AIDS-related lymphoma (ARL) in Asians in the era of HAART and rituximab.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18546-e18546
Author(s):  
Wu Meng Tan ◽  
Soo Yong Tan ◽  
Tat Ming Ng ◽  
Summer Pan ◽  
Richard Hong Hui Quek ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
T Cell ◽  
B Cell ◽  
De Novo ◽  
Clinicopathologic Features ◽  
Hiv Status ◽  
Infection Rates ◽  
Curative Intent ◽  
Ebv Infection ◽  
Aids Related Lymphoma

e18546 Background: We described EBV & HHV8 co-infection rates, histology subtypes (particularly T-cell), prognosticators and outcomes of Asian ARL and compared them to Western series. Methods: We studied clinicopathologic features of 46 HAART-era ARL diagnosed from 1998-2011 in an Asian Tertiary Cancer Centre. To study HIV effect on survival, we applied multivariate analysis to HIV-DLBCL matched against 453 de novo DLBCL from 2000-2008. Results: The 46 patients’ characteristics are presented in the table below. Of note, germinal centre B-cell (GCB) subtype predominated in HIV-DLBCL with evaluable tissue. In multivariate analysis of HIV-DLBCL and matched de novo DLBCL, HIV status did not predict survival (HR1.33, p=0.63); CR was the only significant prognosticator (HR0.30, p=0.048). Conclusions: 1. EBV+ rates appeared to surpass prior Western ARL series. Although concomitant EBV infection appeared to correlate with inferior survival (HR34.5), it was not statistically significant. 2. Alb<30 (p=0.02) & Hb<10 (p=0.003) significantly predicted worse OS, but not CD4 or concurrent HIV&ARL diagnosis. 3. In this predominantly EPOCH-treated population, BL (HR 2.27) non-significantly trended to worse OS than DLBCL. 4. T-cell ARL (2/46, 4%) was rarer than the expected Asian de novo rate. 5. In multivariate analysis, HIV-DLBCL OS was similar to matched de novo DLBCL, suggesting they should be similarly treated with curative intent. CR rates and 5yr OS were comparable to de novo DLBCL. [Table: see text]

scholarly journals B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner

2021 ◽  
pp. annrheumdis-2021-220435
Author(s):  
Theresa Graalmann ◽  
Katharina Borst ◽  
Himanshu Manchanda ◽  
Lea Vaas ◽  
Matthias Bruhn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Expansion ◽  
De Novo ◽  
T Cell Responses ◽  
Type I ◽  
Cell Responses ◽  
T Cell Expansion

ObjectivesThe monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses.MethodsCD8+ T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens.ResultsRituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8+ T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8+ T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8+ T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I.ConclusionsDepending on the stimulus, B cells can modulate CD8+ T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8+ T cell responses.

scholarly journals Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas

Oncotarget ◽  
2017 ◽  
Vol 8 (20) ◽  
pp. 33487-33500 ◽  
Author(s):  
Naoko Tsuyama ◽  
Daisuke Ennishi ◽  
Masahiro Yokoyama ◽  
Satoko Baba ◽  
Reimi Asaka ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Cell Marker ◽  
Large B Cell Lymphoma ◽  
Marker Expression ◽  
Large B Cell

scholarly journals Bispecific T-cell engaging antibodies in B-cell precursor acute lymphoblastic leukemias: focus on blinatumomab

2020 ◽  
Vol 11 ◽  
pp. 204062072091963
Author(s):  
Jose-Maria Ribera ◽  
Eulalia Genescà ◽  
Jordi Ribera
Keyword(s):  
T Cell ◽  
B Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Development Program ◽  
Cell Transplant ◽  
Cell Precursor ◽  
Hematopoietic Stem ◽  
Clinical Development Program

Bispecific T-cell engaging antibodies are constructs engineered to bind to two different antigens, one to a tumor-specific target and the other to CD3-positive T cells or natural killer (NK) cells. Blinatumomab engages CD19 and CD3, performing effective serial lysis. The clinical development program in acute lymphoblastic leukemia (ALL) includes clinical trials in relapsed or refractory (R/R) patients and in B-cell precursor (BCP) ALL patients with measurable residual disease. Several trials are currently being conducted in de novo BCP-ALL, either in induction, consolidation, or before or after hematopoietic stem cell transplant. Combination with other targeted therapies or with other immunotherapeutic approaches are also underway. Several strategies are aimed to optimize the use of blinatumomab either by overcoming the mechanisms of resistance (e.g. inhibition of PD-1/PD-L1) or by improvements in the route of application, among others.

T-cell-rich B-cell lymphomas: diagnosis and response to therapy of 44 patients.

1995 ◽  
Vol 13 (7) ◽  
pp. 1742-1750 ◽  
Author(s):  
J P Greer ◽  
W R Macon ◽  
R E Lamar ◽  
S N Wolff ◽  
R S Stein ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Combination Chemotherapy ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response To Therapy ◽  
B Cell Lymphomas ◽  
Intermediate Grade ◽  
Large B Cell

PURPOSE Clinicopathologic features of 44 patients with well-documented T-cell-rich B-cell lymphomas (TCRBCLs) were reviewed to determine if there were distinguishing clinical characteristics and to evaluate the responsiveness to therapy. PATIENTS AND METHODS Forty-one patients had de novo TCRBCL, while three patients had a prior diagnosis of diffuse large B-cell lymphoma. Seventeen TCRBCLs were identified from a retrospective analysis of 176 lymphomas diagnosed before 1988 as peripheral T-cell lymphoma (PTCLs). The initial pathologic diagnosis was incorrect in 36 of 44 cases (82%), usually due to the absence of adequate immunophenotypic and/or genotypic studies at the initial study. RESULTS The median age of patients was 53 years (range, 17 to 92), and the male-to-female ratio was 1.4:1. B symptoms were present in 22 of 41 patients (54%); splenomegaly was detected in 11 patients (25%). Clinical stage at diagnosis was as follows: I (n = 8), II (n = 6), III (n = 15), IV (n = 14), and unstaged (n = 1). Although therapy was heterogeneous, the disease-free survival (DFS) and overall survival (OS) rates at 3 years for patients with de novo TCRBCL were 29% and 46%, respectively. A complete response (CR) to combination chemotherapy for intermediate-grade lymphomas was observed in 16 of 26 patients (62%); 11 of these patients (42%) had a continuous CR, compared with one of 14 patients (7%) who received radiation therapy or therapy for low-grade lymphoma or Hodgkin's disease (HD) (P < .05). However, there was no difference in OS between patients who received chemotherapy for intermediate-grade lymphoma versus other therapies (49% v 48%) due to a high response rate to salvage therapies, including seven patients without disease after marrow transplantation. CONCLUSION TCRBCLs are difficult to recognize without immunoperoxidase studies. Patients with TCRBCL have clinical features similar to patients with other large B-cell lymphomas, except they may have more splenomegaly and advanced-stage disease; they should receive combination chemotherapy directed at large-cell lymphomas.

Clinical Outcome of the Treatment of Adult Acute Lymphoblastic Leukemia (ALL) with the Hyper-CVAD Protocol.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4588-4588
Author(s):  
Theodoros Marinakis ◽  
Athanasios Zomas ◽  
Athanasios G. Galanopoulos ◽  
Eurydiki Michalis ◽  
George Gortzolidis ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Autologous Transplantation ◽  
Bulky Disease ◽  
Efficient Treatment ◽  
Excellent Outcome ◽  
Small Patient Number

Abstract Hyper-CVAD represents an intensified program for the treatment of acute and chronic lymphoid malignancies. This protocol has been proposed as a highly efficient treatment for adult ALL with acceptable toxicity profile. Purpose: In our Institution, Hyper-CVAD was initiated in September 1999 and used as the primary treatment of adult ALL. We analyse and report here our results focusing on the efficacy and the toxicity of the program. Patients and methods: Patient population consisted of 24 de novo ALL (7 T-cell, 17 B-cell). M/F ratio was 11/13, median age 39 yrs,mean age 42,1 yrs (range 18–68 yrs). 7/24(29,1%) patients were older than 50yrs. Hyperleukocytosis of more than 100x109/L was present in 6/24(25%) cases (3 T-cell,3 B-cell), while splenomegaly, hepatomegaly and bulky disease were documented in 19/24, 17/24 and 1/24 cases respectively. Cytogenetic analysis was performed in 23/24 patients: in 11/23 it was normal, in 1/23 showed del(12), in 1/23 revealed just polyploidy and failed in 10/23 cases. Bcr-abl transcripts were detected in three cases. None of our patients presented with CNS disease (morphology & immunophenotyping). Median follow up was 12,5 months (range 1–65 mo). Treatment consisted of four cycles of Hyper-CVAD (including fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) alternating with four cycles of methotrexate and cytarabine. All patients received intrathecal CNS prophylaxis and granulocyte stimulating factor support. Maintenance therapy consisted of two years of treatment with mercaptopurine, methotrexate, vincristine and prednisone (POMP). Imatinib was added in bcr-abl(+) cases. Results: Hematological complete remission was achieved in 21/24 (87,5%) de novo ALL cases: (11pts <4wk, 10pts >4wk ). Primary resistance was documented in 2/24 cases which subsequently received other therapeutic protocols and eventually deceased. One patient died in early induction. From the group of remmiters 11/21 are alive in CR after median DFS of 21mo (mean DFS 32mo, range 3–57). Another 7/21 remitters-including one post autologous transplantation- relapsed after median of 4,5 mo and six of them deceased. 6/21 patients underwent allogeneic transplantation (4 alive in CR, 2 deceased from complications). Regimen-related toxic deaths occurred in 4/23 cases whilst in remission status. 6/8 Τ-ALLs entered CR but half of them latter relapsed (two in consolidation and one in maintenance). CNS involvement during therapy on hyper-CVAD was not detected in the subgroup of resistant/progressive patients. Conclusions: Within the limitations of the small patient number and relatively short follow up we confirm the effectiveness of hyper-CVAD in de novo ALL, albeight at a lower than expected magnitude. Furthermore, we are unable to confirm the reported excellent outcome in T-ALL. Infectious complications were significant despite the administration of growth factors and prophylactic antibiotics. Hyper-CVAD can prevent leukemia extention to CNS in both responders and non responders.

Low Serum Total Protein and Unfavorable Pathological Subtype Are Independent Unfavorable Factors in Peripheral T-Cell Lymphoma (PTCL) Treated in Prospective Clinical Tirals; Japan Clinical Oncology Group (JCOG) 0108A Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3450-3450
Author(s):  
Yoshitoyo Kagami ◽  
Tomohiro Kinoshita ◽  
Takashi Watanabe ◽  
Kuniaki Itoh ◽  
Harumi Kaba ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
T Cell ◽  
B Cell ◽  
Total Protein ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Serum Total Protein ◽  
Pathological Subtype ◽  
Low Serum

Abstract JCOG consecutively conducted 6 multicenter clinical trials for advanced aggressive lymphoma in 1990s, including 4 CHOP-based chemotherapies (JCOG9505, 9506, 9508 and 9809) and 2 second or third generation, multidrug combination chemotherapies (JCOG9002 and 9203). Among the whole 1,141 enrolled patients (pts), histopathological specimens from 1,084 pts (95%) were reviewed by 6 hematopathologists and diagnosed according to WHO classification. Factors affecting the overall survival (OS) of pts with each B- or T-cell lymphoma were analyzed. In all the 6 trials, major eligibility criteria were as follows: age between 15 and 69 except one trial for elderly pts, pathological subtypes of intermediate- or high-grade lymphoma by Working Formulation excluding adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, and cutaneous T-cell lymphoma. ECOG performance status 4 was excluded. Numbers of the cases of major B-cell lymphoma subtypes were 642 diffuse large B-cell lymphoma(DLBCL), 104 follicular lymphoma(FL), 30 mantle cell lymphoma(MCL) and 24 marginal zone B-cell lymphoma(MZL). One hundred and thirty six cases of PTCL were analyzed, including 18 anaplastic large cell lymphoma (ALCL), 46 angioimmunoblastic T-cell lymphoma (AILT), 53 PTCL unspecified (PTCL-U), 17 extranodal NK/T-cell lymphoma, nasal type (NK/T). Five year OS rates of major subtypes were; 83% for MZL, 76% for FL, 59% for DLBCL, 59% for MCL, 61% for ALCL, 55% for AILT, 41% for NK/T and 38% for PTCL-U. In the whole B-cell lymphomas, 5 year OS rates were discriminated well by International Prognostic Index (IPI); i.e. low (L): 75.0%, low-int (LI): 60.3%, high-int (HI): 45.3%, high(H): 25.7%. On the contrary, those of PTCL could not be discriminated well according to IPI, i.e. L: 63.6% LI: 45.1%, HI: 30.8%, and H: 47.4%. Other factors influencing the OS of pts with PTCL were clarified by the univariate or multivariate analysis. In the univariate analysis of 136 PTCL cases, 4 factors related to unfavorable prognosis were identified as follows: low serum total protein level (TP<6.3g/dl) [hazard ratio (HR) 2.39, (95%CI: 1.50–3.80, p=0.0003)], involvement of gastrointestinal tract [HR 1.81 (95%CI: 1.00–3.28, p=0.049)], low serum albumin level (<3.7g/dl) [HR 1.68(95%CI: 1.08–2.61, p=0.02)], and pathological subtype (ALCL+AILT vs. PTCL-U+NK/T) [HR 0.59 (95%CI:0.38–0.90, p=0.02)]. In multivariate analysis, low TP(<6.3g/dl) [HR 2.20(95%CI:1.27–3.80, p=0.0048)] and pathological subtype (ALCL,AILT vs. PTCL-U,NK/T) [HR 0.59(95%CI:0.36–0.95, p=0.028) ] were significant. These results indicated that pts with PTCL showed worse OS than those with B-cell lymphoma. In B-cell lymphoma, IPI was confirmed as the important prognostic model, however, in PTCL, the significance of IPI is limited by other significant factors, i.e. low TP (< 6.3 g/dl) and unfavorable pathological subtype (PTCL-U and NK/T). In conclusion, in prospective multicenter trials settings, IPI model for aggressive B-cell lymphoma is not suitable for PTCL, and further studies on establishing novel prognostic models for PTCL are warranted.

CLL Cells Can Diversify, Switch, and Differentiate in Response to Autologous T Cell Stimuli Present in a Murine Adoptive Transfer Model

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 315-315
Author(s):  
Piers E.M. Patten ◽  
Shih-Shih Chen ◽  
Davide Bagnara ◽  
Rita Simone ◽  
Sonia Marsilio ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Adoptive Transfer ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Transfer Model ◽  
B Cell Differentiation ◽  
Cell Numbers ◽  
Nsg Mice

Abstract Abstract 315 Adoptive transfer of primary patient CLL cells into NOD/SCID/γcnull(NSG) mice results in engraftment and proliferation of CLL cells if autologous T cells are present. Formation of splenic follicles consisting of B cells interspersed and surrounded by T cells indicates engraftment. However, ultimately these CD20+ cells are lost several weeks later. We describe one of the mechanisms for this apparent loss: differentiation to plasma cells. Peripheral blood cells from 9 IgM+ CLL patients (6 U-CLL and 3 M-CLL) were adoptively transferred into NSG mice with enriched autologous CD3+ cells pre-activated with anti-CD3/28 beads. B and T cell engraftment and subset distributions were analyzed for 47 mice by immunohistochemistry (IHC) and flow cytometry (FC) at the time of sacrifice. The earliest and latest times of assessment were 12 and 124 days, respectively, after CLL cell injection. In some cases, CLL cells were labeled with CFSE to track cell division. At sacrifice, 3 engraftment patterns were observed. Pattern 1 (observed up to day 56) showed small follicles of CD20+ cells with low-moderate numbers of surrounding T cells. Intensely positive CD38 cells were inconspicuous. FC showed CD19+CD5+ cells with no increase in CD38 and variable CFSE dilution indicating lower levels of proliferation. Pattern 2 (observed throughout the study period) showed much higher T and B cell numbers. CD20+ cells were interspersed with and surrounded by principally CD4+ cells which were activated and functional as indicated by expression of Ki-67, PD-1, CD57, and T cell derived cytokines IFNγ and IL5 in plasma. Follicles contained CD20 and cytoplasmic Ig+ (cIg+) cells that double stained for IRF-4 and Blimp-1, transcription factors required for B cell differentiation. While Bcl-6 staining in these cells was minimal or absent, follicles from all 9 patients contained activation-induced deaminase (AID)+ cells. Cells with dim IgM expression localized to follicles; however, cells with intense IgM, IgA, or IgG were present both within, surrounding, and outside follicles matched by similar CD38 staining. Smaller populations of CD138+ cells surrounded follicles and were interspersed throughout non-follicular splenic areas. FC showed a novel CD19+CD5-CFSE-CD38++ population containing a CD138+ subset. Pattern 3 (observed in a limited subset of cases not before day 63) had minimal CD20+ cells by IHC, but noticeable populations of cIg+CD38+ and CD138+ cells interspersed amongst plentiful T cells. Such cells corresponded with cells with plasma cell morphology. Confirmation that differentiated cells were from the patient clone was achieved in 3 ways. First, in FACS sorted CD19+CD5+ and CD19+CD5-38++ cells from a subset of pattern 2 cases, RT-PCR revealed that all fractions contained both IGHC unswitched and switched clones identical to those found in the patients. Second, cases with pattern 3 engraftment generated CLL clonal switched and unswitched cDNA sequences. Finally, adoptive transfer of highly purified CD5+CD19+ patient cells generated IRF-4+Blimp-1+CD138+ cells. The generation of switched cells from all 9 patients indicated functional AID. In one U- CLL case, ultra-deep sequencing on pre-transfer and post-transfer human cells taken from mouse spleen revealed a significant number of new IGHVDJ mutations in spleen-derived cells. Such mutations targeted nucleotides typical for AID's action. In conclusion, CLL cells can diversify, switch, and differentiate in NSG mice in response to autologous T cell signals. The extent of this maturation is a function of T cell numbers and activity and the duration of the experiment. Differentiation without significant Bcl-6 expression suggests that follicles in NSG mice are not recapitulating classic germinal center reactions, possibly giving clues to the origin of CLL. Several features of poor prognosis disease were demonstrated (e.g., increased CD38 and AID expression with the development of clonally related switched transcripts) that might mirror clinical disease features. AID expressed by CLL cells is fully functional as indicated by de novo somatic hypermutation and class switch recombination. Both U-CLL and M-CLL clones respond in a similar manner in this model, suggesting the importance of T– B cell interactions in all types of CLL. Finally, the demonstration that cells can differentiate when appropriately induced may lead to novel therapeutic options for CLL. Disclosures: No relevant conflicts of interest to declare.

Impact Of Epstein-Barr Viral Infection In The Regression Of Methotrexate-Induced Lymphoproliferative Diseases In Patients With Rheumatoid Arthritis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3006-3006 ◽  
Author(s):  
Tokuhira Michihide ◽  
Kimura Yuhta ◽  
Takahashi Yasuyuki ◽  
Tomikawa Tatsuki ◽  
Morihiko Sagawa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Lymphoproliferative Diseases ◽  
Ebv Infection ◽  
Epstein Barr

Abstract Background Recent studies have investigated the pathogenesis of the class of conditions known as “other iatrogenic immunodeficiency-associated lymphoproliferative diseases” (OIIA-LPDs), particularly in patients with rheumatoid arthritis (RA). Methotrexate (MTX) is a potent cause of LPDs, and withdrawal of MTX can result in spontaneous regression of LPD, which suggests that this drug plays an important role in the tumorigenesis of LPDs. In addition, an impaired immunity against Epstein-Barr virus (EBV) has been obserbed in RA patients. A number of reports describe LPD regression in patients with OIIA-LPDs-RA, but its precise etiology and pathogenesis remain unclear. Furthermore, the phenomenon of relapse/regrowth of LPDs after initial regression has not been well documented. This study retrospectively analyzed the clinicopathological features of OIIA-LPDs-RA patients to determine the influence of EBV infection on regression/relapse of the disease. Methods & Results Data were collected from 35 patients with RA who developed LPD and who were treated at our institute between 1998 and 2013. All patients had received treatment with MTX. The diagnosis of RA was made according to the American College of Rheumatology criteria. Based on immunohistochemistry performed on paraffin-embedded tissue sections, diagnoses were as follows: diffuse large B cell lymphoma (DLBCL; n=14), Hodgkin lymphoma (HL; n=7), follicular lymphoma (FL; n=4), mucosal-associated lymphoid tissue (MALT; n=3), Hodgkin-like lymphoma (HL-like; n=3), T-cell lymphoma (n=3), polymorphic LPD (P-LPD; n=2) according to the 4th WHO classification. Regarding EBV infection, 16 patients (44%) were positive. Patients with FL, MALT, and T-cell lymphoma were negative for EBV, except for one patient with T-cell lymphoma. In contrast, EBV infection positivity was prevalent in patients with DLBCL, HL, HL-like and P-LPD (46%, 100%, 100%, and 50%, respectively). Although HL indicated a specific phenotype, such as positivity for CD15 and CD30 (83%, and 100%, respectively), and rarely expressed CD20, OCT2 or BOB1 (0%, 14%, 14%, respectively), the phenotypes of HL-like and P-LPD were supposedly intermediate between DLBCL and HL. The phenotypes of FL, MALT, and T-cell lymphoma were the same as those of de novo cases. LPD regression was observed in 23 (66%) of 35 patients, which is more common than that seen in previous reports. Although LPD regression was not documented in patients with T-cell lymphoma, it did occur in all patients with HL, HL-like and P-LPD. In addition, the incidence of regression among patients with DLBCL, FL and MALT was 46%, 75% and 33%, respectively. The relationship between EBV infection and LPD regression among patients with HL, DLBCL, HL-like and P-LPD was statistically significant (p=0.048, Fisher's exact test). Of 23 patients with regression, 13 patients (56%) subsequently showed relapse/regrowth, and the incidence of this phenomenon was relatively high in patients with HL, HL-like and P-LPD (100%, 67%, and 50%, respectively), whereas a lower incidence was seen in patients with DLBCL, FL, and MALT (7%, 33%, and 0%, respectively). Summary/Conclusions LPD regression was relatively common (66%) in patients with OIIA-LPDs-RA, particularly in patients with B cell phenotypes. There was a significant relationship between LPDs and EBV infection in patients with HL, DLBCL and HL-like, suggesting that underlying EBV infection might influence the immunosuppressant effect of MTX against EBV in those phenotypes. Further, LPD relapse/regrowth was common in patients with HL, HL-like and P-LPD and was unlikely in patients with DLBCL. Further studies would be of benefit to investigate the underlying molecular mechanism of regression/relapse of LPD after withdrawal of MTX. Disclosures: No relevant conflicts of interest to declare.

Clinicopathologic features and treatment outcome of primary intestinal non-Hodgkin lymphoma: A single center experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19523-e19523
Author(s):  
Wei-Hsun Hsu ◽  
Kun-Huei Yeh ◽  
Chung-Wu Lin ◽  
Chih-Hung Hsu ◽  
Ann-Lii Cheng ◽  
...  
Keyword(s):  
Small Intestine ◽  
Treatment Outcome ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Clinicopathologic Features ◽  
Non Hodgkin Lymphoma

e19523 Background: Primary intestinal non-Hodgkin lymphoma (NHL) is a rare but heterogeneous disease in East Asia. However, the benefit of multidisciplinary treatment is still in debate. We characterized the clinicopathologic features, and treatment outcome in a single institute database. Methods: Patients with NHL primarily involving the intestine and treated during 1992 to 2008 were selected from the Cancer Registry of National Taiwan University Hospital. The medical charts and pathology records were carefully reviewed. Results: There were 64 men and 17 women with a median age of 51.5 years. Sites involved were colon/rectum (53.2%), small intestine (30.9%), and duodenum (13%). Histopathology subclassification included diffuse large B-cell lymphoma (DLBCL) (61.7%), mucosa-associated lymphoid tissue lymphoma (11.1%), Burkitt’s lymphoma (8.6%), T cell lymphoma (6.2%), follicular lymphoma (2.5%), mantle cell lymphoma (1.2 %) and others (8.6%). Ann Arbor stage IE to IIE accounted for 61.7%, whereas lower IPI score (1-2) were 54.8%. Among them, 27 patients received surgery plus chemotherapy, 60 received chemotherapy, and 4 had radiotherapy. At average follow-up of 48.7 months, 5 year survival rate were 59%, 43% and 51% for colon/rectum, small intestine, and duodenal NHL, respectively (p=0.45). Surgery plus chemotherapy versus chemotherapy alone showed no survival benefit in lower IPI group (p=0.682) nor in higher IPI (3-5) group (p=0.939). A trend of better median overall survival (mOS) was seen in rituximab group than in non-rituximab group in DLBCL subtypes (not reach vs. 39.8mo, p=0.075). In univariate analysis, stage III/IV (p=0.008), IPI score greater than 2 (p=0.011), and T cell histology (p<0.001) were significant prognostic factors for poor OS. In multivariate analysis, T cell histology remained the independent prognostic factor for inferior OS (p<0.001, HR: 20.3, 95% CI: 5.1-80.4). Conclusions: Although B cell NHL was the majority of primary intestinal NHL in our institute, T cell histology has significant inferior survival. Chemotherapy is still the backbone of treatment for primary intestinal NHL. The benefit of rituximab to intestinal DLBCL needs further confirmation.

scholarly journals In-silico design of a multi-epitope recombinant vaccine against SARS-CoV-2 targeting the receptor binding domain

2020 ◽  
Author(s):  
Harshawardhan Pande
Keyword(s):  
T Cell ◽  
B Cell ◽  
Receptor Binding ◽  
In Silico ◽  
Neutralizing Antibodies ◽  
De Novo ◽  
Recombinant Vaccine ◽  
Binding Domain ◽  
Surface Glycoprotein ◽  
Receptor Binding Domain

The COVID-19 pandemic caused by the SARS-CoV-2 virus is posing a major global challenge due to its rapid infectivity and lethality. Despite a global effort towards creating a vaccine, no viable vaccine currently exists. While multiple bioinformatic studies have attempted to predict epitopes, they have focused on the whole spike protein without considering antibody mediated enhancement or Th-2 immunopathology and have missed some important but less antigenic epitopes in the receptor binding domain. Therefore, this study used in silico methods to design and evaluate a potential multiepitope vaccine that specifically targets the receptor binding domain due to its critical function in viral entry. Immunoinformatic tools were used to specifically examine the receptor binding domain of the surface glycoprotein for suitable T cell and B cell epitopes. The selected 5 B cell and 8 T cell epitopes were then constructed into a subunit vaccine and appropriate adjuvants along with the universal immunogenic PADRE sequence were added to boost efficacy. The structure of the vaccine construct was predicted through a de novo approach and molecular docking simulations were performed which demonstrated high affinity binding to TLR 5 receptor and appropriate HLA proteins. Finally, the vaccine candidate was cloned into an expression vector for use as a recombinant vaccine. Similarities to some recent epitope mapping studies suggest a high potential for eliciting neutralizing antibodies and generating a favorable overall immune response.

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