A Novel and Significant Predictor in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: The Prognostic Nutritional Index (PNI)

Abstract Background: Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis. The prognostic nutritional index (PNI) is reported to be associated with survival in several types of tumors. The prognostic value of PNI in lymphoma remains unclear. The aim of the present study is to evaluate the prognostic significance of PNI in patients with ENKTL. Methods: 157 patients with newly diagnosed ENKTL were retrospectively evaluated between August 2000 and October 2011 at the Sun Yat-sen University Cancer Center. Patients in whom the combined albumin (g /l) +5x total lymphocyte count x 109/l ≥45 were allocated a PNI score of 0. Patients in whom this total was < 45 were allocated a score of 1. Overall survival (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. The significance of differences between survival curves was tested using the log-rank test. Significant variables in the univariate analysis were considered variables for the multivariate survival analysis, which was performed using Cox regression mode. Results: Four-nine patients (31.2%) had an abnormal PNI (PNI=1). The characteristics of both groups are given in Table 1. After a median follow-up duration of 31.0 months, an estimated 5-year OS and PFS rate in 157 patients was 58.4% and 39.4%, respectively. Patients with pretreatment PNI score=1 had lower complete remission rates (P= 0.018) and worse OS (5-year OS: 71.7% vs 21.8.0%,P<0.001) and PFS (P<0.001) compared with PNI score=0 patients. The survival curves according to PNI are shown in Fig. 1. Using the International Prognostic Index (IPI) and peripheral T-cell lymphoma (PIT) scoring systems, more than 70% of all cases were in the low-risk category (with no or one adverse factor), but these two prognostic models failed to differentiate between patients with different outcomes in the low-risk group. PNI could differentiate low-risk patients using IPI and PIT scoring (all P< 0.05). The Korean Prognostic Index (KPI) model balanced distribution of patients into different risk groups better than the IPI and PIT models. However, the KPI model also failed to significantly differentiate between patients with different outcomes in low and low intermediate risk group (P=0.859). PNI also helped to differentiate between patients with different prognosis in low and low intermediate risk group (P=0.000).However, the KPI prognostic model failed to show significant prognostic value among patients with PNI=0 (P=0.646) or among the patients with PNI=1 (P=0.115). The survival curves according to KPI and PNI are shown in Fig. 2. Conclusions: PNI is an independent predictor of survival in ENKTL and is superior to IPI, PIT and KPI. Table 1. Baseline Characteristics of Patients by PNI Level Characteristics PNI score =0 PNI score =1 P 108 49 Age (median [range], yr) 42(9-77) 45(12-76) 0.031 <60 96(88.9) 37(75.5) >60 12(11.1) 12(24.5) Gender 0.444 Female 33(30.6) 18(36.7) Male 75(69.4) 31(63.3) ECOG PS <0.001 0-1 107(99.1) 40(81.6) 2-3 1(0.9) 9(18.4) B symptoms (yes) 45(41.7) 36(73.5) <0.001 LDH >245 U/L 19(17.6) 29(59.2) <0.001 Mass ≥5 cm 12(11.1) 6(12.2) 0.836 Extranodal sites ≥2 30(27.8) 27(55.1) 0.001 Regional LN involvement 60(55.6) 40(81.6) 0.002 Bone marrow involvement 0(0.0) 3(6.1) 0.009 Primary sites 0.006 Nasal/nasopharynx area 93(86.1) 33(67.3) Extra-nasal/nasopharynx 15(13.9) 16(32.7) Ann Arbor stage 0.001 I/II 93(86.1) 31(63.3) III/IV 15(13.9) 18(36.7) IPI score <0.001 0-1 91 (84.3) 24(49.0%) 2-5 17(15.7) 25(51.0%) PIT score <0.001 0-1 106(98.1) 36(73.5) 2-4 2(1.9) 13(26.5) KPI score <0.001 0-1 69(63.9) 9(18.4) 2-4 39(36.1) 40(81.6) Fig. 1 Overall survival (A) and progression free survival (B) based on the PNI for patients with extranodal natural killer/T¨Ccell lymphoma, nasal type. Fig. 1. Overall survival (A) and progression free survival (B) based on the PNI for patients with extranodal natural killer/T¨Ccell lymphoma, nasal type. Fig. 2 KPI model differentiate between patients with different outcomes in low and low intermediate risk group (A) and high and high intermediate risk group (B). PNI differentiate between patients with KPI=0-1 (C) and KPI=2-4(D). KPI model differentiate between patients with PNI=0(E) and PNI=1 (F). Fig. 2. KPI model differentiate between patients with different outcomes in low and low intermediate risk group (A) and high and high intermediate risk group (B). PNI differentiate between patients with KPI=0-1 (C) and KPI=2-4(D). KPI model differentiate between patients with PNI=0(E) and PNI=1 (F). Disclosures No relevant conflicts of interest to declare.

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Concurrent Radiotherapy and Dexamethasone, Etoposide, Ifosfamide, and Carboplatin (DeVIC) for Patients with Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Single Institution Analysis in Japan

Blood ◽

10.1182/blood.v118.21.1611.1611 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1611-1611

Author(s):

Eriko Nara ◽

Masahiro Yokoyama ◽

Kengo Takeuchi ◽

Kenji Nakano ◽

Kyoko Ueda ◽

...

Keyword(s):

T Cell ◽

Natural Killer ◽

Concurrent Chemoradiotherapy ◽

Cell Lymphoma ◽

Progression Free Survival ◽

Free Survival ◽

Nasal Type ◽

Natural Killer T Cell ◽

Concurrent Radiotherapy ◽

Killer T Cell

Abstract Abstract 1611 Background: Extranodal natural killer/T-cell lymphoma (ENKL), nasal type, is a recognized a rare distinct entity strongly associated EBV infection, accounting for 3% to 10% of malignant lymphomas in East Asia. Recent studies suggest that concurrent chemoradiotherapy was effective as first-line therapy for patients with localized ENKL, nasal type. We assess treatment results with concurrent chemoradiotherapy for ENKLs. Patients and methods: From December 2007 to July 2010, newly diagnosed localized ENKL, nasal type, and treated with concurrent radiotherapy (median 50 Gy; range 46–56 Gy) and 3 cycles of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) at the Cancer Institute Hospital, Tokyo, Japan were analyzed retrospectively. All the histopathological samples were reviewed according to the WHO classification by expert hematopathologists. Results: Total of sixteen patients was identified. Baseline patients. characteristics included a median age of 56.5 years (range; 30–76 years), eleven men and five women, thirteen patients (81%) with stage IE and three (19%) with stage IIE. For IPI, patients with low and low-intermediate risks were thirteen patients (81%) and three (19%), respectively. For NKIPI, patients with group 1, 2, and 3 were six patients (37%), seven (44%), and three (19%), respectively. All patients received concurrent chemoradiotherapy, and eleven patients (69%) achieved complete remission, with 2 partial remissions. The overall response rate was 81%. At a median follow-up of 17 months (range; 2–44), the 2-year progression-free survival and overall survival rates were 54.7% and 61.1%, respectively. Seven patients were confirmed progression disease, and six died from progression of lymphoma. Grade 3/4 adverse events were leukopenia (100%), neutropenia (100%), anemia (19%), mucositis (63%), anorexia (81%), and febrile neutropenia (25%), respectively. Seven patients were confirmed progression disease, and six died from progression of lymphoma. No treatment-related deaths were observed. Conclusions: Concurrent radiotherapy and DeVIC for patients with localized ENKL, nasal type, demonstrated favorable outcomes. We are now investigating what factors indicate good or poor prognosis in this regimen. Progression free survival of concurrent radiotherapy and DeVIC regimen Disclosures: Yokoyama: CHUGAI PHARMACEUTICAL CO.,LTD: Consultancy. Mishima:CHUGAI PHARMACEUTICAL CO.,LTD: Consultancy.

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OP0294 SJÖGREN’S SYNDROME ASSOCIATED LYMPHOMAS: CLINICAL DESCRIPTION AND 10-YEAR SURVIVAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2400 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 180-181

Author(s):

L. Chatzis ◽

V. Pezoulas ◽

A. Goules ◽

I. Stergiou ◽

C. Mavragani ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Histologic Type ◽

Single Center ◽

Event Free Survival ◽

Survival Curves ◽

Free Survival ◽

Kaplan Meier

Background:Sjögren’s Syndrome (SS) is a chronic systemic autoimmune disease of unknown etiology, carrying the highest lymphoma risk among autoimmune diseases, with significant impact on mortality and morbidity of patients.Objectives:To describe: i) the clinical phenotype of SS, ii) the histologic type, stage, treatment options regarding lymphomas and iii) the prognosis of patients with SS related lymphoproliferative disorders.Methods:Eight hundred and fifteen consecutive SS patients’ records from a single center fulfilling the 2016 ACR/EULAR were reviewed retrospectively for the purpose of this study. One hundred twenty-one patients with a diagnosis of non-Hodgkin Lymphoma (NHL) were identified and enrolled in the study population. Cumulative clinical, laboratory and histologic data were recorded and overall survival as well as event free survival curves were constructed using the Kaplan-Meier method. An event was defined as a disease progression, lymphoma relapse, treatment failure, histologic transformation, development of a 2nd lymphoma or death from any cause.Results:From 121 pSS patients with lymphoma the most common histologic type encountered was MALT lymphoma (92/121, 76,0%) followed by DLBCL (11/121, 9.0%) and NMZL (8/119, 6.6%). The remaining 10 patients had various lymphomas of B (follicular, lymphoplasmacytic, chronic lymphocytic leukemia} and T cell origin (peripheral T cell lymphoma not otherwise specified, primary cutaneous T cell lymphoma, angioimmunoblastic t-cell lymphoma). Permanent salivary gland enlargement (66.1%, 80/121), palpable purpura (34,7% 42/121), peripheral nervous involvement (9,9%, 12/121), interstitial lung disease (8,2%, 10/121) presence of serum cryoglobulins (38,7%, 43/111) and C4 hypocomplementemia (69,8% 81/116) present at least 1 year before the development of lymphoma were the main pSS related features. The median age at lymphoma diagnosis was 58 years old (range 29-82) while MALT lymphomas developed earlier compared to DLBCL from pSS diagnosis (8 vs 3 OR= 3.84, 95%CI: 0.29 to 10.46; p=0.0266). The commonest biopsy proven extranodal sites included the labial minor salivary (43,8% patients) and parotid glands (30,5%) while 11% of patients had more than 1 extranodal sites affected. Bone marrow involvement was evident in 24,3% of patients (29/119) while nodal involvement in 35,5% (42/118). The majority of patients (65%) had limited disease (stage I or II). A watch and wait therapeutic policy was chosen in 40 patients while the rest received rituximab with or without chemotherapy. The 10-year survival and event free rates were 79% and 45,5% for MALT lymphomas, 40,9% and 24,2% for DLBCL and 46% and 31% for NMZL respectively (Figure 1). The Mantel-Cox log-rank comparison of the overall survival curves revealed a statistically significant difference (p=0.0016) among lymphoma subtypes.Figure 1.Overall and event free survival of SS-associated lymphoma patients. A. Kaplan-Meier overall survival analysis. B. A Kaplan-Meier event free survival analysis.Conclusion:This is the largest single center series of SS- associated lymphoma patients, providing a detailed description of SS and lymphoma related features, combined with a 10-year survival and event free curves for the first time in the literature.Disclosure of Interests:None declared.

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Survival of Limited Stage Peripheral T-Cell Lymphoma Is Similar To Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v106.11.2817.2817 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2817-2817 ◽

Cited By ~ 1

Author(s):

Kerry J. Savage ◽

Mukesh Chhanabhai ◽

Nicholas Voss ◽

Shenkier Tamara ◽

Randy D. Gascoyne ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Free Survival ◽

Limited Stage ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of diseases with an overall poor prognosis. Little information is available regarding the outcome of PTCL patients who present with limited stage disease. We sought to determine the outcome of PTCL patients presenting with limited disease in comparison with a cohort of patients with limited stage diffuse large B-cell lymphoma (DLBCL). Methods: In a retrospective analysis we identified all patients with limited stage (non-bulky (<10cm) stage I/II disease no symptoms) PTCL diagnosed at the British Columbia Cancer Agency (BCCA) between 1983 and 2004. Patients were excluded if they had cutaneous anaplastic large cell lymphoma (CutALCL) (n=13), NK/T-cell lymphoma nasal type (n=9) or primary CNS/ocular involvement (n=6). Results: Thirty-seven patients with PTCL were identified according to the World Health Organization Classification: ALK-neg ALCL 8 (22%); PTCL-unspecified (PTCLUS) 28 (78%); enteropathy associated TCL (EATL) 1 (3 %). The majority received CHOP-type chemotherapy (n=31, 86%), most with brief chemotherapy followed by involved-field radiation (n=19, 61%). The 5 y OS and PFS was similar between PTCLUS and ALK-neg ALCL. There was no difference in survival between extranodal and nodal cases. The outcome of PTCL patients (including ALK-neg ALCL and PTCLUS) was compared to a cohort of limited stage DLBCL patients (excluding CNS/ocular lymphoma) (n=305) diagnosed over the same time period and treated similarly. There was no difference in 5 y OS or PFS (Figure 1,2). Interestingly, there were no late relapses observed in PTCLUS, in marked contrast to DLBCL. Conclusions: Limited stage PTCL is rare, however outcomes appear to be comparable to early stage DLBCL, supporting that they should be treated in a similar manner. Unlike limited stage DLBCL where late relapses occur, a plateau in the progression-free survival curve is observed, highlighting a distinct natural history for limited stage PTCL. Overall Survival Limited Stage PTCL vs DLBCL p=.18 Overall Survival Limited Stage PTCL vs DLBCL p=.18 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07

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Nodal Peripheral T-Cell Lymphoma – a Clinical and Epidemiological Analysis at Medicine School of Sao Paulo University

Blood ◽

10.1182/blood.v124.21.1706.1706 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1706-1706

Author(s):

Luis Alberto de Padua Covas Lage ◽

Marianne Castro Goncalves ◽

Rodrigo Santucci ◽

Renata Oliveira Costa ◽

Debora Levy ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

High Risk ◽

Cell Lymphoma ◽

Progression Free Survival ◽

Large Cell ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Free Survival ◽

Large Cell Lymphoma

Abstract Background: Peripheral T-cell lymphoma (PTCL) are a biologically and clinically heterogeneous group of rare diseases arising from mature or activated post-thymic T lymphocytes. Correspond to 10% to 15% of lymphoid malignancies with marked geographical variation in incidence. According to the WHO classification they are divided into nodal, extranodal, primary cutaneous and leukemic or disseminated and encompass 18 distinct entities. The nodal group involves the peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic lymphoma (AITL), anaplastic large cell lymphoma ALK positive (ALCL-ALK+) and anaplastic large cell lymphoma ALK negative (ALCL-ALK-). The literature of PTCL is scarce, especially in our country where data of epidemiology, clinical features and outcomes are usually rarely available. So, to better understand PTCL we performed a retrospective study with patients treated in a reference service for cancer treatment in Brazil. Methods: Eight-seven nodal PTCL patients treated with anthracyclne-based regimen (CHOP or, CHOEP) from January 2000 to June 2014 were evaluated retrospectively at the Medicine School of Sao Paulo University, Brazil. All patients lower than 60 years were consolidated with autologous hematopoietic stem cell transplantation (ASCT) in first CR or PR except that with ALCL-ALK+ diagnosis. Refractory and relapsed patients were salvaged with 3-4 cycles of IVAC (Ifosphamide 1.5 g/m2 i.v D1-D5, etoposide 100mg/m2 i.v D1-D5, aracytin 2g/m2 i.v twice a day D1-D2) regimen and submitted to ASCT. It was performed a central histopathological review and clinical and epidemiological data were obtained from medical records. Patients were evaluated for overall response (OR) including complete response (CR) and partial response (PR), overall survival (OS) and progression free survival (PFS). Statistical analysis was performed using the STATA-3 program using and a p-value ≤ 0.05 was considered statistically significant. Results: Of the 87 patients, 34 (39.08%) cases were classified as ALCL-ALK-, 27 (31.03%) as PTCL-NOS, 16 (18.39%) as ALCL-ALK+, 6 (6.89%) as AITL and in 4 (4.1%) cases the diagnosis could not be performed and an expansion of the immunohistochemical is ongoing. Thirty-six (45.38%) cases were female and 51(54.62%) were male, 59(67.81%) patients were lower than 60 years. Seventy-six (87.35%) patients presented in advanced stage (III or IV) at diagnosis but 73(83.90%) patients presented an ECOG < 2 and 14(16.10%) ≥ 2. Eighteen (20.70%) patients were of low-risk, 26 (29.88%) of low-intermediate risk and 43(49.42%) of high-intermediate and high-risk of international prognostic index (IPI). The CR and PR was obtained for 44(50.57%) and 8(9.19%), respectively with 59.76% OR. Thirty (34.48%) patients were primary refractory and five remain under treatment. In a median of follow of 30 months, ALCL-ALK+ show higher OS (median 140.98 months) than ALCL-ALK- (44.20 months), PTCL-NOS (median 20.62 months) and AITL (median 7.24 months) (p=0.41) (Figure 1A). The median of PFS was 3.84 months for AITL, 23.44 months for ALCL-ALK+, 40.03 months for PTCL-NOS and was not yet reached for ALCL-ALK- (p=0.0006) (Figure 1B). Figure 1: Overall survival (1A) and Progression Free Survival (1B) of nodal PTCL Figure 1:. Overall survival (1A) and Progression Free Survival (1B) of nodal PTCL Figure 2 Figure 2. Conclusion: In this study we showed that ALCL-ALK+ as well as found in the literature presented a better OS in comparison to others nodal T-cell lymphoma as AITL, PTCL-NOS and ALCL-ALK-. Surprisingly the PFS of ALCL-ALK+ was statistically significant lower than of ALCL-ALK-. We thought that this result may be explained because in our service until to perform this analysis we did not indicate ASCT in first CR for ALCL-ALK+, but for all ALCL-ALK-. This hypothesis may be reinforced as the most of our cases presented high-intermediate and high-risk of IPI and that could equalize the favorable effect of ALK expression. In addition, we changed our approach and we are also indicating ASCT in first line for patients with ALCL-ALK+ with intermediate-high and high-risk of IPI . Disclosures No relevant conflicts of interest to declare.

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Treatments and Outcomes of Patients With Extranodal Natural Killer/T-Cell Lymphoma Diagnosed Between 2000 and 2013: A Cooperative Study in Japan

Journal of Clinical Oncology ◽

10.1200/jco.2016.68.1619 ◽

2017 ◽

Vol 35 (1) ◽

pp. 32-39 ◽

Cited By ~ 59

Author(s):

Motoko Yamaguchi ◽

Ritsuro Suzuki ◽

Masahiko Oguchi ◽

Naoko Asano ◽

Jun Amaki ◽

...

Keyword(s):

T Cell ◽

Natural Killer ◽

Cell Lymphoma ◽

Interleukin 2 ◽

Progression Free Survival ◽

Free Survival ◽

Natural Killer T Cell ◽

Soluble Interleukin 2 Receptor ◽

Killer T Cell

Purpose To elucidate the management and outcomes of patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKL), who were diagnosed between 2000 and 2013 in Japan. Patients and Methods Data from 358 patients with ENKL diagnosed between 2000 and 2013 from 31 institutes were retrospectively analyzed. Results Patients’ median age was 58 years, and 257 (72%) had localized disease. The most common first-line treatment was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%) for localized ENKL and L-asparaginase–containing chemotherapy (30%) for advanced ENKL. With a median follow-up of 5.8 years, overall survival (OS) rates at 5 years for localized and advanced ENKL were 68% and 24%, respectively. The prognostic index of natural killer lymphoma was validated in our study, although only 4% of patients with localized ENKL were classified as high risk. With a median follow-up of 5.6 years, OS and progression-free survival at 5 years in the 150 patients who received RT-DeVIC in clinical practice were 72% (95% CI, 63% to 78%) and 61% (95% CI, 52% to 69%), respectively. Toxicities of RT-DeVIC were comparable to those in a previous trial. Multivariate analysis in patients with localized ENKL who received RT-DeVIC identified elevated soluble interleukin-2 receptor as an independent predictive factor for worse OS and progression-free survival (adjusted hazard ratios, 2.28 and 2.46; 95% CI, 1.24 to 4.23 and 1.42 to 4.28; P = .008 and .0014, respectively). Conclusion Favorable OS in response to new treatments was demonstrated in a large number of patients. Improved treatment approaches are needed for localized ENKL exhibiting elevated pretreatment soluble interleukin-2 receptor.

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Increased body mass index is associated with improved overall survival in extranodal natural killer/T-cell lymphoma, nasal type

Oncotarget ◽

10.18632/oncotarget.13988 ◽

2016 ◽

Vol 8 (3) ◽

pp. 4245-4256 ◽

Cited By ~ 2

Author(s):

Ya-Jun Li ◽

Ping-Yong Yi ◽

Ji-Wei Li ◽

Xian-Ling Liu ◽

Xi-Yu Liu ◽

...

Keyword(s):

Body Mass Index ◽

Overall Survival ◽

T Cell ◽

Natural Killer ◽

Body Mass ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Nasal Type ◽

Natural Killer T Cell ◽

Killer T Cell

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Outcome of Autologous Hematopoietic Cell Transplantation in First Complete Remission(CR1) in Patients with Peripheral T-Cell Lymphomas(PTCLs)

Blood ◽

10.1182/blood-2019-125666 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3315-3315

Author(s):

Shuo Liu ◽

Zhengming Jin ◽

Depei Wu ◽

Haiwen Huang

Keyword(s):

Overall Survival ◽

Stem Cell ◽

T Cell ◽

Cell Transplantation ◽

Cumulative Incidence ◽

Cell Lymphoma ◽

Statistical Significance ◽

Progression Free Survival ◽

T Cell Lymphoma ◽

Free Survival

Abstract Background Patients with peripheral T cell lymphomas (PTCLs) generally have a poor prognosis with conventional chemotherapy. Most studies demonstrates that, compared to the patients who did not achieve complete remission (CR) after initial therapy, the patients of PTCL who received autologous stem cell lymphoma (ASCT) as consolidation treatment show clearly advantage in survival. However, given the absence of randomized controlled studies, it is unproven that clinical value of consolidative ASCT for PTCL patients achieving CR1. There is a possibility that the survival is similar with or without up-front ASCT group. Thus, we collected the data of PTCL patients who attain CR1 following conventional chemotherapy in our center during the past 10 years. And the objective of this study is to evaluate overall survival(OS), progression-free survival(PFS), and cumulative incidence of relapse (CIR) between observation and first-line ASCT group. Patients and Methods Weconducted a retrospective study of patients with PTCL who were treated in our center from January 2009 to April 2019. The histopathologic diagnosis of all PTCL patients according to the World Health Organization classification. Exclusion criteria were the following: (1) anaplastic lymphoma kinase (ALK)-positive anaplastic large T-cell lymphoma; (2) cutaneous T cell lymphoma (CTCL); (3) concurrent B cell lymphomas; (4) natural killer/T-cell lymphoma (NK/TCL); (5) patients who underwent allogeneic stem cell transplantation. Furthermore, patients with PTCL age ≤65 years were included. Overall survival(OS )and progression-free survival(PFS) rates were estimated using the Kaplan-Meier method and Survival was compared using the log-rank test. Cumulative incidence of relapse (CIR) was compared by Gray's test competing risk test statistic. The level of statistical significance was set at p < 0.05. Results A total of 97 patients who met inclusion criteria were enrolled in our center from January 2009 to April 2019. And 59 (59/97, 60.8%)achieved CR1 after receiving induction chemotherapy. Table 1 summarizes the baseline characteristics for the patients in CR1. Of the 59 patients, 43 patients underwent observation and waiting in CR1, 16 patients underwent consolidative ASCT. PTCL NOS accounted for more than 50% at diagnosis in both groups. However, there was significant difference in median age between Non-ASCT group and ASCT group. Patients receiving ASCT were younger and in better physical condition. There were no difference in initial chemotherapy between two groups. Median follow-up time in the entire patient cohort for CR1 (59) was 31months. The median OS and PFS for patients who underwent observation in CR1 was 105 months and 20 months, the median OS and PFS for patients who underwent ASCT as consolidation treatment was 133 months and 91 months. There were no statistical significance in OS (105m vs. 133m, P=0.541) (Figure 1) and PFS (20m vs. 91m, P=0.237) (Figure 2). The estimated 2-year OS was 68.7% and 74.5% in the non-ASCT group and ASCT group, respectively. The estimated 2-year PFS was 41.9% and 62.5%, respectively. When considering incidence of disease relapse, the 2-year cumulative incidence of relapse in the non-ASCT and ASCT group was 41% and 25%, respectively. Again, however, this did not meet statistically significant(P=0.504) (Figure 3). Notably, among patients with advanced-stage disease, elevated LDH, extranodal involvement>1 sites or intermediate-to-high IPI scores, patients who received ASCT as consolidative treatment did not have long time survival compared to the non-ASCT group. Conclusion In conclusion, for PTCL patients achieving CR1 following induction therapy, consolidative ASCT does not extend overall survival and progression-free survival compared to observation. Similarly, consolidative ASCT also failed to reduce cumulative incidence of relapse. We favor proceeding to observe and wait because of high toxic of hematopoietic stem cell transplantation. However, The finding still needs to be confirmed in a larger, prospective study. Table 1 Disclosures No relevant conflicts of interest to declare.

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Clinical Outcomes of Patients with T Cell NHL Undergoing Allogeneic Stem Cell Transplant.

Blood ◽

10.1182/blood.v108.11.3026.3026 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3026-3026 ◽

Cited By ~ 1

Author(s):

Jasmine Zain ◽

J. Palmer ◽

N. Tsai ◽

L. Popplewell ◽

A. Nadamanee ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

B Cell ◽

Sample Size ◽

Clinical Outcomes ◽

Cell Lymphoma ◽

Progression Free Survival ◽

T Cell Lymphoma ◽

Cell Transplant ◽

Free Survival

Abstract Background: T cell NHL represent approximately 10–15% of all lymphomas. Pts with T cell NHL are often treated similarly to patient with B cell NHL, although the clinical outcomes of most patients with T- NHL tend to be worse with the exception of ALK positive anaplastic large cell lymphomas (ALCL). Updated classifications in recent years have recognized specific clinical and pathologic T cell entities with distinct clinical courses and this poses a challenge to the systemic study of these diseases. The exact role of allogenic transplant in T- cell NHL is unknown. Methods: We looked at 45 pts who underwent an allogeneic HSCT for T cell lymphomas between Jan 2000 to Dec 2005. There were 18 males, 27 females. Median age at transplant was 32 (7–74). Histology was Mycosis fungoides /Sezary syndrome (SS/MF) n=10, T cell lymphobalstic leukemia (PTLL) n=16, PTCL including AILD and ALCL n=14, NKT cell n=5. Syngeneic donor 1, Sibs 31, MUD 13. Median time from diagnosis to transplant was 12.5 (3.6–88.3) mo. Source of stem cells BM 9, PBSCT 35, cord blood 1. Conditioning, fully ablative 29, reduced intensity 16. Median number of prior regimens MF/SS 5, PTLL 2, PTCL 3, NKTL 2 with only 2 pts with prior auto transplants. 18 pts were in remission at the time of transplant and 12 pts had induction failure. Results: Median follow up from transplant was 45.3 mo(0.7–64.7) with a 55.6%OS. Incidence of GVHD was Acute n= 27 extensive chronic n=20. Cause of death was transplant related in 16 pts with only 3 pts dying of disease progression. The overall survival is 61.2 % at 1 year,55.4% at 2 years and 48.5% at 5 years with a 5 year progression free survival at 48.5%. Based on different histologies, the results are 50.0% overall survival at 1 year and 40.0% at 2 and 5 years for SS/MF, 55.6% at 1 and 2 years for PTLL, 70.1% at 1 and 2 years and 52.6% at 5 years for PTCL and 80% at 1 year for NKT shown in fig 1 and 2. Conclusion: Allogenic transplant can result in long term survival for some patients with T cell NHL suggesting a graft vs lymphoma effect. Timing of transplant needs to be better defined. Most patients are heavily pretreated which may have resulted in more transplant related mortality with 11/20 pts dying of infection. Most patients did not have a prior auto transplant indicating early progression of disease after standard therapies defined for B cell malignancies. Overall Survival by Histology  T-Cell Lymphoma with Allogenic Transplant  Sample Size: 45 patients Overall Survival by Histology  T-Cell Lymphoma with Allogenic Transplant  Sample Size: 45 patients Progression-Free Survival by Histology  T-Cell Lymphoma with Allogenic Transplant  Sample Size: 45 patients Progression-Free Survival by Histology  T-Cell Lymphoma with Allogenic Transplant  Sample Size: 45 patients

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Driver Mutations Affecting Natural Killer/T Cell Lymphoma

Blood ◽

10.1182/blood.v128.22.4109.4109 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4109-4109 ◽

Cited By ~ 1

Author(s):

Gehong DONG ◽

Qiang Gong ◽

Jinhui Wang ◽

Xiwei Wu ◽

Yuping Li ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Natural Killer ◽

Mutation Frequency ◽

Cell Lymphoma ◽

Survival Curves ◽

Tp53 Mutations ◽

Natural Killer T Cell ◽

Hispanic Patients ◽

Killer T Cell

Abstract Natural killer/T cell lymphoma (NKTCL) is an aggressive subtype of non-Hodgkin lymphoma that is rare overall but has a higher prevalence in Chinese and Hispanic populations. Recent sequencing efforts have improved the understanding of the disease and revealed a number of genes that may drive the pathogenesis of NKTCL. These efforts were largely limited by the number of cases studied. Based on previously reported whole exome sequencing data in NKTCL and other lymphoid malignancies and on the frequency and potential biological significance of the mutant, we designed a 334-gene panel and sequenced 105 NKTCLs. We characterized single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations (CNAs) that may have pathogenic roles. Tumor DNA was isolated from 74 Chinese and 31 Hispanic NKTCL patients. For 7 of these, matched normal DNA was extracted from peripheral blood. The 334 genes in the custom panel were captured using the Agilent SureSelect platform, and the exons of these genes were sequenced on an Illumina HiSeq 2500 instrument. For cases without matched normal samples, we discriminated between somatic and germline variants with an in-house machine learning algorithm which is based on information of public variant databases, variant annotations, and sequencing statistics, and followed by manual inspection. CNAs were determined based on the untargeted sequences using an R package, CopywriteR. We identified a total of 479 SNVs and 113 indels in 155 genes in 102 out of 105 patients. Mutations in STAT3 and JAK3 were identified in 30% and 7% of the cases, respectively. The hotspot mutations Y640F, S614R, and G618R in the SH2 domain of STAT3 and A573V of the JH2 domain of JAK3 were observed in most of these cases. 46% of the cases harbored one or more mutations in epigenetic regulators ARID1A, EP300, MLL2, MLL3, and TET2. Transcription co-repressors BCOR and NCOR2 were mutated in 25 of the cases. 13% of the cases contained mutations in HLA-A or CIITA, most of which were inactivating, suggesting possible defects in immune surveillance. DDX3X and TP53 mutations were detected in 19% and 10% of the cases, respectively. TP53 mutations were mutually exclusive with mutations in DDX3X and, except for one case, with STAT3 also. MGA mutations, which were present in 12% of the cases, were usually concurrent with STAT3 mutations. The mutational profiles of Chinese and Hispanic cases were similar, and only CD58 mutations were significantly more common in Hispanic patients (p=0.03). Comparison between NKTCL with localized and systemic presentation demonstrated that CCR7 was mutated more frequently in systemic cases (p=0.02). Prognostic analysis identified EP300 mutations as a potential marker for poorer survival (p=0.01). Frequent copy loss on chromosome 6q was observed and PRDM1, which is present on 6q, was mutated in 10% of the cases. In summary, we identified the profile of mutated genes in a large series of NKTCL. Most of the genes have been previously reported to be mutated in NKTCL, but the frequencies for some of the mutants were quite different. Interestingly, the mutational profiles of NKTCL in Chinese and Hispanic patients were very similar despite the geographic differences. Mutations leading to abnormal activation of the JAK-STAT3 pathway and abnormal chromatin modification were highly prevalent. BCOR, DDX3X and TP53 mutations were also frequent. Variants in CCR7 and EP300 were potential markers for systemic disease and poor prognosis, respectively. Figure. Mutation profiles of genes with mutation frequency larger than 5%. Genes that are not expressed in normal NK cells were excluded. Figure. Mutation profiles of genes with mutation frequency larger than 5%. Genes that are not expressed in normal NK cells were excluded. Figure. Overall survival curves of cases with and without mutations in EP300. Figure. Overall survival curves of cases with and without mutations in EP300. Disclosures No relevant conflicts of interest to declare.

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