血管免疫母细胞性T细胞淋巴瘤治疗研究进展

 血管免疫母细胞性T细胞淋巴瘤（AITL）是一种系统性、侵袭性外周T细胞淋巴瘤,目前仍然缺乏标准治疗方案。联合化疗没有明显改善预后且缓解持续时间短;靶向药物和免疫抑制治疗研究样本小,不能明确疗效;大剂量化疗联合自体造血干细胞移植（HDT-ASCT）和异基因造血干细胞移植（allo-HSCT）虽然都取得了显著疗效,但HDT-ASCT具有高复发率、远期继发肿瘤等诸多风险,allo-HSCT亦因移植相关死亡率较高而有待进一步探讨。文章就近年来AITL的治疗研究进展加以综述。     

血管免疫母细胞性T细胞淋巴瘤治疗研究进展

血管免疫母细胞性T细胞淋巴瘤（AITL）是一种系统性、侵袭性外周T细胞淋巴瘤,目前仍然缺乏标准治疗方案。联合化疗没有明显改善预后且缓解持续时间短;靶向药物和免疫抑制治疗研究样本小,不能明确疗效;大剂量化疗联合自体造血干细胞移植（HDT—ASCT）和异基因造血干细胞移植（allo-HSCT）虽然都取得了显著疗效,但HDT—ASCT具有高复发率、远期继发肿瘤等诸多风险,allo—HSCT亦因移植相关死亡率较高而有待进一步探讨。文章就近年来AITL的治疗研究进展加以综述。     

异基因造血干细胞移植治疗外周T细胞淋巴瘤现状

外周T细胞淋巴瘤作为一组异质性肿瘤,大多侵袭性强,易出现复发和耐药,预后极差.以化疗和自体造血干细胞移植(ASCT)为基础的治疗,5年无病生存率不足30％.异基因造血干细胞移植(allo-HSCT)治疗外周T细胞淋巴瘤具有移植物抗淋巴瘤效应,治疗复发难治性外周T细胞淋巴瘤的长期无病生存率达35％～50％.allo-HSCT可作为治疗外周T细胞淋巴瘤的有效手段.     

造血干细胞移植治疗淋巴瘤:第56届美国血液学会年会报道

第56届美国血液学会年会关于造血干细胞移植(HSCT)治疗淋巴瘤的摘要171篇,其中自体HSCT(auto-HSCT) 102篇、异基因HSCT(allo-HSCT) 69篇.会议主要讨论了HSCT治疗复发难治霍奇金淋巴瘤及高危、侵袭性非霍奇金淋巴瘤的疗效及其影响疗效的因素,包括移植时机、预处理方案、靶向化疗药物应用、allo-HSCT后移植物抗宿主病预防及移植后临床预测指标等众多方面.     

自体造血干细胞移植治疗B细胞非霍奇金淋巴瘤的研究进展

非霍奇金淋巴瘤(non-hodgkin lymphoma,NHL)是一组起源于包括B-细胞、T细胞及NK细胞的异质性淋巴增殖性疾病.欧美国家B细胞淋巴瘤(B-NHL)约占80％ ～85％[1].我国B细胞淋巴瘤发生率约占NHL的61.6％～74.2％[24].B-NHL包括弥漫大B细胞淋巴瘤、套细胞淋巴瘤、滤泡性淋巴瘤等.NHL的治疗包括化疗、放疗、免疫治疗、放射免疫治疗及造血干细胞移植.近10多年来,由于CD20单克隆抗体(单抗)的应用和自体造血干细胞移植(autologous stem cell transplantation,ASCT)作为巩固治疗使得B-NHL的疗效明显提高[5-6].然而,自体造血干细胞移植是作为该病一线巩固还是待疾病复发后作为挽救性治疗仍待进一步明确.     

Hyper-CVAD方案治疗侵袭性T细胞淋巴瘤的效果和安全性

目的 评价Hyper-CVAD化疗方案治疗侵袭性T细胞淋巴瘤的效果和安全性.方法 对2009年9月至2010年12月在北京协和医院接受Hyper-CVAD方案诱导化疗的34例初诊侵袭性T细胞淋巴瘤患者的疗效和不良反应等资料进行回顾性分析,并进行生存分析.结果 34例患者接受Hyper-CVAD方案诱导化疗后,28例(82.4％)有治疗反应,其中10例(29.4％)获得完全缓解(CR);11例接受造血干细胞移植(包括1例同胞全合异基因造血干细胞移植).中位随访时间16个月(1～82个月),1、3年总生存(OS)率分别为70.2％、41.1％;1、3年无进展生存(PFS)率分别为49.3％、31.6％.化疗不良反应主要为骨髓抑制,18例(52.9％)发生Ⅳ级骨髓抑制;3例因严重感染死亡.Cox多因素分析显示,化疗能否达到CR是PFS的独立影响因素(HR=6.118,95％CI 1.327～28.206,P=0.020);骨髓是否受累(HR=0.270,95％CI 0.101～0.722,P=0.009)和化疗能否达到CR(HR=6.669,95％CI 1.754～25.354,P=0.005)是OS的独立影响因素.结论 Hyper-CVAD方案诱导化疗治疗侵袭性T细胞淋巴瘤的反应率高,但有效持续时间短,远期疗效不佳,同时骨髓抑制严重,感染发生率高.缓解后行自体造血干细胞移植可能提高侵袭性T细胞淋巴瘤的疗效.     

伴纵隔大包块淋巴瘤17例临床分析

目的 分析伴纵隔大包块淋巴瘤的临床特点、病理诊断和治疗方法.方法 回顾性分析2010年1月至2017年1月北京友谊医院诊治的17例伴纵隔大包块淋巴瘤患者临床资料.结果 17例患者均经病理诊断确诊,其中原发纵隔大B细胞淋巴瘤6例,T淋巴母细胞淋巴瘤5例,霍奇金淋巴瘤3例,其他类型非霍奇金淋巴瘤3例.4例采用化疗联合放疗,7例采用单纯化疗,5例采用化疗联合自体造血干细胞移植,1例化疗后进行异基因造血干细胞移植.终止治疗后评估疗效:完全缓解12例,部分缓解1例,疾病稳定1例,死亡3例.结论 伴纵隔大包块淋巴瘤患者的预后与病理类型及治疗反应有关,采用积极的化疗联合放疗及化疗联合自体或异基因造血干细胞移植可能有助于提高疗效.     

侵袭性非霍奇金淋巴瘤治疗进展

研究表明持续给药方式和新型靶向药物有望改善侵袭性B细胞淋巴瘤患者的预后,加大化疗药物剂量未显示疗效提高.侵袭性T细胞淋巴瘤患者的预后近些年有所改善,归因于自然杀伤细胞/T细胞淋巴瘤化疗方案的改进.多发遗传学异常是侵袭性T细胞淋巴瘤不良预后的内因,非清髓性异基因造血干细胞移植和新型靶向药物提示增加治疗疗效.现代放疗技术也是提高侵袭性非霍奇金淋巴瘤疗效的重要手段.     

血管免疫母细胞性T细胞淋巴瘤研究进展

血管免疫母细胞性T细胞淋巴瘤是一种少见的侵袭性淋巴瘤,临床上以周身淋巴结肿大、肝脾肿大、自身免疫现象、溶血性贫血和多克隆高球蛋白血症为特征性表现。AITL有明确的病理学特点,其免疫标志CD10、CXCLB有助于诊断。肿瘤细胞是成熟αβCD4＋CD8-细胞,起源于生发中心滤泡辅助性T细胞。传统化疗效果较差,大剂量化疗联合自体干细胞移植显示较好疗效。     

侵袭性T细胞非霍奇金淋巴瘤的化疗

T细胞非霍奇金淋巴瘤是一组具有独特临床和病理特征的疾病,与B细胞淋巴瘤相比,侵袭性更强,化疗敏感性差。为探索有效的治疗方案,近年来,新的药物如吉西他滨、靶向药物联合化疗及高剂量化疗联合造血干细胞移植被研究用于治疗T细胞淋巴瘤,并取得了一些进展。     

Allogreffes à conditionnement atténué dans les hémopathies lymphoïdes

The role of reducedintensity allogeneic stem cell transplantation in lymphoid hematologic malignancies is not consensual and remains difficult to define mainly because of lack of comparative studies. In myeloma, the topic is extremely controversial in first-line therapy and in more advanced disease. It seems that the procedure might be beneficial in relapsed chemosensitive diffuse large B-cell lymphoma and in advanced follicular lymphoma. In peripheral T-cell lymphoma, the promising results in relapse have stimulated efforts to evaluate allogeneic transplants in first line. However, it is important to note that because of many uncertainties surrounding allogeneic stem cell transplantation in lymphoid malignancies, the best transplant strategy would be to include patients in clinical trials whenever possible.     

Salvage High-dose Melphalan With Autologous Stem cell Transplantation as Bridge to Consolidation Therapy for Chemoresistant Aggressive B-cell Lymphoma

BackgroundPatients suffering from refractory aggressive B-cell lymphoma not responding to salvage chemotherapy have a dismal prognosis. CAR T-cells or allogeneic stem cell transplantation (SCT) are potentially curative approaches. However, obtaining a remission, and lowering tumor burden before consolidation seems crucial for long-term efficacy of both treatment modalities.Materials and MethodsIn this retrospective analysis, we reviewed patients with chemoresistant aggressive B-cell lymphoma, defined as being refractory or progressive to at least second line salvage chemotherapy including the regimen immediately preceding autologous stem cell transplantation (ASCT), treated at 2 tertiary centers, who were eligible for intensive treatment using single agent high-dose (HD) melphalan to obtain a remission before consolidating therapy.ResultsWe identified 36 patients that received single agent HD melphalan and ASCT as remission induction followed by CAR T-cells or allogeneic stem cell transplantation (SCT). Thirteen of the evaluable patients (39.4%) achieved a partial remission and 9 patients (27.73%) a complete remission, resulting in an overall response rate (ORR) of 66.7%. High remission rates were seen across all subgroups including patients with primary refractory lymphoma (ORR 58.3%), uncontrolled disease and high tumor burden as indicated by increased LDH levels (ORR 66.7% for patients with elevated LDH above 2 times upper limit of norm). 22 patients proceeded to allogeneic SCT and 5 to CAR T-cell therapy. Treatment related mortality of ASCT was 5.5% (2 patients, both due to infections). Two-year overall survival of all patients was 15.8%, primarily due to a high non–relapse mortality (45.5%) of allogeneic SCT patients treated with myeloablative conditioning chemotherapy.ConclusionSingle agent HD melphalan produces high remission rates in patients with chemoresistant, uncontrolled aggressive B-cell lymphoma and provides a window of opportunity for consolidation therapy.MicroabstractPatient with refractory/relapsed aggressive B-cell lymphoma after salvage therapy are an unmet medical need because of their very poor prognosis. In our retrospective analysis of 36 patients we showed that single agent high-dose melphalan can achieve high response rates (ORR 66.7%) even in uncontrolled disease enabling consolidation therapy e.g. with allogeneic stem cell transplantation or CAR T-cell therapy.     

High-dose chemotherapy and APSCT as a potential cure for relapsing hemolysing AILD

Angioimmunoblastic lymphadenopathy with dysproteinemia (or dysgammaglobulinemia) (AILD) is a lymphoproliferative disorder with cytogenetic and molecular abnormalities characteristic of malignant T-cell lymphoma (angioimmunoblastic T-cell lymphoma -- AITL). We report the clinical course of a 58-year-old male patient with unusually aggressive AILD, including severe hemolysis and Guillain-Barré syndrome, who entered complete remission after CHOP therapy, but had a full relapse after 2 months. At relapse, treatment with high-dose chemotherapy followed by autologous peripheral stem cell transplantation (APSCT) with CD34 selected cells was shown to be successful. The patient is alive and disease-free 3 years after diagnosis and 32 months after APSCT. Considering the poor prognosis of the majority of patients with AILD, intensive treatment followed by APSCT, may be a subject for further studies.     

Allogeneic Hematopoietic Stem Cell Transplantation: Does It Have a Place in Treating Hodgkin Lymphoma?

Although the majority of patients with Hodgkin lymphoma achieve sustained remission with frontline treatment, there is still a subset of patients with much less favorable prognosis. The current standard of care for Hodgkin lymphoma patients with relapsed or refractory disease is autologous stem cell transplantation. However, no randomized trial has compared autologous stem cell transplantation with allogeneic stem cell transplantation prospectively, and most studies comparing allogeneic stem cell transplantation with historical controls of autologous stem cell transplantation use a myeloablative conditioning reference group. With the more frequent use of reduced-intensity conditioning transplantation in recent studies, the role for allogeneic stem cell transplantation in Hodgkin lymphoma patients is being redefined. In contrast to other types of lymphomas, Hodgkin lymphoma patients are younger at diagnosis, which makes a curative strategy such as allogeneic stem cell transplantation particularly appealing. This review examines the role of allogeneic stem cell transplantation in Hodgkin lymphoma by looking at both retrospective and prospective analyses in the era of reduced-intensity conditioning transplantation, donor lymphocyte infusions, and biologically based treatments.     

An update on the role of high-dose therapy with autologous or allogeneic stem cell transplantation in mantle cell lymphoma

PURPOSE OF REVIEW: Early trials of high-dose therapy with autologous stem cell transplantation in mantle cell lymphoma were discouraging, with no clear survival advantage attributable to the procedure. Most early series were plagued by small numbers, retrospective designs, and short follow-up. Also, until recently, allogeneic stem cell transplantation was not an option for most mantle cell lymphoma patients who were too old or infirm to tolerate standard conditioning regimens. RECENT FINDINGS: New advances in allogeneic transplantation, particularly reduced-intensity conditioning regimens, have increased the availability of this procedure to patients with mantle cell lymphoma. New evidence has emerged during the last several years that suggests autologous stem cell transplantation in first complete remission may provide a survival advantage over conventional chemotherapy in patients with mantle cell lymphoma. Additionally, investigational strategies such as in vivo purging with rituximab and the use of radioimmunotherapy in conditioning regimens may further increase response rates and, hopefully, survival in mantle cell lymphoma patients. Finally, recent studies suggest the existence of a graft-versus-lymphoma effect in mantle cell lymphoma providing strong scientific rationale for the possible curative potential of allogeneic stem cell transplantation in this disease. SUMMARY: This review focuses on recent advances in allogeneic and autologous transplantation for mantle cell lymphoma. Particular emphasis is placed on the role of autologous transplantation in first complete remission, the role of in vivo purging with rituximab, the utility of radioimmunotherapy and, finally, the evolving strategy of reduced-intensity allogeneic stem cell transplantation.     

Bone marrow transplantation for lymphoma CR1

PURPOSE OF REVIEW: Despite several reports showing the superiority of autologous stem cell transplantation over conventional chemotherapy in the salvage treatment of non-Hodgkin lymphoma, its use as part of first-line therapy in this disease is still controversial. The review highlights the most relevant studies on autologous stem cell transplantation for non-Hodgkin lymphoma at diagnosis published over the past year. RECENT FINDINGS: Several recent studies have shown that autologous stem cell transplantation may offer survival benefits in patients with both diffuse large cell lymphoma and follicular cell lymphoma whose prognostic features are poor. An advantage of autologous stem cell transplantation has also been documented for other non-Hodgkin lymphoma subtypes, in particular mantle-cell lymphoma, in which autologous stem cell transplantation is probably the most effective first-line option presently available. Nevertheless, whether autologous stem cell transplantation is definitely better than conventional chemotherapy is still under discussion, and the issue is still less clear, given the new opportunities offered by rituximab combined with chemotherapy. Autologous stem cell transplantation may also benefit from the addition of rituximab as an in vivo purging agent. Thus, large randomized trials are required to fully define the role of autologous stem cell transplantation in first-line treatment for high-risk non-Hodgkin lymphoma. Such trials should compare autologous stem cell transplantation with chemotherapy, both supplemented with rituximab, in the most frequent CD20+ lymphoma subtypes. The up-front use of autologous stem cell transplantation might find support from the recent observation that patients who do not respond to this treatment may still have a good chance of being rescued by reduced-intensity allogeneic transplantation. SUMMARY: Autologous stem cell transplantation remains a valid research strategy in first-line therapy and, along with new agents and nonmyeloablative allogeneic transplantation, may help to increase the cure rate for high-risk non-Hodgkin lymphoma.     

The role of stem cell transplantation in the treatment of follicular lymphoma

Follicular lymphoma (FL) is highly sensitive to chemo- and radiotherapy. However, cure can not be achieved with conventional chemotherapy. Results from several large clinical trials indicate that 50-60% of patients treated with high dose chemo-/radiotherapy (HDT) and autologous blood stem cell transplantation (SCT) for relapse after standard chemotherapy have a 3-5-year chance of disease-free survival (DFS). Overall as well as disease-free survival are improved in patients with negative results in sensitive PCR assays for the disease-specific t(14;18) translocation in bone marrow (BM) or peripheral blood samples taken after transplantation. These data compare favourably to historical results with standard dose chemotherapy. The role of high dose therapy and autologous stem cell transplantation in the primary treatment of follicular lymphoma is presently addressed in randomized trials. Patients with refractory disease or relapsing from standard as well as high dose therapy can achieve long term complete remissions (CR) with allogeneic blood stem transplantation mainly due to the graft-versus-lymphoma effect of the donor immune system.     

A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome

BackgroundThe prognosis for patients with most forms of T-cell lymphoma is poor. Allogeneic hematopoietic stem-cell transplantation (HSCT) may improve the outcome.Patients and methodsThis study examines the outcome of 52 patients who underwent ablative or nonablative allogeneic HSCT for peripheral T-cell lymphoma (PTCL) or advanced mycosis fungoides/Sezary syndrome over a 12-year period at a single institution. We divided the patients into those with predominantly nodal histologies: peripheral T-cell not otherwise specified (PTCL NOS), angioimmunoblastic (AITL), or anaplastic large cell lymphoma, T/null type (systemic) (ALCL), and predominantly extranodal histologies: natural killer (NK)/T cell, enteropathy type, hepatosplenic, subcutaneous panniculitic, mycosis fungoides, or T cell or NK cell other.ResultsMedian follow-up of survivors is 49 months. Non-relapse mortality and relapse at 3 years was 27% and 43%, respectively. The incidence of grade II–IV acute graft-versus-host disease (GVHD) was 21%. The incidence of extensive chronic GVHD at 2 years was 27%. The 3-year progression-free survival was 30%: 45% in patients with predominantly nodal histologies (PTCL NOS, AITL, and ALCL) and 6% in patients with predominantly extranodal histologies (P = 0.016). Overall survival at 3 years was 41% for all patients.ConclusionAllogeneic HSCT can produce long-term remissions in relapsed/refractory T-cell lymphoma, especially those with nodal histologies.     

Treatment of Peripheral T-Cell Lymphoma in Community Settings

BackgroundPeripheral T-cell lymphomas (PTCLs) represent a rare and heterogeneous group of malignancies that do not have consensus treatment recommendations. Strategies extrapolated from B-cell lymphoma have met with limited efficacy, although T-cell–specific salvage therapies have been recently developed.MethodsTo determine treatment patterns and associated outcomes in PTCL not otherwise specified (PTCL-NOS), anaplastic large T-cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL), a retrospective analysis was undertaken at a large US community oncology network among patients treated between January 2010 and April 2015.ResultsAmong 93 patients (44 PTCL-NOS, 30 ALCL, 19 AITL), 23 unique treatments were used in 66 first-line patients and 12 unique second-line treatments were used in 24 relapsed/refractory patients. First-line CHOP and CHOP-like regimens were used in 74% of patients, providing 4-year overall survival (OS) outcomes of 34% (95% confidence interval [CI], 14%-83%) in patients without transplant consolidation (82% in ALCL, 37% in PTCL-NOS, and 0% in AITL). Upfront stem cell transplantation trended toward improved 4-year progression-free survival 77% (95% CI, 54%-100%) versus 34% (95% CI, 14%-80%); (P = .08; hazard ratio [HR] 0.29) with 4-year OS 77% (95% CI, 54%-100%) versus 34% (P = .22; HR 0.41). Brentuximab was the most common second-line therapy, with multiple additional regimens used in sequence (up to 5 salvage regimens) in many.ConclusionsThe significant variability in treatments used for PTCL emphasizes the lack of consensus therapy in this rarer lymphoma and calls for additional organized prospective and registry studies to evaluate comparative effectiveness.