淋巴瘤领域文献更新8月刊-EX.pdf

目 录 肺癌文献更新 2013 年 5 月 1 LYMPHOMA PUBLICATION ALERT AUGUST 2013 淋巴瘤文献更新 本回复仅为学术交流之目的供中华人民共和国境内医学专业人士参考。医疗卫生专业人士做出的任何与治疗有关的决定应参考国家食品药品监督管理局批准的药品说明书；详见 未经授权，该资料不得翻印或散发。目录 LYMPHOMA AUGUST 2013 2 Combination of Rituximab and the Mtor Inhibitor Everolimus(RAD001)In Diffuse Large B Cell Lymphoma.利妥昔单抗联用 mTOR 抑制剂依维莫司（RAD001）治疗弥漫性大 B 细胞淋巴瘤.5 Fludarabine-Mitoxantrone-Rituximab Regimen in Untreated Intermediate/High-Risk Follicular Non-Hodgkinslymphoma:Experience on 142 Patients.未接受过治疗中/高危滤泡性非霍奇金淋巴瘤的氟达拉滨+米托蒽醌联用利妥昔单抗治疗方案：来自 142 例患者的经验.6 The Prognostic Impact of Absolute Lymphocyte and Monocyte Counts at Diagnosis of Diffuse Large B-Cell Lymphoma in the Rituximab Era.利妥昔单抗时代诊断弥漫性大 B 细胞淋巴瘤时淋巴细胞和单核细胞绝对计数的预后影响.7 Early Stage Follicular Lymphoma:What Is The Clinical Impact of The First-Line Treatment Strategy?早期滤泡性淋巴瘤:一线治疗方案的临床疗效是什么?.8 Outcomes of Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma with Progression of Lymphoma after Autologous Stem Cell Transplantation in the Rituximab Era.在利妥昔单抗时代复发/难治性弥漫性大 B 细胞淋巴瘤患者进行自体干细胞移植后的疗效.9 MYC/BCL2 Protein Coexpression Contributes to The Inferior Survival of Activated B-Cell Subtype of Diffuse Large B-Cell Lymphoma and Demonstrates High-Risk Gene Expression Signatures:A Report from The International DLBCL Rituximab-CHOP Consortium Program.MYC/BCL2 蛋白共表达与弥漫性大 B 细胞淋巴瘤活性 B 细胞亚型的不良生存有关并可提示高危基因表达特征：一份来自国际 DLBCL 利妥昔单抗-CHOP 联盟项目的报告.10 Obinutuzumab(GA101)Monotherapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma or Mantle-CellLymphoma:Results From the Phase II GAUGUIN Study.复发/难治性弥漫性大 B 细胞淋巴瘤或套细胞淋巴瘤的 Obinutuzumab（GA101）单药治疗:来自 GAUGUIN 研究的 II 期结果.11 Comparison of Outcomes among Patients Aged 80 and Over and Younger Patients with Diffuse Large B Cell Lymphoma:A Population Based Study.对年龄等于，小于和大于 80 周岁弥漫性大 B 淋巴瘤患者的疗效比较：一项基于人群的研究.12 目录 LYMPHOMA AUGUST 2013 3 Early TARC Reduction and Response Following Panobinostat Treatment in Patients with Relapsed/Refractory Hodgkin Lymphoma Following Autologous Stem Cell Transplant.复发/难治性霍奇金淋巴瘤患者进行自体干细胞移植后接受帕比司他治疗后的早期 TARC 减少和缓解.13 Indications for Hematopoietic Stem Cell Transplantation in Patients with Follicular Lymphoma:A Consensus Project of the EBMT-Lymphoma Working Party.滤泡性淋巴瘤患者造血干细胞移植的标志:EBMT 淋巴瘤工作组的一项共识项目.14 Recognizing Nodal Marginal Zone Lymphoma:Recent Advances and Pitfalls.A Systematic Review.认识淋巴结边缘区淋巴瘤的最新进展和缺陷：一项系统性回顾.15 Intensive Chemotherapy and Immunotherapy in Patients with Newly Diagnosed Primary CNS Lymphoma:CALGB 50202(Alliance 50202).新确诊原发性 CNS 淋巴瘤患者的强化化疗和免疫治疗:CALGB 50202（Alliance 50202）.16 HLA Specificities Are Related To Development and Prognosis of Diffuse Large B-Cell Lymphoma.HLA 特异性与弥漫性大 B 细胞淋巴瘤的发展和预后相关.17 CD30 Targeting with Brentuximab Vedotin:A Novel Therapeutic Approach to Primary Effusion Lymphoma.brentuximab vedotin 靶向 CD30：一种原发性渗出性淋巴瘤的新疗法.18 Autologous Haematopoietic Cell Transplantation for Non-Hodgkin Lymphoma with Secondary CNS Involvement.自体造血干细胞移植治疗继发性 CNS 病变的非霍奇金淋巴瘤.19 Diffuse Large B-Cell Lymphoma(Richter Syndrome)in Patients With Chronic Lymphocytic Leukaemia(CLL):A Cohort Study of Newly Diagnosed Patients.伴有慢性淋巴细胞白血病（CLL）的弥漫性大 B 细胞淋巴瘤（里氏综合征）：一项针对初诊患者的队列研究.20 Molecular Profiling Improves Classification and Prognostication of Nodal Peripheral T-Cell Lymphomas:Results of a Phase III Diagnostic Accuracy Study.分子特征可改善淋巴结外周 T 细胞淋巴瘤的分类和预测：关于诊断准确性的 III 期研究结果.21 Management Of Relapsed/Refractory Mantle Cell Lymphoma:A Review Of Current Therapeutic Strategies.复发性/难治性套细胞淋巴瘤的治疗：一项针对目前治疗方案的回顾性研究.22 目录 LYMPHOMA AUGUST 2013 4 Prognostic Significance of Immunohistochemical Expression of the Angiogenic Molecules Vascular Endothelial Growth Factor-A,Vascular Endothelial Growth Factor Receptor-1 and Vascular Endothelial Growth Factor Receptor-2 in Patients with Classical Hodgkin Lymphoma.经典型霍奇金淋巴瘤患者血管生成分子血管内皮生长因子 A、血管内皮生长因子受体 1 和血管内皮生长因子受体 2 免疫组化表达的预后意义.23 Emerging Issues after The Recognition of in Situ Follicular Lymphoma.识别原位滤泡性淋巴瘤后的新问题.24 LYMPHOMA AUGUST 2013 5 Leuk Lymphoma.2013 Jul 11.Combination of Rituximab and the Mtor Inhibitor Everolimus(RAD001)In Diffuse Large B Cell Lymphoma.利妥昔单抗联用 mTOR 抑制剂依维莫司（RAD001）治疗弥漫性大 B 细胞淋巴瘤 Xu ZZ,Wang WF,Fu WB et al.摘要 我们评估了抗CD20单克隆抗体利妥昔单抗联用mTOR 抑制剂依维莫司治疗弥漫性大 B 细胞淋巴瘤（DLBCL）的疗效。与单药治疗的效果相比，利妥昔单抗联用依维莫司治疗可以更有效地抑制细胞生长。在联合治疗组中，我们观察到细胞G0/G1 期阻滞延长和细胞凋亡数增加。联用利妥昔单抗治疗减少了由依维莫司负反馈回路引起的 p-AKT 过度表达，并可对抑制 mTOR 信号产生增强效应，因此，联用利妥昔单抗是这种协同效应的一个原因。此外，与其它单药治疗相比，联合治疗也对抑制 DLBCL 异种移植的生长更为有效。本研究为利妥昔单抗联用依维莫司治疗DLBCL 提供了临床前证据和理论依据。ABSTRACT We evaluated the effects of the anti-CD20 monoclonal antibody rituximab in combination with a mammalian target of mTOR inhibitor everolimus for treating diffuse large B cell lymphoma(DLBCL).The combination of rituximab and everolimus was more effective for inhibiting cell growth compared with the effect of a single-agent therapy.An increase in G0/G1 cell cycle arrest and an increased population of cells in apoptosis were observed in the combination treatment group.Addition of rituximab reduced the overexpression of p-AKT caused by the negative feedback loop of everolimus and had an enhanced effect on inhibiting mTOR signaling,thus providing a rationale for this synergistic effect.Furthermore,combination treatment was also more effective than treatment with either agent alone for inhibiting the growth of DLBCL xenografts.Our study provided preclinical evidence and a theoretical basis for combination therapy for DLBCL with rituximab and everolimus in DLBCL.返回目录 LYMPHOMA AUGUST 2013 6 Am J Hematol.2013 Jul 10.Fludarabine-Mitoxantrone-Rituximab Regimen in Untreated Intermediate/High-Risk Follicular Non-Hodgkinslymphoma:Experience on 142 Patients.未接受过治疗中/高危滤泡性非霍奇金淋巴瘤的氟达拉滨+米托蒽醌联用利妥昔单抗治疗方案：来自 142 例患者的经验 Zinzani PL,Pellegrini C,Broccoli A et al.摘要 晚期滤泡性淋巴瘤患者的前线最佳化疗方案或该疾病治愈的明确定义尚未达成国际共识。本研究的目的是，在一个预后不良的滤泡性淋巴瘤患者亚组中，特别针对长期无病生存者，检测氟达拉滨+米托蒽醌联用利妥昔单抗治疗的有效性和安全性。我们对接受了氟达拉滨+米托蒽醌联用利妥昔单抗一线治疗方案的 142 例中/高危滤泡性淋巴瘤患者进行了回顾性研究。我们还评估了病情缓解情况、安全性和生存情况。在一个有 56例患者的亚组中，我们也对 PET 的预后价值进行了研究，结果发现，总缓解率为 95.5%，其中完全缓解率 88%，在为期 48 个月的中期随访时，有 18%的患者疾病复发，预计 12 年无病生存率为 72%。所有病例的淋巴瘤均在 40 个月之内复发，在此之后，无病生存曲线达到平稳状态。12年总生存率为 73%。治疗后 PET 阳性仍是疾病进展的一个非常重要的预测因子。使用基于利妥昔单抗联用氟达拉滨+米托蒽醌治疗的方案后，我们观察到了较高的完全缓解率，这似乎是改善无病生存期的第一步。本研究或许是考虑将无病生存期作为未来临床试验中滤泡性淋巴瘤患者一个可能的可选终点的开始。ABSTRACT There is no international consensus on frontline optimal chemotherapy regimen for advanced stage follicular lymphoma patients,or a clear definition of cure for this disease.Aim of this study was to test the degree of effectiveness and the safety of the regimen containing fludarabine,mitoxantrone andrituximab in a subset of poor prognosis follicular lymphoma patients with particular focus on the long-term disease free survival.A retrospective study was conducted on 142 intermediate/high-risk follicular lymphoma patients treated in first-line with fludarabine,mitoxantrone and rituximab regimen.Responses,safety and survival were evaluated.The prognostic value of PET was also investigated in a 56-patients subset.Overall response rate was 95.5%including 88%of complete responses.With a median follow-up of 48 months,18%of patients had disease relapse,yielding an estimated 12-year disease-free survival of 72%.All cases showed the lymphoma recurrence within 40 months:after this timing the disease-free survival curve presented a plateau.Overall survival was 73%at 12 years.Post-treatment PET positivity remains a highly significant predictor of disease progression.The observed high rate of complete responses following the use of fludarabine,mitoxantrone-based regimen in combination with rituximab seems to be the first step to improve disease-free survival.Our study could be the starting point to consider disease-free survival as a potential alternative endpoint of future clinical trials on follicular 返回目录 LYMPHOMA AUGUST 2013 7 Acta Haematol.2013 Jul 11;130(4):242-246.The Prognostic Impact of Absolute Lymphocyte and Monocyte Counts at Diagnosis of Diffuse Large B-Cell Lymphoma in the Rituximab Era.利妥昔单抗时代诊断弥漫性大 B 细胞淋巴瘤时淋巴细胞和单核细胞绝对计数的预后影响 Aoki K,Tabata S,Yonetani N et al.背景：最近的一份报告显示，诊断弥漫性大 B 细胞淋巴瘤（DLBCL）时淋巴细胞绝对计数（ALC）和单核细胞绝对计数（AMC）的结合有助于明确预后评分。然而，该模型需在其它患者队列中进行验证。方法：我们回顾性地评价了诊断中 ALC 联用AMC 对 1 个 299 例 DLBCL 患者队列的预后影响，这些患者于利妥昔单抗时代在同一家医院接受了治疗。结果：在单因素分析中，ALC1.0109/l4 年总生存率（OS）47.0 vs.79.4%；P 0.001和 AMC0.63109/l（4 年 OS 率 52.4 vs.75.6%；P0.001）均与较差 OS 有关。在多变量分析中，ALC1.0109/l 和 AMC0.63109/l 均与较长的 OS 显著相关，这独立于国际预后指数。此外，ALC 和 AMC 的联合可用以识别不良预后患者；ALC1.0109/l 和 AMC0.63109/l 患者的 4年生存率为 18.8%。结论：诊断中 ALC 和 AMC 的联合对 DLBCL 患者的预后分层可能有用。BACKGROUND:A recent report showed that the combination of the absolute lymphocyte count(ALC)and the absolute monocyte count(AMC)at diagnosis gave a prognostic score in diffuse large B-cell lymphoma(DLBCL).However,this model requires validation in other patient cohorts.METHODS:We retrospectively evaluated the prognostic impact of the combination of the ALC and the AMC at diagnosis in a cohort of 299 DLBCL patients who were treated in the rituximab era at a single institution.RESULTS:In univariate analyses,an ALC 1.0 109/l 4-year overall survival(OS)rate 47.0 vs.79.4%;p 0.001 and an AMC 0.63 109/l(4-year OS rate 52.4 vs.75.6%;p 中值和减少量中值）。胸腺活化调节因子（TARC）与临床疗效密切相关。在有缓解的患者中观察到了TARC 的早期减少，在第 1 个疗程的第 15 天（C1D15）减少最甚。在 93 例 C1D15 患者样本中，3 例完全缓解，25 例部分缓解。在 C1D15，与 TARC 减少量 中值相比，减少量中值的小组缓解者更多（1839%vs 1021%）、无进展生存期（PFS10.6 vs 4.9 个月）更长、产生反应的时间更短、总生存期更长。本研究注册于www.clinicaltrials.gov，NCT00742027。ABSTRACT In a phase 2 trial of panobinostat in 129 patients with relapsed or refractory Hodgkin lymphoma,exploratory analyses of chemokines and cytokines were prospectively performed in 109 patients to determine their association with clinical outcomes.Patients were categorized into 2 groups(reductions median and reductions median)based on percentage change from baseline of log10 transformed measurements.Thymus and activation-regulated chemokine(TARC)was most strongly associated with clinical outcome.Early reduction of TARC was observed in responding patients,with the greatest reduction at cycle 1,day 15(C1D15).Of 93 patients with C1D15 samples,there were 3 complete and 25 partial responses.The group with TARC reductions median at C1D15 had more responders(18 39%vs 10 21%),longer progression-free survival(PFS 10.6 vs 4.9 months),shorter time to response,and longer overall survival than the group with reductions median.This study is registered at www.clinicaltrials.gov,NCT00742027.返回目录 LYMPHOMA AUGUST 2013 14 Haematologica.2013 Jul;98(7):1014-21.Indications for Hematopoietic Stem Cell Transplantation in Patients with Follicular Lymphoma:A Consensus Project of the EBMT-Lymphoma Working Party.滤泡性淋巴瘤患者造血干细胞移植的标志:EBMT 淋巴瘤工作组的一项共识项目 Montoto S,Corradini P,Dreyling M et al.摘要 本项目旨在明确欧洲滤泡性淋巴瘤患者中造血干细胞移植的标志。在缺少基于数据证据的情况下，专家组采用了 RAND 改良 Delphi 程序。在预先明确表述之后，则采用 9 点量表，由每位参与者对其进行个人/匿名评分。达成共识如下：1）对于对临床试验之外免疫化学治疗产生应答的患者而言，自体干细胞挽救高剂量疗法并不是巩固首次缓解的适当选择；2）在首次化疗敏感复发的患者中，自体干细胞挽救高剂量疗法是巩固缓解的适当选择，在免疫化学治疗后具有短期缓解或者高危 FLIPI 患者中尤是；3）自体干细胞挽救高剂量疗法也适用于 II 期/随后化疗敏感复发的患者；4）应考虑以同种异体移植(最好是降低强度的同种异体移植)应对自体干细胞援救高剂量疗法后复发的患者。未达成共识的是，在低危首次复发或同种异体移植更可靠时使用自体干细胞挽救高剂量疗法的作用。在缺少基于数据证据的情况下，所采用共识方法是确定滤泡性淋巴瘤造血干细胞移植标志的一个有价值工具。ABSTRACT The aim of this project was to define indications for hematopoietic stem cell transplantation in follicular lymphoma in Europe.In the absence of evidence-based data,a RAND-modified Delphi procedure was used by an expert panel.After pre-defining statements,these were individually/anonymously scored by each participant using a 9-point scale.Consensus was reached that:1)high-dose therapy with autologous stem cell rescue is not an appropriate option to consolidate first remission in patients responding to immuno-chemotherapy outside clinical trials;2)in patients with first chemo-sensitive relapse,high-dose therapy with autologous stem cell rescue is an appropriate option to consolidate remission,especially in patients with a short response after immuno-chemotherapy or with high-risk FLIPI;3)high-dose therapy with autologous stem cell rescue is also appropriate in second/subsequent chemo-sensitive relapses;4)allotransplant(preferably a reduced intensity conditioning-allotransplant)should be considered at relapse after high-dose therapy with autologous stem cell rescue.No consensus was reached on the role of high-dose therapy with autologous stem cell rescue in low-risk first relapse,or on when an allotransplant should be preferred over high-dose therapy with autologous stem cell rescue.In the absence of evidence-based data,the consensus method used was a valuable tool to define indications for hematopoietic stem cell transplant in follicular lymphoma.返回目录 LYMPHOMA AUGUST 2013 15 Haematologica.2013 Jul;98(7):1003-13.Recognizing Nodal Marginal Zone Lymphoma:Recent Advances and Pitfalls.A Systematic Review.认识淋巴结边缘区淋巴瘤的最新进展和缺陷：一项系统性回顾 van den Brand M,van Krieken JH.摘要 淋巴结边缘区淋巴瘤的诊断仍是血液病理学中存在的难题之一。因为尚未建立该淋巴瘤的阳性标记物，所以在诊断中该淋巴瘤常常被漏诊，这使得其与低级 B 细胞淋巴瘤难以区分，甚至无法区分。本系统性回顾总结并讨论了目前淋巴结边缘区淋巴瘤的知识，包括临床特性、流行病学和病因学、组织学以及细胞遗传学与分子特性。我们特别讨论了在诊断和致病原因方面的近期进展。新的免疫组织化学标记物已经可用，能够作为淋巴结边缘区淋巴瘤的阳性标记物。在今后的研究中，这些标记物能够为更多的同类研究小组提供支持。近来有关基因表达的研究和描述特定基因突变的研究也为淋巴结边缘区淋巴瘤的致病原因提供了线索，暗示核因子 kB 通路的失调控。然而，淋巴结边缘区淋巴瘤仍然是一个迷，有待进一步的研究来明确其发病原因，从而达到准确诊断和个性化治疗的目的。然而，近期资料显示，淋巴结边缘区淋巴瘤与脾或淋巴结外淋巴瘤无关，也与淋巴浆细胞性淋巴瘤无关。因此，尽管淋巴结边缘区淋巴瘤的诊断并不总是容易掌控，但是其明确实一种独立性疾病。ABSTRACT The diagnosis of nodal marginal zone lymphoma is one of the remaining problem areas in hematopathology.Because no established positive markers exist for this lymphoma,it is frequently a diagnosis of exclusion,making distinction from other low-grade B-cell lymphomas difficult or even impossible.This systematic review summarizes and discusses the current knowledge on nodal marginal zone lymphoma,including clinical features,epidemiology and etiology,histology,and cytogenetic and molecular features.In particular,recent advances in diagnostics and pathogenesis are discussed.New immunohistochemical markers have become available that could be used as positive markers for nodal marginal zone lymphoma.These markers could be used to ensure more homogeneous study groups in future research.Also,recent gene expression studies and studies describing specific gene mutations have provided clues to the pathogenesis of nodal marginal zone lymphomasuggesting deregulation of the nuclear factor kappa B pathway.Nevertheless,nodal marginal zone lymphoma remains an enigmatic entity,requiring further study to define its pathogenesis to allow an accurate diagnosis and tailored treatment.However,recent data indicate that it is not related to splenic or extranodal lymphoma,and that it is also not related to lymphoplasmacytic lymphoma.Thus,even though the diagnosis is not always easy,it is clearly a separate entity.返回目录 LYMPHOMA AUGUST 2013 16 J Clin Oncol.2013 Jul 1.Intensive Chemotherapy and Immunotherapy in Patients with Newly Diagnosed Primary CNS Lymphoma:CALGB 50202(Alliance 50202).新确诊原发性 CNS 淋巴瘤患者的强化化疗和免疫治疗:CALGB 50202（Alliance 50202）Rubenstein JL,Hsi ED,Johnson JL et al.目的：对全脑放疗（WBRT）认知神经毒性的关注已促成了可替代剂量强化化疗方案作为原发性 CNS 淋巴瘤（PCNSL）巩固治疗的发展。在PCNSL 中，我们进行了不采用 WBRT 高剂量巩固治疗的多中心研究。本研究旨在明确：一，氨甲叶酸，替莫唑胺和利妥昔单抗联用（MT-R）进行缓解诱导治疗后的完全缓解率（CR）；二，使用依托泊苷