RARE DISEASE
Angioimmunoblastic T-cell lymphoma
Angioimmunoblastic T-cell lymphoma
Angioimmunoblastic T-cell lymphoma
Synonyms: AILT, Immunoblastic lymphadenopathy, Lymphogranulomatosis X, T-cell lymphoma, AILD type
Synonyms: AILT, Immunoblastic lymphadenopathy, Lymphogranulomatosis X, T-cell lymphoma, AILD type
Synonyms: AILT, Immunoblastic lymphadenopathy, Lymphogranulomatosis X, T-cell lymphoma, AILD type
Drug discovery
5
drugs
With orphan designations
Overview
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma derived from follicular helper T-cells, characterized by systemic symptoms, immune dysregulation, and frequent advanced-stage presentation at diagnosis. Histopathology reveals polymorphic infiltrates, proliferative vasculature, and CD10/CXCL13-positive malignant T-cells. Despite CHOP-based induction and autologous stem cell transplant consolidation, relapse rates remain high, with a 5-year survival of 30-35% [1][3][11][15].
Burden
Therapies
First-line: CHOP/CHOEP ± autologous transplant; CD30-positive cases may use brentuximab vedotin combinations [1][3][16].
Relapsed/refractory: Epigenetic agents (HDAC inhibitors, hypomethylating agents), PI3K inhibitors, or allogeneic transplant [3][8][15].
Emerging options: Lenalidomide-CHOEP trials (#NCT02561273) and targeted immunotherapy [1][3].
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
728 drug discovery papers about Angioimmunoblastic T-cell lymphoma, with 3 first-in-class and 10 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
728 drug discovery papers about Angioimmunoblastic T-cell lymphoma, with 3 first-in-class and 10 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-11 | Multi-omics analysis identifies GAA as an independent poor prognostic biomarker and candidate therapeutic target in angioimmunoblastic T-cell lymphoma
Background Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma with poor clinical outcomes and limited therapeutic options. The contribution of metabolic reprogramming and immune microenvironmental alterations to AITL progression remains insufficiently defined. Methods We conducted integrative transcriptomic and proteomic analyses of AITL samples compared with reactive lymphoid hyperplasia to identify molecules associated with treatment response and prognosis. Immune infiltration and pathway enrichment analyses were performed, and findings were validated in independent GEO cohorts (GSE19069 and GSE58445). Key protein expression was confirmed by immunohistochemistry and multiplex immunofluorescence. Results Differential expression analyses revealed that lysosomal alpha-glucosidase (GAA), a key enzyme involved in glycogen metabolism, was significantly upregulated at both the RNA and protein levels in patients who failed to respond to standard chemotherapy. Elevated GAA expression was associated with inferior overall survival in multivariate analysis. Immunohistochemistry staining and multiplex immunofluorescence further confirmed the spatial expression pattern of GAA in AITL tissues. Immune deconvolution and pathway enrichment analyses suggested that GAA-high tumors exhibited increased CD8 + T-cell infiltration accompanied by transcriptional features of T-cell exhaustion, as well as transcriptionally inferred metabolic alterations characterized by enhanced glycolysis-related signatures and reduced oxidative phosphorylation-related signatures. These findings were further validated in an independent AITL cohort from the GEO database. Conclusions Our study identifies GAA as a candidate biomarker associated with adverse clinical outcomes, immune microenvironmental features, and metabolic pathway alterations in AITL, highlighting glycogen metabolism as a previously underexplored biological axis and a potential therapeutic vulnerability warranting further functional investigation.
2026-08-08 | Angioimmunoblastic T-cell lymphoma associated with myeloid neoplasms: a case report and literature review supporting a shared clonal origin
血管免疫母细胞性 T 细胞淋巴瘤 (AITL) 常携带 TET2、 DNMT3A、 IDH2等表观调控基因突变, 此类突变在克隆性造血 (CH) 和髓系肿瘤中同样高频存在, 提示淋巴、 髓系恶性肿瘤可能具备共同细胞起源。 既往 AITL 合并骨髓增生异常肿瘤 (MDS) 和急性髓系白血病 (AML) 病例大多为异时发病, 二者克隆同源的直接分子证据较为匮乏。 本文报道 1 例同步确诊 AITL 伴原始细胞增多的骨髓增生异常肿瘤-2 (MDS-IB2) 的87岁男性患者。 患者以全身瘙痒红斑皮损和全血细胞减少为首发表现, 皮肤活检确诊 AITL, 骨髓穿刺结合流式细胞学确诊 MDS-IB2, PET-CT 提示全身骨髓和淋巴结同步出现肿瘤浸润。 对皮肤淋巴瘤组织与配对骨髓样本进行靶向二代测序, 两份标本均检出 IDH2 p.R140Q 和 ASXL1 p.R1415X 共有致病突变; 淋巴病灶独有 TP53、 CIITA、 NOTCH1 突变, 骨髓髓系病灶特有 SRSF2、 STAG2、 BCOR 突变。 分子检测证实两类肿瘤起源于携带早期克隆造血突变的同一造血干祖细胞, 后续各自获得谱系特异性突变, 发生分支克隆演化。 本文汇总既往相关病例, 多数患者在 AITL 发病数月至数年后继发髓系肿瘤, 部分病例经分子检测证实两类肿瘤共享克隆造血相关突变。 本例同步发病病例, 为 AITL 与髓系肿瘤存在共同克隆起源提供了关键直接分子证据。
2026-07-28 | Angioimmunoblastic T-cell lymphoma following Castleman’s disease: diagnostic challenges and literature review
Castleman disease (CD) represents a heterogeneous group of hematologic disorders characterized by distinct histopathological features. While CD is regarded as a pre-lymphomatous condition, its reactive or neoplastic nature is still a matter of controversy. Although rare, lymphoma has been reported in patients with CD, most commonly B-cell lymphomas. Here, we present a case of a 69-year-old man initially diagnosed with CD who subsequently developed angioimmunoblastic T-cell lymphoma (AITL) during treatment. To elucidate the potential biological relationship between these two disease entities, we performed whole-exome sequencing to compare genomic alterations between the two disease states. Additionally, we provide a concise review of published cases documenting lymphoma occurring after or coexisting with CD, summarizing patients’ characteristics and the various treatment strategies employed thus far.
2026-07-23 | Autologous Stem Cell Transplant Consolidation Is Associated With Improved Overall Survival in Angioimmunoblastic T-Cell Lymphoma: A Real-World National Cancer Database Study.
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma with poor outcomes, and the role of autologous stem cell transplantation (ASCT) as consolidation after frontline therapy remains controversial. We conducted a retrospective cohort study using the National Cancer Database, including adults diagnosed with AITL between 2004 and 2020 who received frontline systemic therapy. Patients were categorized as chemotherapy alone (Chemo) or chemotherapy followed by ASCT (Chemo + ASCT). To mitigate immortal time bias, prespecified landmark analyses were performed, with a 6-month landmark analysis as the primary approach and a 9-month landmark analysis as a sensitivity analysis. Multivariable Cox regression and propensity score weighting using inverse probability of treatment weighting for the average treatment effect were used to address measured confounding. Among 3996 patients receiving systemic therapy, 686 (17.2%) underwent ASCT. In the 6-month landmark analysis, ASCT was associated with improved overall survival (HR, 0.53; 95% CI, 0.45-0.62; p < 0.001). Findings were consistent in the 9-month landmark analysis (HR, 0.58; 95% CI, 0.49-0.69; p < 0.001) and IPTW-adjusted model (HR, 0.51; 95% CI, 0.44-0.60; p < 0.001). In this large real-world cohort, ASCT consolidation was consistently associated with improved survival in patients with AITL. Although treatment-response data were unavailable and residual confounding cannot be excluded, these findings provide supportive real-world evidence and warrant prospective studies with treatment-timing and response data to better define patient selection.
2026-07-18 | Chidamide‑augmented BEAM conditioning and maintenance in first-remission T‑cell lymphoma: a single‑arm phase 2 experience
T‑cell lymphoma (TCL) is a rare subset of non‑Hodgkin lymphoma (NHL), accounting for 5–10% of cases in Western countries and 15–20% in Asia [ 1 ]. TCL encompasses multiple pathological subtypes, including nodal T‑follicular helper cell lymphoma, angioimmunoblastic‑type (nTFHL‑AI), peripheral T‑cell lymphoma‑not otherwise specified (PTCL‑NOS), and anaplastic large‑cell lymphoma (ALCL) [ 2 ]. First‑line CHOP‑based regimens yield unsatisfactory outcomes [ 2 ]. Autologous stem cell transplantation (ASCT) is a standard consolidation strategy for TCL in first remission, yet the 2‑year progression‑free survival (PFS) with BEAM conditioning is only 52.9% [ 3 ]. Chidamide, an oral HDAC1/2/3/10 inhibitor, has demonstrated efficacy in relapsed/refractory TCL [ 4 ]. Preclinical studies suggest synergistic effects with chemotherapeutic agents such as cytarabine and etoposide [ 5 ]. However, no study has systematically integrated chidamide into the BEAM (carmustine, etoposide, cytarabine, and melphalan) backbone to improve transplant outcomes.
2026-08-11 | Multi-omics analysis identifies GAA as an independent poor prognostic biomarker and candidate therapeutic target in angioimmunoblastic T-cell lymphoma
Background Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma with poor clinical outcomes and limited therapeutic options. The contribution of metabolic reprogramming and immune microenvironmental alterations to AITL progression remains insufficiently defined. Methods We conducted integrative transcriptomic and proteomic analyses of AITL samples compared with reactive lymphoid hyperplasia to identify molecules associated with treatment response and prognosis. Immune infiltration and pathway enrichment analyses were performed, and findings were validated in independent GEO cohorts (GSE19069 and GSE58445). Key protein expression was confirmed by immunohistochemistry and multiplex immunofluorescence. Results Differential expression analyses revealed that lysosomal alpha-glucosidase (GAA), a key enzyme involved in glycogen metabolism, was significantly upregulated at both the RNA and protein levels in patients who failed to respond to standard chemotherapy. Elevated GAA expression was associated with inferior overall survival in multivariate analysis. Immunohistochemistry staining and multiplex immunofluorescence further confirmed the spatial expression pattern of GAA in AITL tissues. Immune deconvolution and pathway enrichment analyses suggested that GAA-high tumors exhibited increased CD8 + T-cell infiltration accompanied by transcriptional features of T-cell exhaustion, as well as transcriptionally inferred metabolic alterations characterized by enhanced glycolysis-related signatures and reduced oxidative phosphorylation-related signatures. These findings were further validated in an independent AITL cohort from the GEO database. Conclusions Our study identifies GAA as a candidate biomarker associated with adverse clinical outcomes, immune microenvironmental features, and metabolic pathway alterations in AITL, highlighting glycogen metabolism as a previously underexplored biological axis and a potential therapeutic vulnerability warranting further functional investigation.
2026-08-08 | Angioimmunoblastic T-cell lymphoma associated with myeloid neoplasms: a case report and literature review supporting a shared clonal origin
血管免疫母细胞性 T 细胞淋巴瘤 (AITL) 常携带 TET2、 DNMT3A、 IDH2等表观调控基因突变, 此类突变在克隆性造血 (CH) 和髓系肿瘤中同样高频存在, 提示淋巴、 髓系恶性肿瘤可能具备共同细胞起源。 既往 AITL 合并骨髓增生异常肿瘤 (MDS) 和急性髓系白血病 (AML) 病例大多为异时发病, 二者克隆同源的直接分子证据较为匮乏。 本文报道 1 例同步确诊 AITL 伴原始细胞增多的骨髓增生异常肿瘤-2 (MDS-IB2) 的87岁男性患者。 患者以全身瘙痒红斑皮损和全血细胞减少为首发表现, 皮肤活检确诊 AITL, 骨髓穿刺结合流式细胞学确诊 MDS-IB2, PET-CT 提示全身骨髓和淋巴结同步出现肿瘤浸润。 对皮肤淋巴瘤组织与配对骨髓样本进行靶向二代测序, 两份标本均检出 IDH2 p.R140Q 和 ASXL1 p.R1415X 共有致病突变; 淋巴病灶独有 TP53、 CIITA、 NOTCH1 突变, 骨髓髓系病灶特有 SRSF2、 STAG2、 BCOR 突变。 分子检测证实两类肿瘤起源于携带早期克隆造血突变的同一造血干祖细胞, 后续各自获得谱系特异性突变, 发生分支克隆演化。 本文汇总既往相关病例, 多数患者在 AITL 发病数月至数年后继发髓系肿瘤, 部分病例经分子检测证实两类肿瘤共享克隆造血相关突变。 本例同步发病病例, 为 AITL 与髓系肿瘤存在共同克隆起源提供了关键直接分子证据。
2026-07-28 | Angioimmunoblastic T-cell lymphoma following Castleman’s disease: diagnostic challenges and literature review
Castleman disease (CD) represents a heterogeneous group of hematologic disorders characterized by distinct histopathological features. While CD is regarded as a pre-lymphomatous condition, its reactive or neoplastic nature is still a matter of controversy. Although rare, lymphoma has been reported in patients with CD, most commonly B-cell lymphomas. Here, we present a case of a 69-year-old man initially diagnosed with CD who subsequently developed angioimmunoblastic T-cell lymphoma (AITL) during treatment. To elucidate the potential biological relationship between these two disease entities, we performed whole-exome sequencing to compare genomic alterations between the two disease states. Additionally, we provide a concise review of published cases documenting lymphoma occurring after or coexisting with CD, summarizing patients’ characteristics and the various treatment strategies employed thus far.
2026-07-23 | Autologous Stem Cell Transplant Consolidation Is Associated With Improved Overall Survival in Angioimmunoblastic T-Cell Lymphoma: A Real-World National Cancer Database Study.
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma with poor outcomes, and the role of autologous stem cell transplantation (ASCT) as consolidation after frontline therapy remains controversial. We conducted a retrospective cohort study using the National Cancer Database, including adults diagnosed with AITL between 2004 and 2020 who received frontline systemic therapy. Patients were categorized as chemotherapy alone (Chemo) or chemotherapy followed by ASCT (Chemo + ASCT). To mitigate immortal time bias, prespecified landmark analyses were performed, with a 6-month landmark analysis as the primary approach and a 9-month landmark analysis as a sensitivity analysis. Multivariable Cox regression and propensity score weighting using inverse probability of treatment weighting for the average treatment effect were used to address measured confounding. Among 3996 patients receiving systemic therapy, 686 (17.2%) underwent ASCT. In the 6-month landmark analysis, ASCT was associated with improved overall survival (HR, 0.53; 95% CI, 0.45-0.62; p < 0.001). Findings were consistent in the 9-month landmark analysis (HR, 0.58; 95% CI, 0.49-0.69; p < 0.001) and IPTW-adjusted model (HR, 0.51; 95% CI, 0.44-0.60; p < 0.001). In this large real-world cohort, ASCT consolidation was consistently associated with improved survival in patients with AITL. Although treatment-response data were unavailable and residual confounding cannot be excluded, these findings provide supportive real-world evidence and warrant prospective studies with treatment-timing and response data to better define patient selection.
2026-07-18 | Chidamide‑augmented BEAM conditioning and maintenance in first-remission T‑cell lymphoma: a single‑arm phase 2 experience
T‑cell lymphoma (TCL) is a rare subset of non‑Hodgkin lymphoma (NHL), accounting for 5–10% of cases in Western countries and 15–20% in Asia [ 1 ]. TCL encompasses multiple pathological subtypes, including nodal T‑follicular helper cell lymphoma, angioimmunoblastic‑type (nTFHL‑AI), peripheral T‑cell lymphoma‑not otherwise specified (PTCL‑NOS), and anaplastic large‑cell lymphoma (ALCL) [ 2 ]. First‑line CHOP‑based regimens yield unsatisfactory outcomes [ 2 ]. Autologous stem cell transplantation (ASCT) is a standard consolidation strategy for TCL in first remission, yet the 2‑year progression‑free survival (PFS) with BEAM conditioning is only 52.9% [ 3 ]. Chidamide, an oral HDAC1/2/3/10 inhibitor, has demonstrated efficacy in relapsed/refractory TCL [ 4 ]. Preclinical studies suggest synergistic effects with chemotherapeutic agents such as cytarabine and etoposide [ 5 ]. However, no study has systematically integrated chidamide into the BEAM (carmustine, etoposide, cytarabine, and melphalan) backbone to improve transplant outcomes.
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Drug Discovery Landscape
5 orphan drug designations for Angioimmunoblastic T-cell lymphoma.
5 orphan drug designations for Angioimmunoblastic T-cell lymphoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD70 | cell therapies | FDA | 2025-09-12 | — | Nanjing Miracle Biotechnology Co., Ltd. |
imiquimod-ferulic acid | small molecules | FDA | 2025-05-25 | — | Celista Pharmaceuticals LLC |
4-[[(1S)-1-(4, 8-dichloro-1-oxo-2-phenyl-3-isoquinolyl) ethyl] amino]-8H-pyrido[2,3-d] pyrimidin-5-one] | small molecules | FDA | 2024-01-03 | — | Boryung Co., Ltd. |
nanatinostat and valganciclovir | small molecules | FDA | 2019-03-15 | — | Viracta Therapeutics, Inc. |
brentuximab vedotin | antibodies | FDA | 2013-09-13 | — | Seattle Genetics, Inc. |
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