Middle Aged ; Aged ; Adult

OBJECTIVE: To investigate the prognostic value of ¹⁸ F-deoxyglucose (FDG) PET/CT metabolic parameters combined with clinicopathological features for newly diagnosed diffuse large B-cell lymphoma (DLBCL) before treatment, and analyze the relationship between tumor metabolic volume (MTV), total lesion glycolysis (TLG) and clinicopathological features. METHODS: The clinical data of 120 patients with pathologically confirmed DLBCL were retrospectively analyzed and ¹⁸F-FDG PET/CT was performed 1 week before treatment. The metabolic parameters including SUVmax, SUVmean, tumor-to-blood standardized uptake value ratio (TBR), tumor-to-liver standardized uptake value ratio (TLR) were obtained. MTV and TLG of the lesions were obtained with 41% of SUVmax as the threshold, and the correlation of MTV and TLG with clinicopathological features were analyzed. Progression-free survival (PFS) was calculated by follow-up for 6-153 months. Receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier test, log-rank test and Cox proportional hazards model were used to analyze the date. RESULTS: The optimum cut-off values of the SUVmax, MTV, TLG, TBR and TLR for predicting tumor progression were 22.25, 256.05, 5 232.67, 12.97 and 10.60, respectively. The patients were divided into two groups according to the above cut-off values, respectively. Kaplan-Meier survival analysis showed that there were statistically significant differences in PFS between the two group (all P <0.05). The MTV and TLG values were correlated with NCCN-IPI score, Ann Arbor stage, serum lactate dehydrogenase level, and C-MYC, BCL-2, BCL-6 gene rearrangement (all P <0.05). Univariate analysis showed that NCCN-IPI score >3, C-MYC, BCL-2, BCL-6 gene rearrangement positive, SUVmax≥22.25, MTV≥256.05 cm³, TLG≥5 232.67 g and TBR≥12.97 were adverse factors for prognosis (HR: 1.949-5.759, all P <0.05). Multivariate Cox regression analysis showed that C-MYC, BCL-2 gene rearrangement positive and TLG≥5 232.67 g were all independent risk factors affecting PFS (HR: 4.660, 3.350, 4.031, all P <0.05). CONCLUSION The ¹⁸F-FDG PET/CT metabolic parameters SUVmax, MTV, TLG, TBR and TLR can be used as important indicators to predict PFS of DLBCL patients, and combining clinicopathological features can better predict the prognosis of patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; Adult

OBJECTIVE: To investigate the efficacy and safety of chidamide combined with DICE regimen (cisplatin+ ifosfamide + etoposide + dexamethasone) for relapsed/refractory diffuse large B-cell lymphome(R/R DLBCL). METHODS: The clinical data of 31 R/R DLBCL patients treated by chidamide combined with DICE regimen in the Hematology Department of the Fourth Hospital of Hebei Medical University from October 2016 to October 2020 were retrospectively analyzed. The clinical efficacy and adverse events were observed. RESULTS: Among the 31 patients, 20 were male and 11 were female. The median age of the patients was 55 (range: 27-71) years old, 21 cases were < 60 years old, 10 cases were ≥60 years old. 26 cases were refractory and 5 cases were relapsed. There were 13 cases of germinal center B-cell like (GCB), 17 cases of non-GCB, and 1 case had missing Hans type. There were 17 cases of double-expression lymphoma (DEL) and 14 cases of non-DEL. The complete response rate of patients was 38.7%(12/31), the overall response rate was 67.7%(21/31). The median progression-free survival time and the median overall survival time were 9.8(95%CI : 4.048-15.552) months, 13.9(95%CI : 9.294-18.506) months, respectively. Multipvariate analysis showed that GCB and DEL reduced the risk of disease recurrence in R/R DLBCL patients. The main grade 3/4 hematological adverse events in this study were thrombocytopenia, agranulocytosis, anemia and leukopenia. CONCLUSION The chidamide combined with DICE regimen is effective in the treatment of R/R DLBCL, and hematological adverse events should be closely monitored.
Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Middle Aged ; Female ; Male ; Adult ; Aged ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Benzamides/administration & dosage* ; Aminopyridines/administration & dosage* ; Etoposide/therapeutic use* ; Cisplatin/administration & dosage* ; Ifosfamide/administration & dosage* ; Dexamethasone/therapeutic use*

OBJECTIVE: To investigate the relationship between CDKN2A copy number deletion and clinical features of patients with diffuse large B-cell lymphoma (DLBCL) and its prognostic value. METHODS: 155 newly diagnosed DLBCL patients with complete clinical data in the Department of Hematology of People's Hospital of Xinjiang Uygur Autonomous Region from March 2009 to March 2022 were included, formalin-fixed paraffin-embedded tumor tissues were obtained and DNA was extracted from them, and next-generation sequencing technology was applied to target sequencing including 475 lymphoma-related genes, the relationship between CDKN2A copy number deletion and clinical features, high-frequency mutated genes and overall survival (OS) of DLBCL patients were analyzed. RESULTS: CDKN2A copy number deletion was present in 12.9% (20/155) of 155 DLBCL patients, grouped according to the presence or absence of copy number deletion of CDKN2A, and a higher proportion of patients with IPI≥3 were found in the CDKN2A copy number deletion group compared to the group with no CDKN2A copy number deletion (80% vs 51.5%, P =0.015) and were more likely to have bulky disease (20% vs 5.2%, P =0.037). Survival analysis showed that the 5-year OS of patients in the CDKN2A copy number deletion group was significantly lower than that of the non-deletion group (51.3% vs 69.2%, P =0.047). Multivariate Cox analysis showed that IPI score≥3 (P =0.007), TP53 mutation (P =0.009), and CDKN2A copy number deletion (P =0.04) were independent risk factors affecting the OS of DLBCL patients. CONCLUSION CDKN2A copy number deletion is an independent risk factor for OS in DLBCL, and accurate identification of CDKN2A copy number deletion can predict the prognosis of DLBCL patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Prognosis ; Cyclin-Dependent Kinase Inhibitor p16/genetics* ; DNA Copy Number Variations ; Female ; Male ; Middle Aged ; Gene Deletion ; Adult ; Aged

OBJECTIVE: To investigate the clinical characteristics and prognosis of primary pulmonary lymphoma (PPL). METHODS: The clinical data of 17 patients with PPL admitted to Gansu Provincial Hospital from January 2013 to June 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: The median age of the 17 patients was 56 (29-73) years old. There were 8 males and 9 females. According to Ann Arbor staging system, there were 9 patients with stage I-II and 8 patients with stage III-IV. There were 14 patients with IPI score of 0-2 and 3 patients with IPI score of 3-4. All 17 patients had symptoms at the initial diagnosis, most of the first symptoms were cough, and 6 patients had B symptoms.Among the 17 patients, there were 8 cases of diffuse large B-cell lymphoma (DLBCL), 5 cases of mucosa-associated lymphoid tissue (MALT) lymphoma, 1 case of gray zone lymphoma (GZL), and 3 cases of Hodgkin's lymphoma (HL). 15 patients received chemotherapy, of which 3 cases received autologous hematopoietic stem cell transplantation(ASCT) and 3 cases received radiotherapy; 2 patients did not receive treatment. The median number of chemotherapy courses was 6(2-8). The short-term efficacy was evaluated, 12 patients achieved complete remission (CR) and 3 patients achieved partial remission (PR). The age, pathological subtype, sex, Ann Arbor stage, β₂-microglobulin(β₂-MG) level, lactate dehydrogenase(LDH) level were not correlated with CR rate (P >0.05), while IPI score was correlated with recent CR rate (P < 0.05 ). The median follow-up time was 31(2-102) months. One of the 12 CR patients died of COVID-19, and the rest survived. Among the 3 patients who did not reach CR, 1 died after disease progression, while the other 2 survived. One of the 2 untreated patients died one year after diagnosis. Both the median progression-free survival (PFS) time and overall survival (OS) time of the 17 patients were both 31 (2-102) months. CONCLUSION The incidence of PPL is low, and the disease has no specific clinical manifestations, which is easily missed and misdiagnosed. The pathological subtypes are mainly MALT lymphoma and DLBCL, and the treatment is mainly combined chemotherapy. The IPI score is related to the treatment efficacy.
Humans ; Middle Aged ; Male ; Female ; Adult ; Prognosis ; Aged ; Lung Neoplasms/therapy* ; Retrospective Studies ; Neoplasm Staging ; Lymphoma/therapy* ; Lymphoma, Large B-Cell, Diffuse

OBJECTIVE: To explore the expression and clinical significance of XPO1 in newly diagnosed adult diffuse large B-cell lymphoma (DLBCL), and further investigate its functional mechanism. METHODS: Immunohistochemical testing was conducted for XPO1 expression in 93 cases of DLBCL and 30 cases of reactive lymphoid hyperplasia. A risk model was construed to find survival related genes in DLBCL patients. Cell proliferation, apoptosis, and cell cycle assays were performed to explore the effect of XPO1 inhibitor (KPT-8602) and XPO1 knockdown. Differential expression gene (DEG) was examined based on the transcriptomes. RESULTS The expression of XPO1 in DLBCL patients was higher than that of the controls. Compared with XPO1 low-expression group, XPO1 high-expression group had a worse prognosis. The constructed risk model indicated that XPO1 and 14 genes in nucleocytoplasmic transport pathway (NTP) might be potential prediction marker of adverse outcome in DLBCL. Moreover, KPT-8602 as well as the XPO1 knockdown could inhibit cell proliferation, promote apoptosis, and induce cell cycle arrest in two DLBCL cell lines, Farage and SU-DHL-4. Based on the gene expression profiling in the datasets of DLBCL, patients were classified into XPO1 high and XPO1 low expression groups, and the MYBL1 was identified as the down-stream effector of XPO1. Inhibiting the function of XPO1 or reducing its expression can significantly decrease the expression of MYBL1 Conclusion: XPO1 is highly expressed in DLBCL, which is associated with poor prognosis. The oncogenic roles of the new XPO1/MYBL1 signaling are identified in DLBCL and XPO1 inhibitor may be a potential option for newly-diagnosed DLBCL patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Exportin 1 Protein ; Karyopherins/metabolism* ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cell Proliferation ; Apoptosis ; Prognosis ; Cell Line, Tumor ; Clinical Relevance

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation