弥漫大B细胞淋巴瘤治疗进展:第56届美国血液学会年会报道

弥漫大B细胞淋巴瘤(DLBCL)是最常见的非霍奇金淋巴瘤(NHL)之一.自利妥昔单抗问世以来,利妥昔单抗联合化疗一直是DLBCL的一线治疗方案.诱导治疗可使70％左右的患者得到治愈,但仍有30％的患者不能经诱导缓解,特别是对于老年或高危患者,有望获得长期缓解的治疗方案有限,常表现为难治或早期复发.在第56届美国血液学会(ASH)年会报告中,对于复发难治、高危及特殊部位DLBCL治疗方面的进展做了详细的报道,现对其进行总结.     

弥漫大B细胞淋巴瘤研究最新进展

弥漫大B细胞淋巴瘤(DLBCL)是成年人发生率最高的淋巴瘤亚型,是一组高度异质性的肿瘤,不同亚型有不同的生物学特征、临床表现及治疗反应,患者预后差别很大,尽管目前的标准治疗R-CHOP方案为基础的免疫化疗使DLBCL治愈率提高,但仍有约40％的患者治疗早期即出现耐药或达到缓解后复发,预后差.本文结合第59届美国血液学会(ASH)年会有关报道,对DLBCL的新分子分型、新靶点药物研发、复发难治患者治疗等的研究进展进行总结.     

靶向药物治疗弥漫大B细胞淋巴瘤研究进展

弥漫大B细胞淋巴瘤(DLBCL)是侵袭性淋巴瘤中最常见的亚型, 复发难治DLBCL患者预后较差, 临床尚缺少有效的标准治疗方案。如何对复发难治DLBCL患者进行有效治疗一直是研究的热点, 目前的新药/技术研究包括双特异性抗体治疗、嵌合抗原受体T细胞(CAR-T)疗法、抗体偶联药物(ADC)治疗等。文章就第64届美国血液学会(ASH)年会关于DLBCL的靶向药物/细胞治疗进展进行综述。     

弥漫大B细胞淋巴瘤预后研究进展

弥漫大B细胞淋巴瘤(DLBCL)是最常见的非霍奇金淋巴瘤,具有高度异质性,高危患者预后差.如何更好地对DLBCL患者进行危险分层并早期识别高危患者是第58届美国血液学会(ASH)年会的一大热点.国际预后指数(IPI)作为经典的预后评分系统,在利妥昔单抗时代,其地位不断受到挑战,有多种新的预后评分系统被提出.分子生物学标记、基因突变在DLBCL的发生、发展中起重要作用,其预后价值备受关注.一些特殊DLBCL,如原发乳腺DLBCL、血管内大B细胞淋巴瘤、滤泡转化DLBCL以及复发难治DLBCL的预后也在该届年会上受到关注.     

GDP方案治疗复发难治外周T细胞淋巴瘤临床观察

目的:观察GDP方案治疗19例复发难治外周T细胞淋巴瘤的客观缓解率、不良反应.方法: 19例复发外周T细胞淋巴瘤患者采用GDP方案治疗3周期,观察客观缓解率、主要不良反应.结果: 19例患者CR 1例,PR 8例.RR 47.3%.获得缓解的9例患者,复发型8例,难治型1例.获得缓解的IPI低中危组3例,高中危组5例,高危组1例.低中危组与高危组组间差异显著(P<0.05).主要不良反应是骨髓功能抑制,其中III至IV度为4例(21.1%).III至IV度胃肠道反应为2例(10.5%).结论: GDP方案治疗复发外周T细胞淋巴瘤近期疗效确切,安全可行.     

IIVP方案治疗复发难治高危弥漫大B细胞淋巴瘤10例

目的 探讨IIVP方案[去甲氧柔红霉素(IDA)、异环磷酰胺(IFO)、依托泊苷(VP16)治疗复发难治、高危弥漫大B细胞淋巴瘤的治疗效果.方法 IFO 1 g/m2,静脉滴注,第1天至第5天,配合硫乙磺酸钠400 mg/次,0、3、6、9 h静脉推注4次,IDA 10 mg/m2,静脉推注,第1天至第2天,VP16 150 mg/m2,静脉滴注,第1天至第3天,每4周重复.每疗程后进行疗效评价.结果复发难治、高危弥漫大B细胞淋巴瘤10例,完全缓解(CR)2例,不确定的完全缓解(CRu)2例,部分缓解(PR)3例,有效率(cR+CRu+PR)70%.结论 IIVP方案治疗复发难治、高危弥漫大B细胞淋巴瘤可取得较高的缓解率,并为自体干细胞移植创造条件,进一步提高此类患者的治疗效果.     

年轻高危弥漫大B细胞淋巴瘤患者治疗研究进展

弥漫大B细胞淋巴瘤(DLBCL)是成年人淋巴瘤中最常见的一种类型,约占非霍奇金淋巴瘤(NHL)的30％～ 40％.年轻高危DLBCL患者是临床预后不良的一组特殊人群,目前在临床实践中尚无标准治疗方案,常规化疗、联合利妥昔单抗的R-CHOP、R-CHOP样方案、大剂量化疗及自体造血干细胞移植并未完全扭转其预后不良的现实.文章就年轻高危DLBCL患者的治疗现状及未来的治疗方向进行综述.     

泽布替尼联合利妥昔单抗及来那度胺治疗老年原发难治弥漫大B细胞淋巴瘤患者1例并文献复习

目的探讨泽布替尼联合利妥昔单抗及来那度胺方案治疗老年原发难治弥漫大B细胞淋巴瘤(DLBCL)患者的效果及安全性。方法回顾性分析郑州大学附属肿瘤医院2020年3月收治的1例伴有多个预后不良因素且对免疫化疗耐药的老年DLBCL患者的治疗经过, 并进行文献复习。结果患者, 女性, 70岁, 因右颈部肿物, 活组织检查确诊为DLBCL, 接受泽布替尼联合利妥昔单抗及来那度胺方案治疗后疾病快速获得缓解, 且缓解时间持久, 同时不良反应可耐受。结论泽布替尼联合利妥昔单抗及来那度胺方案治疗老年不适合自体移植的复发难治DLBCL患者安全有效, 为这部分患者提供了一种新的治疗方案。     

来那度胺联合利妥昔单抗治疗弥漫大B细胞淋巴瘤一例并文献复习

目的：提高对来那度胺联合利妥昔单抗（R2）为基础治疗弥漫大B细胞淋巴瘤（DLBCL）的认识。方法回顾性分析1例使用以R2为基础治疗的DLBCL患者的病例资料并复习相关文献。结果该患者为非生发中心来源的难治、复发DLBCL,接受R2联合化疗获得完全缓解,未见明显不良反应。结论 R2联合化疗治疗初治DLBCL可以显著提高缓解率,延长无进展生存期,改善非生发中心来源患者的不良预后。 R2方案对于难治、复发患者亦有效、安全。     

R-CHOP方案治疗复发、难治弥漫大B细胞淋巴瘤的临床研究

 【摘要】　目的　观察R-CHOP方案治疗复发、难治弥漫大B细胞淋巴瘤（DLBCL）的临床疗效及患者不良反应。方法　选择30例经病理证实为CD20阳性的DLBCL患者,前期常规方案化疗（不含利妥昔单抗）2～6个疗程后评估为复发或难治患者,其中复发患者16例,难治患者14例。应用R-CHOP方案治疗4～6个周期,每个周期21 d。所有淋巴瘤患者均为Ⅲ～Ⅳ期,搜集治疗前后相关临床资料,采用回顾性分析方法,将R-CHOP方案疗效与文献及自身对照比较,评价其疗效及不良反应。结果　全组30例患者均可评价疗效,完全缓解15例,部分缓解10例,稳定3例,进展2例,完全缓解率为50.0 %（15／30）,总有效率83.3 %（25／30）。出现Ⅱ度白细胞减少3例,Ⅰ度血小板降低1例,恶心等轻微的消化道反应2例。结论　R-CHOP方案对复发、难治DLBCL仍有良好的治疗效果,完全缓解率与总有效率明显优于常规二线化疗方案。接受R-CHOP方案治疗患者不良反应轻微,与常规化疗方案无显著区别,患者耐受良好。     

弥漫性大B细胞淋巴瘤免疫治疗进展

弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）是最常见的非霍奇金淋巴瘤（NHL）亚型,其具有高度异质性和侵袭性。尽管许多患者应用R-CHOP(利妥昔单抗+环磷酰胺+阿霉素+长春新碱+泼尼松)方案一线治疗后达到完全缓解（CR）,但仍有部分患者之后发展为复发和难治性的DLBCL,而一旦发展为复发难治性的DLBCL,常规的放疗和化疗则收效甚微。近年来,免疫治疗逐渐成为研究热点,如单克隆抗体治疗、双特异性抗体治疗、抗体-药物偶连物（ADC）治疗和嵌合体抗原受体修饰T细胞（CAR-T）治疗等。本文现就弥漫性大B细胞淋巴瘤免疫治疗进展进行综述。     

弥漫大B细胞淋巴瘤预后研究进展：第57届美国血液学会年会报道

弥漫大B细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤类型,具有高度异质性,识别高危患者尤为重要,如何更好地区分判断患者的预后成为第57届美国血液学会（ASH）年会的一大热点。国际预后指数（IPI）作为经典的预后积分系统,其地位不断受到挑战,有多种新的预后积分体系被提出;肿瘤微环境在淋巴瘤进展中起重要作用,其对预后的判断价值也受到越来越多的重视;PET-CT对DLBCL的预后价值在本届会议中也得到进一步肯定。     

Factors affecting survival in patients aged 60 and over with diffuse large B cell lymphoma failing first-line therapy

ObjectivesElderly patients with diffuse large B cell lymphoma (DLBCL) without prohibitive co-morbidities may be cured with standard immuno-chemotherapeutic regimens, as used in younger patients. Less is known about the survival prospects in older people, if first-line therapy fails. This study aimed to provide additional information regarding prognosis in this group.Materials and MethodsDatabases were collated from three randomized trials of first-line therapy in those aged 60 and over, deemed fit enough for standard therapy. Overall survival from the point of treatment failure was calculated and comparisons were made between age groups and types of treatment failure.ResultsOverall survival (OS) at 2 years in 862 patients was 46%, 38%, 37% and 23%, respectively, for those aged 60–64, 65–69, 70–74 and > 74. Type of treatment failure impacted on 2 year OS as follows: initial partial remission (PR): 48%; complete response (CR) with late relapse: 37%; CR with early relapse: 17%; and less than PR to initial therapy: 12%.ConclusionOlder patients failing first-line therapy for DLBCL should be counseled differently regarding prognosis depending upon age and type of treatment failure. The chance of survival was greater in those achieving PR or CR with relapse more than 12 months from diagnosis. This data may support the consideration of aggressive salvage therapy in fit patients in these categories, regardless of biological age per se. Palliative management may be more appropriate for those achieving less than PR to initial therapy or who enter CR but relapse within one year of diagnosis.     

Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma and despite recent chemotherapeutic advances up to half of all patients relapse. Here we report the results from a phase 2, single-arm, single-center trial evaluating the safety and efficacy of lenalidomide plus rituximab in elderly patients with relapsed or refractory DLBCL.Patients and MethodsBetween March and June 2009, elderly patients (65 years of age or older) with relapsed/refractory DLBCL who had been heavily pretreated were recruited. Oral lenalidomide (20 mg/d for 21 days of each 28-day cycle) was initiated for four cycles and rituximab (375 mg/m²) was administered on day 1 and day 21 of each 28-day cycle for four cycles. After this induction phase, patients achieving a complete response (CR), partial response (PR), or stable disease (SD) were given lenalidomide maintenance therapy at the same schedule for another 8 months.ResultsA total of 23 patients with a median of three prior treatments (range, 2 to 8) were included. The overall response rate (CR + PR) at the end of the induction phase was 35% (n = 8). Ten patients (7 CR, 1 PR, and 2 SD patients) were eligible for lenalidomide maintenance and 8 of these patients achieved a CR. Adverse events were manageable and the most common included neutropenia and thrombocytopenia.ConclusionOral lenalidomide in combination with rituximab is active in elderly patients with relapsed/refractory DLBCL with a high percentage of patients achieving a continuous CR after lenalidomide maintenance.     

High-dose chemotherapy as primary treatment for poor-risk germ-cell tumors: the Memorial Sloan-Kettering experience (1988-1999)

Although the majority of patients with poor-risk germ-cell tumors (GCTs) will achieve a durable complete remission (CR) with standard first-line therapy, 20% to 30% of them will either relapse or fail to achieve an initial CR and eventually die. For this reason, the strategy of using high-dose (HD) chemotherapy with autologous stem-cell support has been investigated to improve the chances of cure attainable in the salvage setting, but at a cost of significant morbidity and mortality. Treatment using HD therapy in the first-line setting offers the promise of reducing morbidity and mortality while increasing efficacy. At Memorial Sloan-Kettering Cancer Center (MSKCC), trials were conducted to test this hypothesis. Patients at high risk of relapse following conventional therapy were identified, based on post-treatment serum marker concentrations that failed to appropriately decline by predicted half-life after several cycles of standard treatment. These patients received first-line HD treatment. Patients received a 2-drug HD regimen in one trial and an intensified 3-drug regimen in another, each with autologous bone marrow transplantation. These patients had improved overall and event-free survival rates (p = 0.001 and 0.003, respectively) compared with historical controls who underwent standard first-line treatment, with a lower incidence of treatment-related mortality than patients who received HD therapy in the salvage setting. Randomized trials are under way to prospectively verify these results.     

Elevated lactate dehydrogenase levels detected during routine follow-up do not predict relapse in patients with diffuse large B-cell lymphoma who achieve complete remission after primary treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone-like immunochemotherapy

Abstract A significant minority of patients with diffuse large B-cell lymphoma (DLBCL) who enter a complete remission following standard first-line immunochemotherapy will relapse. A primary aim of follow-up is to detect early relapse, with the hope of improving outcome following salvage chemotherapy. It is often routine to measure lactate dehydrogenase (LDH) as part of follow-up; however, the evidence for the utility of LDH as a predictor for relapse is scant. A retrospective analysis of the LDH results recorded during the follow-up of 102 patients with DLBCL who achieved a CR following treatment was undertaken in order to determine the utility of LDH as a predictor for relapse (median follow-up 24 months). Despite the fact that the sensitivity of LDH was 69% (95% confidence interval [CI] 39-91), the positive predictive value (PPV) of a raised LDH was only 9/63, 14% (95% CI 6.7-25). Furthermore, in eight of the nine patients who had a raised LDH prior to relapse, symptoms suggestive of relapse were documented simultaneously. As the PPV of a raised LDH is so low and because a raised LDH may cause unnecessary worry, leading to unnecessary radiological investigations, routine evaluation of LDH in patients with DLBCL who achieve CR and who are asymptomatic is not recommended.     

Late-onset neutropenia following primary treatment of diff use large B-cell lymphoma with rituximab-containing therapy

Abstract Late-onset neutropenia (LON) following rituximab therapy is a recently recognized adverse effect occurring in various clinical settings. However, the true incidence and pathogenesis of this adverse effect are not fully understood. We retrospectively reviewed the medical records of 160 patients with diffuse large B-cell lymphoma (DLBCL) in complete remission (CR) following first-line treatment with rituximab-containing therapy. The incidence of LON was 26.9% (grade 1, 2, 3 and 4) and the incidence of severe LON (grade 3 and 4) was 7.5%. The risk factors for the occurrence of LON were not identified, and overall survival did not differ between patients who developed LON and those who did not. This study suggests that LON is a quite common complication to rituximab therapy. However, more studies are needed in order to elucidate the true mechanism behind and risk factors for LON.     

精准医疗时代利用组织病理报告指导弥漫大B细胞淋巴瘤的初始治疗：第57届美国血液学会年会报道

弥漫大B细胞淋巴瘤（DLBCL）是西方国家非霍奇金淋巴瘤中最常见的亚型,采用标准R-CHOP方案化疗可达到治愈。我们目前处于一个可从遗传学和分子学定义DLBCL异质性的时代,临床试验的目标是给予不同亚型患者合理的特异性治疗。原发性纵隔DLBCL是一种独特的临床病理类型,给予R-CHOP方案可达到良好疗效。但10%的DLBCL患者中存在myc基因重排,即使给予标准R-CHOP方案也存在预后不良,特别是同时存在bcl-2基因重排者,即双打击DLBCL。免疫组织化学显示DLBCL中一个较大的亚群同时存在myc和bcl-2的过表达。通过基因表达谱、免疫组织化学或新的Lymph2Cx方法可分析细胞的来源,以提供预后信息,指导初治和复发患者治疗方案的制定。文章介绍了2015年第57届美国血液学会（ASH）年会报道的关于如何定义DLBCL的特殊亚型及提供特异性的治疗方案,包括目前正在研究中的新方案。了解病理报告的关键特征和DLBCL亚型检测方法的局限性有助于DLBCL的精准治疗。