RARE DISEASE
Enteropathy-associated T-cell lymphoma
Enteropathy-associated T-cell lymphoma
Enteropathy-associated T-cell lymphoma
Synonyms: EATL, ETTL, Enteropathy-associated T-cell lymphoma type 1, Enteropathy-type T-cell lymphoma, Intestinal T-cell lymphoma
Synonyms: EATL, ETTL, Enteropathy-associated T-cell lymphoma type 1, Enteropathy-type T-cell lymphoma, Intestinal T-cell lymphoma
Synonyms: EATL, ETTL, Enteropathy-associated T-cell lymphoma type 1, Enteropathy-type T-cell lymphoma, Intestinal T-cell lymphoma
Drug discovery
1
drug
With orphan designation
Overview
Enteropathy-associated T-cell lymphoma (EATL) is a rare, aggressive peripheral T-cell lymphoma strongly linked to celiac disease (CD). It arises from malignant intraepithelial T-cells, typically in the small intestine, and presents with abdominal pain, weight loss, or bowel perforation [1][13]. Prognosis is poor, with a median survival of 6 months and 5-year survival rates of 8–20% [4][15]. Diagnosis relies on histopathology, often revealing villous atrophy and CD-linked inflammatory changes [5][17].
Therapies
Surgery: Emergency resection for perforation/obstruction; early debulking improves outcomes [3][10][15].
Chemotherapy: Anthracycline-based regimens (e.g., CHOEP) followed by autologous stem cell transplantation in eligible patients [7][15][19].
Emerging therapies: Brentuximab vedotin (anti-CD30) and clinical trials for relapsed/refractory cases [3][7].
Categories: rare gastroenterological diseases, rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
173 drug discovery papers about Enteropathy-associated T-cell lymphoma, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
173 drug discovery papers about Enteropathy-associated T-cell lymphoma, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-07 | [Current status and progress in the diagnosis and treatment of monomorphic epitheliotropic intestinal T-cell lymphoma].
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and highly aggressive type of intestinal T-cell lymphoma. With the application of high-throughput sequencing technologies in recent years, the understanding of this entity has become increasingly comprehensive. The World Health Organization classification of lymphoma now recognizes MEITL as a distinct disease entity. However, the extreme rarity of MEITL poses substantial challenges for clinical diagnosis and management, and patient outcomes remain poor. Based on a systematic review of recent literature, this article summarizes the diagnostic criteria of MEITL, integrating pathology and molecular biology; outlines current multimodal treatment approaches centered on surgery, chemotherapy, and hematopoietic stem cell transplantation; and reviews available clinical and translational data to explore the potential role of epigenetic agents, JAK/STAT pathway inhibitors, and other emerging therapeutic strategies in MEITL. This article summarizes the current status and recent advances in the diagnostic and therapeutic strategies for MEITL in clinical practice and provides a reference for the design of future prospective, multicenter clinical studies.
2026-06-22 | Monomorphic epitheliotropic intestinal T-cell lymphoma presenting as acute small intestinal perforation: a case report and exploratory BCL-2-targeted therapy.
To report a rare case of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) presenting with acute gastrointestinal perforation and to describe the use of an exploratory regimen combining a BCL-2 inhibitor (Venetoclax) with CHOP chemotherapy, highlighting the diagnostic challenges and therapeutic considerations for this aggressive disease. We detail the clinicopathological journey of a 72-year-old male patient who presented with an acute abdomen. The diagnosis was established through surgical pathology and comprehensive immunohistochemistry. Following an initial treatment refusal and a subsequent disease recurrence manifesting as a second perforation, the patient received Venetoclax combined with CHOP. The relevant literature was reviewed to inform the diagnostic and therapeutic decisions. Emergency surgery for perforation revealed MEITL (initially staged as Lugano stage I). The patient initially declined therapy but presented 9 months later with recurrent perforation, confirmed as disease relapse via pathology. Immunohistochemistry showed tumor cells were CD3 (weakly positive), CD8+, CD56+, Bcl-2 (3+), and Ki-67 (~60%). Postoperative PET/CT revealed limited retroperitoneal lymph node involvement. The patient received four cycles of Venetoclax (200 mg/day, days 1-14) plus CHOP, achieving complete metabolic remission on follow-up PET/CT without significant myelosuppression. The 9-month untreated interval despite high Ki-67 is noteworthy. MEITL is a highly aggressive lymphoma often presenting as a surgical emergency. Diagnosis relies on histopathology and a characteristic immunophenotype (CD3+ CD8+ CD56+). This case suggests that incorporating BCL-2 inhibition into the treatment of Bcl-2-high MEITL may represent a biologically rational strategy. Besides, the prolonged untreated interval observed in this patient highlights the potential biological heterogeneity of MEITL. While the observed complete metabolic remission is encouraging, this finding remains hypothesis-generating and requires validation in larger studies.
2026-05-27 | Efficacy and tolerability of duvelisib in relapsed/refractory peripheral T-cell lymphoma: A multicenter real-world analysis.
7067 Background: Relapsed/refractory (R/R) peripheral T-cell lymphomas (PTCL) are a rare group of non-Hodgkin lymphomas with median survival at relapse of 6-10 months and few treatment options. Duvelisib is a g/∆ phosphatidylinositol 3-kinase inhibitor approved in CLL and NCCN compendium listed in PTCL. In indolent lymphomas, concerns for cumulative duvelisib toxicity limit its use. In contrast, studies in R/R PTCL show duvelisib to be well-tolerated. Therefore, we sought to assess the efficacy and tolerability of duvelisib in a real world setting in R/R PTCL. Methods: We conducted a retrospective analysis of patients with R/R PTCL treated with duvelisib from 2012-2025 at 12 centers. Results: We identified 207 patients with PTCL: nodal PTCL with TFH phenotype (n=106, 51%), PTCL-NOS (n=78, 38%), ALCL (n=16, 8%), enteropathy associated T-cell lymphoma (n=4, 2%), NK/T-cell lymphoma (n=2, 1%), adult T-cell leukemia/lymphoma (n=1, 0.5%). 90 patients (43%) were female. Median age was 64; median International Prognostic Index score 3. Median prior lines of therapy was 2 (range 1-9). 26% received frontline transplant (23% auto, 3% allo). 118 patients received single agent duvelisib; 89 patients received duvelisib in combination with other agents (66 romidepsin, 12 bortezomib, 4 azacitadine, 3 ruxolitinib, 4 other). Of patients with response data, ORR was 51% (94/186; 31% CR, 17% PR) with median OS 12 months. ORR in patients with TFH-phenotype vs. non-TFH phenotype was 60% and 41% respectively. ORR in patients treated with single agent duvelisib and duvelisib combinations was 46% (46/99; 29% CR, 17% PR) and 55% (48/87; 39% CR, 16% PR), respectively with no difference in OS. Median duration of therapy was 84 days; the most common reason for discontinuation was progression (41%, 76/186). 13% (25/196) underwent allo-SCT after duvelisib therapy. Toxicity data is summarized in our table. In patients receiving single agent duvelisib therapy, rates of cytopenia were lower (7% vs. 34%, p<0.001) and rates of colitis were higher (17% vs. 7%, p= 0.03). Conclusions: In this real world, multicenter analysis of patients with R/R PTCL treated with duvelisib-based regimens, the ORR of 51% was consistent with published trials. Duvelisib therapy was well tolerated and a minority required hospitalization for toxicity. This suggests that duvelisib is safe in patients with R/R PTCL who have poor prognosis and limited treatment options. Adverse Event Full Cohortn (%)n=207 Single agent n (%)n=118 Combination therapyn (%)n=89 Single vs. Combination p value SteroidGivenn (% full cohort) Hospitalizationn (% full cohort) Rash 41 (20%) 24 (20%) 17 (19%) 0.83 23 (11%) 6 (3%) Colitis 26 (13%) 20 (17%) 6 (7%) 0.03 20 (10%) 16 (8%) Pneumonitis 7 (3%) 4 (3%) 3 (3%) 0.99 5 (2%) 3 (1%) Cytopenia 38(18%) 8 (7%) 30 (34%) <0.001 * * Transaminitis 33 (16%) 21 (18%) 12 (13%) 0.40 * * Infection 66 (32%) 36 (31%) 30 (34%) 0.63 N/A 42 (20%) *Not available.
2026-03-06 | Case report and literature review: Golidocitinib as a potential treatment for monomorphic epitheliotropic intestinal T-cell lymphoma.
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare type of non-Hodgkin lymphoma and a highly aggressive malignancy with a median overall survival of 7 months. Meanwhile, owing to the complex and confusing symptoms including nonspecific gastrointestinal symptoms, systemic manifestations and additional clinical manifestations associated with the extraintestinal involvement organs, MEITL is often diagnosed at an advanced stage. We report three cases of MEITL, and searched PubMed indexed articles between 2016 and 2024 for these terms: "MEITL" and "case report". We found that younger patients, those with intestinal perforation, and those who did not receive chemotherapy had worse prognoses. Importantly, we found that treatment with the JAK-1 inhibitor Golidocitinib in combination with the GDP regimen (Gemcitabine, Dexamethasone and Cisplatin) can improve patient prognosis. The study suggests that Golidocitinib could potentially improve the prognosis of MEITL patients by targeting the JAK-STAT pathway, although further validation of its long-term effectiveness is needed.
2026-02-23 | Case Report: Targeting the Achilles' heel of monomorphic epitheliotropic intestinal T-cell lymphoma.
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and highly aggressive lymphoma with a dismal prognosis and no established standard therapy. Its frequent expression of BCL-2 provides a rationale for targeting this anti-apoptotic protein. We report the case of a 34-year-old female with refractory MEITL who failed prior lines of therapy, including CHOPE and gemcitabine/oxaliplatin (GemOx) combined with golidocitinib. Based on positive BCL-2 expression by immunohistochemistry, a salvage regimen combining venetoclax with Gemox was administered. The treatment induced a rapid and significant clinical improvement. A follow-up PET/CT scan confirmed complete metabolic remission. The main adverse event was grade 4 neutropenia and thrombocytopenia with febrile neutropenia, attributable primarily to the Gemox backbone, which resolved with supportive care. The off-label use was approved by the institutional committee, and informed consent was obtained. To our knowledge, this is the first report of successful treatment of refractory MEITL with a venetoclax-containing regimen. This case validates BCL-2 as a actionable therapeutic target in MEITL. Future efforts should focus on optimizing combination partners for venetoclax to improve efficacy and tolerability. The rationale for exploring venetoclax as post-transplant maintenance therapy in MEITL is also discussed.
cell therapies
2025-11-15 | Long-term disease control of monomorphic epitheliotrophic intestinal T-cell lymphoma (MEITL) with CNS involvement in a caucasian patient by allogeneic hematopoietic cell transplantation
Monomorphic epitheliothrophic intestinal T-cell lymphoma (MEITL), formerly known as type II enteropathic T-cell lymphoma, is an aggressive form of peripheral T-cell lymphoma (PTCL) primarily originating from intraepithelial lymphocytes of the intestine [ 1 ]. Arising mostly in the small intestine with solitary or multifocal, often destructing lesions, it can disseminate in lymph nodes and non-intestinal organs including bone marrow and the central nervous system (CNS) [ 1 , 2 , 3 , 4 ]. It predominantly affects Asian and Hispanic populations but very rarely also Caucasians [ 1 , 5 ]. Generally, MEITL responds poorly to anthracycline-based lymphoma-typic induction chemotherapy, prompting investigators to explore more aggressive first-line treatment including high-dose therapy with autologous hematapoietic cell transplantation (auto-HCT). Although this strategy may be associated with better disease control, almost all patients will eventually relapse [ 6 , 7 ]. Accordingly, the prognosis of MEITL is dismal with median survival times around 12 months and only few long-term survivors [ 2 , 3 , 6 , 7 ]. The outcome is particularly poor if CNS involvement is present, a recent literature review identified only a single survivor among 12 cases reported [ 4 ]. Thus, expert recommendations advocate consolidation of MEITL responses by cellular immunotherapy through allogeneic hematopoietic cell transplantation (alloHCT) in analogy to other aggressive extranodal PTCL with similar biological behavior, such as hepatosplenic T-cell lymphoma [ 8 , 9 ] and acute/lymphoma-type adult T-cell leukemia/lymphoma [ 10 , 11 ], although the evidence basis for this is very poor.
2025-11-03 | Impact of antibiotic exposure on CAR-T cell therapy outcomes: Analysis in multiple Myeloma and lymphoma
Abstract Background: The gut microbiome is known to play a significant role in cancer immunotherapy. Antibiotic use can disrupt the intestinal microbiota and potentially diminish the antitumor efficacy of CAR-T cell therapy. According to a 2023 study by Stein-Thoeringer et al. in Nature Medicine, administration of broad-spectrum antibiotics prior to CAR-T infusion was associated with poorer treatment outcomes. Objective To assess the association between pre-CAR-T antibiotic exposure and clinical outcomes (response rates, progression-free survival [PFS], overall survival [OS]) and treatment-related adverse events (cytokine release syndrome [CRS], immune effector cell-associated neurotoxicity syndrome [ICANS], and prolonged hematologic toxicity) in patients with multiple myeloma (MM) and lymphoma. Methods We retrospectively analyzed the cohorts of CAR-T therapy treated patients in the three disease categories above. Patients were grouped by antibiotic exposure within a defined pre-CAR-T window (4 weeks prior to infusion). A risk-scoring model for severe hematologic toxicity further categorized patients into high-risk (score ≥3) and low-risk (score 0–2) subgroups. Outcomes were compared between groups. Results Among 334 patients, the MM cohort (n=199) showed no significant difference in objective response rate (ORR: 70.0% vs. 81.7%) between antibiotic-exposed (n=90) and non-exposed (n=109) groups, but complete remission (CR) rates were significantly lower in the antibiotic group (40.0% vs. 57.8%). Antibiotic-exposed patients had shorter median PFS (6.7 vs. 13.9 months) and OS (21.9 vs. 36.1 months). CRS (71.1% vs. 69.7%) and ICANS (3.3% vs. 1.8%) incidences were comparable. Similarly, stratified analyses of ATB classes were conducted, yielding consistent results. In the lymphoma cohort (n = 135), 61 (45.2%) patients were exposed to antibiotics. Importantly, the difference in ORR between the two groups was not statistically significant (66.2% vs. 70.5%), nor was there a significant difference in the incidence of CRS (16.4% vs. 21.6%). However, patients who received antibiotics had a significantly shorter median PFS and OS than patients who did not receive antibiotics (P< 0.05). Conclusion Pre-CAR-T antibiotic exposure, particularly to broad-spectrum low-risk antibiotics (HR ABX), reduces complete remission rates and shortens survival across MM and lymphoma, potentially via gut microbiome disruption. While CRS/ICANS risks remain unaffected, judicious antibiotic use is critical to optimize CAR-T efficacy. Future strategies should prioritize microbiome preservation or selective use of low-risk antibiotics (LR ABX).
2025-06-01 | 141 | CD30 CAR‐T IN RELAPSED AND REFRACTORY CD30+ LYMPHOMAS: LONG‐TERM FOLLOW‐UP OF A PHASE IB/II CLINICAL TRIAL
Introduction: CD30 CAR-T is active and safe in relapsed/refractory (r/r) CD30+ lymphomas, including classic Hodgkin lymphoma (cHL) and mature T-cell lymphomas (MTCLs). Here, we share long-term follow-up from our phase Ib/II trial (NCT02690545). Methods: Following cell procurement and CD30 CAR-T manufacturing, patients (pts) received lymphodepletion (LD) followed by CAR-T infusion. Pts could receive bridging between procurement and LD. Two dose levels were assessed in a 3+3 design: 1x108 CAR+ cells/m2 (DL1) and 2x108 CAR+ cells/m2 (DL2). Once dose escalation was completed in adults, children were enrolled on the phase Ib portion. Inclusion criteria include r/r CD30+ lymphoma after ≥ 2 therapies and Karnofsky/Lansky performance status > 60%. LD was initially bendamustine (benda) 90 mg/m2/day on days −5 to −4, but was changed to fludarabine (flu) 30 mg/m2/day and benda 70 mg/m2/day on days -5 to -3 for efficacy. Results: 34 pts received CD30 CAR-T 1/10/2017 to 3/11/2024, including 29 with cHL and 4 with MTCLs (ALK+ ALCL, enteropathy-associated T-cell lymphoma, primary cutaneous ALCL, and Sézary syndrome). Median age was 33 (range 10–68) for cHL and 31 (11–70) for MTCL. The median number of prior lines of therapy was 5 (2–18) in cHL and 4 (2–6) in MTCL. Bridging therapy (new therapy started between procurement and CAR-T infusion) was used in 15 cHL and 3 MTCL pts. In cHL pts, prior therapies—including bridging—included brentuximab vedotin (n = 28), PD-1 inhibitor (PD-1i, n = 23), bendamustine (n = 18), autologous stem cell transplant (SCT, n = 24), and alloSCT (n = 10). At LD, 24 cHL and 4 MTCL pts had active disease (PR or worse) and were evaluable for response to CAR-T. 8 pts with cHL received benda LD; all others received flu/benda LD. Median vein-to-vein time (time from procurement to CAR-T infusion) was 84 days (40–337). 7 pts with cHL and 2 with MTCL were treated on DL1; all others on DL2. In cHL pts, the CR rate with benda LD was 0/5; it was 15/19 with flu/benda LD. 2/4 pts with MTCL achieved CR. Median follow-up was 6.6 years for cHL and 6.0 years for MTCL. For cHL, 6-year progression-free survival (PFS) was 19% (80% CI: 11–32), 6-year duration of response (DOR) was 25% (80% CI: 15–41), and 6-year overall survival (OS) was 84% (80% CI: 73–96) (Figure 1A–C). For MTCL, 6-year PFS was 50% (80% CI: 26–95), 6-year DOR was 67% (80% CI: 40–100), and 6-year OS was 67% (80% CI: 40–100) (Figure 1D–F). In pts with cHL, Flu/benda LD (HR: 0.47, 80% CI 0.26–0.85) and PD-1i ≤ 1 year before CAR-T (HR: 0.44, 80% CI: 0.25–0.79) were associated with superior PFS, whereas increasing lines of therapy and prior alloSCT were associated with inferior PFS (Figure 1G). Conclusions: CD30 CAR-T has encouraging activity and maintains durable responses in a heavily pretreated population with cHL and CD30+ MTCLs. As previously reported, fludarabine-based LD is critical for its efficacy. Our group continues exploring the beneficial impact of PD-1i on CD30 CAR-T outcomes. Research funding declaration: This work was supported by funding from the National Institutes of Health (UNC-Integrated Translational Oncology T32-CA244125 to UNC/DKR) Keywords: cellular therapies; aggressive T-cell non-Hodgkin lymphoma; Hodgkin lymphoma Potential sources of conflict of interest: J. Serody Other remuneration: Carisma Therapeutics, Merck Inc. Glaxo Smith Klein, PIQUE Therapeutics, Triangle Biotechnology G. Dotti Consultant or advisory role: Bellicum Pharmaceuticals, Catamaran Bio, Estrella N. Grover Honoraria: Regeneron Pharmaceuticals, Novartis, BMS, Caribou, Janssen, Kite Other remuneration: Sangamo
2024-12-18 | Enteropathy-associated T-cell lymphoma: A population-based cohort study on incidence, treatment, and outcome in the Netherlands.
Enteropathy-associated T-cell lymphoma (EATL) is a peripheral T-cell lymphoma (PTCL) with a poor prognosis. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide consolidated by autologous stem cell transplantation (ASCT) are recommended for fit PTCL patients. The role of etoposide and ASCT in EATL is unclear. This study reports the incidence, treatment, and outcome of EATL patients using the Netherlands Cancer Registry, with nationwide coverage of >95%. All patients diagnosed in 1989-2021 (n = 351, 77% treated) were identified (median age 67 years, 56% male, 50% limited stage). Time period analysis assessed trends in primary therapy and overall survival (OS). Treatment included chemotherapy (CT) (34%), surgery (18%), surgery and CT (19%) or CT followed by ASCT (7%). The 5-year OS for treated patients with limited versus advanced stage was 19% and 9% respectively. The 2-year OS improved over time (21%-33%, p = 0.06). Surgery only (hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.55-3.01, p < 0.01) and advanced-stage disease (HR 1.67; 95% CI 1.25-2.23, p = 0.01) were predictors of poor prognosis. ASCT (HR 0.31; 95% CI 0.18-0.56) was associated with improved OS. There was no statistical difference in OS between patients treated with or without etoposide. Current first-line treatment is ineffective.
2024-10-11 | Enteropathy-Associated T-Cell Lymphoma Treated With Autologous Hematopoietic Stem-Cell Transplant: A Glimmer of Hope?
We report a case of primary enteropathy-associated T-cell lymphoma in a 50-year-old man presenting with abdominal pain, chronic diarrhea, and significant weight loss over 6 months. Diagnosis was confirmed through endoscopy, biopsy, and positron emission tomography-computed tomography, staging the disease as stage 1E. The patient underwent initial treatment with the cyclophosphamide, doxorubicin (also known as hydroxydaunorubicin), vincristine (also known as oncovin), etoposide, and prednisolone chemotherapy regimen, followed by high-dose hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone chemotherapy and autologous stem cell transplantation. Despite developing febrile neutropenia and septic shock during treatment, the patient achieved disease remission and symptom resolution. This case underscores the potential of autologous stem-cell transplantation as a curative approach for primary enteropathy-associated T-cell lymphoma and highlights the need for further research on its effectiveness.
antibodies
2026-07-04 | Genomic loss of MLH1/PMS2 loci defines a mismatch repair deficient subgroup in monomorphic epitheliotropic intestinal T-cell lymphoma.
Primary intestinal T-cell lymphomas (ITCLs), comprising enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), are rare aggressive tumors. The role of DNA mismatch repair (MMR) deficiency (dMMR) and microsatellite instability (MSI) in the development of ITCLs remains largely unexplored. Here, we investigated the incidence, molecular mechanisms and clinical relevance of dMMR/MSI in 86 ITCLs (30 EATLs, 56 MEITLs) using whole-exome sequencing, PCR-based MSI testing, DNA methylation profiling, and immunohistochemistry for MLH1, MSH2, MSH6 and PMS2. MMR deficiency was detected in 3 of 53 MEITLs (6%) but in none of the EATLs. dMMR MEITLs showed the highest tumor mutational burden (8.3-17.1 mutations/Mb), compared to median TMBs of 1.9 in MEITL and 2.4 in EATL. The complete loss of MLH1/PMS2 expression in two MSI-high tumors and isolated PMS2 loss in the third case were all associated with biallelic deletions of the affected loci. Notably, MLH1 deletions significantly co‑occurred with SETD2 deletions (p = 0.001), the latter representing a major driver of MEITL tumorigenesis. dMMR MEITLs lacked distinctive clinicopathologic features. These findings indicate that dMMR/MSI occurs in a subset of MEITLs probably during tumor progression, rather than being an initiating driver event, and provide a biological rationale to explore the efficacy of immune checkpoint inhibitors in some of this unfavorable subtype of ITCL.
2026-01-04 | A Clinical Review of Collagenous Sprue, Refractory Celiac Disease, Ulcerative Jejunitis, and Enteropathy-Associated T-cell Lymphoma
Celiac disease is a chronic immune-mediated enteropathy caused by gluten exposure. It affects approximately 1% of the world"s population and can present at any age with a wide range of signs and symptoms including malabsorption. Adherence to a gluten-free diet is the basis of treatment; however, a small subset of patients can develop worsening and life-threatening gastrointestinal symptoms despite gluten avoidance. Clinical worsening despite a gluten-free diet should raise concern for other conditions such as collagenous sprue or other more severe forms of celiac disease. Collagenous sprue is characterized by a subepithelial collagen band and celiac-like histologic features in the small bowel mucosa. It is unclear whether collagenous sprue falls within the celiac disease spectrum or represents a distinct entity. Refractory celiac disease is a rare form of celiac disease unresponsive to a gluten-free diet and can be subdivided into types I and II. The latter is defined by a clonal aberrant population of intraepithelial lymphocytes that accumulate lymphomagenic mutations. Refractory celiac disease type II is a premalignant condition that may exhibit ulcerative jejunitis or progress to the very aggressive enteropathy-associated T-cell lymphoma. Immunohistochemistry, flow cytometry, and T-cell receptor clonality testing aid in the diagnosis of refractory celiac disease. Treatment options include immunosuppressants, chemotherapy, and stem cell transplantation. The objective of this paper is to provide an overview of collagenous sprue, refractory celiac disease, ulcerative jejunitis, and enteropathy-associated T-cell lymphoma with a focus on presentation, pathogenesis, diagnosis, and treatment.
2025-11-03 | Brentuximab vedotin plus DHAP as effective salvage therapy in CD30+ peripheral T-cell lymphoma: A retrospective multicenter study
Abstract The prognosis of most nodal peripheral T-cell lymphomas (T-NHL) has not significantly improved over the past 25 years. Stage- or IPI-dependent 5-year overall survival (OS) rates remain around 30%. Recently, for the first time, a significant OS benefit was demonstrated for the combination of brentuximab vedotin (BV) and CHP (cyclophosphamide, doxorubicin, prednisone) compared to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in the first-line treatment of patients with anaplastic large cell lymphoma (ALCL). However, approximately 30% of patients with peripheral T-NHL experience a disease course that is primarily refractory, with dismal prognosis. BV monotherapy achieves high remission rates, particularly in relapsed ALCL, but also in other relapsed T-NHL subentities. For relapsed/refractory (R/R) nodal peripheral T-NHLs other than ALCL, only conventional (multi-agent) chemotherapy is approved by both the European Medicines Agency as well as the Food and Drug Administration, while single-agent BV is approved for R/R ALCL only. Effective treatment options for younger patients with high remission rates for curative intended treatment concepts are urgently needed. In Hodgkin lymphoma, the addition of BV to DHAP (dexamethasone, high-dose cytarabine, cisplatin) has shown promising efficacy as a salvage regimen in a phase II trial. Based on this, we conducted a multicenter retrospective analysis based on the national T-NHL registry platform of the GLA and OSHO study groups to evaluate the efficacy and tolerability of platinum-based salvage therapies in combination with BV in patients with R/R T-NHL. A total of 26 patients treated with either BV-DHAP or BV-ICE between 2015 and 2025 were identified. Median age at diagnosis was 55 years (range 23–77), and 11/26 patients (42.3%) were female. Histologic subtypes included ALCL (11/26, 42.3%), angioimmunoblastic T-cell lymphoma, T-NHL not otherwise specified, enteropathy-associated T-cell lymphoma, and systemic primary cutaneous T-NHL. Most lymphoma expressed CD30 (22/26; 84,6%), 1/26 (3,9%) was assessed as CD30-negative and for 3/26 patients (11,5%) the information was not available. Median number of prior treatment lines was 2 (range 1-7). Eight out of 26 patients (30.8%) had previously received BV, and 4/26 (15.4%) had undergone prior autologous stem cell transplantation. Most patients (24/26, 92.3%) were refractory to the previous therapy or had relapsed within one year. Fourteen patients received BV-ICE, and 12 received BV-DHAP as salvage therapy. Best overall response rate (ORR) in the entire cohort was 53.9% (14/26), including CR in 6/26 (23.1%) and PR in 8/26 (30.8%). In the BV-ICE subgroup, ORR was 35.7% (5/14; CR 1/14 [7.1%], PR 4/14 [28.6%]). In contrast, the BV-DHAP subgroup demonstrated an ORR of 83.3% (10/12; CR 5/12 [41.7%], PR 5/12 [41.7%]). Among BV-DHAP patients, 8 had ALCL and 4 had other T-NHL subtypes. All non-ALCL patients (4/4) and 6/8 (75%) of ALCL patients responded to BV-DHAP. In the BV-ICE group, 3 patients had ALCL and 11 had other T-NHLs; responses were seen in 3/11 (27,3%) non-ALCL patients and 2/3 (66,7%) ALCL patients. Toxicities were manageable, comparable between regimens and primarily included grade 3/4 hematologic adverse events in 18/21 patients (85,7%), febrile neutropenia in 13/21 patients (61,9%), and transient liver enzyme elevations in 20/23 patients (87%). No new cases of peripheral neuropathy were documented. In conclusion, BV-DHAP was particularly effective as a salvage regimen in this high-risk cohort of R/R CD30-positive T-cell non-Hodgkin lymphoma, with manageable toxicity. Further studies are warranted to establish its superiority over BV monotherapy in this setting.
2025-10-13 | Incidence trends and survival analysis of enteropathy-associated T-cell lymphoma.
Enteropathy-associated T-cell lymphoma (EATL) is a rare, aggressive form of T-cell non-Hodgkin lymphoma, primarily affecting the small intestine. Due to its extremely low incidence and poor prognosis, studies on EATL are limited. This study aims to analyze the incidence trends, prognostic factors, and survival outcomes of EATL using the SEER database. We analyzed the incidence trends of EATL using SEER data from 2000 to 2021 and performed multivariate Cox regression to identify independent prognostic factors. Conditional survival (CS) analysis was performed to evaluate survival outcomes, and a CS-nomogram was developed to predict 1-, 3-, and 5-year overall survival (OS) and 5-year CS. The age-adjusted incidence rate of EATL was 0.014 per 100,000, showing a significant upward trend (APC 2.63). Multivariate analysis identified age, tumor site, tumor stage, surgery, and chemotherapy as independent OS risk factors. CS analysis showed that the 5-year survival probability progressively increased from 16% to 48%, 67%, 83%, and 93% after surviving 0, 1, 2, 3, and 4 years post-diagnosis. The dynamic nomogram showed excellent performance in predicting survival and stratifying patients into risk groups. This study provided valuable insights into the epidemiology, prognosis, and survival outcomes of EATL. The increasing incidence and CS outcomes highlighted the importance of early detection and intervention. The dynamic nomogram model developed here offered a more accurate prediction of individual survival outcomes and can aid in clinical decision-making.
2025-10-01 | S3029 Timing of Lymphoproliferative Disorder Diagnosis in Patients With Celiac Disease
Introduction: Celiac disease (CeD) is associated with an increased risk of enteropathy-associated T-cell lymphoma (EATL) and other non-Hodgkin lymphomas (NHL), which contribute to increased mortality risk. In the general population, cases of B-cell NHL far outnumber T-cell NHL. Our aim was to compare CeD patients diagnosed with a lymphoproliferative disorder (LPD) before CeD diagnosis to those diagnosed with an LPD concurrently or after CeD diagnosis. Methods: We performed a retrospective study of adult patients seen at our tertiary referral center between 1980 and 2024. Diagnosis of CeD was confirmed by villous atrophy on duodenal biopsy and/or by positive CeD serology. LPD was defined as a lymphoid malignancy, including multiple myeloma, Hodgkin lymphoma, NHL, and refractory celiac disease type II, considered to be a precursor of EATL. Diagnosis of CeD and LPD within 1 year was considered concurrent. Results: There were 87 cases of LPD identified in 82 patients, with 4 patients developing more than 1 LPD. There were 41 cases of T-cell NHL, with 90% presenting concurrently or after CeD diagnosis. The 4 cases presenting before CeD diagnosis were cutaneous: cutaneous anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, cutaneous T-cell lymphoma (2 cases), and lymphomatoid papulosis type A. There were 36 cases of B-cell NHL, with 31% presenting before and 69% presenting concurrently or after CeD diagnosis. Comparing patients diagnosed with LPD before CeD diagnosis to those diagnosed concurrently or after CeD diagnosis, we found a mean age of CeD diagnosis of 58.6 and 57.6 years (P = 0.9), respectively, and a mean age of LPD diagnosis of 48.5 and 65.5 years (P < 0.001), respectively. Classical CeD presentation was seen in 38.9% and 68.9% of patients (P = 0.021), respectively. After LPD diagnosis, the median survival of patients with B-cell NHL was longer than for those with T/NK-cell NHL (18.6 vs 9.4 years, P = 0.008). Conclusion: In this series, both B-cell and T-cell NHL cases were seen in CeD patients. Patients with B-cell NHL had longer median survival than those with T/NK-cell NHL. Patients diagnosed with LPD concurrently or after CeD diagnosis were more likely to have had a classical CeD presentation. Cases of T-cell NHL presenting before CeD diagnosis consisted of a small, heterogeneous group of cutaneous lymphomas, while the vast majority of T-cell NHLs were diagnosed concurrently or after CeD diagnosis.
proteins
2025-06-01 | 483 | SINGLE‐CELL AND SPATIAL TRANSCRIPTOMIC PROFILING IDENTIFIES M1 MACROPHAGE‐MEDIATED TUMOR SUPPRESSION IN MONOMORPHIC EPITHELIOTROPIC INTESTINAL T‐CELL LYMPHOMA
Z. Zhang and F. Cheng equally contributing author. Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), a rare and highly aggressive intestinal malignancy with predominant incidence in Asian populations, is characterized by an insidious onset and dismal prognosis. Despite its clinical severity, the tumor microenvironment (TME) drivers of MEITL pathogenesis remain poorly defined. Methods: We retrospectively analyzed clinicopathological data from 20 MEITL patients (Asian cohort; median age 55.2 years; 65% male) treated at the first affiliated hospital of Zhejiang University School of Medicine from January 2019 to October 2023. ScRNA-seq and spatial transcriptomics were performed on surgically resected intestinal lesions from four treatment-naïve patients with distinct clinical trajectories. M1 macrophages (CD80+CD68+) were quantified per high-power field and survival correlations were assessed by Kaplan-Meier with log-rank testing. Results: Clinicopathological analysis demonstrated a predominant involvement of the jejunum and ileum (95%), with abdominal pain (85%), diarrhea (75%), and intestinal perforation (60%) representing the most frequent clinical manifestations. Immunophenotypic profiling revealed consistent expression of CD3 (100%), CD8 (85%), and CD56 (95%) in tumor cells, while showing absence of CD5 (95%) and Epstein-Barr virus association (EBER−, 90%). Single-cell transcriptomic analysis delineated eight distinct cellular compartments within the TME, including malignant T/NK-like hybrid cells, intestinal epithelial cells, and macrophage subsets, with a notable absence of conventional NK cells. Spatial transcriptomic mapping uncovered significant topographical co-localization between tumor cells and macrophages, particularly M1-polarized subsets. Differential gene expression analysis of M1 macrophages adjacent to tumor cells revealed marked enrichment of cytotoxic effector pathways (e.g., granzyme B, perforin) and immune regulatory networks (e.g., TNF superfamily, FASLG). Importantly, quantification of M1 macrophage density in pathological sections demonstrated a robust positive correlation with patient survival (R2 = 0.511, p < 0.001). Conclusions: MEITL is characterized by an insidious onset, frequently manifesting as acute abdominal emergencies, and associated with a dismal prognosis. Integrative analysis of single-cell RNA sequencing and spatial transcriptomics reveals that malignant T cells adopt NK-like transcriptional programs while simultaneously depleting endogenous NK cell populations, indicative of a dominant immune niche occupation. The discovery of spatial symbiosis between tumor cells and M1 macrophages challenges the conventional “immune desert” paradigm in T-cell lymphomas. Importantly, M1 macrophages exhibit context-dependent tumor-suppressive functions, supported by their significant correlation with improved patient outcomes. Our findings collectively highlight the therapeutic potential of targeting M1 macrophage modulation in MEITL. Research funding declaration: This work was supported by the National Natural Science Foundation of China (Grant No. 82000221 to J.W.) Keywords: microenvironment; tumor biology and heterogeneity; aggressive T-cell non-Hodgkin lymphoma No potential sources of conflict of interest.
small molecules
2026-07-07 | [Current status and progress in the diagnosis and treatment of monomorphic epitheliotropic intestinal T-cell lymphoma].
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and highly aggressive type of intestinal T-cell lymphoma. With the application of high-throughput sequencing technologies in recent years, the understanding of this entity has become increasingly comprehensive. The World Health Organization classification of lymphoma now recognizes MEITL as a distinct disease entity. However, the extreme rarity of MEITL poses substantial challenges for clinical diagnosis and management, and patient outcomes remain poor. Based on a systematic review of recent literature, this article summarizes the diagnostic criteria of MEITL, integrating pathology and molecular biology; outlines current multimodal treatment approaches centered on surgery, chemotherapy, and hematopoietic stem cell transplantation; and reviews available clinical and translational data to explore the potential role of epigenetic agents, JAK/STAT pathway inhibitors, and other emerging therapeutic strategies in MEITL. This article summarizes the current status and recent advances in the diagnostic and therapeutic strategies for MEITL in clinical practice and provides a reference for the design of future prospective, multicenter clinical studies.
2026-06-22 | Monomorphic epitheliotropic intestinal T-cell lymphoma presenting as acute small intestinal perforation: a case report and exploratory BCL-2-targeted therapy.
To report a rare case of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) presenting with acute gastrointestinal perforation and to describe the use of an exploratory regimen combining a BCL-2 inhibitor (Venetoclax) with CHOP chemotherapy, highlighting the diagnostic challenges and therapeutic considerations for this aggressive disease. We detail the clinicopathological journey of a 72-year-old male patient who presented with an acute abdomen. The diagnosis was established through surgical pathology and comprehensive immunohistochemistry. Following an initial treatment refusal and a subsequent disease recurrence manifesting as a second perforation, the patient received Venetoclax combined with CHOP. The relevant literature was reviewed to inform the diagnostic and therapeutic decisions. Emergency surgery for perforation revealed MEITL (initially staged as Lugano stage I). The patient initially declined therapy but presented 9 months later with recurrent perforation, confirmed as disease relapse via pathology. Immunohistochemistry showed tumor cells were CD3 (weakly positive), CD8+, CD56+, Bcl-2 (3+), and Ki-67 (~60%). Postoperative PET/CT revealed limited retroperitoneal lymph node involvement. The patient received four cycles of Venetoclax (200 mg/day, days 1-14) plus CHOP, achieving complete metabolic remission on follow-up PET/CT without significant myelosuppression. The 9-month untreated interval despite high Ki-67 is noteworthy. MEITL is a highly aggressive lymphoma often presenting as a surgical emergency. Diagnosis relies on histopathology and a characteristic immunophenotype (CD3+ CD8+ CD56+). This case suggests that incorporating BCL-2 inhibition into the treatment of Bcl-2-high MEITL may represent a biologically rational strategy. Besides, the prolonged untreated interval observed in this patient highlights the potential biological heterogeneity of MEITL. While the observed complete metabolic remission is encouraging, this finding remains hypothesis-generating and requires validation in larger studies.
2026-05-27 | Efficacy and tolerability of duvelisib in relapsed/refractory peripheral T-cell lymphoma: A multicenter real-world analysis.
7067 Background: Relapsed/refractory (R/R) peripheral T-cell lymphomas (PTCL) are a rare group of non-Hodgkin lymphomas with median survival at relapse of 6-10 months and few treatment options. Duvelisib is a g/∆ phosphatidylinositol 3-kinase inhibitor approved in CLL and NCCN compendium listed in PTCL. In indolent lymphomas, concerns for cumulative duvelisib toxicity limit its use. In contrast, studies in R/R PTCL show duvelisib to be well-tolerated. Therefore, we sought to assess the efficacy and tolerability of duvelisib in a real world setting in R/R PTCL. Methods: We conducted a retrospective analysis of patients with R/R PTCL treated with duvelisib from 2012-2025 at 12 centers. Results: We identified 207 patients with PTCL: nodal PTCL with TFH phenotype (n=106, 51%), PTCL-NOS (n=78, 38%), ALCL (n=16, 8%), enteropathy associated T-cell lymphoma (n=4, 2%), NK/T-cell lymphoma (n=2, 1%), adult T-cell leukemia/lymphoma (n=1, 0.5%). 90 patients (43%) were female. Median age was 64; median International Prognostic Index score 3. Median prior lines of therapy was 2 (range 1-9). 26% received frontline transplant (23% auto, 3% allo). 118 patients received single agent duvelisib; 89 patients received duvelisib in combination with other agents (66 romidepsin, 12 bortezomib, 4 azacitadine, 3 ruxolitinib, 4 other). Of patients with response data, ORR was 51% (94/186; 31% CR, 17% PR) with median OS 12 months. ORR in patients with TFH-phenotype vs. non-TFH phenotype was 60% and 41% respectively. ORR in patients treated with single agent duvelisib and duvelisib combinations was 46% (46/99; 29% CR, 17% PR) and 55% (48/87; 39% CR, 16% PR), respectively with no difference in OS. Median duration of therapy was 84 days; the most common reason for discontinuation was progression (41%, 76/186). 13% (25/196) underwent allo-SCT after duvelisib therapy. Toxicity data is summarized in our table. In patients receiving single agent duvelisib therapy, rates of cytopenia were lower (7% vs. 34%, p<0.001) and rates of colitis were higher (17% vs. 7%, p= 0.03). Conclusions: In this real world, multicenter analysis of patients with R/R PTCL treated with duvelisib-based regimens, the ORR of 51% was consistent with published trials. Duvelisib therapy was well tolerated and a minority required hospitalization for toxicity. This suggests that duvelisib is safe in patients with R/R PTCL who have poor prognosis and limited treatment options. Adverse Event Full Cohortn (%)n=207 Single agent n (%)n=118 Combination therapyn (%)n=89 Single vs. Combination p value SteroidGivenn (% full cohort) Hospitalizationn (% full cohort) Rash 41 (20%) 24 (20%) 17 (19%) 0.83 23 (11%) 6 (3%) Colitis 26 (13%) 20 (17%) 6 (7%) 0.03 20 (10%) 16 (8%) Pneumonitis 7 (3%) 4 (3%) 3 (3%) 0.99 5 (2%) 3 (1%) Cytopenia 38(18%) 8 (7%) 30 (34%) <0.001 * * Transaminitis 33 (16%) 21 (18%) 12 (13%) 0.40 * * Infection 66 (32%) 36 (31%) 30 (34%) 0.63 N/A 42 (20%) *Not available.
2026-03-06 | Case report and literature review: Golidocitinib as a potential treatment for monomorphic epitheliotropic intestinal T-cell lymphoma.
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare type of non-Hodgkin lymphoma and a highly aggressive malignancy with a median overall survival of 7 months. Meanwhile, owing to the complex and confusing symptoms including nonspecific gastrointestinal symptoms, systemic manifestations and additional clinical manifestations associated with the extraintestinal involvement organs, MEITL is often diagnosed at an advanced stage. We report three cases of MEITL, and searched PubMed indexed articles between 2016 and 2024 for these terms: "MEITL" and "case report". We found that younger patients, those with intestinal perforation, and those who did not receive chemotherapy had worse prognoses. Importantly, we found that treatment with the JAK-1 inhibitor Golidocitinib in combination with the GDP regimen (Gemcitabine, Dexamethasone and Cisplatin) can improve patient prognosis. The study suggests that Golidocitinib could potentially improve the prognosis of MEITL patients by targeting the JAK-STAT pathway, although further validation of its long-term effectiveness is needed.
2026-02-23 | Case Report: Targeting the Achilles' heel of monomorphic epitheliotropic intestinal T-cell lymphoma.
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and highly aggressive lymphoma with a dismal prognosis and no established standard therapy. Its frequent expression of BCL-2 provides a rationale for targeting this anti-apoptotic protein. We report the case of a 34-year-old female with refractory MEITL who failed prior lines of therapy, including CHOPE and gemcitabine/oxaliplatin (GemOx) combined with golidocitinib. Based on positive BCL-2 expression by immunohistochemistry, a salvage regimen combining venetoclax with Gemox was administered. The treatment induced a rapid and significant clinical improvement. A follow-up PET/CT scan confirmed complete metabolic remission. The main adverse event was grade 4 neutropenia and thrombocytopenia with febrile neutropenia, attributable primarily to the Gemox backbone, which resolved with supportive care. The off-label use was approved by the institutional committee, and informed consent was obtained. To our knowledge, this is the first report of successful treatment of refractory MEITL with a venetoclax-containing regimen. This case validates BCL-2 as a actionable therapeutic target in MEITL. Future efforts should focus on optimizing combination partners for venetoclax to improve efficacy and tolerability. The rationale for exploring venetoclax as post-transplant maintenance therapy in MEITL is also discussed.
cell therapies
2025-11-15 | Long-term disease control of monomorphic epitheliotrophic intestinal T-cell lymphoma (MEITL) with CNS involvement in a caucasian patient by allogeneic hematopoietic cell transplantation
Monomorphic epitheliothrophic intestinal T-cell lymphoma (MEITL), formerly known as type II enteropathic T-cell lymphoma, is an aggressive form of peripheral T-cell lymphoma (PTCL) primarily originating from intraepithelial lymphocytes of the intestine [ 1 ]. Arising mostly in the small intestine with solitary or multifocal, often destructing lesions, it can disseminate in lymph nodes and non-intestinal organs including bone marrow and the central nervous system (CNS) [ 1 , 2 , 3 , 4 ]. It predominantly affects Asian and Hispanic populations but very rarely also Caucasians [ 1 , 5 ]. Generally, MEITL responds poorly to anthracycline-based lymphoma-typic induction chemotherapy, prompting investigators to explore more aggressive first-line treatment including high-dose therapy with autologous hematapoietic cell transplantation (auto-HCT). Although this strategy may be associated with better disease control, almost all patients will eventually relapse [ 6 , 7 ]. Accordingly, the prognosis of MEITL is dismal with median survival times around 12 months and only few long-term survivors [ 2 , 3 , 6 , 7 ]. The outcome is particularly poor if CNS involvement is present, a recent literature review identified only a single survivor among 12 cases reported [ 4 ]. Thus, expert recommendations advocate consolidation of MEITL responses by cellular immunotherapy through allogeneic hematopoietic cell transplantation (alloHCT) in analogy to other aggressive extranodal PTCL with similar biological behavior, such as hepatosplenic T-cell lymphoma [ 8 , 9 ] and acute/lymphoma-type adult T-cell leukemia/lymphoma [ 10 , 11 ], although the evidence basis for this is very poor.
2025-11-03 | Impact of antibiotic exposure on CAR-T cell therapy outcomes: Analysis in multiple Myeloma and lymphoma
Abstract Background: The gut microbiome is known to play a significant role in cancer immunotherapy. Antibiotic use can disrupt the intestinal microbiota and potentially diminish the antitumor efficacy of CAR-T cell therapy. According to a 2023 study by Stein-Thoeringer et al. in Nature Medicine, administration of broad-spectrum antibiotics prior to CAR-T infusion was associated with poorer treatment outcomes. Objective To assess the association between pre-CAR-T antibiotic exposure and clinical outcomes (response rates, progression-free survival [PFS], overall survival [OS]) and treatment-related adverse events (cytokine release syndrome [CRS], immune effector cell-associated neurotoxicity syndrome [ICANS], and prolonged hematologic toxicity) in patients with multiple myeloma (MM) and lymphoma. Methods We retrospectively analyzed the cohorts of CAR-T therapy treated patients in the three disease categories above. Patients were grouped by antibiotic exposure within a defined pre-CAR-T window (4 weeks prior to infusion). A risk-scoring model for severe hematologic toxicity further categorized patients into high-risk (score ≥3) and low-risk (score 0–2) subgroups. Outcomes were compared between groups. Results Among 334 patients, the MM cohort (n=199) showed no significant difference in objective response rate (ORR: 70.0% vs. 81.7%) between antibiotic-exposed (n=90) and non-exposed (n=109) groups, but complete remission (CR) rates were significantly lower in the antibiotic group (40.0% vs. 57.8%). Antibiotic-exposed patients had shorter median PFS (6.7 vs. 13.9 months) and OS (21.9 vs. 36.1 months). CRS (71.1% vs. 69.7%) and ICANS (3.3% vs. 1.8%) incidences were comparable. Similarly, stratified analyses of ATB classes were conducted, yielding consistent results. In the lymphoma cohort (n = 135), 61 (45.2%) patients were exposed to antibiotics. Importantly, the difference in ORR between the two groups was not statistically significant (66.2% vs. 70.5%), nor was there a significant difference in the incidence of CRS (16.4% vs. 21.6%). However, patients who received antibiotics had a significantly shorter median PFS and OS than patients who did not receive antibiotics (P< 0.05). Conclusion Pre-CAR-T antibiotic exposure, particularly to broad-spectrum low-risk antibiotics (HR ABX), reduces complete remission rates and shortens survival across MM and lymphoma, potentially via gut microbiome disruption. While CRS/ICANS risks remain unaffected, judicious antibiotic use is critical to optimize CAR-T efficacy. Future strategies should prioritize microbiome preservation or selective use of low-risk antibiotics (LR ABX).
2025-06-01 | 141 | CD30 CAR‐T IN RELAPSED AND REFRACTORY CD30+ LYMPHOMAS: LONG‐TERM FOLLOW‐UP OF A PHASE IB/II CLINICAL TRIAL
Introduction: CD30 CAR-T is active and safe in relapsed/refractory (r/r) CD30+ lymphomas, including classic Hodgkin lymphoma (cHL) and mature T-cell lymphomas (MTCLs). Here, we share long-term follow-up from our phase Ib/II trial (NCT02690545). Methods: Following cell procurement and CD30 CAR-T manufacturing, patients (pts) received lymphodepletion (LD) followed by CAR-T infusion. Pts could receive bridging between procurement and LD. Two dose levels were assessed in a 3+3 design: 1x108 CAR+ cells/m2 (DL1) and 2x108 CAR+ cells/m2 (DL2). Once dose escalation was completed in adults, children were enrolled on the phase Ib portion. Inclusion criteria include r/r CD30+ lymphoma after ≥ 2 therapies and Karnofsky/Lansky performance status > 60%. LD was initially bendamustine (benda) 90 mg/m2/day on days −5 to −4, but was changed to fludarabine (flu) 30 mg/m2/day and benda 70 mg/m2/day on days -5 to -3 for efficacy. Results: 34 pts received CD30 CAR-T 1/10/2017 to 3/11/2024, including 29 with cHL and 4 with MTCLs (ALK+ ALCL, enteropathy-associated T-cell lymphoma, primary cutaneous ALCL, and Sézary syndrome). Median age was 33 (range 10–68) for cHL and 31 (11–70) for MTCL. The median number of prior lines of therapy was 5 (2–18) in cHL and 4 (2–6) in MTCL. Bridging therapy (new therapy started between procurement and CAR-T infusion) was used in 15 cHL and 3 MTCL pts. In cHL pts, prior therapies—including bridging—included brentuximab vedotin (n = 28), PD-1 inhibitor (PD-1i, n = 23), bendamustine (n = 18), autologous stem cell transplant (SCT, n = 24), and alloSCT (n = 10). At LD, 24 cHL and 4 MTCL pts had active disease (PR or worse) and were evaluable for response to CAR-T. 8 pts with cHL received benda LD; all others received flu/benda LD. Median vein-to-vein time (time from procurement to CAR-T infusion) was 84 days (40–337). 7 pts with cHL and 2 with MTCL were treated on DL1; all others on DL2. In cHL pts, the CR rate with benda LD was 0/5; it was 15/19 with flu/benda LD. 2/4 pts with MTCL achieved CR. Median follow-up was 6.6 years for cHL and 6.0 years for MTCL. For cHL, 6-year progression-free survival (PFS) was 19% (80% CI: 11–32), 6-year duration of response (DOR) was 25% (80% CI: 15–41), and 6-year overall survival (OS) was 84% (80% CI: 73–96) (Figure 1A–C). For MTCL, 6-year PFS was 50% (80% CI: 26–95), 6-year DOR was 67% (80% CI: 40–100), and 6-year OS was 67% (80% CI: 40–100) (Figure 1D–F). In pts with cHL, Flu/benda LD (HR: 0.47, 80% CI 0.26–0.85) and PD-1i ≤ 1 year before CAR-T (HR: 0.44, 80% CI: 0.25–0.79) were associated with superior PFS, whereas increasing lines of therapy and prior alloSCT were associated with inferior PFS (Figure 1G). Conclusions: CD30 CAR-T has encouraging activity and maintains durable responses in a heavily pretreated population with cHL and CD30+ MTCLs. As previously reported, fludarabine-based LD is critical for its efficacy. Our group continues exploring the beneficial impact of PD-1i on CD30 CAR-T outcomes. Research funding declaration: This work was supported by funding from the National Institutes of Health (UNC-Integrated Translational Oncology T32-CA244125 to UNC/DKR) Keywords: cellular therapies; aggressive T-cell non-Hodgkin lymphoma; Hodgkin lymphoma Potential sources of conflict of interest: J. Serody Other remuneration: Carisma Therapeutics, Merck Inc. Glaxo Smith Klein, PIQUE Therapeutics, Triangle Biotechnology G. Dotti Consultant or advisory role: Bellicum Pharmaceuticals, Catamaran Bio, Estrella N. Grover Honoraria: Regeneron Pharmaceuticals, Novartis, BMS, Caribou, Janssen, Kite Other remuneration: Sangamo
2024-12-18 | Enteropathy-associated T-cell lymphoma: A population-based cohort study on incidence, treatment, and outcome in the Netherlands.
Enteropathy-associated T-cell lymphoma (EATL) is a peripheral T-cell lymphoma (PTCL) with a poor prognosis. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide consolidated by autologous stem cell transplantation (ASCT) are recommended for fit PTCL patients. The role of etoposide and ASCT in EATL is unclear. This study reports the incidence, treatment, and outcome of EATL patients using the Netherlands Cancer Registry, with nationwide coverage of >95%. All patients diagnosed in 1989-2021 (n = 351, 77% treated) were identified (median age 67 years, 56% male, 50% limited stage). Time period analysis assessed trends in primary therapy and overall survival (OS). Treatment included chemotherapy (CT) (34%), surgery (18%), surgery and CT (19%) or CT followed by ASCT (7%). The 5-year OS for treated patients with limited versus advanced stage was 19% and 9% respectively. The 2-year OS improved over time (21%-33%, p = 0.06). Surgery only (hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.55-3.01, p < 0.01) and advanced-stage disease (HR 1.67; 95% CI 1.25-2.23, p = 0.01) were predictors of poor prognosis. ASCT (HR 0.31; 95% CI 0.18-0.56) was associated with improved OS. There was no statistical difference in OS between patients treated with or without etoposide. Current first-line treatment is ineffective.
2024-10-11 | Enteropathy-Associated T-Cell Lymphoma Treated With Autologous Hematopoietic Stem-Cell Transplant: A Glimmer of Hope?
We report a case of primary enteropathy-associated T-cell lymphoma in a 50-year-old man presenting with abdominal pain, chronic diarrhea, and significant weight loss over 6 months. Diagnosis was confirmed through endoscopy, biopsy, and positron emission tomography-computed tomography, staging the disease as stage 1E. The patient underwent initial treatment with the cyclophosphamide, doxorubicin (also known as hydroxydaunorubicin), vincristine (also known as oncovin), etoposide, and prednisolone chemotherapy regimen, followed by high-dose hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone chemotherapy and autologous stem cell transplantation. Despite developing febrile neutropenia and septic shock during treatment, the patient achieved disease remission and symptom resolution. This case underscores the potential of autologous stem-cell transplantation as a curative approach for primary enteropathy-associated T-cell lymphoma and highlights the need for further research on its effectiveness.
antibodies
2026-07-04 | Genomic loss of MLH1/PMS2 loci defines a mismatch repair deficient subgroup in monomorphic epitheliotropic intestinal T-cell lymphoma.
Primary intestinal T-cell lymphomas (ITCLs), comprising enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), are rare aggressive tumors. The role of DNA mismatch repair (MMR) deficiency (dMMR) and microsatellite instability (MSI) in the development of ITCLs remains largely unexplored. Here, we investigated the incidence, molecular mechanisms and clinical relevance of dMMR/MSI in 86 ITCLs (30 EATLs, 56 MEITLs) using whole-exome sequencing, PCR-based MSI testing, DNA methylation profiling, and immunohistochemistry for MLH1, MSH2, MSH6 and PMS2. MMR deficiency was detected in 3 of 53 MEITLs (6%) but in none of the EATLs. dMMR MEITLs showed the highest tumor mutational burden (8.3-17.1 mutations/Mb), compared to median TMBs of 1.9 in MEITL and 2.4 in EATL. The complete loss of MLH1/PMS2 expression in two MSI-high tumors and isolated PMS2 loss in the third case were all associated with biallelic deletions of the affected loci. Notably, MLH1 deletions significantly co‑occurred with SETD2 deletions (p = 0.001), the latter representing a major driver of MEITL tumorigenesis. dMMR MEITLs lacked distinctive clinicopathologic features. These findings indicate that dMMR/MSI occurs in a subset of MEITLs probably during tumor progression, rather than being an initiating driver event, and provide a biological rationale to explore the efficacy of immune checkpoint inhibitors in some of this unfavorable subtype of ITCL.
2026-01-04 | A Clinical Review of Collagenous Sprue, Refractory Celiac Disease, Ulcerative Jejunitis, and Enteropathy-Associated T-cell Lymphoma
Celiac disease is a chronic immune-mediated enteropathy caused by gluten exposure. It affects approximately 1% of the world"s population and can present at any age with a wide range of signs and symptoms including malabsorption. Adherence to a gluten-free diet is the basis of treatment; however, a small subset of patients can develop worsening and life-threatening gastrointestinal symptoms despite gluten avoidance. Clinical worsening despite a gluten-free diet should raise concern for other conditions such as collagenous sprue or other more severe forms of celiac disease. Collagenous sprue is characterized by a subepithelial collagen band and celiac-like histologic features in the small bowel mucosa. It is unclear whether collagenous sprue falls within the celiac disease spectrum or represents a distinct entity. Refractory celiac disease is a rare form of celiac disease unresponsive to a gluten-free diet and can be subdivided into types I and II. The latter is defined by a clonal aberrant population of intraepithelial lymphocytes that accumulate lymphomagenic mutations. Refractory celiac disease type II is a premalignant condition that may exhibit ulcerative jejunitis or progress to the very aggressive enteropathy-associated T-cell lymphoma. Immunohistochemistry, flow cytometry, and T-cell receptor clonality testing aid in the diagnosis of refractory celiac disease. Treatment options include immunosuppressants, chemotherapy, and stem cell transplantation. The objective of this paper is to provide an overview of collagenous sprue, refractory celiac disease, ulcerative jejunitis, and enteropathy-associated T-cell lymphoma with a focus on presentation, pathogenesis, diagnosis, and treatment.
2025-11-03 | Brentuximab vedotin plus DHAP as effective salvage therapy in CD30+ peripheral T-cell lymphoma: A retrospective multicenter study
Abstract The prognosis of most nodal peripheral T-cell lymphomas (T-NHL) has not significantly improved over the past 25 years. Stage- or IPI-dependent 5-year overall survival (OS) rates remain around 30%. Recently, for the first time, a significant OS benefit was demonstrated for the combination of brentuximab vedotin (BV) and CHP (cyclophosphamide, doxorubicin, prednisone) compared to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in the first-line treatment of patients with anaplastic large cell lymphoma (ALCL). However, approximately 30% of patients with peripheral T-NHL experience a disease course that is primarily refractory, with dismal prognosis. BV monotherapy achieves high remission rates, particularly in relapsed ALCL, but also in other relapsed T-NHL subentities. For relapsed/refractory (R/R) nodal peripheral T-NHLs other than ALCL, only conventional (multi-agent) chemotherapy is approved by both the European Medicines Agency as well as the Food and Drug Administration, while single-agent BV is approved for R/R ALCL only. Effective treatment options for younger patients with high remission rates for curative intended treatment concepts are urgently needed. In Hodgkin lymphoma, the addition of BV to DHAP (dexamethasone, high-dose cytarabine, cisplatin) has shown promising efficacy as a salvage regimen in a phase II trial. Based on this, we conducted a multicenter retrospective analysis based on the national T-NHL registry platform of the GLA and OSHO study groups to evaluate the efficacy and tolerability of platinum-based salvage therapies in combination with BV in patients with R/R T-NHL. A total of 26 patients treated with either BV-DHAP or BV-ICE between 2015 and 2025 were identified. Median age at diagnosis was 55 years (range 23–77), and 11/26 patients (42.3%) were female. Histologic subtypes included ALCL (11/26, 42.3%), angioimmunoblastic T-cell lymphoma, T-NHL not otherwise specified, enteropathy-associated T-cell lymphoma, and systemic primary cutaneous T-NHL. Most lymphoma expressed CD30 (22/26; 84,6%), 1/26 (3,9%) was assessed as CD30-negative and for 3/26 patients (11,5%) the information was not available. Median number of prior treatment lines was 2 (range 1-7). Eight out of 26 patients (30.8%) had previously received BV, and 4/26 (15.4%) had undergone prior autologous stem cell transplantation. Most patients (24/26, 92.3%) were refractory to the previous therapy or had relapsed within one year. Fourteen patients received BV-ICE, and 12 received BV-DHAP as salvage therapy. Best overall response rate (ORR) in the entire cohort was 53.9% (14/26), including CR in 6/26 (23.1%) and PR in 8/26 (30.8%). In the BV-ICE subgroup, ORR was 35.7% (5/14; CR 1/14 [7.1%], PR 4/14 [28.6%]). In contrast, the BV-DHAP subgroup demonstrated an ORR of 83.3% (10/12; CR 5/12 [41.7%], PR 5/12 [41.7%]). Among BV-DHAP patients, 8 had ALCL and 4 had other T-NHL subtypes. All non-ALCL patients (4/4) and 6/8 (75%) of ALCL patients responded to BV-DHAP. In the BV-ICE group, 3 patients had ALCL and 11 had other T-NHLs; responses were seen in 3/11 (27,3%) non-ALCL patients and 2/3 (66,7%) ALCL patients. Toxicities were manageable, comparable between regimens and primarily included grade 3/4 hematologic adverse events in 18/21 patients (85,7%), febrile neutropenia in 13/21 patients (61,9%), and transient liver enzyme elevations in 20/23 patients (87%). No new cases of peripheral neuropathy were documented. In conclusion, BV-DHAP was particularly effective as a salvage regimen in this high-risk cohort of R/R CD30-positive T-cell non-Hodgkin lymphoma, with manageable toxicity. Further studies are warranted to establish its superiority over BV monotherapy in this setting.
2025-10-13 | Incidence trends and survival analysis of enteropathy-associated T-cell lymphoma.
Enteropathy-associated T-cell lymphoma (EATL) is a rare, aggressive form of T-cell non-Hodgkin lymphoma, primarily affecting the small intestine. Due to its extremely low incidence and poor prognosis, studies on EATL are limited. This study aims to analyze the incidence trends, prognostic factors, and survival outcomes of EATL using the SEER database. We analyzed the incidence trends of EATL using SEER data from 2000 to 2021 and performed multivariate Cox regression to identify independent prognostic factors. Conditional survival (CS) analysis was performed to evaluate survival outcomes, and a CS-nomogram was developed to predict 1-, 3-, and 5-year overall survival (OS) and 5-year CS. The age-adjusted incidence rate of EATL was 0.014 per 100,000, showing a significant upward trend (APC 2.63). Multivariate analysis identified age, tumor site, tumor stage, surgery, and chemotherapy as independent OS risk factors. CS analysis showed that the 5-year survival probability progressively increased from 16% to 48%, 67%, 83%, and 93% after surviving 0, 1, 2, 3, and 4 years post-diagnosis. The dynamic nomogram showed excellent performance in predicting survival and stratifying patients into risk groups. This study provided valuable insights into the epidemiology, prognosis, and survival outcomes of EATL. The increasing incidence and CS outcomes highlighted the importance of early detection and intervention. The dynamic nomogram model developed here offered a more accurate prediction of individual survival outcomes and can aid in clinical decision-making.
2025-10-01 | S3029 Timing of Lymphoproliferative Disorder Diagnosis in Patients With Celiac Disease
Introduction: Celiac disease (CeD) is associated with an increased risk of enteropathy-associated T-cell lymphoma (EATL) and other non-Hodgkin lymphomas (NHL), which contribute to increased mortality risk. In the general population, cases of B-cell NHL far outnumber T-cell NHL. Our aim was to compare CeD patients diagnosed with a lymphoproliferative disorder (LPD) before CeD diagnosis to those diagnosed with an LPD concurrently or after CeD diagnosis. Methods: We performed a retrospective study of adult patients seen at our tertiary referral center between 1980 and 2024. Diagnosis of CeD was confirmed by villous atrophy on duodenal biopsy and/or by positive CeD serology. LPD was defined as a lymphoid malignancy, including multiple myeloma, Hodgkin lymphoma, NHL, and refractory celiac disease type II, considered to be a precursor of EATL. Diagnosis of CeD and LPD within 1 year was considered concurrent. Results: There were 87 cases of LPD identified in 82 patients, with 4 patients developing more than 1 LPD. There were 41 cases of T-cell NHL, with 90% presenting concurrently or after CeD diagnosis. The 4 cases presenting before CeD diagnosis were cutaneous: cutaneous anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, cutaneous T-cell lymphoma (2 cases), and lymphomatoid papulosis type A. There were 36 cases of B-cell NHL, with 31% presenting before and 69% presenting concurrently or after CeD diagnosis. Comparing patients diagnosed with LPD before CeD diagnosis to those diagnosed concurrently or after CeD diagnosis, we found a mean age of CeD diagnosis of 58.6 and 57.6 years (P = 0.9), respectively, and a mean age of LPD diagnosis of 48.5 and 65.5 years (P < 0.001), respectively. Classical CeD presentation was seen in 38.9% and 68.9% of patients (P = 0.021), respectively. After LPD diagnosis, the median survival of patients with B-cell NHL was longer than for those with T/NK-cell NHL (18.6 vs 9.4 years, P = 0.008). Conclusion: In this series, both B-cell and T-cell NHL cases were seen in CeD patients. Patients with B-cell NHL had longer median survival than those with T/NK-cell NHL. Patients diagnosed with LPD concurrently or after CeD diagnosis were more likely to have had a classical CeD presentation. Cases of T-cell NHL presenting before CeD diagnosis consisted of a small, heterogeneous group of cutaneous lymphomas, while the vast majority of T-cell NHLs were diagnosed concurrently or after CeD diagnosis.
proteins
2025-06-01 | 483 | SINGLE‐CELL AND SPATIAL TRANSCRIPTOMIC PROFILING IDENTIFIES M1 MACROPHAGE‐MEDIATED TUMOR SUPPRESSION IN MONOMORPHIC EPITHELIOTROPIC INTESTINAL T‐CELL LYMPHOMA
Z. Zhang and F. Cheng equally contributing author. Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), a rare and highly aggressive intestinal malignancy with predominant incidence in Asian populations, is characterized by an insidious onset and dismal prognosis. Despite its clinical severity, the tumor microenvironment (TME) drivers of MEITL pathogenesis remain poorly defined. Methods: We retrospectively analyzed clinicopathological data from 20 MEITL patients (Asian cohort; median age 55.2 years; 65% male) treated at the first affiliated hospital of Zhejiang University School of Medicine from January 2019 to October 2023. ScRNA-seq and spatial transcriptomics were performed on surgically resected intestinal lesions from four treatment-naïve patients with distinct clinical trajectories. M1 macrophages (CD80+CD68+) were quantified per high-power field and survival correlations were assessed by Kaplan-Meier with log-rank testing. Results: Clinicopathological analysis demonstrated a predominant involvement of the jejunum and ileum (95%), with abdominal pain (85%), diarrhea (75%), and intestinal perforation (60%) representing the most frequent clinical manifestations. Immunophenotypic profiling revealed consistent expression of CD3 (100%), CD8 (85%), and CD56 (95%) in tumor cells, while showing absence of CD5 (95%) and Epstein-Barr virus association (EBER−, 90%). Single-cell transcriptomic analysis delineated eight distinct cellular compartments within the TME, including malignant T/NK-like hybrid cells, intestinal epithelial cells, and macrophage subsets, with a notable absence of conventional NK cells. Spatial transcriptomic mapping uncovered significant topographical co-localization between tumor cells and macrophages, particularly M1-polarized subsets. Differential gene expression analysis of M1 macrophages adjacent to tumor cells revealed marked enrichment of cytotoxic effector pathways (e.g., granzyme B, perforin) and immune regulatory networks (e.g., TNF superfamily, FASLG). Importantly, quantification of M1 macrophage density in pathological sections demonstrated a robust positive correlation with patient survival (R2 = 0.511, p < 0.001). Conclusions: MEITL is characterized by an insidious onset, frequently manifesting as acute abdominal emergencies, and associated with a dismal prognosis. Integrative analysis of single-cell RNA sequencing and spatial transcriptomics reveals that malignant T cells adopt NK-like transcriptional programs while simultaneously depleting endogenous NK cell populations, indicative of a dominant immune niche occupation. The discovery of spatial symbiosis between tumor cells and M1 macrophages challenges the conventional “immune desert” paradigm in T-cell lymphomas. Importantly, M1 macrophages exhibit context-dependent tumor-suppressive functions, supported by their significant correlation with improved patient outcomes. Our findings collectively highlight the therapeutic potential of targeting M1 macrophage modulation in MEITL. Research funding declaration: This work was supported by the National Natural Science Foundation of China (Grant No. 82000221 to J.W.) Keywords: microenvironment; tumor biology and heterogeneity; aggressive T-cell non-Hodgkin lymphoma No potential sources of conflict of interest.
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Drug Discovery Landscape
1 orphan drug designation for Enteropathy-associated T-cell lymphoma.
1 orphan drug designation for Enteropathy-associated T-cell lymphoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
brentuximab vedotin | antibodies | FDA | 2016-07-07 | — | Seattle Genetics, Inc. |
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