原发系统型间变性大细胞淋巴瘤48例临床特征及预后分析

目的:探讨原发系统性间变大细胞淋巴瘤(ALCL)患者的临床特征及预后影响因素.方法:回顾性分析2013年1月-2021年3月于北京协和医院诊治的48例ALCL患者的临床资料.结果:48例患者中男31例,女17例,中位发病年龄37(18～79)岁.ALK+ ALCL 14例(29.2％),ALK-ALCL 34例(70....     

Caspase-3和Bcl-2在间变性大细胞淋巴瘤中的表达

选择30例间变性大细胞淋巴瘤（ALCL）患者标本，检测其Caspase-3、Bcl-2的表达情况，发现Caspase-3、Bcl-2在间变性淋巴瘤激酶（ALK）阳性组中表达率分别为92．9％（13／14）和7．1％（1／14），ALK阴性组中分别为50％（8／16）和62．5％（10／16），两组比较差异均有统计学意义（P〈0．05），提示ALCL患者预后与凋亡传递途径有关。     

12例间变性淋巴瘤激酶阳性间变性大细胞淋巴瘤临床分析

目的:分析间变性淋巴瘤激酶(ALK)阳性间变性大细胞淋巴瘤(ALCL)的临床特征,探讨治疗效果、预后影响因素及临床治疗方案。方法:收集2014年12月—2021年12月在徐州医科大学附属医院初治的12例ALK⁺ALCL患者的临床资料,回顾性分析其临床特点、治疗效果及预后生存情况。结果:12例患者的中位发病年龄为28(14～45)岁,其中男11例。11例(91.67%)患者初诊时评估晚期(Ⅲ～Ⅳ期),7例(58.33%)患者合并B症状,5例(41.67%)患者LDH升高,4例(33.33%)患者以浅表淋巴结肿大为首发部位,7例(58.33%)患者伴有腹腔淋巴结肿大。6例(50.00%)患者伴有结外侵犯,3例(25%)患者≥2个结外部位侵犯。2例(16.67%)患者IPI评分为高中危/高危组(3～5分);7例(58.33%)患者aaIPI评分为高中危/高危组(3～5分)。Ki-67≥80%、结外侵犯≥2处、aaIPI 3～5分、一线化疗方案是影响初始化疗后达CR的不良因素。CRP升高、结外侵犯≥2处、IPI 3～5分、aaIPI 3～5分、Ki-67≥80%、一线化疗...     

结缔组织病合并原发骨间变性大细胞淋巴瘤1例并文献复习

<正>间变性大细胞淋巴瘤(anaplastic large cell lymphomas,ALCL)属于非霍奇金淋巴瘤的一种特殊类型,约占非霍奇金淋巴瘤的2%~8%,属于侵袭性淋巴瘤。Stein等〔1〕最初于1985年对其命名,并描述了其组织学特征。ALCL分为原发系统型和皮肤型两种类型,原发系统型根据肿瘤细胞是否表达间变淋巴瘤激酶(ALK)分为ALK+ALCL和     

23例间变性大细胞淋巴瘤临床特征及预后分析

目的探讨间变性大细胞淋巴瘤（ALCL）的临床特征和免疫组化特点,并分析其预后因素。方法收集23例ALCL患者的临床资料。从临床特征和预后因素等几方面进行回顾性分析。结果本文完全缓解率68.75%,3 a生存率为60.82%;单因素分析显示,Ann Arbor分期、LDH及国际预后指数（IPI）与疾病预后相关。IPI≥3是ALCL的独立的预后不良因素。结论Ann Arbor分期、LDH与国际预后指数对预测患者长期生存和指导治疗有重要意义。     

间变性大细胞淋巴瘤的临床细胞病理学分析

目的:探讨间变性大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)的临床细胞病理学特点、免疫表型及鉴别诊断,提高对ALCL的认识。方法:分析经组织病理学证实的13例ALCL的临床表现、细胞病理学形态及免疫表型,并结合相关文献进行讨论。结果:13例ALCL患者中,ALK阳性11例,ALK阴性2例;全部表达CD30,部分表达EMA、CD3、CD45RO、CD43,不表达CD3、CD56、CD20、CD79a、PCK、CD117;Ki67LI 60%~100%。结论:ALCL是一种少见的非霍奇金淋巴瘤,依据其细胞病理学形态特征,细胞病理学可以做出正确的诊断,但应注意与霍奇金淋巴瘤、弥漫大B细胞淋巴瘤、恶性黑色素瘤、未分化癌等进行鉴别;当鉴别诊断有困难时,应行活检及免疫组织化学染色以确诊。     

间变性淋巴瘤激酶阴性的间变性大细胞淋巴瘤1例

<正>间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)阴性的间变性大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)极为少见,我院近期收治1例,现已完成1个周期CDOP方案(环磷酰胺CTX Cyclophosphamide 1.0,d 1、脂质体阿霉素PLD Pegylated Liposomal Doxorubicin 30 mg,d 1、长春地辛VDS Vindesine 3 mg,d 1、地塞米松片DEX Dexamethasone,15mg,d 1)及5个周期CHOP化疗方案(环磷酰胺CTX Cyclophosphamide 1.0,d 1,吡柔比星THP theprubicin,     

老年恶性淋巴瘤的临床特点和疗效分析

目的:探讨老年恶性淋巴瘤(ML)的临床特点、治疗及国际预后指数(IPI)的应用价值。方法:回顾性分析1998~2003年间59例首程治疗的老年ML患者的临床资料。本组患者37例接受治疗,大部分单纯采用联合化疗的方法,部分采用局部放疗加化疗或手术后加化疗的方法。结果:59例ML患者1、3、5年生存率分别为77.9%(46/59),41.1%(23/56),9.4%(5/53),而治疗组1、3、5年生存率分别为81.1%(30/37),45.9%(17/37),13.5%(5/37),其中存活5年以上者均为达完全缓解(CR)者。非霍奇金淋巴瘤(NHL)根据IPI分组,低危组、低中危组、中高危组、高危组中位生存期(MST)分别为88个月、60个月、52个月、6个月,其生存时间差异有统计学意义(P<0.01),各组之间的CR率也存在统计学意义(P<0.01)。Cox多因素分析显示,影响预后的独立因素为病理类型和IPI。结论:IPI是判断老年ML预后的重要指标,老年ML仍应考虑积极的综合治疗。     

间变大细胞淋巴瘤的诊疗进展

正间变大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)是一种临床少见且异质性明显的恶性肿瘤,约占成人非霍奇金淋巴瘤的3%及儿童淋巴瘤的10%~15%~([1-2])。1985年Stein等~([3])首先将一组高表达CD30(Ki-1)、以大细胞增殖为主的淋巴瘤命名为ALCL。Morris等~([4])发现了ALCL中最常见的染色体异常t(2;5)(p23;q35),即2号染色体上的间变淋巴瘤激酶(ALK)基因和5号染色体上的核磷蛋白基因融合产生了融合基因NPM-ALK。根据ALK蛋白的表达状态,可将     

CTOP与CHOP方案治疗老年非霍奇金淋巴瘤的临床对照研究

目的:探讨CTOP方案治疗初治的老年非霍奇金淋巴瘤(NHL)患者的疗效,缓解率、不良反应,T-cell淋巴瘤的有效率.方法:2002年1月～2006年1月我院收治的64例老年NHL,随机分为A、B 2组,A组:CTOP方案(环磷酰胺加吡柔比星加长春新碱加泼尼松),B组:CHOP方案以同等剂量的阿霉素(ADM)取代THP,余同A组.完成4周期后,根据病情放疗或加用博来霉素化疗.结果:A组完全缓解(CR) 71.9%,T-cell淋巴瘤CR 76.5%,2年总生存率53.1%.B组CR 62.5%,T-cell淋巴瘤CR47.1%,2年总生存率50%.A、B 2组比较CR率及2年生存率差异无统计学意义(均P>0.05),但T-cell淋巴瘤,CTOP方案优于CHOP方案,其CR率A组、B组分别为76.5%∶47.1%(P<0.01),脱发及心脏毒性CHOP增加.结论:CTOP方案适合老年NHL的治疗,尤其是对T-cell淋巴瘤有优势,明显降低毒性反应,尤其是心脏毒性反应.     

Anaplastic large cell (CD30/Ki-1+) lymphoma in HIV+ patients: clinical and pathological findings in a group of ten patients

We compared the clinical and pathological features of 10 HIV⁺ CD30⁺ anaplastic large cell lymphoma (ALCL) patients with 28 HIV⁺ CD30⁺ non-Hodgkin's lymphoma (NHL) patients. The incidence of ALCL among 38 HIV⁺ systemic NHL patients was 26%. Clinical features were similar in all the HIV-related NHL cases, but ALCL patients seemed to differ from HIV⁺ CD30⁻ systemic NHL only in the greater frequency of lung tumours (40% v 21%) without concomitant mediastinal mass, bone marrow (75% v 18%) and gastroenteric involvement (40% v 25%). Among the HIV⁺ ALCL patients, histologic subtypes did not differ in frequency from ALCL in the general population. The B phenotype was predominant (50%) as in other HIV-related NHL. EBV genoma, studied in all HIV⁺ ALCL patients, was present in 3/10 by in situ hybridization (ISH) and in 5/10 cases using PCR. The clinical course of lymphomas was similar in CD30 positive and negative NHL patients. Overall survival also was short in our series, particularly in HIV⁺ ALCL (84 v 188 d), probably because of profound immunodepression of the ALCL patients.
Our findings suggest that severe immunodepression due to HIV infection determines — more than any other factor — the clinical features of HIV⁺ ALCL, making them very similar to those of other high-grade systemic HIV⁺ NHL.     

Anaplastic large cell lymphoma in Japanese children: retrospective analysis of 34 patients diagnosed at the National Research Institute for Child Health and Development

This report presents a retrospective study of 34 Japanese children diagnosed at a single laboratory as having anaplastic large cell lymphoma (ALCL). Most of the pathological features of the Japanese ALCL children observed, such as anaplastic lymphoma kinase protein expression, in addition to most of the clinical characteristics and the outcomes of the patients, are very similar to those reported by European groups. To our knowledge, this is the first report describing the details of the clinicopathological features of Japanese ALCL patients. A further International study, including Japanese patients, might contribute to the establishment of an optimal treatment for paediatric ALCL.     

Systemic anaplastic large-cell lymphoma: results from the non-Hodgkin's lymphoma classification project

Anaplastic large-cell lymphoma (ALCL) is a heterogeneous process that may have a T-cell, B-cell, or indeterminant (null) phenotype and which may or may not express the anaplastic lymphoma kinase (ALK) oncoprotein. Because the clinical significance of these variants of ALCL is unclear, we evaluated the cases of ALCL-T/null and ALCL-B identified in the Non-Hodgkin's Lymphoma Classification Project. We evaluated 1,378 cases of non-Hodgkin's lymphoma (NHL), and a consensus diagnosis of ALCL-T/null was made in 33 patients (2.4%) with a diagnostic accuracy of 85%. Compared to 96 patients with other forms of peripheral T-cell lymphoma (PTCL), those with ALCL-T/null were significantly younger, less likely to have advanced-stage disease or bone marrow involvement, more likely to have a low International Prognostic Index score, and had a significantly better survival. Among those with ALCL-T/null, there were no significant differences in the clinical features or survival on the basis of ALK expression. A consensus diagnosis of ALCL-B was made in 15 patients (1.1%), and the diagnostic accuracy was 67%. However, compared to 366 patients with other forms of diffuse large B-cell lymphoma (DLBCL), those with ALCL-B were no different with regard to clinical features or survival. We conclude that patients with ALCL-T/null have favorable prognostic features and excellent survival and should be separated from those with other forms of PTCL for prognostic and therapeutic purposes. In contrast, patients with ALCL-B appear to be similar to those with other forms of DLBCL.     

Pretargeted antibody-guided radioimmunotherapy in a child affected by resistant anaplastic large cell lymphoma

Anaplastic large cell lymphoma (ALCL) is characterized by preferential paracortical and intrasinusoidal lymph node involvement by large anaplastic tumor cells expressing the CD30 antigen. Up to 80% of pediatric patients with ALCL can be cured with multi-agent chemotherapeutic regimens. Patients resistant to chemotherapy or suffering from early relapse have a poor prognosis and a poor chance of survival. In these cases, the highly aggressive clinical course of ALCL, associated with systemic symptoms and extranodal involvement, has been treated with different approaches in various cooperative trials, including conventional chemotherapy and human stem cell transplantation (HSCT). However, the optimal treatment has not yet been defined, in particular in cases of relapse. More recently, radioimmunotherapy has been studied with encouraging results in cancer patients, including non-Hodgkin's lymphoma. Here we describe the case of a pediatric ALCL, relapsing after HSCT, treated with pretargeted antibody-guided radioimmunotherapy, obtaining a complete remission, with excellent quality of life over the past 10 months.     

A Phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma

SGN-30, a chimeric anti-CD30 monoclonal antibody, has demonstrated potent preclinical antitumour activity in both Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). We conducted an open-label, Phase II study to determine the safety and objective response rate of SGN-30 in 79 patients with refractory/recurrent HL ( n  = 38) or systemic ALCL ( n  = 41). Each course of SGN-30 comprised 6 weekly intravenous infusions, followed by a 2-week treatment-free period. Patients had received a median of 3 (range 1–5) prior regimens of chemotherapy or systemic therapy. The initial 40 patients received 6 mg/kg weekly; the latter 39 patients received 12 mg/kg weekly. In the ALCL group, two patients achieved a complete response and five additional patients achieved a partial response, with response durations ranging from 27 to 1460+ d. No objective responses were observed in the HL group; however, 11 patients (29%) had stable disease (duration 62–242 days). Although adverse events were common, most were mild or moderate, and no specific pattern of adverse events was observed in either disease group. These results demonstrate that weekly administration of SGN-30 is safe, with modest clinical activity in patients with ALCL.     

Autologous stem cell transplantation for anaplastic large-cell lymphomas: results of a prospective trial

Autologous stem cell transplantation (ASCT) in the front line treatment of non-Hodgkin's lymphoma (NHL) remains controversial. Anaplastic large-cell lymphoma (ALCL) is known to have its own clinical and biological features. The outcome of ALCL patients treated with high-dose chemotherapy and ASCT as part of their first-line therapy was analysed in 202 intermediate or high-grade NHL patients in a prospective randomized trial. First-line chemotherapy comprised two alternating anthracycline-containing regimens. Responding patients were autografted after a BEAM (BCNU, cytarabine, etoposide and melphalan) regimen. Patients with bulky or residual masses were irradiated. Fifteen patients with ALCL were identified by morphological and immunological features (CD30 was expressed in 14 out of 15 patients, three patients expressed B-cell markers, five patients expressed T-cell markers and seven patients did not express cell markers). Anaplastic lymphoma kinase (ALK) expression was confirmed in seven cases. The median age was 39 years with a predominant male sex ratio (2.75). Thirteen patients were stage >/= III and six presented with two or more adverse prognostic factors. According to the international age-adjusted prognostic index, the expected complete remission (CR), event-free survival (EFS) and overall survival (OS) rates were 69%, 71% and 69%. Two deaths were observed (one due to interstitial pneumonitis, one due to pulmonary carcinoma). All patients entered CR, no relapse occurred and EFS and survival reached 87% with a follow-up of more than 5 years. These results differ significantly from those observed in the other 176 lymphoma patients: event-free survival was only 53 +/- 5% and OS reached 60 +/- 4% with a median follow-up of 56 months (P = 0.006). Intensified chemotherapy with autologous stem cell support appeared effective in the treatment of ALCL, offering patients the real chance of a cure.     

Disease site as a determinant of survival outcome in patients with systemic anaplastic lymphoma kinase positive anaplastic large cell lymphoma with extranodal involvement: an analysis of 1306 cases from the US National Cancer Database

Systemic anaplastic lymphoma kinase positive (ALK+) anaplastic large cell lymphoma with extranodal involvement (ALCL‐E) is a rare form of non‐Hodgkin lymphoma. No large study in the literature has compared the survival outcomes among different primary extranodal sites of involvement in ALK+ ALCL‐E. We identified 1306 patients with ALK+ ALCL‐E diagnosed between 2004 and 2014 in the US National Cancer Database, among whom 387 had primary extranodal site in the chest/abdomen/pelvis, 103 in the bone, 62 in the central nervous system, 134 in the head and neck and 620 in the cutaneous/soft tissue. Younger age, lower Charlson‐Deyo score, lower clinical stage, receipt of chemotherapy and receipt of radiotherapy were predictors of longer overall survival. Patients with extranodal involvement of central nervous system and chest/abdomen/pelvis had shorter overall survival than those with involvement of head and neck, bone, and cutaneous/subcutaneous tissue after adjusting for confounding variables. We recommend treating these patients upfront with more aggressive therapy.     

Anaplastic lymphoma kinase‐positive anaplastic large cell lymphoma: current and future perspectives in adult and paediatric disease

Anaplastic large cell lymphoma (ALCL) is a rare T‐cell lymphoma seen in both adults and children. ALCL is associated with a characteristic chromosomal translocation, t(2;5)(p23;35) which fuses the anaplastic lymphoma kinase (ALK) gene on chromosome 2 with the nucleophosmin (NPM) gene on chromosome 5, resulting in a NPM‐ALK fusion protein, ALK over‐expression and constitutive tyrosine kinase activity. This aggressive lymphoma is more prevalent in males and can present with extranodal involvement (lung, skin and marrow infiltration) and haemophagocytic lymphohistocytosis. The long‐term overall survival is approximately 70–90% in children and over 70% in adults. Staging systems and prognostic risk factors are different in both childhood and adult ALCL. Treatment in adults is typically anthracycline‐based, with autologous stem cell transplantation (ASCT) salvaging patients in relapsed disease. There is evidence for ALL‐like therapy or intensive, pulsed anthracycline‐based induction in children. ASCT, allogeneic SCT and vinblastine maintenance are all considered reasonable options in relapsed childhood disease. The anti‐CD30 immunoconjugate Brentuximab Vedotin and the specific ALK inhibitor Crizotinib are changing the treatment paradigm in ALCL (ALK‐positive or negative) and ALK‐positive ALCL respectively. Both agents have shown encouraging responses in relapsed ALCL. It remains to be seen how these novel agents are used, but it is very possible that they may improve overall responses and survival in both children and adults. This review highlights the presentation, histopathological features, prognostic factors, and evidence‐based treatment approaches in the first line and relapsed setting in ALK‐positive ALCL. The review concludes by discussing the novel approaches using Brentuximab and Crizotinib which are being tested in clinical trials.