Angioimmunoblastic T-cell lymphoma: treatment strategies and prognostic factors from a retrospective multicenter study in China.

Angioimmunoblastic T-cell lymphoma (AITL) is a unique sub-type of peripheral T-cell lymphoma (PTCL). We aimed to evaluate treatment programs and prognostic factors of 121 newly diagnosed patients with AITL in China from January 2001 to December 2018. The median age was 58 years with male predominance. Bone marrow involvement appeared in only 8.3% of patients, which was different from the previously published literature. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) were 29.7% and 44.0%, respectively. Univariate and multivariate analyses showed that involvement of >5 nodal areas, age and Beta-2 microglubulin were highly predictive of OS but only the involvement of fewer than five nodal areas was significant for PFS. We identified a novel prognostic model including the three factors that may be applied in clinical practice and offer an alternative to IPI and PIT.

Development of a Novel Clinical Prognostic Model for Patients With Angioimmunoblastic T-Cell Lymphoma.

In this study we aimed to identify a set of prognostic factors for angioimmunoblastic T-cell lymphoma (AITL) and establish a novel prognostic model. The clinical data of 64 AITL patients enrolled to the Fourth Hospital of Hebei Medical University (from 2012 Jan to 2017 May) were retrospectively analyzed. The estimated 5-year overall survival and progression-free survival of this cohort of patients were 45.8% and 30.8%, respectively. Univariate analysis showed that age > 60 years, performance status ≥2, Ann Arbor stage III/IV, lactate dehydrogenase > 250 U/L, serum albumin (ALB) < 30 g/l, Coombs test positive, and Ki-67 rate ≥ 70% were significantly associated with poor prognosis. Multivariate analysis demonstrated that age > 60 years, ALB < 30 g/l, Ki-67 rate ≥ 70%, and Coombs test positive were independent prognosis factors for AITL. Here a new prognostic model, named as AITLI, was constructed using the top 5 significant prognostic factors for AITL prognostic prediction. The AITL patients were stratified into 3 risk groups: low, intermediate, and high risk groups. The new prognostic model AITLI showed better performance in predicting prognosis than the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) that were wisely used to predict the outcome for patients with other subtypes of lymphoma.

Advances in understanding of angioimmunoblastic T-cell lymphoma.

It has been nearly half a century since angioimmunoblastic T-cell lymphoma (AITL) was characterized in the early 1970's. Our understanding of the disease has dramatically changed due to multiple discoveries and insights. One of the key features of AITL is aberrant immune activity. Although AITL is now understood to be a neoplastic disease, pathologists appreciated that it was an inflammatory condition. The more we understand AITL at cellular and genetic levels, the more we view it as both a neoplastic and an inflammatory disease. Here, we review recent progress in our understanding of AITL, focusing on as yet unsolved questions.

EBV status has prognostic implication among young patients with angioimmunoblastic T-cell lymphoma.

Epstein-Barr virus (EBV)-positive B cells have been detected in 66%-86% of patients with angioimmunoblastic T-cell lymphoma (AITL). However, it remains controversial whether EBV status has an impact on the survival of patients with AITL. In this study, we aimed to reevaluate the impact of EBV on the clinicopathological characteristics of AITL. In particular, we focused on the impact of EBV in younger patients with AITL. In total, 270 cases of AITL were studied. Epstein-Barr virus-positive B cells were detected in 191 (71%) cases (EBER+ group). Among the patients who received anthracycline-based therapy, the EBER status did not affect the overall survival (OS) or progression-free survival (PFS). In the younger group of AITL (≤60 years), PFS was significantly worse in the EBER- group compared to the EBER+ group (P = .0013). Furthermore, the multivariate analysis identified EBER-negative status, thrombocytopenia, and elevated serum IgA level as significant adverse prognostic factors for PFS (P < .001, P < .001, and P = .002). Based on these findings, we constructed new prognostic model for the younger group, based on three adverse factors. We classified the patients into two risk groups: low risk (no or 1 adverse factor) and high risk (2 or 3 adverse factors). This new model for younger patients with AITL showed that both OS and PFS were significantly related to the level of risk (P < .0001). In summary, this study showed that, among younger patients with AITL, an EBER+ status significantly improved prognosis compared to an EBER- status. Our new prognostic model should be applicable to younger patients with AITL.

Immunoglobulinopathies in patients with angioimmunoblastic T-cell lymphoma.

AIM: The aim of the study was to characterize quantitative and qualitative immunoglobulinopathies in patients with AITL at the onset of the disease. MATERIALS AND METHODS: 55 patients with newly diagnosed AITL were enrolled in the study, the male/female ratio was 30/25; median age was 61 (29-81) years. Diagnosis was based on standard WHO criteria. Immunochemical studies of blood serum included serum protein electrophoresis/immunofixation, nephelometric quantification of total immunoglobulins, serum free light chain assay. RESULTS: Quantitative and qualitative immunoglobulinopathies were determined in 49 (89,1%) of 55 pts. Quantitative immunoglobulinopathies were revealed in 47 (85.5%) of 55 cases, qualitative - in 14 (25,5%). Combination quantitative and qualitative immunoglobulinopathies was observed in 12 (21,8%) of 55 pts. The detected immunoglobulinopathies were divided into 4 groups: polyclonal hypergammaglobulinaemia, hypogammaglobulinaemia, oligoclonal gammapathy, and monoclonal gammapathy. Polyclonal hypergammaglobulinaemia was marked in 41 (74.5%) of 55 pts, elevated level of IgG was determined in 27 (49,15%) of 55 cases, IgM - in 18 (32,7%) and IgA - in 21 (38.2%). Interestingly, polyclonal IgE hypergammaglobulinaemia was detected in 12 (48,0%) of 25 cases of performed studies. Hypogammaglobulinaemia was detected in 8 (14,5%) of 55 cases. Oligoclonal gammapathy was determined in 4 (7.3%) of 55 pts. Monoclonal gammapathy was revealed in 11 (20,0%) of 55 cases. The amount of monoclonal immunoglobulin varied from 2.6 to 14.1 g/l. Monoclonal immunoglobulin Gk was detected in 5 of 11 pts, Gλ - in 2, Mλ - in 2, Mk - in 2. Monoclonal gammapathy was accompanied by polyclonal hypergammaglobulinaemia in 9 of 11 cases, hypogammaglobulinaemia - in 2. CONCLUSION: Quantitative and qualitative immunoglobulinopathies are observed in most patients at the onset of AITL. Quantitative abnormalities were determined more often than qualitative. Monoclonal gammapathy can be a manifestation of lymphoproliferation and other concomitant disorders. The prognostic value of immunochemical parameters is still unclear and requires dynamic observation and study.

No survival improvement for patients with angioimmunoblastic T-cell lymphoma over the past two decades: a population-based study of 1207 cases.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare lymphoid malignancy with dismal prognosis. We conducted a large population-based study using the Surveillance, Epidemiology, and End Results (SEER) database (1973-2010) to determine the temporal survival trends and prognostic factors of AITL patients. A total of 1207 patients with AITL were included in this study, with a median age at diagnosis of 69 years. At presentation, most patients (79.5%) had an advanced-stage disease. Overall survival (OS) probabilities at 2, 5 and 10 years were 46.8%, 32.9%, and 21.9% respectively. Two-year, 5-year, and 10-year disease-specific survival (DSS) rates were 56.1%, 44.0%, and 35.9% respectively.On multivariate analysis, age older than 70 years, advanced-stage disease and male sex were identified adverse predictors for OS and DSS. We failed to find any survival differences among subgroups diagnosed in the 5 periods studied (1992 to 1998, 1999 to 2001, 2002 to 2004, 2005 to 2007, and 2008 to 2010). The current study represents the largest specific series of patients with AITL and the first investigation on temporal changes in survival of AITL patients. There has been no survival improvement for AITL patients over the past two decades. Further investigations are warranted to develop more effective treatment for AITL.

A targeted mutational landscape of angioimmunoblastic T-cell lymphoma.

The genetics of angioimmunoblastic T-cell lymphoma (AITL) are very poorly understood. We defined the mutational landscape of AITL across 219 genes in 85 cases from the United States and Europe. We identified ≥2 mutations in 34 genes, nearly all of which were not previously implicated in AITL. These included loss-of-function mutations in TP53 (n = 4), ETV6 (n = 3), CCND3 (n = 2), and EP300 (n = 5), as well as gain-of-function mutations in JAK2 (n = 2) and STAT3 (n = 4). TET2 was mutated in 65 (76%) AITLs, including 43 that harbored 2 or 3 TET2 mutations. DNMT3A mutations occurred in 28 (33%) AITLs; 100% of these also harbored TET2 mutations (P < .0001). Seventeen AITLs harbored IDH2 R172 substitutions, including 15 with TET2 mutations. In summary, AITL is characterized by high frequencies of overlapping mutations in epigenetic modifiers and targetable mutations in a subset of cases.

Retropharyngeal lymphadenopathy in patients with nasopharyngeal carcinoma: a computed tomography-based study.

BACKGROUND: The purpose of this study was to investigate the incidence and prognostic value of retropharyngeal lymphadenopathy in nasopharyngeal carcinoma patients using contrast enhanced computed tomography (CT). METHODS: From January 1989 to December 1991, 364 patients with newly diagnosed nasopharyngeal carcinoma without distant metastasis had a baseline CT performed. All patients had radiotherapy as their primary treatment. Eighty-seven patients also received neoadjuvant chemotherapy for locally advanced disease. All patients with clinical N0 disease had prophylactic lymph node irradiation. The contrast enhanced CT given prior to all treatment was evaluated for the presence of retropharyngeal lymphadenopathy. Criteria for involved lymph nodes included a lymph node size of 10 mm or more, the presence of central necrosis within the lymph node, or the presence of a contrast enhancing rim. RESULTS: The incidence of retropharyngeal lymphadenopathy was 29.1%. A higher incidence of retropharyngeal lymph node involvement was observed in Ho's T2/T3 disease compared with T1 disease, and a higher incidence was also found in patients with cervical lymph node disease compared with those with clinical N0 disease. No significant differences in relapse free survival rates, local control rates, lymph node control rates, or distant failure rates were observed between patients with or without retropharyngeal lymphadenopathy after adjusting for T and N classifications. In 134 patients with clinical N0 disease, retropharyngeal lymphadenopathy was found in 21 patients, whereas 113 had no evidence of retropharyngeal lymphadenopathy. However, no significant difference in treatment outcome was observed between the two groups. CONCLUSIONS: Using CT imaging, the presence of retropharyngeal lymphadenopathy in patients with nasopharyngeal carcinoma does not appear to affect the prognosis. In patients with clinical N0 disease, the identification of retropharyngeal lymphadenopathy based only on CT imaging is not sufficient evidence for an N1 classification.

[Angioimmunoblastic lymphadenopathy with dysproteinemia. The first reported case at the "Santo Tomás" Hospital]. / Linfadenopatiá angioinmunoblástica con disproteinemia. Primer caso reportado en el Hospital "Santo Tomás".

Description of the first case of angio-immunoblastic lymphadenopathy with dysproteinemia diagnosed in a male patient 64 years old and which preceded the development of a lymphoma. The importance of this study is the association that may exist between certain drugs and the development of angioimmunoblastic lymphadenopathy, which occurred in our patient with the use of diphenylhydantoin. This disease can present itself up to 22 years after exposure to the agent.

[Persistent generalized lymphadenopathies in homosexuals and drug addicts: changes in humoral and cellular immunity]. / Lymphadénopathies persistantes généralisées chez les homosexuels et les toxicomanes: altérations de l'immunité humorale et cellulaire.

In two groups of subjects at risk for acquired immune deficiency syndrome (AIDS), homosexual males and intravenous drug users with persistent generalized lymphadenopathy, humoral and cell-mediated immunity were compared. A small group of patients with definite AIDS were also studied. It was found that levels of immunoglobulins, serological markers for virus and other infections, cell-mediated immunity and histology of lymph nodes were similar in homosexuals and drug users, whereas the lymphocyte sub-populations differed completely. The number of T4+ lymphocytes was markedly decreased in homosexuals but normal in drug users; the number of T8+ lymphocytes was much higher in drug users than in homosexuals. This discrepancy may explain the extremely low prevalence of AIDS cases observed among Swiss drug users as compared with the high frequency noted among homosexuals.

The Vancouver Lymphadenopathy-AIDS Study: 1. Persistent generalized lymphadenopathy.

The Vancouver Lymphadenopathy-AIDS (acquired immune deficiency syndrome) Study is an ongoing prospective study of over 700 homosexual men attending six primary care practices in central Vancouver. A case-control study of risk factors for persistent generalized lymphadenopathy in homosexual men was conducted in five of the practices. The participants completed a questionnaire and underwent a complete physical examination at the time of enrollment and at a subsequent visit not less than 3 months later, and laboratory tests were performed after both visits. Persistent generalized lymphadenopathy was defined as the presence of lymph nodes greater than 1 cm in diameter at two or more extrainguinal sites for more than 3 months. Of the 519 patients who had completed both visits by February 1984, 126 (24%) were found to have the disease, and two controls without lymphadenopathy were frequency-matched on the basis of age and practice to each subject. More than 100 male sexual partners during one's lifetime, frequent receptive anal intercourse, a history of gonorrhea, use of illicit drugs and sexual contact in Los Angeles were identified as independent risk factors for persistent generalized lymphadenopathy. The similarity of these risk factors to those established for AIDS supports the hypothesis of a common etiology for the two diseases, and the high prevalence rate of persistent generalized lymphadenopathy further supports the hypothesis that AIDS is an uncommon response to a relatively common agent.