scholarly journals "Real-World" Peripheral T-Cell Lymphomas Experience in Portugal: Is There Reason for Optimism?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5287-5287
Author(s):  
Ivan Dlouhy ◽  
Rita Gavancha ◽  
Inês Coelho ◽  
Catalina Gomez ◽  
Inês Barbosa ◽  
...  
Keyword(s):  
T Cell ◽  
Single Agent ◽  
Treatment Strategies ◽  
Large Cell ◽  
New Drugs ◽  
Response To Treatment ◽  
Hematopoietic Stem ◽  
Histologic Subtype ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Introduction: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of mature T-cell neoplasms with aggressive behavior and dismal outcomes. Anthracycline-based chemotherapy is commonly used upfront; hematopoietic stem-cell transplantation (HSCT) is employed as consolidation by some groups. Refractory/relapsed cases (R/R) have a median survival of less than 6 months. Our objective was to analyze the outcomes of all consecutive PTCLs diagnosed and treated in a single center during 16 years according to histological subtype, disease phase (first line and R/R) and treatment strategies. Patients and methods: All adult PTCL patients referred to our center between 2003 and 2019 were included. All cases were locally diagnosed based on the current WHO classification by an expert hemato-pathologist. Initial clinical features, treatment and outcomes were analyzed, as well as salvage strategies. Results: A total of 188 patients were included (118 male, 70 female; median age 62 years). Median OS was 22.7 months, with a median follow up of 54 months. Histological subtypes, initial features, response to treatment and survival are detailed in table 1. Briefly, most cases were diagnosed at advanced stages, with extranodal involvement in 69% and elevated beta-2 microglobulin (B2m) in 77%; half had B symptoms. OS according to different subtypes is shown in figure 1. Of note, anaplastic large cell lymphoma (ALCL)-ALK+ patients had a 5-year OS of 88%. Interestingly, fifteen patients had circulating lymphoma cells (12 PTCL not otherwise specified [NOS], 2 hepatosplenic lymphoma and 1 angioimmunoblastic lymphoma [AITL]), with no impact on outcome. PTCL-NOS was the most prevalent subtype (40%) followed by AITL; unexpectedly, the proportion of PTCL-NOS cases increased while AITL cases decreased after 2008. Seven cases belonging to the recently recognized nodal PTCL with T follicular helper (TFH) phenotype were observed, with baseline characteristics and outcome similar to other PTCLs. IPI score index stratified patients into 4 groups with 24-month OS of 71%, 55%, 42% and 16% for low, int-low, int-high and high risk patients, respectively (P=.049). Only B2m and IPI score maintained independent significance for OS (HR= 3.2 and 1.8, respectively, P<.01) in a multivariate analysis that also included histologic subtype and frontline treatment. Most patients were treated with CHOP (75%), although other regimens were increasingly used in recent years, including CHOEP (9%). Young (<65 years) PTCL-NOS patients had a better outcome when treated with CHOEP compared to CHOP (24-month OS of 100% vs. 37%, P=.04); this difference was not noted in ALCL-ALK- and in AITL cases. Twenty-three patients (21% of transplant-eligible cases) underwent HSCT (18 autologous, 5 allogeneic), mostly (16/23) in first remission. As expected, patients not responding to frontline therapy or relapsing after CR showed a dismal outcome (median OS of 4.1 months from R/R date). Intensive platinum-based salvage treatments (26 cases) led to a median OS from relapse of only 6 months. In contrast, single-drug Gemcitabine at first relapse showed a median OS 17.4 months in 5 elderly patients. Of 76 R/R transplant eligible patients, only 7 underwent HSCT(4 allogeneic, 3 autologous), with a 5-year OS of 86%. Eight patients (4 AITL, 4 ALCL) received Brentuximab-Vedotin (BV) at first or later relapse, with improved outcomes compared to other regimes (24-month OS of 63% vs. 22%, P=.03). Conclusion: Initial features, treatments and outcomes for PTCL have not significantly changed in a 16-year period. Only a minority of cases underwent HSCT or received new agents. Ideal salvage regimens are not defined and, in our experience, single agent Gemcitabine or BV performed better than more aggressive combinations. Although promising new drugs have been recently approved for PTCL, their impact on outcome is still not clear. Recent progresses in molecular characterization of the disease may translate into better outcomes through prospective collaborative efforts in the near future. Disclosures Silva: Gilead Sciences: Consultancy, Other: Travel support, Research Funding; Janssen Cilag: Consultancy, Other: Travel support; Abbvie: Consultancy, Other: Travel support; Celgene: Consultancy; Roche: Consultancy, Other: Travel support.

scholarly journals Therapies for Peripheral T-Cell Lymphomas

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 515-524 ◽  
Author(s):  
Kerry J. Savage
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Treatment Strategies ◽  
Large Cell ◽  
Cure Rate ◽  
Limited Evidence ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Histologic Subtypes ◽  
Peripheral T Cell Lymphomas

AbstractPeripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of disorders that, for the most part, are associated with a very poor prognosis. The standard therapy for PTCLs is CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or a comparable CHOP-like regimen that incorporates anthracyclines. With the exception of anaplastic lymphoma kinase–positive anaplastic large cell lymphoma (ALK+ ALCL), the cure rate for PTCLs with CHOP is low, and limited evidence suggests that anthracyclines do not improve the prognosis. However, there is no compelling evidence that any other regimen or approach is superior. It remains challenging to compare alternative therapies or treatment strategies with CHOP because the majority of data are retrospective and include diverse patient populations. Recently, prospective studies have been initiated exclusively for PTCL, and in some, select histologic subtypes are evaluated in an effort to remove heterogeneity. Encouragingly, there have been several new therapies emerging with activity in PTCLs and exciting novel combinations under consideration that will hopefully move the field forward and improve outcome in this challenging group of diseases.

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 CRISPR genome editing of murine hematopoietic stem cells to create Npm1-Alk causes ALK+ lymphoma after transplantation

2019 ◽  
Vol 3 (12) ◽  
pp. 1788-1794 ◽  
Author(s):  
Soumya Sundara Rajan ◽  
Lingxiao Li ◽  
Mercedes F. Kweh ◽  
Kranthi Kunkalla ◽  
Amit Dipak Amin ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Hematopoietic Stem Cells ◽  
Large Cell ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
T Cell Lymphomas ◽  
Long Latency ◽  
Key Points ◽  
Genomic Editing

Key Points CRISPR/Cas9 genomic editing of wild-type hematopoietic stem cells generates Npm1-Alk, leading to ALK+ large-cell lymphomas in recipients. CD30+ postthymic T-cell lymphomas are polyclonal but transplantable to secondary recipients with long latency.

Pathobiology and Molecular Profiling of Peripheral T-Cell Lymphomas

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 272-279 ◽  
Author(s):  
Laurence de Leval ◽  
Philippe Gaulard
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
Clinical Manifestations ◽  
Large Cell ◽  
Molecular Profiling ◽  
Good Prognosis ◽  
Molecular Features ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare diseases, usually manifesting clinical aggressiveness. Although important novel insights into the pathobiology of nodal PTCL have been gained recently from molecular profiling studies and clinico-pathological analyses, the pathogenetic molecular lesions remain to be deciphered for most entities. Angioimmunoblastic T-cell lymphoma (AITL) comprises CD4+ CXCL13+ neoplastic cells displaying overlapping immunophenotypical and molecular features with normal follicular helper T cells. This derivation might account for the presence of a prominent non-neoplastic component in AITL tissues and the clinical manifestations of the disease reflective of an immunological dysfunction. ALK+ anaplastic large cell lymphoma (ALCL), defined by ALK gene translocation with various gene partners, is composed of CD30+ ALK+ cells with a cytotoxic phenotype and usually carries a good prognosis. ALK– ALCL, now considered as a distinct disease entity, is morphologically and immunophenotypically similar to ALK+ ALCL, except for ALK expression, but has distinctive molecular features. PTCL, not otherwise specified (PTCL, NOS), the largest PTCL category, which is derived from activated CD4+ (or CD8+) T cells, is markedly heterogeneous, including at the molecular level. Gene expression profiling approaches have identified novel biomarkers of potential therapeutic interest, and suggest the existence of molecularly distinct PTCL, NOS subgroups.

scholarly journals IL-2– and IL-15–induced activation of the rapamycin-sensitive mTORC1 pathway in malignant CD4+ T lymphocytes

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 2181-2189 ◽  
Author(s):  
Michal Marzec ◽  
Xiaobin Liu ◽  
Monika Kasprzycka ◽  
Agnieszka Witkiewicz ◽  
Puthiyaveettil N. Raghunath ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Cell Transformation ◽  
Single Agent ◽  
Large Cell ◽  
Dependent Manner ◽  
T Cell Lymphomas ◽  
Mtorc1 Signaling ◽  
Mtorc1 Pathway ◽  
Mtorc1 Activation

We examined functional status, activation mechanisms, and biologic role of the mTORC1 signaling pathway in malignant CD4+ T cells derived from the cutaneous T-cell lymphoma (CTCL). Whereas the spontaneously growing CTCL-derived cell lines displayed persistent activation of the TORC1 as well as the PI3K/Akt and MEK/ERK pathways, the IL-2–dependent cell lines activated the pathways in response to IL-2 and IL-15 but not IL-21. Activation of mTORC1 and MEK/ERK was nutrient dependent. The mTORC1, PI3K/Akt, and MEK/ERK pathways could also be activated by IL-2 in the primary leukemic, mitogen-preactivated CTCL cells. mTORC1 activation was also detected in the CTCL tissues in the lymphoma stage–dependent manner with the highest percentage of positive cells present in the cases with a large cell transformation. Rapamycin inhibited mTORC1 signaling and suppressed CTCL cell proliferation but showed little effect on their apoptotic rate when used as a single agent. Activation of the mTORC1, PI3K/Akt, and MEK/ERK pathways was strictly dependent on the Jak3 and Jak1 kinases. Finally, mTORC1 activation was transduced preferentially through the PI3K/Akt pathway. These findings document the selective γc-signaling cytokine-mediated activation of the mTORC1 pathway in the CTCL cells and suggest that the pathway represents a therapeutic target in CTCL and, possibly, other T-cell lymphomas.

Frontline Autologous Stem Cell Transplantation As Intensive Consolidation in Patients with Peripheral T Cell Lymphomas: Multicenter Phase II Trial in Korea

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4477-4477 ◽  
Author(s):  
Jae-Sook Ahn ◽  
Deok-Hwan Yang ◽  
Yee Soo Chae ◽  
Sang Kyun Sohn ◽  
Jae-Yong Kwak ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Large Cell Lymphoma ◽  
Peripheral T Cell Lymphomas

Abstract Abstract 4477 Peripheral T cell lymphomas (PTCLs) are an aggressive subtype of non-Hodgkins lymphoma and they have shown the shorter survival compared with B cell lymphoma. High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (HDT/ASCT) for PTCLs has a potential meaning of consolidating remission for PTCLs. However, the effectiveness of ASCT on distinct conditioning regimens, the optimal transplant timing in the frontline or relapsed are still unclear. We investigated the clinical outcomes of HDT/ASCT as frontline intensification in 46 patients with newly diagnosed PTCLs except ALK(+) anaplastic large cell lymphoma. Patients underwent ASCT with a uniform conditioning regimen (busulfex, cyclophosphamide and etoposide). The median age was 47 years (17–65). The histological subtypes were 47.9% PTCL-NOS (n=23), 18.8% anaplastic large cell lymphoma (n=9), 4.2% angioimmunoblastic T cell lymphoma (n=2), 25% extranodal NK/T cell, nasal type (n=12), 2.1% hepatosplenic T cell lymphoma (n=1) and 2.1% enteropathy-associated T cell lymphoma. Thirty patients (62.6%) presented with advanced stage disease (III/IV) and 16 (33.3%) had B symptoms. At diagnosis, 21 patients (43.8%) were classified as high-intermediate/high risk by the age-adjusted IPI (aaIPI) and 10 (20.9%) were classified as high-risk (more than 2 factors) by the prognostic index for PTCL (PIT). Thirty-one patients (67%) could undergo HDT/HSCT and disease status at pretransplant consisted of 23 patients (50 %) with CR and 8 patients (17.4%) with PR. 6 out of 8 patients with PR at pretransplantation improved the response to CR after HDT/ASCT. There was no significant difference of the response rate between CHOP alone or CHOP-like chemotherapy and non-anthracycline-based chemotherapeutic regimen. At a median follow-up of 32.9 months, 23 patients (50%) are alive. The 5-year probability of overall and progression-free survival (PFS) was 48.2 ± 8.1 % and 47.4 ± 8.1%, respectively. However, the 5-year OS and PFS rate in transplanted patients was 57.3± 10.2 % and 55.3 ± 11.3 %, respectively. Conclusion: Frontline HDT/ASCT in patients with PTCL could be performed with a high response rates and a substantial impact on improving outcome for PFS. Our findings also indicate that busulfex, cyclophosphamide and etoposide is a feasible conditioning regimen in ASCT for PTCLs. Disclosures: No relevant conflicts of interest to declare.

Novel Therapies and Role of Transplant in the Treatment of Peripheral T-Cell Lymphomas

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 289-296 ◽  
Author(s):  
Steven M. Horwitz
Keyword(s):  
T Cell ◽  
Case Series ◽  
New Drugs ◽  
High Dose ◽  
High Dose Therapy ◽  
T Cell Lymphomas ◽  
Phase Ii Studies ◽  
Prospective Trials ◽  
Peripheral T Cell Lymphomas

AbstractPeripheral T-cell lymphomas (PTCL) are an uncommon, heterogeneous group of non-Hodgkin lymphomas that carry a much poorer prognosis than their more common B-cell counterparts. The most commonly used treatment is CHOP or its variations. However, while the results with CHOP are inadequate, there is little compelling data to suggest a preferred alternate strategy. Many of these alternate strategies have been assembled from retrospective data, small case series, subset analyses, phase II studies and individual experience. The greatest experience with alternative treatments has been with the use of high-dose therapy as consolidation. These approaches are promising, but most of the studies are retrospective and include patients with diverse prognoses, making interpretation difficult. Preliminary results of prospective trials in PTCL are only recently being reported. Perhaps more exciting have been the increasing numbers of new therapies being studied for patients with PTCL. The activities of new drugs are being described in studies specifically for PTCL, and attempts at novel combinations are beginning.

Peripheral T-cell lymphomas: analysis of histology, staging and response to treatment of 208 cases at a single institution

2013 ◽  
Vol 54 (11) ◽  
pp. 2392-2398 ◽  
Author(s):  
Florence Broussais-Guillaumot ◽  
Diane Coso ◽  
Nawel Belmecheri ◽  
Vadim Ivanov ◽  
Jean-Marc Schiano de Collela ◽  
...  
Keyword(s):  
T Cell ◽  
Response To Treatment ◽  
Single Institution ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas
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