scholarly journals Primary T-Cell Non-Hodgkin Lymphoma of the Vagina

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
J. L. Herraiz ◽  
A. Llueca ◽  
Y. Maazouzi ◽  
D. Piquer ◽  
A. Palmeiro ◽  
...  

The primary vaginal T-cell non-Hodgkin lymphoma is a rare form of lymphoma. Most of the previously published cases were about B-cell non-Hodgkin lymphomas. We present the case of a vaginal mass in an 82-year-old patient presenting vaginal bleeding. The results of the immunohistological studies of the mass revealed the presence of a cytotoxic T-cell non-Hodgkin lymphoma, which is the least common subtype.

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1945-1945 ◽  
Author(s):  
Wenqun Zhang ◽  
Bo Hu ◽  
Ling Jing ◽  
Jing Yang ◽  
Shan Wang ◽  
...  

Background:Outcomes for pediatric patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) are poor despite use of high-intensity chemotherapy. CAR-T has shown efficacy in treating refractory/relapsed leukemia in pediatric patients and non-Hodgkin lymphoma in adult patients. Objectives:To assess the safety and efficacy of sequential CAR-T in the treatment of refractory/ relapsed B-NHL in pediatric patients. Design/Methods:In our ongoing clinical trial (ChiCTR1800014457), we enrolled and treated 17 pediatric patients with refractory/relapsed B-NHL. Following leukapheresis, T cells were activated with CD3 and CD28 antibodies for 24h, then transduced with lentivirus encoding anti-CD19-CD3zeta-4-1BB CAR and cultured for 5-6 days in serum-free media containing IL2, IL7, IL15, IL21. Meanwhile, all patients briefly received lympho-depleting chemotherapies consisting of fludarabine (30 mg/m2/day) and cyclophosphamide (250 mg/m2/day) on days −5, −4 and −3 according to tumor burden and patient state. On day 0, all patients received a single-dose infusion of CAR-T cells. CAR-T cell dose ranged from 0.5 to 3 million/kg. CAR-T cell numbers and cytokines were measured weekly. Tumor responses were evaluated at day 30 and day 60 post infusion and every two months thereafter. Adverse events were graded according to CTCAEv4 except cytokine release syndrome (CRS) was graded according to Lee et al. Results:Treated patients had relapsed/refractory Burkitt lymphoma (BL) (13/17), diffuse large B cell lymphoma (DLBCL) (2/17), B-lymphoblastic lymphoma (B-LBL) (2/17), and ranged from 4.5-18.0 years old. By St Jude's staging, 9 cases (46.7%) were in stage III, 8 cases (53.3%) were in stage IV. There were 3 cases with CNS involvement (17.6%) and 7 cases with bone marrow involvement (41.2%). They all failed at prior treatment including an average of 8.9 (6-15) courses of chemotherapy. They were then treated with sequential CAR-T cell therapy. A total of 26 courses of CAR-T cell infusion were administered. The overall complete response rate (CRR) was 41.7% (7/17) when first course of CAR-T therapy was conducted, which were all CD19 targeted. Among the 10 patients who did not achieve CR, 2 patients achieved PR with ongoing response, 1 patient died of severe CRS and progression at day 6 and another patient refused to continue the following therapy when tumor progressed at day 99, and he died 1 week later, the other 6 continued to receive second course of CAR-T therapy targeting CD20 or CD22, and 3 of them achieved CR. Thus the overall CRR increased to 58.8% (10/17). The 3 patients, who still did not achieve CR, continued to receive third course of CAR-T therapy targeting CD20 or CD22. Two of them finally achieved CR and the other failed to get CR and is now retreated with chemotherapy and oral Olaparib and Venclexta. Thus, with a median follow-up of 6.2 months (1-18 months), the overall response rate of sequential CAR-T therapy was 94.1% (16/17) and the overall CRR was 70.6% (12/17). Toxicity information through day 30 revealed the occurrence of mild CRS in 8 subjects (47.1%, grade I n=8, grade II n=0), severe CRS in 9 subjects (52.9%, grade III n=8, grade IV n=1). Neurotoxicity was observed in 7 cases (41.2%, seizure in 3 cases, tremor in 4 cases, headache in 1 cases). One case who died rapidly at day 6 of therapy suffered severe CRS (high fever, Capillary leak syndrome, severe pleural effusion, respiratory failure, shock, cardiopulmonary arrest) and neurotoxicity besides disease progression. Other patients with severe CRS and neurotoxicity recovered fully after glucocorticoid use and symptomatic treatment including anti-epilepsy, fluid, dehydrating agent. No case used tocilizumab. Response assessments were performed at day 15, 30, 45, 60. Updated enrollment, toxicity and response assessments will be presented. Conclusion: CD19/CD20/CD22-CAR-T therapy showed promising efficacy for pediatric patients with r/r B-NHL and the toxicities are tolerable with proper symptomatic and supportive treatment. Sequential CAR-T therapy can improve the efficacy compared with a single course of CAR-T infusion. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4187-4187 ◽  
Author(s):  
Zixun Yan ◽  
Wen Wang ◽  
Zhong Zheng ◽  
Ming Hao ◽  
Su Yang ◽  
...  

Abstract Introduction JWCAR029 is a novel CD19-directed 4-1BB stimulated chimeric antigen receptor T (CAR-T) cell type, which is different from JWCAR017 with independent production of CD4 and CD8 T cells and transfusion in non-fixed ratio. We conducted a single arm, open-label, dose escalation Phase I trial of JWCAR029 in relapsed and refractory B-cell non-Hodgkin lymphoma (NCT03355859). Methods From January to July 2018, 10 patients have been enrolled in this trial, including eight diffused large B cell lymphoma (DLBCL) and two MALT lymphoma, with median age of 47 years (range 32 to 59 years). All the patients received immunochemotherapy as induction and more than two lines of salvage treatment. Two patients received bridging chemotherapy after T-cell collection due to rapid tumor progression, followed by re-evaluation before CAR-T cell infusion. Lymphodepletion preconditioning was accomplished by fludarabine 25mg/m2/d and cyclophosphamide 250mg/m2/d on Day-4 to D-2, followed by CAR-T cell infusion on Day0. JWCAR029 was administrated as a single infusion in escalation dose levels, from 2.5×107 CAR-T cells (dose level 1, DL1) to 5.0×107 CAR-T cells (dose level 2, DL2) and to 1.0×108 CAR-T cells (dose level 3, DL3) according to mTPI-2 algorithm. Circulating blood count, serum biochemistry, and coagulation status were follow-up after infusion. Cytokines were assessed on a Luminex platform. Tumor evaluation was performed on Day 29 by PET-CT. PK data were detected by flow cytometry and real-time quantitative polymerase chain reaction system. All the adverse events were recorded. The study was approved by the Shanghai Rui Jin Hospital Review Board with informed consent obtained in accordance with the Declaration of Helsinki. Results The demographic characteristics of the patients were demonstrated in Table 1. Among six evaluable patients (3 of DL1 and 3 of DL2), the ORR was 100% on Day 29, including four complete remission and 2 partial remission. Cytokine release syndrome (CRS) was 100% in Gr 1, with main symptoms as fever (<39.0 degrees), fatigue, and muscle soreness. No neurotoxicity was observed. Four of the six patients with fever >38.0 degrees used prophylactic IL-6 Inhibitor (8mg/kg, ACTEMRA, two patients administered twice). No patients received steroids. The CRS showed no difference between dose level groups (p>0.99). Adverse effects included leukopenia (Gr 3-4: 83.3%, Gr 1-2: 16.7%), hypofibrinogenemia (Gr 1: 16.7%, Gr 2-4: 0%), liver dysfunction (Gr 1: 33.3%, Gr 2-4: 0%), elevated CRP (Gr 1: 83.3%, Gr 2-4: 0%), ferritin (Gr 1-2: 83.3%, Gr 2-4: 0%), or IL-6 (Gr 1-2:100%, Gr 3-4: 0%, Table 2). Conclusion Although long-term follow-up was needed, the preliminary data of six patients in this trial have demonstrated high response rates and safety of JWCAR029 in treating relapsed and refractory B-cell non-Hodgkin lymphoma. Disclosures Hao: JW Therapeutics: Employment, Equity Ownership.


2020 ◽  
Vol 26 (3) ◽  
pp. S326 ◽  
Author(s):  
Kitsada Wudhikarn ◽  
Martina Pennisi ◽  
Martha Garcia Recio ◽  
Molly A. Maloy ◽  
Gunjan L. Shah ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4734-4734
Author(s):  
Jun Takizawa ◽  
Sadao Aoki ◽  
Kazue Takai ◽  
Tohri Kurasaki ◽  
Keiichiro Honma ◽  
...  

Abstract Introduction CHOP chemotherapy has been accepted as the standard treatment for patients with non-Hodgkin lymphoma (NHL), but in some histological or clinical subtypes the results are not satisfactory. We have shown the efficacy and safety of high-dose biweekly THP-COP with G-CSF support (HDBW-TCOP(G)) for NHL. In this regimen, we choose pirarubicin in stead of doxorubicin because it was proven high efficacy against NHL and the lower toxicity than doxorubicin. Recently, the combination of rituximab and standard CHOP has been shown to have a synergistic effect for NHL. We performed a phase II multicentric clinical study to assessed the feasibility and toxicity of the combination chemotherapy of rituximab and HDBW-TCOP(G) (HDBW-R-TCOP(G)) compared with those of HDBW-TCOP(G). Patients and methods Between August 1998 and December 2004, Forty-one Japanese patients with previously untreated NHL from whom informed consent was obtained were included in this study. Median age was 45 (range 19–63) years. There were 19 males and 22 females. According to WHO-classification diagnoses, histological subtypes included follicular lymphoma (FL) 15(37%); nodal marginal zone B-cell lymphoma (NMZBCL) 2(5%); mantle cell lymphoma (MCL) 3(7%); anaplastic large cell lymphoma (ALCL) 1(2%), diffuse large B-cell lymphoma (DLBCL) 18(44%); peripheral T-cell lymphoma (PTCL) 1(2%), angioimmunoblastic T-cell lymphoma (AILT) 1(2%). Of 41 patients, one patient was stage 1, stage 2, 11 stage 3 and 16 stage 4. International prognostic index (IPI) included L 6; LI 22; HI 7; H 6. HDBW-TCOP(G) consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 orally from day 1 to 5; lenograstim 2.0 μg/kg/day from day 3. Fifteen patients who enrolled after rituximab was approved in Japan received therapy combined HDBW-TCOP(G) with rituximab 375mg/ m2 on day -2 (HDBW-R-TCOP(G)). Six cycles were administered at intervals of two weeks. Results Of the 41 patients treated, 32 (78.0%) achieved a complete remission (CR) and nine (22.0%) achieved a partial remission (PR), for an overall response rate of 100%. After median follow-up of 36 months (range 2.9– 81.8), progression free survival (PFS) and overall survival (OS) were 68.2% and 97.5%, respectively. PFS was 90.9% for HDBW-R-TCOP(G), and 69.5% for HDBW-TCOP(G), but no significant differences was found among two regimen. There was no significant difference in the PFS and OS between aggressive and indolent histological subtypes. 76% of patients developed Grade4 leukopenia (according to NCI criteria) but no patients experienced febrile neutropenia. 15% of patients developed G4 anemia and 17% of patients G4 thrombocytopenia. Other adverse effects were minimal. Conclusion Both HDBW-TCOP(G) and HDBW-R-TCOP(G) are feasible for NHL with acceptable toxicity. The excellent result suggests they are effective for aggressive NHL patients with poor prognostic factors and advanced stage indolent NHL.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4336-4336
Author(s):  
Shazia Zafar ◽  
Sathish Srinivasan ◽  
Zafar Nawaz

Abstract Over the past decade considerable progress has been made in cloning and characterization of potential tumor suppressor genes. Tumor suppressors have a repressive effect on the regulation of the cell cycle or promote apoptosis and sometimes do both. The function of tumor suppressor proteins fall into several categories, tumor suppressor genes are presumed to encode negative regulator of proliferation and inhibit mitotic activity. Loss of tumor suppressor protein or function of a tumor suppressor protein has been shown to be associated with the cancer formation. Continued investigation into the biochemical and cell biological functions of the tumor suppressor is critical to elucidate the mechanisms by which they normally inhibit proliferation/tumor development and to provide a molecular explanation for their frequent inactivation in cancer. Our laboratory has previously shown that the expression of E6-associated protein (E6-AP), which is an E3 ubiquitin-protein ligase and a coactivator of nuclear hormone receptors, is significantly reduced in human cancers having epithelial cell origin such as breast cancer. In this prospective study, we want to extend our observation to the cancers originating from lymphoid tissue. Non-Hodgkin lymphoma is a cancer of lymphoid tissue. The main cell type found in lymphoid tissue is the lymphocyte. The 2 main types of lymphocytes are B-lymphocytes (B-cells) and T-lymphocytes (T-cells). B-cell lymphomas are much more common than T-cell lymphomas. In the U. S., 85% of all cases of non-Hodgkin lymphoma come from B lymphocytes (B-cell) and 15% from T lymphocytes (T-cell). We performed immunohistochemistry analysis to investigate the expression pattern of E6-AP in normal lymph nodes and lymphoid tumors. Tissue micro arrays representing samples from 60 different patients were analyzed in this study. Our analysis suggest that on an average there was about 55 % reduction in E6-AP protein levels in B-cell lymphomas (P =0.0001) and 98.5 % reduction in E6-AP levels in T-cell lymphomas (P =0.0002) compared to normal lymph node. Based on our previous studies in breast and prostate tumors and considering our current finding of reduced/loss of E6-AP in lymphoid tumors, we propose that E6-AP may act as a potential tumor suppressor protein. This proposed idea is consistent with our in vivo data generated from E6-AP null mice which shows that the number of B- and T-cells are significantly increased in spleen compared to normal wild-type animals. Taken together our data establish the role of E6-AP as a potential growth and tumor suppressor protein.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5299-5299
Author(s):  
Yonghong Zhang ◽  
Ling Jin ◽  
Jing Yang ◽  
Yanlong Duan ◽  
Chunjv Zhou ◽  
...  

Abstract One hundred and nineteen children with non-Hodgkin lymphoma were treated between February 2003 and December 2006 in Beijing Children’s Hospital on BCH-2003-NHL protocol. The diagnosis was made by histopathology of the biopsied tissue and/or bone marrow, and disease was classified according to WHO-2001 pathologic classification. We applied modified LMB89 protocol to cases with B-cell lymphoma; modified BFM90-ALL protocol for lymphoblastic lymphoma and cutaneous T-cell/NK cell lymphoma; and modified BFM90-ALCL protocol for anaplastic large-cell lymphoma (ALCL). There were 50 cases (42%) of B cell lymphoma including 32 cases of Burkitt¡’s lymphoma, 10 cases of Burkitt-like lymphoma and 8 cases of diffuse large B cell lymphoma; 44 cases (37%) of lymphoblastic lymphoma; 19 cases (16%) of ALCL; and 6 cases (5%) of cutaneous T-cell/NK cell lymphoma. The 85 boys and 34 girls (ratio, 2.5:1) ranged in age from 2 to 15 years (median, 7.8 years) at diagnosis. B cell lymphoma typically presented as abdomen mass and acute abdomen; nasopharynx and tonsil were also common sites of involvement. Lymphoblastic lymphoma generally presented with mediastinal mass and bone marrow involvement. There was no typical presentation for ALCL. According to the St. Jude staging system, 19 cases had stage I–II, and 94 cases stage III–VI diseases (exclude 6 cases of cutaneous T-cell/NK cell lymphoma). Seven cases had CNS involvement and 25 cases involved bone marrow. The treatment duration was 2 to 8 months for B-cell lymphoma, 2.5 to 3 years for lymphoblastic lymphoma and 1 to 1.5 years for ALCL. The follow-up rate was 100% and median observation period was 23 months. The overall survival (OS) at 3 years was 90.7% and the 3-year event-free survival (EFS) estimate was 82.3%. For B-cell lymphoma, 3-year OS was 88.68% and 3-year EFS was 81.8%. For lymphoblastoma lymphoma, the rates were 89.3% and 69.4%, respectively. All cases of ALCL are alive with on undergoing treatment for relapse. Patients with ALCL achieved the best 3-year OS (100%) and had 3-year EFS of 94.2%. Grade 3 or 4 bone marrow suppression occurred in 97.5% of patients with B-cell lymphoma, 100% of those with lymphoblastic lymphoma and 89.5% of cases with ALCL. As of to date, 11 patients have died, the causes of death include infection (n=4), abandonment of therapy (n=6) and relapse (n=1). Univarate analysis showed that stage IV disease, failure to achieve complete remission after 3 months of treatment, and bulky mass are were associated with poor prognosis £all P values &lt;0.05£©. In summary, we have achieved excellent treatment results using modified international protocols. Infection and financial problem remained the main reasons of treatment failure.


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 ◽  
...  

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.


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