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Dose-adjusted EPOCH-R vs.R-CHOP in frontline management of Waldeyer’s ring diffuse large B-cell lymphoma:a retrospective study from a single institution

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Chinese Medical Journal 2023年第2期136卷 167-175页

作者： Yuanzheng Liang Xindi Liu Jing Yang Henan Wang Yingshi Piao Liqiang Wei Liang Wang Department of Hematology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Pathology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China

background: To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer’s ring diffuse large B-cell lymphoma (WR-DLbCL) at a single institution. Methods: This retrospective study included 115 newly diagnosed patients with WR-DLbCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS). Results: During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P = 0.025 and P = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4-99.8%) and 95.2% (95% CI: 89.0-100.0%), respectively, and 80.5% (95% CI: 69.3-93.6%) and 90.5% (95% CI: 52.8-99.8%) in the R-CHOP group. Patients without b symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11;95% CI: 0.01-0.88) and 0.042 (HR: 0.19;95% CI: 0.04-0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups. Conclusion: Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLbCL.

关键词： Waldeyer’s ring B-cell lymphoma DA-EPOCH-R R-CHOP

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Immune cells in the B-cell lymphoma microenvironment: From basic research to clinical applications

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中华医学杂志(英文版) 2024年第7期137卷 776-790页

作者： Zhang Wenli Liu Mengmeng Li Wei Song Yongping Department of Hematology The First Affiliated Hospital of Zhengzhou University 3. Zhengzhou 4. Henan 450052 5. China Academy of Medical Sciences Zhengzhou University

B-cell lymphoma is a group of hematological malignancies characterized by variable genetic and biological features and clinical behaviors. The tumor microenvironment (TME) is a complex network in tumors, which consists of surrounding blood vessels, extracellular matrix, immune and non-immune cells, and signaling molecules. Increasing evidence has shown that the TME, especially immune cells within, is a double-edged sword, acting either as a tumor killer or as a promoter of tumor progression. These pro-tumor activities are driven by subpopulations of immune cells that express typical markers but have unique transcriptional characteristics, making tumor-associated immune cells good targets for human anti-cancer therapy by ablating immunosuppressive cells or enhancing immune-activated cells. Thus, exploring the role of immune cells in the TME provides distinct insights for immunotherapy in B-cell lymphoma. In this review, we elucidated the interaction between immune cells and tumor cells and their function in the initiation, progression, and prognosis of B-cell lymphoma, from preclinical experiments to clinical trials. Furthermore, we outlined potential therapeutic approaches and discussed the potential clinical value and future perspectives of targeting immune cells in patients with B-cell lymphoma.

关键词： Tumor microenvironment B-cell lymphoma Immune cells Immunotherapy Targeted therapy

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Fcγ receptor IIIA polymorphisms and efficacy of rituximab therapy on Chinese diffuse large B-cell lymphoma

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Chinese Medical Journal 2010年第2期123卷 198-202页

作者： ZHANG Wei WANG Xuan Li Jian DUAN Ming-hui ZHOU Dao-bin Department of Hematology Peking Union Medical College Hospital Beijing 100730 China

background Rituximab is used extensively in combination with chemotherapy to cure non-Hodgkin＇s lymphoma （NHL）, and not only accelerates short-term improvement, but also prolongs patient survival and decreases relapse. The aim of this study was to evaluate the impact of Fcγ receptor IliA （FcyRIIIA） gene polymorphisms on the response to rituximab therapy for newly diagnosed B-cell lymphomas. Methods Patients with newly diagnosed histologically-proven CD20-positive B-cell lymphoma were eligible for the study. All of the patients received rituximab combined with chemotherapy （CHOP）. The FcyRIIIA type was analyzed by PCR. The initial efficacy was assessed after 6 cycles and the long-term survival was determined. Results Thirty-four patients were recruited between October 2005 and April 2006. The FcyRIIIA distribution was as follows： 11 patients were VV, 5 were FF, and 18 were VE After a median of 6 cycles （range 4-8） of rituximab combined chemotherapy, the overall response rate was 79% （82% in the VV group, 83% in the VF group, and 60% in the FF group; P=0.04）. After a median follow-up time of 37 months （range 34-41）, there were 12 relapses among 27 responders （44%）; 5 of 9 patients （5/9） in the VV group, 5 of 15 patients （33%） in the VF group, and 2 of 3 patients （2/3） in the FF group （P=0.21）. The 1-year overall survival in the VV, FF, and VF groups was 80%, 60%, and 80%, respectively, and the 3-year overall survival was 58%, 40%, and 69%, respectively （P=0.08）. After analysis by COX regression, only the international prognosis index and response to initial treatment were significantly related to overall survival. Conclusions The distribution of FcyRIIIA polymorphisms in this B-cell lymphoma population shows that VF is most frequently expressed, followed by VV and FE Patients with the FcyRIIIA VV and VF types are more sensitive to the initial treatment of rituximab combined with chemotherapy and have superior long-term survival compared with those with FF. Nevertheless, FcyRIIIA polymorphisms do not predict prognos

关键词： B-cell lymphoma rituximab Fcγ receptor IliA prognosis

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Pancreatic cancer secondary to intraductal papillary mucinous neoplasm with collision between gastric cancer and B-cell lymphoma: A case report

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World Journal of Clinical Cases 2021年第10期9卷 2400-2408页

作者： Yu-Hong Ma Tatsuya Yamaguchi Tomoki Yasumura Toru Kuno Shoji Kobayashi Takashi Yoshida Takeshi Ishida Yasuaki Ishida Shinya Takaoka Jiang-Lin Fan Nobuyuki Enomoto Department of Gastroenterology Ningxia Hui Autonomous Region People’s HospitalYinchuan 750021Ningxia Hui Autonomous RegionChina Department of the First Internal Medicine Faculty of MedicineUniversity of YamanashiChuo 409-3898YamanashiJapan Department of Molecular Pathology Interdisciplinary Graduate School of Medicine and EngineeringUniversity of YamanashiChuo 409-3898YamanashiJapan

bACKGROUND Patients with intraductal papillary mucinous neoplasm(IPMN)have an increased risk of pancreatic and extrapancreatic malignancies.lymphomas are rare extrapancreatic malignancies,and in situ collisions of early gastric cancer and diffuse large B-cell lymphoma(DLbCL)are even rarer.Here,we report the first case of pancreatic cancer comorbid with in situ collision of extrapancreatic malignancies(early gastric cancer and DLbCL)in a follow-up IPMN patient.Furthermore,we have made innovations in the treatment of such cases.CASE SUMMARY An 81-year-old Japanese female diagnosed with IPMN developed elevated carbohydrate antigen(CA)19-9 levels during follow-up.because her CA19-9 levels continued to rise,endoscopic ultrasound(EUS)was performed and revealed a suspicious lesion at the pancreatic tail.However,lesions in the pancreas were not found by computed tomography,magnetic resonance imaging,or endoscopic retrograde cholangiopancreatography.To make an exact pathological diagnosis,EUS-guided fine needle aspiration was performed.To our supprise,early gastric cancer was found in preoperative gastroscopy.The gastric cancer was completely resected through endoscopic submucosal dissection before postoperative pathology identified early adenocarcinoma collided with DLbCL.Subsequent EUS-guided fine needle aspiration provided pathological support forthe pancreatic cancer diagnosis, and then laparoscopic distal pancreatectomy andsplenectomy were performed. CA19-9 levels returned to normal postoperatively.CONCLUSION Endoscopic submucosal dissection is appropriate for submucosal lymphomas inpatients intoleratant of chemotherapy. EUS can detect small IPMN-relatedpancreatic tumors.

关键词： Stomach neoplasms Pancreatic intraductal neoplasms Pancreatic neoplasms B-cell lymphoma Treatment Case report

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Mda-7/IL-24 induces the differentiation of b cell lymphoma via activation of P38 MAPK signalling pathway

Mda-7/IL-24 induces the differentiation of B cell lymphoma v...

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第十一届全国免疫学学术大会

作者： Ming Ma The fourth hospital of hebei medical university

Mda-7/IL-24 has been shown to inhibit the proliferation of various human tumor cell lines, but its effect on the differentiation of b cell lymphoma is not yet clear. This study investigated the effects of Mda-7/IL-24 overexpression on the differentiation of human b cell lymphoma as well as its mechanism of action. The proliferation of stable Mda-7/IL-24 overexpressing Raji and Daudi cells was assessed by the MTS method. cell cycle distribution, apoptosis and the immunophenotype of Raji and Daudi cells were assayed by flow cytometry(FCM). The expression of blimp1 and bcl6 were analyzed by western blotting. In addition, western blotting analysis assay were used to investigate the effect of Mda-7/IL-24 on activity of P38 MAPK signalling pathway in Raji and Daudi cells. Growth of Mda-7/IL-24 overexpressing Raji and Daudi cells was inhibited significantly, compared with those of non-transfected cells and cells transfected with vector alone. The cell cycle is arrested in G1 phase and apoptosis is not involved in the growth inhibition of Raji and Daui cells overpressing Mda-7/IL-24. Overexpressing Mda-7/IL-24 resulted in the significantly decreased expression of CD10, and increased expression of CD45 and CD138 in cell surface of Raji and Daudi cells. The expression of blimp1 was higher, while the levels of bcl6 protein was lower, in Mda-7/IL-24 overexpressing Raji and Daudi cells. Futhermore, the activities of P38 MAPK signalling pathway in Raji and Daudi cells were upregulated. These results indicated that Mda-7/IL-24 could induce terminal differentiation of b lymphoma cells by altering the expression of blimp1 and bcl6 via regulating P38 MAPK signalling pathway, suggesting that Mda-7/IL-24 may therefore be a potential candidate for differentiation treatment of b cell lymphomas.

关键词： Mda-7/IL-24 B-cell lymphoma Differentiation induction P38 MAPK

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Rare Primary Diffuse Large B-cell lymphoma of a Male breast

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Case Reports in Clinical Medicine 2021年第4期10卷 99-107页

作者： Hani Alothaid Umama Yezdani Mahmoud M. Habibullah Saad Saeed Alamri Mazen M. Ghaith Mohammad Gayoor Khan Department of basic Medical Sciences Faculty of Applied Medical Sciences Al-Baha University Al-Baha Saudi Arabia Department of Pharmacy Practice MRM College of Pharmacy Hyderabad India Medical Laboratory Technology Department Faculty of Applied Medical Sciences Jazan University Jazan Saudi Arabia Research Center King Fahad Medical City Riyadh Saudi Arabia Laboratory Medicine Department Faculty of Applied Medical Science Umm Al-Qura University Makkah Saudi Arabia UCb Unit Department of Pharmacovigilance Bioclinica Mysore India

background: breast lymphomas are typical extranodal types of lymphoma, also known as Extranodal-lymphoma (ENL), which occur extremely infrequently, aggregating into a very small proportion of malignant breast tumors. The rarity of breast lymphomas is attributed to the scant lymphoid tissue content of the chest wall. Aims of Study: This case report is aimed at providing an up-to-date review of the literature on breast lymphomas for clinicians to, therefore, consider the possibility of this disease entity while treating a breast mass. Case Presentation: A case was reported of a 52-year man with chief mammary non-Hodgkin breast ENL when fine-needle aspiration cytology (FNAC) was not leading to a firm conclusion or result. Following an incisional biopsy, he was found to have a primary breast lymphoma. Later, the patient was diagnosed with the diffuse large b-cell type of lymphoma also known as non-Hodgkin’s lymphoma (NHL). He had a complete reduction and disappearances of all the signs and symptoms of the disease after a course of neoadjuvant chemotherapy: Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (CHOP). CONCLUSION: based on the above case presentation, it is vital for health care professionals and oncologists to recognize the disease by assessing the breast mass accurately with more entities so that proper diagnosis via core biopsy (incisional biopsy) can eliminate the PbL before further treatment is required.

关键词： Non-Hodgkin’s lymphoma PbL B-cell lymphoma breast Cancer CHOP ENL

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Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

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Frontiers of Medicine 2022年第5期16卷 815-826页

作者： Suning Chen Weili Zhao Jianyong Li Depei Wu on behalf of Lymphoid Disease Group,Chinese Society of Hematology,Chinese Medical Association National Clinical Research Center for Hematologic Diseases Suzhou 215006China Jiangsu Institute of Hematology the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalCollaborative Innovation Center for Cancer Personalized MedicineNanjing 210029China

Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma(bCL)due to their reliable efficacy,manageable safety,high accessibility,and convenience for use.Still,no guidelines or consensus focusing on oral drug therapies for bCL is available.To provide a reference of oral agent-based treatment for mature bCL,a panel of experts from the Lymphocyte Disease Group,Chinese Society of Hematology,Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese bCL patients on the basis of the current application status of oral drugs in China,combined with the latest authoritative guidelines in the world and current research reports.This consensus reviewed the application of oral drugs in the treatment of bCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive bCL patients.With the deepening of research and the development of standardized clinical applications,oral medications will bring better treatment to bCL patients,enabling more patients to benefit from them.

关键词： B-cell lymphoma oral drug targeted therapy immunotherapy COVID-19 pandemic

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Composite b-cell and T-cell lymphomas:clinical,pathological,and molecular features of three cases and literature review

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Journal of Zhejiang University-Science b(biomedicine & biotechnology) 2023年第8期24卷 711-722页

作者： Xueli JIN Hui LIU Jing LI Xibin XIAO Xianggui YUAN Panpan CHEN boxiao CHEN Yun LIANG Fengbo HUANG Department of Hematology the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Department of Pathology the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Department of Nuclear Medicine the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China School of Medicine Zhejiang UniversityHangzhou 310029China

Composite lymphoma(CL)involving B-cell lymphoma and T-cell lymphoma is extremely rare.Herein,we report three such cases using immunohistochemistry,flow cytometry,and the next-generation sequencing(NGS)to identify the pathological and molecular characteristics of CL.In the first case,the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body.An excisional biopsy of the skin lesions showed T-cell lymphoma.At the same time,the staging bone marrow(bM)biopsy revealed a diffuse large B-cell lymphoma(DLbCL).After R-CHOP(rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone)therapies,the patient produced a good response with substantial dissipation of the rashes and relief of skin.The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLbCL and follicular lymphoma(FL)after core needle biopsy of lymph nodes,bM biopsy,bM aspiration,and flow cytometry.Following R-CHOP and R-COP(rituximab,cyclophosphamide,vincristine,and prednisone)therapies,they achieved complete remission unconfirmed(CRu)and complete remission(CR).However,one or two years later,they suffered a relapse of lymphadenopathy.The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma(PTCL)and angioimmunoblastic T-cell lymphoma(AITL).NGS findings identified DNA methyltransferase 3a(DNMT3a),isocitrate dehydrogenase 2(IDH2),Ras homolog gene family,member A(RHOA),splicing factor 3b subunit 1(SF3b1),and tumor protein p53(TP53)mutations.After immunochemotherapy,these patients achieved CRu and CR again.Nevertheless,they suffered a second relapse of T-cell lymphoma.Finally,they died due to progression of disease.We found that the occurrence of CL is associated with Epstein-barr virus infection and DNMT3a,IDH2,and TP53 mutations,and the prognosis of the disease is closely related to the T-cell lymphoma components.

关键词： Composite lymphoma B-cell lymphoma T-cell lymphoma

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Developing potent bTK^(C481S)PROTACs for ibrutinib-resistant malignant lymphoma

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Chinese Chemical Letters 2023年第6期34卷 437-442页

作者： Yonghui Sun Xin Luo Zimo Yang Wenxing Lv Lixia Chen Hua Li Yu Rao MOE Key Laboratory of Protein Sciences School of Pharmaceutical SciencesMOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical BiologyTsinghua UniversityBeijing 100084China Wuya College of Innovation Key Laboratory of Structure-Based Drug Design&DiscoveryMinistry of EducationShenyang Pharmaceutical UniversityShenyang110016China Institute of Structural Pharmacology&TCM Chemical biology College of PharmacyFujian University of Traditional Chinese MedicineFuzhou 350122China

Ibrutinib is a first-line treatment drug for b-cell malignancies.However,resistance to ibrutinib has been reported due to bTKC481Smutation.Although PROTAC strategy is expected to overcome this clinical resistance,it has limitations such as large molecular weight and moderate bioactivity,which restrict its potential clinical application.Herein,we report a new type of potent bTKC481S-targeting PROTAC degrader.Through design,computer-assisted optimization and SAR studies,we have developed a representative bTKC481Sdegrader L6 with a much smaller molecular weight and improved solubility.Notably,L6 demonstrates better bTK degrading activity and lower IC50value in ibrutinib-resistant cell line than the first-generation bTK degrader P13I.Optimization strategy of L6 provides a general approach in the development of PROTACs targeting bTK and other proteins for future study.

关键词： Drug design Ibrutinib resistance bTK degraders PROTACs B-cell lymphoma

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Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers

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Cancer biology & Medicine 2020年第4期17卷 1026-1038页

作者： Ying Cheng Xiaodong Zheng Xuefu Wang Yongyan Chen Haiming Wei Rui Sun Zhigang Tian Haoyu Sun Hefei National Laboratory for Physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Sciences and MedicineInstitute of ImmunologyUniversity of Science and Technology of ChinaHefei 230027China Research Unit of NK cell Study Chinese Academy of Medical SciencesBeijing 100864China

Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic products.Methods:We constructed a trispecific killer engager(TriKE)consisting of anti-CD16,IL-15,and anti-CD19.This TriKE was designed to attract CD19^(+)tumor cells to CD16^(+)NK cells,whereas IL-15 sustained the proliferation,development,and survival of NK cells.Results:Treatment with 161519 TriKE in the presence of CD19^(+)targets upregulated expression of CD69,CD107 a,TRAIL,IFN-γ,and TNF-α in NK cells,and significantly improved the proliferation and cytotoxicity of NK cells.NK cells"armed"with 161519 TriKE showed stronger cytolysis against CD19+targets compared with that of"unarmed"NK cells.A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE,when compared with that in control mice or mice treated with 1619 biKE.Combined use of IL-2 was a more effective treatment with 1619 biKE,when compared with that using 161519 TriKE.Conclusions:The newly generated 161519 TriKE enhanced the proliferation,activation,cytokine secretion,and cytotoxicity of NK cells in the presence of CD19+tumor cells.The 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts,and could be used to treat CD19-positive cancers.

关键词： Trispecific antibody trispecific killer engager(TriKE) NK cell B-cell lymphoma tumor immunotherapy

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