Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

Objective:To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).Results:The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P=0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P<0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients ( P=0.001), while TP53 ( P=0.024) and BCL2 ( P=0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years ( HR=3.439, 95% CI=1.318~9.874), presence of B symptoms ( HR = 2.871, 95% CI=1.133~7.307), and elevated lactate dehydrogenase ( HR=3.528, 95% CI=1.231~10.66) as independent adverse prognostic factors. Conclusion:Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Guided by the cancer toxin theory of TCM master Professor Zhou Zhongying,and absorbing the thoughts of academician Tong Xiaolin's theory of state-target,the pathogenesis of multiple myeloma is summarized as deficiency of healthy qi,bone erosion and marrow damage,cancer toxin accumulation,phlegm and stasis mingling,the combat between healthy qi and evil qi,and dynamic evo-lution;a full-cycle anti-cancer and detoxification prevention and treatment strategy for multiple myeloma is proposed that incorporates the ideas of nourishing deficiency and strengthening healthy qi,preventing cancer and detoxification,resolving phlegm and removing stasis throughout the entire treatment process.The scientific connotation of the pathogenesis theory of"healthy qi deficiency and cancer toxin"in multiple myeloma is explained from multiple aspects such as protein overload and tumor microenvironment,and a prescrip-tion-drug medicine system with Xuanbi Xiaoliu Formula as the core is constructed,which provides new ideas and scientific basis for the clinical diagnosis and treatment plan and full-cycle prevention and control model of multiple myeloma combining Chinese and West-ern medicine.

Guided by the cancer toxin theory of TCM master Professor Zhou Zhongying,and absorbing the thoughts of academician Tong Xiaolin's theory of state-target,the pathogenesis of multiple myeloma is summarized as deficiency of healthy qi,bone erosion and marrow damage,cancer toxin accumulation,phlegm and stasis mingling,the combat between healthy qi and evil qi,and dynamic evo-lution;a full-cycle anti-cancer and detoxification prevention and treatment strategy for multiple myeloma is proposed that incorporates the ideas of nourishing deficiency and strengthening healthy qi,preventing cancer and detoxification,resolving phlegm and removing stasis throughout the entire treatment process.The scientific connotation of the pathogenesis theory of"healthy qi deficiency and cancer toxin"in multiple myeloma is explained from multiple aspects such as protein overload and tumor microenvironment,and a prescrip-tion-drug medicine system with Xuanbi Xiaoliu Formula as the core is constructed,which provides new ideas and scientific basis for the clinical diagnosis and treatment plan and full-cycle prevention and control model of multiple myeloma combining Chinese and West-ern medicine.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

Objective:To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).Results:The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P=0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P<0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients ( P=0.001), while TP53 ( P=0.024) and BCL2 ( P=0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years ( HR=3.439, 95% CI=1.318~9.874), presence of B symptoms ( HR = 2.871, 95% CI=1.133~7.307), and elevated lactate dehydrogenase ( HR=3.528, 95% CI=1.231~10.66) as independent adverse prognostic factors. Conclusion:Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

ObjectiveTo investigate the effect of Qiling Baitouweng Tang （QLBTWT） on proliferation and apoptosis， Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway and interleukin-10 （IL-10） in diffuse large B-cell lymphoma （DLBCL）. MethodWith human DLBCL cells OCI-LY10 and U2932 as research objects， cell proliferation was detected by cell counting kit-8 （CCK-8） assay. After treatment with 0， 4.6， 9.3， 18.7， 37.5， 75， 150 mg·L^-1 QLBTWT for 24 h， the half-inhibitory concentration （IC₅₀） of OCL-LY10 and U2932 cells was calculated to be 9.33， 16.13 mg·L^-1， respectively， based on which， 9.5， 19， 38 mg·L^-1 QLBTWT were selected for subsequent experiments. After 0， 9.5， 19， 38 mg·L^-1 QLBTWT treatment for 24 h， the zymogen activities of Caspase-3， Caspase-8 and Caspase-9 in OCI-LY10 and U2932 cells were detected using corresponding activity assay kits （colorimetric）， and the IL-10 expression was detected by enzyme-linked immuno sorbent assay （ELISA）. The apoptosis rate and cell cycle of OCI-LY10 and U2932 cells treated with different concentrations of QLBTWT for 24 h were detected by flow cytometry. The expressions of apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved poly adenosine diphosphate ribose polymerase （cleaved PARP）， cleaved Caspase-3］， JAK2， STAT3， phospho-JAK2 （p-JAK2）， phospho-STAT3 （p-STAT3） pathway proteins， and c-Myc protein in OCL-LY10 and U2932 cells after 24 h treatment with 0， 9.5， 19， 38 mg·L^-1 QLBTWT were all tested by Western blot. ResultAfter QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， cell proliferation was inhibited in each QLBTWT group compared with that in the control group （P<0.05， P<0.01）. The zymogens of Caspase-3， Caspase-8 and Caspase-9 were activated （P<0.01）， and there was an increase in cell apoptosis （P<0.05， P<0.01） and cell cycle arrest at Gap phase1 （G₁） phase in 9.5， 19 and 38 mg·L^-1 QLBTWT group （P<0.05， P<0.01）. After 9.5， 19 and 38 mg·L^-1 QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， the expressions of Bcl-2， p-JAK2 and p-STAT3 proteins were decreased （P<0.01）， and the expressions of Bax， cleaved PARP and cleaved Caspase-3 proteins were increased （P<0.01）， but no significant change was observed in the expressions of JAK2 and STAT3 proteins. Compared with the conditions in the control group， the expressions of c-Myc， p-JAK2， and p-STAT3 proteins were down-regulated in 19 mg·L^-1 QLBTWT group and 19 mg·L^-1 QLBTWT+10 μg·L^-1 IL-10 group （P<0.05， P<0.01）， and up-regulated in 10 μg·L^-1 IL-10 group （P<0.05， P<0.01）， while there was no difference in JAK2/STAT3 proteins. ConclusionQLBTWT can inhibit proliferation and induce apoptosis of human DLBCL cells OCI-LY10 and U2932， and the potential mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.