Enteropathy-associated T-cell Lymphoma Research Articles

A Case Report of Monomorphic Epithelial Intestinal T-Cell Lymphoma and Literature Review

Background: Monomorphic epithelial intestinal T-cell lymphoma (MEITL), previously known as type II Enteropathy-associated T-cell lymphoma (EATL), is a rare intestinal tumor with strong invasiveness, poor prognosis, atypical clinical manifestations, and is difficult to diagnose. Aim: The clinical manifestations, imaging, histopathology, and immunohistochemical characteristics, treatment and prognosis of this case of MEITL were analyzed retrospectively, and combined with literatures learning to provide the experiences and lessons for diagnosis and treatment. Case Presentation: Here, we present a 68-year-old Asian woman with unexplained intestinal perforation and lung imaging changes as the first manifestation, and gradually appearing refractory diarrhea and pulmonary cavities. During the period, due to the unknown diagnosis, all treatments were mainly based on anti-infection and antidiarrhea, but her symptoms had no improvement after therapy, even died of poor basic physical conditions. Colonoscopy biopsy showed atypical lymphocyte infiltration-like growth and the formation of local superficial ulcers. Immunohistochemical tests showed that T-lymphocyte hyperplasia was predominant and led to a diagnosis of MEITL. Conclusion: MEITL is mainly manifested by gastrointestinal symptoms and lacks specific symptoms. The diagnosis of MEITL should be based on comprehensive judgment of clinical manifestations, pathological features and immunohistochemical detection results. Positive biopsy confirmed and timely chemotherapy may be conductive to a better prognosis.

Long-term remission in multiply relapsed enteropathy-associated T-cell lymphoma following CD30 CAR T-cell therapy

Long-term remission in multiply relapsed enteropathy-associated T-cell lymphoma following CD30 CAR T-cell therapy

Микобиота пелагиали Одесского региона северо-западной части Чёрного моря

Mycobiota of the marine area of Odessa region was studied (30°70′00′′-31°00′00′′N, 46°23′00′′-46°60′00′′E) (See Fig. 1). Hydrological and hydrochemical regimes of the marine area of Odessa region in the northwestern Black Sea are affected by the discharge of the Dnieper (93.4%) and the Southern Bug (5.7%) rivers, the permanent anthropogenic discharges of the cities of Odessa, Chernomorsk (Ilyichyovsk), Yuzhnyi and their ports, shipping, dredging, and the open sea. The aim of this work was to study the species composition, the number of colony forming units (CFU) and the dynamics of the spatiotemporal distribution of reared microfungi as a function of abiotic factors and the trophic level of seawater in this area. Water samples were taken in summer and autumn 2008-2012 in the surface (1 m depth) and bottom (7-24 m depth) layers. The samples were taken, at least, in three replicates. The results of processing 258 samples from 22 stations were analyzed. The effects of environmental factors (water temperature, salinity, dissolved oxygen, five-day biochemical oxygen demand, petroleum hydrocarbons, dissolved metals Cu, Zn, Ni, Cd and suspended particulate matter) were studied in 140 samples (See Table 1). Micromycetes were isolated on Czapek’s medium prepared in sea water. 1 ml of sample water was added to a Petri dish and filled with medium cooled to approximately 36-40 °C. To suppress the growth of bacteria, 0.03% chloramphenicol was added to the medium (by volume of the medium). Cultivation was carried out at a temperature of 18-20 °С for 2-8 weeks. Micromycetes were identified by morphological and cultural characteristics according to Vera Bilay and Eleonora Koval’ (1988) and GS De Hooh ea tl. (2000). Nomenclature, and taxonomy of fungi correspond to The Index Fungorum database. The ecological analysis of mycocomplexes was carried out according to: species composition, the number of species in complexes, frequency of occurrence of a species and the number of colony-forming units (CFU / L). In this research, 50 fungal species of 19 genera, 14 families, 9 orders, 4 classes of the division Ascomycota were revealed. Fungal taxa from Odessa region were grouped into families. The family Aspergillaceae included the genera Aspergillus, Penicillium and Talaromyces (27 species); the family Pleosporaceae included the genera Alternaria and Stemphylium (8); and there were 3 species of the genus Cladosporium from the family Cladosporiaceae. In total, 76.0% of species found were from the three families (See Table 2). Using Average Taxonomic Distinctness index, AvTD (Δ+), and Variation in Taxonomic Distinctness index, VarTD (Λ+), features of the taxonomic diversity of mycocomplexes were revealed. These indices were calculated from a matrix of micromycete species from the region under study combined with the fungi list (master list, 219 species) of the Black Sea pelagic zone. In the analysis, the taxonomy levels from Species to Kingdom were included. For the indices Δ+ and Λ+, 95% probability funnel graphs were plotted, and their mean expected values were calculated for mycobiota of the region under study and for mycocomplexes from each station. It was found out that the mean expected values of the index Δ+ for mycobiota of the marine area of Odessa region and the stations are considerably lower, and index Λ+ values are higher than those for the sea as a whole (See Fig. 2 and 3). According to literature sources, no significant seasonal and inter-annual changes in the trophic status of the region occurred in 1992-2010. It was transitional between mesotrophic and eutrophic. The long-term mean TRIX value was 5.3 (4-5: medium trophic level; 5-6: high trophic level and poor water quality). In the species composition and numerical structure of mycocomplexes of the mesotrophic and eutrophic zones, no significant differences were detected. Over the entire period of this research, a relatively uniform distribution of the mean abundance of fungi over the area and depth was noted (See Table 3). No significant correlation was found between abiotic parameters under study and micromycete abundance over the horizons, seasons, sampling dates, location of stations, as well as mesotrophic and eutrophic zones. In the region, 44% of fungi-indicators of different kinds of pollution were registered. In the areas of stormwater runoff and wastewater treatment plant discharges, the indicator value (IndVal) was the largest for melanin-containing fungi Cladosporium cladosporioides (28.3%), Alternaria alternata (17.5%), and Aspergillus niger (12.3%), which are resistant to several adverse environmental factors. In the eutrophic zone, large values of the indices were found in Aspergillus clavatus (21,2%), Penicillium expansum (17,7%), Penicillium citrinum (16,1%), Al. tenuissima (12,5%), and in A. fumigatus (60%), Al. alternata (40%) and A. niger (35,7%) in places of local oil pollution. It is established that in the entire marine area of Odessa region, the formed mycocomplexes have a high similarity in species and numerical structure, and therefore, they can be considered as a single community.

Enteropathy associated T cell lymphoma with Reed-Sternberg-like cells of B cell phenotype and genotype associated with Epstein-Barr virus infection

EBV-positive B cell proliferations have been recognized in the setting of some T cell lymphomas. These B cell proliferations often differ to varying degrees in morphology and immunophenotype with a great proportion being Epstein-Barr virus (EBV)-positive with Reed-Sternberg (RS)-like morphology. We describe a case of a 76-year-old Caucasian male who presented to the Emergency Department (ED) with weight loss, abdominal pain, and multiple episodes of vomiting and diarrhea. He underwent a laparotomy with an intraluminal mass seen in the cecum. Histology showed atypical intermediate- to large-sized cells involving the full thickness of the bowel wall with numerous mitotic figures and apoptotic bodies. The adjacent uninvolved mucosa demonstrated villous blunting, increased intraepithelial lymphocytes, crypt elongation, and lamina propria plasmacytosis, consistent with the celiac enteropathy. Rare large transformed cells morphologically consistent with Reed-Sternberg cells (RS cells) were also identified in the mesenteric lymph nodes. Immunophenotyping showed the intermediate- to large-sized cells to be of T cell origin with strongly CD3, CD45, and TIA-1 positive; moderately positive for CD5; and variably positive for CD2, CD25, CD57, perforin, and granzyme B, with an aberrant loss of CD7. The large cells were moderately positive for PAX-5, CD79a, CD20, CD30, and MUM1. They also were positive for EBV latent membrane protein (EBV-LMP) and Epstein-Barr virus-encoded small RNA (EBER). Based on morphology and immunoprofile, a diagnosis of enteropathy associated T cell lymphoma (EATL) with Reed-Sternberg-like cells associated with EBV virus infection was made. This is a rare phenomenon; the presence of large B cell proliferations in EATL, to our knowledge, is yet to be reported.

Early Complete Remission By Functional Imaging and Intensified Frontline Therapy Are Associated with an Improved Clinical Outcome in Patients with Newly Diagnosed T-Cell Lymphoma- a Single Center Experience

Objectives: T-cell lymphomas (TCL) pose a significant therapeutic challenge due to their aggressive behavior and poor response to treatment. Significant controversy exists regarding the benefit of intensification of therapy in the frontline and relapse settings due the lack of randomized studies in this rare and heterogenous population. We performed a retrospective analysis of survival outcomes in our cohort of TCL patients (pts) to assess the impact of intensification of therapy and other baseline disease, treatment and response characteristics. Methods: Adult pts with TCL diagnosed between January 2001 to December 2018 at Roswell Park Comprehensive Cancer Center were included in this single institution, retrospective chart review. Pts were classified according to the 2008 WHO classification of lymphomas. Demographics, pathology and treatment data were collected across all subtypes. Survival outcomes were summarized by treatment type using standard Kaplan-Meier methods. Comparisons were made using the log-rank test. All other statistics were descriptive. Results: Eighty-seven pts were included in our study. Histological subtypes of TCL included: 27 (31%) peripheral TCL-unspecified (PTCL-U), 15 (17%) Angioimmunoblastic TCL (AITL), 30 (34.5%) anaplastic large cell lymphoma (ALCL), out of which 10/30(33%) were ALK+ ALCL, 11(12.6%) NK TCL, 4(4.6%) enteropathy associated TCL (EATCL). Median age at diagnosis was 62 yrs (range, 20-92), 39 pts (68%) had stage IV disease, 11 pts (12.6%) had ECOG performance status >2, 21 (24%) with IPI risk of 3-4. Fourteen pts (18.6%) received Hyper-CVAD, 54 pts (72%) received CHOP and 7 pts (9.3%) received CHOEP. Others were treated with either less intensive chemotherapy (n=10), SMILE (n=1) or CMED (n=1). With a median follow up of 94 months (mo), the median OS for the entire cohort was 79 mo (95% CI 45.9-127.4). Complete remission (CR) on interim PET (after 2 cycles of therapy) was seen in 29 pts (53.7%) and this was associated with significantly higher CR rates at the end of treatment as well as improved PFS and OS (NR vs 6.7 mo; p=0.001; NR vs 48 mo; p=0.003) (Figure 1). Impact of frontline therapy was assessed in PTCL pts excluding NK TCL and EATCL (Total n=67). Pts treated with Hyper CVAD or those with CHOP/CHOEP followed by high dose chemotherapy and autologous stem cell transplant (HDC-ASCT) were grouped into the Intensive upfront therapy (IUT) group and compared with less intensive upfront therapy (LIUT) that included CHOP/CHOEP or other chemotherapy (Table 1). IUT (n=17; 25.4%) as compared to LIUT (n=50; 74.6%) had improved PFS (5yr PFS 64 mo vs 33 mo, p=0.037), although OS did not reach statistical significance (5yr OS 70 mo vs 48 mo, p=0.24). (Figure 2). A total of 48 pts (55%) in the entire cohort had relapse/progression(R/P). Pts with early relapse (ER) <12 mo from diagnosis compared to late relapse (LR) > 12 mo were associated with a significantly lower 5 yr OS (18%; 95% CI 7-33; vs 53%; 95 % CI 29-72). For pts with ER, median OS after progression was only 2.4 mo, as compared to those with LR (14.2 mo). Notably, among pts who received IUT, 4 pts had ER (23.5%); whereas 23 pts (46%) with LIUT had ER. While, this did not meet statistical significance, our cohort may be underpowered to find a true effect. At R/P, 20 pts (41.7%) received multiagent salvage (mostly ICE/CHOP or cytarabine based), 18 pts (37.5%) received single agent therapy (mostly romidepsin), while 10 pts (20.8%) were placed on hospice. As compared to single agent therapy, multiagent salvage was associated with improved median PFS2 and OS2 (calculated from time of R/P to second progression or death) [mPFS 10.4 vs 3.4 mo; p= 0.01; mOS 14.2 vs 5.8 mo; p= 0.004] (Figure 3). Conclusions: While the ideal front-line therapy for TCL continues to be a subject of debate, the use of intensified front-line chemotherapy and/or early HDC-ASCT appears to be associated with better PFS in our cohort of TCL. Attaining an early CR by functional imaging was associated with improved survival. Pts with early relapse of disease or refractoriness to frontline therapy had a dismal overall survival. Use of multiagent intensive salvage therapy over single agent therapy at the time of relapse may improve outcomes. Further analysis on factors influencing choice of salvage treatment strategy at relapse would be important to study. Disclosures No relevant conflicts of interest to declare.

Gastrointestinal (GI) Involvement with Non-Hodgkin's Lymphoma (NHL) Impacts Outcome; A Retrospective Single Tertiary Care Center Analysis of Clinico-Pathologic Characteristics Provides an Alternate Insight to Presentation and Outcome

Introduction Historically, the GI tract is involved in 10-15% of patients with newly diagnosed NHL. Despite being the predominant extranodal site for lymphoma involvement little is known about its pathophysiologic presentation given its overall rarity. Nonetheless its evaluation, diagnosis, prognosis and management is distinct from lymphomas at other sites hence their recognition irrespective of whether being the primary site is prudent. Methods We performed a single center retrospective study of patients to describe clinical characteristics and outcome of newly diagnosed NHL presenting with GI involvement defined by tissue biopsy between January 2003 and April 2019. Descriptive statistics were calculated by Fisher's exact test and Chi2 test for categorical variables and rank-sum analyses for continuous variables. Results We identified 91 patients with one patient presenting with 2 different GI NHL involvement. The median age at presentation was 70 years (range 33-92) and 61 were male. 41 (45%) patients had diffuse large B cell lymphoma (DLBCL) and 5 had concomitant low grade component, 28 (30.8%) mucosal associated lymphoid tissue (MALT) lymphoma, 10 (11%) mantle cell lymphoma (MCL), 4 (4.4%) enteropathy associated T cell lymphoma (EATL), 3 (3.3%) follicular lymphoma, 2 (2.2%) Burkitt's lymphoma and 2 (2.2%) EBV driven lymphoproliferative disorder (LPD). There were 1 case each of plasmablastic lymphoma and extranodal NK/T-cell lymphoma, nasal type. 37 with DLBCL and 2 with MCL had primary GI involvement. Gastric involvement was the commonest site, 43 (55.8%) cases followed by the large intestine, 22 (28.6%). PET-CT scan was done in 42 cases with high grade NHL; GI involvement by FDG avidity was noted in 23 cases and negative in 19 (45.2%). Serum albumin at presentation was available in all patient. Patients with presenting serum albumin < 25 g/L were more likely to die in the first 30-days post diagnosis; p<0.0001. A total of 20 patients died as a result of lymphoma; presenting serum albumin was significantly lower in that group (mean 29 g/L versus 37 g/L; p=0.0077). H pylori status was assessed by either antigen testing in stool and/or histology. This was known in 50 patients and was available by the 2 assessment methods in 31 cases but discordant in 17. A positive result was more likely noted with the antigen test. None of the T-cell LPD were H pylori positive. 12 of the 26 DLBCL and 9 (53%) of the 17 MALT lymphoma patients were H pylori status was known were positive. Nonetheless all H pylori negative MALT lymphoma cases were localized to the stomach and responded to triple eradication therapy and Rituximab monotherapy +/- surgical resection. In the DLBCL cohort, the cell of origin was known in 22 of 39 cases; 17 were non-germinal center phenotype. In the MCL cohort, all patients whom underwent surveillance endoscopies irrespective of symptoms and/or radiologic finding had histologic evidence of GI involvement with lymphoma with only 3 (18%) patients being symptomatic +/- had radiologic finding in keeping with GI involvement. Conclusions Despite the relatively small sample size this real-world data of GI lymphomas outlines some of its recognized features; advanced age at diagnosis, male prevalence and gastric involvement as the commonest site of involvement. Presenting serum albumin <25 g/L was associated with higher 30-day mortality highlighting its relevance and need for its inclusion as a biomarker in risk stratification of NHL where GI tract is involved. There is however several other significant findings not previously recognized; the incidence of GI involvement in MCL is much higher than reported; 100% in all patients whom have undergone endoscopy in our cohort suggesting that GI involvement is a feature of MCL. With only 53% of MALT lymphoma being H pylori positive which is much lower than previously described this renders the prototypical association of H pylori infection in MALT lymphoma pathogenesis void and suggests an alternate etiology. Nonetheless their response to antibiotic therapy with only minimal additional systemic therapy in some indicates that H pylori status does not necessary predict its efficacy and should be considered when treating MALT lymphomas irrespective of H pylori status. CT scans but also PET-CT scans are insensitive in detecting GI involvement even in high grade NHL. Endoscopy with random mapping biopsies even with normal macroscopic GI findings remains the gold standard. Disclosures No relevant conflicts of interest to declare.

A Phase II Study of Nivolumab in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma

A Phase II Study of Nivolumab in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma

Preliminary Results from a Phase 2 Trial of Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed By BV Consolidation in Patients with CD30-Positive Peripheral T-Cell Lymphomas

Preliminary Results from a Phase 2 Trial of Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed By BV Consolidation in Patients with CD30-Positive Peripheral T-Cell Lymphomas

Central Nervous System Involvement in Peripheral T-Cell Lymphoma

Background: Central nervous system (CNS) involvement by peripheral T cell lymphoma (PTCL) is a rare condition. Among primary CNS lymphomas, only 2% are secondary to PTCL, while the risk of CNS relapse in all cases of PTCL is estimated at 2% to 6%. Little is known about the presentation and outcomes of PTCL patients with CNS involvement given the rarity of this entity. In this study, we describe patient characteristics, histology, and clinical course of patients with CNS involvement by PTCL. Methods: The Mayo Clinic Lymphoma Database was used to identify PTCL patients with primary or secondary CNS involvement seen at our institution between 2000 and 2018. A total of 12 patients were identified and their medical records were reviewed for patient and disease characteristics, CNS-directed treatment modality, and outcomes. The Kaplan-Meier method was used for time-to-event analysis. Results: The median age at CNS diagnosis was 63 years (range 41 to 76) and 11 (93%) patients were male. The histological diagnoses were PTCL, NOS in 9 (75%) patients, enteropathy-associated T-cell lymphoma in 2 (17%) patients, and angioimmunoblastic T-cell lymphoma in 1 (8%) patient. Five patients presented with primary T-cell CNS lymphoma (all with a PTCL, NOS histology), while the remaining 7 (58%) patients also had systemic involvement. All patients presented with neurologic symptoms at the time of CNS involvement diagnosis including: focal motor deficits in 6 patients (unilateral upper extremity weakness, gait impairments, and hemiparesis), cognitive decline in 5 patients (memory impairments, reduced attention, and confusion), headache in 4 patients, and seizure in 3 patients. The CNS disease location included the brain parenchyma in 9 (75%) patients, leptomeninges in 1 (8%) patient, and lumbar plexus in 1 (8%) patient. One patient (8%) had positive CSF finding only without radiologic evidence of involvement. CSF analysis was performed in 11 patients. Elevated protein levels were noted in 3 (27%) patients, malignant cells in 2 (18%), and no clear abnormalities in the remaining 6 (55%) patients. Concomitant bone marrow involvement was seen in only 1 patient. Elevated LDH was seen in 2 patients. The a median LDH was 195 U/L (range 139 to 4,360) The most common CNS-directed therapies were: high-dose methotrexate (MTX)-based regimens in 8 (67%) patients, including high-dose MTX in combination with temozolomide (n=2), or cytarabine and thiotepa (n=2). Intrathecal MTX, temozolomide and dexamethasone, lenalidomide, high-dose steroids, and surgical resection were the treatment modality used for one patient each. At a median follow up of 18 months, eight (75%) out of 12 patients were not alive at the time of last follow up. The median overall survival (OS) from diagnosis was 16 months (95% CI: 2.8-173). The median progression free survival (PFS) from initiation of CNS-directed therapy was 9 months (95% CI: 1.6-33) (figure). Four patients had a PFS longer than 12 months. These 4 patients were treated with: temozolomide/dexamethasone, high-dose MTX, lenalidomide, and high-dose MTX followed by cytarabine/thiothepa. Conclusion: CNS involvement by T-cell lymphoma is a rare complication that carries a poor prognosis. Early onset of neurologic symptoms should trigger prompt investigation of CNS involvement. Despite the short OS and PFS, some patients may achieve a relatively longer disease free interval. Disclosures Bennani: Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board. Cerhan:Celgene: Research Funding; NanoString: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Nowakowski:Celgene: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Curis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Genentech, Inc.: Research Funding; MorphoSys: Consultancy, Research Funding; NanoString: Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees. Ansell:Mayo Clinic Rochester: Employment; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding. Paludo:Celgene: Research Funding; Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding.

Peripheral Blood Involvement By Flow Cytometry As a Prognostic Factor in Aggressive T Cell Lymphomas Following Autologous Stem Cell Transplantation

Introduction: Aggressive T cell lymphomas (TCL) are a heterogenous group of lymphomas that are frequently associated with poor outcomes. Autologous stem cell transplantation (ASCT) is recommended according to the NCCN guidelines and by practice standards for most subtypes as a consolidation for patients in first remission. A large prospective study of up-front ASCT by the Nordic Lymphoma group identified age, ECOG performance status <2, and bone marrow involvement as important prognostic factors. We have identified peripheral blood involvement by flow cytometry at diagnosis in up to one third of patients with aggressive TCL and analyzed whether this was a prognostic factor for outcomes after ASCT. Methods: We retrospectively analyzed data from consecutively treated patients (pts) with aggressive T-cell lymphomas who underwent ASCT at our institution from July 2009 to February 2019. Patient and disease characteristics were summarized using descriptive statistics. Kaplan-Meier analysis was used to estimate progression free survival (PFS) that was defined as the time from SCT to the first evidence of recurrence, and overall survival (OS) that was defined as the time from SCT to death or last institutional follow up with a hematologist. We collected data on age, co-morbidities, disease subtype, stage, response to therapy and treatment both pre and post SCT. Flow cytometry was obtained at diagnosis and phenotype of atypical circulating cells was compared with immunophenotype from tumor biopsy specimens. Results: 50 pts with TCL who received ASCT were identified for this analysis. Of this population, 41 (80%) of pts had peripheral blood flow available at the time of initial diagnosis. T-cell lymphoma types included peripheral T cell lymphoma not otherwise specified (PTCL NOS, 17 pts), angioimmunoblastic T cell lymphoma (AITCL, 15pts), ALK negative anaplastic large cell lymphoma (ALCL, 1pt), enteropathy-type T-cell lymphoma (EATL, 2pts), extranodal natural killer T-cell lymphoma (NKTCL, 2pts) and panniculitis like T cell lymphoma (2 pts) (Table 1). Median age of the cohort was 62 years (range 20-75 years) and all patients included had an ECOG PS 0-1 at the time of diagnosis. The majority had stage 4 disease (36/41, 87.8%), but analysis included a small number of patients with stage 2 (1/41, 2.4%) and stage 3 (4/41,9.7%) disease. Bone marrow involvement by morphologic criteria was noted on bone marrow biopsy in 8/41 (19.5%) pts; bone marrow was negative in 28/41 or 61% pts and not evaluated in 8/41 or 19.5% pts. Flow cytometry of peripheral blood performed as part of initial staging was positive for circulating malignant cells in 13/41 pts (31.7%) at the time of diagnosis. All patients underwent ASCT in first remission. The median PFS and OS were 15.2 and 29.9 months respectively in the flow positive group, while neither median PFS nor OS were reached in the flow negative group (Figures 1 and 2). Flow cytometry results from time of diagnosis was not strongly associated with PFS (log rank, p = 0.39), however, it was associated with overall survival (log rank, p = 0.012). There were 11 deaths in the cohort- 4 in the flow negative group and 7 in the flow positive group. Further, when bone marrow involvement was evaluated, 7 of 13 pts with positive flow cytometry (53.8%) and 5 of 28 (17.8%) pts with negative flow cytometry had BM involvement, suggesting a correlation between positive bone marrow and detection of lymphoma cells in the peripheral blood at the time of diagnosis. Conclusions: We demonstrate in our cohort of patients that detection of circulating lymphoma cells at diagnosis by flow cytometry was associated with a worse outcome in patients with aggressive T cell lymphomas undergoing ASCT as a consolidation in first remission. Larger cohorts will be needed to validate these findings, but these results suggest peripheral blood involvement by sensitive flow cytometry may identify patients with worse outcomes who might benefit from a more aggressive strategy such as allogeneic stem cell transplantation or alternative consolidation strategies. Disclosures Huntington: Bayer: Consultancy, Honoraria; Pharmacyclics: Honoraria; Celgene: Consultancy, Research Funding; DTRM Biopharm: Research Funding; Genentech: Consultancy; AbbVie: Consultancy. Isufi:Celgene: Consultancy; Novartis: Consultancy; Astra Zeneca: Consultancy. Foss:Seattle Genetics: Consultancy, Other: fees for non-CME/CE services ; Mallinckrodt: Consultancy; miRagen: Consultancy; Spectrum: Other: fees for non-CME/CE services ; Eisai: Consultancy; Acrotech: Consultancy.

Epidemiological, pathological and immunohistochemical aspects of 125 cases of feline lymphoma in Southern Brazil.

A retrospective study compiling cases of feline lymphoma diagnosed during 12 years (2004-2016) in Southern Brazil was performed. A total of 125 cases of lymphoma diagnosed in cats were reviewed, and information including age, breed, sex and tumour topography were collected. FeLV and FIV immunohistochemical tests were performed, as well as immunophenotyping of lymphomas. The alimentary form represented the most common presentation (42/125), followed by mediastinal lymphoma (35/125). Out of 125 cases, 79 presented positive retroviral immunostaining in tumour tissue (52 FeLV alone, 14 FIV alone and 13 presented FIV and FeLV co-infections), 66/125 of the cases were of T-cell origin and 59/125 of the cases were of B-cell origin. The median age of cats with T-cell lymphoma was 120 months (10-240 months), and 60 months (6-204 months) for cats with B-cell lymphoma. The most frequent alimentary tumour presentation was the enteropathy-associated T-cell lymphoma (type 1), and the major type of mediastinal tumour observed was diffuse large B-cell lymphoma. Considering only mediastinal and alimentary lymphomas (n = 77), the prevalence of mediastinal lymphoma in FeLV-positive cats was 2.21 times higher than the prevalence of this type of tumour in FeLV-negative cats (P = .036). Mediastinal lymphoma was more frequently observed in younger cats, and the prevalence of mediastinal tumours in these animals was 3.06 times higher than the prevalence of this tumour form in old cats (P = .0125). The present study indicates that retroviral infections still play an important role in the development of feline lymphomas in southern Brazil.

Gastrointestinal T- and NK-cell lymphomas and indolent lymphoproliferative disorders

Primary gastrointestinal (GI) T- and NK-cell lymphomas constitute a heterogeneous group of uncommon and aggressive neoplasms, which have unique clinical and pathologic features. The intestines are the most frequent sites of disease, but almost any GI organ may be involved. Enteropathy associated T-cell lymphoma (formerly EATL type 1) and monomorphic epitheliotropic intestinal T-cell lymphoma (formerly EATL type 2) represent the two most common entities. However, other types of peripheral T-cell lymphomas can also occur in the GI tract or involve it secondarily. Moreover, indolent T- and NK-cell lymphoproliferative disorders (LPDs) of the GI tract have also recently been recognized. In this review, we describe the salient clinical, histopathologic, immunophenotypic, and molecular characteristics of primary GI T/NK-cell lymphomas and indolent LPDs, which form the basis for classification of the different entities, and an algorithmic approach to the diagnosis of these rare diseases.

Insufficient awareness of celiac disease in China: population-based screening is needed.

Insufficient awareness of celiac disease in China: population-based screening is needed.

Anaplastic Large T-Cell Lymphoma in the Intestine of Dogs.

Anaplastic large T-cell lymphoma (ALTCL) is a rare subtype of non-Hodgkin T-cell lymphoma that occasionally occurs in the gastrointestinal tract of humans. Enteropathy-associated T-cell lymphoma (EATL) type 1 is the most common type of intestinal lymphoma in dogs, and ALTCL has not previously been reported in the intestinal tract of dogs. Thirteen dogs with intestinal masses diagnosed as intestinal lymphoma with anaplastic morphology were reviewed. Clinical data, including treatment protocols, were available for 11 cases. Immunohistochemistry for CD3, CD20, and CD30 was performed for all cases in addition to PCR for Antigen Receptor Rearrangements (PARR) for assessment of clonality. Eight (62%) of the cases presented with intestinal perforation, and all cases had 1 or more masses arising from the small intestine. Histologically, all cases were characterized by transmural infiltrates of large, CD3-positive and frequently CD30-positive cells. Neoplastic T cells had marked anisocytosis and anisokaryosis, prominent nucleoli, and occasionally indented to reniform nuclei. There was abundant necrosis and inflammation with occasional vascular invasion within neoplastic masses. All cases had a monoclonal T-cell receptor γ gene rearrangement. The median survival time was 5 days, with 1 dog surviving 2 years after the initial diagnosis. ALTCL can occur as an aggressive transmural lymphoma in the gastrointestinal tract of dogs and commonly causes intestinal perforation. ALTCL can be differentiated from EATL type 1 and might have implications for accurate prognostication and selection of therapeutic options in the future.

PS1096 INTERIM UPDATE FROM A MULTI‐CENTER STUDY OF PRALATREXATE IN ASIAN PATIENTS WITH RELAPSED OR REFRACTORY(R/R) PERIPHERAL T‐CELL LYMPHOMA (PTCL)

Background:Peripheral T‐cell lymphomas (PTCL) are a group of rare, aggressive and diverse lymphoproliferative disorder. When patients are in the relapsed/refractory setting, the survival is mostly less than 6 months. Pralatrexate, a folate analogue metabolic inhibitor, was the first monotherapy approved to treat R/R PTCL patients. As the subtypes difference between western and eastern countries, we would like to investigate the efficacy/safety of pralatrexate in Taiwanese patients.Aims:This single‐arm, multi‐center study aims to demonstrate the efficacy/ safety of pralatrexate in R/R PTCL patients. The patients who undergo Hematopoietic Stem Cell Transplantation (HSCT) or not after pralatrexate will be also investigated individually.Methods:Eligibility criteria included age ≧ 20 with PTCL according to the NCCN diagnosis criteria, the Revised European American Lymphoma (REAL), and WHO disease classification with the following subtypes: Peripheral T‐cell lymphoma, NOS (PTCL‐NOS), Angioimmunoblastic T‐cell lymphoma (AITL), Extranodal NK/T‐cell lymphoma, nasal type (ENKL), Enteropathy‐type T‐cell lymphoma (EATL), Hepatosplenic T‐cell lymphoma (HSTCL), Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) and Adult T‐cell lymphoma/leukemia (human T‐cell leukemia virus [HTLV] 1+) (ATLL). Patients were documented disease progression after prior treatment. Intravenous pralatrexate was administrated weekly for 6 weeks in 7‐week cycles up to 5 cycles with concurrent vitamin B12 and folic acid. Patients who complete at least 1 cycle of pralatrexate and have at least 1 post‐treatment tumor assessment are defined as evaluable patients. The primary end point is Objective Response Rate (ORR, CR + PR). Secondary end points include Progression‐Free Survival (PFS), Duration of response (DoR) and Overall Survival (OS).Results:Twenty‐two patients were evaluable for efficacy per protocol definition. The subtype distribution included PTCL‐NOS (n = 9, 40.9%), AITL (n = 5, 22.7%), ENKL (n = 5, 22.7%), EATL (n = 1, 4.5%), SPTCL (n = 1, 4.5%) and ATLL (n = 1, 4.5%). The ORR was 54.5% with CR 18.2% (n = 4) and PR 36.3% (n = 8). When divided into 2 groups based on if patients received HSCT after pralatrexate, the ORR in HSCT group (n = 5) was 60% with CR 20% (n = 1) and PR 40% (n = 2), while ORR in non‐HSCT group (n = 17) was 53% with CR 18% (n = 3) and PR 35% (n = 6). At the time of data cut‐off, median PFS was 5 months (95% C.I. 5.51, 12.93), median DOR was 5.4 months (95% C.I. 2.64, 13.10) and OS not reached yet. It's notably that, among 5 patients that received HSCT successfully after pralatrexate, 4 patients are ENKL and the other is PTCL‐NOS. Except one who experienced disease progression after HSCT, the others still remain in response. It indicated that pralatrexate may play a beneficial role in bridging to transplantation in PTCL patients, especially in ENKL. Safety population analysis (n = 27) showed the most common TEAEs (grades 3–4) were: anemia (33%), stomatitis (26%), peripheral edema (22%), thrombocytopenia (15%) and leukopenia (11%).Summary/Conclusion:This interim update of this multi‐center study demonstrated the efficacy of pralatrexate monotherapy in R/R PTCL is 54.5%. Interestingly, most ENKL patients received HSCT after obtaining good disease control with pralatrexate. In addition, it showed tolerable safety profile. This is the first data demonstrated benefits of pralatrexate in R/R PTCL patients with intention or no intention to receive transplantation.image

PB1813 FRONTLINE AUTOLOGOUS STEM CELL TRANSPLANTATION IN PERIPHERAL T-CELL LYMPHOMA: A SINGLE CENTER EXPERIENCE

Background: Peripheral T-cell lymphoma (PTCL) is a rare heterogeneous lymphoma with a poor long-term survival. Aims: Our purpose was to assess the efficacy and prognosis of autologous stem cell transplantation (ASCT) as a frontline treatment for PTCL. Methods: Patients (pts) with primary diagnosed PTCL received 6–8 weeks of pre transplant induction chemotherapy. If in complete or partial remission, they proceeded to consolidation with BEAM based ASCT. We retrospectively analyzed all consecutive patients with PTCL treated with ASCT in the Tunisian National Center of Bone Marrow transplantation from January 2004 to February 2017. PTCL diagnosis confirmed by immunohistochemistry according to 2016 WHO classification criteria. Results: In all, 32 pts were enrolled. Median age at ASCT was 41 years (range 24 to 60 years) and 23 patients (72%) were male. PTCL subtypes included ALK-negative anaplastic T cell lymphoma (TCL) (n = 12); PTCL not otherwise specified, (n = 9); angioimmunblastic TCL (n = 2); enteropathy type TCL (n = 2); extra nodal natural killer TCL, nasal type (n = 2); and hepato splenic TCL (n = 2). 81.2% had advanced disease (Ann Arbor stage III or IV). Three patients (9,4%) had bone marrow involvement and 47 % had elevated serum lactate dehydrogenase. 72 % of all patients had a good PS (WHO 0 to 1). According to IPI, pts were classified low risk (33%), low intermediate (53%) or high intermediate (13%). Pre-transplant first line chemotherapy was CHOP/CHOEP regimen (60%) or ACVBP regimen (40%). 30% of pts had refractory disease and received second line chemotherapy. Pts achieved CR (61%) or PR (39%) prior to ASCT. The median time to neutrophil engraftment was 9 days (range 7 to 16) and the median time to platelet engraftment was 11 days (range 6 to 18). The median hospital stay was 33 days (range 17 to 99). After a median follow-up post ASCT of 23 months (range 5 to 150), 12 patients remained alive. The main cause of death was lymphoma progression (73%). Non-relapse mortality was 3%. The 5-year DFS and OS rate was 35% and 38% respectively. Patients transplanted in CR had a 5-year OS rate of 42%, compared with an OS of 31% in patients in PR. Summary/Conclusion: Frontline ASCT following conventional chemotherapy in PTCL is safe and may be beneficial

Le syndrome de cavitation ganglionnaire mésentérique, complication rare de la maladie cœliaque de l’adulte : à propos de quatre cas et revue de la littérature

IntroductionMesenteric lymph node cavitation is an exceptional complication of celiac disease. We report four original observations of this syndrome, completed by a literature review. DiscussionThe analysis of 38 cases showed that this complication occurred exclusively in adults, with a mean age at diagnosis of 54 years. It revealed the celiac disease in the majority of cases. Hyposplenism was almost systematically associated. The risk of lymphoma appeared higher, especially enteropathy-associated T-cell lymphoma. The prognosis was poor with nearly 50% mortality and seemed related to the clinical response to the gluten-free diet. ConclusionThe severity of this complication deserves to be known and should lead to its research in celiac patients, especially in cases diagnosed in adulthood or in case of refractory disease.

Response to A+CHP by CD30 expression in the ECHELON-2 trial.

7538 Background: Brentuximab vedotin (BV) is an antibody-drug conjugate that targets CD30. The ECHELON-2 (E-2) study demonstrated significantly longer progression-free and overall survival with BV plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus CHOP in frontline treatment of patients (pts) with CD30+ peripheral T-cell lymphoma (PTCL). Complete remission (CR) rate (A+CHP 68%; CHOP 56%) and objective response rate (ORR) (A+CHP 83%; CHOP 72%) were also significantly increased. Expression of CD30 is universal in systemic anaplastic large-cell lymphoma (sALCL) but variable among non-sALCL subtypes. As ORR is a direct measure of antitumor activity, we examined response to A+CHP by CD30 expression. Methods: Pts with CD30+ (≥10% by local review) PTCL were included in E-2. Eligible histologies included ALK+ sALCL (IPI ≥2), ALK− sALCL, PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), adult T-cell leukemia/lymphoma, enteropathy-associated T-cell lymphoma, and hepatosplenic T-cell lymphoma. We analyzed the relationship between CD30 expression (IHC Ber H2 antibody) above and below the median (median CD30=18% PTCL-NOS; 25% AITL) and CR rate, ORR, and duration of CR (DOCR) in pts with AITL and PTCL-NOS treated with A+CHP. Results: Most (26/29, 90%) AITL pts had CD30 expression between 10% and 30%. PTCL-NOS pts were more evenly distributed across levels of CD30 expression ranging from 10% to 100%. CD30 levels were neither predictive of response (Table) nor significantly associated with DOCR in pts with AITL (P=0.30) or PTCL-NOS (P=0.90) (log-rank test). Response by CD30 expression. Clinical trial information: NCT01777152. Conclusions: CD30 expression above vs below median (or at 10%) did not predict response to A+CHP in E-2 non-ALCL subtypes, as responses were seen across CD30 levels. This may be due to intra- and inter-tumoral heterogeneity of CD30 expression, limitations of IHC, the nature of CD30 on the cell surface, and multiple mechanisms of action of BV. Further evaluation of the expression-response relationship in PTCL pts with CD30 <10% is warranted.[Table: see text]

AB165. 18. A rare case of enteropathy associated T-cell lymphoma presenting as a small bowel perforation

AB165. 18. A rare case of enteropathy associated T-cell lymphoma presenting as a small bowel perforation

Rare T-Cell Subtypes.

There are a number of rare T-cell lymphoma subtypes that may be encountered in clinical practice. In recent years, improved immunohistochemical techniques and molecular tumor profiling have permitted refinement of some of the diagnostic categories in this group, as well as the recognition of distinct conditions not previously well elucidated. In this chapter, we cover the diagnostic and clinical features of some of the more common of these conditions, including subcutaneous panniculitis-like T-cell lymphoma, cutaneous gamma-delta T-cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, CD4-positive small/medium T-cell lymphoproliferative disorder, and acral CD8-positive T-cell lymphoma. Given the rarity of these conditions, optimal treatments approaches are not always well established, not least as data from large-scale clinical trials are lacking. In this chapter, we aim to provide a summation of current thinking around best treatment, as well as highlighting some controversies in the management of these diagnoses.