非霍奇金淋巴瘤合并乙型肝炎病毒感染经化疗后肝炎病毒再激活研究进展

我国的乙型肝炎病毒(hepatitis B virus,HBV)感染率一直居高不下,许多罹患其他疾病的患者均合并有HBV感染,在血液系统疾病中最常见的就是非霍奇金淋巴瘤(non-Hodgkin's lymphoma, NHL)合并HBV感染.用来治疗淋巴瘤的药物可能会引起HBV不同程度的再激活,严重者甚至可导致肝功能衰竭或者死亡.目前,有关利妥昔单纯和(或)化疗对NHL合并HBV感染患者肝炎病毒再激活的研究,已日益受到学者的关注.本文旨在对相关研究进展进行综述,以期为进一步的研究提供背景资料.     

侵袭性T细胞非霍奇金淋巴瘤的化疗

T细胞非霍奇金淋巴瘤是一组具有独特临床和病理特征的疾病,与B细胞淋巴瘤相比,侵袭性更强,化疗敏感性差。为探索有效的治疗方案,近年来,新的药物如吉西他滨、靶向药物联合化疗及高剂量化疗联合造血干细胞移植被研究用于治疗T细胞淋巴瘤,并取得了一些进展。     

淋巴瘤患者化疗后胸腺反应性增生临床分析

目的 分析淋巴瘤患者化疗后胸腺反应性增生的临床发生情况.方法 对2010年1月至2015年5月初治的22例淋巴瘤患者行CT评估疗效,当出现前上纵隔肿块时,推荐行PET-CT或活组织检查明确肿块性质,CT密切监测肿块变化情况.结果22例淋巴瘤患者中,14例在全部化疗结束后随诊期间出现胸腺增生,8例在化疗期间出现胸腺增生.CT显示胸腺中位最大直径为3.7 cm(2.5~6.8 cm).11例患者行PET-CT检查,均显示纵隔肿块无肿瘤活性,1例进一步行纵隔肿块穿刺活组织检查明确为胸腺反应性增生.结论 恶性淋巴瘤患者在强化疗后可出现胸腺反应性增生,临床上应注意鉴别,避免过度治疗.     

艾迪注射液配合化疗治疗非霍奇金淋巴瘤临床观察

为观察艾迪注射液配合化疗治疗非霍奇金淋巴瘤 (NHL)的增效、减毒、改善生活质量的作用 ,将 91例NHL患者随机分为观察组和对照组。观察组 44例 ,化疗同期采用艾迪注射液 5 0mL溶于 5 %葡萄糖或生理盐水 10 0～ 2 5 0mL中静脉滴入 ,1次 d ,连用 10～ 14d ;对照组 47例 ,采用单纯化疗。结果发现两组间的近期疗效差异无显著意义 ,P >0 0 5 ;胃肠道症状及血液学等毒副作用观察组明显低于对照组。初步研究结果提示 ,艾迪注射液能够显著降低化疗毒副作用 ,提高患者生存质量     

利妥昔单抗联合化疗治疗弥漫型大B细胞淋巴瘤的临床观察

目的: 探讨利妥昔单抗联合化疗治疗弥漫型大B细胞淋巴瘤患者的临床疗效和安全性.方法: 回顾性分析100例病理确诊为弥漫型大B细胞淋巴瘤患者的临床资料.所有患者均接受2～8次的利妥昔单抗治疗,利妥昔单抗的平均治疗次数为5.8次.同时,所有患者均接受了化疗.评价疗效和不良反应.结果: 100例患者中达完全缓解者46例(46%).达部分缓解者37例(37%),总有效率(完全缓解+部分缓解)为83%(83/100).红细胞沉降率、国际预后指数评分、是否为初治患者、B症状以及利妥昔单抗治疗周期数对疗效有显著影响(P<0.05),而性别、年龄、原发部位和功能状态评分对疗效无影响(P>0.05).1、2、3和5年生存率分别为87.5%、72.8%、60.8%和60.8%.COX回归模型多因素分析发现,国际预后指数评分、利妥昔单抗治疗周期数和治疗后的疗效对生存的影响有统计学意义(P<0.05).100例患者中共有11例因静脉输注利妥昔单抗而发生输液不良反应.结论: 利妥昔单抗联合化疗治疗弥漫型大B细胞淋巴瘤的临床缓解率较高,患者酎受良好且生存时间较长.     

长春地辛联合化疗治疗非霍奇金淋巴瘤的临床观察

目的 观察３８例非霍奇金淋巴瘤（ＮＨＬ）接受以长春地辛为主的联合化疗的疗效和毒性。方法分别采用ＣＨＶＰＹ不磷酰胺、阿霉素、长春地辛、泌尼松）和ＣＶＭＰ方案（环磷酰胺、长春地辛、甲氨喋啶、泌尼松）。结果 总有效率为８６．３％,ＣＲ１６例,ＰＲ１７例。主要不良反应有白细胞减少（６８．４％）,脱发（４２．１％）和恶心呕吐（４４．７％）。结论以长春地辛为主的联合化疗对非霍奇金淋巴瘤疗效肯定,毒性可耐受。     

HBsAg(-)伴HBcAb(+)淋巴瘤患者免疫化疗后肝炎病毒再激活临床观察

乙肝病毒(hepatitis B virus,HBV)再激活是慢性乙型肝炎患者接受化疗后的一种严重并发症,在非霍奇金淋巴瘤患者的发生率较高[1],化疗前预防性应用抗病毒药物在临床上已达成共识.近年来,国外一些研究显示,某些乙型肝炎表面抗原阴性伴核心抗体阳性即HBsAg(-)/HBcAb(+)的淋巴瘤患者,在应用了含利妥昔单抗的免疫化疗后,也发生了HBV再激活.但不同研究之间所报道的发生率差异较大,为2.2%～23.8%[2-4],是否需要常规抗病毒预防治疗目前也存在争议.本研究旨在明确HBsAg(-)/HBcAb(+)患者在接受含利妥昔单抗的免疫化疗后,出现乙肝再激活的发生率,探索危险因素,为治疗提供依据.     

淋巴瘤免疫化疗HBV再激活预防和治疗中国专家共识

1引言淋巴瘤是起源于淋巴造血系统的恶性肿瘤,全球常见。在我国淋巴瘤年发病率约为6.68/10万人[1],即每年大约有10万新发患者,且呈不断上升趋势。近年来,对于淋巴瘤的诊治进展显著,规范化综合治疗理念已为大家熟知。随着临床研究和治疗的进步,治愈淋巴瘤业已成为可能,特别是B细胞非霍奇金淋巴瘤采用免疫化疗效果突出,但是在治疗过程中往往存在多种并发症。已知淋巴瘤的     

利妥昔单抗联合化疗治疗B细胞淋巴瘤后乙肝病毒激活情况的回顾性研究(英文)

Objective:The aim of the study was to investigate the reactivations of hepatitis B virus(HBV)after rituximab-containing chemotherapy in patients with B-cell lymphoma with surface antigen of hepatitis B virus(HBsAg)-positive,or hepatitis B core antibody(HBcAb)-positive.Methods:A retrospective study of HBV-related markers was performed before and after rituximab-containing treatment in 189 consecutive patients with CD20-positive B-cell lymphoma.Results:Among the 189 non-Hodgkin’s lymphoma(NHL)patients who rec...     

Successful treatment with lamivudine for fulminant reactivated hepatitis B infection following intensive therapy for high-grade non-Hodgkin's lymphoma

Chronic carriers of Hepatitis B virus (HBV) infection, who are treated for malignant lymphoma, are at high risk of mortality from reactivated HBV infection. We report a case of a 29-year-old male chronic HBV carrier who developed fulminant reactivated HBV infection following intensive chemotherapy for stage IV^B large cell B-cell non-Hodgkin's lymphoma associated with extensive central nervous system and bone marrow involvement. Prior to chemotherapy the patient had normal liver function tests and was negative for HBV DNA by semi-quantitative PCR assay. Fulminant HBV reactivation was confirmed following clinical deterioration, massive rises in hepatic transaminases (peak alanine aminotransferase = 2,850 U/l), liver biopsy and rising levels of serum HBV DNA. Following treatment with lamivudine 150 mg bd for 18 weeks dramatic and sustained recovery ensued. Symptoms and liver function tests improved within days and HBV DNA became negative within 12 weeks. Our patient later died from relapsed lymphoma but without evidence of reactivated HBV infection. We advise that lamivudine should be considered during intensive chemotherapy treatment of chronic carriers of HBV.     

Hepatitis B virus reactivation and role of antiviral prophylaxis in lymphoma patients with past hepatitis B virus infection who are receiving chemoimmunotherapy

BACKGROUND:

Individuals who had past hepatitis B virus (HBV) infection appeared to clear their serum hepatitis B surface antigen (HBsAg) while producing antibody to the hepatitis B core antigen (HBcAb), which is detectable in their serum. Currently, it is uncertain whether patients with past HBV infection require routine antiviral prophylaxis during chemotherapy, although some cancer agencies recommend its routine use. The objective of the current study was to determine the prevalence of past HBV infection in patients with lymphoma and its relevance in terms of HBV‐related complications.

METHODS:

The authors reviewed 430 patients with lymphoma from May 2006 to May 2008.

RESULTS:

Among the 430 patients, 233 had both the HBsAg and HBcAb tests performed, whereas 197 had only the HBsAg test performed. Among those with both tests performed, 34.3% (80 of 233) were HBcAb positive only. Of these 80 patients, 58 had a concomitant HBV DNA level test, which was positive in 3 (5.2%). Of the 67 patients with past and 26 with chronic HBV infection who received chemotherapy, HBV reactivation occurred in 1.5% and 42.3% of patients, respectively (P<.0001). Prophylactic lamivudine was administered in 7 (10.4%) patients with past HBV infection and in 18 (69.2%) with chronic HBV infection.

CONCLUSIONS:

The low rate of HBV reactivation reported in our study coupled with the high prevalence of past HBV infection in an endemic area suggests that routine usage of antiviral prophylaxis may not be required for all patients with past HBV infection. Close surveillance remains a reasonable and viable option for the majority of patients. Cancer 2010. © 2010 American Cancer Society.     

拉米夫定联合微波消融治疗原发性肝癌40例

目的:探讨拉米夫定联合经皮微波消融 (PMCT)治疗乙肝病毒DNA阳性的肝细胞癌(HCC)患者的疗效.方法:乙肝病毒DNA阳性的原发性肝癌(PHC)患者40例为研究组,同时接受PMCT+拉米夫定,单纯PMCT治疗的40例同类患者为对照组,观察比较两组患者乙肝病毒DNA定量和ALT水平.结果:治疗1周及2周时,两组患者乙肝病毒DNA 定量、ALT值比较无显著差异(P＞0.05),治疗4周时,研究组乙肝病毒DNA量和ALT水平明显小于对照组 (P＜0.05).结论:拉米夫定联合PMCT治疗乙肝病毒DNA阳性的HCC患者,可抑制乙型肝炎病毒复制,减轻肝脏炎症,保护患者肝功能.     

恶性淋巴瘤伴乙型肝炎病毒感染率调查分析

目的:了解初诊恶性淋巴瘤患者中乙型肝炎病毒(hepatitis B virus,HBV)的感染状况。方法:2008-01-2008-12对459例患者(恶性淋巴瘤276例,肺癌183例)临床资料进行回顾性分析。采用电化学发光技术检测患者血清标本的HBV表面抗原(HBsAg)、HBV表面抗体(HBsAb)、HBVe抗原(HBeAg)、HBVe抗体(HBeAb)及HBV核心抗体(HBcAb)的阳性率。结果:恶性淋巴瘤组HBsAg阳性率为11.95%(33/276),明显高于肺癌组患者(4.92%,9/183),P=0.010 4。其中B细胞淋巴瘤组HBsAg阳性率最高(14.77%,26/176),P=0.005 2。结论:恶性淋巴瘤患者HBsAg阳性率较高,与其他肿瘤化疗相比,恶性淋巴瘤患者化疗中更需要对HBV进行监测,更要重视乙型肝炎发作的预防和治疗。     

Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy:risk factors and survival

Introduction:Hepatitis B virus (HBV) reactivation has been reported in B-cel lymphoma patients with resolved hepatitis B (hepatitis B surface antigen [HBsAg]-negative and hepatitis B core antibody [HBc...     

Prophylactic antiviral therapy for hepatitis B virus surface antigen-positive patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy

We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)-positive patients with diffuse large B-cell lymphoma (DLBCL) and 278 HBsAg-negative patients with DLBCL, as a control cohort, who received rituximab-containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation-related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg-positive patients were divided into three groups based on anti–HBV prophylactic therapy: no nucleos(t)ide analogue (non–NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4-year cumulative incidence (CI) of hepatitis in HBsAg-positive and HBsAg-negative patients was 21.1% and 14.6% (P = .081), respectively. The 4-year CI of HBV reactivation-related hepatitis was higher in HBsAg-positive patients than in HBsAg-negative patients (8.0% vs 0.4%; P < .001). Among HBsAg-positive patients, the 4-year CI of HBV reactivation-related hepatitis was the highest in the non–NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P < .001). Of note, 3 non–NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation-related hepatitis and mortality in HBsAg-positive DLBCL patients receiving rituximab-containing chemotherapy.     

Use of lamivudine to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patients

In parts of Asia, about 10% of the population have chronic hepatitis B virus (HBV) infection, and cancer patients who are HBV carriers are frequently complicated by HBV reactivation while receiving cytotoxic chemotherapy. The condition may result in varying degrees of liver damage, causing disruption in chemotherapy and compromising the patients prognosis. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Recent reports have suggested that the anti-viral agent, lamivudine, may reduce HBV reactivation and its associated morbidity. However, most studies are based on small series of lymphoma patients, while information on the other high risk population, namely breast cancer patients, has been lacking. In this study, we studied the role of lamivudine in preventing HBV reactivation and its associated morbidity in breast cancer patients with chronic HBV infection who were planned for chemotherapy. Two groups were studied. One group consisted of 31 patients who received prophylactic lamivudine prior to and until 8 weeks after discontinuing chemotherapy. The other comprised of 61 historical controls who underwent chemotherapy without prophylactic lamivudine. The outcomes, in terms of the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity during chemotherapy were compared. The results revealed that in the prophylactic lamivudine group, despite a significantly higher proportion receiving anthracyclines, there was significantly fewer incidences of hepatitis (12.9 vs. 59.0%, p < 0.001), less HBV reactivation (6.5. vs. 31.1%, p=0.008), and less disruption of chemotherapy (16.1% vs. 45.9%, p=0.006). We conclude that prophylactic lamivudine significantly reduces the incidence of HBV reactivation and the overall morbidity of breast cancer patients undergoing chemotherapy.     

B细胞淋巴瘤化疗研究现状

非霍奇金淋巴瘤（non—Hodgkin’s lymphoma,NHL）是原发于淋巴结和其他器官淋巴组织的恶性肿瘤,不是单一的疾病,是一组异质性较大的疾病。它有多种形态特征、免疫表型、生物学规律、发展速度和治疗反应各不相同的类型。2001年,在REAL分型的基础上,由世界各国100多位病理学家、血液病学家和肿瘤学家共同参与制订了2001WHO淋巴瘤分类。在2001WHO NHL分类中,NHL分为B细胞、T细胞和NK细胞等类型,尤以B细胞淋巴瘤发病率为高。故我们重点对B细胞淋巴瘤化疗的现状阐述如下。     

非霍奇金淋巴瘤患者乙型肝炎病毒感染状态分析

目的：了解非霍奇金淋巴瘤（NHL）患者中乙型肝炎病毒（HBV）的感染状况。方法：对129例NHL患者乙肝五项检测结果进行回顾性分析,分析HBsAg阳性患者的比率。随机选取同期住院129例初诊的其他恶性肿瘤患者（原发性肝癌除外）及129例健康体检者作为对照。结果：NHL患者组HBsAg阳性率（22．5％）明显高于其他恶性肿瘤患者组（12．4％）和健康体检者组（9．3％）,男性NHL患者HBsAg阳性率高于女性患者（P〈0．05）,不同病理及不同分期的NHL患者HBsAg阳性率无统计学差异（P〉0．05）。结论：NHL患者HBsAg阳性率高于其他恶性肿瘤患者（原发性肝癌除外）及普通人群。