补体依赖细胞毒作用通路与利妥昔单抗耐药

利妥昔单抗是针对B细胞表面标志CD20抗原的单克隆抗体,利妥昔单抗联合化疗显著改善了B细胞淋巴瘤患者的预后。但是仍有部分患者对利妥昔单抗治疗无效或在治疗有效后短期内复发,说明利妥昔单抗联合化疗不足以彻底清除淋巴瘤细胞,提示存在着一定的耐药性肿瘤细胞。补体依赖细胞毒作用(complement-dependent cytotoxicity,CDC)是利妥昔单抗对淋巴瘤细胞的主要杀伤机制之一,CDC作用通路中的任何一个环节异常都有可能影响利妥昔单抗的疗效。CD20抗原是利妥昔单抗发挥作用的基础,CD20抗原的表达强度、其编码基因的多态性以及其在细胞膜上的承载结构———脂质筏均可能影响CDC作用;此外,补体的基因多态性(如C1q、CD11b)、血清补体水平及补体调节蛋白的水平均可能影响着CDC作用通路中的不同环节,从而影响利妥昔单抗作用的发挥。随着利妥昔单抗的广泛应用,对其耐药机制的研究日益深入。本文将对目前关于利妥昔单抗CDC作用通路中可能影响其疗效的主要因素进行综述。     

利妥昔单抗导致的骨髓抑制及急性肿瘤溶解综合征1例

近年来,随着利妥昔单抗（rituximab）的问世,对弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）的治疗取得了重大突破.作为针对B淋巴细胞表面CD20抗原的靶向治疗药物,其与标准的CHOP化疗方案联合显著提高了肿瘤缓解率和患者存活率,同时并没有增加传统细胞毒药物的不良反应.利妥昔单抗常见的毒性包括过敏及输液相关反应、发热以及轻度低血压等.由于造血细胞表面并没有CD20抗原表达,因此理论上利妥昔单抗不会直接导致骨髓抑制的毒性.     

抗体依赖细胞介导的细胞毒作用在利妥昔单抗耐药机制中的研究进展

利妥昔单抗是一种在B细胞非霍奇金淋巴瘤（B-NHL）中广泛应用的单抗类靶向药物,作用于CD20抗原.其联合化疗显著改善了B细胞淋巴瘤患者的预后.但是仍有部分患者对利妥昔单抗治疗无效或在治疗有效后短期内复发,提示可能存在利妥昔单抗的耐药.利妥昔单抗对B细胞淋巴瘤细胞的杀伤机制主要包括直接诱导凋亡、抗体依赖细胞介导的细胞毒作用（ADCC）、补体依赖细胞毒作用（CDC）等,不同的作用机制可能存在不同的耐药机制,其中哪一种发挥了主要作用尚不明确.文章对利妥昔单抗ADCC作用机制中可能存在的影响疗效的因素进行综述.     

利妥昔单抗联合化疗治疗原发CD5阳性弥漫大B细胞淋巴瘤二例并文献复习

目的 探讨原发CD5阳性(CD5+)弥漫大B细胞淋巴瘤的生物学特性及利妥昔单抗联合不同化疗方案的治疗效果.方法 总结既往报道的1例及山西医科大学第二医院血液科收治的1例CD5+弥漫大B细胞淋巴瘤患者的临床特点,分析骨髓及淋巴结细胞形态学、流式细胞术、免疫组织化学和分子生物学特征,评估利妥昔单抗联合不同化疗方案的治疗反应,并复习相关文献.结果 例1患者初诊明确诊断为原发CD5+弥漫大B细胞淋巴瘤(白血病期),伴复杂核型,利妥昔单抗联合VCTP(4周方案)诱导化疗1个疗程后骨髓达完全缓解,脾脏及淋巴结明显缩小,后予R-VCTP(2周方案)×1、R-Hyper-CVAD×3、R-HD-MTX×4方案巩固强化治疗8次,阿糖胞苷联合甲氨蝶呤鞘内注射10次,随访21个月,疾病持续缓解,无中枢神经系统侵犯表现.例2为高龄患者,明确诊断为原发CD5+弥漫大B细胞淋巴瘤(鼻型),给予利妥昔单抗联合VP方案及单药治疗3个疗程,鼻骨肿物完全回缩,局部骨质修复;自行停药半年后出现多发皮肤病变,给予利妥昔单抗联合COP方案再次化疗后皮肤病变缓解,但磁共振成像提示脑实质浸润,放疗后症状缓解,浸润灶大部分吸收;随访21个月,疾病稳定.结论 原发CD5+弥漫大B细胞淋巴瘤易合并结外病变,以骨髓、皮肤及中枢神经系统受累多见.利妥昔单抗联合急性淋巴细胞白血病整体治疗及鞘内注射方案可能有助于降低转移性中枢神经系统病变发生率,提高无病生存率.     

利妥昔单抗治疗弥漫大B细胞淋巴瘤诱发急性肿瘤溶解综合征一例并文献复习

目的 提高对利妥昔单抗诱发急性肿瘤溶解综合征（ATLS）的认识.方法 回顾性分析1例利妥昔单抗治疗弥漫大B细胞淋巴瘤诱发ATLS患者的临床资料并复习相关文献.结果 患者ATLS确诊后,立即暂缓化疗,补液、碱化尿液,但患者肾功能持续恶化,后经血液透析,肾功能逐渐恢复正常.2周后患者再次接受R-CHOP方案化疗,未再发生ATLS.经外周血造血干细胞移植,患者淋巴瘤完全缓解.结论 在应用利妥昔单抗治疗血液系统恶性肿瘤时需警惕肿瘤溶解综合征的发生,及时诊治可使患者获得较好预后.     

以泽布替尼和利妥昔单抗为基础联合化疗治疗伴复杂核型及TP53基因突变的CD5阳性弥漫大B细胞淋巴瘤并发噬血细胞综合征1例并文献复习

目的探讨以泽布替尼和利妥昔单抗为基础联合化疗治疗伴复杂核型及TP53基因突变CD5阳性弥漫大B细胞淋巴瘤(CD5+ DLBCL)并发噬血细胞综合征患者的效果。方法回顾性分析黑龙江省医院2021年8月收治的1例伴复杂核型及TP53基因突变CD5+ DLBCL并发噬血细胞综合征患者的临床资料, 使用以泽布替尼和利妥昔单抗为基础联合化疗方案治疗, 并对相关文献进行复习。结果该患者结合病史、骨髓穿刺、流式细胞术等检查确诊为双表达、非生发中心B细胞型DLBCL ⅣB期并发噬血细胞综合征。接受4个周期以泽布替尼和利妥昔单抗为基础联合化疗方案治疗后, 复查骨髓及彩色超声、CT提示完全缓解, 染色体核型、基因突变、流式分析结果均转阴, 疗效评价为完全缓解;8个周期后复查PET-CT仍提示完全缓解。后续给予来那度胺维持治疗, 至2022年4月无进展生存10个月。结论在二代测序技术指导下, 应用以泽布替尼和利妥昔单抗为基础联合化疗方案治疗可改善CD5+ DLBCL患者预后并延长生存期。     

利妥昔单抗联合化疗治疗霍奇金淋巴瘤一例并文献复习

 【摘要】　目的　分析利妥昔单抗联合化疗方案治疗霍奇金淋巴瘤（HL）的疗效。方法　采用利妥昔单抗联合ABVD方案治疗1例经典型HL（cHL）并复习文献。结果　HL组织中有CD+20 表达,结节性淋巴细胞为主型表达率98 %～100 %,经典型表达率18 %～32 %。RS干细胞中亦有CD+20 表达。利妥昔单抗针对CD+20 细胞,清除RS细胞,抑制RS干细胞及反应性背景B细胞,阻断肿瘤细胞存活信号。利妥昔单抗单药治疗的临床反应率在结节性淋巴细胞为主型83 %～100 %,经典型22 %;与化疗联合应用,明显延长病情缓解期,提高治疗反应率。临床Ⅱ期观察利妥昔单抗联合ABVD方案治疗cHL患者,完全缓解率达81 %～93 %,5年无瘤生存率及总体生存率分别为83 %和96 %。该例患者治疗获得缓解,随访1年,健康生存。结论　利妥昔单抗联合化疗治疗HL安全有效。     

自体造血干细胞移植联合利妥昔单抗治疗CD+20B细胞淋巴瘤

 采用自体造血干细胞移植（AHSCT）治疗中,高危侵袭性淋巴瘤已获得了较好疗效,但仍有部分移植患者因复发而死亡。复发的根源主要为微小残留病变,包括体内残留的肿瘤细胞和移植物中的肿瘤细胞污染。利妥昔单抗可靶向性清除CD+20 B细胞,因此,对CD+20 B细胞淋巴瘤患者,移植前后应用利妥昔单抗可起到体内净化和清除残留病灶作用,AHSCT联合利妥昔单抗有望进一步提高CD+20 B细胞淋巴瘤的疗效。     

嵌合抗原受体T细胞在B细胞淋巴瘤中的研究进展

B细胞淋巴瘤的预后在利妥昔单抗出现之后有了明显改善,但仍有一部分患者会复发进展.嵌合抗原受体T细胞（CAR T细胞）是通过基因修饰的方法获得的针对肿瘤细胞表面特定抗原的特异性T细胞,在复发难治B细胞淋巴瘤的治疗中取得了很好疗效,目前研究最多的是针对B细胞淋巴瘤表面的CD19抗原.文章综述了抗CD19 CAR T细胞在复发难治B细胞淋巴瘤中的疗效、不良反应及目前存在的问题.     

利妥昔单抗治疗B细胞非霍奇金淋巴瘤的耐药机制研究进展

 抗CD20单克隆抗体利妥昔单抗已经成为治疗B细胞非霍奇金淋巴瘤（NHL）的重要组成部分。尽管临床应用广泛,但肿瘤细胞对利妥昔单抗的耐药机制尚不明确。文章阐述了利妥昔单抗的作用机制、耐药的发生以及潜在的耐药机制,并对调节抗体、肿瘤细胞和宿主的免疫状况等克服耐药的方法进行了探讨。     

Experience with Impedance Phlebography Compared with Venography

Venography is a particularly reliable method for the diagnosis of deep venous thrombosis but is not suitable as a screening test. Impedance phlebography represents another attempt to discover a simple, non-invasive and reliable method of detecting deep venous thrombosis. It does not, however, meet these criteria.     

Compliance with guidelines and correlation with outcome in patients with advanced germ-cell tumours

PurposeTo evaluate prior compliance with guidelines in patients treated with salvage chemotherapy for advanced germ-cell tumours (GCT).Patients and methodsData concerning the initial management of patients requiring salvage chemotherapy for GCT at Institut Gustave Roussy between 2000 and 2010 were obtained and correlated with recommendations for treatment. Criteria of non-compliance were defined based on guidelines. Compliance with guidelines, predictive factors for non-compliance and the impact on outcome were analysed.ResultsAmong 82 patients treated in the salvage setting, guidelines to initial treatment were followed in only 41 cases (50%). The most common non-compliance criteria were non-adherence to the planned dose (16%), an inappropriate interval between first-line chemotherapy cycles (16%), the lack of post-chemotherapy surgery (16%) and a long interval to post-chemotherapy surgery (48%). Compliance with standard care was better in cancer centres than in other hospitals (private or public) (Odd Ratio (OR): 6.9, P = 0.001). A poor-risk status according to the International Germ Cell Cancer Collaborative Group (IGCCCG) was also predictive of compliance in univariate but not in multivariate analysis. No significant difference in outcome after salvage chemotherapy was observed. Patients relapsing after non-compliant first-line therapy tended to be more easily salvaged, which is consistent with the fact that their initial treatment was inadequate. Some of these relapses were therefore probably not due to true biologically refractory disease.ConclusionGuidelines for first-line treatment are adhered to in only half the patients requiring salvage chemotherapy. As the only predictive factor for non-compliance was the treating centre, centralisation of patients with GCT in well-trained hospitals should be recommended.     

Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer

BackgroundMethylnaltrexone (MNTX), a peripherally acting μ-opioid receptor (MOR) antagonist, is FDA-approved for treatment of opioid-induced constipation (OIC). Preclinical data suggest that MOR activation can play a role in cancer progression and can be a target for anticancer therapy.Patients and methodsPooled data from advanced end-stage cancer patients with OIC, despite laxatives, treated in two randomized (phase III and IV), placebo-controlled trials with MNTX were analyzed for overall survival (OS) in an unplanned post hoc analysis. MNTX or placebo was given subcutaneously during the double-blinded phase, which was followed by the open-label phase, allowing MNTX treatment irrespective of initial randomization.ResultsIn two randomized, controlled trials, 229 cancer patients were randomized to MNTX (117, 51%) or placebo (112, 49%). Distribution of patients' characteristics and major tumor types did not significantly differ between arms. Treatment with MNTX compared with placebo [76 days, 95% confidence interval (CI) 43–109 versus 56 days, 95% CI 43–69; P = 0.033] and response (laxation) to treatment compared with no response (118 days, 95% CI 59–177 versus 55 days, 95% CI 40–70; P < 0.001) had a longer median OS, despite 56 (50%) of 112 patients ultimately crossing over from placebo to MNTX. Multivariable analysis demonstrated that response to therapy [hazard ratio (HR) 0.47, 95% CI 0.29–0.76; P = 0.002) and albumin ≥3.5 (HR 0.46, 95% CI 0.30–0.69; P < 0.001) were independent prognostic factors for increased OS. Of interest, there was no difference in OS between MNTX and placebo in 134 patients with advanced illness other than cancer treated in these randomized studies (P = 0.88).ConclusionThis unplanned post hoc analysis of two randomized trials demonstrates that treatment with MNTX and, even more so, response to MNTX are associated with increased OS, which supports the preclinical hypothesis that MOR can play a role in cancer progression. Targeting MOR with MNTX warrants further investigation in cancer therapy.Clinical trials numberNCT00401362, NCT00672477.     

Sarcopenia is associated with survival in patients with urothelial carcinoma treated with systemic chemotherapy

International Journal of Clinical Oncology - Sarcopenia impacts perioperative outcomes and prognosis in various carcinomas. We aimed to investigate whether sarcopenia at the time of chemotherapy...     

Costs associated with complications are lower with capecitabine than with 5‐fluorouracil in patients with colorectal cancer

BACKGROUND:

Capecitabine, an oral alternative to 5‐fluorouracil (5‐FU) in patients with colorectal cancer (CRC), has equal clinical efficacy and a favorable safety profile; however, its use may be limited because of unit cost concerns. In this study, the authors measured the cost of chemotherapy‐related complications during treatment with capecitabine‐ and 5‐FU–based regimens.

METHODS:

Patients with CRC who received at least 1 administration of capecitabine or 5‐FU during 2004 and 2005 were identified from the Thomson MarketScan research databases. Monthly frequency and cost for 23 complications were recorded. Logistic regression was used to predict complication probability. General linear models were used to predict monthly complication cost and total monthly expenditure.

RESULTS:

In total, 4973 patients with CRC met the inclusion criteria for this analysis. Although the most frequently observed complications were the same between capecitabine and 5‐FU (nausea and vomiting, infection, anemia, neutropenia, diarrhea), each was observed with greater frequency in 5‐FU–based regimens. The mean predicted monthly complication cost was significantly higher (by 136%) with 5‐FU monotherapy than with capecitabine monotherapy (difference, $601; 95% confidence interval [95% CI], $469‐$737). In addition, the mean predicted monthly complication cost for 5‐FU+oxaliplatin was higher than the cost with capecitabine plus oxaliplatin (difference, $1165; 95% CI, $892‐$1595). When acquisition, administration, and complication costs were taken into consideration, there were no significant differences in the total cost between capecitabine regimens and 5‐FU regimens.

CONCLUSIONS:

Capecitabine compared well with 5‐FU–based therapy in patients with CRC and was associated with lower complication rates and associated costs. Cancer 2009. © 2009 American Cancer Society.     

超声心动图诊断26例心脏黏液瘤

应用经胸二维超声心动图（2DE）、彩色血流显像（CDFI）及频谱多普勒显像（Doppler）诊断26例心脏黏液瘤（27个瘤体）,对团块的位置、数目、大小、形状、瘤蒂附着点和活动度、心腔内及瓣膜口血流等进行探查及分析．认为心脏超声检查是心脏黏液瘤的首选检查方法,具有实时、经济、简便易行等优点。     

Living with secondary breast cancer: coping with an uncertain future with unmet needs

JOHNSTON S.R.D. (2010) European Journal of Cancer Care 19 , 561–563 Living with secondary breast cancer: coping with an uncertain future with unmet needs