Serum IgA level, monocyte count, and international prognostic index are independently associated with overall survival in patients with HTLV-I-negative nodal peripheral T cell lymphoma

Abstract Abstract Peripheral T-cell lymphoma (PTCL) is the highly aggressive lymphoid malignancies, treatment outcome is very poor. There are increasing evidence about the role of Epstein-Barr virus (EBV) in PTCL. Because of its rarity, there was few studies about the prognostic factors incorporating EBV in PTCL. The aim of this study was to evaluate the role of EBV as prognostic factors in PTCL. We retrospectively reviewed the 174 PTCL patients (peripheral T-cell lymphoma, not otherwise specified; n=123, anaplastic large cell lymphoma; n=19, angioimmunoblastic T-cell lymphoma; n=26, enteropathy related T-cell lymphoma, n=5, hepatosplenic gammadelta T-cell lymphoma; n=1). Median age of the patients was 63 (20~94) years with 107 (61.5%) male patients. One-year OS and PFS was 55.5%, 37.5%, respectively. Stage 3 or 4 patients were 150 (86.2%). Bone marrow involvement were detected 73 (42.0%) patients among 163 available patients. For IPI scores, 29 (16.7%) patients were classified as low risk, 42 (24.1%) as low-intermediate risk, 57 (32.8%) as high-intermediate risk, and 46 (26.4%) as high risk. For PIT scores, 18 (11.1%) patients were classified in group 1, 41 (25.2%) in group 2, 58 (35.6%) in group 3, and 46 (28.2%) in group 4. Upfront autologous hematopoietic stem cell transplantation (n=17) improved OS and PFS (P=0.001 and P<0.001, respectively). In univariate analysis, poor performance status (ECOG ¡Ã2) (P <0.001 and P <0.001, respectively), low absolute lymphocyte counts (<1000/mm3) (P=0.022 and P=0.038, respectively), high ferritin (¡Ã1,000/mm3) (P =0.002 and P =0.002, respectively), EBV viremia in the whole blood (positive) (P=0.016 and P <0.001, respectively), low protein level (<6.3 g/dL) (P <0.001 and P <0.001, respectively) and low albumin level (<3.5 g/dL) (P =0.001 and P =0.001, respectively) were related with inferior OS and PFS. High international prognostic index (IPI) and prognostic index for PTCLu (PIT) were related with inferior OS and PFS (P<0.001, P=0.029 and P=0.019, P=0.278, respectively) (Figure 1A, 1B, 2A, 2B). In multivariate analysis, poor performance status, extranodal involvement more than one site and EBV viremia were related with OS and PFS in multivariate analysis. (P <0.001, P =0.024, P =0.001 and P =0.001, P=0.002, P=0.031, respectively). We made a new prognostic score model using statistically significant 3 variables in multivariate analysis: low, no adverse factors; intermediate, one factor; high, two or three factors. This model could identify three groups of patients for OS and PFS (Figure 3A,3B.) This study suggests that prognostic models including EBV for PTCL showed good risk classification. There will be need to investigate the mechanism of EBV and specific treatment strategy for EBV-related patients. These patients will be need to consider more effective therapeutic strategy to improve the poor survival in PTCL. Figure 1. Overall survival and progression free survival according to international prognostic index Figure 1. Overall survival and progression free survival according to international prognostic index Figure 2. Overall survival and progression free survival according to prognostic index for PTCLu Figure 2. Overall survival and progression free survival according to prognostic index for PTCLu Figure 3. Overall survival and progression free survival according to new prognostic model Figure 3. Overall survival and progression free survival according to new prognostic model Disclosures No relevant conflicts of interest to declare.

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Monocytosis As Prognostic Factor in Aggressive, Non-Primary Cutaneous Peripheral T-Cell Lymphoma: A Study of 251 Cases

Blood ◽

10.1182/blood.v120.21.1608.1608 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1608-1608

Author(s):

Brady E Beltran ◽

Erick Cotacallapa ◽

Jorge J Castillo

Keyword(s):

Overall Survival ◽

T Cell ◽

Who Classification ◽

Cell Lymphoma ◽

Statistical Significance ◽

Prognostic Index ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Worse Prognosis

Abstract Abstract 1608 Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous family of entities with a worse prognosis, stage by stage, than their B-cell counterparts. We have previously reported that an absolute lymphocyte count (ALC) <1000/uL is associated with a worse prognosis in Peruvian patients with PTCL (Castillo et al. 2010). The goal of this study is to investigate the prognostic value of absolute monocyte count (AMC) in the survival of patients with PTCL. Methods: A total of 251 cases of aggressive, non-primary cutaneous PTCL diagnosed at our institution between January 1997 and January 2012 were reviewed, reevaluated according to their morphological, immunological and clinical characteristics, and reclassified according to the 2008 WHO classification of lymphoid neoplasms. Characteristics will be presented descriptively. Kaplan-Meier method was used to estimate overall survival (OS) curves, which were compared using the log-rank test. The multivariate analysis was performed using the Cox proportional-hazard regression test. Results: According to the new WHO classification of lymphoid neoplasms, 104 cases (41%) were classified as adult T-cell leukemia/lymphoma (ATLL), 103 cases (41%) as PTCL, unspecified (PTCLU), 27 cases (11%) as analplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), 11 cases (4%) as extranodal NK/T-cell lymphoma (NKTCL), nasal type, 4 cases (2%) as angioimmunoblastic lymphoma (AIL), and 2 cases (1%) were diagnosed with ALK+ ALCL. The median age at diagnosis was 57 years (range 14–92 years); 47% of patients were >60 years. The male-to-female ratio was 1:1. ECOG performance status >1 was seen in 51%, LDH was elevated in 67%, advanced stage was seen in 73%, and >1 extranodal sites were seen in 22% of the patients. Bone marrow involvement was reported in 30% and B symptoms in 64% of patients. An International Prognostic Index (IPI) score 3–5 was seen in 55%, and a Prognostic Index for PTCLU (PIT) score of 2–4 in 63%. The median overall survival (OS) for the whole group was 10 months. The IPI score, the PIT score, ALC <1000/uL and AMC >800/uL (Figure) showed statistical significance in the univariate survival analysis (p<0.001, p<0.001, p=0.001 and p=0.001, respectively). In the multivariate analysis, PIT score and AMC >800/uL showed statistical significance (p=0.006, p=0.046, respectively). Conclusions: Monocytosis, defined as AMC >800/uL, and the PIT score were independent prognostic factors for OS in patients with aggressive, non-primary cutaneous PTCL. Disclosures: No relevant conflicts of interest to declare.

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Prognostic Value of NCCN-IPI and Interim PET/CT Based on Visual Assessment in the Treatment of Peripheral T Cell Lymphomas

Blood ◽

10.1182/blood.v128.22.1822.1822 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1822-1822

Author(s):

Seo-Yeon Ahn ◽

Ho-Young Yhim ◽

Young Rok Do ◽

Sung-Hoon Jung ◽

Jae-Sook Ahn ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

High Risk ◽

Cell Lymphoma ◽

Prognostic Index ◽

Visual Assessment ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Interim Pet ◽

Pet Ct

Abstract Background It has been well known that peripheral T cell lymphoma (PTCL) has undergone poor prognosis compared with other non-Hodgkin lymphomas (NHL). Although the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) has been proposed to determining prognosis for patients with diffuse large B-cell lymphoma (DLBCL) at 2014, there is no study examines whether NCCN-IPI could apply to the T-cell NHLs. In addition, a few studies suggest prognostic utility of interim PET/CT in PTCL, but the role of interim PET/CT is not clear. Purpose We evaluate the predictive efficacy of the NCCN-IPI and interim PET/CT based on visual assessment in patients with newly diagnosed PTCLs. Methods This study included 153 patients with de novo peripheral PTCLs, diagnosed from January 2010 to August 2015. The NCCN-IPI was calculated as following the original references. Survival outcomes were compared with a matched result of IPI and/or Prognostic Index for peripheral T cell lymphoma, unspecified (PIT). Visual assessment of interim PET/CT based on Deauville five point scales was performed at the time of diagnosis, mid-treatment and completion of CHOP/CHOP-like or other non-anthracycline chemotherapy. Results The subtypes of PTCLs included PTCL, not otherwise specified (PTCL-NOS) (26%), angioimmunoblastic T cell lymphoma (20%), anaplastic large cell lymphoma (13%), extranodal NK/T cell lymphoma, nasal type (35%), and the others (6%). The NCCN-IPI showed better risk-based prognostic discrimination than IPI and PIT, especially between high-intermediate and high risk subgroups (3-year overall survival 40% vs. 27% vs. 26% among the high-intermediate risk group, respectively; 3-year overall survival 15% vs. 33% vs. 32% among the high risk group, respectively) with a median follow-up of 25.1 months (Figure 1). The absolute difference of survival rates between the low and high risk groups was 75% based on the NCCN-IPI stratification compared with 45% on the IPI stratification or 54% on the PIT stratification, respectively. When divided into two histologic subgroups (nodal vs. extra-nodal type), the NCCN-IPI showed considerable discriminatory capacity in both histologic groups. However, the IPI or PIT classification could not have discrimination in extra-nodal PTCLs. The interim PET-CT was significantly predicting for progression free survival in all PTCL patients, however, it also showed no predictive value in the patients with extranodal PTCLs, especially NK/T cell lymphoma. Conclusions The NCCN-IPI is a powerful prognostic model in PTCLs predicting overall survival among high-intermediate and high risk patients. Also, interim PET/CT response based on visual assessment could be a valuable prediction tool in nodal PTCLs, however, it should be carefully interpreted in the treatment of extranodal subtypes. Disclosures No relevant conflicts of interest to declare.

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Baseline and interim functional imaging with PET effectively risk stratifies patients with peripheral T-cell lymphoma

Blood Advances ◽

10.1182/bloodadvances.2018024075 ◽

2019 ◽

Vol 3 (2) ◽

pp. 187-197 ◽

Cited By ~ 12

Author(s):

Neha Mehta-Shah ◽

Kimiteru Ito ◽

Kurt Bantilan ◽

Alison J. Moskowitz ◽

Craig Sauter ◽

...

Keyword(s):

Multivariate Analysis ◽

T Cell ◽

Confidence Interval ◽

Cell Lymphoma ◽

Univariate Analysis ◽

International Prognostic Index ◽

Prognostic Index ◽

Standardized Uptake Value ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma

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 (>125 cm3; HR, 3.92; P = .003), and positive iPET (HR, 3.57; P < .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 < .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 < .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 < .001) and OS (HR, 10.243; 95% confidence interval, 4.052-25.891; P < .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.

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Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project

Blood ◽

10.1182/blood-2010-09-310342 ◽

2011 ◽

Vol 117 (12) ◽

pp. 3402-3408 ◽

Cited By ~ 228

Author(s):

Dennis D. Weisenburger ◽

Kerry J. Savage ◽

Nancy Lee Harris ◽

Randy D. Gascoyne ◽

Elaine S. Jaffe ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Cell Lymphoma ◽

International Prognostic Index ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Bulky Disease ◽

Free Survival ◽

Not Otherwise Specified ◽

Pathologic Features

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.

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Enteropathy-associated T-cell lymphoma: clinical and histological findings from the International Peripheral T-Cell Lymphoma Project

Blood ◽

10.1182/blood-2011-02-335216 ◽

2011 ◽

Vol 118 (1) ◽

pp. 148-155 ◽

Cited By ~ 161

Author(s):

Jan Delabie ◽

Harald Holte ◽

Julie M. Vose ◽

Fred Ullrich ◽

Elaine S. Jaffe ◽

...

Keyword(s):

T Cell ◽

Nk Cell ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

T Cell Lymphoma ◽

World Health ◽

Peripheral T Cell Lymphoma

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.

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A novel lncRNA TCLlnc1 promotes peripheral T cell lymphoma progression through acting as a modular scaffold of HNRNPD and YBX1 complexes

Cell Death and Disease ◽

10.1038/s41419-021-03594-y ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Ping Zhao ◽

Meng-Meng Ji ◽

Ying Fang ◽

Xiao Li ◽

Hong-Mei Yi ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

T Cell Lymphoma ◽

Small Interfering Rnas ◽

Transcription Activator ◽

Peripheral T Cell Lymphoma

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.

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Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project

Blood ◽

10.1182/blood-2008-10-185256 ◽

2009 ◽

Vol 113 (17) ◽

pp. 3931-3937 ◽

Cited By ~ 436

Author(s):

Wing-yan Au ◽

Dennis D. Weisenburger ◽

Tanin Intragumtornchai ◽

Shigeo Nakamura ◽

Won-Seog Kim ◽

...

Keyword(s):

T Cell ◽

Natural Killer ◽

Clinical Features ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

T Cell Lymphoma ◽

Clinical Feature ◽

Peripheral T Cell Lymphoma ◽

Nk T Cell

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.

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