scholarly journals Increased Expression of Phosphorylated FADD in Anaplastic Large Cell and Other T-Cell Lymphomas

2014 ◽  
Vol 9 ◽  
pp. BMI.S16553 ◽  
Author(s):  
Suketu Patel ◽  
Derek Murphy ◽  
Eugenia Haralambieva ◽  
Zainalabideen A. Abdulla ◽  
Kah Keng Wong ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Death Receptor ◽  
Adaptor Protein ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Death Domain ◽  
Normal Tissues ◽  
T Cell Lymphomas ◽  
Human T Cell

FAS-associated protein with death domain (FADD) is a major adaptor protein involved in extrinsic apoptosis, embryogenesis, and lymphocyte homeostasis. Although abnormalities of the FADD/death receptor apoptotic pathways have been established in tumorigenesis, fewer studies have analyzed the expression and role of phosphorylated FADD (pFADD). Our identification of FADD as a lymphoma-associated autoantigen in T-cell lymphoma patients raises the possibility that pFADD, with its correlation with cell cycle, may possess role(s) in human T-cell lymphoma development. This immunohistochemical study investigated pFADD protein expression in a range of normal tissues and lymphomas, particularly T-cell lymphomas that require improved therapies. Whereas pFADD was expressed only in scattered normal T cells, it was detected at high levels in T-cell lymphomas (eg, 84% anaplastic large cell lymphoma and 65% peripheral T cell lymphomas, not otherwise specified). The increased expression of pFADD supports further study of its clinical relevance and role in lymphomagenesis, highlighting phosphorylation of FADD as a potential therapeutic target.

scholarly journals Epidemiology of Non-Hodgkin’s Lymphoma

2021 ◽  
Vol 9 (1) ◽  
pp. 5
Author(s):  
Krishna C. Thandra ◽  
Adam Barsouk ◽  
Kalyan Saginala ◽  
Sandeep Anand Padala ◽  
Alexander Barsouk ◽  
...  
Keyword(s):  
T Cell ◽  
Radiation Treatment ◽  
Cell Lymphoma ◽  
Breast Implants ◽  
Occupational Exposures ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Human Herpes Virus 8 ◽  
Human T Cell

Non-Hodgins’s lymphoma (NHL) is the most common hematological malignancy worldwide, accounting for nearly 3% of cancer diagnoses and deaths. NHL is the seventh most prevalent cancer and has the sixth highest mortality among cancers in the US. NHL accounts for 4% of US cancer diagnoses, and incidence has increased 168% since 1975 (while survival has improved 158%). NHL is more common among men, those >65 years old, and those with autoimmune disease or a family history of hematological malignancies. NHL is a heterogenous disease, with each subtype associated with different risk factors. Marginal zone lymphoma (MZL) is strongly associated with Sjogren’s syndrome (SS) and Hashimoto’s thyroiditis, while peripheral T-cell lymphoma (PTCL) is most associated with celiac disease. Occupational exposures among farm workers or painters increases the risk of most of the common subtypes. Prior radiation treatment, obesity, and smoking are most highly associated with diffuse large B-cell lymphoma (DLBCL), while breast implants have been rarely associated with anaplastic large cell lymphoma (ALCL). Infection with Epstein–Barr Virus (EBV) is strongly associated with endemic Burkitts lymphoma. HIV and human herpes virus 8 (HHV-8), is predisposed to several subtypes of DLBCL, and human T-cell lymphoma virus (HTLV-1) is a causative agent of T-cell lymphomas. Obesity and vitamin D deficiency worsen NHL survival. Atopic diseases and alcohol consumption seem to be protective against NHL.

Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 2213-2219 ◽  
Author(s):  
Marcel W. Bekkenk ◽  
Maarten H. Vermeer ◽  
Patty M. Jansen ◽  
Ariënne M. W. van Marion ◽  
Marijke R. Canninga-van Dijk ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Size ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Skin Lesions ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Nor Phenotype ◽  
Peripheral T Cell Lymphomas

Abstract In the present study the clinicopathologic and immunophenotypic features of 82 patients with a CD30– peripheral T-cell lymphoma, unspecified, presenting in the skin were evaluated. The purpose of this study was to find out whether subdivision of these lymphomas on the basis of cell size, phenotype, or presentation with only skin lesions is clinically relevant. The study group included 46 primary cutaneous CD30– large cell lymphomas and 17 small/medium-sized T-cell lymphomas as well as 17 peripheral T-cell lymphomas with both skin and extracutaneous disease at the time of diagnosis. Patients with primary cutaneous small- or medium-sized T-cell lymphomas had a significantly better prognosis (5-year-overall survival, 45%) than patients with primary cutaneous CD30– large T-cell lymphomas (12%) and patients presenting with concurrent extracutaneous disease (12%). The favorable prognosis in this group with primary cutaneous small- or medium-sized T-cell lymphomas was particularly found in patients presenting with localized skin lesions expressing a CD3+CD4+CD8– phenotype. In the primary cutaneous T-cell lymphoma (CTCL) group and in the concurrent group, neither extent of skin lesions nor phenotype had any effect on survival. Our results indicate that peripheral T-cell lymphomas, unspecified, presenting in the skin have an unfavorable prognosis, irrespective of the presence or absence of extracutaneous disease at the time of diagnosis, cell size, and expression of a CD4+ or CD8+ phenotype. The only exception was a group of primary cutaneous small- or medium-sized pleomorphic CTCLs with a CD3+CD4+CD8– phenotype and presenting with localized skin lesions.

The T-Cell Activation Markers CD30 and OX40/CD134 Are Expressed in Nonoverlapping Subsets of Peripheral T-Cell Lymphoma

Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3487-3493 ◽  
Author(s):  
Dan Jones ◽  
Christopher D.M. Fletcher ◽  
Karen Pulford ◽  
Aliakbar Shahsafaei ◽  
David M. Dorfman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Tnf Receptor ◽  
T Cell Lymphomas ◽  
Tumor Types ◽  
Tnf Receptor Family ◽  
Receptor Family

The tumor necrosis factor (TNF) receptor family includes several important markers of activation in T cells. We examined expression patterns of two T-cell-associated members of these receptors, namely CD30 and OX40/CD134, in 148 cases of T-cell lymphoma to identify possible objective immunohistochemical criteria for subclassification of these tumors. CD30 expression was characteristic of tumors with an anaplastic (46/47 cases [98%]) or large-cell (10/21 [48%]) morphology and was seen in only scattered cells in other tumor types. In contrast, large numbers of OX40/CD134+ tumors cells were typical of angioimmunoblastic lymphoma (15/16 [94%]), angiocentric lymphoma (4/4), a subset of large-cell lymphomas (10/21 [48%]), and lymphomas with a prominent histiocytic component (6/7 [86%]). Strong OX40/CD134 and CD30 coexpression was seen in only 4% of tumors, typically those with an anaplastic/Hodgkin’s-like appearance. OX40/CD134 expression was characteristic of tumors composed of activated CD4+ T cells and was not seen in small-cell T-cell lymphomas, lymphoblastic lymphomas, or other tumor types, including B-cell lymphomas or carcinomas. These results suggest that immunostaining for OX40/CD134 may be helpful in subclassification of peripheral T-cell lymphomas and that the patterns of TNF receptor family expression in these tumors may parallel those seen within nonneoplastic helper T-cell subsets.

Brentuximab vedotin in real life, a seven year experience in patients with refractory/relapsed CD30+ T cell lymphoma

2020 ◽  
pp. 107815522096861
Author(s):  
Lucie Oberic ◽  
Faustine Delzor ◽  
Caroline Protin ◽  
Sophie Perriat ◽  
Camille Laurent ◽  
...  
Keyword(s):  
T Cell ◽  
Combination Treatment ◽  
Cell Lymphoma ◽  
Real Life ◽  
Progression Free Survival ◽  
Large Cell ◽  
Complete Response ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas

Introduction Brentuximab vedotin (Bv) has been approved for the treatment of Refractory/Relapsed (R/R) Anaplastic Large Cell Lymphomas (ALCL) and cutaneous T-Cell Lymphomas, but is also effective in other CD30+ malignancies. We report here the outcomes of patients with various R/R Peripheral T Cell Lymphoma (PTCL) treated with Bv in real life practice. Method This was a retrospective, single-center study based on medical records of patients with R/R PTCL treated either with Bv alone or in combination with chemotherapy. Results Among 27 patients treated with Bv, neutropenia was the main serious adverse event observed in particular when Bv was used as combination treatment. The complete Response Rates (CRR) was 40.7%; it was significantly improved when Bv was used as combination treatment. The majority of eligible patients (7/10) underwent Stem Cell Transplantation. Median Progression Free Survival (PFS) and Overall Survival (OS) were 5.2 months and 12.5 months respectively. Conclusion Our current study shows that Bv used in combination with chemotherapy provides a high CRR and thereby allows SCT in R/R PTCL. The use of Bv treatments in this setting warrants further investigation.

scholarly journals Molecular insights into pathogenesis and targeted therapy of peripheral T cell lymphoma

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Caiqin Xie ◽  
Xian Li ◽  
Hui Zeng ◽  
Wenbin Qian
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
The Common ◽  
Poor Outcomes ◽  
Almost All ◽  
Generation Sequencing

AbstractPeripheral T-cell lymphomas (PTCLs) are biologically and clinically heterogeneous diseases almost all of which are associated with poor outcomes. Recent advances in gene expression profiling that helps in diagnosis and prognostication of different subtypes and next-generation sequencing have given new insights into the pathogenesis and molecular pathway of PTCL. Here, we focus on a broader description of mutational insights into the common subtypes of PTCL including PTCL not other specified type, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, and extra-nodal NK/T cell lymphoma, nasal type, and also present an overview of new targeted therapies currently in various stages of clinical trials.

FDG-PET Scans as a Staging Study for T-Cell Lymphomas: High Rates of Positivity Do Not Result in Frequent Changes in Stage.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2399-2399 ◽  
Author(s):  
Steven M. Horwitz ◽  
Francine Foss ◽  
Shari Goldfarb ◽  
Ana Molina ◽  
Paul A. Hamlin ◽  
...  
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Fdg Pet ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Large Cell Lymphoma ◽  
Pet Scans

Abstract FDG-PET is emerging as a standard staging study for diffuse large B-cell lymphoma and Hodgkin’s disease. There is little experience with PET in staging T-cell lymphomas (TCL). TCL often involve extranodal sites not well imaged by standard CT. We hypothesized that PET would add to staging by detecting additional sites of disease. To address this question we reviewed our TCL database to identify patients (pt) who had PET as part of complete staging at initial diagnosis or at relapse. Each pt was included once. Staging included physical exam, CT scan of the chest/abdomen/pelvis alone or as part of a PET/CT combination, and bone marrow (BM) biopsy. Studies such as MRI of the sinus or ultrasound of the testes were done as clinically indicated. We reviewed 107 pt who met the above criteria. Histologies were as follows: peripheral T-cell lymphoma NOS (PTCL), angioimmunoblastic T-cell lymphoma (AILT), anaplastic large cell lymphoma, ALK-1-, (ALCL−), anaplastic large cell lymphoma, ALK-1+, (ALCL+), mycosis fungoides (MF), subcutaneous panniculitis-like T-cell lymphoma (SPTCL), adult T-cell lymphoma (ATL), NK lymphoma nasal type (NK-Nas), lymphoblastic lymphoma (LL), enteropathy associated T-cell lymphoma (EATCL), blastic NK lymphoma (BLNK), primary cutaneous ALCL (ALCL-Cut), and hepatosplenic T-cell lymphoma (HSPTCL). All pt with MF had suspicion of extracutaneous disease. Overall 95/107 (89%) had a PET interpreted as positive by visual review. Standard uptake values (SUV) varied from 1.1–20.5 g/ml. Of the 12 pt with negative PET scans, 7(58%) had no evidence of disease on CT including PTCL (n=3, stage I resected), HSPTCL (n=2, liver, spleen, BM disease only), ALCL-Cut (n=2, skin only). T-cell Lymphoma-PET Results Histology N PET + % positive SUV Range (g/ml) ALL PT 107 95 89% 1.1–20.5 PTCL 27 24 88% 2–20 AILT 19 16 84% 2–11.7 ALCL− 12 12 100% 3–19.6 ALCL+ 4 4 100% 4–12 MF 12 10 83% 1.8–17.6 SPTCL 8 8 100% 1.4–13.1 ATL 5 5 100% 2.9–19.7 NK-Nas 5 5 100% 3.4–13.1 LL 3 3 100% 5.5–20.5 EATCL 3 3 100% 3.5–9.9 ALCL-Cut 5 3 60% 1.1–1.4 BLNK 2 2 100% 1.929.5 HSPTCL 2 0 0 N/A PET detected additional sites of disease in 34/107 (32%). These sites detected by PET were skin/subcut (n=9), bone (n=7), lymph node (n=6), spleen (n=3), nasopharynx/sinus (n=2), liver (n=2), BM (n=1), bowel (n=1), muscle (n=1), kidney (n=1), tonsil (n=1), testes (n=1). Three new malignancies were incidentally detected by PET including lung cancer (n=1), metastatic renal cell to the parotid (n=1), and mantle cell lymphoma (n=1 in a pt with ALCL-cut). Despite these additional sites, stage was changed in only 10/107 (9%). We did not use negative PET to downstage. Sites resulting in higher stage included bone (n=3), lymph node (n=2), subcut/muscle (n=3), testes (n=1), liver (n=1). Skin lesions were noted on physical exam and therefore did not change stage. In conclusion, TCL are almost universally PET positive. PET often adds information by identifying extranodal disease. However, partly due to many pt being stage IV by other modalities, PET resulted in a change of stage in <10% of pt. PET may be particularly useful in assessing of skin sites. These data suggest that it may be beneficial to include PET in the response assessment of TCL, as has been proposed for DLBCL and HL in revised NHL response criteria.

A Retrospective Comparison of Autologous Vs. Allogeneic Transplantation for Peripheral T-Cell Lymphoma: A Single Institution Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4392-4392
Author(s):  
Frederick Lansigan ◽  
Stuart Seropian ◽  
Dennis Cooper ◽  
Francine Foss
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Unrelated Donor ◽  
T Cell Lymphomas ◽  
First Remission

Abstract Peripheral T-cell Lymphomas (PTCL) are a heterogenous group of malignanices that represent 10–15% of non-Hodgkin lymphoma (NHL). This group has a worse prognosis with conventional chemotherapy compared to B-cell lymphomas. Both autologous (AutoSCT) and allogeneic stem cell transplantation (AlloSCT) have been used as consolidation in first remission and at relapse, but the role of transplantation has not been clearly defined. We report a retrospective analysis of 42 patients with PTCL who underwent AutoSCT (24) or AlloSCT (18) between 8/1997 and 12/2007. The AlloSCT group consisted of 4 PTCL unspecified (PTCLu), 3 angioimmunoblastic T-cell lymphomas (AITL), 2 panniculitic T-cell lymphomas, 2 cutaneous T-cell lymphomas (CTCL) with large cell transformation, 2 NK-cell lymphomas, 2 anaplastic large cell lymphomas (ALCL, 1 Alk+, 1 Alk unknown), 1 hepatosplenic T-cell lymphoma, 1 enteropathic T-cell lymphoma, and 1 refractory CTCL. The AutoSCT group consisted of 6 PTCLu, 12 ALCL (5 Alk+, 5 Alk−, 2 Alk unknown), 4 AITL, 1 CTCL with transformation, and 1 T-lymphoblastic lymphoma. The median age of the AlloSCT and AutoSCT groups was 51 (range 29–72) and 52 years (range 19–67), respectively. The median number of prior treatments of the AlloSCT and AutoSCT groups were 3 (range 1 to 5) and 1 (range 1 to 5), respectively. Within the AlloSCT group there were 14 matched-related donor transplants, and 4 matched-unrelated donor transplants; 7 were ablative and 11 were reduced-intensity transplants; the AlloSCT conditioning regimens varied. The AutoSCT group predominantly received BEAM as their conditioning regimen. Median time from diagnosis to AlloSCT or AutoSCT was 18.4 (range 6.9 to 109) and 7.5 (range 3.9 to 25) months, respectively. Median follow-up times for the AlloSCT and AutoSCT groups were 28.6 and 23.5 months, respectively. The day 100 transplant-related mortality rates in the AlloSCT and AutoSCT groups were 11% and 0%, respectively. Within the AlloSCT group the relapse and non-relapse mortalities were 11% and 33%, respectively. In the AutoSCT group, the relapse mortality was 33%. The 1- and 2-year overall survival (OS) rates were similar within the AlloSCT and AutoSCT groups (78% vs 74%, and 67% vs 60%, respectively). The 1- and 2-year progression-free survival (PFS) rates for the AlloSCT vs AutoSCT groups were 68% vs 52%, and 53% vs 45%, respectively (p = 0.28). Within the AutoSCT group, 14 patients (58%) were transplanted in first complete remission (CR1), and 10 (42%) in second complete remission (CR2), beyond CR2, or partial remission (PR). Patients in CR1 had significantly better PFS (57 vs 17 months, p=0.007) and OS (76 vs 29 months, p=0.004) than those in CR2, PR2, or beyond. Within the AlloSCT group, there was a trend toward poorer OS in 6 patients (33%) who had prior AutoSCT (32 vs 60 months, p=0.15). One patient (6%) was transplanted in CR1, and is still alive. We conclude that outcomes for AutoSCT are best in CR1. For patients with resistant or relapsed disease, AlloSCT should be strongly considered rather than AutoSCT. Prior AutoSCT may affect the outcome of AlloSCT. These results suggest that a prospective randomized trial comparing AutoSCT and AlloSCT for aggressive PTCL in first remission is warranted.

Comparison of Referring and Final Pathology for T-Cell Lymphomas in the NCCN

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1610-1610
Author(s):  
Alex F Herrera ◽  
Allison Crosby-Thompson ◽  
Jonathan W. Friedberg ◽  
Gregory A. Abel ◽  
Myron S. Czuczman ◽  
...  
Keyword(s):  
T Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Final Diagnosis ◽  
Outcome Data ◽  
Molecular Techniques ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Therapeutic Decisions

Abstract Abstract 1610 Background: T-cell lymphomas (TCL) are an uncommon group of diseases recently updated in the WHO classification. Accurate diagnosis requires immunophenotyping and molecular techniques. Diagnostic accuracy of TCLs utilizing the WHO classification has not previously been evaluated. Methods: The NCCN NHL database prospectively collects clinical, treatment, and outcome data for patients seen at 7 comprehensive cancer centers. Using this unique resource, we evaluated diagnostic concordance between referring and NCCN centers for TCLs, including peripheral T-cell lymphoma, NOS (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), and ALK-negative ALCL utilizing pathology reports, immunohistochemical stains, flow cytometry, fluorescence in situ hybridization/cytogenetics, T-cell gene rearrangement, and progress notes. Results: Of 98 eligible patients enrolled from April 2007 to March 2011, 38 (39%) cases were concordant and 60 (61%) were non-concordant. Among non-concordant cases, 34 (57%) had a provisional diagnosis before referral, 6 (10%) were discordant with no additional studies performed, 17 (28%) were discordant with additional studies performed, and 3 (5%) required an additional biopsy. Concordance was highest for ALK+ ALCL at 73%, while the remaining subtypes had low concordance: PTCL NOS 28%, AITL 28%, ALK- ALCL 47%. In 13 (13%) discordant cases (referral diagnosis was benign, a B-cell NHL, or ALK status was undefined) patients may have experienced a significant change in treatment with pathologic reclassification. Conclusions: In patients with TCL, the likelihood of a concordant final diagnosis at a referring institution was low. Among non-concordant cases, the majority were referred with provisional diagnoses, and many referral diagnoses were discordant. Establishing a precise diagnosis is critical for prognosis and impacts both therapeutic decisions and clinical trial enrollment. As current and future therapies, such as brentuximab vedotin, target subsets of TCLs, our data suggest that all suspected TCLs may benefit from evaluation by an expert hematopathologist. Disclosures: Kaminski: Allos: Consultancy, Honoraria.

scholarly journals An Update in Management of Noncutaneous T-Cell Lymphomas

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Y. Y. Hwang ◽  
R. H. S. Liang
Keyword(s):  
T Cell ◽  
Treatment Approach ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Conventional Chemotherapy ◽  
High Dose Therapy ◽  
T Cell Lymphomas ◽  
Alk Positive

T-cell lymphoma is a heterogeneous group of diseases. Except for ALK positive anaplastic large cell lymphoma, T-cell lymphoma responds to conventional chemotherapy unfavourably, and most patients carry poor prognosis. In recent years, efforts have been made to improve the outcome of T-cell lymphoma patients. Novel agents, high-dose therapy, and allogeneic stem cell transplantation are studied, and various results are reported in literature. This paper looks into the prognostication and treatment approach of different entities of noncutaneous T-cell lymphoma and would focus on the latest updates in its management.

scholarly journals Detection of the human T cell lymphoma virus p19 in cells of some patients with cutaneous T cell lymphoma and leukemia using a monoclonal antibody.

1981 ◽  
Vol 154 (6) ◽  
pp. 1957-1964 ◽  
Author(s):  
M Robert-Guroff ◽  
F W Ruscetti ◽  
L E Posner ◽  
B J Poiesz ◽  
R C Gallo
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Natural Reservoir ◽  
T Cell Lymphomas ◽  
Human T Cell ◽  
Type C

A monoclonal antibody specific for the internal p19 protein of a type-C retrovirus (HTLV) isolated from human neoplastic T cells has been developed. Its specificity has been shown by radioimmune precipitation and by affinity chromatography of iodinated HTLV proteins. By indirect immune fluorescence this antibody recognizes only HTLV-producing cells. Examination of cells from patients with cutaneous T cell lymphomas and leukemias and with other types of lymphomas and leukemias indicated that HTLV p19 expression is rare. The monoclonal antibody will be useful in determining the natural reservoir of HTLV, possibly in a subset of mature T cell neoplasias.

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