滤泡性淋巴瘤研究进展

滤泡性淋巴瘤(FL)起源于生发中心B细胞,是我国最常见的惰性B细胞非霍奇金淋巴瘤(NHL),目前仍是一种不可治愈的疾病.在第59届美国血液学会(ASH)年会上,FL为NHL领域报道最多的亚型.目前FL的研究热点为诱导后维持治疗、新药联合诱导治疗及维持治疗、去化疗治疗FL以及寻找新的预后生物学标志.     

原发性皮肤滤泡性淋巴瘤研究进展

邱丙森教授于上世纪 5 0年代初即已从事皮肤病学基础研究与临床实践 ,半个世纪以来 ,在该领域进行了坚持不懈的努力 ,获得了丰硕成果 ,为我国皮肤病学资深专家。本文综述了皮肤滤泡性淋巴瘤 ( CFL )近年来的研究进展 ,特别是对原发性皮肤滤泡性淋巴瘤 ( PCFL)的诊断要点以及与 B-小淋巴细胞淋巴瘤、套细胞淋巴瘤、B细胞淋巴样增生和皮肤边缘区淋巴瘤的鉴别进行了较为全面的阐述 ,对病理与临床医师有一定的参考价值。现将邱丙森教授应约为本刊撰写的“原发性皮肤滤泡性淋巴瘤研究进展”一文刊登于此 ,以飨读者     

滤泡性淋巴瘤预后因素的研究进展

滤泡性淋巴瘤(follicular lymphoma,FL)是一组在生物学特征、临床表现及预后等方面存在高度异质性的血液肿瘤,多种因素影响其预后。既有的FL预后模型,包括滤泡淋巴瘤国际预后指数(follicular lymphoma international prognostic index,FLIPI)、FLI PI-2等主要强调基线临床及实验室检查特点对预后的影响,且价值有限。近年来随着分子影像学、基因测序等现代技术的发展,肿瘤代谢负荷参数、分子生物学特征(如肿瘤微环境特点、表观遗传学改变等)等在FL预后预测方面的价值逐渐被挖掘,尤其与既有临床预后指数结合(如包含7个基因突变情况的临床遗传学风险模型m7-FLIPI)时更是提高了预测的准确性。除基线预后因素外,FL治疗反应的预后价值也是近年来研究的热点。本文根据国内外研究进展,从组织学特点、肿瘤代谢负荷、基于临床特征建立的预后模型、肿瘤微环境、治疗反应、分子遗传学特征等方面对影响FL患者预后的因素进行综述。     

滤泡淋巴瘤治疗研究进展

滤泡淋巴瘤（FL）是起源于滤泡生发中心的惰性非霍奇金淋巴瘤。第58届美国血液学会（ASH）年会上,多篇研究报道了FL治疗的最新进展。 GA101联合化疗、苯达莫司汀（BR）联合90Y替伊莫单抗（90YIT）治疗中晚期FL的临床试验结果鼓舞人心;自体造血干细胞移植与非清髓同种异基因造血干细胞移植（allo-SCT）序贯治疗给复发、难治的FL患者带来更好的疗效,PI3K抑制剂、bcl-2抑制剂、抗体-药物共轭物等新药接连涌现,复发、难治FL的治疗效果和缓解程度不断提高。     

复发难治性滤泡性淋巴瘤研究进展

滤泡性淋巴瘤（FL）是一种起源于滤泡生发中心的惰性非霍奇金淋巴瘤。复发难治性FL通常需要多线治疗,随着新药的不断问世和一大批临床试验的进行,FL的治疗模式也在发生改变。大剂量治疗联合造血干细胞移植给复发难治性FL患者带来了更好的效果,PI3K抑制剂、程序性死亡受体1（PD-1）抑制剂、来那度胺、抗体-放射性核素共轭物等新药随着临床试验的进展也为FL患者的治疗提供了更多的选择。     

滤泡型淋巴瘤的治疗进展

滤泡型淋巴瘤（Follicular lymphoma,FL）是最常见的惰性淋巴瘤,通常认为单纯化疗不能治愈该病。单克隆抗体的引入使FL治疗发生了革命性变化,多个临床试验显示FL病人的无病生存率和总体生存率明显提高。     

滤泡型淋巴瘤的治疗进展

滤泡型淋巴瘤(Follicular lymphoma,FL)是最常见的惰性淋巴瘤,通常认为单纯化疗不能治愈该病.单克隆抗体的引入使FL治疗发生了革命性变化,多个临床试验显示FL病人的无病生存率和总体生存率明显提高[1].     

滤泡性淋巴瘤与反应性淋巴滤泡增生的免疫组化及DNA图像分析研究

目的：观察滤泡性淋巴瘤（ＦＬ）与反应性淋巴滤泡增生（ＲＦＨ）中滤泡生发中心细胞（ＧＣＣｓ）核ＤＮＡ含量、倍体情况以及ｂｃｌ－２癌基因蛋白、免球蛋白轻链（ＩｇＬ）表达情况，探讨它们对于二都鉴别诊断的意义。方法：对２１例ＦＬ及２１例ＲＦＨ进行ｂｃｌ－２蛋白、Ｋｆｐｐａ、Ｌａｍｂｄａ轻链蛋白免疫组化检测及ＤＮＡ图像细胞分析。结果：６１．９％ＦＬ中ＧＣＣｓ有ｂｃｌ－２表达而ＲＦＨ的ＧＣＣｓ均为ｂｃｌ－２阴     

Excessive toxicity of the high dose thiotepa and etoposide regimen when combined with radiation: Long-term autologous transplantation experience in follicular and mantle cell lymphoma

We recently described a novel thiotepa plus etoposide high-dose therapy (HDT) conditioning regimen for aggressive histology non-Hodgkin's lymphoma (NHL) that had low regimen-related toxicity (RRT) and an efficacy rate comparable to other NHL HDT regimens. In this report, we describe the UW experience with the addition of total body irradiation (TBI) and pre-transplant involved-field radiation (IFRT) to the thiotepa + etoposide HDT regimen. Between 1992 and 1999, 28 patients with indolent or mantle cell lymphoma were treated on this protocol. With a median follow-up of 64 mo, the median event-free survival (EFS) was 24 months, and the median overall survival (OS) had not been reached. The median number of grade 3  -  4 non-hematologic toxicities was five. There were five deaths (18%) in the first three months after HDT due to RRT. In contrast, the thiotepa + etoposide conditioning regimen (without TBI or IFRT) given to 65 intermediate grade NHL patients resulted in only one treatment-related death and considerably fewer grade 3  -  4 toxicities. Given the relatively short EFS in this cohort of indolent NHL patients, we conclude that the combination of IFRT and TBI plus thiotepa and etoposide resulted in a HDT regimen with excessive toxicity and this protocol was closed at our institution.     

Fludarabine in Alkylator-Resistant Follicular Non-Hodgkin's Lymphoma

Follicular small cell and follicular mixed small and large cell lymphoma (FL) are incurable with conventional chemotherapy, and generally follow a relapsing course, eventually becoming resistant to first-line therapy with alkylating agents. Fludarabine is a novel chemotherapeutic agent that is effective in FL, but its role in alkylator-resistant disease remains unclear. We conducted a retrospective review of all patients with alkylator-resistant FL treated with fludarabine. Patients were identified from pharmacy records and included if they fulfilled criteria for alkylator-resistant FL. Resistance was defined as failure to achieve a partial response, progression while on therapy, or relapse within six months of completing therapy. Seventeen patients met the criteria of alkylator-resistant FL and were included in the analysis. All patients received fludarabine 25 mg/m² for five days. A median of 2.5 courses of fludarabine was given. One patient had a complete remission and eight patients had partial remissions, for an overall response rate of 53%. Median progression-free survival was 5.4 months and median overall survival was 15.4 months for all patients. Four patients underwent subsequent autologous stem cell transplantation; all required additional salvage chemotherapy for post-fludarabine relapses. Three patients remain in remission more than 12 months post-transplantation. Fludarabine produces partial responses in patients with advanced refractory FL; however, the duration of the response limits its utility in alkylator-resistant disease.     

Follicular large cell lymphoma: long-term follow-up of 62 patients treated between 1973-1981.

Purpose:Investigators disagree on whether follicular large celllymphoma (FLCL) behaves like other follicular lymphomas, with no plateau inthe survival curve, or as a more aggressive but potentially curable lymphoma.We reported in 1984 results for 62 FLCL patients treated at our institution;the current report updates those results. Patients and methods:Sixty-two patients referred from1973–1981, including fifteen (24%) patients with Ann Arbor stageI–II and forty-seven (76%) with stage III–IV FLCL. Sevenpatients received radiation (XRT) alone, forty patients XRT and chemotherapy,and fifteen patients received chemotherapy alone. Results:The median follow-up was 14.7 years. The median survivalwas 5.1 years, with 21% alive at 15 years. The failure-free survival(FFS) at 10 years was 31%. Univariate analysis revealed that age, AnnArbor stage, and the International Index correlated with survival. Performancestatus, number of platelets, and LDH correlated with failure-freesurvival. Conclusions:FLCL responds to doxorubicin-based regimens similarlyto diffuse large cell lymphoma. Patients with FLCL have the potential forprolonged failure-free survival. Variables that predict the survival inaggressive lymphomas apply as well in this type of lymphoma.     

Follicular lymphoma: an Institutional Analysis

Background: Follicular lymphoma (FL) is second most common lymphoma in adult, constituted 20% of all lymphoma cases in the west. There is limited information is available on FL from India. Methods: The clinico-pathological profile, treatment outcome and prognostic factors for survival were assessed retrospectively in 181 patients of FL seen at our center over a period of 17 years ( 1996-2012). Results: There were 120 males and 61 females. The median age was 51 years (24-80 years). The common presenting features were lymphadenopathy 71%, fatigue 23% and fever 20%. Ann Arbor stage distribution was: stage I - 9%, stage II - 11%, stage III -22 % and stage IV - 58%. Extra nodal involvement and bulky disease were present in 22% and 19% patients respectively. Follicular Lymphoma International Prognostic Index (FLIPI) 1 score : Low -25%, Intermediate-45% and high risk in 30% of cases. One forty five patients (80%) received treatment at presentation or during follow-up. Chemotherapeutic regimen used were: CHOP-45 , CVP-51, chlorambucil and prednisolone -7 , BR ( bendamustine and rituximab)-12, RCHOP- 14 RCVP – 7 and other regimen were used in 5 cases. The overall response (ORR) and complete remission (CR) rates were 70% and 35% respectively. Median overall survival (OS) and event free survival (EFS) was 5.5 years and 2.5 years respectively, with median follow up period of 3.0 years. Grade 3 histology, failure to attain CR, low serum albumin, and high risk FLIPI were significantly associated with lower event free survival. High risk FLIPI (HR 1.46, 95% CI 1.03-2.10, p=0.003) and failure to attain CR (HR 2.64, CI 1.10-4.30, p=0.001) were predictors of poor OS. Conclusions: FL represents 9 % of all lymphoma in adult. This is the largest data from single institute from India. Eighty percentage of patients presented in stage III/IV disease. High risk FLIPI and failure to attain CR were important prognostic variables for OS.     

大剂量化疗联合自体造血干细胞移植治疗淋巴瘤的疗效

目的:观察大剂量化疗联合自体造血干细胞移植治疗恶性淋巴瘤的疗效。方法:选择2009年12月－2015年12月于我科住院治疗的恶性淋巴瘤病例30例,均接受大剂量化疗联合自体造血干细胞移植治疗。结果:1例患者造血干细胞回输后因严重肺部感染死亡,其余均成功植入并快速重建造血;随访至2016年3月1日,有22例存活,无病生存19例,9例复发,中位复发时间为4.5(1~15)个月,其中6例复发后3年内死亡,2例治疗后重新评估为CR随访至今未再复发,1例为单一椎体复发至今仍存活。移植相关死亡率为6.7%。结论:大剂量化疗联合自体造血干细胞移植能很快重建造血,是治疗恶性淋巴瘤安全有效的方法。     

自体干细胞移植支持下的大剂量化疗一线治疗恶性淋巴瘤

背景与目的:目前自体干细胞移植(autologous stem cell transplantation,ASCT)支持下的大剂量化疗(high-dose chemotherapy,HDC)已成为复发或难治性恶性淋巴瘤(malignant lymphoma,ML)的标准治疗方法,但是对于一些选择的ML是否可作为一线治疗方案目前尚不明确.本文旨在通过回顾性分析探讨HDC/ASCT作为一线方案治疗ML的疗效.方法:自2000年9月至2007年6月, 连续收治28例ML患者,中位年龄32岁(8～60岁),其中男性17例,女性11例.组织学类型包括24例非霍奇金淋巴瘤,4例霍奇金淋巴瘤.自体外周血干细胞动员采用化疗药物联合重组人粒细胞集落刺激因子方案.HDC方案采用BEAC(BCNU、CTX、Ara-C 、VP-16)方案.随访日期自干细胞回输之日期开始,末次随访日期为2007年7月30日.结果:28例患者均移植成功,重建造血功能.移植前CR 14例,PR 14例,移植后CR 22例,PR 6例.随访截止日期为2007年7月30日,中位随访时间为28个月(1.5～82个月),移植后4例病情进展,其中2例死亡,3年生存率及无进展生存率分别为89%和76%.大剂量化疗期间不良反应均可耐受,无移植相关死亡.结论:HDC/ASCT作为一线方案治疗ML是安全、可行及有效的治疗方法.     

利妥昔单抗时代滤泡性淋巴瘤移植治疗的现状及前景

 滤泡性淋巴瘤（FL）是来源于滤泡生发中心的B细胞淋巴瘤。作为最常见的惰性淋巴瘤,FL总体预后较好,但其转归又具有异质性。利妥昔单抗的应用改善了疾病的疗效和预后。对于复发、难治患者,尤其是前期接受过含利妥昔单抗的一线方案治疗者,移植治疗是其重要选择。与传统清髓性预处理方案相比,减低强度预处理（RIC）方案降低了非复发死亡（NRM）率,扩展了可接受异基因移植的患者选择,但移植后复发率偏高是其主要缺陷。移植后应用供体淋巴细胞输注治疗可以减少和治疗疾病复发。未来,移植策略改进和新药应用会为FL治疗带来新的思路和机会。     

Intensified therapy followed by autologous stem‐cell transplantation (ASCT) versus conventional therapy as first‐line treatment of follicular lymphoma: a meta‐analysis

There are two different international standards for the treatment of follicular lymphoma (FL): intensified therapy followed by autologous stem‐cell transplantation (ASCT) and conventional therapy in the first‐line setting. However, their role remains unclear. Our aim was to define the treatment effect of intensified therapy followed by ASCT compared with conventional therapy as first‐line treatment of patients with FL in terms of overall survival (OS) and event‐free survival (EFS). We searched for randomised controlled trials in Medline, Embase, the Cochrane controlled trials register and the Science Citation Index (1985 to June 2011). Effect measures used were hazard ratios (HR) for OS, EFS and secondary tumour rate. Two independent review authors extracted data and assessed quality of trials. Four trials were identified, covering a total of 941 subjects. The random‐effects summary HR by comparing the treatment effect on OS between intensified and conventional therapy was 0.95 [0.70, 1.30] (p = 0.75), indicating that no additional survival benefit was derived from the intensified therapy followed by ASCT. A significant benefit of intensified therapy followed by ASCT as first‐line treatment was detected in terms of EFS: the random‐effects summary HR (intensified versus conventional therapy) was 0.59 [0.44, 0.79] (p < 0.001). This meta‐analysis showed that despite its superior EFS, intensified therapy followed by ASCT does not improve the OS compared with conventional therapy. Copyright © 2012 John Wiley & Sons, Ltd.     

高剂量化放疗联合自体造血干细胞移植治疗霍奇金淋巴瘤11例报告

背景与目的：高剂量化放疗（high dose chemoradiotherapy,HDT)联合自体造血干细胞移植（autologous hemotopoietic stem cell,ASCT)巳成为复发与耐药霍奇金淋巴瘤（HL）患者重要的解救治疗手段之一,但对于初治晚期患者的作用还不明确。本论文的目的是进一步评价HDT联合ASCT在HL综合治疗中的地位,特别是探讨其对于初治晚期具有明显不良预后因素患者的作用。方法：11例复发和具有不良预后因素的晚期HL患者,其中初始9例,复发2例;自体骨髓移植（autologus bone marrow transplantation,ABMT)1例,自体外周血干细胞移植（autologous peripheral bllod stem cell transplantation,APBSCT)10例。诱导治疗后4例完全缓解（CR）,7例部分缓解（PR）。7例采用高剂量化疗联合全身照射（total body irradiation,TBI)或全淋巴结照射（total lymph node irradiation,TLI)/次全淋巴结照射（subtatal lymph node irradiation,STLI)作用预处理方案,4例采用单纯高剂量化疗作为预处理方案。5例患者于移植后进行了原发部位的补量放疗。结果：移植前达CR者为巩固治疗,达PR后移植后2例达CR,1例达PR,4例稳定（SD）;SD者均为骨受侵。中位随访13（1-84）个月,所有患者全部生存。4例无病生存;4例骨受侵者疾病无进展生存;3例复发,其中1例经复发部位放疗后,目前又无瘤生存42个月,另外2例正进一步治疗中;根据寿命表法分析,全组6年累积疾病无进展生存率（progression-free survival,PTS)为55.68%,6年累积总生存率（OS）为100%;初治患者6年PFS为62.5%。移植相关毒性主要为IV度骨髓抑制,未见明显心、肝、肾毒性,无移植相关死亡。结论：HDT联合ASCT是治疗复发和具有不良预后因素的晚期HL的一种值得进一步探讨的方法。