R-CHOP与CHOP方案治疗初治弥漫大B细胞型淋巴瘤在中国的多中心随机对照研究

背景与目的:CHOP化疗方案是目前治疗弥漫性大B细胞型非霍奇金淋巴瘤(non-HodgkinTslymphoma,NHL)的标准方案。利妥昔单抗(美罗华)作为一种针对CD20抗原表达阳性的B细胞的嵌合型单克隆抗体,对弥漫性大B细胞型淋巴瘤具有良好的疗效。在欧洲和美国,利妥昔单抗联合标准化疗方案治疗进展型NHL已经获得批准。本研究旨在比较利妥昔单抗加标准CHOP方案与标准CHOP方案治疗中国人CD20阳性的弥漫大B细胞型NHL患者的疗效和安全性。方法:2003年9月至2004年11月在全国9个研究中心进行,共有63例患者入组,其中CHOP组32例,R-CHOP组31例。所有入组患者均签署并提供知情同意书。CHOP组患者接受每3周为1个疗程共6个疗程的CHOP方案治疗;R-CHOP组患者在每个疗程开始的第1天联用利妥昔单抗的CHOP治疗方案。比较两组的完全缓解率、总体缓解率以及不良反应情况。结果:R-CHOP组和CHOP组的完全缓解率相似(41.9%vs.37.5%,P=0.719),而总体缓解率前者要高于后者(83.8%vs.65.6%,P=0.096),但无显著性差异。治疗期间CHOP组有21.9%的患者疾病进展,而R-CHOP组仅为3.2%,两组有显著性差异(P=0.026)。R-CHOP组和CHOP组的不良反应发生率相似(65.6%vs.67.7%),差异无显著性(P=0.859)。最常见的不良反应均为白细胞下降;R-CHOP组其次常见不良反应是发热和寒战,可能与输注利妥昔单抗有关。两组的临床相关毒副作用相似,差异无显著性。结论:利妥昔单抗联合CHOP方案治疗CD20阳性的弥漫大B细胞型NHL与单纯CHOP方案相比,能显著降低治疗失败率,同时并不增加化疗的毒副反应。     

利妥昔单抗联合CHOP化疗上调钙网蛋白表达提高对NHL的疗效

目的:探讨利妥昔单抗(rituximab)联合CHOP化疗治疗B细胞非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)的临床疗效及其对钙网蛋白(calreticulin,CRT)表达的影响.方法:选取南通大学附属医院2008年7月至2011年2月期间48例初治B细胞NHL,分为利妥昔单抗联合CHOP化疗组(R-CHOP组,25例)和CHOP组(23例)两组,6个疗程后比较两组患者的临床疗效、不良反应,以及外周血中CD20+B细胞表面CRT的表达.结果:R-CHOP组B细胞NHL患者完全缓解率为80.0％,总有效率为92.0％;CHOP组完全缓解率为56.5％,总有效率为69.6％;R-CHOP组患者完全缓解率以及总有效率高于CHOP组(P＜0.05).两组间不良反应相似,R-CHOP联合治疗没有增加NHL患者治疗后的不良反应.R-CHOP组患者治疗后外周血中CD20+B细胞表面CRT的表达明显高于CHOP组[(255.00 ±5.57) vs (216.00 ±3.61),P＜0.05].结论:利妥昔单抗联合CHOP化疗治疗B细胞NHL较常规CHOP化疗效果好,可能与联合治疗上调CRT表达有关.     

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。     

CHO和CHOP方案治疗中度恶性非霍奇金淋巴瘤的疗效比较

背景及目的：不少非霍奇金淋巴瘤（non-Hodgkin‘s lymphoma,NHL)患者诊断时伴发不同程度的糖尿病,所以,在用CHOP方案（阿霉素＋环磷酰胺＋长度新碱＋泼尼松强的松）治疗这些患者时,不仅要考虑到糖皮质激素对患者有利的一面,同时也要考虑到糖皮质激素可能引起的不良反应,如诱发或加重糖尿病。为此,本研究拟比较不含强的松的CHO方案与标准的CHOP方案治疗中度恶性NHL的临床疗效。方法：对我科1991年6月－1999年5月期间收治的经病理证实的53例中度恶性NHL伴发糖尿病患者的临床资料进行回顾分析。结果：CHO组22例,CHOP组31例,两组患者特征具有可比性（P＞0．05）,CHO组的有效率为81．8％,中位生存期31个月,3年总生存率及无病生存率分别为44．1％和31．2％,CHOP组的有效率为90．4％,中位生存期33个月,3年总生存率及无病生存率分别为47．3％和33．8％,两组不良反应中,除了CHO组患者的恶心呕吐较CHOP组多见（P＝0．015）外,其余的均无显著性差异（P＞0．05）,结论：不含激素的CHO方案治疗中度恶性CHL伴发糖尿病患者,近期及远期疗效与标准的CHOP方案相似,副作用也无差异,在行化疗时可考虑使用。     

利妥昔单抗联合CHOP方案治疗B细胞非霍奇金淋巴瘤的疗效分析

目的：探讨利妥昔单抗联合CHOP方案治疗B细胞型非霍奇金淋巴瘤（NHL）的临床效果和不良反应。方法选择96例CD20阳性的B细胞NHL患者分为研究组49例和对照组47例,研究组采用利妥昔单抗与CHOP方案联合治疗方案,对照组只采用CHOP化疗方案。应用4个疗程后评价两组疗效及不良反应。结果研究组治疗有效率为90.0%,高于对照组的72.3%,差异有统计学意义（P﹤0.05）。而且两组的白细胞下降、脱发、恶心呕吐、便秘、血小板减少、贫血、肺部感染等不良反应比较,差异无统计学意义（P﹥0.05）。研究组1年、3年、5年无进展生存率（PFS）分别为81.6%、61.2%、26.5%,生存率分别为89.8%、65.3%、30.6%,均高于对照组,差异均有统计学意义（P﹤0.05）。结论采用利妥昔单抗与CHOP联合方案治疗B细胞非霍奇金淋巴瘤,可以提高临床疗效和远期生存率,且不因联合化疗而增加不良反应。     

CHOP为主的化疗方案治疗中高度恶性非霍奇金淋巴瘤疗效评价

目的：进一步提高对CHOP为主方案治疗中高度恶性非霍奇金淋巴瘤（NHL）疗效的认识。方法：用国际预后指数（IPI）对31例以CHOP为主方案治疗的中高度恶性NHL患者的疗效进行评价。根据IPI将患者分为低危和高危两大组,比较两组患者的生存状况。结果：低危和高危组完全缓解患者分别为16／21例（76％）和3／10例（30％）,部分缓解分别为3／21例（14％）和4／10例（40％）,复发／进展分别为2／21例（10％）和3／10例（30％）。中位生存期分别为84（3－132）月和6．5（0．75－52）月,两组差异显著（P＝0．0032）。1．5年总生存率（OS）分别为75．89％和20％,低危组5年OS为59．15％,10年OS为33．83％。结论：CHOP为主的第一代化疗方案对于不同危险程度的进展性NHL患者疗效明显不同。CHOP对于低危患者仍可作为首选和标准方案,对于高危患者可以考虑更强的或实验性的化疗方案。     

DICE方案治疗复发或难治中高度恶性非霍奇金淋巴瘤的疗效分析

目的：目前对于复发或难治中高度恶性非霍奇金淋巴瘤（non-Hodgkin＇s lymphoma，NHL）尚无标准解救化疗方案，本文旨在探讨DICE方案（地塞米松、异环磷酞胺、顺铂及VP-16）治疗复发或难治中高度恶性NHL的疗效和不良反应。方法：22例复发或难治中高度恶性NHL患者，既往均接受过2～6个周期的CHOP化疗方案无缓解或复发。现采用DICE方案化疗，中位疗程数4个周期（2～7个周期），所有患者均可评价疗效和不良反应。对患者进行解救治疗，并对毒副反应加以评估、预防及治疗。结果：22例患者DICE方案化疗后，总有效率为63.6%，完全缓解率为40.9%；T、B细胞NHL有效率分别为75.0%、57.1%，完全缓解率分别为37.5%、42.9%（P〉0.05）；LDH升高、伴有巨大肿块是影响复发耐药患者近期疗效的高危因素（P均〈0.05）。经DICE方案治疗的患者，骨髓抑制、消化系统反应、脱发是较常见的并发症，经过治疗均恢复，无治疗相关死亡。结论：DICE方案治疗难治和复发性NHL有效。     

吉西他滨联合洛铂和地塞米松治疗非生发中心型弥漫大B细胞淋巴瘤的近期疗效观察

目的:探讨GDL(吉西他滨、地塞米松、洛铂)与R -GDL、R-CHOP和CHOP治疗非生发中心型弥漫大B细胞淋巴瘤的近期疗效以及最佳治疗方案.方法:对确诊的非生发中心型弥漫大B细胞淋巴瘤109例患者,24例应用R-GDL方案治疗,28例应用GDL方案,25例应用R-CHOP方案,32例应用CHOP方案.前瞻性的随机对照比较R-GDL、GDL、R-CHOP和CHOP方案治疗患者的近期疗效,并评估治疗安全性.结果:R-GDL组完全缓解(CR) 15例,部分缓解(PR)6例,总有效率为87.5％ (21/24);GDL组CR 8例,PR 7例,总有效率为53.6％(15/28),R-CHOP组总有效率为64.0％(16/25),CHOP组43.8％(14/32).其中GDL组显著优于CHOP组,P=0.04;加用美罗华组较单纯化疗组差异有统计学意义,P值分别为0.006、0.045.GDL组1年的无进展生存率(57.1％)显著优于CHOP组(46.9％),P=0.04;含美罗华组显著优于单纯化疗组,P值分别为0.034、0.002.含洛铂的方案血小板下降明显,需预防性应用升血小板的药物,其肝肾心脏毒性较小,加或不加美罗华不良反应率无明显改变.结论:吉西他滨联合洛铂、地塞米松方案有效率比R-GDL、R-CHOP和CHOP方案治疗非生发中心型弥漫大B细胞淋巴瘤略高,但骨髓抑制较重,在化疗的基础上增加美罗华能进一步提高疗效.     

放化疗联合治疗韦氏环非霍奇金淋巴瘤临床疗效分析

目的：观察CHOP方案化疗联合放疗治疗早期韦氏环NHL淋巴瘤的疗效及不良反应.方法：44例早期韦氏环NHL淋巴瘤患者,CHOP方案先化疗3周期,序贯受累野放疗,放疗后再给予3周期CHOP方案化疗.近期疗效根据恶性淋巴瘤Cheson疗效判定标准.结果：44例患者均可评价疗效,其中CR 30例,CRu 8例,PR 6例,近期总有效率100％.不良反应经治疗后均缓解,未出现严重肝肾功能损害及心脏损害.3年生存率97.7％.结论：CHOP方案化疗联合放疗治疗早期韦氏环NHL淋巴瘤的疗效较好及不良反应患者耐受性.     

美罗华联合CHOP治疗B细胞性非霍奇金淋巴瘤的临床研究

为了评价美罗华与CHOP联合治疗B细胞性非霍奇金淋巴瘤(non-Hodgkin’s lymphoma,NHL)的临床效果及不良反应,用同期对照的前瞻性研究方法,将22例B细胞性NHL患者分为研究组(美罗华组)和对照组,研究组11例用CHOP方案(环磷酰胺、多柔比星、长春新碱和泼尼松)联合美罗华治疗;对照组11例单用CHOP方案。结果美罗华组完全缓解率(CR)达72.7%(8/11),总有效率90.9%(10/11);对照组CR为36.4%(4/11),总有效率为54.6%(6/11),两组疗效差异有统计学意义,P=0.0018。初步研究结果提示,美罗华联合CHOP方案治疗CD20阳性的B细胞性NHL的疗效显著,不良反应与单纯化疗相似,可作为该病目前的首选方案。     

Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).

PURPOSE: Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years. In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFNalpha). All patients older than 65 years received IFNalpha maintenance. RESULTS: R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131). No differences were observed for progression-free survival. Toxicity was acceptable, with no major differences between the two therapeutic groups. CONCLUSION: The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.     

侵袭性B细胞淋巴瘤新的标准治疗方案

实施CHOP方案(环磷酰胺、阿霉素、长春新碱和泼尼松)治疗20多年来,侵袭性B细胞淋巴瘤已成为可治愈的疾病,CHOP方案也已成为治疗这一疾病的标准方案。但其治愈率只有35%~40%,半数以上复发。随着抗B细胞表面抗原CD20的人鼠嵌合型单克隆抗体利妥昔(rituximab)的应用,侵袭性B细胞淋巴瘤的治疗已发生了根本改变。多项大型Ⅲ期随机临床研究结果证实,利妥昔与CHOP方案或CHOP样方案联合应用,比单纯联合化疗能明显改善侵袭性B细胞淋巴瘤的有效率,无事件生存和长期生存结果,无论是老年或年轻患者,低危预后还是高危预后患者,均有显著的统计学差异。因此,利妥昔加CHOP或CHOP样方案的联合治疗已成为侵袭性B细胞淋巴瘤新的标准治疗方案。     

Observation of the Curative Effect of Mabthera in Combination with the CHOP Regimen in Treating Invasive B-Cell Lymphoma: A Report of 45 Cases

OBIECTIVE To observe the clinical efficacy and toxic effects of Mabthera(rituximab)in combination with the CHOP(R-CHOP)regimen for treating invasive B-cell non-Hodgkin's lymphoma.METHODS A total of 45 patients with CD20 positive B-cell non-Hodgkin's lymphoma were randomly divided into the R-CHOP(22 cases) and CHOP groups(23 cases for controls).They received the regimens of Mabthera in combination with CHOP or single CHOP therapy respectively.An appraisement of the curative effect could only be performed following 4 cycles of chemotherapy for the 45 patients.Follow-up was conducted to observe the conditions ot survival.RESULTS The rate of complete remission(CR)in the R-CHOP group was 68.2%,with a total effective rate of 81.8%,and in the CHOP group these rates were 34.8% and 78.3%respectively.There was a significant difference in comparing the CR rates between the two groups (P<0.05).The 1,2 and 3-year overall survival (OS) rates of the RCHOP group were 90.9%,81.8% and 77.3%,respectively.In the CHOP group,the OS rates were respectively 91.3%,69.5% and 47.8%.The difference in the 3-year OS between the two groups was significant (P<0.05).The toxic effects of the two groups were mainly a slight and moderate bone marrow depression and a gastrointesinal reaction,with similar tolerable toxic effects in the two groups (P>0.05).Adverse effects related to the Mabthera infusions occurred in 6 cases of the R-CHOP group(27.2%).These effects lessened after symptomatic treatment.CONCLUSION The therapeutic regimen Of Mabthera,in combination with CHOP(R-CHOP)has an obvious curative effect for treating invasive B-cell non-Hodgkin's lymphoma,with a favorable tolerance.It is highly recommended as the treatment ot choice.     

Early response assessment using 3'-deoxy-3'-[18F]fluorothymidine-positron emission tomography in high-grade non-Hodgkin's lymphoma.

PURPOSE: To evaluate 3'-deoxy-3'-[(18)F]fluorothymidine-positron emission tomography (FLT-PET) for early monitoring response of high-grade non-Hodgkin's lymphoma to treatment with cyclophosphamide-adriamycin-vincristine-prednisone chemotherapy with or without rituximab immunotherapy (R-CHOP/CHOP). EXPERIMENTAL DESIGN: Twenty-two patients with histologically proven high-grade non-Hodgkin's lymphoma scheduled to undergo first line treatment with R-CHOP/CHOP were included. All patients received baseline imaging before therapy with FLT-PET. For noninvasive assessment of treatment response, FLT-PET was repeated at following time points: group 1 (n = 6), 1 and 6 weeks after R-CHOP/CHOP; group 2 (n = 16), 2 days after rituximab and 2 days after CHOP application. Emission images were acquired 45 min after injection of 300 to 370 MBq of FLT. FLT uptake was quantified by region-of-interest technique on a lesion basis. Maximum standardized uptake values (SUV) for FLT were calculated using circular region of interest (diameter, 1.5 cm). RESULTS: In all patients, morphologically proven lesions showed initially high FLT uptake (mean SUV, 8.1 +/- 3.9). In group 1, mean FLT SUV decreased 7 days after R-CHOP/CHOP by 77% (P < 0.001), the reduction in FLT SUV from baseline was 85% after 40 days (P = 0.003). In group 2, FLT uptake in patients without dexamethasone pretreatment revealed no significant reduction after rituximab (P = 0.3) but significantly decreased 2 days after CHOP to 32% compared with the baseline value (P = 0.004). CONCLUSIONS: Administration of R-CHOP/CHOP is associated with an early decrease in lymphoma FLT uptake. Interestingly, there was no reduction of FLT uptake after rituximab alone, indicating no early antiproliferative effect of immunotherapy. FLT-PET seems to be promising for early evaluation of drug effects in lymphoma.     

金克联合化疗对复发性非霍奇金淋巴瘤的疗效

目的探讨金克在复发性中、高度恶性非霍奇金淋巴瘤（ＮＨＬ）再化疗中应用的疗效。方法选用有明确病理诊断且既往用过化疗的复发性非霍奇金淋巴瘤共３６例，随机分为两组，进行前瞻必至比治疗。两组均采用相同的ＣＨＯＰ方案化疗。治疗组１８例用金克联合化疗，对照组１８例单用化疗，分别评定近期疗效，Ｔ细胞亚群分布状态，毒副反应。结果 治疗组ＣＲ率为６１．０％，对照组为３３．０％，差异有显著性，治疗组化疗后Ｔ细胞亚群。     

Addition of rituximab is not associated with survival benefit compared with CHOP alone for patients with stage I diffuse large B-cell lymphoma

Background

The role of rituximab in combination with CHOP regimen in patients with stage I diffuse large B-cell lymphoma (DLBCL) remains to be defined. We aimed to compare CHOP plus rituximab (R-CHOP) with CHOP alone and determine the value of radiotherapy in these patients.

Methods

Between 2003 and 2009, 140 untreated patients with stage I DLBCL were retrospectively analyzed in this study.

Results

Seventy-eight patients were treated in R-CHOP group and 62 in CHOP group. Ninety-one patients received additional radiotherapy at the end of chemotherapy. The different treatment groups were well-balanced with respect to baseline characteristics. Complete response (CR) rate was 77% both in R-CHOP and CHOP groups (P=0.945). After a median follow-up period of 56 months, patients received R-CHOP regimen had similar 5-year progression-free survival (PFS) (76% vs. 85%; log-rank P=0.215) and 5-year overall survival (OS) (90% vs. 96%; log-rank P=0.175) compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone (86% vs. 71%; log-rank P=0.005). At multivariate analysis, patients who had CR (P=0.008) and received radiotherapy (P=0.003) were significantly associated with superior PFS.

Conclusions

CHOP alone could be as effective as R-CHOP regimen and additional radiotherapy would be necessary for stage I or stage I non-bulky DLBCL patients.