scholarly journals Aggressive Peripheral T-Cell Lymphomas (Specified and Unspecified Types)

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 267-277 ◽  
Author(s):  
Kerry J. Savage
Keyword(s):  
T Cell ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Large Cell ◽  
Risk Groups ◽  
T Cell Lymphomas ◽  
Widespread Availability ◽  
Alk Positive ◽  
Peripheral T Cell Lymphomas

Abstract Peripheral T-cell lymphomas (PTCLs) are a biologically diverse and uncommon group of diseases. Compared to their B-cell counterparts, PTCLs remain largely unexplored and the optimal treatment ill-defined due to disease rarity and biological heterogeneity. For the majority of PTCL subtypes, prognosis is poor with a 5-year overall survival of approximately 30% in most series. The notable exception is ALK-positive anaplastic large-cell lymphoma (ALK-pos ALCL), which has a superior outcome. The international prognostic index can be used to some extent to define risk groups within some PTCL subtypes, including PTCL unspecified (PTCLUS). It is likely that the observed clinical heterogeneity reflects differences at the molecular level. With the more widespread availability of gene expression profiling, it may be possible in the future to further refine the classification of PTCLs and elucidate novel therapeutic targets. Future clinical trials are needed that focus specifically on PTCL to advance our understanding and define the optimal management in this disease.

Efficacy of a Dose-Intensified CHOP (Double-CHOP) Regimen for Peripheral T-Cell Lymphomas

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4855-4855
Author(s):  
Hiromichi Takahashi ◽  
Noriyoshi Iriyama ◽  
Yoshihiro Hatta ◽  
Katsuhiro Miura ◽  
Yujin Kobayashi ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Conflicts Of Interest ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
High Dose ◽  
Chop Regimen ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Abstract 4855 Background: Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of non-Hodgkin lymphomas, often resulting in poor prognoses. The CHOP chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, and prednisone, had been used previously to treat other types of lymphomas. Here, we examined the efficacy and safety of a dose-intensified CHOP regimen (Double-CHOP), which was followed by autologous stem-cell transplantation (ASCT) or high-dose methotrexate (HDMTX), in PTCL patients. Patients and Methods: Twenty-eight PTCL patients, who received 3 courses of Double-CHOP at our institution, were retrospectively studied from 1996 to 2012. Patients with anaplastic lymphoma-kinase-positive anaplastic large-cell lymphoma (ALK+–ALCL) were excluded from this study. The Double-CHOP regimen consisted of 3 courses of intravenous (iv) administration of cyclophosphamide (750 mg/m2, days 1–2, over 2 h), doxorubicin (50 mg/m2, days 1–2, over 30 min), vincristine (1.4 mg/m2, day 1, max 2 mg/Kg body weight), and per os (p.o.) prednisone (50 mg/m2, days 1–5). For patients aged >60, cyclophosphamide and doxorubicin doses were modified. The third cycle of Double-CHOP regimen was used for stem cell mobilization. Consolidating high-dose therapy (HDT) regimen consisted of cyclophosphamide (60 mg/kg, day 6 and 7, iv, over 3 h), etoposide (500 mg/m2; day 4, 5, and 6; iv; over 6–8 h), and ranimustine (250 mg/m2, day 2 and 3, iv, over 1 h). ASCT was performed on day 0 and G-CSF administered from day 1 until neutrophil engraftment. As an alternative to HDT/ASCT, HDMTX (8 g/m2, day 1, iv, over 4 h) was indicated for patients who could not yield a sufficient number of stem cells or were ineligible for HDT/ASCT. Results: Patients' median age was 58 years (range: 17–69). They had low-intermediate (n = 11), high-intermediate (n = 10), or high (n = 7) risk according to the International Prognostic Index (IPI). The overall complete remission (CR) rate following Double-CHOP treatment was 68%. Of all the CR patients, 10 could successfully tolerate a consolidated HDT followed by ASCT, and 7 received HDMTX. Only a single case of treatment-related mortality was recorded during the study. On a median 31-month follow-up, the estimated 3-year overall survival (OS) rate and 3-year relapse-free survival (RFS) rate after CR were 68% and 60%, respectively. Conclusion: Although this study included elderly and excluded low-risk IPI and ALK+–ALCL patients, both RFS and OS results were superiorly favorable, indicating the efficacy of this Double-CHOP regimen and Double-CHOP followed by ASCT/HDMTX consolidations is safe and may achieve prolonged EFS, especially in patients with poor prognostic factors. However, an effective treatment strategy for refractory or relapsing patients needs to be validated and established. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters

Blood ◽  
2012 ◽  
Vol 120 (7) ◽  
pp. 1466-1469 ◽  
Author(s):  
François Lemonnier ◽  
Lucile Couronné ◽  
Marie Parrens ◽  
Jean-Philippe Jaïs ◽  
Marion Travert ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
T Cell Lymphoma ◽  
Not Otherwise Specified ◽  
T Cell Lymphomas ◽  
Stage Disease ◽  
Peripheral T Cell Lymphomas

Abstract Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (TFH) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed TFH markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.

Prognosis and Primary Therapy in Peripheral T-Cell Lymphomas

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 280-288 ◽  
Author(s):  
Kerry J. Savage
Keyword(s):  
T Cell ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Classification Systems ◽  
Cell Phenotype ◽  
Primary Therapy ◽  
T Cell Lymphomas ◽  
Alk Positive ◽  
Peripheral T Cell Lymphomas

AbstractPeripheral NK/T-cell neoplasms are an uncommon group of diseases that show distinct racial and geographic variation. The prognostic significance of the T-cell phenotype has been clearly defined in recent studies by using modern lymphoma classification systems. However, within this heterogenous group of neoplasms, some have a more favorable prognosis, such as ALK-positive anaplastic large-cell leukemia (ALCL) and primary cutaneous ALCL, and some have ultimately fatal courses with standard chemotherapy programs (e.g., hepatosplenic γδ T-cell lymphomas). Further, unlike the benefits observed with CHOP chemotherapy in the treatment of diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphomas (PTCL), other than ALK-positive ALCL, are relatively chemoresistant to this regimen. Given disease rarity and biological heterogeneity, advances in diagnosis, prognosis and treatment have lagged behind DLBCL. Recently, however, studies are emerging that focus specifically on PTCLs with the ultimate goal of better understanding disease biology and developing more effective therapies.

scholarly journals Tricky and Terrible T-Cell Tumors: These are Thrilling Times for Testing: Molecular Pathology of Peripheral T-Cell Lymphomas

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 336-343 ◽  
Author(s):  
Laurence de Leval ◽  
Philippe Gaulard
Keyword(s):  
T Cell ◽  
Current Knowledge ◽  
Large Cell ◽  
Disease Classification ◽  
Molecular Characteristics ◽  
Molecular Alterations ◽  
T Cell Lymphomas ◽  
Genetic Features ◽  
Alk Positive ◽  
Peripheral T Cell Lymphomas

Abstract Peripheral T-cell lymphomas (PTCLs) encompass a group of rare and usually clinically aggressive diseases. The classification and diagnosis of these diseases are compounded by their marked pathological heterogeneity and complex clinical features. With the exception of ALK-positive anaplastic large cell lymphoma (ALCL), which is defined on the basis of ALK rearrangements, genetic features play little role in the definition of other disease entities. In recent years, hitherto unrecognized chromosomal translocations have been reported in small subsets of PTCLs, and genome-wide array-based profiling investigations have provided novel insights into their molecular characteristics. This article summarizes the current knowledge on the best-characterized genetic and molecular alterations underlying the pathogenesis of PTCLs, with a focus on recent discoveries, their relevance to disease classification, and their management implications from a diagnostical and therapeutical perspective.

Expression Pattern and Prognostic Impact of Vascular Endothelial Growth Factors VEGF and VEGF-C and Their Receptors Flt-1, KDR and Flt-4 in Peripheral T-Cell Lymphomas.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 689-689
Author(s):  
Judit M. Jørgensen ◽  
Flemming B. Sørensen ◽  
Knud Bendix ◽  
Johan L. Nielsen ◽  
Anette D. Funder ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Mrna Expression ◽  
International Prognostic Index ◽  
Large Cell ◽  
Prognostic Impact ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract The vascular endothelial growth factor family (VEGF, VEGF-B, -C and -D) is the main regulator of angiogenesis and lymphangiogenesis via their receptors, Flt-1, KDR and Flt-4. The aim of the present study was to estimate the microvascular density and investigate the expression of VEGF, VEGF-C and its receptors Flt-1, KDR and Flt-4 in peripheral T-cell lymphomas (PTCL). Material and methods: Microvessel density (MVD) was determined after CD34 immunohistochemical (IH) staining of endothelial cells in pre-therapeutic lymph-node biopsies from 107 cases of PTCL (64 unspecified, 1 angiocentric, 10 angioimmunoblastic and 32 anaplastic large cell T/0). 44 of these cases (28 unspecified, 1 angiocentric, 4 angioimmunoblatic and 11 anaplastic large cell T/0) were investigated for expression of angiogenic molecules, VEGF, VEGF-C and their receptors by IH at protein level. Furthermore, VEGF and VEGF-C mRNA expression was detected by non-isotopic ′in situ′ hybridization. The angiogenic scores were correlated to pre-therapeutic clinical parameters, treatment response and survival. Results: Tumoral expression of VEGF, VEGF-C and of their receptors was detected in the majority of the PTCL biopsies investigated (VEGF mRNA: 73%, VEGF protein: 95%; VEGF-C mRNA: 79%; VEGF-C protein: 79%; Flt-1 and KDR: 100%; Flt-4: 26%). All biopsies contained VEGF, Flt-1 and KDR positive vessels and VEGF-C was also widely expressed by the endothelial cells (3 negative cases), while endothelial Flt-4 expression was detected only in 43% of cases. High MVD scores correlated with an advanced clinical stadium (Ann Arbor) (p=0.047). A strong diffuse VEGF mRNA expression significantly correlated with a poorer overall survival (p=0.0015) as compared to focal or negative ISH signal. The predictive value of this parameter persisted at multivariate level independently of the International Prognostic Index (HR: 3.95, p=0.012, Cox regression). Conclusion: VEGF, VEGF-C and their receptors are expressed by both lymphoma and endothelial cells in the majority of PTCL cases. VEGF expression seems to have an adverse impact on survival. Larger studies of angiogenesis/lymphangiogenesis in PTCL are needed to clarify the biological role of these molecules and identify possible therapeutic targets.

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.

Improved Outcome After Allogeneic Stem-Cell Transplantation (SCT) As Compared to Non-Allogeneic SCT Therapies in Patients with High-Risk Peripheral T-Cell Lymphomas in First Response.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3111-3111
Author(s):  
Margot Robles ◽  
Loic Ysebaert ◽  
Stephane Vigouroux ◽  
Anne Huynh ◽  
Marie Parrens ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
T Cell Lymphomas ◽  
Alk Positive ◽  
Peripheral T Cell Lymphomas

Abstract Abstract 3111 Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of rare malignancies usually occurring in middle-aged to elderly patients (pts), with an advanced disease and unfavorable international prognostic index (IPI) scores. Excluding ALK-positive anaplastic large cell lymphomas (ALCL) and indolent mycosis fungoides, they are often characterized by a poor prognosis. There is no consensus about optimal therapy and the role of allogeneic stem-cell transplantation (allo-SCT) as first line therapy remains to be investigated. In an effort to explore this therapeutic option in younger pts, we undertook a retrospective analysis in 2 french centers. The records of all pts aged between 18 and 65 years diagnosed with PTCL in Bordeaux and Toulouse between January 2005 and April 2012 were reviewed. Cutaneous T-cell lymphomas and ALK-positive ALCL were excluded. Patients with an IPI score at diagnosis of 0/1 were excluded as well as those who never reached at least a 1st partial response according to the criteria reported by Cheson. Patients relapsing within 3 months after the 1st response and thus ineligible for allo-SCT were also excluded. The primary objective was to compare the outcome of allo-SCT (allo group) as compared to non-allogeneic SCT therapies (no-allo group) in these pts with high-risk PTCL in 1st response. Thirty-three patients were included (16 in the allo group, 17 in the no-allo group). Fifteen pts in the allo group were treated in Bordeaux where allo-SCT was always pursued during the study period in responding pts with an IPI score ≥ 2 at diagnosis. In Bordeaux, the absence of allo-SCT in 1st response was explained by the absence of a suitable donor or the refusal of the patient. The therapeutic strategy in Toulouse was different with 11 pts in the no-allo group, allowing us to undertake this retrospective comparison. In the allo group, conditioning regimes were of reduced intensity (n=12) or myeloablative (n=4). The sources of stem cells were PB (n=13), BM (n=2) or cord blood (n=1). Donors were matched related (n=7), matched unrelated (n=6), mismatched unrelated (n=2). In the whole cohort, the first chemotherapy regimes were CHOP or CHOP-like (n=31), DHAP (n=1), ICE (n=1). In the allo vs no-allo groups, the median ages at diagnosis were 54 years (20–65) vs 59 years (29–64), p = 0.5; the number of pts diagnosed before 2009 were 7 vs 9, p=0.6; the lymphoma subtypes were PTCL-NOS (4 vs 9, p=0.1), angioimmunoblastic (8 vs 6, p=0.4), others (4 vs 2, p=0.3); the IPI scores at diagnosis were 2 (5 vs 5, p=0.9), 3 (6 vs 3, p=0.2), 4/5 (5 vs 9, p=0.2); the number of pts in CR1 and PR1 were 13 vs 13, p = 0,7 and 3 vs 4, p=0.7; the number of chemotherapy lines to reach the 1st response were 1 (8 vs 15, p=0.02), 2 (4 vs 2, p=0.3) or 3 (4 vs 0, p=0.03). Five patients in the no-allo group were treated with an autologous SCT in 1st response. Three patients in the allo group were treated with autologous SCT to reach the 1st response. With a median follow-up of 34 months (8–74) after the 1st response, in the allo vs no-allo groups, the 2-year OS (figure 1) were 87% ± 8% vs 49% ± 13%, respectively (p= 0.06); the 2-year EFS (figure 2) were 81% ± 10% vs 33% ± 12%, respectively (p = 0.007). In the allo and no-allo groups, 3 and 12 pts respectively, have relapsed. In the allo and no-allo groups, 2 and 8 pts respectively, have died, all from disease progression. The modest size of our study and the potential biases inherent to such a restrospective design preclude the declaration of any firm conclusion. However, these preliminary data suggest that patients under 65 years of age with high-risk PTCL (IPI ≥2) might benefit from allo-SCT in 1st response, in comparison with non-allogeneic SCT therapies. Randomized studies are warranted to further delineate the optimal first line therapy in these patients. Our center is currently participating to such an ongoing european study comparing allo-SCT vs auto-SCT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures: No relevant conflicts of interest to declare.

CHOEP-21 Chemotherapy without Autologous Stem Cell Transplantation (ASCT) for Newly Diagnosed Nodal Peripheral T-Cell Lymphomas (PTCLs) in the Northern Part of Thailand

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4857-4857
Author(s):  
Ekarat Rattarittamrong ◽  
Lalita Norasetthada ◽  
Adisak Tantiworawit ◽  
Chatree Chai-adisaksopa ◽  
Weerasak Nawarawong
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
Newly Diagnosed ◽  
Chop Regimen ◽  
T Cell Lymphomas ◽  
Alk Positive ◽  
Grade 3 ◽  
Peripheral T Cell Lymphomas

Abstract Abstract 4857 Background: Several previous studies demonstrated the poor treatment outcomes for the patients with nodal peripheral T-cell lymphomas (PTCLs) including PTCL, not otherwise specified (PTCL-NOS), ALK-negative anaplastic large cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL) when compared with ALK-positive ALCL and aggressive B-cell lymphomas. For the treatment of T-cell lymphomas, promising results of chemotherapy regimens including etoposide in several studies were evidenced. We conducted the prospective study to determine the effectiveness and tolerability of the combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP-21) for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs) treated at Maharaj NakornChiang Mai Hospital in the Northern part of Thailand. Method: From October 2008 to November 2011, patients ages 18–60 years with newly diagnosed nodal PTCLs excluding ALK-positive ALCL were enrolled to receive CHOEP-21 (CHOP plus etoposide 100 mg/m2 days 1–3) every 3 weeks for 8 cycles with granulocyte colony-stimulating factor (G-CSF) starting from day 4–11. None of them proceeded to undergo autologous stem cell transplantation (ASCT) due to financial problems. Event-free survival (EFS) which is the primary endpoint, was calculated from the date of diagnosis until disease progression or relapsed, change to other treatment, or death from any cause. Secondary end point of the study was overall survival (OS), response rate and toxicities of regimen. Results: 24 patients were enrolled. Twenty of them were male with a mean age of 49 years. Majority of the patients had PTCL, NOS (n = 16), 7 patients had AITL and only one ALK-negative ALCL patient. Almost all except one were in stage III-IV with 62% of the patients had international prognostic index (IPI) ≥ 2. From median follow up of 16 months, overall response (OR) was 58% (33% CR) but 28.5% of these patients eventually relapsed as shown in table 1. Estimated 2-year EFS and OS were 33.8% and 55%, respectively. When compared with the 11 historical control receiving CHOP regimen, the outcomes including EFS, OS and OR were not statistically different, even though patients receiving CHOEP had more advanced stage and bone marrow involvement than those receiving CHOP regimen (Table 2, Figure 1 and 2). Infection (grade 3–4 of 8.3%) and hematologic toxicities were the most common adverse effects with acceptable grade 3–4 neutropenia (7.6%) and thrombocytopenia (4.6%). Conclusion: The CHOEP-21 without following ASCT did not seem to improve outcomes in patients with nodal PTCLs. Other treatment strategies are warranted to study in these groups of patients. Disclosures: No relevant conflicts of interest to declare.

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