国产利妥昔单抗治疗弥漫大B细胞淋巴瘤的疗效及安全性

摘要 目的：探讨弥漫大B细胞淋巴瘤患者采用国产利妥昔单抗为基础的化疗方案的疗效及安全性。方法：回顾性分析2020年3月至2022年5月份在安徽省第二人民医院血液内科诊治的弥漫大B淋巴瘤患者31例,均接受国产利妥昔单抗为基础的联合方案化疗,其中非生发中心来源的弥漫大B细胞淋巴瘤患者25例,生发中心来源的弥漫大B细胞淋巴瘤患者6例。21~28 d为一个疗程,这些患者至少接受2~8个疗程的联合化疗,并且2个疗程以后进行疗效评估及不良反应监测。结果：①本研究31例弥漫大B细胞淋巴瘤患者接受利妥昔单抗为基础的联合化疗方案治疗后,疗效评估为完全缓解CR 16例（51.6%）,部分缓解PR 10例（32.3%）,疾病稳定SD 2例（6.5%）,疾病进展PD 3例（9.7%）,总体反应率ORR 83.9%。②31例弥漫大B细胞淋巴瘤患者接受国产利妥昔单抗治疗后,常见的不良反应发生率依次为：血液学毒性29.0%（9/31）,包括中性粒细胞减少、血小板减少等等。其次为感染19.4%（6/31）、消化道症状16.1%（5/31）,包括腹痛、腹泻、便秘等等。所有常见不良反应经过对症处理后均可好转。仅有1例患者发生过敏反应3.2%（1/31）,1例患者因病情严重而死亡。结论：国产利妥昔单抗在弥漫大B细胞淋巴瘤患者的治疗中具有良好的临床疗效及安全性,不良反应较少,值得进一步探讨和应用。     

利妥昔单抗注射液联合化疗治疗B细胞非霍奇金淋巴瘤的疗效观察

目的:观察利妥昔单抗注射液联合化疗治疗B细胞非霍奇金淋巴瘤(B-NHL)的疗效。方法:将2013年1月至2014年12月我院收治的71例B-NHL患者分为对照组(n=35例)和观察组(n=36例)。对照组给予常规化疗方案进行治疗,观察组在此基础上加用利妥昔单抗进行治疗,3个周期后评价其疗效及安全性。结果:观察组总有效率为91.67%,明显高于对照组的68.57%,对比差异有统计学意义(x2=5.979,P0.05);观察组不良反应总发生率为41.67%,略低于对照组的45.71%,但无统计学差异(x2=0.118,P0.05)。结论:利妥昔单抗注射液联合化疗治疗B-NHL中期疗效显著,且无严重不良反应,值得临床推广。     

利妥昔单抗注射液联合CHOP化疗方案治疗B细胞非霍奇金淋巴瘤的效果

目的探讨利妥昔单抗注射液联合CHOP化疗方案治疗B细胞性非霍奇金淋巴瘤的临床效果。方法选择2016年4月～2017年11月于我院进行治疗的B细胞NHL患者60例为研究对象,按照数字法分为观察组和对照组,每组各30例,对照组给予常规CHOP方案进行治疗,观察组给予利妥昔单抗注射液与CHOP方案联合治疗,比较两组患者的疗效和毒副反应。结果观察组患者有效率是93.33%,对照组患者有效率是73.33%,观察组患者有效率高于对照组(P0.05)。两组患者均有出现血小板减少、畏寒发热、恶心呕吐以及脱发现象,且两组出现毒副反应人数差异不大(P0.05)。结论对B细胞NHL使用利妥昔单抗注射液与CHOP联合治疗,可以有显著改善患者临床症状和毒副反应发生率,值得推广。     

利妥昔单抗联合化疗治疗非霍奇金淋巴瘤的药物经济学评价

目的：系统评价利妥昔单抗联合化疗治疗非霍奇金淋巴瘤的药物经济学价值。方法：用计算机检索PubMed、ScienceDirect、Springer Link、Elsevier 等英文数据库以及CNKI、维普、万方等中文数据库1998—2013 年间公开发表的利妥昔单抗联合化疗治疗非霍奇金淋巴瘤的药物经济学评价文献,对文献质量、研究结果进行系统评价。结果：所有英文文献的 ICER 值均在各国的意愿支付范围内;国内外利妥昔单抗药物经济学评价在数据来源、研究方法等方面存在差异。结论：利妥昔单抗联合化疗治疗非霍奇金淋巴瘤在国外具有成本-效果;需开展高质量的研究来探索利妥昔单抗联合化疗治疗非霍奇金淋巴瘤在我国的经济性。     

利妥昔单抗维持治疗弥漫大B 细胞淋巴瘤的初步研究

目的:对弥漫大B细胞淋巴瘤患者进行利妥昔单抗维持治疗(Maintenance Rituximab,MR)的安全性及疗效的研究和探讨.方法:38例患者诱导治疗结束后根据患者及家属意见和经济条件分为MR组和观察组.每组19例.诱导治疗阶段两组患者均接受6～8个疗程R-CHOP(每3周)或R-EPOCH方案治疗.维持阶段,利妥昔单抗在诱导治疗完成后4-8周开始,375mg/m2,每3个月1次共2年(8次)或直至疾病复发、进展、死亡.维持前均经影像学检查证实无复发.结果与结论:MR对R-EPOCH或R-CHOP的诱导治疗后达到CRu/CR初治DLBCL病人,有很好的近期疗效,能提高其DFS率,但OS率无改善,而且其毒副反应小,可以耐受.     

利妥昔单抗联合CHOP化疗治疗感染乙肝病毒的非霍奇金淋巴瘤患者的安全性分析

目的:观察利妥昔单抗与CHOP化疗联合治疗感染乙肝病毒(HBV)的非霍奇金淋巴瘤(NHL)患者的有效性及安全性。方法:选取2010年6月至2013年6月35例B细胞NHL住院患者,分为两组,观察组(n=13)为感染HBV患者,接受利妥昔单抗-CHOP化疗方案;对照组(n=22)为非感染HBV的患者,单纯接受CHOP化疗方案,两组治疗4~6疗程,观察两组患者治疗的疗效及肝功能。结果:观察组完全缓解率(CR率)为76.92%,对照组CR率为40.91%(P0.05),两组差异有统计学意义。观察组肝功能损害I~Ⅱ级发生率为23.07%,对照组肝功能损害I~Ⅱ级发生率18.18%(P0.05),观察组毒副反应发生率为30.77%,对照组毒副反应发生率为22.72%(P0.05),两组在肝功能损害及毒副反应上差异无统计学意义。两组患者HBV均未再激活。结论:感染HBV的B细胞NHL患者用R-CHOP联合化疗方案治疗,以及在化疗时预防性、足疗程的抗病毒治疗,可以减少HBV再激活的发生,并且可以降低肝功损害率。     

利妥昔单抗治疗肾病综合征患者效果观察及对视黄醇结合蛋白、微循环状态的影响分析

摘要 目的：探讨与分析利妥昔单抗（RTX）治疗肾病综合征患者效果观察及对视黄醇结合蛋白（RBP）、微循环状态的影响。方法：2018年9月到2021年11月选择在本院诊治的肾病综合征患者66例作为研究对象,所有患者按入院先后顺序编号,依据治疗方法分为利妥昔单抗组和对照组各33例,对照组给予糖皮质激素治疗,利妥昔单抗组在对照组治疗的基础上给予利妥昔单抗治疗,治疗观察3个月,观察与检测血清RBP、微循环状态变化情况。结果：治疗后利妥昔单抗组的总有效率为97.0 %,明显高于对照组的81.8 %（P<0.05）。两组治疗后的尿蛋白定量、尿蛋白定性水平低于治疗前,利妥昔单抗组明显低于对照组,而血浆白蛋白较治疗前高,且利妥昔单抗组高于对照组（P<0.05）。两组治疗后的甲襞微循环管绊形态、流态评分明显低于治疗前,利妥昔单抗组明显低于对照组（P<0.05）。两组治疗后的血清RBP含量低于治疗前,利妥昔单抗组明显低于对照组（P<0.05）。两组治疗期间不良反应对比无明显差异（P>0.05）。结论：利妥昔单抗治疗肾病综合征患者能有效改善微循环状态,抑制血清RBP的表达,能提高治疗效果,还可促进改善肾功能,具有安全性。     

西妥昔单抗联合化疗治疗K-Ras野生型转移性结直肠癌的疗效及其影响因素分析

目的:探讨西妥昔单抗联合化疗治疗K-Ras野生型转移性结直肠癌(mCRC)的疗效及其影响因素。方法:选取2013年1月～2015年1月河北北方学院附属第一医院收治的K-Ras野生型mCRC患者96例,按照随机数字表法将患者分为对照组(n=48)和观察组(n=48)。对照组给予常规化疗方案治疗,观察组在此基础上给予西妥昔单抗治疗。比较两组临床疗效、中位无进展生存期(PFS)、中位总生存期(OS)以及不良反应发生情况,并分析观察组治疗疗效的影响因素。结果:观察组客观有效率(ORR)和疾病控制率(DCR)分别为54.17%和91.67%,均高于对照组的31.25%和81.25%(P0.05)。观察组患者中位PFS和中位OS均较对照组长(P0.05)。观察组皮肤痤疮样病变发生率高于对照组(P0.05)。单因素分析显示,西妥昔单抗联合化疗治疗K-Ras野生型mCRC的ORR、DCR与年龄、肿瘤部位、肿瘤转移部位、肿瘤分化程度以及西妥昔单抗治疗时间有关(P0.05)。结论:西妥昔单抗联合化疗治疗K-Ras野生型mCRC疗效确切,预后较好,患者对不良反应可耐受,患者年龄、肿瘤部位、转移部位、分化程度及西妥昔单抗治疗时间可能是其疗效的影响因素。     

Hyper-CVAD/MA治疗复发或难治性弥漫大B 细胞淋巴瘤的临床研究

目的:探讨Hyper-CVAD/MA方案治疗复发或难治弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的疗效及安全性。方法:观察26例经系统化疗后复发或难治的DLBCL患者接受Hyper-CVAD/MA方案化疗,21-28天为1周期,连续2个周期评价疗效及安全性,分析生存情况。结果:全组26例患者中,总有效率为46.15%,其中完全缓解(complete remission,CR)3例(11.54%),部分缓解(partial remission,PR)9例(34.61%),全组患者中位生存时间为10(2-25)个月,1年和2年总生存率分别为28.57%、14.29%。不良反应主要表现为III-IV度骨髓抑制及继发的肺部感染,其他包括胃肠道反应、口腔炎、肝功能异常等。结论:Hyper-CVAD/MA治疗复发难治DLBCL有一定的疗效,且患者可耐受,可作为二线方案的一个选择。     

西妥昔单抗和贝伐珠单抗治疗晚期结直肠癌的有效性和安全性比较

目的:比较西妥昔单抗和贝伐珠单抗治疗晚期结直肠癌的有效性和安全性。方法:选取2014年1月～2017年8月我院收治的晚期结直肠癌患者100例,根据患者入院先后顺序随机分为两组,所有患者均给予FOLFIRI方案进行化疗,A组在化疗的基础上给予贝伐珠单抗进行治疗,B组在化疗的基础上给予西妥昔单抗进行治疗。比较两组患者临床治疗的缓解率、控制率及不良反应的发生情况,对所有患者随访1年,记录并比较两组患者的无进展生存期。结果:两组患者的缓解率、控制率、恶心呕吐、头晕、延迟性腹泻、肝肾损伤、白细胞减少、血小板减少和尿蛋白的发生率相比均无统计学差异(P0.05),但B组患者骨髓抑制和皮疹的发生率显著高于A组(P0.05);两组患者的无进展生存期相比无统计学差异(P0.05)。结论:西妥昔单抗和贝伐珠单抗治疗晚期结直肠癌的临床效果相当,且不良反应较轻,以Ⅰ～Ⅱ度为主,患者均可耐受,对症治疗后均有所缓解。西妥昔单抗易引发骨髓抑制和皮疹,在临床应用过程中需注意并进行有效预防和积极处理。     

Homozygous A polymorphism of the complement C1qA 276 correlates with prolonged overall survival in patients with diffuse large B cell lymphoma treated with R-CHOP

ABSTRACT: BACKGROUND: The precise mechanism of action for rituximab (R) is not fully elucidated. Besides antibodydependent cellular cytotoxicity (ADCC), complements may also play an important role in the clinical response to rituximab-based therapy in diffuse large B cell lymphoma (DLBCL). The purpose of this study was to explore the relationship between C1qA[276] polymorphism and the clinical response to standard frontline treatment with R-CHOP in DLBCL patients. METHODS: Genotyping for C1qA[276A/G] was done in 164 patients with DLBCL. 129 patients treated with R-CHOP as frontline therapy (R [greater than or equal to] 4 cycles) were assessable for the efficacy. RESULTS: Patients with homozygous A were found to have a higher overall response rate than those with heterozygous or homozygous G alleles (97.3% vs. 83.7%,P = 0.068). The complete response rate in patients with homozygous A was statistically higher than that in AG and GG allele carriers (89.2% vs. 51.1%,P = 0.0001). The overall survival of patients with homozygous A was longer than that of the G allele carriers (676 days vs. 497 days, P = 0.023). Multivariate Cox regression analysis showed that C1qA A/A allele was an independent favorable prognostic factor for DLBCL patients treated with R-CHOP as firstline therapy. CONCLUSION: These results suggest that C1qA polymorphism may be a biomarker to predict response to RCHOP as frontline therapy for DLBCL patients.     

Combined treatment of rituximab,idarubicin, dexamethasone,cytarabine, methotrexate with radiotherapy for primary central nervous system lymphoma

The overall response rates and long‐term survival of primary central nervous system lymphoma (PCNSL) are still significantly inferior to the results achieved in similar subtypes of extranodal non‐Hodgkin's lymphoma. It is clearly necessary to investigate new therapeutic methods on PCNSL. We encountered three patients histologically documented PCNSL as diffuse large B‐cell lymphoma (DLBCL). They were treated with R‐IDARAM which comprised rituximab, idarubicin, dexamethasone, cytarabine and methotrexate. Patient 1 received stereotactic brachytherapy (SBT) prior to chemotherapy performed with iodine‐125 seeds (cumulative therapeutic dose 50 Gy). After six cycles of R‐IDARAM at 3‐weekly intervals, radiotherapy was applied at a dosage of 2000–4000 cGy in conventional schedule (180 or 200 cGy/day) to whole brain or spinal cord in all patients. Complete remission (CR) was achieved after first two cycles of R‐IDARAM in all patients. All three patients remained in CR at the time of this report with a median duration of follow‐up of 23 months (ranging from 13 to 41 months). Three patients have been alive for 41, 13, 16 months respectively until now. The patient with the longest survival time was the one given SBT prior to chemotherapy. This study suggests that R‐IDARAM combining with radiotherapy maybe a high effective regimen in PCNSL patients especially those with primary central nervous system DLBCL. A comprehensive treatment combining internal radiotherapy by SBT, modified R‐IDARAM and followed reduced external radiotherapy may be a new treatment concept for PCNSL with higher efficiency and lower toxicity.     

Survival and consolidative radiotherapy in patients living with HIV and treated for diffuse large B-cell lymphoma

ObjectivesCurrent guidelines tend to treat HIV positive (HIV+) patients as their seronegative counterparts with diffuse large B-cell lymphoma (DLBCL) but little is known about their radiotherapy responses differences.Patients and MethodsA retrospective cohort of all consecutive HIV+ DBCL patients treated with chemotherapy between 2004 and 2018 was assessed. All patients had biopsy-proven lymphomas. They were included if the proposed radical treatment was done without progression or death during chemotherapy and had at least 6 months of follow-up or were followed until death.ResultsFifty-three (53) patients were selected, with a median age at diagnosis of 41.39 years (20–65 years). Median follow-up of 35.16 months (1.4–178.7 months). Male patients accounted for 54.7% and most had a good performance in the ECOG scale at diagnoses (81.1% are ECOG 0−1). Median overall survival was not reached. Mean OS was 41.5 months with 16 deaths. Age had an impact on OS, with patients older than 60 years at more risk (p = 0.044), as did longtime use of HAART, with those that started antiretroviral therapy within the diagnose of the lymphoma at greatest risk (p = 0.044). RT did not have an impact on OS (p = 0.384) or PFS (p = 0.420), although survival curves show better OS in the radiotherapy group. Toxicities were rare, since none of the patients had grade 3 or superior toxicity.ConclusionRT did not impact survival or progression in our limited sample, but a longer OS may occur after the first-year post RT. RT should be tested in prospective data in the HIV+ population with DLBCL.     

Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab- CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL)

ABSTRACT: BACKGROUND: The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland. METHODS: Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed. RESULTS: Complete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001). CONCLUSIONS: Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.     

Disseminated Cryptococcosis in a Non-Hodgkin’s Lymphoma Patient with Late-Onset Neutropenia Following Rituximab-CHOP Chemotherapy: A Case Report and Literature Review

Rituximab-related late-onset neutropenia (R-LON) is an adverse event associated with rituximab. A 65-year-old woman presented with diffuse large B-cell lymphoma of the kidney without bone marrow involvement. She was treated with 4 cycles of CHOP chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine, and prednisolone at 4-week intervals. Rituximab was also administrated of the second, third, fourth CHOP cycles. She developed a high fever of 38°C, nausea, and severe neutropenia following the four cycles of R-CHOP chemotherapy. Her leukocyte count was 160/μl without neutrophils. Initially, a blood and pleural fluid and cerebrospinal fluid cultures were positive for Cryptococcus neoformans. Once she became asymptomatic following treatment with fluconazole and neutropenia was recovered with lenograstim, she had neck stiffness and admitted soon. Cerebro-spinal fluid (CSF) culture was positive for Cryptococcus neoformans. Treatment with amphotericin B(AMPH-B) and flucytosine(5-FC) was initiated as diagnosis of cryptococcus meningitis. Lenograstim was administrated for 9 months, and amount of dose was 9,750 μg. Cryptococcosis with malignant lymphoma is rare disease, and previously 17 cases were reported. Of note, mortality of disseminated cryptococcosis with malignant lymphoma is 54%. The more and more rituximab is widely used; the cases of severe infection in R-LON may increase.     

Blood Lymphocyte-to-Monocyte Ratio Identifies High-Risk Patients in Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Background

Recent research has shown a correlation between immune microenvironment and lymphoma biology. This study aims to investigate the prognostic significance of the immunologically relevant lymphocyte-to-monocyte ratio (LMR), in diffuse large B-cell lymphoma (DLBCL) in the rituximab era.

Methodology/Principal Findings

We analyzed retrospective data from 438 newly diagnosed DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. We randomly selected 200 patients (training set) to generate a cutoff value for LMR by receiver operating characteristic (ROC) curve analysis. LMR was then analyzed in a testing set (n = 238) and in all patients (n = 438) for validation. The LMR cutoff value for survival analysis determined by ROC curve in the training set was 2.6. Patients with low LMR tended to have more adverse clinical characteristics. Low LMR at diagnosis was associated with worse survival in DLBCL, and could also identify high-risk patients in the low-risk IPI category. Multivariate analysis identified LMR as an independent prognostic factor of survival in the testing set and in all patients.

Conclusions/Significance

Baseline LMR, a surrogate biomarker of the immune microenvironment, is an effective prognostic factor in DLBCL patients treated with R-CHOP therapy. Future prospective studies are required to confirm our findings.     

Ofatumumab, the first human anti-CD20 monoclonal antibody for the treatment of B cell hematologic malignancies

Ofatumumab is the first human anti-CD20 monoclonal antibody to be approved for patients in the United States and the European Union. Ofatumumab received accelerated approval from the U.S. Food and Drug Administration in October 2009 and was granted a conditional marketing authorization by the European Medicines Agency in April 2010 for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab, based on interim results of a pivotal phase 2 trial. Preliminary positive results for ofatumumab in combination with chemotherapy in patients with CLL are currently being confirmed in larger randomized trials in both the frontline setting and the relapsed/refractory setting. Ofatumumab has also shown potential in treating B cell non-Hodgkin's lymphoma, such as follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), and Waldenstr?m's macroglobulinemia. Additional trials are ongoing to confirm activity of ofatumumab as monotherapy and in combination with chemotherapy in patients with FL or DLBCL.     

Immunofluorescent labeling of CD20 tumor marker with quantum dots for rapid and quantitative detection of diffuse large B-cell non-Hodgkin's lymphoma

Fluorescent semiconductor quantum dots (QDs) are newfound nanocrystal probes which have been used in bioimaging filed in recent years. The purpose of this study is to evaluate the diagnostic value of specific QDs coupled to rituximab monoclonal antibody against CD20 tumor markers for patients with diffuse large B-cell lymphoma (DLBCL). In current study rituximab-conjugated quantum dots (QDs-rituximab) were prepared against CD20 tumor markers for detection of CD20-positive cells (human Raji cell line) using flowcytometry. A total of 27 tumor tissue samples were collected from patients with DLBCL and 27 subjects with negative pathological tests as healthy ones, which stained by QD-rituximab. The detection signals were obtained from QDs using fluorescence microscopy. The flowcytometry results demonstrated a remarkable difference in fluorescent intensity and FL2-H + (CD20-positive cells percentage) between two groups. Both factors were significantly higher in Raji in comparison with K562 cell line (P < 0.05). Lot of green fluorescence signals was observed due to the selectively binding of QD-rituximab to CD20 tumor markers which overexpressed in tumor tissues and a few signals observed on the defined healthy ones. Based on these observations the cut-off point was 46.8 dots and the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 89.5%, 91.3%, and 100%, respectively (LR+, 9.52; LR−, 0). The QD - rituximab could be beneficial as a bioimaging tool with high sensitivity to provide an accurate molecular imaging technique for identifying CD20 tumor markers for early diagnosis of the patients with DLBCL.