Search Results (53)

Nodal marginal zone lymphoma (NMZL) is an indolent B-cell lymphoma that may pose diagnostic challenges due to the absence of distinct markers. In rare atypical cases, an overabundance of PD1+ T follicular helper (TFH) cells in tumor tissue may mimic peripheral T-cell lymphoma (PTCL) of TFH origin, further complicating the diagnosis. A 72-year-old woman with progressive lymphadenopathy had a cervical lymph node biopsy showing a disrupted architecture with monomorphic nodules of CD20+/MNDA+ B-cells and a prominent central population of proliferating CD4+/PD1+ T-cells, initially suggestive of a PTCL-TFH. The bone marrow contained aggregates of CD20+ B-cells intermixed with CD3+/CD4+/PD1+ T-cells. Next-generation sequencing (NGS) revealed clonal immunoglobulin heavy-chain rearrangements in the lymph node and bone marrow, with T-cell receptor genes displaying a polyclonal pattern. Targeted NGS showed no PTCL-related alterations but identified NMZL-associated mutations with different distributions across lymph node and bone marrow compartments. NOTCH2 mutations (c.6418C>T; p.Gln2140*) were found in both tissues, while the (c.69+2T>A; p.?) TNFRSF14 gene mutation was only detected in the lymph node. The KMT2D gene displayed a frameshift variant in the lymph node (c.4801_4802delinsT; p.Arg1601Leufs*3) and an in-frame deletion (c.11756_11758del; p.Gln3919del) in the bone marrow. Notably, NGS and digital droplet PCR confirmed a TP53 frameshift mutation (c.902del; p.Pro301Glnfs*44) with a fractional abundance of 0.31% in the lymph node and a (c.742C>T; p.Arg248Trp) mutation (0.309%) in the bone marrow. Results underscore the importance of NGS-based clonality to diagnose NMZL with prominent PD1+ T-cell hyperplasia, and prompt further investigation into tissue-specific mutational signatures in these unusual cases. Full article

Despite recent progress in lymphoma immunotherapy, outcomes for patients with peripheral T cell lymphomas (PTCLs) remain poor. The challenge of PTCLs reflects the profound biological heterogeneity and relative rarity of this disease group and its resistance to conventional chemotherapy, as well as the formidable challenge of generating definitive clinical evidence. However, deepening insight into the immunogenomic and microenvironmental basis of PTCL has revealed diverse mechanisms of immune escape, spanning defects in antigen presentation, apoptotic signaling, adhesion, and extensive tumor microenvironmental remodeling. These vulnerabilities provide a sound rationale for novel immunotherapeutic strategies—checkpoint inhibitors, CAR-T and NK cell platforms, bispecific antibodies, oncolytic viruses, and immunomodulatory agents. Early studies show encouraging but inconsistent activity, and the variability in response highlights the urgent need for biomarker-driven stratification to deliver personalized approaches and clinically meaningful efficacy. This review synthesizes the current literature on the immune dysregulation of PTCLs, as well as advances in PTCL immunotherapy, outlining the biological rationale underpinning these approaches. We discuss approaches to molecular, transcriptomic, and microenvironmental profiling with circulating biomarkers that could enable adaptive trial designs and personalized treatment strategies. Together, these developments chart a path away from empiricism and toward precision therapy in PTCLs. Full article

Primary aggressive oral lymphomas (PAOL) are a rare subset of extranodal non-Hodgkin lymphomas arising in the oral cavity without evidence of other systemic involvement at diagnosis. PAOL accounts for only about 2–3% of all lymphomas. They most commonly belong to aggressive B-cell subtypes such as Diffuse large B-cell lymphoma (DLBCL) and plasmablastic lymphoma (PBL), with occasional cases of Burkitt lymphoma and T-cell/NK-cell lymphomas. Clinically, these malignancies often present with non-specific symptoms (e.g., swelling, pain, ulceration, tooth mobility) that mimic benign dental conditions, leading to diagnostic delays. An integrated diagnostic approach—combining thorough oral examination, imaging (CT, MRI, PET), and definitive biopsy with immunohistochemistry and genetic studies—is critical for accurate diagnosis and staging. Treatment typically involves systemic chemotherapy, often combined with rituximab for CD20+ tumors and adjunctive radiotherapy for localized disease. Ongoing research into the genomic and microenvironmental landscape of PAOL is paving the way for novel targeted therapies to improve outcomes. In HIV+ or transplant patients, PAOL are often driven by viral co-infections (EBV, HHV-8) and may require tailored therapy, including optimization of immune status. The dentist’s role encompasses not only diagnosis but also active participation in cancer therapy through preventive and supportive dental care, and persists thereafter by monitoring for recurrence and treating chronic treatment sequelae. This review provides a comprehensive overview of PAOL‘s epidemiology, clinical-pathologic and molecular features, current and emerging treatments, and the essential collaborative role of dentists and hematologists in patient care. Full article

Background: Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphomas (PTCL), not otherwise specified (NOS), share overlapping histology and T-follicular helper (TFH) biology but often show divergent outcomes and treatment needs. The clinical significance of KMT2A rearrangement (KMT2A-r) in nodal PTCL remains undefined. We aimed to investigate the clinicogenomic features and prognostic impact of KMT2A-r in AITL and PTCL-NOS. Methods: We retrospectively analyzed consecutive patients diagnosed with AITL or PTCL-NOS between 2021 and 2024 at two centers. All patients underwent 523-gene DNA/RNA next-generation sequencing. Gene co-variation and diagnostic splits were summarized using network and decision-tree analyses. Results: Overall, 37 patients were included (AITL: 14; PTCL-NOS: 23), with similar baseline clinical characteristics. In AITL, TFH markers were more frequently expressed, and RHOA mutations were enriched. KMT2A-r occurred in 24% of cases without histology-specific enrichment. AITL showed better 2-year overall survival (OS) than PTCL-NOS (70.7% vs. 38.8%; p = 0.040) but similar progression-free survival (PFS). Univariate analysis revealed that KMT2A-r, lactate dehydrogenase elevation, and bone-marrow involvement predicted inferior PFS (Hazard ratio for KMT2A-r: 2.56). Median PFS was 5.9 versus 12.5 months in the KMT2A-r and non-KMT2A-r groups, respectively (p = 0.039). Brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone did not significantly improve OS or PFS overall; however, exploratory analysis indicated improved PFS in the KMT2A-r subset. Conclusions: KMT2A-r delineates an adverse-risk biology in nodal PTCL, aligns with non-TFH genomic hubs and markers of tumor burden, and may serve as a stratifier and hypothesis-generating target for BV-based strategies. Full article

Background: Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), is a rare and aggressive form of lymphoma. Its characteristics and treatment outcomes remain poorly understood. Methods: We identified 15 patients who were diagnosed with pcPTCL-NOS between January 2014 and August 2024 at Tianjin Medical University Cancer Institute and Hospital (TMUCIH) in this retrospective study. The clinical and immunophenotypic features, treatment regimens, and outcomes of these patients were investigated. Results: All patients (4 men, 11 women; median age 54 years) presented with skin lesions, including five stage T1, four stage T2 and six stage T3 lesions. pcPTCL-NOS manifests clinically either with solitary or disseminated rapidly growing nodules/tumors and papules and, less often, ulcers. The lesion sites in patients presenting with solitary/localized tumors (stage T1 and T2) were the head and limbs, and those in patients presenting with disseminated lesions (stage T3) were the trunk, head, and limbs. The CD4/CD8 immunophenotypic characteristics were as follows: CD4+/CD8− 53.33%; CD4+/CD8+ 26.67%; CD4−/CD8− 13.33%; and CD4−/CD8+ 6.67%. One patient had a T follicular helper (TFH) phenotype. Five patients had aberrant expression of the B-cell marker CD20 by tumor cells. All patients received CHOP or CHOP-like regimens as the initial treatment, with three patients undergoing complete lesion resection before chemotherapy, seven patients receiving treatment combined with chidamide (tucidinostat), two patients receiving treatment combined with brentuximab vedotin, two patients receiving treatment combined with mitoxantrone liposomes (Lipo-Mit), three patients receiving treatment combined with radiotherapy, and two patients receiving ASCT after the first-line treatment. The OS rates at 1 year, 2 years, and 3 years were 80%, 77.8%, and 77.8%, respectively; the PFS rates were 60%, 44.4%, and 33.3%, respectively. With a median follow-up of 40 months, the median PFS was 21 months, and the median OS was not reached. Univariate analyses revealed that patients with B symptoms and the CD4−/CD8− phenotype had inferior outcomes (p < 0.05). Age, sex, tumor stage, PIT score, Ki-67 index, elevated β2-MG levels, expression of CD20 or PD1, and treatment selection were not associated with the prognosis. A trend of a survival benefit in patients with solitary (T1) tumors compared with patients with disseminated (T2, T3) tumors was observed, suggesting that it is possible to reduce the intensity of treatment in patients with T1 tumors in the future. Conclusions: pcPTCL-NOS is an aggressive but poorly characterized lymphoma that may require early and active systemic treatment. However, for patients with T1 tumors, reducing the intensity of treatment with CHOP should be appropriately considered. Full article

Peripheral T-cell lymphomas (PTCLs) present a significant clinical challenge despite recent advances in the development of novel therapeutic agents, guided by a deeper understanding of the pathobiology and the genetic and molecular characteristics underlying this complex and heterogeneous group of aggressive non-Hodgkin lymphomas (NHLs) [...] Full article

CD30 is overexpressed in many T-cell lymphoma (TCL) entities, including subsets of peripheral T-cell lymphomas (PTCL) and cutaneous T-cell lymphomas (CTCL). The antibody–drug conjugate brentuximab vedotin (BV), targeting CD30-positive cells, has been approved for the treatment of relapsed or refractory (R/R) systemic anaplastic large cell lymphoma (sALCL), and primary cutaneous anaplastic large cell lymphoma or mycosis fungoides in patients who have received previous systemic therapy. However, many patients still experience disease progression after BV monotherapy. Extensive efforts have been dedicated to investigating effective combinations of BV. A phase III clinical study demonstrated that the combination of BV with cyclophosphamide, doxorubicin, and prednisone (CHP) is superior to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for CD30-positive PTCL. This study led to the approval of BV with CHP as the first-line therapy for CD30-positive PTCL (sALCL in Europe). We summarize the encouraging combination applications of BV in this review. Ongoing studies on combination therapies of BV are also listed, highlighting potential directions for the future application of BV. We focus on dissecting the underlying mechanisms of BV, discussing its effects on both tumor cells and the tumor microenvironment. Exploring resistance mechanisms in TCL provide valuable insights for optimizing BV-based therapies in the future. Full article

Background: T-cell lymphomas (TCLs) are rare and aggressive malignancies associated with poor outcomes, often because of the development of acquired drug resistance as well as intolerance to the established and often toxic chemotherapy regimens in elderly and frail patients. The many subtypes of TCL are well established to exhibit marked geographic variation. The epidemiology, clinical presentation, diagnosis, prognosis, and treatment of TCLs in the Middle East (ME) are yet to be explored; hence, limited data are available about these entities in this part of the world. Aim: Therefore, in this review article, we aim to discuss the available data regarding the T-cell neoplasms in the ME, including the incidence of specific subtypes of peripheral T-cell lymphoma (PTCL), as well as the trends in survival and treatment, all in an effort to understand the natural history of these complex entities across the ME. Full article

Background/Objectives: The tumour microenvironment (TME) plays an important role in the development and progression of cancer and it differs among lymphomas, both with respect to the composition and quantity of specific tumour-infiltrating immune cells (TICs), such as FoxP3⁺ regulatory T cells (Tregs). The role of FoxP3⁺ Tregs in the TME of peripheral T-cell lymphomas (PTCLs) is complex, and their impact on overall survival (OS) remains unclear. Consequently, we aim to evaluate and compare the FoxP3⁺ cell quantity in nodal PTCLs and reactive lymph nodes (LNs), with a focus on investigating their impact on OS. Methods: excisional lymph node (LN) biopsies from 105 nodal PTCLs and 17 reactive LNs are immunohistochemically stained for FoxP3. Visual scoring of FoxP3⁺ cells is performed, and different cut-off values are used to evaluate the impact of FoxP3⁺ cell quantity on OS. Results: FoxP3⁺ cells are present in the TME of all cases, except for four cases where FoxP3⁺ is expressed in lymphoma cells. Lower FoxP3⁺ cell quantities are observed in certain nodal PTCL subtypes compared to reactive LNs. Patients with high FoxP3⁺ cell quantities show improved OS. However, the FoxP3⁺ cell quantity is not confirmed as an independent prognostic biomarker. Conclusions: these findings underscore the promise of FoxP3⁺ cell quantities as added value in prognosis and highlight the potential benefits of Treg-stimulating therapies in PTCLs. Full article

While antibody-based immunotherapeutic strategies have revolutionized the treatment of B-cell lymphomas, progress in T-cell lymphomas has suffered from suboptimal targets, disease heterogeneity, and limited effective treatment options. Nonetheless, recent advances in our understanding of T-cell biology, the identification of novel targets, and the emergence of new therapies provide hope for the future. In this review, we explore four areas of current and evolving antibody-based strategies for the treatment of peripheral T-cell lymphoma (PTCL): monoclonal antibodies (mAbs), bispecific antibodies (BsAs), chimeric antigen receptor T-cell therapy (CAR-T), and antibody–drug conjugates (ADCs). As part of this discussion, we will also include limitations, lessons learned, and potential future directions. Full article

Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphomas (PTCLs), a heterogeneous group of aggressive malignancies with an unfavorable prognosis. Recent evidence has shown that HDACis are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to conventional treatments. Several clinical trials have demonstrated that HDACis, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCLs, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor effects by regulating gene expression through the inhibition of histone deacetylases, which leads to cell cycle arrest, induction of programmed cell death, and,the transformation of cancerous T cells, as demonstrated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACis presents a significant and beneficial treatment choice for PTCLs. However, although HDACis showed potential effectiveness, they could not cure most patients. Therefore, new combinations with conventional drugs as well as new targeted agents are under investigation. Full article

Cytosine methylation contributes to the regulation of gene expression and normal hematopoiesis in mammals. It is catalyzed by the family of DNA methyltransferases that include DNMT1, DNMT3A, and DNMT3B. Peripheral T–cell lymphomas (PTCLs) represent aggressive mature T–cell malignancies exhibiting a broad spectrum of clinical features with poor prognosis and inadequately understood molecular pathobiology. To better understand the molecular landscape and identify candidate genes involved in disease maintenance, we profiled DNA methylation and gene expression of PTCLs. We found that the methylation patterns in PTCLs are deregulated and heterogeneous but share 767 hypo- and 567 hypermethylated differentially methylated regions (DMRs) along with 231 genes up- and 91 genes downregulated in all samples, suggesting a potential association with tumor development. We further identified 39 hypomethylated promoters associated with increased gene expression in the majority of PTCLs. This putative oncogenic signature included the TRIP13 (thyroid hormone receptor interactor 13) gene whose genetic and pharmacologic inactivation inhibited the proliferation of T–cell lines by inducing G2-M arrest and apoptosis. Our data thus show that human PTCLs have a significant number of recurrent methylation alterations that may affect the expression of genes critical for proliferation whose targeting might be beneficial in anti-lymphoma treatments. Full article

Romidepsin is an important therapeutic option for patients with peripheral T-cell lymphoma (PTCL). However, the timing of romidepsin administration remains controversial. The objective of this study was to characterize the safety and efficacy of romidepsin as consolidation therapy after gemcitabine, dexamethasone, and cisplatin (GDP) therapy (GDPR). This study of patients treated between March 2019 and March 2021 was registered with the Japan Registry of Clinical Trials (registration number: jRCT0000000519). If complete response, partial response, or stable disease was confirmed after 2–4 GDP cycles, romidepsin was administered every 4 weeks for 1 year. Seven patients with relapsed/refractory (R/R) PTCL (T-follicular helper phenotype [n = 1] and angioimmunoblastic T-cell lymphoma [n = 6]) were included in this prospective study (PTCL-GDPR). After a median follow-up of 34 months of patients in PTCL-GDPR, the 2-year overall survival rate was 71%, and the overall response rate after treatment was 57%. Common adverse events in patients with PTCL-GDPR included hematological toxicities such as neutropenia, which improved with supportive treatment. There were no treatment-related mortalities. GDPR might be safe and effective in elderly transplant-ineligible patients with R/R PTCL; however, further investigation is required. Full article

Brentuximab vedotin (BV) monotherapy (BV-M) and combination (BV-C) therapies are safe and effective for classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphomas (PTCLs). Although the sample sizes have been small (12–29 patients), in clinical studies, response rates of 53–88% have been reported for BV retreatment in patients with an initial BV response. We evaluated the real-world characteristics and treatment patterns of cHL/PTCL patients who received BV and were retreated in the United States. Symphony Health Patient Claims (11/2013–1/2022) were retrospectively analyzed to identify cHL/PTCL patients treated with BV and retreated with BV-M, BV-C, or non-BV therapy. Patient characteristics were described by retreatment, and predictors of BV-M retreatment were identified. Among the cHL and PTCL patients treated with BV (n = 6442 and 2472, respectively), 13% and 12%, respectively, were retreated with BV; the median times from initial BV to BV-M retreatment were 5 and 7 months, respectively; and the numbers of BV-M retreatment doses were 4 and 5, respectively. Among cHL patients, the predictors of BV-M retreatment were age (18–39 vs. ≥60 years), sex (women vs. men), and previous stem cell transplantation (yes vs. no). Among PTCL patients, the only predictor of BV-M retreatment was systemic anaplastic large-cell lymphoma subtype (yes vs. no). Real-world data support clinical study results suggesting earlier BV treatment be considered, as BV retreatment may be an option. Full article

Over the past three decades, the treatment of lymphoproliferative disorders has undergone profound changes, notably due to the increasing availability of innovative therapies with the potential to redefine clinical management paradigms. A major impact is related to the development of monoclonal antibodies, checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T (CAR-T) cell therapies. This review discusses the current landscape of clinical trials targeting various hematological malignancies, highlighting promising early-phase results and strategies to overcome resistance. Lymphoproliferative disorders encompass a range of conditions: while in Hodgkin lymphoma (HL) the goal is to reduce chemotherapy-related toxicity by integrating immunotherapy into the frontline setting, peripheral T cell lymphoma (PTCL) lacks effective targeted therapies. The review emphasizes a shifting therapeutic landscape towards precision medicine and treatment modalities that are less toxic yet more effective. Full article