Hepatosplenic T-cell Lymphoma Research Articles

Molecular features of non-anaplastic peripheral T-cell lymphoma in children and adolescents.

Non-anaplasticperipheral T-cell lymphomas (PTCL) are rare tumors in children, adolescents, and young adults (CAYA) with poor prognosis and scarce genetic data. We analyzed lymphoma tissue from 36 patients up to 18years old with PTCL, not otherwise specified (PTCL-NOS), hepatosplenic T-cell lymphoma, Epstein-Barr virus (EBV)-positive T-lymphoproliferative diseases, subcutaneous panniculitis-like T-cell lymphoma, and other PTCL types. Twenty-three patients (64%) had at least one genetic variant detectable, including TET2, KMT2C, PIK3D, and DMNT3A. TP53 and RHOA variants, commonly found in adults, were not identified. Eight of 20 (40%) CAYA PTCL-NOS had no detectable mutations. The genetic findings suggest that CAYA PTCL differ from adult cases.

Gamma/Delta (γδ) T Cells: The Role of the T-Cell Receptor in Diagnosis and Prognosis of Hematologic Malignancies.

There are 2 types of T cells: αβ and γδ T cells, named based on the composition of the T-cell receptor. γδ T cells are rare, making up 0.5%-10% of T cells. Although most leukemias, lymphomas, and immune-mediated conditions derive from αβ T cells, a handful of rare but important diseases are generally derived from γδ T cells, particularly primary cutaneous γδ T-cell lymphoma, hepatosplenic T-cell lymphoma, and monomorphic epitheliotropic intestinal T-cell lymphoma. There are also malignancies that may evince a γδ TCR phenotype, including large granulocytic lymphocyte leukemia, T-cell acute lymphobplastic leukemia (T-ALL), and mycosis fungoides, although such cases are rare. In this article, we will review the genesis of the T-cell receptor, the role of γδ T cells, and the importance of TCR type and methods of detection and outline the evidence for prognostic significance (or lack thereof) in lymphomas of γδ T cells. We will also highlight conditions that rarely may present with a γδ TCR phenotype and assess the utility of testing for TCR type in these diseases.

γδ TCR T lymphoblastic leukemia in a child presenting with marked hyperleukocytosis.

γδ TCR T lymphoblastic leukemia is rare in children and should be differentiated mainly from hepatosplenic T‐cell lymphoma in this age group.

Outcomes in Patients with Enteropathy-Associated T-Cell Lymphoma (EATL) and Hepatosplenic T-Cell Lymphoma (HSTCL): A Population Based Analysis Using the SEER Data

Introduction and AimHepatosplenic T-cell lymphoma (HSTCL) and Enteropathy-associated T-cell Lymphoma (EATL) are rare aggressive peripheral T-cell lymphomas with dismal outcomes. Due to their rarity there is paucity of data on disease epidemiology and survival outcomes. We analyzed these rare diseases using Surveillance, Epidemiology and End Results (SEER) data to identify patient and disease factors that impact survival.MethodsUsing the SEER data, cases of HSTCL and EATL diagnosed between 1996 and 2014 were identified based on the ICD-O3 codes 9716 and 9717, respectively. Proportions were compared using chi-squared tests. Multivariable Cox proportional hazards models and stepwise regression were used to analyze disease-specific overall survival. Computations were performed in R.ResultsWe identified 122 patients with HSTCL and 163 with EATL; both had male predominance with 69% in HSTCL and 58% in EATL (p=0.07). Median age was 38 years (range 4-83) in HSTCL and 64 years (range 23-96) in EATL patients. The HSTCL group was much younger with 79% aged <55 years compared to only 26% in the EATL group (P=<0.0001) (Table 1). Although both groups were primarily Caucasian - 61% in HSTCL and 77% in EATL, 27% of HSTCL patients were of African American race. While the majority of the HSTCL (53%) were diagnosed in 2008-2014, 55% of EATL pts were diagnosed in 1996-2008. Disease characteristics also differed between these entities with HSTCL mostly being advanced stage (81%) and EATL largely early stage (58%) at diagnosis; 79% of HSTCL patients had stage IV compared to only 31% in EATL (p<0.0001). Treatments in HSTCL pts included chemotherapy (83%) surgery (43%) radiation therapy (10%). On the contrary, surgery (70%) was the most common treatment in EATL followed by chemotherapy (55%) and radiation therapy (3%). Median OS for EATL and HSTCL were 9 (95% CI 715) and 5 months (95% CI 37), respectively (log-rank P= 0.0018 (Figure 1A). In univariate analysis, surgery (HR: 0.62, 95% CI: 0.39-0.96, p=0.032), and radiation therapy (HR: 0.3, 95% CI: 0.16-0.96, p=0.042) was associated with superior OS, while there was increased risk of mortality with advanced age (HR: 1.6, 95% CI: 1.01-2.79, p=0.043) in HSTCL patients. Sex, race, marital status, year of diagnosis, use of chemotherapy and stage failed to predict survival in HSTCL. However, in EATL advanced stage (HR: 1.48, 95% CI: 0.99-2.20, p=.052) was associated with inferior OS and use of chemotherapy (HR: 0.46, 95% CI: 0.31-0.67, p=.0001) was a positive predictor for OS. On stepwise regression analysis, surgery (HR 0.57; p=0.014) and radiation therapy (HR 0.33; p= 0.019) were associated with improved survival in patients with HSTCL, whereas in EATL patients receiving chemotherapy improved survival (HR 0.42; p<0.001) (Figure 1B) and advanced stage correlated with reduced survival (HR 1.60; p=0.01).ConclusionTo our knowledge, this is the first and largest United States population based study of patients diagnosed with HSTCL and EATL. Our analysis showed that HSTCL is commonly diagnosed in younger, males with increased incidence in African American population compared to EATL. Although surgical interventions were commonly used in both entities, it was more frequent in EATL. While surgery and radiation improved survival in HSTL, chemotherapy was the significant factor in EATL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Successful Treatment of Mature T-Cell Lymphoma with Allogeneic Stem Cell Transplantation: The Largest Multicenter Retrospective Analysis

Successful Treatment of Mature T-Cell Lymphoma with Allogeneic Stem Cell Transplantation: The Largest Multicenter Retrospective Analysis

P358 An observational, prospective cohort study to evaluate the long term safety and effectiveness of intravenous CT-P13 (biosimilar of infliximab) in patients with Crohn’s Disease or Ulcerative Colitis

Abstract Background CT-P13 is the world’s first approved biosimilar infliximab for all indications of the reference infliximab. The purpose of this study was to assess long term safety and effectiveness of CT-P13 intravenous (IV) in patients with Crohn’s Disease (CD) and Ulcerative Colitis (UC). We now present the result of safety and effectiveness of CT-P13 in patient with CD, UC for up to 5 years from this longitudinal, observational, prospective cohort Phase IV study. Methods The study was conducted from 17 April 2014 to 28 February 2020 in 22 and 21 study centres, in Korea and European Union, respectively. Patients were administered 5 mg/kg of CT-P13 by IV at weeks 0, 2 and 6 and every 8 weeks thereafter. The primary objective was to evaluate adverse events of special interest (AESI) including HBV reactivation, congestive heart failure, opportunistic infections, serious infection including sepsis, tuberculosis, serum sickness (delayed hypersensitivity reactions), hematologic reactions, systemic lupus erythematosus/lupus like syndrome, demyelinating disorders, lymphoma, hepatobiliary events, hepatosplenic T cell lymphoma (HSTCL), intestinal or perianal abscess (in CD), serious infusion reactions during a re-induction regimen following disease flare, sarcoidosis/sarcoid-like reactions, paediatric malignancy, leukaemia, malignancy, colon carcinoma, dysplasia (in UC), skin cancer, pregnancy exposure and bowel stenosis, stricture and obstruction (in CD). Results A total of 470 patients with inflammatory bowel disease (IBD) were analysed. Overall 352 (74.9%) patients have been continuously treated for more than 1 year and the mean duration of drug exposure was 26.3 months. The safety profile of CT-P13 and switching from the reference infliximab to CT-P13 was well-tolerated. A total of 329 (70.0%) patients experienced at least one treatment-emergent adverse event (TEAE). Adverse events of special interest of CT-P13 were analysed by safety analysis set (Table 1). Immunogenicity testing was optional and 72 (15.3%) patients had at least one ADA positive after first infusion of study drug. The incidence of TEAEs in ADA positive subset (83.3%) were slightly higher compared to the incidence of TEAEs in ADA negative subset (76.6%). The effectiveness results of clinical remission for each indication was generally well maintained after the study drug administration (Table 2). Conclusion The results show that CT-P13 was well-tolerated and efficacious in IBD patients. There was no new safety and effectiveness findings in patients who have been exposed to CT-P13 or patients who have switched treatment from the reference infliximab to CT-P13.

CD94 expression patterns in reactive and neoplastic T-cell and NK-cell proliferations

Lymphomas and leukemias of T-cell and NK-cell lineages are highly heterogeneous disorders and lack effective therapeutic strategies. Targeted therapies including anti-CD94 agents are currently under clinical investigation, but studies of CD94 expression on mature T/NK-cell neoplasms are limited. In this study, we investigated the landscape of CD94 protein expression in 15 patients with reactive T/NK-cell proliferations and 124 patients with various T/NK cell neoplasms. CD94 expression was detected at a high level in reactive NK-cells, with a lower level of expression in a subset of reactive CD8 + T-cells; reactive CD4 + T-cells were negative for CD94 expression. All NK-cell neoplasms surveyed had high-level CD94 expression, which was significantly higher than that in T cell neoplasms (p = 0.0174). In neoplastic T-cell proliferations, CD94 expression was positive in all 10 hepatosplenic T-cell lymphoma cases tested, with a high mean fluorescence intensity. Fifty-six percent of T-cell large granular lymphocytic leukemia cases were positive for CD94 expression in a subset of neoplastic cells. All T-cell prolymphocytic leukemia and 97 % of peripheral T-cell lymphoma cases showed no CD94 expression. Our findings demonstrate a broad range of CD94 expression among T/NK-cell neoplasms, in some at levels that suggest therapeutic vulnerability to CD94-targeted therapies.

Hypercalcaemia: An Extremely Rare Presentation of Hepatosplenic T-Cell Lymphoma.

Hepatosplenic T-cell lymphoma (HSTCL) is difficult to diagnose, has a poor prognosis and usually presents with hepatosplenomegaly, B symptoms and cytopenias.Hypercalcaemia is an extremely rare clinical presentation of HSTCL.Severe hypercalcaemia is a life-threatening condition and should always be corrected and investigated.

Identification of Key Genes and Pathways Associated with Hepatosplenic T-Cell Lymphoma (HSTCL) by Bioinformatics Analysis.

Prognosis of Hepatosplenic T-Cell Lymphoma (HSTCL) is very poor, while the molecular mechanism of this disease has rarely been investigated and remains mysterious. The aim of the study is to screen differentially expressed genes (DEGs) of patients with HSTCL and normal controls, explore the pathogenesis, and provide guidance for the gene diagnosis and precise treatment of HSTCL. The genetic chip data GSE57520 of HSTCL was searched from the GEO database, and the quality control and DEGs screening were performed through BART online tools. In addition, FunRich software was used to perform gene enrichment and pathway analysis on the screened DEGs. Subsequently protein interaction network (PPI) was constructed via the STRING database and analyzed using the visual module of Cytoscape software. A total of 4,759 DEGs were obtained, including 2,501 up-regulated genes and 2,258 down-regulated genes (p < 0.05). The analysis of gene ontology (GO) showed that DEGs in cytology component (CC) mainly involved cytoplasm, nucleus, plasma membrane, Golgi apparatus, lysosome, and endoplasmic reticulum. Besides, DEGs in molecular function (MF) mainly included transcription factor activity, catalytic activity, transporter activity, transcription regulator activity, receptor signaling pathway complex, receptor activity. Moreover, DEGs in biological processes (BP) are mainly involved in base regulation, transport, energy pathways, metabolism, protein metabolism, and apoptosis. The results of the Kyoto Gene and Genome Encyclopedia (KEGG) analysis showed that the DEGs mainly include TRAIL, Beta1 integrin, integrin family, proteoglycan, S1P, and ErbB. Combined with Cytoscape software cytoHubba plug-in, protein interaction network (PPI) analysis showed that KIF20A, DLGAP5, PBK, TOP2A, ASPM, NEK2, KIF14, and DEPDC1B were the most abundant core genes. Module analysis showed that the three gene modules with the highest scores were mainly related to mitosis, epithelial cell adhesion and signal transduction, and the process of DNA damage. The DEGs of HSTCL patients versus healthy control groups were obtained through a variety of bioinformatics methods. KIF20A and DLGAP5 may become potential therapeutic targets for HSTCL. Also, the most abundant signaling pathway in DEGs was the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) - related pathway. Besides, related genes and expression characteristics of HSTCL pathogenesis were reanalyzed from distinctive perspectives, which might provide specific diagnostic markers and targeted therapy for HSTCL.

Risk of Cancer in Pediatric-Onset Inflammatory Bowel Diseases: A Nation-Wide Study from the Epi-Iirn

Background: Pediatric-onset IBD (PIBD) is characterized by a more extensive phenotype than adults and a higher utilization of immunosuppressive medications; both may be associated with malignancy. We aimed to assess the risk of cancer in a nationwide cohort of PIBD and to explore the risks associated with medical treatments. Methods: PIBD cases were included from the epi-IIRN cohort , covering 98% of the Israeli population from 2005, linked to the national cancer registry. We matched PIBD cases to non-IBD children for calculating the cumulative incidence of cancer. Finding: 3,944 PIBD cases were included (2,642 [67%] Crohn's disease, 1,302 [33%] ulcerative colitis) translating into 23,635 person-years of follow-up , individually matched to 13,005 non-IBD children. By 30 years of age, 14 IBD patients (0.35%, 5.9/10,000 patient-years) were diagnosed with cancer and one (0.03%) with haemophagocytic-lymphohistiocytosis (HLH), compared with 14 (0.11%, 1.9/10,000 patient-years) cases of cancer (OR 2.5 [95%CI 1.05-6.2]; p=0.04) and no HLH in the comparison-group. There were no cases of hepatosplenic T-cell lymphoma, adenocarcinoma or cholangiocarcinoma. Cancer risk was 15.6 cases/10,000 person-years in those treated with thiopurines alone (OR compared with those never exposed to either thiopurines or anti-tumor necrosis factor (TNF) 1.8 (95%CI 0.6-6.1); p=0.2), 11.1/10,000 in those treated with anti-TNF alone (OR 1.3 [95%CI 0.3-6.6]; p=0.5), and 23.1/10,000 treated with combination therapy of anti-TNF and thiopurines (OR 2.8 [95%CI 0.6-13.8]; p=0.2). Interpretation: PIBD confers an increased risk for malignancy compared with non-IBD children. The risk was not statistically associated with treatment, likely since the absolute risk was very low. Funding Statement: None to declare. Declaration of Interests: ID- Has received consultation fee, research grant or honorarium from Janssen, Pfizer, Abbvie, Takeda, Genentech/Roche, Neopharm, Ferring, Rafa Laboratories, Falk Pharma, Nestle, Given Imaging/Medtronic, Gilead, Celgene, Arena, Sublimity, Celltrion Altman Research; DT - Has received consultation fee, research grant, royalties, or honorarium from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Biogen, Neopharm, Uniliver, Atlantic Health, Shire, Celgene, Lilly, Roche; all other authors have nothing to declare. Ethics Approval Statement: This study was approved by the local ethics committee.

The Role of Ethnicity in Hepatosplenic T-Cell Lymphoma: A Retrospective Survival Analysis in Texas

Background Hepatosplenic T-Cell lymphoma (HSTCL) is an aggressive type of lymphoma with extremely low incidence. It has a high fatality rate with a 5-year overall survival (OS) of &amp;lt;10% (Am J Surg Pathol, PMID: 26872013). Although there is no therapy that has proven to produce sustained remission, recent studies suggest improvement in outcomes with allogeneic stem cell transplant (allo-SCT) (Leukemia, PMID: 25234166). Clinical characteristics and therapeutic outcomes have been previously reported; however, documentation of outcomes in minorities such as Hispanics (HI) are lacking. Given the growth of the HI population in the US it is imperative to understand the difference in outcomes and patterns of care (CA Cancer J Clin, PMID: 30285281). The present study aims to fill this gap in the literature; therefore, the present population-based study evaluates the impact of ethnicity in clinical outcomes for HSTCL. Material and Methods We retrospectively searched for cases of HSTCL recorded in the Texas Cancer Registry. Inclusion criteria included and established pathologic diagnosis of HSTCL using the International Classification of Diseases for Oncology Third Edition (ICD-O-3) code list. Patients were divided between HI and non-Hispanics (NH). Demographic, socioeconomic, clinical and survival outcomes were recorded. Statistical analysis included Fisher's Exact test, Pearson's Chi-square test, T-test or Wilcoxon test. Survival analysis was calculation in years from date of primary diagnosis to date of death or last date of follow up. Survival distributions were described with Kaplan-Meier curves, and long rank testing was used to assess significance of variation in median survival with ethnicity. All statistical testing was two-sided with a significance level of 5%. The R language [R Core Team (2013). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria] was used throughout. Results From 2006-2016, a total of 25 patients were diagnosed with HSTCL; 23 (92%) were NH and 2 (7%) were HI [&amp;lt;0.0001]. The median age at diagnosis was 46 for HI and 48 for NH. It was predominantly seen in males for both HI and NH. The patients mostly self-identified as white (HI: n=2, Nh: n=16), and there were 7 (30%) NH patients that self-identified as black. For HI, one patient was in the bracket of poverty indicator of 10-19.9% and the other one was in the 20-100%; for the NH patients the bracket that prevailed was 10-19.9% [p-value 0.56]. Both HI patients had private insurance (PI); insurance status on NH patients included 7 (33.3%) with PI, 5 (23.8%) with Medicare, and 7 (33.3%) was unknown [p-value 0.64]. The majority of HI and NH patients were located in the metropolitan, non-border area. Stage at diagnosis for NH was mostly III-IV; one HI had a stage III-IV HSTCL and the other was unstaged [p-value 1.0]. From a therapeutic standpoint, the majority of HI and NH patients received chemotherapy, with 13 patients (HI: n=2, NH: n=11) receiving multiple agents as first-line therapy [p-value 0.84]. From the two groups, only 3 (13%) NH patients underwent allo-SCT [p-value 0.014]. The majority of HI and NH did not undergo radiation (Figure 1A). The median overall survival was 0.5 years in HI and 0.6 in NH. The survival probability at 2 years for HI and NH was 0.5 (CI=0.16, 1) and 0.29 (CI=0.15, 0.56) respectively; at 5 years for HI was 0.5 (CI 0.16, 1) and for NH was 0.23 (CI=0.10, 0.51) (Figure 1B). The overall survival probability at 10 years was not statistically different for HI vs NH [p-value 0.53] (Figure 1C). Conclusions Survival analysis shows that HSTCL is usually fatal with a median overall survival of less than a year, and no difference in survival probability at 10 years for both HI and NH. The majority of patients in our study were non-Hispanic white males. A significant finding was that NH patients had access to allo-SCT as opposed to the HI patients. No statistically significant difference in survival was noted depending on the insurance or poverty levels. No other demographics or sociocultural variables seemed to have an impact in outcomes. The main limitation of our study is our sample size that limits generalizability and power of our statistical analysis. Further studies using multiple cancer registries are warranted to assess the clinical characteristics and survival outcomes in HI with HSTCL. Disclosures Diaz Duque: ADCT Therapeutics: Research Funding; Molecular Templates: Research Funding; AstraZeneca: Research Funding; Hutchinson Pharmaceuticals: Research Funding; Seattle Genetics: Speakers Bureau; Verastem: Speakers Bureau; AbbVie: Speakers Bureau.

Long-Term Outcomes of Patients with Peripheral T-Cell Lymphoma after Autologous Hematopoietic Cell Transplantation

Introduction: Patients with T-cell lymphoma have variable clinical manifestations and outcomes depending on the histology and their response to therapies. However, the overall outcomes are not as good as their B-cell lymphoma counterpart with induction chemotherapy alone. Therefore, autologous transplant is often used as consolidation in first remission or at relapse because of the poor outcomes with conventional therapy. We have reported previously on Stanford experience of these patients who underwent autologous transplant before 2007 (BBMT 2008, 14:741). Here, we reported a retrospective review of patients in the modern era (2008-2018) with emphasis on the impact of pre-transplant disease status on outcomes and post-transplant relapse management. Method: Between July 1, 2008 and July 31, 2018, 102 consecutive patients with T-cell lymphoma received high dose chemotherapy/autologous hematopoietic cell rescue at Stanford and constitute the study cohort (Figure 1). This study cohort was selected for adequate follow-up (&amp;gt;2 years) after transplant. Progression free survival (PFS) and overall survival (OS) was estimated from the date of transplant using the Kaplan-Meier method. PFS and OS were compared between groups with different pre-transplant disease status based on response to the last pre-transplant therapies (CR1 vs. PR1 vs. CR2). Result: This study cohort included patients with peripheral T-cell lymphoma, non-specified (n=21), angioimmunoblastic T-cell lymphoma (n=50), ALK-negative anaplastic large-cell lymphoma (n=14), ALK-positive anaplastic large-cell lymphoma (n=5), extranodal NK/T cell lymphoma (n=9), enteropathy-type T-cell lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1) and hepatosplenic T-cell lymphoma (n=1). It had a male/female ratio of 61/41, and a median age of 58 years (range 23-71). At diagnosis the majority of the patients had stage III/IV disease (70%) and B symptoms (56%). The median time from diagnosis to transplant was 8.1 months (range 4-176). The majority of patients were in first complete remission (CR1, n=79) at the time of transplant, while others were in PR1 (n=11) or in CR2 (n=12) from last pre-transplant therapies. Ninety-one (89%) patients received high dose cyclophosphamide/carmustine/etoposide(CBV) and 11 patients received high dose carmustine/etoposide/cytarabine/melphalan (BEAM) prior to autograft infusion. Median follow-up post-transplant was 36.8 months (range 0.7-130) for the entire cohort. The estimated 3-year PFS and OS were 60% (95% CI 49-68%) and 75% (95% CI 65-82%), respectively (Figure 2A). Patients who were in CR1 had significantly better median PFS compared to patients in PR1 or CR2 (7.04 vs 1.19 years, p=0.039; 7.04 vs 0.48 years p=0.004, Figure 2B). The estimated 3-year PFS were 67% (95% CI 55-76%), 36% (95% CI 11-63%), and 29% (95% CI 8-56%) for the CR1, PR1 and CR2 groups respectively. Patients who were in CR1 also had significantly better median OS compared to patients in PR1 or CR2 (not reached vs 2.30 years, p=0.018; not reached vs 3.76 years p=0.045, Figure 2C).The estimated 3-year OS were 82% (95% CI 71-89%), 44% (95% CI 14-70%), and 53% (95% CI 21-78%) for the CR1, PR1 and CR2 groups respectively. In this cohort, there were no significant differences in either PFS or OS between different histology. Forty patients experienced disease relapse after transplant. The majority (n=28, 70%) of these patients received additional therapies including chemotherapy (n=13), brentuximab vedotin (n=12), HDAC inhibitor (n=7), and radiation (n=3) with a median systemic therapy of 2 (range 1-5). Thirteen patients eventually underwent allogeneic hematopoietic cell transplantation. The median OS after post-transplant relapse was 21.3 months (Figure 3). Both brentuximab vedotin and allogeneic transplant seemed to provide prolonged survival for these relapsed patients, with estimated 2-year post-relapse OS were 75% (95% CI 13-96%) and 63% (95% CI 28-84%) for the two groups respectively. Conclusion: Autologous transplant remains to be a good option as consolidation for patients with T-cell lymphoma, mostly in patients with first complete remission. While close to 40% of the patients experienced relapse after autologous transplant, additional therapies such as brentuximab vedotin or/and allogeneic transplant can provide long-term benefit for these patients. Disclosures Shizuru: Jasper Therapeutics, Inc: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Shiraz:Kite, a Gilead Company: Research Funding; ORCA BioSystems: Research Funding. Muffly:Servier: Research Funding; Amgen: Consultancy; Adaptive: Research Funding. Sidana:Janssen: Consultancy. Meyer:Orca Bio: Research Funding. Rezvani:Pharmacyclics: Research Funding. Miklos:Novartis: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents &amp; Royalties, Research Funding; Allogene Therapeutics Inc.: Research Funding; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy, Other: Travel support; Miltenyi Biotec: Research Funding; Adaptive Biotech: Consultancy, Other: Travel support, Research Funding. Negrin:Magenta Therapeutics: Consultancy, Current equity holder in publicly-traded company; Biosource: Current equity holder in private company; Amgen: Consultancy; BioEclipse Therapeutics: Current equity holder in private company; UpToDate: Honoraria; KUUR Therapeutics: Consultancy.

Impact of Comorbidities on Outcomes of Peripheral T Cell Lymphoma in Elderly Patients: An International Retrospective Study

Background: Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphoid neoplasms with poor outcomes. Many patients are elderly with increased comorbidities. Single-center retrospective studies describe outcomes in elderly PTCL patients and suggest comorbidity adversely affects outcomes. Little is known about the treatment, outcomes and impact of comorbidity in a large cohort of elderly PTCL patients. This study aims to describe outcomes of elderly PTCL patients in a large unselected international patient cohort. Methods: Patients with PTCL age ≥ 70 diagnosed from January 1, 2010 - December 31, 2015 in the Swedish Lymphoma Registry (SLR) and California Cancer Registry (CCR) were identified. The SLR covers ~ 95% of adult lymphoma patients in Sweden and the CCR includes information on all cancers diagnosed in California. Patients with precursor T-cell malignancies, primary cutaneous lymphomas, and leukemic subtypes were excluded. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI) and clinical outcomes of the cohort were extracted. Statistical analysis: Patient characteristics, clinical variables and outcomes were summarized using descriptive statistics and compared by Chi-square or Fisher's exact test. Outcomes of interest included overall survival (OS) and cause of death. Kaplan-Meier estimates of OS stratified by groups were calculated and presented in figures. Median OS was reported with 95% confidence interval (CI). Comparisons between groups for OS were done by log-rank test. Univariate and multiple Cox proportional hazards models provided hazards ratio estimates and 95% CI for risk factors. Tests for significance were two-tailed and a p-value less than the 0.05 significance level was considered statistically significant. Analyses were performed using software SAS version 9.4 (2013). Results: A total of 839 patients were included (SLR, n = 176, CCR, n = 663). Median age was 78 (SLR) and 79 (CCR) years, respectively. Included subtypes were AITL, n = 226; ALCL, n = 122; EATL, n = 31; Hepatosplenic TCL, n = 7; NK/T-cell lymphoma, n = 10; and PTCL NOS, n = 443. ECOG performance status was not available. CCI data was available in 731 patients (87 %), and CCI scores were divided into groups = 0-1 (61 %) and CCI &amp;gt; 1 (39 %). Male patients more often had a CCI score &amp;gt; 1 (p = 0.024). No other significant baseline differences were seen between the 2 groups (Table 1). Patients in the SLR more often received multiagent treatment compared to the CCR (63 % vs 44 %, p &amp;lt; 0.001). Age &amp;gt; 80 years, CCI &amp;gt; 1 and advanced Ann Arbor stage (III-IV) were significant prognostic factors for worse outcome. No difference in survival was seen between men and women nor the SLR and CCR (Table 2). Patients with a CCI &amp;gt;1 had a statistically significant worse survival compared to patients with a CCI =0-1 (0.36 years v 0.91 years, p=0.0001). Of the PTCL subtypes, AITL patients had a significantly better outcome (median OS = 1.26 years) compared to ALCL (OS = 0.57 years) and PTCL NOS (OS = 0.66 years). Patients receiving multiagent therapy had improved survival compared to patients not receiving multiagent therapy. When comparing OS in patients diagnosed in 2010-2012 with 2013-2015, no improvement was seen for the later period (Figures 1-4). Lymphoma was the most common cause of death with &amp;gt; 70 % of deaths related to lymphoma irrespective of CCI score (Table 3). Discussion: At the time of submission, this study presents the largest international cohort of elderly patients with PTCL. Prognosis is poor and comorbidity seems to further worsen . In contrast to younger patient series, patients with AITL had a better survival than patients with PTCL NOS and ALCL, and were more common in the CCR than in the SLR. Multiagent treatment was associated with improved outcome. A possible confounder could be that fit patients are also the ones receiving treatment, and it is a setback that adjustment for ECOG was not possible, making treatment data somewhat difficult to interpret. As expected, advanced stage (Ann Arbor III-IV) was associated with worse survival. Conclusion: We believe this is one of the largest cohorts presented in elderly patients with PTCL. Comorbidity is an important adverse factor in this group, whereas treatment seems to improve outcome. The majority of these patients die of lymphoma within a year from diagnosis, and development of new treatments represents an unmet clinical need. Disclosures Jerkeman: Abbvie: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Roche: Research Funding.

NCCN Guidelines Insights: T-Cell Lymphomas, Version 1.2021.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.

Abstract PO-51: Drug combination analytics platform for accurate prediction of treatment response in refractory and relapsed lymphomas

Abstract While 5-year survival rates for non-Hodgkin lymphoma have improved with effective first-line therapies, refractory and relapsed lymphomas continue to suffer from poor response rates and low median overall survival. The increased availability of targeted therapies has been critical to improving response rates in lymphomas. As the number of therapeutic options increases, however, identifying the most appropriate patient-specific drug combination from among a range of available drug sets is virtually impossible by conventional methods due to the large search space. Further complicating this clinical decision is the diversity in interpatient therapeutic responses due to lymphoma patient heterogeneity. Math and AI-based analytical tools are beginning to positively impact all facets of drug development and personalized medicine. Rather than aggregating large datasets from other sources (data repositories, text mining, etc.) to develop predictive models, we developed an experimentally driven small dataset analytics platform, Quadratic Phenotypic Optimization Platform (QPOP), to identify and rank drug combinations from a specific drug set search space. QPOP identifies optimal drug combinations from queried drug sets against specific biologic systems of interests, including patient-derived primary cancer cells. Utilizing small datasets built from drug combination tests designed by orthogonal array composite design, QPOP analyzes drug combination sensitivity data to identify and rank possible drug combinations. Recently, we applied QPOP towards patient-specific clinical decision support applications in refractory and relapsed non-Hodgkin lymphoma. Utilizing 1 million patient-derived primary lymphoma cells for 155 drug combination tests, QPOP ranked 531,441 possible therapeutic options from a 12-drug search set within 6 days of patient sample biopsy. Across a series of refractory and relapsed T-cell lymphoma patients, effective treatment options were accurately predicted that included both standard salvage regimens, such as gemcitabine-dexamethasone-cisplatin, as well as targeted regimens, such as bortezomib-panobinostat. For a hepatosplenic T-cell lymphoma case that had previously progressed following 6 lines of treatment, analysis by QPOP was able to accurately identify patient-specific bortezomib-panobinostat treatment that resulted in a complete response. Furthermore, QPOP-predicted drug combination sensitivity results from our study were compared to historical outcomes of a phase 2 trial of bortezomib-panobinostat in peripheral T-cell lymphoma (NCT00901147), with 20% predicted response in our QPOP-analyzed cohort mirroring 21.7% complete response observed in the previous trial. These results provide evidence that ex vivo drug combination sensitivity platforms may be useful tools for clinical decision support, for both personalized medical applications as well as enhanced clinical trial patient selection and parallel outcome tracking. Citation Format: Jasmine Goh, Sanjay de Mel, Anand D. Jeyasekharan, Edward K.H. Chow. Drug combination analytics platform for accurate prediction of treatment response in refractory and relapsed lymphomas [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-51.

Hepatic involvement by T-cell neoplasms: a clinicopathologic study of 40 cases

Hepatic involvement by a T-cell neoplasm is rare and often challenging to diagnose in liver biopsies. We collected 40 cases of T-cell neoplasms diagnosed in the liver from five large academic institutions to assess the clinicopathologic features. The patients included 11 women and 29 men, with a median age of 54 (range: 2-75) years and a high mortality rate (31/37, 83.8%). Fourteen (35%) patients were diagnosed with hepatosplenic T-cell lymphoma (HSTCL), 13 (32.5%) peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and 13 (32.5%) other types of T-cell neoplasms. Patients with HSTCL were much younger and had worse survival than PTCL-NOS and other T-cell neoplasms (P<0.05). On imaging studies, 20 cases (50%) showed abnormalities, including 10 with mass lesions that correlated with normal or cholestatic pattern enzyme elevation. Histomorphological analysis revealed four main patterns; with the exception of mass forming lesions (pattern 4; n=8), cases with sinusoidal predominant (pattern 1; n=12), portal predominant with sinusoidal infiltrates (pattern 2; n=13) or lobular aggregates (pattern 3; n=5) demonstrated small to medium lymphocytes resembling a reactive/inflammatory process. In addition, we described two cases of T-cell large granular lymphocytic leukemia that mimicked HSTCL, and a case of aggressive post-transplant lymphoproliferative disorder that developed after chronic Epstein-barr virus (EBV) infection, suggesting the importance of EBV testing in some lymphoma cases. As the largest cohort of T-cell neoplasms in liver, our study provides critical data on disease frequency, distribution, and clinicopathologic features that are essential for accurate diagnosis.

Hepatosplenic Gamma Delta T-cell Lymphoma Presenting as Progressive Hepatosplenomegaly Highlighted during Pregnancy

Hepatosplenic T-cell lymphoma (HSGDTL) is a rare variant of T-cell lymphoma with few reported cases in literature. It usually presents with hepatosplenomegaly and constitutional symptoms, primarily in young to middle aged patients. The prognosis is generally poor, with maximum reported survival periods of 2-3 years. There is a link to immunodeficiency and some biological treatments. Liver biopsy with flow cytometry is required to confirm the diagnosis.

Cell morphological analysis of hepatosplenic T-cell lymphoma gamma-delta type

Objective: To analyze the cell morphological features of hepatosplenic T-cell lymphoma (HSTCL) gamma-delta (γδ) type, differentiate from acute leukaemia (AL). Methods: This was a retrospective study. The clinical data of four cases of HSTCL γδ type who were treated in Hebei Yanda Ludaopei Hospital from 2009 to 2014 were collected. Their initial morphology diagnoses in other hospitals were all acute leukemia or myelodysplastic syndrome (MDS). Morphological analysis and cytochemical stains to their bone marrow (BM) aspiration and peripheral blood (PB) smears were completed when they had no response to previous chemotherapies, and the morphological reports were compared with results of immunophenotyping, chromosome, and T cell receptor (TCR) gene rearrangement. Results: The percentages of malignant cells in four patients' BM aspirations were 7.6%-40.0%, and in two patients' PB was 9% and 10%, respectively. The morphology of four cases had a very high similarity in Wright's stain. Predominantly medium-sized cells were seen, with rich cytoplasm and frequently one big conspicuous nucleolus. The malignant cells resembled blasts, especially monoblasts, but with coarse granular chromatin, more compact than that in monoblasts. When comparing to malignant myeloblast and lymphoblasts, HSTCL cells were larger and more irregular in cell shape, with more abundant cytoplasm and prominent nuclear irregularity. The cytochemistric stain played an important role in differential diagnosis. HSTCL malignant cells showed non-specific esterase (NSE) negative or focal punctate activity which couldn't be inhibited by sodium fluoride. Periodic acid-Schiff (PAS) stain was negative or positive with a form of coarse granules. The myeloperioxdase (MPO) stain was negative. Conclusion: Malignant cells of HSTCL γδ type have very distinct morphological features of mature lymphocytic neoplasm. The quality of Wright's stain, being short of complete cytochemical stains, lacking of awareness of this disease, and acute leukemia or MDS like appearance in some cases, result in the possibility of diagnostic error as malignant blast, and probably are main causes of misdiagnosis of HSTCL γδ type.

Rare non-Hodgkin lymphoma of childhood and adolescence: A consensus diagnostic and therapeutic approach to pediatric-type follicular lymphoma, marginal zone lymphoma, and nonanaplastic peripheral T-cell lymphoma.

Pediatric-type follicular (PTFL), marginal zone (MZL), and peripheral T-cell lymphoma (PTCL) account each for <2% of childhood non-Hodgkin lymphoma. We present clinical and histopathological features of PTFL, MZL, and few subtypes of PTCL and provide treatment recommendations. For localized PTFL and MZL, watchful waiting after complete resection is the therapy of choice. For PTCL, therapy is subtype-dependent and ranges from a block-like anaplastic large cell lymphoma (ALCL)-derived and, alternatively, leukemia-derived therapy in PTCL not otherwise specified and subcutaneous panniculitis-like T-cell lymphoma to a block-like mature B-NHL-derived or, preferentially, ALCL-derived treatment followed by hematopoietic stem cell transplantation in first remission in hepatosplenic and angioimmunoblastic T-cell lymphoma.

Hepatosplenic T-cell lymphoma: The Mayo Clinic experience.

e20036 Background: Hepatosplenic T cell lymphoma (HSTL) is a rare subtype of mature T cell lymphomas accounting for less than 1 percent of non-Hodgkin lymphomas. it has been associated with poor prognosis. It typically involves sinusoids in the spleen, liver, and bone marrow. Methods: Following IRB approval, we retrospectively evaluated patients with HSTL treated at the Mayo Clinic Cancer Center 1996-2019. Kaplan-Meier survival analysis and univariate analysis to identify prognostic factors were performed. We investigated clinical characteristics and outcomes among patients with HSTL. Results: 22 patients (15 males) with median age of 45.5 years (range- 15.5-80.6) were identified. The majority of patients had B symptoms (12/22), cyotpenias (20/22), massive splenomegaly (16/22), liver involvement (13/22), and/or bone marrow involvement (14/22). Additionally, 42% tested positive for peripheral blood involvement and 8/22 (36%) were on chronic immunosuppression related to solid organ transplant (2), inflammatory bowel disease (2), and rheumatologic disorders (4). Phenotypically, the majority of patients were positive for gamma/delta (18/22), isochromosome 7q (8/13), and 4/9 (44%) tested positive for trisomy 8. Initial therapies included CHOP/CHOEP (14), ICE (2), EPOCH (1), pentostatin (1), and radiation (1). The median follow-up was 33 months (range 2,137). Progression free survival and overall survival (OS) were 9.5 months (95% CI; 1.8, 16.3) and 12 months (95% CI; 4.9, 18.5) respectively. 10/22 (45%) underwent splenectomy with one patient receiving splenectomy alone as treatment. 8/22 (36%) had stem cell transplant (SCT- 5 allogeneic and 3 autologous). Out of the 22 patients 4 (18%) were long-term survivors with 55, 74, 95, and 137 months; 3/4 had splenectomy at diagnosis and 2/4 had allogeneic SCT. The longest survivor had splenectomy only. Liver involvement was associated with worse OS; 10 months (95% CI; 1.6, 18) vs 35 months (95% CI; 4, NR), p = 0.036. Immune suppression at diagnosis was associated with worse OS; 5 months (95% CI; 1.3, 18) vs 18 months (95% CI; 9, 74), p = 0.036. A trend for better OS was seen with splenectomy and SCT. Conclusions: HSTL is a rare lymphoma with poor prognosis. Long-term survival was seen in 18% only. Liver involvement and immune suppression had a negative impact on OS. A larger cohort is needed to better evaluate the impact of different treatment options.