套细胞淋巴瘤治疗进展

套细胞淋巴瘤(MCL)是一种侵袭性的非霍奇金淋巴瘤(NHL),占成年人NHL的6%~8%,常表现为淋巴结、胃肠道、骨髓等受累,虽最初治疗有效,但易复发或耐药.第58届美国血液学会年会关于MCL的研究涵盖了基础研究、临床治疗、新药研究等多个方面,一些新动物模型的建立、信号通路靶点的研究为完善MCL发病机制及新药研究提供了基础;VcR-CVAD、VCR方案及对于年轻、 老年患者治疗新方案的尝试都取得了不错的效果;周期蛋白依赖性激酶(CDK)抑制剂、 磷脂酰肌醇3激酶(PI3K)抑制剂、bcl-2抑制剂等新型药物在初期临床试验中也显示出令人欣喜的结果,IACS-010759等小分子的出现为MCL治疗提供了新方向.     

套细胞淋巴瘤发病机制的研究进展

套细胞淋巴瘤(MCL)是一种罕见的B细胞淋巴瘤, 其发病率在逐年升高。MCL兼具惰性淋巴瘤和侵袭性淋巴瘤的共同特点, 病情进展迅速且预后不佳。最新研究认为, MCL的发病机制是一个连续统一体, 细胞周期失调、SOX11过表达、表观遗传畸变等多种因素在疾病的不同阶段发挥作用。文章主要从分子遗传学角度讨论MCL的发病机制和不同亚型的新发现, 进一步分析MCL的临床多样性。同时, 通过对MCL发病机制的认识, 旨在为MCL未来的治疗提供潜在的治疗靶点。     

外周T细胞淋巴瘤研究进展:第57届美国血液学会年会报道

外周T细胞淋巴瘤(PTCL)约占所有非霍奇金淋巴瘤(NHL)的10%~15%,呈高度异质性且侵袭性强,容易出现耐药和疾病进展,目前尚无标准的治疗方案.第57届美国血液学会年会关于PTCL的报告涵盖了基础和临床多个方面.基础研究方面,新型ALK伙伴基因的发现进一步完善了ALK阳性间变性大细胞淋巴瘤(ALK+ALCL)的发病机制.预后指标方面,免疫组织化学检测GATA3表达等为PTCL的预后监测提供了新的指标.治疗方面,belinostat联合CHOP、brentuximab vedotin联合CHP、罗米地辛联合ICE等新方案及移植的合理使用为PTCL患者的治疗提供了新方向,以alisertib、darinaparsin及denileukin diftitox等为代表的新型药物开展了初期临床试验,为PTCL的治疗提供了新希望.     

套细胞淋巴瘤中SOX11差异性表达的研究进展

套细胞淋巴瘤(MCL)中CCND1的过表达以及t(11;14)(q13;q32)染色体移位是其重要标志,但有部分MCL缺乏CCND1的表达.SOX11在CCND1阴性的MCL中存在过表达,可以将其作为CCND1阴性MCL的生物学标志物.SOX11是一种神经转录因子,其过表达与组蛋白修饰和DNA甲基化密切相关.SOX11差异性表达与浆细胞的分化密切相关,并且与MCL的预后和生存时间之间存在一定关系.利用SOX11 cDNA检测MCL的微小残留病灶(MRD)比传统方法更灵敏.随着对SOX11的不断深入研究,SOX11不仅可以成为MCL诊断及预后的重要依据,而且也为MCL的靶向治疗研究提供了一个新的思路.     

Bruton酪氨酸激酶抑制剂在套细胞淋巴瘤中的研究进展

套细胞淋巴瘤（MCL）是一种高度异质性的疾病,其临床表现多种多样,对常规化疗药物多不敏感,预后相对较差。以依鲁替尼（ibrutinib）为代表的新型Bruton酪氨酸激酶（BTK）靶向药物的出现为MCL的治疗提供了新希望。文章就BTK抑制剂在MCL治疗中的最新研究进展进行综述。     

套细胞淋巴瘤的治疗进展

套细胞淋巴瘤(mantle cell lymphoma,MCL)是来源于相对成熟的B淋巴细胞的特殊淋巴瘤亚型,兼具惰性淋巴瘤的难治愈性以及侵袭性淋巴瘤的缓解期短的特征。同时具有独特的生物学、病理学、免疫表型。如不行造血干细胞移植,目前尚无有效的治愈方法,预后较差。近年,新的靶向药物不断研发和临床应用,给MCL的治疗提供更多的选择,同时很大的改善了治疗效果。     

套细胞淋巴瘤诊治进展

套细胞淋巴瘤（MCL）是小 B 细胞淋巴瘤中一组高侵袭性的非霍奇金淋巴瘤（NHL）,约占NHL 的6%。MCL 起病隐匿、侵袭性强、恶性程度高、预后差,因此,MCL 的诊断及鉴别诊断至关重要。另外,MCL 分子病理模型、细胞周期蛋白 D1阴性 MCL、MCL 分期预后及分层治疗选择均值得关注。     

靶向药物治疗套细胞淋巴瘤的研究进展

套细胞淋巴瘤(MCL)是一种少见的非霍奇金淋巴瘤亚型.MCL临床表现有两种类型:一种为惰性表现,病情进展缓慢;另一种为侵袭性表现,病程进展迅速.近年,一些用于MCL治疗的新靶向药物已经问世.这些靶向药物较常规化疗提高了对复发/难治性MCL的疗效,其治疗MCL的靶点为B细胞淋巴瘤表面抗原、B细胞受体信号和肿瘤细胞微环境等.文章介绍了MCL靶向药物的研究进展.     

套细胞淋巴瘤治疗研究进展

套细胞淋巴瘤(MCL)是一种独特的B细胞非霍奇金淋巴瘤,其生物学行为具有侵袭性,恶性程度高,临床进展快,对常规治疗反应差,接受标准治疗后缓解期较短,至今依然被认为是一种不可治愈的淋巴瘤类型.第59届美国血液学会(ASH)年会报告中,涵盖了MCL新靶点的研发、耐药机制的研究、临床试验方案的优化等方面研究进展.文章结合会议报道对MCL治疗研究进展进行综述.     

侵袭性B细胞淋巴瘤研究进展：第19届欧洲血液学会年会报道

侵袭性B细胞淋巴瘤恶性程度高,进展较快,易出现治疗耐药和疾病复发.第19届欧洲血液学会（EHA）年会关于侵袭性B细胞淋巴瘤的研究报告涵盖多个方面：引入正电子发射型计算机断层扫描显像（PET）-CT检查,提供新的疗效监测及预后评估工具;提高利妥昔单抗剂量可改善老年男性患者的治疗效果;硼替佐米、ABT-199、靶向联合治疗、中枢神经系统预防等新型药物及方法的临床试验显示出令人鼓舞的结果,为侵袭性B细胞淋巴瘤的治疗带来了新的希望.     

外周T细胞淋巴瘤治疗进展:第56届美国血液学会年会报道

外周T细胞淋巴瘤(PTCL)是一组高度异质性的侵袭性非霍奇金淋巴瘤,在目前的治疗框架下大部分患者预后较差.第56届美国血液学会年会关于PTCL治疗的研究报告涵盖多个领域,其中针对PTCL患者高效低毒新型治疗策略的探索成为会议的一大热点.THP-COP方案、罗米地辛单用或联合其他药物、硼替佐米联合帕比司他、brentuximab vedotin及移植等新方案的组合和合理使用为PTCL治疗提供了新方向,同时以Duvelisib(IPI-145)、克唑替尼和抗程序性细胞死亡-1(PD-1)抗体等为代表的新型药物出现也为PTCL的治疗提供了新的希望.     

Radiotherapy in mantle cell lymphoma: A literature review

Mantle cell lymphoma (MCL) is a B-cell malignancy, comprising between 3% and 10% of all adult-onset non-Hodgkin lymphomas. MCL is considered incurable with current treatment modalities and most patients require multiple lines of treatment during their lifetime. MCL is very sensitive to radiotherapy (RT), even when delivered in low doses. In limited-stage MCL, RT can enable the de-escalation of systemic therapy. RT monotherapy is a valid option for frail patients. In advanced-stage disease, RT is very potent mode of palliation, even in heavily pretreated and chemo-resistant patients. Furthermore, it can provide a respite during which systemic treatment is unnecessary. In general, RT has a favorable toxicity profile and can be repeated as necessary for local relapse or distant disease. This effective, safe, and relatively inexpensive modality of therapy has been underutilized for patients with MCL. In this review, we will outline the use of RT for limited and advanced-stage disease and its potential application in combination with novel drugs.     

Mantle cell lymphoma: Therapeutic strategies are different from CLL

Opinion statement In contrast to the typical course of chronic lymphocytic lymphoma and despite an indolent lymphoma-like presentation, the clinical outcome of mantle cell lymphoma (MCL) is dismal, with a median survival time of 3 years and virtually no long-term survivors. Most patients are diagnosed with advanced stage III/IV disease. Although clinical studies did not prove a clear superiority of anthracyclin-containing combinations, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like regimens represent the standard therapeutic approach in MCL. Recent randomized studies have shown a benefit of a combined immunochemotherapy strategy (chemotherapy plus rituximab) increasing the complete and overall response rates, whereas further followup is pending for evaluation of the progression-free and overall survival. In patients younger than 65 years, a dose-intensive consolidation comprising high-dose radiochemotherapy and subsequent autologous stem cell transplantation after a CHOP-like induction results in an improved progression-free survival. However, despite the benefits of this multimodal approach, most patients relapse even after high-dose therapy. The only curative approach is allogeneic stem cell transplantation, which may be adapted to the elderly MCL patient cohort by modified dose-reduced conditioning regimens. Prospective randomized trials remain critical to further improve the clinical course of MCL with the addition of newer treatment modalities, such as radioactively labeled antibodies and targeted therapies (eg, flavopiridol and PS-341).     

Bortezomib: clinical profile in lymphoproliferative malignancies

In addition to its efficacy in the treatment of multiple myeloma, the proteasome inhibitor bortezomib appears to be active against a variety of other haematological malignancies. In a phase II trial, bortezomib, given twice weekly for 2 weeks of a 3 week cycle to patients with relapsed, refractory or untreated indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL), produced durable responses in 2/7 MCL patients and stable disease in five. Six of eight patients with follicular NHL achieved a durable response (1 CR, 5 PR). In another study, bortezomib was administered to patients with relapsed or refractory indolent or aggressive B-cell lymphoma. Durable responses were seen in 7/12 MCL patients, including three CR. This apparent activity in MCL is particularly encouraging, given its poor prognosis. These early trial results demonstrate that further clinical testing of bortezomib and additional exploration of the multiple biologic effects of proteasome inhibition are warranted in lymphoproliferative malignancies.     

替西罗莫司治疗套细胞淋巴瘤的研究进展

套细胞淋巴瘤（MCL）是一种少见、独特的B细胞非霍奇金淋巴瘤（NHL）亚型.现有不少治疗MCL的药物和方案,均有一定疗效,但疗效维持时间短,不够理想.目前认为MCL是难以治愈的,预后不良.文章着重介绍了一种治疗MCL的新药替西罗莫司.该药是雷帕霉素的衍生物,它通过下调淋巴瘤的Cyclin D1和Ki-67,阻断细胞周期,诱导肿瘤缩小,抑制肿瘤生长.研究显示替西罗莫司能诱导MCL患者缓解和延长生存,特别对复发性或难治性MCL患者有一定疗效.另外,替西罗莫司与利妥昔单抗,或与其他化疗药物联合应用,能获得比单用替西罗莫司更好的效果.     

Mantle cell lymphoma – Current standards of care and future directions

Over the past decade we have seen significant changes in the biological characterization and strategies for treatment of mantle cell lymphoma (MCL). MCL is heterogeneous a disease, and so are the people that have it; although guidelines are appropriate, therapeutic approaches must be individualized based on a variety of factors. In this review, we summarize data on the range of therapeutic options, from observation in patients with slowly progressive low-tumor-burden MCL, to bendamustine-based regimens in typical MCL, to high-dose cytarabine-based regimens in young, fit patients. The management of previously treated MCL is evolving with the availability of new agents and more changes are expected. Several recent and ongoing clinical trials have the potential to provide new options for patients and are discussed as future directions. Additionally, prognostic tools, measurement of minimal residual disease, and assessment of toxicity are already common research tools and may soon impact therapeutic strategies as a standard of care. Indeed, there has never been a time that management of MCL was as complicated while the promise for real improvements in outcomes is so great.     

Quantitative monitoring of cyclin D1 expression: a molecular marker for minimal residual disease monitoring and a predictor of the disease outcome in patients with mantle cell lymphoma

In mantle cell lymphoma (MCL), minimal residual disease (MRD) is an indicator of the disease outcome. Quantitative methods used so far do not provide a suitable molecular marker in 30-70% patients with MCL (depending on the technique used). We tested cyclin D1 as a marker for quantitative MRD monitoring. The real-time PCR of cyclin D1 mRNA was performed in 144 bone marrow (BM) specimens including 95 BMs from MCL patients, 39 BMs from patients with other B-cell non-Hodgkin's lymphomas and 10 BMs from healthy volunteer donors. In 73 BMs obtained from 20 MCL patients we examined the cyclin D1 level during the treatment and follow-up period. We detected a cyclin D1 overexpression exclusively in BMs infiltrated with MCL, including minimal residual infiltration. Dynamics of cyclin D1 correlated with the patient's clinical status in 69/73 BMs. Individual monitoring of patients during the disease course showed cyclin D1 quantitative changes accompanying either the disease relapse or a successful treatment response or the disease-free survival (remission) and it showed a predictive significance. Cyclin D1 detection is a promising approach for the quantitative MRD monitoring in MCL patients, and the individual monitoring of the cyclin D1 dynamics represents a suitable indicator of the disease course.     

Targeting the proteasome in mantle cell lymphoma: a promising therapeutic approach

Mantle cell lymphoma (MCL) is a distinctive non-Hodgkin's lymphoma sub-type, characterized by over-expression of cyclin D1 as a consequence of chromosomal translocation t(11;14)(q13;q32). MCL remains an incurable disease, combining the unfavorable clinical features of aggressive and indolent lymphomas. The blastic variant of MCL, which is often associated with additional cytogenetic alterations, has an even worse prognosis and new treatment options are clearly needed. The 26S proteasome is a large multi-catalytic multi-protein complex, present in all eukaryotic cells. It is responsible for the degradation of a variety of short-lived proteins and exhibits a key position in cellular processes including apoptosis and cell cycle progression. Targeting the ubiquitin - proteasome pathway has only recently been identified as a promising new therapeutic option for cancer patients. Interestingly, an increased activity of the proteasome pathway has been described in MCL cells and the inhibition of the proteasome seems to be a promising therapeutic approach for this incurable disease.