慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的治疗进展

慢性淋巴细胞白血病（CLL）/小淋巴细胞淋巴瘤（SLL）是一种慢性B淋巴细胞增殖性疾病。随着人们对CLL/SLL在临床和分子水平上的深入了解,CLL/SLL的新型治疗方案也不断涌现,包括靶向治疗、嵌合抗原受体T细胞免疫疗法和异基因造血干细胞移植。其中靶向治疗包括：布鲁顿氏酪氨酸激酶抑制剂、磷脂酰肌醇3激酶抑制剂、B细胞淋巴瘤因子2抑制剂和蛋白激酶Cβ抑制剂。除新型药物的不断涌现,各疗法之间的联合治疗和对固定疗程的探索在CLL/SLL的治疗中也备受关注。文章结合相关文献对CLL/SLL的最新治疗进展进行总结。     

B7-H1与头颈部鳞状细胞癌免疫治疗

B7-H1(又称programmed death receptor ligand 1,PD-L1)是一种细胞表面糖蛋白,属于共刺激分子B7家族。研究证明B7-H1大量表达于肺癌、卵巢癌、结肠癌、黑素瘤、头颈肿瘤和乳腺肿瘤等少数肿瘤细胞系,存在于肿瘤内皮细胞及上皮细胞中,且与肿瘤免疫逃避有关。近年来发现大多数头颈部鳞状细胞癌(SCCHN)新鲜标本可见B7-H1在细胞膜或细胞质内表达,并且阻断其共刺激通路可增强肿瘤免疫疗法的疗效。本文通过综述B7-H1在各种肿瘤治疗方法,如细胞因子疗法、抗体及其偶联物疗法、免疫活性细胞过继疗法、肿瘤疫苗疗法等方法中的应用前景,来探讨B7-H1研究在头颈部鳞状细胞癌免疫治疗研究中的突破性作用。     

伊布替尼联合CD19嵌合抗原受体T细胞治疗慢性淋巴细胞白血病的研究进展

慢性淋巴细胞白血病(CLL)是一种B淋巴细胞的克隆性恶性疾病(T淋巴细胞少见), 好发于老年人, 且有高度可变的临床过程, 中位生存期一般为35～63个月。在免疫化疗时代, CLL患者的生存得到明显改善, 但仍有大部分患者存在原发耐药及治疗后复发。布鲁顿酪氨酸激酶抑制剂的出现彻底改变了CLL的治疗模式, 使CLL的治疗进入靶向时代, 伊布替尼联合CD19嵌合抗原受体T细胞治疗具有较好的效果, 可改善患者预后。     

伴幼淋巴细胞增多的慢性淋巴细胞白血病三例并文献复习

 【摘要】　目的　探讨伴幼淋巴细胞增多的慢性淋巴细胞白血病（CLL／PL）的临床特征与预后,为临床诊治提供依据。方法　回顾性分析3例CLL／PL患者的临床资料并复习相关文献,讨论其临床特征及预后。结果　CLL／PL在临床表现、免疫表型、细胞遗传学、分子生物学等方面具有特殊性。结论　CLL伴幼淋巴细胞增多与其临床特征密切相关,提示预后不良。     

热疗与树突状细胞联合治疗肿瘤的研究进展

热疗可通过提高机体免疫效应细胞活性、诱导免疫效应细胞再分布、影响细胞因子表达等作用调节机体的免疫功能,抑制肿瘤生长和转移.基于热疗可调节机体免疫功能,研究热疗与各种免疫疗法联合应用的协同效应,为利用热效应治疗肿瘤提供实验依据.目前,树突状细胞(DC)的免疫治疗在抗肿瘤研究中备受关注,热疗与DC联合治疗肿瘤,二者取长补短,产生协同作用,从而提高抗肿瘤免疫.     

热疗与树突状细胞联合治疗肿瘤的研究进展

热疗可通过提高机体免疫效应细胞活性、诱导免疫效应细胞再分布、影响细胞因子表达等作用调节机体的免疫功能,抑制肿瘤生长和转移.基于热疗可调节机体免疫功能,研究热疗与各种免疫疗法联合应用的协同效应,为利用热效应治疗肿瘤提供实验依据.目前,树突状细胞(DC)的免疫治疗在抗肿瘤研究中备受关注,热疗与DC联合治疗肿瘤,二者取长补短,产生协同作用,从而提高抗肿瘤免疫.     

恶性胸水的过继免疫治疗

应用淋巴因子激活的杀伤细胞（ＬＡＫ细胞），肿瘤浸润淋巴细胞（ＴＩＬ细胞）联合过继免疫疗法（ＡＩＴ）治疗恶性胸水１０例。其中肺癌伴胸膜转移８例，胃癌和食管癌术后胸膜转移各１例。经ＬＡＫ细胞，ＴＩＬ细胞及白细胞介素Ⅱ治疗后显示，８例病人在治疗后２－４周胸水完全消失，１例明显减少，自觉症状均有明显改善。作者探讨了过继免疫治疗的疗效与效应细胞扩增倍数、扩增培养时间和活性的关系，认为应用过继免疫疗法治疗恶性     

慢性淋巴细胞白血病治疗进展

慢性淋巴细胞白血病（CLL）是一种慢性B淋巴细胞增殖性疾病。目前临床上常用的治疗方案（如FCR、BR、伊布替尼等）已取得了较好的疗效,但仍有患者面临疾病复发和进展。为进一步提高疗效,新型的针对CLL联合治疗方案不断涌现。文章结合第62届美国血液学会年会相关报道对CLL的最新治疗进展进行总结。     

IL-2和LAK细胞抗肿瘤免疫疗法的临床进展

内细胞介素-2/淋巴因子激活杀伤细胞疗法(以下简称IL-2/LAK细胞疗法)是近年来问世的以免疫调节为基础的抗肿瘤免疫疗法。这一疗法的临床研究及应用已取得了很大进展。     

5-FC/CD 自杀基因疗法结合热休克蛋白-多肽复合物瘤苗治疗小鼠黑色素瘤的研究

 目的　研究 5 -氟尿嘧啶 /胞嘧啶脱氨酶 (5 FC/ CD)基因疗法与热休克蛋白 -多肽复合物 (HSP- PC)瘤苗免疫疗法联合抗肿瘤效果。方法　将携带 CD基因的重组腺病毒注射到小鼠黑色素瘤体内 ,腹腔注射 5 - FC,同时皮下接种 HSP70 - PC。结果　经联合治疗后 ,70 %荷瘤小鼠肿瘤体积缩小、消退 ,小鼠存活期延长 ,肿瘤组织明显坏死 ,炎症细胞、CD+4 及 CD+8T细胞浸润明显。结论5 - FC/ CD基因疗法结合 HSP- PC瘤苗免疫疗法抗小鼠黑色素瘤作用显著 ,具有临床应用前景。     

慢性淋巴细胞白血病及部分淋巴瘤治疗迎来一个崭新时代：第55届美国血液学会年会报道

第55届美国血液学会（ASH）年会报道了有关慢性淋巴细胞白血病（CLL）和部分淋巴瘤的多项新的靶向治疗药物,这些药物多靶向于B细胞不同的信号转导通路关键靶点.尽管这些靶向药物单独应用并没有提高CLL的疗效,但多项临床试验结果显示联合治疗明显提高了CLL的疗效及延长了CLL患者的无进展生存时间.因此,专家们认为靶向药物的联合治疗和序贯治疗将开启一个CLL治疗的新时代.文章仅就这些最新进展与国内读者共享.     

慢性淋巴细胞白血病治疗研究进展

近年来,慢性淋巴细胞白血病（CLL）的治疗取得了巨大进展,尤其是新药的应用获得了令人鼓舞的疗效。2016年第58届美国血液学会（ASH）年会上报道了CLL多方面的临床研究结果,包括布鲁顿酪氨酸激酶抑制剂（BTKi）长期应用结果和联合其他药物的治疗效果、bcl-2抑制剂的近期疗效、来那度胺维持治疗的效果;而CD19-CART细胞治疗CLL也取得了较好疗效。另外,在传统治疗方面,长期随访结果再次巩固了FCR方案的地位,而异基因干细胞移植在CLL中的应用指征更加严格,但仍有一定地位。     

Inhibiting B-Cell Receptor Signaling Pathways in Chronic Lymphocytic Leukemia

B-cell receptor (BCR) signaling is a central pathologic mechanism in B-cell malignancies, including chronic lymphocytic leukemia (CLL), in which it promotes leukemia cell survival and proliferation, and modulates CLL cell migration and tissue homing. BCR signaling now can be targeted with new, small molecule inhibitors of the spleen tyrosine kinase (Syk), Bruton’s tyrosine kinase (Btk), or phosphoinositide 3′-kinase (PI3K) isoform p110δ (PI3Kδ), which have recently entered the clinical stage and show promising results in patients with CLL. During the first weeks of therapy, these agents characteristically induce rapid resolution of lymphadenopathy and organomegaly, accompanied by a transient surge in lymphocyte counts due to “mobilization” of tissue-resident CLL cells into the blood. Then, often after months of continuous therapy, a major proportion of patients achieve remissions. This article reviews key biologic aspects of BCR-associated kinases in CLL and other B cell neoplasias, and develops perspectives for future development of this exciting new class of kinase inhibitors.     

Update on risk-stratified management for chronic lymphocytic leukemia

Major recent advances in understanding the biology of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) have improved clinical evaluation and influenced treatment decisions. CLL can be diagnosed early and accurately, and biological measurements can be used to predict a prognosis at diagnosis. Individual patient care can be risk stratified to optimize benefit and minimize complications of therapy. Purine analogs and monoclonal antibodies have markedly improved the efficacy of initial therapy but are not curative. The treatment of relapsed and refractory CLL is less successful. However, recent developments suggest that allogeneic stem cell transplant could have a larger role in a selected group of these patients. Potential new treatment modalities include targeted molecules that interrupt key components of CLL cell survival pathways, and active and passive immunotherapy. The management of CLL is in a dynamic phase of rapid evolution. Risk stratification using biological prognostic markers can improve current patient care and direct future clinical research.     

Improving therapy of chronic lymphocytic leukemia with chimeric antigen receptor T cells

Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and redirecting the immune system against cancer. This review will briefly summarize T-cell therapies in development for CLL disease. We discuss the role of T-cell function and phenotype, T-cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL.     

Co-Occurrence of EBV-Positive Mucocutaneous Ulcer (EBV-MCU) and CLL/SLL in the Head and Neck Region

EBV-positive mucocutaneous ulcer (EBV-MCU) was classified as a rare new entity of the lymphoproliferative B-cell diseases by the WHO in 2017 and must be distinguished from head and neck squamous cell carcinoma by early biopsy. The aim of the study is to raise awareness of the disease and to give a review of the current literature and a recommendation for EBV-MCU management. All EBV-MCU cases of the head and neck region published so far were included. We also report a case of a pharyngeal EBV-MCU in an 89-year-old patient who was immunosuppressed by chronic lymphatic leukaemia/small lymphocytic lymphoma (CLL/SLL). In contrast to all previously described cases, histopathology showed a co-infiltration of EBV-MCU and CLL/SLL. A total of 181 cases were identified on PubMed and summarised. EBV-MCU was predominantly caused by immunosuppressive drug therapy. Complete remission could be achieved in 68% of cases and was mainly attributed to a reduction of the immunosuppressive therapy alone (72%). However, some severe cases require more aggressive treatment. Regarding the various histopathologic similarities to other lymphoproliferative disorders, the diagnosis of EBV-MCU can be misleading, with a great impact on patient care and treatment. This diagnosis must be made with caution and requires a combination of clinical, morphological and immunophenotypic features.     

Chronic lymphocytic leukemia

Opinion statement Historically, treatment of chronic lymphocytic leukemia (CLL) essentially had been palliative. During the past two decades, effective new therapies for the treatment of CLL have emerged. The advent of fludarabine, a purine analog with activity against chlorambucil-resistant CLL, showed promising results with high response rates in previously untreated patients. These improvements in response and delays in disease progression have not translated into a survival benefit, indicating that chlorambucil may be the preferred first-line therapy when treatment is indicated. Allogeneic hematopoietic stem cell transplantation, by combining the cytoreductive effects of conditioning with a potent graft-versus-tumor effect, is the only treatment modality with the prospect of cure for patients with CLL. However, conventional hematopoietic stem cell transplantation can be offered only to select patients with CLL because of older age and comorbid conditions. Novel methods of transplantation exploiting the graft-versus-leukemia effect while reducing the toxicity of the pretransplant conditioning are promising approaches that may enable more patients to benefit from this therapy. Monoclonal antibodies such as rituximab or alemtuzumab (Campath-1H; llex Pharmaceuticals, San Antonio, TX) are agents with activity in untreated and resistant CLL. Efforts are being focused on combining these monoclonal antibodies with chemotherapy and the development of rationally designed drugs.     

Effect of therapy on T cell subpopulations in patients with chronic lymphocytic leukemia

We have previously demonstrated functional and quantitative imbalances in two human thymic (T) cell subpopulations. Tγ and Tμ, in chronic lymphocytic leukemia (CLL) patients. Serial evaluations of the numbers of Tγ and Tμ subsets in CLL were performed in order to delineate more completely the patterns of T cell abnormalities. Two groups of CLL patients were studied: (1) previously untreated (n = 3) and (II) stable CLL on chemotherapy (n = 12). In Group I, two of three patients had significantly increased percentages of Tγ cells (mean ± S.E.M. = 57 ± 5 vs 18 ± 2 for controls). There was defective in vitro appearance of Tμ cells in both groups. In Group II, repeated studies of T cell subsets revealed persistently elevated Tγ cells despite various modes of oral chemotherapy. In three CLL patients who required splenectomy a dramatic decrease in the percentages of Tγ, cells was noted post-splenectomy (51 ± 3 to 15 ± 3). In all cases the spleen was diffusely involved with CLL. These findings indicate: (1) abnormalities of T cell subsets are present early in CLL. (2) chemotherapy does not affect the levels of Tγ cells in stable patients and (3) removal of infiltrated CLL spleens results in a dramatic decrease in the proportion of Tγ cells. This latter finding plus the increase in Tγ cells in progressive disease post-splenectomy suggest Tγ cells may be an important determinant of the course of CLL.     

B细胞受体通路抑制剂在慢性淋巴细胞白血病治疗中的研究进展：第57届美国血液学会年会报道

随着Bruton酪氨酸激酶（BTK）抑制剂依鲁替尼（ibrutinib）及磷脂酰肌醇-3-激酶（PI3K）抑制剂idelalisib在复发／难治非霍奇金淋巴瘤（NHL）治疗中的成功,一系列新的B细胞受体（BCR）通路抑制剂也逐步进入临床试验。第57届美国血液学会（ASH）年会继续对依鲁替尼和idelalisib单药或联合用药治疗慢性淋巴细胞白血病（CLL）的探索保持了高度热情。另外脾酪氨酸激酶（SYK）抑制剂及新的BTK和PI3K抑制剂也崭露头角,为改善依鲁替尼和idelalisib耐药患者的疗效提供了新的选择。文章就第57届ASH年会中关于BCR通路抑制剂治疗CLL的进展进行介绍。