放疗对早期弥漫大B细胞淋巴瘤化疗后CR患者的价值研究

目的 探讨放疗在早期弥漫大B细胞淋巴瘤(DLBCL)化疗后达CR患者中的地位。方法 回顾分析2004—2012年本院治疗的376例Ⅰ、Ⅱ期DLBCL患者资料,均接受至少3个周期CHOP和利妥昔单抗+CHOP方案化疗(R-CHOP)后达CR者。R-CHOP组92例,R-CHOP+放疗组79例,CHOP+放疗组98例,CHOP组107例。放疗为累及野照射30~56 Gy。Kaplan-Meier法计算生存率并Logrank法检验,Cox回归模型多因素预后分析。结果 5年样本量为188例。全组5年DFS、OS分别为80.7%、87.6%,R-CHOP+放疗组和R-CHOP组的分别为94.9%和88.1%(P=0.030)、97.9%和86.0%(P=0.026),CHOP+放疗组和CHOP组的分别为74.2%和71.4%(P=0.623)、87.0%和82.1%(P=0.420)。多因素分析显示吸烟指数<500、IPI<2、加用利妥昔单抗是预后有利因素(P=0.034~0.000)。结论 放疗对早期DLBCL可以提高R-CHOP化疗后CR者的DFS和OS。建议DLBCL使用含利妥昔单抗的化疗,R-CHOP化疗后应接受放疗。希望开展随机对照研究进一步证明该结果。     

利妥昔单抗联合CHOP与单用CHOP方案治疗初治弥漫大B细胞型淋巴瘤的对比研究

目的：比较利妥昔单抗（商品名：美罗华）联合CHOP（环磷酰胺,阿霉素,长春新碱和泼尼松）与单用CHOP方案化疗治疗弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）的临床疗效。方法：根据患者的意愿,49例DLBCL患者分别接受6疗程CHOP方案或CHOP加利妥昔单抗方案化疗,每3周1疗程,共6个疗程。结果：R-CHOP组的CR率高于CHOP组,但差异无统计学意义（82.6%VS 65.4%,P=0.173）。中位随访时间为35月（4-66月）,R-CHOP组及CHOP组的3年OS分别为75.0%±19.6%,54.9%±20.4%,P=0.043;而3年EFS分别为69.7%±20.9%,45.8%±20.6%,P=0.029。R-CHOP组的3年OS及EFS优于CHOP组,差异有统计学意义。两组患者的不良反应无明显差别。结论：与单用CHOP方案相比,利妥昔单抗联合CHOP方案明显提高DLBCL患者的EFS及OS,而不良反应无明显增加。     

含聚乙二醇脂质体多柔比星的CHOP样方案治疗初治老年晚期弥漫大B 细胞淋巴瘤的Ⅱ期临床研究*

目的:评价含聚乙二醇脂质体多柔比星（PLD ）的CHOP 样方案治疗初治老年晚期弥漫大B 淋巴瘤（DLBCL）的疗效和安全性。方法:2011年11月至2014年3 月共入组30例患者,中位年龄70（63～80）岁,24例（80.0%）国际预后指数≥3 分;21例联合应用利妥昔单抗。进行前瞻性II 期临床研究,以含PLD 的CHOP 样方案治疗初治老年晚期DLBCL。PLD 剂量为30mg/m2,环磷酰胺、长春新碱和强的松采用标准CHOP 方案中的剂量。CD20阳性的患者可联合利妥昔单抗,计划完成6 个周期。结果:客观缓解率为86.7% ,其中完全缓解率为66.7% 。中位随访20.1（0.7～38.5）个月,18个月总生存率及无进展生存率分别为 82.4% 及70.1% 。主要不良反应为中性粒细胞减少。24例（80.0%）发生3～4 级中性粒细胞减少。研究中患者左室射血分数及血清肌钙蛋白T 无显著变化。4 例（13.3%）在PLD 输注后新发无症状性心电图异常。结论:含PLD 的CHOP 样方案是治疗初治老年晚期DLB-CL患者毒性可接受的备选方案,缓解率较高,心脏安全性较好。      

白细胞介素2联合R-CHOP方案治疗弥漫性大B细胞淋巴瘤初步临床观察

 目的　探讨白细胞介素2（IL-2）联合R-CHOP方案扩增NK细胞数及增强利妥昔单抗临床疗效的可行性。建立IL-2与R-CHOP联合治疗弥漫大B细胞淋巴瘤（DLBCL）的临床用药方法。方法　选取2008年8月至2009年3月住院治疗的初治DLBCL患者24例，进行前瞻性非随机同期对照研究，治疗组12例采用IL-2联合R-CHOP方案治疗；对照组12例仅采用R-CHOP治疗。通过流式细胞术（FCM）检测治疗组与对照组NK细胞数的变化，并观察临床疗效及不良反应。结果　治疗组完全缓解（CR）率为60 %（6／10），总有效（OR）率为80 %（8／10）；对照组CR率50 %（5／10），OR率70 %（7／10）。治疗组NK细胞绝对值较对照组显著升高（P＝0.015）。治疗组化疗前后NK细胞百分率降低的幅度低于对照组，差异具有统计学意义（P＝0.005）。化疗后使用IL-2后NK细胞百分率较使用IL-2前明显升高（P＝0.03）。治疗组10例患者中出现腹泻3例、发热3例。结论　IL-2联合R-CHOP可以提高DLBCL患者体内NK细胞数量，可能减弱化疗对NK细胞的杀伤作用，且不良反应可以耐受，值得进一步研究。     

重组人粒-巨噬细胞集落刺激因子联合R-CHOP方案治疗初治弥漫大B细胞淋巴瘤效果观察

目的:观察重组人粒-巨噬细胞集落刺激因子（rhGM-CSF）联合R-CHOP方案治疗初治弥漫大B细胞淋巴瘤的临床效果及安全性。方法:回顾性分析2017年2月至2019年11月海军军医大学（第二军医大学）长海医院39例接受rhGM-CSF联合R-CHOP方案及39例接受R-CHOP方案治疗的初治DLBCL患者的临床资料,比较两组患者的总反应率（ORR）、完全缓解（CR）率、总生存（OS）、无进展生存（PFS）及不良反应发生情况。结果:rhGM-CSF联合R-CHOP方案组及R-CHOP方案组的ORR分别为87.2%（34/39）、82.1%（32/39）,差异无统计学意义（ χ2=0.394, P=0.53）,CR率分别为71.8%（28/39）、56.4%（22/39）,差异亦无统计学意义（ χ2=2.006, P=0.157）。随访截至2020年9月19日,rhGM-CSF联合R-CHOP方案组生存32例,死亡7例,其中1例死于肠癌,原发病仍处于CR状态;R-CHOP方案组生存32例,死亡7例。rhGM-CSF联合R-CHOP方案组及R-CHOP方案组2年OS率分别为82.5%、73.9%（ χ2=0.038, P=0.845）,2年PFS率分别为67.1%、55.2%（ χ2=0.457, P=0.499）。亚组分析结果显示,rhGM-CSF联合R-CHOP方案组及R-CHOP方案组的生发中心B细胞型亚组间、非生发中心B细胞型亚组间、Lugano分期Ⅰ~Ⅱ期亚组间、Lugano分期Ⅲ~Ⅳ期亚组间、年龄<60岁亚组间、年龄≥60岁亚组间CR率分别比较,差异均无统计学意义（均 P>0.05）。主要不良反应为骨髓抑制及其所致感染,两组3~4级血液学不良反应及感染发生率比较,差异均无统计学意义（均 P>0.05）。予支持治疗后,所有患者均安全度过骨髓抑制期,无治疗相关死亡。 结论:rhGM-CSF联合R-CHOP方案用于初治DLBCL患者安全有效。     

利妥昔单抗联合CHOP与单用CHOP方案治疗初治弥漫大B细胞型淋巴瘤的对比研究

目的:比较利妥昔单抗(商品名:美罗华)联合CHOP(环磷酰胺,阿霉素,长春新碱和泼尼松)与单用CHOP方案化疗治疗弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)的临床疗效。方法:根据患者的意愿,49例DLBCL患者分别接受6疗程CHOP方案或CHOP加利妥昔单抗方案化疗,每3周1疗程,共6个疗程。结果:R-CHOP组的CR率高于CHOP组,但差异无统计学意义(82.6%VS 65.4%,P=0.173)。中位随访时间为35月(4-66月),R-CHOP组及CHOP组的3年OS分别为75.0%±19.6%,54.9%±20.4%,P=0.043;而3年EFS分别为69.7%±20.9%,45.8%±20.6%,P=0.029。R-CHOP组的3年OS及EFS优于CHOP组,差异有统计学意义。两组患者的不良反应无明显差别。结论:与单用CHOP方案相比,利妥昔单抗联合CHOP方案明显提高DLBCL患者的EFS及OS,而不良反应无明显增加。     

麻疹疫苗联合 CHOP 方案治疗弥漫大 B 细胞淋巴瘤的临床研究

目的：探讨麻疹疫苗（measles vaccine）联合CHOP方案治疗弥漫大B细胞淋巴瘤（DLBCL）的临床疗效和毒副反应.方法：选择2006年1月至2011年12月住院治疗的DLBCL患者60例,随机分为观察组（30例）和对照组（30例）,观察组采用麻疹疫苗联合CHOP方案治疗,对照组采用单纯CHOP方案化疗.全部患者完成6个周期化疗.比较两组治疗效果,随访观察生存情况.结果：观察组总有效 （OR）率（CR＋PR）为83.3%（25/30）,对照组总有效（OR）率（CR＋PR）为60%（18/30）,比较差异有显著性（P＜0.05）.观察组和对照组1年PFS率为76.7%及50%（P＜0.05）,1年总生存率为90%及66.7%（P＜0.05）.结论：麻疹疫苗联合CHOP方案治疗弥漫大B细胞淋巴瘤有安全、有效、不良反应少、生存率高等优点,值得进一步研究.     

乳腺癌不同剂量表柔比星联合辅助化疗的疗效分析

目的：比较不同剂量表柔比星方案辅助化疗治疗乳腺癌的近期疗效及不良反应。方法：选取2005-01-01-2008-06-30大连医科大学附属第二医院采用含表柔比星方案辅助化疗的309例Ⅰ~Ⅲ期乳腺癌患者,分为表柔比星大剂量（100mg/m2）组和小剂量（75mg/m2）组,回顾性分析比较两组间1、3、5年无病生存率（disease-free survival,DFS）、总生存率（overall survival,OS）及不良反应,并采用Cox回归分析预后影响因素。Log-rank法比较两组生存差异,并分层分析筛选出从大剂量中获益的人群。结果：大剂量组与小剂量组1年DFS分别为95.05%和96.15%,3年DFS分别为84.16%和80.77%,5年DFS分别为77.23%和74.52%;1年OS分别为97.03%和98.08%,3年OS分别为93.07%和90.87%,5年OS分别为87.13%和83.17%。大剂量组疗效略高于小剂量组,但两组DFS（P=0.543）及OS（P=0.396）差异无统计学意义。Cox风险比例模型分析再次验证化疗方案中表柔比星的剂量不是影响DFS及OS的重要因素。分层分析结果显示,ER/PR阴性表达（P=0.026）及三阴性乳腺癌（P=0.044）患者大剂量组平均DFS高于小剂量组,差异有统计学意义。大剂量组的胃肠道毒性（P=0.042）及血液毒性（P=0.010）均较小剂量组大,差异有统计学意义。结论：表柔比星大、小不同剂量组之间近期疗效差异无统计学意义;仅ER和PR表达阴性及三阴性乳腺癌的患者能从大剂量表柔比星辅助化疗中获益。大剂量组化疗胃肠道毒性和血液毒性明显大于小剂量组。     

参麦注射液对接受表柔比星化疗的恶性肿瘤患者心肌酶水平的影响

心脏毒性是表柔比星应用过程中,发生率相对较高且较严重的一种毒副反应。为控制表柔比星的心脏毒性,从而使化疗顺利进行,本文将参麦注射液与含表柔比星方案联用,化疗后采用ELISA法检测患者血清肌酸激酶同工酶（CK—MB）、肌钙蛋白T（cTnT）水平,并以单用含表柔比星方案作为对照,以此评估参麦注射液对接受含表柔比星方案化疗的恶性肿瘤患者心脏毒性的影响。     

利妥昔单抗联合化疗治疗弥漫大B细胞淋巴瘤临床分析

 目的　观察利妥昔单抗（商品名：美罗华）联合化疗治疗弥漫大B细胞淋巴瘤（DLBCL）的临床疗效及淋巴瘤国际预后指数（IPI）评分对预后的影响;探讨利妥昔单抗在DLBCL自体外周血干细胞移植（APBSCT）中的应用。方法　DLBCL 患者21例,IPI评分低危和中低危（0～2分）14例,中高危和高危（3～5分）7例。采用利妥昔单抗联合CHOP（环磷酰胺、多柔比星、长春新碱、泼尼松）方案4～8个疗程,其中有5例接受APBSCT,动员方案为利妥昔单抗联合环磷酰胺加依托泊苷,预处理方案为CBV （环磷酰胺、卡莫司汀、依托泊苷）方案。结果　21例患者中CR 13例（61.9 %）,总有效率90.5 %（19／21）;2年疾病无进展生存率为（69.74±10.43）%,2年总生存率为（84.44±8.35）%。IPI评分0～2分患者CR率92.9 %,总有效率100 %,3～5分患者CR率0,总有效率71.4 %,IPI 0～2分患者CR率高于3～5分患者（P＜0.01）;5例接受APBSCT的患者采集的中位单个核细胞（MNC）为7.34×108／kg,中位CD+34细胞为8.82×106／kg,造血恢复中性粒细胞＞0.5×109／L的中位时间＋9天,血小板＞20×109／L的中位时间＋12天;主要不良反应是输注相关的不良反应（14.3 %）以及化疗相关的血液学不良反应。结论　利妥昔单抗联合化疗治疗DLBCL疗效满意,IPI 0～2分患者的完全缓解率明显高于3～5分患者;利妥昔单抗不影响外周造血干细胞的采集及造血重建;利妥昔单抗应用安全性较好。     

Bcl-2 gene expression as a predictor of outcome in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with a 5-year survival rate of 35%-60%. Various clinical factors included in the International Prognostic Index have failed to identify the patients with DLBCL who will not benefit from the standard R-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone plus rituximab) treatment regimen. Bcl-2 has been implicated in conferring resistance to chemotherapy in non-Hodgkin's lymphoma and is therefore a candidate prognostic marker in DLBCL. To identify the correlation between Bcl-2 expression and response to rituximab-containing treatment regimens, histologic materials were analyzed from 292 elderly patients with confirmed DLBCL. Of these, 155 patients had received R-CHOP (53%) and 137 had received CHOP (47%). One hundred ninety-three patients (66%) were found to express high levels of Bcl-2 protein in > 50% of the tumor cells. Of the 193 Bcl-2-positive patients, the patients who received R-CHOP had a better 5-year overall rate than patients treated with CHOP (56% vs. 42%; P = 0.01), whereas in the patients with Bcl-2-negative disease, there was no statistically significant difference in the 5-year overall survival rates between the R-CHOP and CHOP regimens (58% vs. 52%; P = 0.6). Therefore, the addition of rituximab to the standard chemotherapy regimen seems to have overcome the Bcl-2-associated resistance to chemotherapy.     

Bcl-2 Gene Expression as a Predictor of Outcome in Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with a 5-year survival rate of 35%–60%. Various clinical factors included in the International Prognostic Index have failed to identify the patients with DLBCL who will not benefit from the standard R-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone plus rituximab) treatment regimen. Bcl-2 has been implicated in conferring resistance to chemotherapy in non-Hodgkin's lymphoma and is therefore a candidate prognostic marker in DLBCL. To identify the correlation between Bcl-2 expression and response to rituximabcontaining treatment regimens, histologic materials were analyzed from 292 elderly patients with confirmed DLBCL. Of these, 155 patients had received R-CHOP (53%) and 137 had received CHOP (47%). One hundred ninety-three patients (66%) were found to express high levels of Bcl-2 protein in > 50% of the tumor cells. Of the 193 Bcl-2-positive patients, the patients who received R-CHOP had a better 5-year overall rate than patients treated with CHOP (56% vs. 42%; P = 0.01), whereas in the patients with Bcl-2-negative disease, there was no statistically significant difference in the 5-year overall survival rates between the R-CHOP and CHOP regimens (58% vs. 52%; P = 0.6). Therefore, the addition of rituximab to the standard chemotherapy regimen seems to have overcome the Bcl-2-associated resistance to chemotherapy.     

Nonpegylated liposomal doxorubicin (Myocet™) combination (R-COMP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL): results from the phase II EUR018 trial

BackgroundTo evaluate the activity and safety of nonpegylated liposomal doxorubicin (Myocet™) when substituted for doxorubicin in the R-CHOP regimen (R-COMP).Patients and methodsSeventy-five elderly patients with diffuse large B-cell lymphoma (DLBCL) were studied. Only patients with left ventricular ejection fraction (LVEF) ≥50% were allowed. R-COMP regimen was administered every 3 weeks for three cycles, followed by additional five cycles in case of complete response (CR) or partial response.ResultsFrom November 2002 to April 2005, 75 patients were registered, of which 72 were evaluated. Median age was 72 years (range 61–83); 56% of patients had high or high–intermediate International Prognostic Index score. Median LVEF at baseline was 61%. Thirty-eight patients had history of abnormal cardiovascular conditions. The overall response rate was 71%, with a CR rate of 57%. After a median follow-up of 33 months, the 3-year overall survival, failure-free survival, and progression-free survival rates were 72%, 39%, and 69%, respectively. Neutropenia (54%) was the most frequent grade 3–4 adverse event (AE); 21% of patients experienced cardiac AEs, graded as 3–4 in 4% of the cases.ConclusionR-COMP is an effective regimen for the treatment of DLBCL in elderly patients, with an acceptable tolerability profile.     

SIL index, comprising stage, soluble interleukin-2 receptor, and lactate dehydrogenase, is a useful prognostic predictor in diffuse large B-cell lymphoma

Rituximab (R) plus doxorubicin, cyclophosphamide, vincristine, and prednisolone (CHOP) chemotherapy (R-CHOP) is widely accepted as standard care for diffuse large B-cell lymphoma (DLBCL) patients. The revised International Prognostic Index (R-IPI) was established in 2007 after the addition of rituximab to standard DLBCL treatment. To reassess the utility of R-IPI, we carried out a retrospective analysis of patients with DLBCL uniformly treated with standard R-CHOP. Progression-free survival (PFS) curves in "very good" and "good" risk groups as defined by the R-IPI showed no statistical difference. We added soluble interleukin-2 receptor (sIL-2R) level to the factors comprising the R-IPI. Five levels of sIL-2R were weighed with respect to their impact on PFS. sIL-2R of >2500 U/mL was determined as the most appropriate threshold. We developed a new prognostic SIL index, which includes three independent prognostic risk factors: clinical stage (S); sIL-2R level over 2500 U/mL (I); and elevated lactate dehydrogenase level (L). This index indicates standard risk (0 or 1 risk factors, 4-year PFS 83%, 4-year overall survival 91%) and high risk (2 or 3 risk factors, 4-year PFS 52%, 4-year overall survival 67%) outcomes. The SIL index is a simple and objective prognostic index for DLBCL patients to identify candidates for experimental therapy other than R-CHOP.     

高龄弥漫大B细胞淋巴瘤患者的临床特征及预后分析

目的 探讨高龄弥漫大B细胞淋巴瘤(DLBCL)患者的临床特征和预后情况.方法 回顾性分析2016年1月至2018年12月上海交通大学医学院附属第九人民医院收治的13例高龄(年龄≥75岁)DLBCL患者的临床病理资料,均接受了R-CHOP方案为基础的个体化治疗,观察其临床特征、治疗疗效及预后情况.结果 高龄DLBCL患者...     

Rituximab and CHOP chemotherapy plus GM-CSF for previously untreated diffuse large B-cell lymphoma in the elderly: a Wisconsin oncology network study

PurposeHuman recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) may potentiate rituximab activity by upregulating CD20 expression and activating effector cells necessary for antibody-dependent cellular cytotoxicity. GM-CSF was combined with standard rituximab + CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy (R-CHOP) in the treatment of elderly patients with de novo diffuse large B-cell lymphoma (DLBCL).Patients and MethodsThirty-eight patients over the age of 60 years with newly diagnosed DLBCL were treated with R-CHOP every 21 days for 6–8 cycles and GM-CSF 250 μg/m² per day on days 3–10. Patients were evaluated for response after cycles 4, 6, and 8. The primary endpoint was the rate of complete response, and secondary endpoints were progression-free survival (PFS), event-free survival, and overall survival (OS).ResultsThirty-eight patients were enrolled, with a median age of 72 years, and 29% of patients having high-risk disease (International Prognostic Index [IPI] score ≥ 4). A complete or unconfirmed complete response (CR) was achieved in 53% of patients. After a median follow-up of 51.1 months, the 3-year PFS and OS were 78% and 84%. Twenty-one percent of patients discontinued protocol treatment because of chemotherapy-related toxicity and 16% because of GM-CSF toxicity. Dose intensity for planned chemotherapy cycles was 81.1%.ConclusionThese data suggest that survival outcomes may be modestly improved when GM-CSF is combined with R-CHOP in the treatment of elderly DLBCL. GM-CSF had toxicity precluding planned administration in 16% of patients, which may limit usefulness of this agent. Further investigation of GM-CSF in combination with rituximab-containing chemotherapy is warranted.     

“Diffuse Large B-Cell Lymphoma in the Elderly: Real-World Outcomes From a Developing Country”

BackgroundTreatment of Diffuse Large B-Cell Lymphoma (DLBCL) in the elderly aims to achieve disease remission while minimizing treatment-related toxicities. The use of anthracycline in the elderly is associated with increased risk of cardiotoxicity and myelosuppression. Non-anthracycline-based regimens have commonly been used in patients with cardiac contraindications or anticipated severe toxicities to anthracyclines.MethodsWe retrospectively analyzed the treatment outcomes of patients, aged 60 years and above, newly diagnosed with DLBCL at our center. Of a total of 218 patients, 71 patients received the R-CHOP regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone) and 137 received R-CE (Etoposide) OP chemotherapy. The decision to substitute etoposide for doxorubicin was based on physician's discretion depending on the performance status, cardiac comorbidities and frailty as well as available resources for supportive care.ResultsThe 2-year progression-free survival (PFS) rate in the R-CHOP group was higher than that in the R-CEOP group (79.1% vs 49.6%, P-value < .001) and this superiority of R-CHOP was seen in both early and advanced disease. The incidence of febrile neutropenia and grade III/IV hematological toxicities was significantly higher in the R-CHOP group in the age group of 60 to 65 years’. ECOG PS at presentation, NCCN-IPI and the chemotherapy regimen were found to be significant factors for 2-year PFS rate by multivariate analysis.ConclusionAnthracycline-based regimen should be used in elderly fit patients without absolute cardiac contraindications wherever feasible with adequate access to supportive care.     

R-CHOP versus R-COMP: Are They Really Equally Effective?

The first-line standard treatment for diffuse large B-cell lymphoma (DLBCL) is the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). It is associated with cardiotoxicity, which is why new treatment strategies are needed. Liposomial doxorubicin has been proven to reduce these side-effects, but until now a direct comparison regarding efficacy has not yet been published. We retrospectively assessed 364 consecutive DLBCL patients who underwent either R-CHOP (218; 60%) or R-COMP (doxorubicin replaced by non-pegylated liposomal doxorubicin; 146; 40%) in first line and compared outcome and survival. We provide evidence that both regimens induce a high and comparable number of complete remissions and that both are able to cure patients with DLBCL. Confirmatory data are needed.