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Oncology Research 2024年第6期32卷 1031-1036页

作者： CONSTANTINE N.LOGOTHETIS NATHAN P.HORVAT TONY KURIAN CELESTE BELLO JULIO CHAVEZ LEIDY ISENALUMHE BIJAL SHAH LUBOMIR SOKOL HAYDER SAEED JAVIER PINILLA SAMEH GABALLA Department of Internal Medicine University of South FloridaTampaFL33602USA College of Medicine University of South Florida MorsaniTampaFL33602USA H.Lee Moffitt Cancer Center and Research Institute TampaFL33612USA

Extranodal marginal zone lymphoma(EMZL)encompasses 70%of cases of marginal zone *** bendamustine and rituximab(BR)were derived from trials involving other indolent non-Hodgkin’s *** one trial has evaluated frontline BR prospectively in *** retrospective study reports outcomes among EMZL patients receiving frontline ***-five patients were included with a median age of 69 years(40–81).Five(20.0%)patients had stage Ⅰ/Ⅱ disease,and 20(80.0%)had stage Ⅲ/Ⅳ *** median number of cycles was 6.0(3.0–6.0).Maintenance rituximab was administered to 10(41.7%)*** response rate(ORR)was 100.0%(60.0%complete response,40.0%partial response).Medians of overall survival and progression-free survival were not *** estimated 2-year progression-free survival was 85.2%and overall survival was 100.0%.Four(16.6%)patients had infections related to treatment;3(12.0%)transformed to diffuse large B-cell lymphoma;5(20.8%)had a relapse or progression of EMZL;and 3(12.0%)died unrelated to *** is an efficacious and well-tolerated front-line regimen for EMZL with response data consistent with existing literature.

关键词： Extranodal marginal zone lymphoma bendamustine Rituximab Front-line therapy

bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study

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Chinese Medical Journal 2021年第11期134卷 1299-1309页

作者： Yuan-Kai Shi Xiao-Nan Hong Jian-Liang Yang Wei Xu Hui-Qiang Huang Xiu-Bin Xiao Jun Zhu Dao-Bin Zhou Xiao-Hong Han Jian-Qiu Wu Ming-Zhi Zhang Jie Jin Xiao-Yan Ke Wei Li De-Pei Wu Shen-Miao Yang Xin Du Yong-Qian Jia Ai-Chun Liu Dai-Hong Liu Zhi-Xiang Shen Lian-Sheng Zhang Leonard James Edward Hellriegel Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted DrugsBeijing 100021China Department of Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200030China Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China Department of Medical Oncology 307 Hospital of Chinese People’s Liberation ArmyBeijing 100071China Department of Lymphoma Peking University Cancer Hospital&InstituteBeijing 100142China Department of Hematology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Oncology Jiangsu Cancer Hospital&Jiangsu Institute of CancerNanjingJiangsu 210009China Department of Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Hematology The First Affiliated Hospital of Zhejiang University College of MedicineHangzhouZhejiang 310003China Department of Hematology Peking University Third HospitalBeijing 100191China Department of Oncology Jilin University First Affiliated HospitalChangchunJilin 130021China Department of Hematology Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215006China Department of Hematology Peking University Institute of HematologyPeking University People’s HospitalBeijing 100044China Department of Hematology Guangdong General HospitalGuangzhouGuangdong 510062China Department of Hematology and Research Laboratory of Hematology West China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Medical Oncology Harbin Medical University Cancer HospitalHarbinHeilongjiang 150001China Department of Hematolo

Background:bendamustine was approved in China on May 26th,2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma(NHL).The current study was the registration trial and the first reported evaluation of the efficacy,safety,and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab ***:This was a prospective,multicenter,open-label,single-arm,phase 3 study(NCT01596621;C18083/3076)with a 2-year follow-up *** patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles(and up to eight cycles).The primary endpoint was the overall response rate(ORR);and secondary endpoints were duration of response(DoR),progression-free survival(PFS),safety,and *** were classified according to their best overall response after initiation of *** of patients in each response category(complete response[CR],partial response[PR],stable disease,or progressive disease)were summarized along with a twosided binomial exact 95%confidence intervals(CIs)for the ***:A total of 102 patients were enrolled from 20 centers between August 6th,2012,and June 18th,*** the time of the primary analysis,the ORR was 73%(95%CI:63%–81%)per Independent Review Committee(IRC)including 19%CR and 54%*** the follow-up period,the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment;the median PFS was 18.6 months and 15.3 months,*** most common non-hematologic adverse events(AEs)were gastrointestinal toxicity,pyrexia,and *** 3/4 neutropenia was reported in 76%of *** AEs were reported in 29 patients and five patients died during the *** analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent

关键词： bendamustine Non-Hodgkin lymphoma B-cell malignancy Relapsed disease Clinical trial

Effects of chemotherapeutic agent bendamustine for nonhodgkin lymphoma on spermatogenesis in mice

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The Journal of Biomedical Research 2018年第6期32卷 442-453页

作者： Minbo Zang Qiao Zhou Yunfei Zhu Mingxi Liu Zuomin Zhou State Key Laboratory of Reproductive Medicine Department of Histology and EmbryologyNanjing Medical University

Non-Hodgkin lymphoma(NHL) is one of the most common cancers affecting men of reproductive age. The high response rate of bendamustine as first-line treatment for NHL, coupled with young age of patients, makes elucidation of the impact of treatment on male reproduction important. Our aim was to determine the effects of bendamustine on male reproduction by animal model. Male mice were treated with bendamustine(40 mg/kg) through tail vein injection while cisplatin was given as a standard(3 mg/kg) through intraperitoneal injection. After 3 weeks, bendamustine induced weight loss and sperm morphology abnormalities were compared to the control. Additionally, sperm with folded tails were the most frequent abnormality in bendamustine-treated mice. But the mechanism of sperm abnormality induced by bendamustine remains to be elucidated. These results indicate bendamustine may affect spermatozoa of patients who have been treated for NHL.

关键词： Non-Hodgkin lymphoma chemotherapy bendamustine mice spermatozoa toxicology

A bendamustine resistance gene signature in diffuse large B-cell lymphoma and multiple myeloma

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Cancer Drug Resistance 2021年第1期4卷 208-222页

作者： Issa Ismail Issa Rasmus Froberg Brøndum Hanne Due Linnea Schmidt Martin Bøgsted Karen Dybkær Department of Haematology Aalborg University HospitalAalborg 9000Denmark Department of Clinical Medicine Aalborg UniversityAalborg 9000Denmark.

Aim:bendamustine is primarily used for treatment of indolent lymphomas but has shown efficacy in some patients with diffuse large B-cell lymphoma(DLBCL)and multiple myeloma(MM).Molecular-based patient stratification for identification of resistant patients,who will benefit from alternative treatments,is *** aim of this study was to develop a resistance gene signature(REGS)from bendamustine dose-response assays in cultures of DLBCL and MM cell lines,enabling prediction of bendamustine response in DLBCL and MM ***:bendamustine response was determined in 14 DLBCL and 11 MM cell *** baseline gene expression profiles and degree of growth inhibition after bendamustine exposure,a bendamustine REGS was developed and examined for the risk stratification potential in DLBCL(n=971)and MM(n=1,126)patients divided into prognostic ***:bendamustine resistance significantly correlated with resistance to cyclophosphamide in DLBCL and melphalan in MM cell *** bendamustine REGS showed significantly lower bendamustine resistance probabilities in DLBCL patients with GCB subtype tumors and in tumors of the differentiation dependent centrocyte and plasmablast *** MM patients,pre-BII classified tumors displayed high bendamustine resistance probabilities and the plasma cell subtype had lower bendamustine resistance probability than memory ***,tumors belonging to the 4p14,MAF,and D2 TC subclasses consistently displayed high bendamustine resistance ***:Significant differences in predicted response to bendamustine were found in molecular subtypes of DLBCL and MM,encouraging validation in prospective bendamustine-treated cohorts with available gene expression profiles and follow-up data.

关键词： bendamustine diffuse large B-cell lymphoma multiple myeloma resistance gene signature

苯达莫司汀（bendamustine）诱导小鼠乳腺癌细胞凋亡及其机制的研究

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苯达莫司汀（Bendamustine）诱导小鼠乳腺癌细胞凋亡及其机制的研...

作者：孔芳山东大学

学位级别：硕士

背景：乳腺癌是人类最常见的恶性肿瘤之一，其发病率近年来呈上升趋势。在多种治疗乳腺癌的方法中，化疗仍是最为常用且效果较明显的重要手段之一。然而现有的化疗药物或多或少都会引起药物耐受性的产生，因此，寻找有效杀伤乳腺癌细胞... 详细信息

背景：乳腺癌是人类最常见的恶性肿瘤之一，其发病率近年来呈上升趋势。在多种治疗乳腺癌的方法中，化疗仍是最为常用且效果较明显的重要手段之一。然而现有的化疗药物或多或少都会引起药物耐受性的产生，因此，寻找有效杀伤乳腺癌细胞的化疗药物已成为研究者当前的主要任务之一。临床研究表明，作为氮芥类药物且具多种功能的烷化剂，苯达莫司汀(bendamustine)对乳腺癌有较好的疗效。然而，相关的研究数据有限，作用机制不清楚。由于很多小分子化疗药物可通过影响肿瘤细胞周期和诱导细胞凋亡来抑制肿瘤细胞的生长，因此我们重点研究苯达莫司汀对体外培养的小鼠乳腺癌C127细胞周期和诱导凋亡的作用及作用机制，以期为肿瘤生物学和肿瘤化疗提供理论依据。目的：观察抗癌药物苯达莫司汀对体外培养的小鼠乳腺瘤细胞系C-127生长抑制及其作用机制，以期在细胞水平上为治疗乳腺癌提供相关的理论依据。方法：细胞增殖检测方法：采用形态学观察和细胞记数法检测苯达莫司汀对C127细胞形态和存活率的影响;细胞凋亡检测方法：用吖啶橙染色法，在荧光显微镜下观察细胞核的形态变化和凋亡小体;TUNEL法检测DNA的片段化;细胞凋亡和坏死的鉴别：检测乳酸脱氢酶(LDH)的释放区分坏死和凋亡;p53蛋白表达测定：免疫荧光结合激光共聚焦扫描显微技术测定细胞中p53的表达情况;细胞周期的变化：流式细胞术检测苯达莫司汀对C127细胞周期的影响。结果： 1．相差显微镜观察显示：苯达莫司汀20μg／ml作用C127细胞24h之后细胞形态无明显变化，48h后细胞表现出凋亡的特征，细胞突起变少，细胞中颗粒和空泡增加，细胞核明显增大。苯达莫司汀40μg／ml作用C127细胞24h，48h后细胞都表现出凋亡的特征，48h后可见少量的凋亡小体 2．细胞计数表明：苯达莫司汀对C127的生长有明显抑制作用，并呈明显的剂量时间依赖性。 3．吖啶橙染色显示：苯达莫司汀可使C127细胞核内染色质凝集、核片段化以及出现凋亡小体。 ***检测表明：药物处理后，C127细胞呈现DNA的片断化以及核片断化。 ***活性检测显示：C127细胞采用苯达莫司汀20μg／ml处理48h后，与对照组相比培养液中LDH含量无明显差异(P＞0.05)，苯达莫司汀40μg／ml处理48小时，与对照组相比培养液中LDH含量明显升高(P＜0.05)。 6．免疫荧光试验表明：苯达莫司汀可使C127的p53的表达升高(P＜0.05)。 7．分析细胞DNA含量发现：苯达莫司汀作用细胞24-48h后可使细胞分别阻抑在G2／M和G1／S期，并呈现时间依赖性。结论： 1．苯达莫司汀对小鼠乳腺癌细胞的生长有明显抑制作用，并呈明显的剂量和时间依赖性。 2．不同浓度的苯达莫司汀引起细胞的死亡方式不同，低浓度以凋亡为主，高浓度则表现为坏死。 3．苯达莫司汀可能是通过是上调p53蛋白的表达来传递凋亡信号。 4．苯达莫司汀对C127细胞周期的影响与时间长短有关，作用24-48h后，使细胞周期先后阻滞在G2／M和G1／S期。

关键词：小鼠乳腺癌细胞C127 细胞增殖细胞凋亡细胞周期坏死 p53 bendamustine

bendamustine或将成为霍奇金淋巴瘤的一线标准治疗药

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药学进展 2010年第3期34卷 133-133页

作者：范鸣

依据在美国新奥尔良召开的美国血液病学会(ASH)会议上专家们披露的一项独立的Ⅲ期临床数据，Cephalon公司开发的新型化疗药物bendamustine(商品名:Treanda)或将成为与抗CD20单克隆抗体药物利妥昔单抗联用于惰性霍奇金淋巴瘤(NHL)的新一... 详细信息

依据在美国新奥尔良召开的美国血液病学会(ASH)会议上专家们披露的一项独立的Ⅲ期临床数据，Cephalon公司开发的新型化疗药物bendamustine(商品名:Treanda)或将成为与抗CD20单克隆抗体药物利妥昔单抗联用于惰性霍奇金淋巴瘤(NHL)的新一线标准治疗药物.

关键词： bendamustine 霍奇金淋巴瘤一线标准治疗药

注射用化疗药物bendamustine在美国获准上市

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药学进展 2009年第4期33卷 192-192页

作者：范鸣

Management of mantle cell leukemia with cardiac involvement leading to cardiogenic shock

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Frontiers of Medicine 2014年第2期8卷 254-258页

作者： Muhammad Furqan Yamei Chen Akintunde Akinleye Judy Sarungbam Alan Gass Karen Seiter Delong Liu Division of Hematology and Oneology Department of Medicine Westchester Medical Center 100 Woods Rd Valhalla NY 10595 USA Department of Hematology Xiamen Zhongshan Hospital Xiamen University Xiamen 361004 China Department of Pathology Westehester Medical Center 100 Woods Rd Valhalla NY 10595 USA Division of Cardiology Department of Medicine Westchester Medical Center 100 Woods Rd Valhalla NY 10595 USA

Mantle cell lymphoma is an aggressive subtype of B cell non-Hodgkin lymphoma. It can progress to leukemic phase but frank leukemic picture at initial presentation is not common. Leukemic phase indicates advance stage of the disease and generally associated with extensive extra-nodal involvement. Pericardial invasion has been reported, however we could not find a report of myocardial infiltration by this disease since the appraisal of the term ＂mantle cell lymphoma＂ in 1992. Here we report a case of cardiac involvement by mantle cell leukemia leading to cardiogenic shock which complicates the treatment decisions.

关键词： mantle cell lymphoma bendamustine cardiogenic shock

COVID-19 (SARS-CoV-2 infection) in lymphoma patients: A review

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World Journal of Virology 2021年第6期10卷 312-325页

作者： Valentina Bonuomo Isacco Ferrarini Michele Dell'Eva Eugenio Sbisà Mauro Krampera Carlo Visco Section of Haematology Department of MedicineUniversity of VeronaVerona 37134Italy

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection now has a global resonance and represents a major threat for several patient *** from initial case series suggested that cancer patients in general might have an unfavorable outcome following coronavirus disease 2019(COVID-19),due to their underlying conditions and cytotoxic *** recently,data regarding the incidence and clinical evolution of COVID-19 in lymphomas have been reported with the aim to identify those more frequently associated with severe complications and *** with lymphoma appear particularly vulnerable to SARS-CoV-2 infection,only partly because of the detrimental effects of the anti-neoplastic regimens(chemotherapy,pathway inhibitors,monoclonal antibodies)on the immune ***,we systematically reviewed the current literature on COVID-19 in adult patients with lymphoma,with particular emphasis on disease course and prognostic *** also highlighted the potential differences in COVID-19 clinical picture according to lymphoma subtype,delivered treatment for the hematological disease and its relationship on how these patients have been managed thus far.

关键词： Lymphoma SARS-CoV-2 infection Hematological malignancies COVID-19 Rituximab bendamustine

Overall Survival and Health Care Costs of Medicare Patients with Previously Treated Chronic Lymphocytic Leukemia

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Journal of Cancer Therapy 2018年第7期9卷 576-587页

作者： Carolina Reyes Genevieve Gauthier Sherry Shi Annie Guerin Genentech Inc. South San Francisco CA USA Analysis Group Inc. Montreal Canada

Background: bendamustine-based regimens are often used in the management of patients with chronic lymphocytic leukemia (CLL) but few studies have analyzed the comorbidity- and/or adverse event (CAE)-related healthcare costs in patients receiving these regimens in a real-world setting. Aims: To describe all-cause and CAE-related healthcare costs in relapse/refractory (R/R) elderly patients with CLL treated with bendamustine-based regimens in a real-world setting. Methods: Adult patients with R/R CLL who received bendamustine-based regimens on/after January 2010 were selected from the Medicare Limited Data Set (LDS) 5% Standard Analytic Files. Selected patients were classified into cohorts based on the two most prevalent bendamustine-based regimens observed (index treatment): 1) bendamustine + rituximab (BR cohort) and 2) bendamustine monotherapy (B-mono cohort). For each cohort, all-cause and CAE-related healthcare costs, while on treatment, were reported per-patient-per-month (PPPM). Overall survival (OS) rates following initiation of the index treatment were described using age- and gender-adjusted Kaplan-Meier curves. Results: A total of 275 patients were included in the BR cohort and 100 patients in the B-mono cohort. Most patients were male and the mean age was approximately 75 years old. During treatment, total all-cause healthcare costs were $14,520 PPPM for the BR cohort and $13,125 PPPM for the B-mono cohort—outpatient costs (mainly driven by CLL-drug costs) represented 86.1% of the total all-cause healthcare costs for the BR cohort and 69.8% for the B-mono cohort. CAE costs accounted for 58.3% of the total all-cause healthcare costs for the BR cohort and 66.9% for the B-mono cohort. Median OS was 35 months in the BR cohort and 21 months in the B-mono cohort. Conclusion: In this population of elderly patients with R/R CLL treated with bendamustine-based regimens, CAEs were common and translated into important medical costs. Median OS was also relatively shor

关键词： Chronic Lymphocytic Leukemia Relapse/Refractory bendamustine Economic Burden Overall Survival Adverse Events