Nodal PTCL Research Articles

Sintilimab plus GemOx is an effective salvage therapy in patients with refractory/relapsing nodal peripheral T cell lymphomas

PurposeThe retrospective study was to explore the effectiveness and safety of GemOx (gemcitabine, oxaliplatin) plus sintilimab (belongs to the class of drugs known as immune checkpoint inhibitors, particularly targeting the PD-1 receptor) in relapse or refractory nodal PTCLs.MethodsPatients with nodal PTCL who initiated salvage therapy with sintilimab and GemOx between January 2020 to September 2021 were identified from the database of the hematology department of the Second Affiliated Hospital of Zhejiang University School of Medicine. All patients received 2–4 cycles (3 weeks/cycle) of treatment of sintilimab (200 mg, I.V, D1) in combination with GemOx. Treatment response was assessed every six weeks during the salvage treatment phase. Eligible patients received maintenance therapy according to the investigator’s decision. Follow-ups were routinely conducted every three months.Results31 patients with r/r nodal PTCLs were enrolled, including 23 PTCL-NOS, 4 AITL, and 4 ALCL. 21 (67.7%) patients received at least two lines of therapy. 71.0% (95% CI, 53.4%-83.9%) of patients documented objective response of 2–4 cycles of sintilimab plus GemOx therapy, including 9 complete response and 13 partial response. 21 (67.7%) patients received consolidation therapy, including 5 autologous stem-cell transplantation and 12 histone deacetylase inhibitors. After a median 25.6 months follow-up, the median PFS was 22.0 (95% CI,11.8–24.7) months, and the median OS was 26.2 (95% CI, 24.4 –NA) months. 29 (93.5%) patients experienced at least one adverse event, and 26 (83.9% patients only had mild (grade 1–2) AEs.Univariable Cox regression showed the progression risk of AITL is 22.7 (3.9- 131.0, p < 0.01) times of PTCL-NOS, while the HR of ALCL was 1.14 (0.33–3.96,p = 0.833).ConclusionSintilimab plus GemOx showed encouraging activity and manageable toxicity for patients with r/r PTCL.

Brazilian Non-Hodgkin T Cell Registry: An Exploratory Analysis of Extranodal Sites

Introduction: T cell lymphomas (NHL-T) account for 10-15% of all non-Hodgkin lymphomas (NHL). They are a heterogeneous group of infrequent neoplasms with a variable clinical course but prevalently aggressive behavior and high mortality rates. Diagnosis is still challenging and there has been little change in the overall prognosis over the last two decades. In spite of IPI (International Prognostic Index) that include extranodal (EN) site in its variables, lack is known regarding EN involvement in nodal peripheral T cell lymphomas- PTCL (PTCL-NOS, TFH and ALCL ALK+/ALK-) location or impact on prognosis). Objective: We aim to evaluate number of extranodal (EN) sites in nodal PTCL lymphomas (PTCL-NOS, TFH and ALCL ALK+/ALK-) and its specific location as a surrogate for overall survival (OS) and progression free survival (PFS). Also generate hypothesis for further molecular analysis. Methodology: Brazil T-cell project is a national, ambispective study of patients with histological diagnosis of PTCL diagnosed from January 2015 to December 2022. Approval for the study was obtained at the coordinating center (Samaritano Hospital - São Paulo) and at each participating center as per the institutional standard before initiation. Those selected for the study were previously untreated patients age ≥ 19 years, with de novo PTCL or natural killer/T-cell lymphoma. At each institution, the local pathologist reviewed the diagnose. Clinical information included coded patient and site identifiers, sex, date of birth, date and site of diagnostic biopsy, sites of disease, EN (location and number), methodology of staging (clinical, CT or Pet) and Ann Arbor stage. Initial therapy and response; details of remission, progression, or relapse; and subsequent therapies, along with survival status and cause of death. Treatment outcome was determined by OS and PFS. REDcap Platform (by Vanderbilt) has been used to collect and store data and for descriptive analysis the IBM-SPSS version 24 was applied. Kaplan-Meier method estimated the OS, whereas Log-Rank tests to compare its curves. This trial is registered at Clinical trials (NCT03207789). Results: Of 621 registered we selected 198 patients (pts) diagnosed with nodal PTCL with at least one EN involvement [Cohort 1 EN involvement equal to one (148 pts) and Cohort 2 EN involvement ³ 2 (50 patients)]. Considering all 198 pts (Cohort 1 and 2) there was a slight male predominance (63%); median age 53 years; 79% were staged III or IV; 81.5 were IPI 2 or more. Most frequently histology was PTCL-NOS (46%), followed by ALCL ALK+ (32%), ALCL ALK- (12.5%) and TFH (9.5%). The majority had B Symptoms (63%); 37.5% had Bone Marrow infiltration. The chemotherapy most frequently chosen were CHOEP (54.5%) followed by CHOP (19.5%). Transplant was used as consolidation in 20% of the cases. Almost half of patients achieved complete response after first line (44%), although 38% relapsed. Cohort 1 (EN=1) and 2 (EN ³ 2) were similar regarding clinical characteristics, except, for stage III-IV (73% vs 96%; p &amp;lt;.0001); IPI ³ 3 (37.5% vs. 82%; p &amp;lt;.0001) and ECOG (22 vs. 48%; p=.001), respectively. Therefore, translating in a more advanced disease in Cohort 2. The most common extranodal location in Cohort 1 (EN=1) was Skin/ Subcutaneous (35%), followed by gastrointestinal tract (18%) and lung (16%). NHL-T subtypes behaved similarly in this EN exploratory analysis, with a better OS and PFS in ALCL ALK+, followed by ALK- and PTCL-NOS. There was no difference in PFS in Cohort 1 (EN=1) and 2 (EN ³ 2), but there was a slight difference in Overall survival (55% vs. 42% in 12 months; p=0.06), suggesting EN sites involvement assessed by CT and PET-CT as possible surrogate for outcomes in this population. Conclusion: NHL-T is still unmet medical need considering suboptimal outcome in treatment and survival. New biological and clinical finding are still necessary to adequate stratify this group of patients, considering poor performance of IPI and PIT scores. Number and location of EN sites involvement may be a possible surrogate for outcome, which can be a reflect of a distinct biology, that needs further investigation. Registries are of importance considering rarity and poor prognosis of this diseases and an adequate instrument to hypothesis generation.

Systemic VSV-IFNβ-NIS oncolytic virotherapy in patients with relapsed refractory T-cell lymphoma.

7530 Background: Oncolytic virotherapy is a novel immunomodulatory therapeutic approach currently under study for relapsed refractory (R/R) hematologic malignancies. The engineered Vesicular Stomatitis Virus VSV-IFNβ-NIS used in this study encodes interferon beta (IFNβ) and sodium iodine symporter (NIS). Virally-encoded IFNβ serves as an index of viral proliferation and enhances host anti-tumor immunity. Herein, we report the updated results of the phase 1 clinical trial NCT03017820 of a one-time administration of systemic VSV-IFNβ-NIS among patients (pts) with R/R multiple myeloma (MM), T cell Lymphoma (TCL) and Acute myeloid Leukemia (AML) with particular focus on the TCL cohort treated at the highest dose level (DL4) without Ruxolitinib. Methods: VSV-IFNβ-NIS was administered as a single IV dose following a classical 3+3 phase I trial, starting at 5e9 TCID50 DL1 through 1.7e11 TCID50 DL4. A dose expansion cohort of 8 additional R/R TCL pts was added at DL4 in view of an initial signal of activity. The primary objective was to determine the maximum tolerated dose of VSV-IFNβ-NIS as a single agent. Secondary objectives were determination of safety profile and preliminary efficacy of VSV-IFNβ-NIS. Adverse events (AEs) are reported based on CTCAE V4; cytokine release syndrome (CRS) grading was based on Lee (Blood 2014) criteria. Results: To date, a total of 43 pts received VSV-IFNβ-NIS: MM (N=21), TCL (N=21) and AML (N=1). In the TCL cohort: at DL4 Group A (no Ruxolitinib), 12 pts were registered, but only 11 pts were treated (mycosis fungoides (MF) N=3; ALK- ALCL N=1; PTCL-NOS N=2; AITL N=4; Nodal PTCL, TFH N=2; ages 33-79). These pts received a median of 3 lines of therapy (range: 1-5). No dose limiting toxicities were observed. Grades 3 and higher AEs were hematologic with transient lymphopenia (63.6%), neutropenia (36.4%) being the most common. The non-hematologic AEs observed included unique toxicities such as CRS grades 1-2 (81.8%); the transient transaminitis grade 1-2 (36.4%) and grade 3 (27.3%) along with thrombocytopenia grade 1-2 (63.6%) and grade 3 (18.2%) were a reflection IFNβ toxicity. All the AEs observed were short lived. Responses were seen in pts with PTCL. At DL4, in pts with systemic PTCL (N=9), there were 5 responses including 3 complete responses (CR) with two long-lasting at 24 months, an ongoing 15 month CR, and a 5 month CR, and 2 partial responses (PR) lasting 5 months in one pts and 6 months in the other. Conclusions: These updated results of single agent VSV-IFNβ-NIS which include pts with PTCL treated at the highest dose level and a dose expansion cohort demonstrates not only the safety of VSV-IFNβ-NIS but also a strong efficacy signal in pts with PTCL with impressive durable responses. Two expansion cohorts at DL4 have been added (20 additional PTCL, 10 B-cell lymphoma pts) to obtain additional data on tolerability and efficacy and biomarkers of response in these pts. Clinical trial information: NCT03017820 .

High Tumor Mutation Burden in Epigenetic Regulatory Genes Predicts Decreased Overall Survival in Nodal Peripheral T-Cell Lymphomas

Introduction: Nodal peripheral T-cell lymphomas (nPTCL) constitute a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena involving genes that control DNA-methylation and histone deacetylation, such as IDH2, DNMT3A, TET2 and RhoA, play a central role in their pathogenesis. Tumor mutation burden (TMB) has emerged as a prognostic biomarker in numerous solid neoplasms. Furthermore, TMB reflects the process of clonal evolution, with progressive acquisition of additional molecular-genetic abnormalities. Recent studies were capable to establish a relationship between TMB and response to anti-cancer treatments. In 2021 Fachi et cols. established a correlation between high TMB in epigenetic regulatory genes and higher response rates to 5-azacytidine and romidepsin in nPTCL. However, the potential prognostic impact of epigenetic TMB remains unknown in nPTCL. Based on this premise, here we aimed, in a pioneering way, to search for a correlation between epigenetic high TMB and adverse prognosis in nPTCL. Methods: This is a retrospective, observational and single-center study, involving 59 patients with nPTCL diagnosed and treated at the Department of Hematology, University of São Paulo, Brazil, from January 2000 to December 2019. Formalin-fixed paraffin-embedded (FFPE) diagnostic tumor samples were submitted to Sanger sequencing with a target-panel, involving IDH2, DNMT3A, TET2 and RhoA genes to search for recurrent mutations. Only non-synonymous mutations were considered for prognostic association. Survival curves were constructed using the Kaplan-Meier method and the Log-Rank test was used to establish a relationship between TMB and outcomes. Results were presented as hazard ratio (HR) and 95% confidence interval (95% CI), and a p-value < 0.10 was considered statistically significant. Results: The median age was 50 years (IqR 38-61), and 57.6% (34/59) were male. Thirty-nine percent (23/59) had bulky disease ≥ 7 cm, 83% (49/59) had B-symptoms, 94.9% (56/59) had advanced stage III/IV, 27.1% (16/59) had ECOG ≥ 2, 27.1% (16/59) had ≥ 2 extranodal sites involved by lymphoma, and 55.9% (33/59) had intermediate-high/high-risk IPI. Seventy-six percent (45/59) received up-front therapy with CHOP-like regimens (CHOP or CHOEP), 23.7% (14/59) experienced radiotherapy, and 33.3% (20/59) were consolidated with ASCT. With a median follow-up of 3.7 years (95% CI: 0.9-12.4), the estimated 2-year OS and PFS were 57.1% (95% CI: 45.5-70.4) and 49.2% (95% CI: 34.0-59.2), respectively. Missense, non-sense or frameshift mutations in the IDH2 gene were observed in 3.3% (2/59) of cases, DNMT3A in 3.3% (2/59), RhoA in 23.7% (14/59) and TET2 in 37.2% (22/59). Among the 59 patients included, 23/59 (38.9%) had no mutations in the target-genes, 25/59 (42.4%) had 1 mutation, and 11/59 (18.6%) had two or more mutations. Therefore, the cases were categorized into low TMB (< 2 mutations) [n=48/59 - 81.3%] or high TMB (≥ 2 mutations) [n=11/59 - 18.7%]. The median overall survival was 51.4 months (95% CI: 0-124.1) for low TMB and only 3.1 months (95% CI: 3.1-15.2) for high TMB, p=0.08. The estimated 2-year OS was 64.3% (95% CI: 50.6-78.0) for low TMB and 36.4% (95% CI: 8.0-65.0) for high TMB [Figure 1]. Similarly, median progression-free survival was 13.3 months (95% CI: 0-29.4) for low TMB and 6.3 months (95% CI: 0.9-11.6) for high TMB, p=0.319. The estimated 2-year PFS was 46.1% (95% CI: 20.0-72.1) for low TMB and 25.0% (95% CI: 17.5-67.5) for high TMB. Conclusion: In a pioneering way, we demonstrated that the high epigenectic tumor mutation burden (TMB), defined by the presence of 2 or more mutations involving epigenetic regulatory genes, was associated with decreased overall survival in Brazilian patients with nodal PTCL. Although preliminary, these data support the potential impact of epigenetic TMB as a prognostic biomarker in nPTCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Identifying Primary Refractory Disease and Early Relapses in Peripheral T-Cell Lymphoma Using Baseline Characteristics, Minimal Residual Disease, and Mutational Profiling

INTRODUCTION: Despite approvals in the relapsed/refractory setting for T-cell lymphomas, upfront advances have been more difficult to realize. A critical component in improving treatment paradigms is a greater ability to identify patients at diagnosis with high-risk for chemorefractory disease who may benefit from alternative induction programs and distinguish them from patients who fare well with standard approaches. In order to characterize such cases, we analyzed patients treated at Memorial Sloan Kettering (MSK) with curative intent to identify features associated with primary refractoriness or early relapse (<1 year). METHODS: We identified patients ≥ 18 years of age with PTCL-NOS, AITL, or ALCL who either were consecutively treated at our center at the time of diagnosis or were seen during initial therapy from 1/1/2001-10/1/2021. All patients had histologically-confirmed disease and were treated with curative intent. Patients were grouped into two sub-cohorts: (1) primary refractory disease/early relapse (< 1 year), or (2) relapse-free at 1 year from initiation of first-line therapy. Patients without relapse but < 1 year of followup were excluded. A univariate logistic regression was performed to compare baseline features between the sub-cohorts using the Wilcoxon rank sum test and Pearson's Chi-squared test. A multivariate model was then constructed using histology and baseline IPI apriori and any factor significant in univariate analyses to produce odds ratios (OR) for primary refractory disease/early relapse. In a separate analysis of patients who underwent autologous transplant (autoHCT) in 1st remission, the impact of bone marrow (BM) minimal residual disease (MRD) on PFS was evaluated. Finally, in a subset of patients who underwent targeted mutational profiling at diagnosis (Ptashkin et al., Cancer Res 2019), genomic results were analyzed. Genes were characterized into oncogenic pathways (Sanchez-Vega et al., Cell 2018) and included in analyses if mutations were present in ≥ 5% of patients. A Cox regression model was performed for altered genes/pathways to obtain hazard ratios (HR) for progression/death, with significance testing using the false discovery rate correction for multiple testing (q-value). RESULTS: A total of 349 patients were identified (Table 1). With a median followup time of 60 months (m) among survivors (IQR: 23-95), median PFS and OS of the entire cohort was 19 (95% CI 13-28) and 73 m (60-128), respectively. By histology, 2-year PFS for PTCL-NOS, AITL, ALK- ALCL, and ALK+ ALCL was 33%, 43%, 66%, and 79%, respectively (p<0.001); 5-year OS was 41%, 54%, 75%, and 92%, respectively (p<0.001, Figure 1). In comparing those with primary refractory disease/early relapse versus those relapse-free at 1-year, patients with PTCL-NOS, stage III/IV disease, >1 extranodal site, BM involvement, and cutaneous involvement were significantly more likely to have primary refractory disease/early relapse. On multivariable analysis, a diagnosis of PTCL-NOS (OR for AITL: 0.42, 95% CI 0.22-0.81), advanced IPI (OR for IPI 4-5: 4.88, 95% CI 1.56-16.8), BM involvement (OR: 2.28, 95% CI 1.14-4.68), and cutaneous involvement (OR: 2.47, 95% CI 1.04-6.21) all conferred increased risk of primary refractory disease/early relapse. In the subgroup analysis of BM MRD status in patients who underwent autoHCT, the presence of MRD did not significantly impact PFS (5-year PFS 45% MRD+ vs. 45% MRD, p=0.55). Finally, in evaluation of mutational profiles (n=86), mutations in TET2 (59%), RHOA (30%) and DNMT3A (23%) were the most commonly altered genes. Although rare (n=6), alterations in DNA damage response pathways significantly increased risk of progression (HR 5.08, 95% CI 2.05-12.6, q-value=0.007) and death (HR 9.9, 95% CI 3.22-30.8, q-value=0.001). CONCLUSIONS: This is one of the largest cohorts of nodal PTCL in the 21st century. Despite prolonged survival in some patients, primary refractory disease/early relapses remain common. On multivariate analyses, a histological diagnosis of PTCL-NOS, advanced IPI, BM involvement, and cutaneous involvement predicted primary refractoriness/early relapse. Efforts to improve frontline strategies in PTCL should focus on identifying and exploiting biological vulnerabilities in such patients, and trials of intensified regimens/alternative platforms should prioritize evaluation of these patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen-Results of a Real-Life Study From a Middle-Income Country.

Nodal peripheral T-cell lymphoma (nPTCL) constitute a heterogeneous group of neoplasms with aggressive behavior and poor-survival. They are more prevalent in Latin America and Asia, although data from Brazil are scarce. Its primary therapy is still controversial and ineffective. Therefore, we aim to describe clinical-epidemiological characteristics, outcomes, predictors factors for survival and compare the results of patients treated with CHOP and CHOEP regimens. Retrospective, observational and single-center study involving 124 nPTCL patients from Brazil treated from 2000 to 2019. With a median follow-up of 23.7 months, the estimated 2-year overall survival (OS) and progression-free survival (PFS) were 59.2% and 37.3%, respectively. The median age was 48.5 years and 57.3% (71/124) were male, 81.5% (101/124) had B-symptoms, 88.7% (110/124) had advanced disease (stage III/IV) and 58.1% (72/124) presented International Prognostic Index (IPI) score ≥3, reflecting a real-life cohort. ORR to first-line therapy was 58.9%, 37.9% (N=47) received CHOP-21 and 35.5% (N=44) were treated with CHOEP-21; 30.1% (37/124) underwent to consolidation with involved field radiotherapy (IF-RT) and 32.3% (40/124) were consolidated with autologous hematopoietic stem cell transplantation (ASCT). The overall response rate (ORR) was similar for CHOP-21 (76.6%) and CHOEP-21 (65.9%), P=.259. Refractory disease was less frequent in the CHOEP-21 group (4.5% vs. 21.2%, P=.018). However, few patients were able to complete 6-cycles of CHOEP-21 (31.8%) than to CHOP-21 (61.7%), P=.003. Delays ≥2 weeks among the cycles of chemotherapy were more frequent for patients receiving CHOEP-21 (43.1% vs. 10.6%), P=.0004, as well as the toxicities, including G3-4 neutropenia (88% vs. 57%, P=.001), febrile neutropenia (70% vs. 38%, P=.003) and G3-4 thrombocytopenia (63% vs. 27%, P=.0007). The 2-year OS was higher for CHOP (78.7%) than CHOEP group (61.4%), P=.05, as well as 2-year PFS (69.7% vs. 25.0%, P < .0001). In multivariate analysis, high LDH (HR 3.38, P=.007) was associated with decreased OS. CR at first line (HR: 0.09, P < .001) and consolidation with ASCT (HR: 0.08, P=.015) were predictors of increased OS. In the largest cohort of nPTCL from Latin America, patients had poor survival and high rate of chemo-resistance. In our cohort, the addition of etoposide to the CHOP-21 backbone showed no survival benefit and was associated with high-toxicity and frequent treatment interruptions. Normal LDH values, obtaintion of CR and consolidation with ASCT were independent factors associated with better outcomes.

HIGH TUMOR MUTATION BURDEN IN EPIGENETIC REGULATORY GENES PREDICTS DECREASED OVERALL SURVIVAL IN NODAL PERIPHERAL T-CELL LYMPHOMAS

Nodal peripheral T-cell lymphomas (nPTCL) constitute a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena involving genes that control DNA-methylation and histone deacetylation, such as IDH2, DNMT3A, TET2 and RhoA , play a central role in their pathogenesis. Tumor mutation burden (TMB) has emerged as a prognostic biomarker in numerous solid neoplasms. Furthermore, TMB reflects the process of clonal evolution, with progressive acquisition of additional molecular-genetic abnormalities. Recent studies were capable to establish a relationship between TMB and response to anti-cancer treatments. In 2021 Fachi et cols. established a correlation between high TMB in epigenetic regulatory genes and higher response rates to 5-azacytidine and romidepsin in nPTCL. However, the potential prognostic impact of epigenetic TMB remains unknown in nPTCL. Based on this premise, here we aimed, in a pioneering way, to search for a correlation between epigenetic high TMB and adverse prognosis in nPTCL. This is a retrospective, observational and single-center study, involving 59 patients with nPTCL diagnosed and treated at the Department of Hematology, University of São Paulo, Brazil, from January 2000 to December 2019. FFPE diagnostic tumor samples were submitted to Sanger sequencing with a target-panel, involving IDH2, DNMT3A, TET2 and RhoA genes to search for recurrent mutations. The median age was 50 years (IqR 38-61), and 57.6% (34/59) were male. Thirty-nine percent (23/59) had bulky disease ≥ 7 cm, 83% (49/59) had B-symptoms, 94.9% (56/59) had advanced stage III/IV, 27.1% (16/59) had ECOG ≥ 2, 27.1% (16/59) had ≥ 2 extranodal sites involved by lymphoma, and 55.9% (33/59) had intermediate-high/high-risk IPI. Seventy-six percent (45/59) received up-front therapy with CHOP-like regimens (CHOP or CHOEP), 23.7% (14/59) experienced radiotherapy, and 33.3% (20/59) were consolidated with ASCT. With a median follow-up of 3.7 years (95% CI: 0.9-12.4), the estimated 2-year OS and PFS were 57.1% (95% CI: 45.5-70.4) and 49.2% (95% CI: 34.0-59.2), respectively. Missense, non-sense or frameshift mutations in the IDH2 gene were observed in 3.3% (2/59) of cases, DNMT3A in 3.3% (2/59), RhoA in 23.7% (14/59) and TET2 in 37.2% (22/59). Among the 59 patients included, 23/59 (38.9%) had no mutations in the target-genes, 25/59 (42.4%) had 1 mutation, and 11/59 (18.6%) had two or more mutations. Therefore, the cases were categorized into low TMB (< 2 mutations) [n = 48/59 – 81.3%] or high TMB (≥ 2 mutations) [n = 11/59 – 18.7%]. The median overall survival was 51.4 months (95% CI: 0-124.1) for low TMB and only 3.1 months (95% CI: 3.1-15.2) for high TMB, p = 0.08. The estimated 2-year OS was 64.3% (95% CI: 50.6-78.0) for low TMB and 36.4% (95% CI: 8.0-65.0) for high TMB. Similarly, median progression-free survival was 13.3 months (95% CI: 0-29.4) for low TMB and 6.3 months (95% CI: 0.9-11.6) for high TMB, p = 0.319. The estimated 2-year PFS was 46.1% (95% CI: 20.0-72.1) for low TMB and 25.0% (95% CI: 17.5-67.5) for high TMB. In a pioneering way, we demonstrated that the high epigenectic TMB, defined by the presence of 2 or more mutations involving epigenetic regulatory genes, was associated with decreased overall survival in Brazilian patients with nodal PTCL. Although preliminary, these data support the potential impact of epigenetic TMB as a prognostic biomarker in nPTCL.

Nodal cytotoxic peripheral T-cell lymphoma occurs frequently in the clinical setting of immunodysregulation and is associated with recurrent epigenetic alterations

AbstractNodal peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) with cytotoxic phenotype is overall rare, with most reports coming from Asia. Given its elusive pathobiology, we undertook a clinicopathological and molecular study of 54 Western patients diagnosed with PTCL, NOS expressing cytotoxic molecules, within a lymph node. More commonly males (M/F-2,6/1) with median age of 60 years were affected. Besides lymphadenopathy, 87% of patients had ≥1 involved extranodal site. High-stage disease (III-IV), International Prognostic Index >2, B symptoms, LDH level, and cytopenia(s) were observed in 92, 63, 67, 78, and 66% of cases, respectively. Ten patients had a history of B-cell malignancies, one each of myeloid neoplasm, breast or prostate cancer, and 4 others had underlying immune disorders. Most patients (70%) died, mostly of disease, with a median overall survival of 12.7 months. Immunophenotypically, the neoplastic lymphocytes were T-cell receptor (TCR) αβ + (47%), TCR-silent (44%) or TCRγδ+ (10%), commonly CD8 + (45%) or CD4-CD8- (32%). All except one had an activated cytotoxic profile, and 95% were subclassified into PTCL-TBX21 subtype based on CXCR3, TBX21, and GATA3 expression pattern. Seven patients (13%) disclosed EBER + tumor cells. Targeted DNA deep-sequencing (33 cases) and multiplex ligation-dependent reverse transcription-polymerase chain reaction assay (43 cases) identified frequent mutations in epigenetic modifiers (73%), including TET2 (61%) and DNMT3A (39%), recurrent alterations affecting the TCR (36%) and JAK/STAT (24%) signaling pathways and TP53 mutations (18%). Fusion transcripts involving VAV1 were identified in 6/43 patients (14%). Patients with nodal cytotoxic PTCL, NOS have an aggressive behavior and frequently present in a background of impaired immunity, although the association with Epstein-Barr virus is rare. The recurrent alterations in genes involved in DNA methylation together with genes related to cytokine or TCR signaling, suggest that co-operation of epigenetic modulation with cell-signaling pathways plays a critical role in the pathogeny of these lymphomas.

Comprehensive comparison of international prognostic indexes for follicular helper T-cell lymphoma.

In 2016, World Health Organization classification of lymphoid neoplasms separated firmly-follicular helper (Tfh) cell origin lymphomas from peripheral T-cell lymphoma-not specified (PTCL-NOS) based on their unique immunogenic characteristics. Generally, Tfh cell origin lymphoma, which has an approximately 25% incidence, is classified into three categories: angioimmunoblastic T-cell lymphoma (AITL), follicular peripheral T-cell lymphoma (F-PTCL), and nodal peripheral T-cell lymphoma with a T-follicular helper phenotype (nodal PTCL with Tfh cell phenotype). Their prognosis has been estimated using four traditional prognostic tools for T-cell lymphoid malignancies: the international prognostic index (IPI), the prognostic index for peripheral T-cell lymphoma unspecified (PIT), the modified PIT (mPIT) and the international T-cell lymphoma project index. In addition, the AITL score that reflects AITL characteristics well has been introduced recently. However, there are no clear guidelines for evaluating the prognosis of Tfh cell lymphoma. Thus, we performed a comparative analysis to determine which of these five indexes is most suitable for Tfh cell lymphoma. We evaluated the accuracy of classification according to risk score and predicted survival rate. Based on review by lymphoma pathology experts, we enrolled 198 patients diagnosed with Tfh cell lymphoma in this retrospective study. AITL was the most common subtype (n = 168), followed by F-PTCL (n = 21) and nodal PTCL with Tfh cell phenotype (n = 9). The median progression-free survival and overall survival with front-line treatment was 0.8years (95% confidence interval [CI], 0.6-1.1years) and 2.9years (95% CI, 1.6-4.2years), respectively. The AITL score showed better differentiation than other scoring systems in terms of classification according to risk score. However, for predicting PFS (concordance-index [C-index], IPI vs. PIT vs. modified PIT vs. international T-cell lymphoma project index vs. AITL score; 0.617 vs. 0.605 vs. 0.576 vs. 0.591 vs. 0.592) and OS (C-index, IPI vs. PIT vs. modified PIT vs. international T-cell lymphoma project index vs. AITL score; 0.663 vs. 0.651 vs. 0.612 vs. 0.672 vs. 0.583), the IPI, and the international T-cell lymphoma project index showed better performance. In conclusion, there are unmet needs to develop a prognostic index for Tfh cell lymphoma because its characteristics differ from PTCL-NOS. Although the AITL score reflects Tfh cell-origin lymphoma characteristics well and clearly shows their power of classification according to risk score, there are concerns about accurate prediction of survival outcomes. Therefore, it seems too early to settle on a single scoring system in Tfh cell origin lymphoma. In the future, along with classification, a more effective tool for survival prediction needs to be developed that reflects the specific characteristics of T-cell lymphoma.

Rhoa Mutation Is a Potential Biomarker Associated with Adverse Prognosis and High- Tumor Burden in Patients with Nodal Peripheral Lymphomas with T-Helper Follicular Phenotype (nPTCL-Thf): Data from a Brazilian Retrospective Cohort of Nodal PTCL

Introduction: Nodal PTCL constitute a rare group of aggressive malignancies with heterogeneous clinical-biological presentation and outcomes. In the last decade, its pathophysiological knowledge has been improved, with descriptions of gene mutations associated with epigenetic phenomena (IDH2, TET2 and DNMT3A) and of the RHOA G17V mutation playing a fundamental role in the lymphomagenesis. However, the prognostic impact of these alterations is still controversial, and particularly, in the case of the RHOA mutation, it has never been previously accessed in the literature. Our group has described and validated biomarkers with potential prognostic impact in nPTCL patients, including overexpression of the genes CCNA2, GATA3 and monocytosis in peripheral blood [1,2,3]. The identification of new potential molecular biomarkers can refine the prognostic stratification of these tumors and allow identification of targets for future specific therapies. The aim of this study was to evaluate the frequency and prognostic impact of mutations in the IDH2, TET2, DNMT3 and RHOA genes in Brazilian patients with nPTCL.Methods: In this observational, retrospective and unicentric study, we analyzed the clinical-epidemiological characteristics, outcomes and mutational profile of 59 Brazilian patients with nPTCL treated at the HC-FMUSP, from January 2000 to December 2017. All cases were submitted to centralized histopathological review and were classified according to the criteria proposed by WHO-2008. Cases initially categorized as PTCL/NOS were later reclassified according to WHO-2016 criteria. FFPE-tumor samples from patients with PTCL/NOS, AITL, ALK+/ALCL and ALK-/ALCL were submitted to DNA extraction using QIAmp DNA FFPE kit. For amplification of specific products of target-genes primers flanking the hot spots regions were designed. After this step, the PCR products were submitted to first generation sequencing in 3500 Genetic Analyzer. Absolute and relative frequencies of mutations were accessed for the total cohort and its pathological subtypes. OS and PFS curves were constructed using the Kaplan-Meier method. Log-rank test was used to estimate the prognostic impact of mutations.Results: The clinical-epidemiological characteristics of the 59 Brazilian-patients with nPTCL are summarized in Table 1. With a median follow-up of 3.70 years (0.90-12.4 years), the estimated 2-years OS and PFS were 59.1% and 47.2%, respectively. ORR was 55.9% (33/59), with early relapse rate (< 12 months) of 14.3% (5/59) and global death rate of 52.5% (31/59). In the total cohort, we found a mutation frequency of 3.4% (2/59) for the IDH2 gene, 62.7% (37/59) for DNMT3A, 23.7% (14/59) for RHOA and 50.8% (30/59) for TET2. There was no statistically significant difference in the frequency distribution of IDH2, DNMT3A and TET2 mutations between the different histological subtypes of nPTCL. However, there was a statistical trend towards a higher occurrence of the RHOA mutation in the AITL and PTCL/NOS subtypes (3/9-33.3% and 7/16-43.7%, respectively; p=0.07). Among 7 cases with RHOA mutation classified as PTCL/NOS according WHO-2008 criteria, 6/7 (85.7%) expressed the PD-1 marker in immunohistochemistry, being reclassified as nPTCL with THf phenotype according to WHO-2016 criteria. So, the mutation RHOA was predominantly found in THf cell-derived neoplasms in our cohort. The mutational status of DNMT3A, RHOA and TET2 genes had no prognostic impact on OS, with p=0.85, p=0.13 and p=0.95, respectively. The same was observed in relation to PFS for the DNMT3A (p=0.70) and TET2 (p=0.52) mutations. However, the presence of the RHOA mutation was associated with the unfavorable PFS in our cohort (HR:1.98, p=0.05). We observed 2-year PFS of 28.6% (95% CI: 8.8-52.4%) for mutated-RHOA cases versus 52.9% (95% CI: 37.3-66.3%) for wild-type-RHOA patients (p=0.05) [Figure 1]. We also demonstrated that RHOA mutation was a predictor of lower ORR to first-line therapy (p=0.01) and was associated with high tumor burden (p=0.03) [Figure 2].Conclusion: In this study, for the first time was demonstrated the unfavorable prognostic impact of the RHOA mutation in patients with nPTCL-Thf (AITL and nPTCL-THf), making it a potential molecular biomarker predictor of poor-PFS, associated with resistance to primary therapy and with high tumor burden. Such results are preliminary and will need to be validated in series with a larger number of cases. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

High Toxicity and Poor Survival with Association CHOP Plus Etoposide Compared to CHOP Regimen in 124 Brazilian Patients with Nodal PTCL Lymphomas (nPTCL): A Real-Life Experience

Introduction: Nodal PTCL constitute a heterogeneous group of rare malignancies derived from CD4+ T-helper, CD8+ T-cytotoxic or follicular T-helper lymphocytes. It presents aggressive clinical-biological behavior and distinct outcomes [1]. These tumors have significant geographic variation, making important studies of clinical and epidemiological characteristics and outcomes of patients in specific areas of the word. Latin American data on nPTCL are scarce in the literature [2] and its first-line treatment is still controversial and ineffective, due to high rates of primary chemo-resistance. Therefore, this study aims to describe clinical, laboratory and epidemiological characteristics, identify prognostic factors and analyze the outcomes of patients with nPTCL treated with CHOP/CHOP-like regimens as first-line therapy in Brazil.Methods: This is a retrospective, observational and unicentric study involving 124-Brazilian patients with nPTCL treated at HC/FMUSP from January 2000 to December 2017. All cases were submitted to centralized histopathological review and classified according to WHO-2016 criteria on PTCL/NOS, AITL, ALK+/ALCL or ALK-/ALCL. Clinical-laboratory and outcomes data were obtained from digital medical records. Descriptive variables were arranged in absolute numbers and relative frequencies. OS and PFS curves were estimated by the Kaplan-Meier method. Univariate Cox analysis was used to determine factors with prognostic impact through the association between categorical variables and survival curves. Variables that were significant in the univariate analysis were tested in a multivariate analysis to establish independent variables. Statistical analysis was performed using SPSS V.22 software and p-values ≤ 0.05 were considered statistically significant.Results: The clinical-laboratory characteristics of 124 nPTCL patients were summarized in Table 1. With a median age of 48.5 years (18-87 years) and 57.3% of male, about 81.5% had B-symptoms, 88.7% with CS III/IV and 58.1% had IPI ≥ 3. ORR to first-line treatment was 58.9%, 37.9% (47/124) were treated with CHOP regimen and 35.5% (44/124) with CHOEP, 30.1% (37/124) were submitted to radiotherapy and 32.3% (40/124) were consolidated with ASCT. We observed a higher 2-year OS for patients treated with CHOP versus CHOEP (78.7% vs. 61.4%; p=0.05), as well as a better 2-year PFS for the same regimen (69.7% vs. 25.0%; p<0.0001) - Figure 1. CHOEP treatment was associated with higher rates of G3-4 neutropenia, febrile neutropenia and G3-4 thrombocytopenia (57% x 88% p=0.001, 38% x 70% p=0.003 and 27% x 63% p=0.0007, respectively). Overall mortality was 55.6% (69/124) during all follow-up, with disease progression being the major cause of death (29/69 - 42.0%). With a median follow-up of 23.7 months (0.10-278.6 months), medians of OS and PFS were 48.0 months (95% CI: 9.0-86.9) and 8.8 months (95% CI: 3.9-13.7), respectively. Estimative of 2-year OS and PFS for the global cohort were 61.3% and 41.5%, respectively. In the univariate analysis, factors with a favorable prognostic impact on OS were: IPI < 3 (HR: 0.30; 95% CI: 0.15-0.58; p<0.0001), absence of bone marrow infiltration (HR: 0.39; 95% CI: 0.20-0.75; p=0.005), LDH < 480 U/L (HR: 0.36; 95% CI: 0.19-0.68; p=0.002), radiotherapy (HR: 0.23; 95% CI: 0.10-0.55; p=0.001) and ASCT (HR: 0.28; 95% CI: 0.004-0.30; p<0.0001). Factors associated with better 2-year PFS were: IPI < 3 (HR: 0.36; 95% CI: 0.18-0.71, p=0.004), absence of bone marrow infiltration (HR: 0.30; 95% CI: 0.26-0.55; p=0.03 ), LDH < 480 U/L (HR: 0.36; 95% CI: 0.19-0.67; p=0.001), radiotherapy (HR: 0.17; 95% CI: 0.06-0.44; p<0.0001) and ASCT (HR: 0.03 ; 95% CI: 0.004-0.23); p=0.001). In the multivariate analysis, factors associated with better 2-year OS were: LDH < 480 U/L (HR: 0.40; 95% CI: 0.21-0.76); p=0.005) and ASCT (HR: 0.47; 95% CI: 0.006-0.34; p=0.003). LDH < 480 U/L (HR: 0.45; 95% CI: 0.23-0.87; p=0.01) and ASCT (HR: 0.07; 95% CI: 0.01-0.54; p=0.01) were also associated with higher 2-year PFS.Conclusion: This is the largest real-life Latin American nPTCL cohort published to date. Patients with nPTCL have poor survival and high rate of chemo-resistance. In our cohort, adding etoposide to the CHOP regimen showed no survival benefit and was associated with high toxicity. Normal values of LDH and consolidation with ASCT were independent factors associated with better outcomes in Brazilian patients with nPTCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Peripheral T-cell lymphoma: molecular profiling recognizes subclasses and identifies prognostic markers

AbstractPeripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of approximately 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform (NanoString Technologies, Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways, and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH] phenotype; PTCL not otherwise specified [NOS]) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers, and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells, and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH, and PTCL-NOS. The main differences among the 3 nodal PTCL classes involved the RHOAG17V mutations (P < .0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these 3 categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL.

Acute Epstein‐Barr virus associated haemophagocytosis in an Asian female: What is the diagnosis?

Acute <scp>Epstein‐Barr</scp> virus associated haemophagocytosis in an Asian female: What is the diagnosis?

Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas

BackgroundThe 2016 World Health Organization (WHO) classification introduced nodal lymphomas of T follicular helper (Tfh) cell origin, such as angioimmunoblastic T-cell lymphoma (AITL), follicular peripheral T-cell lymphoma (F-PTCL), and nodal peripheral T-cell lymphoma with T follicular helper phenotype (nodal PTCL with TFH phenotype). However, the accurate incidence rate and clinical characteristics of F-PTCL and nodal PTCL with TFH are unstudied.MethodsBetween February 2012 to June 2020, a total of 207 cases diagnosed with nodal lymphomas of T follicular helper (Tfh) cell origin and PTCL-NOS were reviewed for clinical and histopathologic data. PTCL-NOS was defined to not correlate to any of the specific entities of mature T cell lymphoma in the WHO 2016 classification. We attempted to classify PTCL-GATA3 and PTCL-TBX21 by IHC staining. Target gene analysis was performed on a few patients with sufficient blood and tissue samples additionally.ResultsAmong 207 patients, 111 patients (53.6%) had AITL, 67 patients (32.4%) had PTCL-NOS, 19 patients (9.2%) had F-PTCL, and 10 patients (4.8%) had nodal PTCL with TFH phenotype. We re-defined and analyzed F-PTCL and nodal PTCL with TFH phenotype into other TFH lymphomas. AITL (N = 101/111, 91.0%) was found to have a higher frequency of stage III/IV cancers compared to other TFH lymphomas (N = 22/29, 75.0%) and PTCL-NOS (N = 53/67, 79.1%; p-value = 0.03). The OS of AITL and other TFH lymphomas was similarly superior to PTCL-NOS (p-value = 0.02). AITL and other TFH lymphomas showed the TBX21 subtype more commonly than the GATA3 subtype. Mutations related to the RAS family (RHOA) and those related to epigenetic regulators (IDH2, DNMT3A, and TET2) were shown mainly in AITL and other TFH lymphomas.ConclusionsOther TFH lymphomas appear to be a rare disease entity around one-quarter in nodal lymphomas of T follicular helper (Tfh) cell origin. Their less aggressive clinical feature than we did not expect is utterly different from PTCL-NOS and AITL. On the other hand, other TFH lymphomas share some characteristics, such as the cell of origin, a more common TBX21 subtype, and genetic variation such as RAS family mutation and epigenetic regulators, with AITL.

Multi-Center Phase II Study of Oral Azacitidine (CC-486) Plus CHOP As Initial Treatment for Peripheral T-Cell Lymphoma (PTCL)

Multi-Center Phase II Study of Oral Azacitidine (CC-486) Plus CHOP As Initial Treatment for Peripheral T-Cell Lymphoma (PTCL)

CDKN2A deletion is a frequent event associated with poor outcome in patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS).

Nodal peripheral T-cell lymphoma not otherwise specified (PTCLNOS) remains a diagnosis encompassing a heterogenous group of PTCL cases not fitting criteria for more homogeneous subtypes. They are characterized by a poor clinical outcome when treated with anthracycline-containing regimens. A better understanding of their biology could improve prognostic stratification and foster the development of novel therapeutic approaches. Recent targeted and whole exome sequencing studies have shown recurrent copy number abnormalities (CNA) with prognostic significance. Here, investigating five formalinfixed, paraffin embedded cases of PTCL-NOS by whole genome sequencing, we found a high prevalence of structural variants and complex events, such as chromothripsis likely responsible for the observed CNA. Among them, CDKN2A and PTEN deletions emerged as the most frequent aberration, as confirmed in a final cohort of 143 patients with nodal PTCL. The incidence of CDKN2A and PTEN deletions among PTCL-NOS was 46% and 26%, respectively. Furthermore, we found that co-occurrence of CDKN2A and PTEN deletions is an event associated with PTCLNOS with absolute specificity. In contrast, these deletions are rare and never co-occur in angioimmunoblastic and anaplastic lymphomas. CDKN2A deletion was associated with shorter overall survival in multivariate analysis corrected by age, International Prognostic Index, transplant eligibility and GATA3 expression (adjusted Hazard Ratio =2.53; 95% Confidence Interval: 1.006-6.3; P=0.048). These data suggest that CDKN2A deletions may be relevant for refining the prognosis of PTCLNOS and their significance should be evaluated in prospective trials.

CLINICOPATHOLOGICAL DIFFERENCES OF NODAL PTCL WITH TFH PHENOTYPE FROM AITL AND PTCL, NOS, AND DETECTION OF PROGNOSTIC MARKER OF NODAL PTCL WITH TFH PHENOTYPE

CLINICOPATHOLOGICAL DIFFERENCES OF NODAL PTCL WITH TFH PHENOTYPE FROM AITL AND PTCL, NOS, AND DETECTION OF PROGNOSTIC MARKER OF NODAL PTCL WITH TFH PHENOTYPE

Epidemiology and Pathology of T- and NK-Cell Lymphomas.

This review will describe and update readers on the recent changes in the 2017 WHO classification regarding peripheral T-cell lymphomas. Signficant advances in molecular studies have resulted in revisions to the classification as well as introduction to provisional entities such as breast implant-associated ALCL and nodal PTCL with T-follicular helper phenotype. Major advances in molecular and gene expression profiling has expanded our knowledge of these rare and aggressive diseases.

Peripheral T-Cell Lymphomas in Spain: Profiling Clinical, Phenotypic and Genetic Characteristics in Spanish Population

PurposeThe objective of this study was to investigate clinicopathologic features and prognostic factors of patients diagnosed with PTCL in 13 sites across Spain.Patients and MethodsA multicenter, retrospective study was carried out between September 2015-November 2017.Medical charts of patients diagnosed with PTCLs between January 2008 and December 2013 that have signed the approved informed consent form were reviewed. PTCLs were then classified according to the 2016 revision of the WHO classification of lymphoid neoplasms. Clinical characteristics,history, standard immunohistochemistry (IHC) data, International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (TCL) (PIT) were also assessed. Medians (range), mean (standard deviation) and frequency as the number of patients (n) and percentages (%) with confidence intervals at 95% (CI95%) were calculated. Overall Survival (OS) and Progression Free Survival (PFS) were analyzed using the Kaplan Meier method.Results175 (88.4%) patients were successfully analyzed, the male/female ratio was 1.7:1.0, and the median age was 67.2 years (range: 24.8 years -95.8 years). ECOG performance status >1 was reported for 31.9% patients. Ann Arbor stages were III and IV 27.4% and 45.7%, respectively, and LDH levels were elevated to 92 patients (52.6%). Those with B symptoms accounted for 39.4%, while soft tissue was the most frequent location (23,7%) among the 76 patient with extranodal disease; bone marrow infiltration was confirmed in 18.3% patients.Relevant clinical antecedents related to immunological aspects were also frequently reported, including previous neoplasia (18.9%), autoimmune disease (16%), immunosuppressive treatments (7.3%) and previous viral diseases (HIV, HBV or HCV, 5.7%, 4.6% and 7.4%, respectively).Most patients presented with angioimmunoblastic TCL (31.4%); similar proportions of patients were observed among nodal PTCL with TFH phenotype (13.1%, PTCL not otherwise specified (12.0%) and extranodal NK/TCL nasal type (11.4%). CD30 expression and staining pattern (ranged 1-4) allowed the stratification of patients according CD30 intensity (n= 121; weak: 35, moderate: 57, and intense: 29); Patients were also classified based on CD30 expression considering the median value of quantitative CD30 in our sample (15%) the cut-off point: n=132; Negative <15%: 64; Positive, ≥15%: 68).First-line treatment with a CHOP/CHOP-like regimen was the most common finding (69.7%). Best response was observed after a median of 4 months since the start of first-line treatment (range 0.0 months - 65.2 months). Overall response rate after first-line treatment was 66.9%, with 61/151 patients reaching complete response (CR).Median PFS (n=157) and OS (n=175) of this series were 7.87 months (CI95%: 4.98 months-10.75months) and 15.77 months (CI95%: 10.23 months -21.30 months), respectively. Overall, IPI and PIT scores influenced the PFS and OS (p<0.001). A higher number of adverse factors was associated with a shorter survival.Reaching a CR was associated with a better PFS (CR: 62.6m; CI95%: 20.2 months -105.1 months) than the rest of patients (3.97m: CI95%: 3.08 months -4.85m; p<0.001). Response was also associated with OS; patients with CR showed an average OS of 67.01 months (CI95%: 58.2 months -75.9 months) that were significantly longer than that of patients with No-CR (median: 7.34 months; CI95%: 5.85 months -8.83 months; p<0.001).ConclusionThis is the largest series of T cell Lymphoma reported in Spain and has allowed the description of distribution of PTCL subtypes, analyzed through central hematopathologists reanalysis and reclassification of samples from 175 PTCL patients, according to the WHO 2016 classification of lymphoid neoplasms.Our data confirm the poor prognosis of these patients, as well as the impact of prognostic indexes and the response to first line treatment on their outcome. DisclosuresRodriguez-Pinilla:Takeda: Honoraria. Piris:Takeda: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Kura: Honoraria. Ruiz-Zorrilla:Takeda: Employment. Montoto:Takeda: Employment.

Updates of Peripheral T Cell Lymphomas Based on the 2017 WHO Classification

This review will describe and update the readers on the recent changes of the 2017 WHO classification in regard to peripheral T cell lymphomas. Significant advances in molecular studies have resulted in revisions of the classification as well as introduction of provisional entities (such as breast implant-associated ALCL, nodal PTCL with TFH phenotype). Major advances in molecular and gene expression profiling have expanded our knowledge of T cell lymphomas, including updates in the diagnostic criteria and sub-classification which will facilitate in improving patient care and research.