scholarly journals Targeted Approaches to T-Cell Lymphoma

2021 ◽  
Vol 11 (6) ◽  
pp. 481
Author(s):  
Sean Harrop ◽  
Chathuri Abeyakoon ◽  
Carrie Van Der Van Der Weyden ◽  
H. Miles Prince
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Rapid Expansion ◽  
Critical Pathways ◽  
Current State ◽  
T Cell Lymphomas ◽  
Hodgkin's Lymphomas ◽  
Rare Group ◽  
Subsequent Identification

The T-cell lymphomas are a rare group of Non-Hodgkin’s lymphomas derived from mature T-lymphocytes. They are divided broadly into the Peripheral T-cell lymphomas and the Cutaneous T-cell lymphomas. Clinical outcomes vary widely but are generally unsatisfactory with current treatments. The development of an understanding of the various critical pathways in T-cell lymphogenesis and subsequent identification of therapeutic targets has led to a rapid expansion of the previously underwhelming T-cell lymphoma armament. This review aims to provide an up-to-date overview of the current state of targeted therapies in the T-cell lymphomas, including novel antibody-based treatments, small molecule inhibitors and immune-based therapies.

Alemtuzumab in Combination with CHOP and ESHAP as First-Line Treatment in Peripheral T-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4740-4740 ◽  
Author(s):  
Tanin Intragumtornchai ◽  
Udomsak Bunworasate ◽  
Thanyaphong Na Nakorn ◽  
Ponlapat Rojnuckarin
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Pneumocystis Carinii ◽  
Elevated Serum ◽  
T Cell Lymphoma ◽  
Newly Diagnosed ◽  
Bulky Disease ◽  
T Cell Lymphomas ◽  
Hodgkin's Lymphomas ◽  
Cmv Disease

Abstract Patients diagnosed with peripheral T-cell lymphomas (PTCL) generally had a poorer prognosis compared to B-cell non-Hodgkin’s lymphomas. With conventional treatment, the 5-year overall and failure-free survivals (OS and FFS) were 36% and 23%, respectively (Vose et al, Blood2005;106:abstract 811). Between February 2005 and January 2006, 13 consecutive patients newly diagnosed with PTCL (5, extranodal nasal NK/T-cell lymphoma, 4 subcutaneous panniculitis-like, 3 PTCL, unspecified and 1 enteropathy type) were enrolled. The median age was 44 years (range, 21–56) and male:female was 1.6:1. Fifty-four percent had stage III/IV, 31%, PS 2–3, 69%, B-symptoms, 15%, bulky disease, 46%, > 1 extranodal site, 38%, elevated serum LDH and 39%, aaIPI 2–3. Twenty-three percent had thrombocytopenia. Patients were treated with alemtuzumab 30 mg. sc. D1-3 of cycle 1–5 plus CHOP (day 1 of cycle 1, 3, 5) and ESHAP (day 1 of cycle 2, 4, 6) at 28-day intervals. Valacyclovir 500 mg tid and trimethoprim/sulfamethoxazole were given for prophylaxis of CMV and Pneumocystis carinii infection, respectively. Of the evaluable 10 patients, complete remission was obtained in 8 patients, 1 had partial remission and 1 had CNS progression while on treatment. Infection was a major adverse complication: 54% had CMV reactivation (1 had CMV disease), 54%, febrile neutropenia and 15%, tuberculosis. With a median follow-up time of 8 months, the 2-year OS and FFS were 75% (95%CI, 41–92) and 48% (95%CI, 14–76), respectively. From the standpoint of this result, alemtuzumab in combination with CHOP and ESHAP is an effective front-line therapy for patients newly diagnosed with PTCL.

scholarly journals STAT3 Dysregulation in Mature T and NK Cell Lymphomas

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1711 ◽  
Author(s):  
Seffens ◽  
Herrera ◽  
Tegla ◽  
Buus ◽  
Hymes ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Ex Vivo ◽  
T Cell Lymphoma ◽  
Inflammatory Microenvironment ◽  
Stat3 Signaling ◽  
T Cell Lymphomas ◽  
Models Of Disease ◽  
Hodgkin's Lymphomas

Abstract: T cell lymphomas comprise a distinct class of non-Hodgkin’s lymphomas, which include mature T and natural killer (NK) cell neoplasms. While each malignancy within this group is characterized by unique clinicopathologic features, dysregulation in the Janus tyrosine family of kinases/Signal transducer and activator of transcription (JAK/STAT) signaling pathway, specifically aberrant STAT3 activation, is a common feature among these lymphomas. The mechanisms driving dysregulation vary among T cell lymphoma subtypes and include activating mutations in upstream kinases or STAT3 itself, formation of oncogenic kinases which drive STAT3 activation, loss of negative regulators of STAT3, and the induction of a pro-tumorigenic inflammatory microenvironment. Constitutive STAT3 activation has been associated with the expression of targets able to increase pro-survival signals and provide malignant fitness. Patients with dysregulated STAT3 signaling tend to have inferior clinical outcomes, which underscores the importance of STAT3 signaling in malignant progression. Targeting of STAT3 has shown promising results in pre-clinical studies in T cell lymphoma lines, ex-vivo primary malignant patient cells, and in mouse models of disease. However, targeting this pleotropic pathway in patients has proven difficult. Here we review the recent contributions to our understanding of the role of STAT3 in T cell lymphomagenesis, mechanisms driving STAT3 activation in T cell lymphomas, and current efforts at targeting STAT3 signaling in T cell malignancies.

Graft-Versus-Lymphoma Effect for Aggressive T-Cell Lymphomas in Adults: A Study by the Société Française de Greffe de Moëlle et de Thérapie Cellulaire

2008 ◽  
Vol 26 (14) ◽  
pp. 2264-2271 ◽  
Author(s):  
Steven Le Gouill ◽  
Noel Milpied ◽  
Agnès Buzyn ◽  
Régis Peffault De Latour ◽  
Jean-Paul Vernant ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Human Leukocyte ◽  
Lymphocytic Leukemia ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Nk T Cell ◽  
Thérapie Cellulaire ◽  
Hodgkin's Lymphomas

Purpose Aggressive T-cell lymphomas (ATCLs) represent 10% to 15% of non-Hodgkin's lymphomas (NHLs) in adults. ATCLs show a worse prognosis than B-cell lymphomas. Patients and Methods On behalf of the Société Française de Greffe de Moëlle et de Thérapie Cellulaire, we conducted a retrospective analysis including 77 ATCL patients who underwent allogeneic stem-cell transplantation (alloSCT). Results The different diagnosis included anaplastic large-cell lymphoma (ALCL; n = 27), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n = 27), angioimmunoblastic T-cell lymphoma (AITL; n = 11), hepatosplenic γ/δ lymphoma (HSL; n = 3), T-cell granular lymphocytic leukemia (T-GLL; n = 1), nasal natural killer (NK)/T-cell lymphoma (nasal-NK/L; n = 3) or non-nasal NK/T-cell lymphoma (non-nasal-NK/L; n = 2), enteropathy-type T-cell (n = 1), and human T-lymphotropic virus (HTLV)-1 lymphoma (n = 2). Fifty-seven patients received a myeloablative conditioning regimen. Donors were human leukocyte antigen (HLA)-matched in 70 cases and related in 60 cases. Thirty-one patients were in complete remission (CR) at the time of alloSCT, whereas 26 were in partial response (PR). Five-year toxicity-related mortality (TRM) incidence was 33% (95% CI, 24% to 46%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57% (95% CI, 45% to 68%) and 53% (95% CI, 41% to 64%), respectively. In multivariate analysis, chemoresistant disease (stable, refractory, or progressing disease) at the time of alloSCT and the occurrence of severe grade 3 to 4 acute graft-versus-host disease (aGVHD) were the strongest adverse prognostic factors for OS (P = .03 and .03, respectively). Disease status at transplantation significantly influenced the 5-year EFS (P = .003), and an HLA-mismatched donor increased TRM (P = .04). Conclusion We conclude that alloSCT is a potentially efficient therapy for NK/T lymphomas and is worth further investigation through prospective clinical trials.

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.

scholarly journals Successful Treatment of Advanced Primary Cutaneous Peripheral T-Cell Lymphoma with Oral Bexarotene Monotherapy

2018 ◽  
Vol 11 (1) ◽  
pp. 212-215 ◽  
Author(s):  
Yota Sato ◽  
Taku Fujimura ◽  
Yumi Kambayashi ◽  
Akira Hashimoto ◽  
Setsuya Aiba
Keyword(s):  
T Cell ◽  
Successful Treatment ◽  
Cell Lymphoma ◽  
Skin Lesions ◽  
Retinoid X Receptor ◽  
T Cell Lymphoma ◽  
Third Generation ◽  
Peripheral T Cell Lymphoma ◽  
Not Otherwise Specified ◽  
T Cell Lymphomas

Bexarotene is a third-generation retinoid X receptor-selective retinoid that is widely used for the early treatment of advanced-stage cutaneous T-cell lymphomas. In this report, we describe a case of successful treatment of advanced primary cutaneous peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) with oral bexarotene monotherapy. After the administration of oral bexarotene at a dose of 300 mg/m2/day, all skin lesions and lymph nodes regressed, and complete remission was achieved for 1 year. Our case suggested that bexarotene monotherapy could be one of the possible therapies for the treatment of primary cutaneous PTCL-NOS.

Results From a Prospective, Open-Label, Phase II Trial of Bendamustine in Refractory or Relapsed T-Cell Lymphomas: The BENTLY Trial

2013 ◽  
Vol 31 (1) ◽  
pp. 104-110 ◽  
Author(s):  
Gandhi Damaj ◽  
Rémy Gressin ◽  
Krimo Bouabdallah ◽  
Guillaume Cartron ◽  
Bachra Choufi ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
T Cell Lymphoma ◽  
Open Label ◽  
Previous Response ◽  
Angioimmunoblastic Lymphadenopathy ◽  
Prior Chemotherapy ◽  
T Cell Lymphomas

Purpose To determine the efficacy and safety of bendamustine as a single agent in refractory or relapsed T-cell lymphomas. Patients and Methods Patients with histologically confirmed peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma who progressed after one or more lines of prior chemotherapy received bendamustine at 120 mg/m2 per day on days 1 through 2 every 3 weeks for six cycles. The primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results Of the 60 patients included, 27 (45%) were refractory to their last prior chemotherapy, and the median duration of the best previous response was 6.6 months. Histology was predominantly angioimmunoblastic lymphadenopathy and PTCL not otherwise specified. The disease was disseminated in the majority of patients (87%). The median number of previous lines of chemotherapy was one (range, one to three). Twenty patients (33%) received fewer than three cycles of bendamustine, mostly because of disease progression. In the intent-to-treat population, the ORR was 50%, including complete response in 17 patients (28%) and partial response in 13 patients (22%). Bendamustine showed consistent efficacy independent of major disease characteristics. The median values for DoR, PFS, and OS were 3.5, 3.6, and 6.2 months, respectively. The most frequent grade 3 to 4 adverse events were neutropenia (30%), thrombocytopenia (24%), and infections (20%). Conclusion Bendamustine showed an encouraging high response rate across the two major PTCL subtypes, independent of age and prior treatment, with acceptable toxicity in refractory or relapsed T-cell lymphoma.

scholarly journals Peripheral T cell lymphoma: immunologic and cell-kinetic observations associated with morphological progression

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 980-989 ◽  
Author(s):  
CD Winberg ◽  
K Sheibani ◽  
R Krance ◽  
H Rappaport
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
Sheep Erythrocyte ◽  
S Phase ◽  
T Cell Lymphoma ◽  
Cell Kinetic ◽  
Mixed Cell ◽  
Hla Dr ◽  
Hodgkin's Lymphomas

Abstract Peripheral T cell lymphomas (PTCLs) form a morphologically heterogeneous group of non-Hodgkin's lymphomas that are generally considered to have immunophenotypes associated with mature T cells, usually those of helper T cells. We now describe and correlate the clinical, morphological, immunologic, and cell-kinetic findings based on the evaluation of eight tissue samples obtained at various times from a 13-year-old girl with PTCL. The early morphological expressions of this patient's PTCL were those of diffuse mixed-cell lymphoma and focal large-cell lymphoma (LCL) evolving from the histologic picture of an atypical immune response (AIR). These morphological findings were associated with an immature T cell immunophenotype associated with cortical thymocytes--namely, sheep erythrocyte rosette (sER)+, T11+, Leu-2a+, Leu-3a+, HLA-DR+, OKT6-, OKT9+, OKT10+--and with cell-kinetic findings that showed no evidence of aneuploidy and few cells in S phase. Diffuse pleomorphic LCL developed, which was associated with further dedifferentiation of the neoplastic T cells to the immunophenotype sER-, T11+, Leu-2a-, Leu-3a-, HLA-DR+, OKT6-, OKT9+, OKT10- and with cell-kinetic findings that demonstrated a distinct aneuploid population and a dramatic increase in the percentage of cells in the S phase. The immunophenotype of the PTCL at the time of the patient's death was T11-, Leu-2a-, Leu-3a-, HLA-DR+, OKT6-, OKT9+, OKT10-, an immunophenotype indistinguishable from that of a non-B non-T cell lymphoma. The immunologic findings in this case also suggest that an AIR in some cases may represent a prelymphomatous state or may be a morphological expression of PTCL. These observations indicate that PTCLs may be characterized by rapidly changing clinical, morphological, immunologic, and cell kinetic findings which are best evaluated by multidisciplinary studies.

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.

Direct comparisons of peripheral T-cell lymphoma with diffuse B-cell lymphoma of comparable histological grades--should peripheral T-cell lymphoma be considered separately?

1989 ◽  
Vol 7 (6) ◽  
pp. 725-731 ◽  
Author(s):  
A L Cheng ◽  
Y C Chen ◽  
C H Wang ◽  
I J Su ◽  
H C Hsieh ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Induction Chemotherapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Grade ◽  
Peripheral T Cell Lymphoma ◽  
Laboratory Features ◽  
Hodgkin's Lymphomas

Peripheral T-cell lymphoma (PTCL) forms a morphologically heterogeneous group of non-Hodgkin's lymphomas (NHL) with distinct immunophenotypes of mature T cells. Progress has been slow in defining specific clinicopathological entities to this particular group of NHL. In order to elucidate the specific characteristics of PTCL, a direct comparison of PTCL with a group of diffuse B-cell lymphomas (DBCL) was performed. Between June 1983 and December 1987, we studied 114 adults with NHL, using a battery of immunophenotyping markers. Adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, mycosis fungoides/Sézary syndrome, follicular lymphoma, well-differentiated lymphocytic lymphoma, and true histiocytic lymphoma were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunophenotypes. Of the remaining 75 patients, 70 who had adequate clinical information were analyzed, and of these, 34 were PTCL and 36 were DBCL. Classified according to the National Cancer Institute (NCI) Working Formulation (WF), 68% of PTCL and 31% of DBCL were high-grade lymphomas. Clinical and laboratory features were similar, except PTCL had a characteristic skin involvement and tended to present in more advanced stages with more constitutional symptoms. Induction chemotherapy was homogeneous in both groups, and complete remission rates were 62% for PTCL and 67% for DBCL. Patients with DBCL had a better overall survival than patients with PTCL, but the survival benefit disappeared after patients were stratified according to intermediate- or high-grade lymphoma. A subgroup of PTCL patients who had received less intensive induction chemotherapy was found to have a very unfavorable outcome. We conclude that (1) PTCL follows the general grading concept proposed in WF classification; (2) within a given intermediate or high grade, PTCL and DBCL respond comparably to treatment; (3) the intensity of induction chemotherapy has a crucial impact on the outcome of PTCL patients; and (4) with a few exceptions, the clinical and laboratory features of PTCL and DBCL are comparable.

scholarly journals Non Hodgkin T cell lymphoma: an atypical clinical presentation

2013 ◽  
Vol 88 (2) ◽  
pp. 264-267
Author(s):  
Paula Maio ◽  
Diogo Bento ◽  
Raquel Vieira ◽  
Ana Afonso ◽  
Fernanda Sachse ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Presentation ◽  
Cell Lymphoma ◽  
Systemic Disease ◽  
Skin Lesions ◽  
T Cell Lymphoma ◽  
Lymphocyte Population ◽  
T Cell Lymphomas ◽  
Atypical Clinical Presentation ◽  
New Skin

Cytotoxic lymphomas comprise a spectrum of peripheral T-cell lymphomas that can have a initial or late cutaneous presentation. We describe a 46-year-old man from Cape Verde, with a dermatosis involving his face and trunk, consisting of monomorphic papules with a smooth surface and both motor and sensory polyneuropathy.The hypothesis of leprosy was supported by the clinical and initial hystopathological findings and the patient was referred to our hospital with suspected Hansen's disease. In the new skin and lymph node biopsies a lymphocyte population was identified whose immunohystochemistry study allowed the diagnosis of T-cell lymphoma with expression of cytotoxic markers. The patient was started on chemotherapy with initial remission of the skin lesions but, subsequently, progression of systemic disease.

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