Recombinant human interferon-alpha induced cytoreduction in chronic myelogenous leukemia

Summary Fourteen patients with Ph'-chromosome positive chronic myelogenous leukemia (CML) in first chronic phase were treated with recombinant interferon-_2c. Interferon-_2c 5 to 10×10⁶ units s.c. was given for 12 weeks as an induction therapy. Maintenance treatment consisted of interferon-_2c 5 × 10⁶ units twice weekly s.c.. Two patients (14%) attained a complete clinical remission and 6 (43%) a partial remission, 3 of whom developed progressive disease during maintenance therapy. A complete disappearance of Ph'-chromosome was achieved in 1 patient. All patients had a more than 45% initial decline of the leukocyte count. Four out of ten patients with an initially enlarged spleen demonstrated reduction in spleen size. Influenza-like symptoms, anorexia, nausea, weight loss and fatigue were common side effects. Interferon-alpha is active in CML but additional clinical investigations are warranted to assess more precisely the therapeutic value of the interferons in this disease.     

博尔泰力（苦参素）治疗慢性乙型肝炎临床疗效观察

目的：探讨博尔泰力治疗慢性乙肝的合理剂量及远期疗效。方法：博尔泰力注射液I组（400mg)治疗慢性乙肝74例,Ⅱ组（600mg)治疗慢性乙肝90例,与α－干扰素（IFN－α）治疗的慢性乙肝75例比较并随访1年。结果：博尔泰力I组HBeAg阴转率32．4％,HBV－DNA阴转率37．8％;II组分别为36．7％和40．0％;IFN－α组分别为41．3％和44．0％（P＞0．05）。1年后随访博尔泰力I组二项阴转率分别为36．1％和27．9％;II组二项阴转率分别为38．5％和29．5％;IFN－α组二项阴转率分别为42．4％和42．4％（P＞0．05）,结论：博尔泰力注射液治疗Ⅰ,Ⅱ组对慢 性乙肝远期疗效均良好,可与干扰素媲美,有望成为治疗慢性乙肝的有效药物。     

骨髓增殖性肿瘤研究进展:JAK2 V617F基因突变发现后10年

结合大量的临床实践和近10年来对骨髓增殖性肿瘤(MPN)[骨髓增殖性疾病(MPD)]在JAK2 V617F基因突变等分子水平的大量研究,更加深了对MPN(MPD)的分子发病机制和临床价值的认识.研究者们探讨了JAK2 V617F基因突变如何促进MPN(MPD)发病的机制,分析了JAK2 V617F基因突变的分子机制和JAK2 V617F基因突变如何引起MPN(MPD)不同临床表型,以及MPN(MPD)基因组突变图谱及其生物学意义,指出了MPN(MPD)病理克隆的复杂性.JAK2 V617F基因突变在研究和诊治MPN(MPD)的过程中发挥着重大作用,其促使MPN(MPD)的研究和应用深入到基因/分子水平,治疗更趋于靶向性,更加精确,特别是使那些常规检验无法明确诊断的患者获得了及时诊治,避免了合并疾病的发生.MPN(MPD)的防治焦点是及时诊治,预防并避免血栓/出血性并发症的发生.推荐首选干扰素α(IFN-α)治疗,对于年龄大于60岁的患者,羟基脲是可以采用的.MPN(MPD)患者的预后大多数良好,发生恶变的风险不高,这是反复建议对中国MPD患者避免使用MPN称谓的主要理由.     

干扰素α干预对大鼠胰腺纤维化的影响

目的 观察干扰素α(INF-α)对DDC诱导的胰腺纤维化大鼠模型纤维增生程度、胰腺星状细胞活化标志物α-平滑肌肌动蛋白(α-SMA)和细胞外基质成分Ⅲ型胶原蛋白表达的影响.方法 Wistar大鼠40只随机数字法分成对照组、纤维化组和干扰素组.纤维化组和干扰素组每周2次腹腔内注射DDC,干扰素组在造模同时每天皮下注射INF-α10万U.6周末取材,光镜下观察胰腺病理学变化.免疫组化法测定胰腺组织中α-SMA、Ⅲ型胶原蛋白的表达.结果 第4周起纤维化组大鼠体重增长缓慢甚至下降,干扰素组体重仍缓慢增长,5周后两组差异显著[(309.8±19.7)g与(277.3±19.9)g,P＜0.05].纤维化组胰腺组织纤维化表现明显,纤维化分值、Masson染色值、α-SMA和Ⅲ型胶原蛋白相对表达量分别为2.679±0.899、218.713±36.102、148.971±30.686和88.142±42.581;干扰素组纤维化减轻,上述指标分别为1.952±0.219、114.732±24.912、77.237±9.275和59.952±25.498,均较纤维化组显著降低(P＜0.05).结论 给予INF-α能显著减轻纤维化程度和α-SMA、Ⅲ型胶原表达,对DDC诱导的大鼠胰腺纤维化有一定的预防作用.     

Interferon Alpha-2b Therapy in Chronic Hepatitis Delta

Background:

Approximately 5% of hepatitis B virus (HBV) carriers are coinfected with hepatitis D virus (HDV). HBV/HDV coinfection is a major cause of cirrhosis and end stage liver disease in chronic HBsAg carriers. The only approved therapy for chronic hepatitis delta is interferon alpha (IFN α) in either pegylated or conventional forms. Although higher doses and longer durations of IFN α therapy in HBV/HDV coinfected patients are currently applied, yet treatment response is low.

Objectives:

We aimed to determine the efficacy of IFN α-2b therapy in patients with HBV/HDV coinfection.

Patients and Methods:

In this cross sectional study, 20 HBsAg carriers with positive Anti-HDVAb and RT-PCR for HDV RNA were recruited and treated for three year duration with 5 million units (MU) of IFN α-2b, three times weekly or one year with 5 MU of IFN α-2b daily. Sustained virological response (SVR) was defined as a negative qualitative HDV RT-PCR, 6 months after treatment cessation.

Results:

Overall, 3 (15%) subjects achieved SVR, 10 cases (50%) relapsed after treatment cessation and 7 (35%) patients did not clear HDV during the treatment.

Conclusions:

HDV coinfection with HBV had very low response rate to high doses and long durations of IFN α-2b therapy.     

Novel Immunotherapeutic Strategies in Development for Renal Cell Carcinoma

Context

The purpose of this report is to review immunotherapies under investigation for patients with renal cell carcinoma (RCC), the most common form of kidney cancer, for which the incidence and mortality rate continue to increase.

Objective

To summarize and evaluate current data on immunotherapies for RCC and discuss issues to be resolved before integration into the RCC treatment paradigm.

Evidence acquisition

A search of Medline, clinicaltrials.gov, and congress abstracts/treatment guidelines was performed in May 2012 using the following terms (and variations): metastatic renal cell carcinoma, practice guidelines, response/resistance to current treatments, immunotherapy, novel immunotherapeutic strategies, T-cell modulation, immune priming, innate immunity, and combination therapy.

Evidence synthesis

Prior to the advent of novel agents targeting the vascular endothelial growth factor and mechanistic target of rapamycin pathways, interleukin-2 (IL-2) and interferon-α were the mainstays of RCC treatment. IL-2 remains one of the only treatments capable of curing advanced RCC, albeit in few patients. Despite recent advances, unmet need still exists for patients in the adjuvant setting, those with poor prognostic factors, and those who have progressed on prior targeted therapies. Improved understanding of host–tumor immune interactions has led to development of novel immunotherapeutic agents, including antibodies against immune checkpoint proteins (eg, programmed death-1 and cytotoxic T-lymphocyte antigen-4), and various vaccines. Because many of these compounds are in development, clinical experience with them is limited, although some have demonstrated activity in preliminary studies.

Conclusions

It is not yet clear where these new immunotherapies will fit into RCC treatment paradigms, but they may provide new options for patients whose current choices are limited. Furthermore, predictive biomarkers are needed to identify patients who will derive the greatest benefit from immunotherapy.     

慢性病毒性肝炎干扰素治疗后致甲状腺功能异常的临床特征及危险因素分析

目的 探讨慢性病毒性肝炎患者干扰素治疗后致甲状腺功能异常的临床特征及其相关危险因素.方法 回顾性分析干扰素治疗的96例慢性病毒性肝炎患者的临床资料,观察甲状腺功能的血清学指标及甲状腺自身抗体变化,治疗结束后继续随访1年,采用Logistic回归分析甲状腺功能异常发生的相关危险因素.结果 96例患者中,干扰素治疗后未发生甲状腺功能异常84例（正常组）;发生甲状腺功能异常12例（异常组）,发生率为12.5％（12/96）,依次为桥本甲状腺炎5例,Graves病和破坏性甲状腺炎各3例,非自身免疫性甲状腺功能减退1例.治疗后发生甲状腺功能异常的时间为2 ～ 7（3.8±1.9）个月,甲状腺功能异常持续时间l～ 11（4.2±0.9）个月.5例进行内分泌治疗,2例停用干扰素.治疗结束后随访1年,所有患者甲状腺功能均恢复正常.Logistic多元回归分析结果显示,女性（OR=3.767）和抗甲状腺过氧化物酶抗体（OR=1.117）是发生甲状腺功能异常的独立危险因素.结论 慢性病毒性肝炎患者干扰素治疗后致甲状腺功能异常以桥本甲状腺炎、Graves病、破坏性甲状腺炎和非自身免疫性甲状腺功能减退为主要类型.接受干扰素治疗的慢性病毒性肝炎患者在治疗过程中均应密切监测甲状腺功能及甲状腺自身抗体,尤其是女性及已有甲状腺自身抗体者.     

慢性HBV感染者外周血单个核细胞分泌干扰素α功能初探

目的：旨在检测慢性HBV感染者外周血单个核细胞（PBMC）分泌干扰素α（IFN-α）的情况,以探究其外周血浆细胞样树突状细胞（pDC）和单核细胞功能是否存在缺陷。方法前瞻性纳入2012年7月至2013年3月北京协和医院肝炎门诊就诊的慢性乙型肝炎（CHB）患者16例,同期选取与之年龄相匹配的HBV携带者16例和健康人18例。采集血样,分离PBMC,分别与含未甲基化的胞嘧啶鸟嘌呤二核苷酸序列的寡脱氧核苷酸2216（CPG ODN2216）、聚肌苷酸胞苷酸（poly I：C）刺激共培养,并用酶联免疫吸附试验（ELISA）测量其分泌IFN-α量。结果经ODN2216刺激后,CHB组患者PBMC分泌IFN-α量平均为31.20（7.33～44.04）pg/ml,HBV携带者组PBMC分泌IFN-α量平均为109.91（13.74～240.27）pg/ml,健康对照组PBMC分泌IFN-α量平均为107.95（48.59～227.33）。CHB患者组显著低于健康对照组,差异具有统计学意义（Z=-2.691,P=0.007）。CHB患者组显著低于HBV携带者组,差异具有统计学意义（Z=-2.206,P=0.027）。经poly（I：C）刺激后,三组PBMC分泌IFN-α量差异无统计学意义（F=0.628,P=0.427）。结论较HBV携带者和健康对照组,CHB患者体内PBMC中树突状细胞分泌IFN-α明显下降,而单核细胞分泌IFN-α量无显著性降低。     

Aicardi–Goutières syndrome with systemic lupus erythematosus and hypothyroidism

We report a case of Aicardi–Goutières syndrome with systemic lupus erythematosus and hypothyroidism. A 3-year-old girl, diagnosed with Aicardi–Goutières syndrome at 9 months, was transferred to our hospital for fever of unknown origin. Severe spasticity with dystonic posturing and flexion contracture of the limbs were noted. Interstitial pneumonia with pleural effusion was evident. Immunological investigations revealed positive antinuclear antibodies and reduced thyroid function. Prompt treatment with steroids, cyclophosphamide, and levothyroxine sodium hydrate elicited a good response. It is necessary to emphasize that its possible relationship between Aicardi–Goutières syndrome and systemic lupus erythematosus and/or hypothyroidism.