Activity of gallium nitrate in refractory peripheral T-cell lymphoma

Peripheral T-cell lymphomas (PTCLs) are post-thymic malignancies characterized by an aggressive clinical course and an inferior outcome with standard therapies. The authors report significant clinical activity of infusional gallium nitrate in a patient with stage IV PTCL disease refractory to chemotherapy.     

Novel therapies in peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of disorders associated with a very poor prognosis. Historically, treatment protocols have been largely based on regimens used to treat aggressive B-cell lymphomas; unfortunately, the efficacy of these regimens has been suboptimal, with most patients experiencing relapse after initial therapy. An improved understanding of the molecular biology, pathogenesis, and progression of these disorders has led to the development of a variety of novel targeted agents that may improve outcomes in patients with PTCLs. The purpose of this review is to focus on these novel agents and the various treatment approaches that are currently being evaluated in PTCLs.     

Novel therapies in peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of disorders associated with a very poor prognosis. Historically, treatment protocols have been largely based on regimens used to treat aggressive B-cell lymphomas; unfortunately, the efficacy of these regimens has been suboptimal, with most patients experiencing relapse after initial therapy. An improved understanding of the molecular biology, pathogenesis, and progression of these disorders has led to the development of a variety of novel targeted agents that may improve outcomes in patients with PTCLs. The purpose of this review is to focus on these novel agents and the various treatment approaches that are currently being evaluated in PTCLs.     

SOHO State of the Art Updates and Next Questions: Pathology and Pathogenesis of Nodal Peripheral T-Cell Lymphomas

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous and often clinically aggressive group of neoplasms derived from mature post-thymic T-lymphocytes. These neoplasms are rare and usually diagnostically challenging. Our understanding of the pathogenesis of PTCL is increasing and this improved knowledge is leading us to better molecular characterization, more objective and accurate diagnostic criteria, more effective risk assessment, and potentially better treatments. The focus of this paper is to present a brief overview of the current pathology criteria and molecular and genetic features of nodal peripheral T-cell lymphomas focusing on distinct genetically and molecularly defined subgroups that are being recognized within each major nodal PTCL category. It is expected that the molecular stratification will improve the diagnosis and will provide novel therapeutic opportunities (biomarker-driven and targeted therapies) that might benefit and change the outcomes of patients with these neoplasms.     

Comparison of peripheral T-cell lymphomas and diffuse large B-cell lymphoma

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are a biologically heterogeneous subgroup of lymphomas with poor prognosis. In this study, the authors analyzed the clinical behaviors of PTCLs and diffuse large B-cell lymphoma (DLBCL). METHODS: The authors compared the characteristics and outcomes of 59 patients with PTCLs, including 33 angioimmunoblastic T-cell lymphomas and 26 unspecified peripheral T-cell lymphomas, with the characteristics and outcomes of 193 patients with DLBCLs who were treated in the era before rituximab. RESULTS: Based on the clinical characteristics, elevated lactate dehydrogenase (LDH), poor PS, advanced stage, higher International Prognostic Index score, and B symptoms were more common in patients with PTCLs, and bulky mass was more common in patients with DLBCL. The rates of complete response (CR) or an unconfirmed CR (CRu) were higher in patients with DLBCL (72%) than in patients with PTCLs (56%; P = .03). The 5-year overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) rates were 31%, 26%, and 47%, respectively, in patients with PTCLs and 59%, 55%, and 73%, respectively, in patients with DLBCL (P = .001, P < .001, and P = .003, respectively). Although multivariate analysis identified several risk factors that were significant in PTCLs, but not in DLBCLs, for the CR/CRu, OS, PFS, and DFS rates, the immunophenotype was not identified as a risk factor. CONCLUSIONS: The poor response and survival of patients who had PTCLs, compared with patients who had DLBCL, was caused by numerous initial risk factors. T-cell phenotype itself did not appear to have a significant impact on either response or survival.     

Peripheral T-cell lymphomas, unspecified (or not otherwise specified): a review

Peripheral T-cell lymphomas (PTCL) comprises a heterogeneous group of haematological tumours, which originate from mature T-cells, and constitute less than 15% of all non-Hodgkin's lymphomas (NHLs) in adults. The current WHO classification recognizes nine distinct clinicopathologic peripheral T-cell NHLs, being the 'unspecified variant' (PTCL-U) the most common subtype. These neoplasms often present in advanced stage at diagnosis, and most commonly have an aggressive clinical course requiring prompt treatment. The rarity of these tumours requires additional studies to better understand their biology and search for new therapies which may hopefully improve the dismal outcome of most patients. This review aims to describe the pathobiological aspects as well the clinical characteristics and current therapeutic strategies of the PTCLs, with special attention to the group of PTCL-U.     

New drug therapies in peripheral T-cell lymphoma

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous collection of lymphomas that are associated with very poor prognosis. Conventional therapies, historically based on protocols for aggressive B-cell lymphomas, deliver less than adequate outcomes; the majority of patients experience early relapse after front-line treatment and current 5-year overall survival is only 10–30%. Clearly, new approaches are needed. In recent years there has been a plethora of novel agents showing activity in PTCL, often in patients with advanced relapsed or refractory disease. These agents include antifolate drugs (pralatrexate), histone deacetylase inhibitors (vorinostat, romidepsin, panobinostat and belinostat), nucleoside analogues (gemcitabine, forodesine and clofarabine), monoclonal antibodies (anti-CD52, anti-CD4 and anti-CD2), fusion toxins (denileukin diftitox), immunomodulatory agents (lenalidomide) and proteasome inhibitors (bortezomib). This is an exciting time in the treatment of PTCL, as our ever improving understanding of the distinguishing features, pathogenesis, molecular biology and progression of PTCL, and the knowledge of the mechanism and efficacy of novel therapies, may see a real improvement in outcomes for patients. The purpose of this article is to focus on these novel therapies and the results of recent clinical trials in PTCL.     

外周T细胞淋巴瘤临床治疗进展

外周T细胞淋巴瘤是一组起源于胸腺后成熟T细胞的侵袭性非霍奇金淋巴瘤,具有高度的异质性,目前临床研究进展滞后于B细胞淋巴瘤。现有治疗方案治愈率低,总体预后差,目前仍缺乏标准治疗方案。采用常规的CHOP类化疗疗效欠佳,放疗在早期患者中的价值尚有待确定,造血干细胞移植是高危患者巩固治疗的首选,新型药物在外周T细胞淋巴瘤疗效仍需进一步证实。PET/CT在外周T细胞淋巴瘤患者中的预后判断中发挥着越来越重要的作用。     

New drug therapies in peripheral T-cell lymphoma

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous collection of lymphomas that are associated with very poor prognosis. Conventional therapies, historically based on protocols for aggressive B-cell lymphomas, deliver less than adequate outcomes; the majority of patients experience early relapse after front-line treatment and current 5-year overall survival is only 10-30%. Clearly, new approaches are needed. In recent years there has been a plethora of novel agents showing activity in PTCL, often in patients with advanced relapsed or refractory disease. These agents include antifolate drugs (pralatrexate), histone deacetylase inhibitors (vorinostat, romidepsin, panobinostat and belinostat), nucleoside analogues (gemcitabine, forodesine and clofarabine), monoclonal antibodies (anti-CD52, anti-CD4 and anti-CD2), fusion toxins (denileukin diftitox), immunomodulatory agents (lenalidomide) and proteasome inhibitors (bortezomib). This is an exciting time in the treatment of PTCL, as our ever improving understanding of the distinguishing features, pathogenesis, molecular biology and progression of PTCL, and the knowledge of the mechanism and efficacy of novel therapies, may see a real improvement in outcomes for patients. The purpose of this article is to focus on these novel therapies and the results of recent clinical trials in PTCL.     

The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin''s lymphomas that are incurable in the majority of patients with current therapies. Outcomes associated with anthracycline-based therapies are suboptimal, but remain the standard of care for most patients, even though the benefits of this approach remain uncertain. This study retrospectively examined outcomes in a cohort of North American PTCL patients treated with both anthracycline- and nonanthracycline-containing regimens. The incorporation of anthracycline-containing regimens was associated with improved progression-free survival (PFS) and overall survival (OS). Patients treated with nonanthracycline-containing regimens were more likely to have high-risk features and were less likely to undergo high-dose therapy and stem cell transplantation. However, anthracycline use remained an independent predictor of improved PFS and OS when adjusting for these confounding variables. Anthracycline-based regimens and consolidation with high-dose therapy and autologous stem cell transplantation in appropriately selected patients remains a viable option for patients unable to participate in a clinical trial. Long-term disease-free survival is not optimal, highlighting the need for an improved understanding of disease pathogenesis, and the development of novel therapeutic strategies.     

外周T细胞淋巴瘤的诊疗进展

外周T细胞淋巴瘤（peripheral T-cell lymphomas,PTCLs）是一类相对少见的淋巴细胞恶性增生性疾病,约占非霍奇金淋巴瘤（non-Hodgkin's lymphoma,NHL）的10%~15%。不同亚型PTCLs预后差异较大,以蒽环类药物为基础的联合化疗方案是目前的标准治疗;大剂量化疗联合干细胞移植也是部分患者的合理治疗选择。然而,除间变性淋巴瘤激酶阳性（ALK+）间变性大细胞淋巴瘤（ALCL）外,其它类型PTCLs复发率均较高。近年来,多种新型药物,如普拉曲沙、组蛋白去乙酰化酶抑制剂、蛋白酶体抑制剂等,在PTCLs治疗上显示出良好的疗效和广阔的应用前景。本文,就将近年来PTCLs的诊疗进展作一综述总结。     

Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified

Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK−. Differentially expressed miRNAs were validated in an independent set of 20 PTCLs/NOS, 20 AITLs, 19 ALCLs/ALK− and 15 ALCLs/ALK+. Two hundred and thirty-six miRNAs were found to differentiate PTCLs/NOS from activated T-lymphocytes. To assess which miRNAs impacted on GEP, a multistep analysis was performed, which identified all miRNAs inversely correlated to different potential target genes. One of the most discriminant miRNAs was selected and its expression was found to affect the global GEP of the tumours. Moreover, two sets of miRNAs were identified distinguishing PTCL/NOS from AITL and ALCL/ALK−, respectively. The diagnostic accuracy of this tool was very high (83.54%) and its prognostic value validated.     

Treatment of refractory peripheral T-cell lymphoma with denileukin diftitox (ONTAK)

Peripheral T-cell lymphomas (PTCLs) are an uncommon and heterogeneous group of well-differentiated, post-thymic T-cell malignancies that can present in the skin as cutaneous T-cell lymphomas. In general, their prognosis is poor, and specific therapy is not well defined. We report the successful treatment of a patient with relapsed, refractory PTCL who after failing 13 standard single and multiple chemotherapy regimens and experimental agents had a dramatic prolonged response to diftitoxin denileukin (ONTAK). This fusion protein, composed of diphtheria toxin coupled to interleukin-2, is approved for cutaneous T-cell lymphomas, including mycosis fungoides, and should be considered for treatment of the rare subset of peripheral T-cell lymphomas.     

Beyond the guidelines in the treatment of peripheral T-cell lymphoma: new drug development

Peripheral T-cell lymphomas (PTCLs) are a rare and diverse group of neoplasms with a poor prognosis. Management of these disorders has been largely extrapolated from the treatment of aggressive B-cell lymphomas; however, therapeutic responses to this approach are neither adequate nor durable for most patients with PTCL. Given the rarity of PTCL, much of the literature consists of studies with small sample size and anecdotal case reports. Therefore, no consensus exists on the best therapeutic strategy for either newly diagnosed or relapsed/refractory PTCL. This article reviews promising novel approaches in the treatment of PTCL and its subtypes. Investigation into the pathogenesis of PTCL has also identified new targets for treatment. These emerging therapies include new uses of existing agents and the development of novel agents specifically targeted against T-cell lymphoma. Results using antimetabolites, immunotherapies, and histone deacetylase inhibitors have been particularly encouraging. These novel therapies are being tested as single agents and in combination with conventional lymphoma regimens in the frontline and salvage settings. Because of the rarity and heterogeneity of PTCL, national and international cooperation is needed to conduct the clinical studies required for the development of more effective treatment paradigms. These efforts are ongoing and will hopefully guide new strategies to improve the historically poor outcome of PTCL.     

外周T细胞淋巴瘤抗血管生成研究进展

 外周T细胞淋巴瘤（PTCL）对传统的化疗方案不敏感,与B细胞淋巴瘤相比预后差,目前缺乏有效的治疗方案。血管生成在恶性肿瘤的生长过程中具有重要的作用,研究显示血管内皮生长因子（VEGF）的表达与PTCL的临床特征及预后相关。同时,具有抗血管生成作用的药物在PTCL的初步临床研究中显示出了疗效。     

初诊外周T细胞淋巴瘤治疗进展

外周T细胞淋巴瘤(peripheral T-cell lymphoma,PTCL)为一组高度异质性的侵袭性非霍奇金淋巴瘤,整体预后差,目前一线治疗以CHOP(环磷酰胺+阿霉素+长春新碱+泼尼松)方案为主,但复发率较高,最近多项研究报道了初诊PTCL的治疗进展,主要涉及新的化疗方案的探索、新药联合治疗的尝试、自体干细胞移...     

Pathology and Pathogenesis of T-Cell Lymphoma

Peripheral T cell lymphomas (PTCLs) are a heterogeneous and often clinically aggressive group of neoplasms derived from mature post-thymic T lymphocytes. These neoplasms are rare and usually diagnostically challenging. Our understanding of the pathogenesis of PTCL is increasing and this improved knowledge is leading us to better molecular characterization, more objective diagnostic criteria, more effective risk assessment, and potentially to better treatments for these neoplasms.     

Update on the World Health Organization classification of peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of lymphoproliferative disorders of postthymic origin. Progress in elucidating the pathobiology and appropriate therapy of these neoplasms has been slow, primarily because of their rarity, but also because until the early 1990s, they were generally grouped together and combined with B-cell lymphomas. It is now understood that most PTCLs are highly aggressive and respond poorly to standard chemo therapy, and thus they have a significantly poorer prognosis than their B-cell counterparts. In 1994, the Revised European and American Lymphoma classification provided the first uniform system to classify lymphoproliferative disorders on the basis of morphology, phenotype, genetics, and clinical features. Since then, the World Health Organization (WHO) has refined this system as additional information has evolved to further elucidate the origin of these neoplasms. More recently, several new distinct and provisional categories in the updated WHO classification have been defined. This review summarizes the changes in the fourth edition of the WHO classification of lymphoid tumors, with particular focus on the aggressive subtypes.     

Targeting Chemokine Receptor CCR4 in Adult T-Cell Leukemia-Lymphoma and Other T-Cell Lymphomas

Peripheral T-cell lymphoma (PTCL) is a group of lymphoid malignancy that remains difficult to treat, as most PTCL becomes refractory or relapses, and thus there is an unmet medical need for novel treatment modalities. CC chemokine receptor 4 (CCR4) is expressed in various types of PTCL including adult T-cell leukemia-lymphoma (ATL), which has the worst prognosis among them. A phase II study of a defucosylated, humanized anti-CCR4 monoclonal antibody, mogamulizumab (KW-0761), yielded an overall response rate of 50?% (13/26) and a median progression-free survival of 5.2?months in relapsed patients with CCR4-positive ATL who had been previously treated with chemotherapy. Mogamulizumab also showed potential efficacy for cutaneous T-cell lymphoma in a US phase I/II study. Further preclinical and clinical investigations are needed to examine whether concomitant use of this novel agent with other agents with different mechanisms of action would be more effective for ATL and other PTCLs.     

Oral fludarabine in combination with doxorubicin and dexamethasone as first-line therapy for nodal peripheral T-cell lymphomas: early results of a prospective multicenter study

Purpose  

Nodal peripheral T-cell lymphomas (PTCLs) have particularly poor prognoses. Few data enabling establishment of an accepted standard treatment modality for PTCLs are available. We hypothesized that fludarabine-based regimens are tolerable and effective in treatment for nodal PTCLs. Therefore, this study was to analyze the toxicity of, response rate for, and outcome of treatment for nodal PTCLs with oral fludarabine, doxorubicin, and dexamethasone (FAD).