Peripheral T-Cell Lymphoma, Not Otherwise Specified: A Clinicopathologic Study of 340 Cases from the International T-Cell Lymphoma Project.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2458-2458
Author(s):  
Dennis D. Weisenburger ◽  
Wyndham H. Wilson ◽  
Julie M. Vose

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is an uncommon lymphoma in which the clinical and pathological features of prognostic importance are not well understood. Therefore, we collected 340 cases of PTCL-NOS from 21 centers in 13 countries around the world to study this entity. PTCL-NOS was the most common subtype of PTCL in the project (29.3%) and consisted mainly of PTCL unspecified (88.5%) and the lymphoepithelial type (8.2%). The median age of the patients was 60 years, 66% were males, and 69% had stage III/IV disease at diagnosis. Anthracycline-based chemotherapy was given in 80% and a complete response was obtained in 56% of the patients. However, the 5-year overall and failure-free survivals for the entire group were only 32% and 20%, respectively. The International Prognostic Index (IPI) was highly predictive of survival (p<0.001). Other clinical prognostic factors identified in multivariate analysis (MVA) included hypergammaglobulinemia (HR 0.5), mass >10 cm (HR 2.5), and platelets <150,000/mm3 (HR 2.2). Pathologic features predictive of survival included >70% transformed cells (HR 1.7) and <10% CD8+ background T-cells (HR 1.8). However, in final MVA, only the IPI and >70% transformed cells were predictive of survival. In conclusion, PTCL-NOS is an aggressive disease in which the IPI and the percentage of transformed cells could be used to select patients for risk-adapted therapies.

Blood ◽  
2011 ◽  
Vol 117 (12) ◽  
pp. 3402-3408 ◽  
Author(s):  
Dennis D. Weisenburger ◽  
Kerry J. Savage ◽  
Nancy Lee Harris ◽  
Randy D. Gascoyne ◽  
Elaine S. Jaffe ◽  
...  

Abstract The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (≥ 10 cm), thrombocytopenia (< 150 × 109/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.


Blood ◽  
2012 ◽  
Vol 120 (7) ◽  
pp. 1466-1469 ◽  
Author(s):  
François Lemonnier ◽  
Lucile Couronné ◽  
Marie Parrens ◽  
Jean-Philippe Jaïs ◽  
Marion Travert ◽  
...  

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.


2019 ◽  
Vol 3 (2) ◽  
pp. 187-197 ◽  
Author(s):  
Neha Mehta-Shah ◽  
Kimiteru Ito ◽  
Kurt Bantilan ◽  
Alison J. Moskowitz ◽  
Craig Sauter ◽  
...  

Abstract The prognosis of peripheral T-cell lymphoma (PTCL) is heterogenous. Baseline or interim imaging characteristics may inform risk-adapted treatment paradigms. We identified 112 patients with PTCL who were consecutively treated with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)/CHOP-like regimens with the intent to consolidate with an autologous transplant. Baseline (n = 93) and interim (after 4 cycles, n = 99) positron emission tomography (PET) images were reevaluated, and we calculated baseline total metabolic tumor volume (TMTV). Interim PET (iPET) responses were graded visually by 5-point score (i5PS) and by percentage change of standardized uptake value. By univariate analysis, predictors of event-free survival (EFS) included Prognostic Index for Peripheral TCL (PIT) higher than 1 (hazard ratio [HR], 1.83; P = .021), International Prognostic Index (IPI) higher than 3 (HR, 2.01; P = .021), high TMTV (&gt;125 cm3; HR, 3.92; P = .003), and positive iPET (HR, 3.57; P &lt; .001). By multivariate analysis, high baseline TMTV predicted worse overall survival (OS; HR, 6.025; P = .022) and EFS (HR, 3.861; P = .005). Patients with i5PS of 1 to 3 had a longer median OS and EFS (104 months, 64 months) than those with i5PS of 4 to 5 (19 months, 11 months; P &lt; .001). Four-year OS and EFS for patients with i5PS of 1 to 3 and PIT of 1 or less were 85% and 62%, respectively. However, 4-year OS and EFS for those with i5PS of 4 to 5 and PIT higher than 1 were both 0% (P &lt; .001). In multivariate analysis, after controlling for IPI and PIT, i5PS was independently prognostic for EFS (HR, 3.400 95% confidence interval, 1.750-6.750; P &lt; .001) and OS (HR, 10.243; 95% confidence interval, 4.052-25.891; P &lt; .001). In conjunction with clinical parameters, iPET helps risk stratify patients with PTCL and could inform risk-adapted treatment strategies. Prospective studies are needed to confirm these findings.


Blood ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 148-155 ◽  
Author(s):  
Jan Delabie ◽  
Harald Holte ◽  
Julie M. Vose ◽  
Fred Ullrich ◽  
Elaine S. Jaffe ◽  
...  

Abstract Few large, international series of enteropathy-associated T-cell lymphoma (EATL) have been reported. We studied a cohort of 62 patients with EATL among 1153 patients with peripheral T-cell or natural killer (NK)–cell lymphoma from 22 centers worldwide. The diagnosis was made by a consensus panel of 4 expert hematopathologists using World Health Organization (WHO) criteria. Clinical correlations and survival analyses were performed. EATL comprised 5.4% of all lymphomas in the study and was most common in Europe (9.1%), followed by North America (5.8%) and Asia (1.9%). EATL type 1 was more common (66%) than type 2 (34%), and was especially frequent in Europe (79%). A clinical diagnosis of celiac sprue was made in 32.2% of the patients and was associated with both EATL type 1 and type 2. The median overall survival was only 10 months, and the median failure-free survival was only 6 months. The International Prognostic Index (IPI) was not as good a predictor of survival as the Prognostic Index for Peripheral T-Cell Lymphoma (PIT). Clinical sprue predicted for adverse survival independently of the PIT. Neither EATL subtype nor other biologic parameters accurately predicted survival. Our study confirms the poor prognosis of patients with EATL and the need for improved treatment options.


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Ping Zhao ◽  
Meng-Meng Ji ◽  
Ying Fang ◽  
Xiao Li ◽  
Hong-Mei Yi ◽  
...  

AbstractLong noncoding RNAs (lncRNAs) play an essential role in tumor progression. Few researches focused on the clinical and biological relevance of lncRNAs in peripheral T cell lymphoma (PTCL). In this research, a novel lncRNA (ENST00000503502) was identified overexpressed in the main subtypes of PTCL, and designated as T cell lymphoma-associated lncRNA1 (TCLlnc1). Serum TCLlnc1 was associated with extranodal involvement, high-risk International Prognostic Index, and poor prognosis of the patients. Both in vitro and in vivo, overexpression of TCLlnc1 promoted T-lymphoma cell proliferation and migration, both of which were counteracted by the knockdown of TCLlnc1 using small interfering RNAs. As the mechanism of action, TCLlnc1 directly interacted with transcription activator heterogeneous nuclear ribonucleoprotein D (HNRNPD) and Y-box binding protein-1 (YBX1) by acting as a modular scaffold. TCLlnc1/HNRNPD/YBX1 complex upregulated transcription of TGFB2 and TGFBR1 genes, activated the tumor growth factor-β signaling pathway, resulting in lymphoma progression, and might be a potential target in PTCL.


Blood ◽  
2009 ◽  
Vol 113 (17) ◽  
pp. 3931-3937 ◽  
Author(s):  
Wing-yan Au ◽  
Dennis D. Weisenburger ◽  
Tanin Intragumtornchai ◽  
Shigeo Nakamura ◽  
Won-Seog Kim ◽  
...  

Abstract Among 1153 new adult cases of peripheral/T-cell lymphoma from 1990-2002 at 22 centers in 13 countries, 136 cases (11.8%) of extranodal natural killer (NK)/T-cell lymphoma were identified (nasal 68%, extranasal 26%, aggressive/unclassifiable 6%). The disease frequency was higher in Asian than in Western countries and in Continental Asia than in Japan. There were no differences in age, sex, ethnicity, or immunophenotypic profile between the nasal and extranasal cases, but the latter had more adverse clinical features. The median overall survival (OS) was better in nasal compared with the extranasal cases in early- (2.96 vs 0.36 years, P < .001) and late-stage disease (0.8 vs 0.28 years, P = .031). The addition of radiotherapy for early-stage nasal cases yielded survival benefit (P = .045). Among nasal cases, both the International Prognostic Index (P = .006) and Korean NK/T-cell Prognostic Index (P < .001) were prognostic. In addition, Ki67 proliferation greater than 50%, transformed tumor cells greater than 40%, elevated C-reactive protein level (CRP), anemia (< 11 g/dL) and thrombocytopenia (< 150 × 109/L) predicts poorer OS for nasal disease. No histologic or clinical feature was predictive in extranasal disease. We conclude that the clinical features and treatment response of extranasal NK/T-cell lymphoma are different from of those of nasal lymphoma. However, the underlying features responsible for these differences remain to be defined.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4849-4849
Author(s):  
Ikuo Shimizu ◽  
Wataru Takeda ◽  
Takehiko Kirihara ◽  
Keijiro Sato ◽  
Yuko Fujikawa ◽  
...  

Abstract Abstract 4849 Background: Peripheral T-cell lymphoma (PTCL) is an intractable entity with limited response to CHOP-like regimens or more intensive regimens. Although some relapsed or refractory patients may benefit from allogeneic stem cell transplantation, management of elderly patients remains problematic. Sobuzoxane (MST-16) is an oral topoisomerase II inhibitor developed and approved in Japan (Narita T et al. Cancer Chemother Pharmacol 1990). Some anecdotal reports revealed its activity against refractory or relapsed PTCLs as a single-drug regimen or in combination regimens. Patients and Methods: We retrospectively reviewed consecutive cases of patients with angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) who were refractory to or relapsed after CHOP-like chemotherapy during the period spanning January 1990 to March 2012 at Nagano Red Cross Hospital (Nagano, Japan). Diagnosis was performed by certified pathologists based on biopsy samples and flow cytometry. We compared efficacy, safety, and survival time between patients who underwent MST-16-containing regimens and other salvage regimens, including autologous or allogeneic stem cell transplantation. Results: Among 40 patients with AITL or PTCL-NOS, 27 (median age, 65 years; range, 48–86) were administered salvage chemotherapy. The MST-16 group (n=13) received MST-16 alone (9), MST-16 and etoposide (3), or MTX-HOPE (methotrexate, hydrocortisone, vincristine, MST-16, and etoposide) (1). The median number of previous regimens was 3 (range 1–4). The non-MST-16 group (n=14) consisted of multiple regimens including EPOCH (2), ESHAP (2), CEPP (cyclophosphamide, etoposide, procarbazine, and prednisolone) (1), IVAM (2), DeVIC (1), DHAP (1), ABEP (doxorubicin, bleomycin, etoposide, and prednisolone) (1), or high dose therapy with autologous or allogeneic stem cell transplantation (3). Patients in the MST-16 group were of significantly higher age (p=0.027) and had less hepatosplenomegaly (p=0.028) compared to those in the non-MST-16 group. No significant difference was observed in patient performance status, B symptoms, LDH, immunoglobulin values, International Prognostic Index (IPI) scores, and Prognostic Index for T-cell lymphoma (PIT) scores between the two groups. Among MST-16 group, overall response rate was 62.1% (CR 31.0%, PR 31.0%). Notably, additional patients (14.3%) achieved durable SD by palliative MST-16 chemotherapy. With a median observation period of 25 months, median survival time was significantly longer in the MST-16 group compared to the non-MST-16 group (23 months vs. 4 months, respectively; p=0.027). Those with a longer remission period over 6 months due to a CHOP-like regimen tended to respond better to MST-16 salvage regimens (p=0.059). With respect to adverse events, two deaths occurred (one patient with pulmonary aspergillosis following ABEP, and one patient with pneumocystis pneumonia following MST-16). Conclusions: Although this study was of a small scale and retrospective, it supports the notion that MST-16-containing regimens may present a promising approach for relapsed/refractory AITL or PTCL-NOS patients, particularly for those who relapse following a long remission of over 6 months due to a CHOP-like regimen, those not indicated for SCT, and those for whom steroid use is difficult. Given the pleomorphic nature of these entities, there remains the possibility that selection bias may have accounted for the difference observed between the two arms. Further prospective studies with other approaches (e.g., biological or immunohistopathological) may lead to the identification of pathologies other than hepatosplenomegaly that benefit from MST-16. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3059-3059
Author(s):  
Yuhei Shibata ◽  
Nobuhiko Nakamura ◽  
Senji Kasahara ◽  
Toshiki Yamada ◽  
Michio Sawada ◽  
...  

Abstract BACKGROUND: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is relatively rare, accounting for only 10% to 15% of non–Hodgkin's lymphomas, and is characterized by disseminated disease, with systemic symptoms, bone marrow involvement, and extranodal disease. There is no general consensus regarding the preferred induction chemotherapy for PTCL-NOS. CHOP regimen consisting of cyclophosphamide (CPA), doxorubicin (DOX), vincristine (VCR) and prednisone (PSL) has been the most frequently employed regimen for PTCL-NOS, but the overall survival in each IPI category appears lower in patients with most PTCL-NOS than seen in diffuse large B-cell lymphoma. Pirarubicin (tetrahydropyranyladriamycin: THP), a derivative of DOX, is reportedly an anthracyclin with less cardiotoxicity than DOX, because the cardiac sympathetic dysfunction and cardiac mitochondrial damage were less common with THP than those with doxorubicin. We previously reported THP-COP regimen consisting of THP, CPA, VCR, and PSL produced resulted equivalent to CHOP regimen regarding efficacy and safety in patients with aggressive non-Hodgkin's lymphoma (Tsurumi H et al. JCRCO 2004). In addition The Japanese Clinical Study Group of THP Lymphomas in the Elderly reported that T-cell lymphomas had a significantly better response to THP-COP than CHOP, and no such difference was observed in B-cell lymphoma. Therefore, we conducted a retrospective analysis to confirm the efficacy of THP-COP in the treatment of PTCL-NOS. PATIENTS AND METHODS: The study protocol employed a retrospective, consecutive entry design. We retrospectively analyzed 61 patients with PTCL-NOS who had received THP-COP or CHOP in 5 institutes of Gifu Hematology Study Group between December 1995 and March 2013. A diagnosis of PTCL-NOS was confirmed histrogically according to the World Health Organization classification. We exclude patients who had previously treated with any chemotherapy for lymphoma, and were diagnosed as Adult T-cell leukemia/lymphoma or angioimmunoblastic T-cell lymphoma. CHOP regimen composed CPA (750 mg/m2), DOX (50 mg/m2), VCR (1.4 mg/m2, maximal dose 2.0 mg) and PSL (100mg/body, administered for 5 days). In THP-COP regimen, THP (50 mg/m2) was used instead of DOX. These regimens were performed every 14 to 21 days. Thirty patients received THP-COP, 31 received CHOP. There were no significant differences in known prognostic factors include the international prognostic index (IPI) and prognostic index for T-cell lymphoma (PIT) between two groups. The median cycles of treatment were 6 in both groups. The median follow-up times were 25 and 19 months, respectively. RESULT: Complete remission (CR) rates in the patients with THP-COP and CHOP were 53% and 55% (P=0.906), 3-yr overall survival (OS) rate 68% and 51% (P=0.096), and 3-yr progression free survival (PFS) rate 46% and 27% (P=0.078), respectively. Although there were no significant differences between two groups, THP-COP regimen had a tendency of better prognosis. In patients with low IPI (Low or Low-intermediate), THP-COP had significantly better 3yr-OS (100% vs 63%, P=0.002) and 3yr-PFS (69% vs 34%, P=0.002). Same difference was observed in patients with low PIT (group1 or 2), but was not observed in patients with high IPI (High-intermediate or High) or PIT (Group3 or 4). Fatal non-hematological adverse event did not occur in both groups. CONCLUSION: Our study showed THP-COP produced resulted equivalent to CHOP regarding efficacy and safety in patients with PTCL-NOS. Moreover, THP-COP had a tendency of better prognosis compared with CHOP. In patients with low IPI or PIT, THP-COP had significantly better prognosis. This result indicates that THP-COP is an effective and well tolerated regimen for patients with PTCL-NOS, and might be translated into improving survival in comparison with CHOP. Further large study is needed to clarify the difference between the two regimens. Disclosures No relevant conflicts of interest to declare.


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