Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials

AbstractTo evaluate the prognostic significance of clinicobiologic and pathological features in angioimmunoblastic T-cell lymphoma (AITL), 157 AITL patients were retrieved from the GELA LNH87-LNH93 randomized clinical trials. One hundred forty-seven patients received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)–like regimen with intensified courses in half of them. Histologically, 41 cases were classified as “rich in large cells” and 116 as “classic” (including 19 rich in epithelioid cells, 14 rich in clear cells, and 4 with hyperplastic germinal centers). Sixty-two cases were scored for CD10 and CXCL13 expression according to the abundance of positive lymphoid cells. Median age was 62 years, with 81% advanced stage, 72% B symptoms, 65% anemia, 50% hypergammaglobulinemia, and 66% elevated LDH. Overall 7-year survival was 30%. In multivariate analysis, only male sex (P = .004), mediastinal lymphadenopathy (P = .041), and anemia (P = .042) adversely affected overall survival. Increase in large cells and high level of CD10 and CXCL13 did not affect survival. Intensive regimen did not improve survival. In conclusion, AITL is a morphologically heterogeneous T-cell lymphoma commonly expressing CXCL13 and CD10 and carrying few prognostic factors. It portends a poor prognosis even when treated intensively. However, AITL is not always lethal with 30% of patients alive at 7 years.

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Ultra-high level of serum soluble interleukin-2 receptor at diagnosis predicts poor outcome for angioimmunoblastic T-cell lymphoma

Leukemia & Lymphoma ◽

10.3109/10428194.2014.1001985 ◽

2015 ◽

Vol 56 (9) ◽

pp. 2592-2597 ◽

Cited By ~ 6

Author(s):

Souichi Shiratori ◽

Mizuha Kosugi-Kanaya ◽

Akio Shigematsu ◽

Hajime Kobayashi ◽

Satoshi Yamamoto ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Interleukin 2 ◽

T Cell Lymphoma ◽

Angioimmunoblastic T Cell Lymphoma ◽

Interleukin 2 Receptor ◽

Poor Outcome ◽

Soluble Interleukin 2 Receptor ◽

High Level

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3D investigation shows walls and wall-like structures around human germinal centres, probably regulating T- and B-cell entry and exit

PLoS ONE ◽

10.1371/journal.pone.0242177 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242177

Author(s):

Miguel Thomos ◽

Patrick Wurzel ◽

Sonja Scharf ◽

Ina Koch ◽

Martin-Leo Hansmann

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Cell Lymphoma ◽

Selection Process ◽

Lymphoid Cells ◽

T Cell Lymphoma ◽

Tissue Slices ◽

Angioimmunoblastic T Cell Lymphoma ◽

Germinal Centres

This study deals with 3D laser investigation on the border between the human lymph node T-zone and germinal centre. Only a few T-cells specific for antigen selected B-cells are allowed to enter germinal centres. This selection process is guided by sinus structures, chemokine gradients and inherent motility of the lymphoid cells. We measured gaps and wall-like structures manually, using IMARIS, a 3D image software for analysis and interpretation of microscopy datasets. In this paper, we describe alpha-actin positive and semipermeable walls and wall-like structures that may hinder T-cells and other cell types from entering germinal centres. Some clearly defined holes or gaps probably regulate lymphoid traffic between T- and B-cell areas. In lymphadenitis, the morphology of this border structure is clearly defined. However, in case of malignant lymphoma, the wall-like structure is disrupted. This has been demonstrated exemplarily in case of angioimmunoblastic T-cell lymphoma. We revealed significant differences of lengths of the wall-like structures in angioimmunoblastic T-cell lymphoma in comparison with wall-like structures in reactive tissue slices. The alterations of morphological structures lead to abnormal and less controlled T- and B-cell distributions probably preventing the immune defence against tumour cells and infectious agents by dysregulating immune homeostasis.

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Angioimmunoblastic T-Cell Lymphoma: A Clinicopathologic Study of 158 Patients Treated in GELA (Groupe d’ Etude des Lymphomes de l’ Adulte) Trials.

Blood ◽

10.1182/blood.v108.11.397.397 ◽

2006 ◽

Vol 108 (11) ◽

pp. 397-397 ◽

Cited By ~ 2

Author(s):

Nathalie Mourad ◽

Nicolas Mounier ◽

Josette Brière ◽

Emmanue Raffoux ◽

Thierry Molina ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

T Cell ◽

Clinical Presentation ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

Germinal Centers ◽

Lymphoid Cells ◽

T Cell Lymphoma ◽

Angioimmunoblastic T Cell Lymphoma

Abstract Background: Angioimmunoblastic T-cell lymphoma (AITL), the second most frequent peripheral T-cell lymphoma, is characterized by a distinct clinical presentation and a spectrum of biological and morphologic features with little available data on prognostic factors in the literature. Objective: to evaluate the prognostic significance of clinical, biological and pathological features in AITL. Methods: between 1987 and 1998, 158 AITL patients were retrieved from the GELA LNH87 and LNH93 trials. Most patients received an anthracycline based polychemotherapy. Histologically, cases were reviewed by a panel of expert hematopathologists. For each case, at least 2 hematoxylin eosin slides were available for review together with an appropriate immunohistochemical staining including CD3, CD20 and CD21/CNA42. Cases were classified as “transformed” (>10% large B and/or T cells) and “classic” (including cases rich in clear cells, rich in epithelioid cells and with hyperplastic germinal centers). 62 cases were evaluated for CD10 and CXCL13 expression and scored according to the number of positive lymphoid cells. Results: there was a slight male predominance (M/F=1.53). Median age was 62 years. 81%, 50%, 67% and 39% of patients had respectively an advanced stage, a non ambulatory PS, an IPI>2 and a PIT>2 (age>60y, PS>=2, LDH>=normal and bone marrow involvement). Anemia, positive coombs test and bone marrow involvement were observed in 65%, 33% and 47% of cases respectively. Hypergammaglobulinemia, elevated LDH levels and skin rash were observed in 15%, 66% and 44% of patients respectively. 41 cases were classified as transformed and 117 as classic including 20 epithelioid-cell rich, 14 clear-cell rich and 4 with hyperplastic germinal centers. CD10 and CXCL13 were clearly positive, in a fraction of the lymphoid infiltrate, in 71% and 73% of cases respectively. CR/CRu remission was observed in 46% of patients after induction therapy. With a median follow-up of 69 months, the 5y overall survival rate was 33%, reaching a plateau level around 6 years. Concerning PIT, patients with 0–1 factors and 3–4 factors had a 5y OS of 37% and 38% respectively. In univariate analysis, absence of CR/CRu (p<0.0001), hepatomegaly (p=0.0004), male gender (p=0.004), and anemia (p=0.05) were poor prognostic indicators for overall survival. Classic and transformed AITL were not different regarding clinical presentation, biological findings, and outcome except for a higher frequency of elevated serum LDH (p=0.0266) and b2 microglobulin levels (p=0.0456) within the transformed group. IPI and PIT were not predictive of survival. Conclusion: despite of various intensive regimens with an anthracycline based chemotherapy, AITL pursues an aggressive clinical course and carries a poor prognosis. Our large series emphasizes the morphologic heterogeneity of AITL, without any clinical impact, and further confirms the common expression of CD10 and CXCL13.

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Heterozygosity for Roquinsan leads to angioimmunoblastic T-cell lymphoma-like tumors in mice

Blood ◽

10.1182/blood-2011-07-365130 ◽

2012 ◽

Vol 120 (4) ◽

pp. 812-821 ◽

Cited By ~ 26

Author(s):

Julia I. Ellyard ◽

Tiongsun Chia ◽

Socorro-Maria Rodriguez-Pinilla ◽

Jaime L. Martin ◽

Xin Hu ◽

...

Keyword(s):

T Cell ◽

Lymph Nodes ◽

Cell Lymphoma ◽

Tumor Development ◽

T Cell Lymphoma ◽

Angioimmunoblastic T Cell Lymphoma ◽

Genetic Manipulations ◽

Tfh Cells ◽

Follicular Helper ◽

Pathologic Features

Abstract Angioimmunoblastic T-cell lymphoma (AITL) is the second most common peripheral T-cell lymphoma with unusual clinical and pathologic features and a poor prognosis despite intensive chemotherapy. Recent studies have suggested AITL derives from follicular helper T (TFH) cells, but the causative molecular pathways remain largely unknown. Here we show that approximately 50% of mice heterozygous for the “san” allele of Roquin develop tumors accompanied by hypergammaglobulinemia by 6 months of age. Affected lymph nodes displayed the histologic features diagnostic of AITL, except for the presence of expanded FDC networks. Accumulation of TFH cells preceded tumor development, and clonal rearrangements in the TCR-β genes were present in most tumors. Furthermore, TFH cells exhibited increased clonality compared with non-TFH cells from the same lymph nodes, even in the absence of tumors. Genetic manipulations that prevent TFH development, such as deletion of ICOS, CD28, and SAP, partially or completely abrogated tumor development, confirming a TFH-derived origin. Roquinsan/+ mice emerge as a useful model to investigate the molecular pathogenesis of AITL and for preclinical testing of therapies aimed at targeting dysregulated TFH cells or their consequences.

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Clinical and pathologic features of skin involvement by angioimmunoblastic T-cell lymphoma: Report of the University of Iowa experience and review of the literature

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2009.11.659 ◽

2010 ◽

Vol 62 (3) ◽

pp. AB98

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Skin Involvement ◽

Review Of The Literature ◽

University Of Iowa ◽

Angioimmunoblastic T Cell Lymphoma ◽

Pathologic Features ◽

The University

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Retrospective analysis of prognostic factors for angioimmunoblastic T-cell lymphoma: a multicenter cooperative study in Japan

Blood ◽

10.1182/blood-2011-08-374371 ◽

2012 ◽

Vol 119 (12) ◽

pp. 2837-2843 ◽

Cited By ~ 53

Author(s):

Takashi Tokunaga ◽

Kazuyuki Shimada ◽

Kazuhito Yamamoto ◽

Dai Chihara ◽

Takuji Ichihashi ◽

...

Keyword(s):

Prognostic Factors ◽

T Cell ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

T Cell Lymphoma ◽

Mediastinal Lymphadenopathy ◽

Major Type ◽

Clinicopathologic Characteristics ◽

Angioimmunoblastic T Cell Lymphoma

Abstract Angioimmunoblastic T-cell lymphoma (AITL) is a major type of peripheral T-cell lymphoma (PTCL). To elucidate the clinicopathologic characteristics and prognosis of AITL in Japan, we retrospectively analyzed 207 patients with AITL. The median patient age was 67 years (range, 34-91 years), with 73% of patients older than 60 years. With a median follow-up of 42 months in surviving patients, 3-year overall survival (OS) was 54% and progression-free survival (PFS) was 38%. The International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) were predictive for OS in this analysis. Multivariate analysis found that age older than 60 years, elevated white blood cell (WBC) and IgA levels, the presence of anemia and thrombocytopenia, and extranodal involvement at > 1 site were significant prognostic factors for OS, and IgA, anemia, and mediastinal lymphadenopathy were significant prognostic factors for PFS. A novel prognostic model consisting of the prognostic factors for OS was successfully constructed. In conclusion, IPI and PIT were still useful for prognostication of AITL, and other factors, including those not used in IPI, such as IgA, anemia, WBC count, thrombocytopenia, and mediastinal lymphadenopathy, also significantly affected prognosis. Future investigations for IgA as a unique prognostic factor are warranted.

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