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Sample records for follicular lymphoma results

  1. Follicular Lymphoma Diagnosed With Medical Thoracoscopy.

    PubMed

    Ahmad, Sumera R; Lee, Paul J; Ghasemi, Mitra; Sosa, Andres F

    2016-01-01

    Non-Hodgkin lymphomas may present with a recurrent pleural effusion, usually with involvement of other thoracic or extrathoracic sites. Lymphomas typically presenting with pleural disease include primary effusion lymphoma and pyothorax-associated lymphoma. We describe an unusual case of recurrent pleural effusion secondary to follicular lymphoma with no other known extrathoracic involvement at the time of diagnosis. PMID:26496088

  2. Follicular lymphoma of the submandibular salivary gland

    PubMed Central

    Shashidara, R.; Prasad, Priyanka R.; Jaishankar; Joseph, Thomas

    2014-01-01

    Lymphomas are neoplastic diseases of lymph nodes. Lymphoma of the salivary gland is rare accounting for less than 5% of lymphomas overall. Furthermore, lymphomas arising in the submandibular gland are reported to comprise 916% of all salivary gland lymphomas. Among lymphomas originating from salivary glands, the ratio of follicular lymphoma is very low. They can also be seen in the lymph nodes of the salivary glands which is an uncommon presentation. Here, we present a case follicular lymphoma which presented as a salivary gland tumour. PMID:25364171

  3. Pegfilgrastim and Rituximab in Treating Patients With Untreated, Relapsed, or Refractory Follicular Lymphoma, Small Lymphocytic Lymphoma, or Marginal Zone Lymphoma

    ClinicalTrials.gov

    2015-11-20

    Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  4. Bilateral conjunctival follicular lymphoma in a child.

    PubMed

    Wall, Palak B; Traboulsi, Elias I; Hsi, Eric D; Singh, Arun D

    2015-04-01

    Follicular lymphoma is exceedingly rare in children. We present the case of a 10-year-old patient with a conjunctival lesion on the left eye who later developed a similar lesion on the right eye. Excisional biopsy of the left eye lesion revealed follicular lymphoma. The patient was treated with systemic rituximab. To our knowledge, only 4 other cases of pediatric conjunctival follicular lymphoma have been reported, all of which were isolated lesions that were treated with excisional biopsy alone. PMID:25824110

  5. Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma

    ClinicalTrials.gov

    2016-06-15

    Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma

  6. Rituximab and Oblimersen in Treating Patients With Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-04

    Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  7. Follicular lymphoma: evolving therapeutic strategies.

    PubMed

    Kahl, Brad S; Yang, David T

    2016-04-28

    Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. After decades of stagnation, the natural history of FL appears to have been favorably impacted by the introduction of rituximab. Randomized clinical trials have demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Maintenance rituximab strategies can improve progression-free survival. Even chemotherapy platforms have changed in the past 5 years, as bendamustine combined with rituximab has rapidly become a standard frontline strategy in North America and parts of Europe. Recent discoveries have identified patients at high risk for poor outcomes to first-line therapy (m7-Follicular Lymphoma International Prognostic Index [m7-FLIPI]) and for poor outcomes after frontline therapy (National LymphoCare Study). However, several unmet needs remain, including a better ability to identify high-risk patients at diagnosis, the development of predictive biomarkers for targeted agents, and strategies to reduce the risk of transformation. The development of targeted agents, exploiting our current understanding of FL biology, is a high research priority. A multitude of novel therapies are under investigation in both the frontline and relapsed/refractory settings. It will be critical to identify the most appropriate populations for new agents and to develop validated surrogate end points, so that novel agents can be tested (and adopted, if appropriate) efficiently. PMID:26989204

  8. Nature and importance of follicular lymphoma precursors

    PubMed Central

    Mamessier, Emilie; Broussais-Guillaumot, Florence; Chetaille, Bruno; Bouabdallah, Reda; Xerri, Luc; Jaffe, Elaine S.; Nadel, Bertrand

    2014-01-01

    It is now widely recognized that cancer development is a protracted process requiring the stepwise acquisition of multiple oncogenic events. In humans, this process can take decades, if not a lifetime, blurring the notion of ‘healthy’ individuals. Follicular lymphoma exemplifies this multistep pathway of oncogenesis. In recent years, variants of follicular lymphoma have been recognized that appear to represent clonal B-cell expansions at an early stage of follicular lymphoma lymphomagenesis. These include follicular lymphoma in situ, duodenal follicular lymphoma, partial involvement by follicular lymphoma, and in the blood circulating follicular lymphoma-like B cells. Recent genetic studies have identified similarities and differences between the early lesions and overt follicular lymphoma, providing important information for understanding their biological evolution. The data indicate that there is already genomic instability at these early stages, even in instances with a low risk for clinical progression. The overexpression of BCL2 in t(14;18)-positive B cells puts them at risk for subsequent genetic aberrations when they re-enter the germinal center and are exposed to the influences of activation-induced cytidine deaminase and somatic hypermutations. The emerging data provide a rationale for clinical management and, in the future, may identify genetic risk factors that warrant early therapeutic intervention. PMID:24790058

  9. Localized Low-Dose Radiotherapy for Follicular Lymphoma: History, Clinical Results, Mechanisms of Action, and Future Outlooks

    SciTech Connect

    Ganem, Gerard; Cartron, Guillaume; Girinsky, Theodore; Haas, Rick L.M.; Cosset, Jean Marc; Solal-Celigny, Philippe

    2010-11-15

    The extreme radiosensitivity of indolent lymphomas was reported in the early years of radiotherapy (RT). The efficacy of low-dose total body irradiation (1.5-2 Gy) was particularly demonstrative. Higher doses were considered appropriate for localized disease. The optimal (or conventional) dose of curative RT derived from the early studies was determined to be 30-35 Gy. Nevertheless, in older series addressing the tumoricidal radiation dose in non-Hodgkin's lymphomas, investigators noted that a significant number of 'nodular' lymphomas were controlled with a dose of <22 Gy for >3 years. The idea of reintroducing localized low-dose radiotherapy (LDRT) for indolent non-Hodgkin's lymphomas came from a clinical observation. The first study showing the high efficacy of LDRT (4 Gy in two fractions of 2 Gy within 3 days) in selected patients with chemoresistant, indolent, non-Hodgkin's lymphomas was published in 1994. Since this first report, at least eight series of patients treated with localized LDRT have been published, showing a 55% complete response rate in irradiated sites, with a median duration of 15-42 months. How LDRT induces lymphoma cell death remains partly unknown. However, some important advances have recently been reported. Localized LDRT induces an apoptosis of follicular lymphoma cells. This apoptotic cell death elicits an immune response mediated by macrophages and dendritic cells. Follicular lymphoma is probably an ideal model to explore these mechanisms. This review also discusses the future of LDRT for follicular lymphoma.

  10. Treatment approaches to asymptomatic follicular lymphoma.

    PubMed

    Sarkozy, Clémentine; Salles, Gilles

    2013-12-01

    Follicular lymphoma is a heterogeneous disease in which some patients present an indolent evolution for decades and others, a rather aggressive form of the disease requiring immediate therapy. While immunochemotherapy has emerged as a standard of care for symptomatic patients, treatment of the asymptomatic population remains controversial. Since the disease is still considered incurable, delayed initiation of therapy is an acceptable option. However, four single injections of rituximab can result in an acceptable clinical response and can improve the duration of the interval without cytotoxic therapy. With recent therapeutic approaches that enable substantial improvements in life expectancy for follicular lymphoma patients, limiting short- or long-term treatment toxicities appears as a new concern in the asymptomatic population. Based on these options, the challenge is to preserve patient quality of life and prolong survival: from the patient's perspective, his/her opinion is therefore of significant importance. PMID:24219551

  11. Rituximab Retreatment for Low-Tumor Burden Follicular Lymphoma

    Cancer.gov

    A summary of results from a randomized clinical trial of patients with low–tumor burden follicular lymphoma that compared maintenance therapy with rituximab versus retreatment with rituximab only when there was evidence of disease progression.

  12. Rituximab, Lenalidomide, and Ibrutinib in Treating Patients With Previously Untreated Stage II-IV Follicular Lymphoma

    ClinicalTrials.gov

    2016-08-24

    Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  13. Genetics of follicular lymphoma transformation

    PubMed Central

    Pasqualucci, Laura; Khiabanian, Hossein; Fangazio, Marco; Vasishtha, Mansi; Messina, Monica; Holmes, Antony B.; Ouillette, Peter; Trifonov, Vladimir; Rossi, Davide; Tabbò, Fabrizio; Ponzoni, Maurilio; Chadburn, Amy; Murty, Vundavalli V.; Bhagat, Govind; Gaidano, Gianluca; Inghirami, Giorgio; Malek, Sami N.; Rabadan, Raul; Dalla-Favera, Riccardo

    2014-01-01

    Summary Follicular lymphoma (FL) is an indolent disease, but 30-40% of cases undergo histologic transformation to an aggressive malignancy, typically represented by diffuse large B cell lymphoma (DLBCL). The pathogenesis of this process remains largely unknown. Using whole-exome sequencing and copy-number analysis, here we show that the dominant clone of FL and transformed FL (tFL) arise by divergent evolution from a common mutated precursor through the acquisition of distinct genetic events. Mutations in epigenetic modifiers and anti-apoptotic genes are introduced early in the common precursor, while tFL is specifically associated with alterations deregulating cell-cycle progression and DNA-damage responses (CDKN2A/B, MYC, TP53), as well as with aberrant somatic hypermutation. The genomic profile of tFL shares similarities with that of germinal center B-cell-type de novo DLBCL, but also displays unique combinations of altered genes, with diagnostic and therapeutic implications. PMID:24388756

  14. Tonsillar follicular lymphoma in a child.

    PubMed

    Amit, Sonal; Purwar, Neetu; Agarwal, Asha; Lalchandani, Devendra

    2012-01-01

    Follicular lymphomas (FL) are among the most common non-Hodgkin's lymphoma (NHL) in adults. However, they are rare in children making up less than 3% of paediatric NHL cases. They occur most commonly in the head and neck region, lymph nodes or tonsils, with occasional extra-nodal occurrences. Distinction of FL from potentially clonal but, reactive follicular hyperplasia is important. We report a case of a 6-year-old male child presenting with night stridor since 6 months. Clinical examination revealed asymmetrical enlargement of the left tonsil. Routine left tonsillectomy was performed and the specimen was sent for histopathological examination. Diagnosis of follicular lymphoma was made on histopathological examination and further confirmed by immunohistochemistry. PMID:23188842

  15. Ofatumumab and Bendamustine Hydrochloride With or Without Bortezomib in Treating Patients With Untreated Follicular Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-08-24

    Grade 3a Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  16. Early lesions of follicular lymphoma: a genetic perspective

    PubMed Central

    Mamessier, Emilie; Song, Joo Y.; Eberle, Franziska C.; Pack, Svetlana; Drevet, Charlotte; Chetaille, Bruno; Abdullaev, Ziedulla; Adelaïde, José; Birnbaum, Daniel; Chaffanet, Max; Pittaluga, Stefania; Roulland, Sandrine; Chott, Andreas; Jaffe, Elaine S.; Nadel, Bertrand

    2014-01-01

    The pathogenesis of follicular lymphoma is a multi-hit process progressing over many years through the accumulation of numerous genetic alterations. Besides the hallmark t(14;18), it is still unclear which other oncogenic hits contribute to the early steps of transformation and in which precursor stages these occur. To address this issue, we performed high-resolution comparative genomic hybridization microarrays on laser-capture micro-dissected cases of follicular lymphoma in situ (n=4), partial involvement by follicular lymphoma (n=4), and duodenal follicular lymphoma (n=4), assumed to represent, potentially, the earliest stages in the evolution of follicular lymphoma. Cases of reactive follicular hyperplasia (n=2), uninvolved areas from follicular lymphoma in situ lymph nodes, follicular lymphoma grade 1–2 (n=5) and follicular lymphoma grade 3A (n=5) were used as controls. Surprisingly, alterations involving several relevant (onco)genes were found in all entities, but at significantly lower proportions than in overt follicular lymphoma. While the number of alterations clearly assigns all these entities as precursors, the pattern of partial involvement by follicular lymphoma alterations was quantitatively and qualitatively closer to that of follicular lymphoma, indicating significant selective pressure in line with its faster rate of progression. Among the most notable alterations, we observed and validated deletions of 1p36 and gains of the 7p and 12q chromosomes and related oncogenes, which include some of the most recurrent oncogenic alterations in overt follicular lymphoma (TNFRSF14, EZH2, MLL2). By further delineating distinctive and hierarchical molecular and genetic features of early follicular lymphoma entities, our analysis underlines the importance of applying appropriate criteria for the differential diagnosis. It also provides a first set of candidates likely to be involved in the cascade of hits that pave the path of the various progression phases

  17. Sugar-coated signaling in follicular lymphoma.

    PubMed

    Strout, Matthew P

    2015-10-15

    In this issue of Blood, complementary studies by Amin et al and Linley et al demonstrate that sugar moieties linked to surface immunoglobulin (sIg) of follicular lymphoma (FL) cells directly interact with endogenous lectins within the lymphoma niche and lead to activation of downstream B-cell receptor (BCR) signaling pathways. In addition to providing further insight into the role of the microenvironment in lymphomagenesis, these findings expose a unique molecular interaction that may represent a viable target for therapeutic intervention. PMID:26472734

  18. Ileal follicular lymphoma with atypical endoscopic findings.

    PubMed

    Yamada, Satoshi; Koshikawa, Yorimitsu; Minami, Naoki; Honzawa, Yusuke; Matsuura, Minoru; Nakase, Hiroshi

    2016-03-01

    A 72-year-old woman presented with symptomatic anemia without abdominal symptoms. She had no history of abdominal surgery or use of non-steroidal anti-inflammatory drugs. Enhanced computed tomography of the abdomen revealed swelling of multiple intraperitoneal lymph nodes and a high density of mesenteric adipose tissue. Fluorodeoxyglucose (FDG-) positron emission tomography showed high FDG accumulation at the intraperitoneal lymph nodes. Double-balloon enteroscopy detected severe stenosis with an annular ulcer in the lower ileum. She was diagnosed with ileal follicular lymphoma based on histologic examination and fluorescence in situ hybridization analysis of the biopsy specimen. The ileal ulcer was successfully treated by chemotherapy with rituximab and bendamustine for 1 year. We strongly recommend consideration of gastrointestinal follicular lymphoma in the differential diagnosis of annular ulcers in the small intestine. PMID:27004251

  19. Computerized microscopic image analysis of follicular lymphoma

    NASA Astrophysics Data System (ADS)

    Sertel, Olcay; Kong, Jun; Lozanski, Gerard; Catalyurek, Umit; Saltz, Joel H.; Gurcan, Metin N.

    2008-03-01

    Follicular Lymphoma (FL) is a cancer arising from the lymphatic system. Originating from follicle center B cells, FL is mainly comprised of centrocytes (usually middle-to-small sized cells) and centroblasts (relatively large malignant cells). According to the World Health Organization's recommendations, there are three histological grades of FL characterized by the number of centroblasts per high-power field (hpf) of area 0.159 mm2. In current practice, these cells are manually counted from ten representative fields of follicles after visual examination of hematoxylin and eosin (H&E) stained slides by pathologists. Several studies clearly demonstrate the poor reproducibility of this grading system with very low inter-reader agreement. In this study, we are developing a computerized system to assist pathologists with this process. A hybrid approach that combines information from several slides with different stains has been developed. Thus, follicles are first detected from digitized microscopy images with immunohistochemistry (IHC) stains, (i.e., CD10 and CD20). The average sensitivity and specificity of the follicle detection tested on 30 images at 2×, 4× and 8× magnifications are 85.5+/-9.8% and 92.5+/-4.0%, respectively. Since the centroblasts detection is carried out in the H&E-stained slides, the follicles in the IHC-stained images are mapped to H&E-stained counterparts. To evaluate the centroblast differentiation capabilities of the system, 11 hpf images have been marked by an experienced pathologist who identified 41 centroblast cells and 53 non-centroblast cells. A non-supervised clustering process differentiates the centroblast cells from noncentroblast cells, resulting in 92.68% sensitivity and 90.57% specificity.

  20. Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-28

    Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  1. [Diffuse large B-cell lymphoma developed newly after 9-year remission of a follicular lymphoma].

    PubMed

    Hirano, Taichi; Tsuji, Takahiro; Yamasaki, Hiroshi; Toyozumi, Yasuo; Arima, Nobuyuki; Tsuda, Hiroyuki

    2016-02-01

    Follicular lymphoma (FL) occasionally transforms into diffuse large B-cell lymphoma (DLBCL). This is generally associated with a poor prognosis, necessitating more potent chemotherapy as salvage treatment. However, de novo DLBCL, but not DLBCL transformed from FL, can be treated as primary DLBCL. We encountered a 63-year-old woman who developed DLBCL after a 9-year remission following treatment of FL. To differentiate DLBCL transformed from FL and de novo DLBCL, VDJ gene rearrangements in IgH were examined by PCR using biopsy specimens from both lymphomas. The results revealed the two lymphomas to be different clones. Thus, she was diagnosed with primary DLBCL. Therefore, routine chemotherapy and radiation therapy were conducted for the primary DLBCL with a limited stage, achieving complete remission. Treatment based on the clonality assessment of VDJ gene rearrangements is potentially useful for treating late relapse of B-cell lymphoma according to the pathological conditions of patients. PMID:26935635

  2. Cell of origin of transformed follicular lymphoma

    PubMed Central

    Kridel, Robert; Mottok, Anja; Farinha, Pedro; Ben-Neriah, Susana; Ennishi, Daisuke; Zheng, Yvonne; Chavez, Elizabeth A.; Shulha, Hennady P.; Tan, King; Chan, Fong Chun; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Sehn, Laurie H.; Marra, Marco A.; Shah, Sohrab P.; Steidl, Christian; Connors, Joseph M.; Scott, David W.

    2015-01-01

    Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell–like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell–like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL. PMID:26307535

  3. Cell of origin of transformed follicular lymphoma.

    PubMed

    Kridel, Robert; Mottok, Anja; Farinha, Pedro; Ben-Neriah, Susana; Ennishi, Daisuke; Zheng, Yvonne; Chavez, Elizabeth A; Shulha, Hennady P; Tan, King; Chan, Fong Chun; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Sehn, Laurie H; Marra, Marco A; Shah, Sohrab P; Steidl, Christian; Connors, Joseph M; Scott, David W; Gascoyne, Randy D

    2015-10-29

    Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL. PMID:26307535

  4. IMMUNOGLOBULIN LIGHT CHAIN IMMUNOHISTOCHEMISTRY REVISITED, WITH EMPHASIS ON REACTIVE FOLLICULAR HYPERPLASIA VS. FOLLICULAR LYMPHOMA

    PubMed Central

    Weiss, Lawrence M.; Loera, Sofia; Bacchi, Carlos E.

    2009-01-01

    The identification of monotypic light chains is an important adjunct to the diagnosis of B-cell lymphoma, yet is often difficult to reliably perform on formalin-fixed paraffin sections. We have evaluated a new set of monoclonal antibodies to kappa and lambda light chain that are reactive in paraffin sections. In reactive lymphoid tissues, polytypic staining was noted in greater than 95% of cases, with strong staining of plasma cells, moderate staining of the follicular dendritic cell network, and weak staining of mantle zone cells. Strong staining for the appropriate light chain was seen in each of 7 cases of multiple myeloma. In a series of 58 cases of B-cell lymphoma, correlation between the results of immunohistochemistry and flow cytometry was obtained in 36 cases (62%), including 32 cases (21 kappa and 11 lambda) in which a single light chain was expressed. Monotypic staining also seen in 6 additional cases (10%) in which the flow cytometry had been negative. Thirty of 46 cases (65%) of follicular lymphoma showed monotypic light chain expression, in contrast to 64 of 67 cases (95%) of reactive lymphoid hyperplasia, which showed polytypic light chain expression. These antibodies may provide an effective adjunct to the diagnosis of B-cell lymphoma in routine diagnostic work. PMID:20042853

  5. Initial management strategies for follicular lymphoma

    PubMed Central

    Chen, Qiushi; Ayer, Turgay; Nastoupil, Loretta J; Seward, Miray; Zhang, Hongzheng; Sinha, Rajni; Flowers, Christopher R

    2013-01-01

    SUMMARY Follicular lymphoma (FL) can vary markedly in its initial presentation, and no single standard approach for its initial management has been adopted. Available options for the initial management of FL include watchful waiting, radiation, single-agent rituximab and combination of rituximab and chemotherapy with strategies segregated for patients who have low and high tumor burden disease based on established criteria. However, marked debate occurs regarding the role of watchful waiting in the modern era for low tumor burden, asymptomatic patients, the optimal timing of rituximab, the selection of chemotherapy regimen to partner with rituximab in high tumor burden patients, and strategies for the management of relapsed disease. We provide an evidence-based discussion on these and other issues regarding the management of FL, and propose a mathematical modeling approach for addressing some of these questions. PMID:23476737

  6. 90-yttrium-ibritumomab tiuxetan consolidation of fludarabine, mitoxantrone, rituximab in intermediate/high-risk follicular lymphoma: updated long-term results after a median follow-up of 7 years.

    PubMed

    Casadei, Beatrice; Pellegrini, Cinzia; Pulsoni, Alessandro; Annechini, Giorgia; De Renzo, Amalia; Stefoni, Vittorio; Broccoli, Alessandro; Gandolfi, Letizia; Quirini, Federica; Tonialini, Lorenzo; Morigi, Alice; Argnani, Lisa; Zinzani, Pier Luigi

    2016-06-01

    Radioimmunotherapy (RIT) after an induction phase with conventional chemoimmunotherapy became an attractive strategy of consolidation for patients with advanced follicular lymphoma: in particular, in many studies RIT was represented by yttrium-90-ibritumomab tiuxetan ((90) Y-IT). Independently by the different front-line treatment, updates on the long-term follow-up of these studies are needed because the disease course of follicular lymphoma is characterised by multiple relapses and progressively shorter durations of response. We report updated long-term efficacy and toxicity results of a multicenter phase II study on sequential treatment with four cycles of fludarabine, mitoxantrone, and rituximab followed by (90) Y-IT as front-line therapy for untreated patients with intermediate/high-risk follicular lymphoma. With a median follow-up of 84 months, only 19/49 (38.8%) complete response patients relapsed, yielding an estimated long-term disease-free survival of 62.6%. The 7-year overall survival was 72.7%. Four (7.3%) second acute myeloid leukemia occurred, with a median time following RIT of 42 months. A relevant patients' responsiveness to subsequent therapies occurred: approximately 65% of relapsed patients obtained a good clinical response after the second-line treatment. These data represented the first evidence of a real role even in the long period of 90Y-IT after a fludarabine-containing regimen plus rituximab in the treatment of high-risk follicular lymphoma. PMID:26990782

  7. An unusual case of composite lymphoma involving chronic lymphocytic leukemia follicular lymphoma and Hodgkin disease.

    PubMed

    Copur, M Sitki; Ledakis, Peter; Novinski, Daniel; Fu, Kai; Hutchins, Mark; Frankforter, Scot; Mleczko, Kris; Sanger, Warren G; Chan, Wing C

    2004-05-01

    Composite lymphomas constitute the presence of two different types of non-Hodgkin lymphoma or Hodgkin and non-Hodgkin lymphoma at the same anatomic site. We report an unusual case of a 73-year-old woman who initially presented with a composite lymphoma of chronic lymphocytic leukemia (CLL) and follicular lymphoma. After 5 years of follow-up and intermittent treatment, she developed Hodgkin disease with diffuse liver involvement. Biopsy of the liver showed Reed-Sternberg cells with typical morphology and immunophenotype. While fluorescent in situ hybridization (FISH) analyses for t(14;18) were positive in the lymph node tissue with follicular lymphoma, we were unable to show the same in the liver biopsy specimen. Here, we describe the clinical, morphologic, immunophenotypic, and cytogenetic features of this unusual composite lymphoma case involving CLL and follicular lymphoma, with the subsequent development of a Hodgkin lymphoma. PMID:15291370

  8. Activating STAT6 mutations in follicular lymphoma

    PubMed Central

    Yildiz, Mehmet; Li, Hongxiu; Bernard, Denzil; Amin, Nisar A.; Ouillette, Peter; Jones, Siân; Saiya-Cork, Kamlai; Parkin, Brian; Jacobi, Kathryn; Shedden, Kerby; Wang, Shaomeng; Chang, Alfred E.; Kaminski, Mark S.

    2015-01-01

    Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in the Western world. FL cell-intrinsic and cell-extrinsic factors influence FL biology and clinical outcome. To further our understanding of the genetic basis of FL, we performed whole-exome sequencing of 23 highly purified FL cases and 1 transformed FL case and expanded findings to a combined total of 114 FLs. We report recurrent mutations in the transcription factor STAT6 in 11% of FLs and identified the STAT6 amino acid residue 419 as a novel STAT6 mutation hotspot (p.419D/G, p.419D/A, and p.419D/H). FL-associated STAT6 mutations were activating, as evidenced by increased transactivation in HEK293T cell–based transfection/luciferase reporter assays, heightened interleukin-4 (IL-4) –induced activation of target genes in stable STAT6 transfected lymphoma cell lines, and elevated baseline expression levels of STAT6 target genes in primary FL B cells harboring mutant STAT6. Mechanistically, FL-associated STAT6 mutations facilitated nuclear residency of STAT6, independent of IL-4–induced STAT6-Y641 phosphorylation. Structural modeling of STAT6 based on the structure of the STAT1-DNA complex revealed that most FL-associated STAT6 mutants locate to the STAT6-DNA interface, potentially facilitating heightened interactions. The genetic and functional data combined strengthen the recognition of the IL-4/JAK/STAT6 axis as a driver of FL pathogenesis. PMID:25428220

  9. miR-31 and miR-17-5p levels change during transformation of follicular lymphoma.

    PubMed

    Thompson, Mary Ann; Edmonds, Mick D; Liang, Shan; McClintock-Treep, Sara; Wang, Xuan; Li, Shaoying; Eischen, Christine M

    2016-04-01

    The 30% of patients whose indolent follicular lymphoma transforms to aggressive diffuse large B-cell lymphoma (DLBCL) have poor survival. Reliable predictors of follicular B-cell lymphoma transformation to DLBCL are lacking, and diagnosis of those that will progress is challenging. MicroRNA, which regulates gene expression, has critical functions in the growth and progression of many cancers and contributes to the pathogenesis of lymphoma. Using 5 paired samples from patients who presented with follicular lymphoma and progressed to DLBCL, we identified specific microRNA differentially expressed between the two. Specifically, miR-17-5p levels were low in follicular lymphoma and increased as the disease transformed. In contrast, miR-31 expression was high in follicular lymphoma and decreased as the lymphoma progressed. These results were confirmed in additional unpaired cases of low-grade follicular lymphoma (n = 13) and high-grade follicular lymphoma grade 3 or DLBCL (n = 17). Loss of miR-31 expression in DLBCL was not due to deletion of the locus. Changes in miR-17-5p and miR-31 were not correlated with immunophenotype, genetics, or status of the MYC oncogene. However, increased miR-17-5p expression did significantly correlate with increased expression of p53 protein, which is indicative of mutant TP53. Two pro-proliferative genes, E2F2 and PI3KC2A, were identified as direct messenger RNA targets of miR-31, suggesting that these may contribute to follicular lymphoma transformation. Our results indicate that changes in miR-31 and miR-17-5p reflect the transformation of follicular lymphoma to an aggressive large B-cell lymphoma and may, along with their targets, be viable markers for this process. PMID:26997445

  10. A case of conjunctival follicular lymphoma mimicking mucosa-associated lymphoid tissue lymphoma.

    PubMed

    Abd Al-Kader, Lamia; Sato, Yasuharu; Takata, Katsuyoshi; Ohshima, Koh-Ichi; Sogabe, Yuka; Fujii, Kazuhiro; Iwaki, Noriko; Yoshino, Tadashi

    2013-01-01

    Ocular adnexal lymphoma may involve the eyelids, conjunctiva, orbital tissue, or lacrimal structures. The majority are non-Hodgkin's B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphoma type. Follicular lymphomas represent a small percentage of ocular adnexa lymphomas, particularly in Japan. We report a 68-year-old female patient who presented with a salmon pink patch-like lesion of the left conjunctiva, suspected of being (MALT) lymphoma. However, histologic and immunohistologic examinations were consistent with follicular lymphoma. This case demonstrates the importance of considering such rare lymphomas when making a diagnosis of ocular adnexal lymphoid neoplasms. [J Clin Exp Hematop 53(1): 49-52, 2013]. PMID:23801133

  11. Impact of the tumor microenvironment on prognosis in follicular lymphoma is dependent on specific treatment protocols

    PubMed Central

    de Jong, Daphne; Koster, Ad; Hagenbeek, Anton; Raemaekers, John; Veldhuizen, Dennis; Heisterkamp, Sabien; de Boer, Jan Paul; van Glabbeke, Martine

    2009-01-01

    Background The clinical behavior of follicular lymphoma is largely determined by properties of the non-malignant tumor microenvironment. The precise nature of the cell populations is still unclear and published data on their prognostic significance are highly conflicting. This may be partly due to heterogeneous composition and treatments. Design and Methods Pre-treatment biopsy samples of patients with follicular lymphoma treated in an EORTC/BNLI trial comparing fludarabine to cyclophosphamide, vincristine and prednisone (CVP) chemotherapy could be retrieved for 61 patients in five European countries. Immunohistochemical investigations were performed evaluate tumor cell characteristics, T-cell subsets, follicular dendritic cells and macrophages and associations with clinical outcome were studied. Results Some markers showed a homogeneous prognostic impact, while others had a different nd sometimes opposite effect in the treatment arms. CD69 expression on tumor cells was a poor prognostic sign and an interfollicular infiltrate of FoxP3-positive T cells was a good prognostic sign irrespective of the treatment arm. It is suggestive that a dense infiltrate of FoxP3-positive T cells, dense and interfollicular infiltrate of CD68-positive macrophages and complete follicular dendritic meshworks were associated with a favorable time to progression in CVP-treated patients, while being poor prognostic sign in fludarabine-treated patients. Conclusions Our results suggest that characteristic properties of the microenvironment in follicular lymphoma determines the responses to essentially different chemotherapeutic approaches. These data may provide an explanation for the highly conflicting results on immunohistochemical markers and the prognostic role of the microenvironment in follicular lymphoma reported thus far and lay the basis for the development of predictive assays to tailor treatment in patients with follicular lymphoma. PMID:19059937

  12. Rituximab, Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Low-Grade Follicular Lymphoma, Waldenstrom Macroglobulinemia, or Mantle Cell Lymphoma

    ClinicalTrials.gov

    2016-04-13

    Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  13. Follicular lymphoma: first-line treatment without chemotherapy for follicular lymphoma.

    PubMed

    Reagan, Patrick M; Friedberg, Jonathan W

    2015-07-01

    Opinion statement: The optimal initial treatment of follicular lymphoma (FL) is not known, and initial management of patients varies considerably between providers and institutions. The assertion that patients with low tumor burden can be observed for a period of time is being challenged owing to the safety and tolerability of novel therapeutics and the movement of the field away from traditional chemotherapy agents. Single agent rituximab has become increasingly popular as initial management of patients with low tumor burden disease, and there is evidence that prolonged treatment with rituximab can improve progression-free survival (PFS) when compared to induction with rituximab or observation. Radioimmunotherapy (RIT) has similarly shown efficacy in low tumor burden disease. Novel agents such as lenalidomide, idelalisib, and ibrutinib are being studied in the first-line setting. Importantly, none of these strategies have demonstrated an improved overall survival in a randomized study versus observation. It is the opinion of the authors that endpoints such as PFS alone, while important, should not drive changes in management with limited resources. Composite endpoints including quality of life are more informative on the true impact of treatments on patients with follicular lymphoma. Providers should encourage all patients to be treated in the context of an appropriate clinical trial when possible. If a patient is not a clinical trial candidate, we typically treat patients with advanced stage and high tumor burden with chemoimmunotherapy. The decision to give maintenance rituximab is individualized to the patient, as there is no overall survival benefit. In patients with early stage disease, we favor consideration of radiation therapy if the patient is a candidate. Our initial recommendation to patients with advanced stage, low tumor burden disease, is close observation or "watch and wait." We have observed that most patients become comfortable over time with an

  14. Follicular Lymphoma: The Role of the Tumor Microenvironment in Prognosis.

    PubMed

    Sugimoto, Takumi; Watanabe, Takashi

    2016-01-01

    The microenvironment of follicular lymphoma (FL) is composed of tumor-infiltrating CD8(+) T cells, follicular regulatory T cells, lymphoma-associated macrophages and mast cells, follicular helper T cells, follicular dendritic cells, and follicular reticular cells, all of which have been reported to have relevance in the prognosis of FL patients. In addition, some of these cells play a role in the histologic transformation of FL. Macrophages contribute to a poor prognosis in FL patients treated in the pre-rituximab era, but are associated with good prognosis in those treated in the rituximab era. T-cell immunoglobulin and mucin domain protein (TIM) 3 are markers of T-cell exhaustion, and T cells co-expressing programed death 1 (PD1) in peripheral blood and lymph nodes secrete interleukin (IL)-12 in the serum. Serum CXCL9, IL-2 receptor, and IL-1 receptor agonist are associated with shorter survival of FL patients. Agents for manipulation of the microenvironment surrounding FL cells include the immunomodulatory drug lenalidomide, immune check-point inhibitors, and cyclophosphamide prior to rituximab. To battle FL and to improve the outcomes of FL patients, understanding the relationship between neoplastic cells and the various microenvironmental cellular components is crucial for developing therapeutics against the microenvironment. PMID:27334853

  15. [Peripheral T-Cell Lymphoma, Not Otherwise Specified Occurring After the Treatment of Relapsed Follicular Lymphoma].

    PubMed

    Fukushima, Hiroko; Inoue, Takeshi; Ishi, Naomi; Okuno, Takahiro; Son, Reika; Soejima, Chiaki; Horiuchi, Mirei; Ueda, Hideya; Yoshida, Masahiro; Hagihara, Kiyoyuki; Kanashima, Hiroshi; Nakao, Takafumi; Yamane, Takahisa

    2015-09-01

    A 77-year-old-man was diagnosed with follicular lymphoma (FL), grade 3A. After six courses of R-THP-COP (rituximab, pirarubicin, cyclophosphamide, vincristine and prednisolone) therapy, he achieved complete remission (CR). He achieved a second CR after radiotherapy, a third CR after six courses of bendamustine /rituximab (BR) therapy, and a fourth CR after six courses of BR therapy. However 2 months after the last chemotherapy, his tumor progressed rapidly and he died. Autopsy results showed medium and large lymphoid cells with pleomorphic, irregular nuclei and prominent nucleoli infiltrated in multiple lymph nodes, the liver, the lung, and the spleen. The lymphoid cells were positive for CD3, CD8, granzymeB, TIA-1 and negative for CD4, CD20, CD79a, CD10, and CD56. Autopsy diagnosis was peripheral T-cell lymphoma, not otherwise specified. Occurrence of lymphoma in T-cell lineage should be considered, if the course of low-grade B-cell lymphomas, such as FL rapidly progresses. PMID:26731890

  16. DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control.

    PubMed

    Kretzmer, Helene; Bernhart, Stephan H; Wang, Wei; Haake, Andrea; Weniger, Marc A; Bergmann, Anke K; Betts, Matthew J; Carrillo-de-Santa-Pau, Enrique; Doose, Gero; Gutwein, Jana; Richter, Julia; Hovestadt, Volker; Huang, Bingding; Rico, Daniel; Jühling, Frank; Kolarova, Julia; Lu, Qianhao; Otto, Christian; Wagener, Rabea; Arnolds, Judith; Burkhardt, Birgit; Claviez, Alexander; Drexler, Hans G; Eberth, Sonja; Eils, Roland; Flicek, Paul; Haas, Siegfried; Hummel, Michael; Karsch, Dennis; Kerstens, Hinrik H D; Klapper, Wolfram; Kreuz, Markus; Lawerenz, Chris; Lenze, Dido; Loeffler, Markus; López, Cristina; MacLeod, Roderick A F; Martens, Joost H A; Kulis, Marta; Martín-Subero, José Ignacio; Möller, Peter; Nagel, Inga; Picelli, Simone; Vater, Inga; Rohde, Marius; Rosenstiel, Philip; Rosolowski, Maciej; Russell, Robert B; Schilhabel, Markus; Schlesner, Matthias; Stadler, Peter F; Szczepanowski, Monika; Trümper, Lorenz; Stunnenberg, Hendrik G; Küppers, Ralf; Ammerpohl, Ole; Lichter, Peter; Siebert, Reiner; Hoffmann, Steve; Radlwimmer, Bernhard

    2015-11-01

    Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas. PMID:26437030

  17. Follicular lymphoma presenting with hypercalcaemia: an unusual mechanism of hypercalcaemia.

    PubMed

    Martens, P; Addissie, B; Kumar, R

    2015-06-01

    Hypercalcaemia is a frequent finding in patients with cancer. In up to 30% of malignancies, the disease course is complicated with hypercalcaemia. For hospitalized patients, cancer is the most common cause of hypercalcaemia. In normal physiological circumstances, the ionized calcium is kept in check by the influence of two important hormones, parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D). However, cancer can misbalance the calcium homeostasis by generating certain humoural mediators. Overproduction of parathyroid hormone-related peptide (PTH-rp), intact PTH, 1,25(OH)2D, and cytokines all cause hypercalcaemia. Hypercalcaemia is frequent in certain haematological cancers such as multiple myeloma and aggressive lymphomas. But hypercalcaemia is rare in patients with indolent lymphomas such follicular lymphoma. This case illustrates as a first to our knowledge the involvement of cytokines and chemokines in the pathophysiology of lymphoma-related hypercalcaemia. A pathophysiological mechanism is offered based upon the current understanding of cytokines and chemokines related to follicular lymphoma. PMID:25475431

  18. Emerging issues after the recognition of in situ follicular lymphoma.

    PubMed

    Carbone, Antonino; Gloghini, Annunziata

    2014-03-01

    This article reviews knowledge derived from the introduction of the concept of in situ follicular lymphoma (FL). The following questions are addressed: (1) How should in situ lymphomas be defined and diagnosed? (2) Is in situ lymphoma an early step of lymphomagenesis? (3) Is the concept of early neoplasia applicable to the lymphoma setting? (4) How should patients with in situ lymphoma be managed? The commonly used term of in situ FL, also called FL in situ (FLIS), has been adopted to define a B-cell lymphoid neoplasia with an intrafollicular growth pattern. The neoplastic B cells are localized within the germinal center, without invasion of surrounding structures. Pathological diagnosis requires recognizing strong immunostaining of BCL2 and CD10 by neoplastic B cells inside the affected follicles. Fluorescence in situ hybridization (FISH) analysis for t(14;18) is mandatory in doubtful cases in which immunohistochemistry data are ambiguous. In situ FL is probably the earliest stage of development of FL, while the concept of "early" lymphoma is applicable when minimal disease extends beyond the boundaries of the follicular compartment. From a clinical point of view, in situ FL has an uncertain clinical behavior and unknown risk to progression to overt lymphoma. How to approach and monitor patients with in situ FL is currently uncertain. An asymptomatic patient with stage 1 in situ FL requires the same treatment plan as an asymptomatic patient with stage 1 conventional FL. For patients with concomitant overt malignancy, therapy must be applied according to the malignant counterpart. PMID:23713483

  19. Follicular lymphoma in the palate with clinical appearance similar to salivary gland tumors.

    PubMed

    Lima, Marina de Deus Moura; Artico, Gabriela; Soares, Fernando Augusto; Martins, Marília Trierveiler; Alves, Fabio Abreu

    2010-09-01

    Intraoral presentation of follicular lymphoma is rare, and only three cases in the palate have been reported to date. The present case report describes an uncommon case of follicular lymphoma affecting the palate. The clinical aspect was similar to salivary gland neoplasm, and an incisional biopsy was important to establish the correct diagnosis and consequently to plan the treatment. Also discussed is the differential diagnosis among follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, and follicular lymphoid hyperplasia with regard to the histopathologic and immunohistochemical features. PMID:20657855

  20. In situ follicular lymphoma: pathologic characteristics and diagnostic features.

    PubMed

    Carbone, Antonino; Gloghini, Annunziata; Santoro, Armando

    2012-03-01

    The diagnosis of in situ follicular lymphoma (FL) is feasible when immunohistochemical characterization is carried out and genetic abnormalities are assessed. We usually use a selected diagnostic panel of antibodies (CD10, CD20, CD23, BCL2, BCL6, and Ki67) in lymph nodes with follicular hyperplasia only when we analyze an unexplained lymphadenopathy. Molecular studies, for example, fluorescence in situ hybridization analysis for t(14;18), are restricted to doubtful cases in which immunohistochemistry data are ambiguous. Immunohistochemically, the involved follicles show strongly positive staining for BCL2 and CD10. The BCL2+ cells are confined only to germinal centers and are not seen in the interfollicular region or elsewhere in the lymph node. The BCL2 staining in the abnormal follicles is notable for its high-level and uniform intensity. In situ FL may be associated with overt FL or with lymphomas other than FL or with other malignancies. The crucial point relies on distinguishing in situ FL arising in asymptomatic patients from cases with presence of lymphoma at the same or other sites. Other open questions remain on the frequency with which in situ FLs occur and the frequency of concomitant systemic disease. PMID:21560142

  1. Bortezomib, Rituximab, and Dexamethasone With or Without Temsirolimus in Treating Patients With Untreated or Relapsed Waldenstrom Macroglobulinemia or Relapsed or Refractory Mantle Cell or Follicular Lymphoma

    ClinicalTrials.gov

    2016-07-11

    Cognitive Side Effects of Cancer Therapy; Fatigue; Neurotoxicity Syndrome; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Therapy-Related Toxicity; Waldenstrom Macroglobulinemia

  2. Primary follicular lymphoma of the testis in children and adolescents.

    PubMed

    Lones, Mark A; Raphael, Martine; McCarthy, Keith; Wotherspoon, Andrew; Terrier-Lacombe, Marie-Josee; Ramsay, Alan D; Maclennan, Ken; Cairo, Mitchell S; Gerrard, Mary; Michon, Jean; Patte, Catherine; Pinkerton, Ross; Sender, Leonard; Auperin, Anne; Sposto, Richard; Weston, Claire; Heerema, Nyla A; Sanger, Warren G; von Allmen, Daniel; Perkins, Sherrie L

    2012-01-01

    This study reports 6 cases of primary follicular lymphoma of the testis (PFLT) in children and adolescents correlated with clinical presentation, pathologic features, treatment, and outcome. All 6 patients (age, 3 to 16 y; median, 4 y) had PFLT grade 3 with disease limited to the testis, completely resected and treated with 2 courses of chemotherapy (cyclophosphamide, vincristine, prednisone, doxorubicin). Event-free survival was 100% (follow-up: median, 73 mo; mean, 53 mo; range, 6 to 96 mo). In conclusion, clinical outcome in children and adolescents with PFLT is excellent with treatment including complete surgical resection and 2 courses of cyclophosphamide, vincristine, prednisone, doxorubicin. PMID:22215099

  3. Rituximab in combination with multiagent chemotherapy for pediatric follicular lymphoma.

    PubMed

    Kumar, Riten; Galardy, Paul J; Dogan, Ahmet; Rodriguez, Vilmarie; Khan, Shakila P

    2011-08-01

    Given the rarity of follicular lymphoma (FL) in children, there is limited data on which to base treatment recommendations. Herein, we report our institutional experience of using rituximab with multiagent chemotherapy for pediatric FL. Six pediatric patients were diagnosed with FL from 2000 to 2009. All patients received rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for varying durations. Five of the six patients remain in remission with a median follow-up of 31 months. Larger randomized trials are indicated to establish the efficacy of this regimen for pediatric FL patients. PMID:21462303

  4. Stromal cell contribution to human follicular lymphoma pathogenesis.

    PubMed

    Mourcin, Frédéric; Pangault, Céline; Amin-Ali, Rada; Amé-Thomas, Patricia; Tarte, Karin

    2012-01-01

    Follicular lymphoma (FL) is the prototypical model of indolent B cell lymphoma displaying a strong dependence on a specialized cell microenvironment mimicking normal germinal center. Within malignant cell niches in invaded lymph nodes and bone marrow, external stimuli provided by infiltrating stromal cells make a pivotal contribution to disease development, progression, and drug resistance. The crosstalk between FL B cells and stromal cells is bidirectional, causing activation of both partners. In agreement, FL stromal cells exhibit specific phenotypic, transcriptomic, and functional properties. This review highlights the critical pathways involved in the direct tumor-promoting activity of stromal cells but also their role in the organization of FL cell niche through the recruitment of accessory immune cells and their polarization to a B cell supportive phenotype. Finally, deciphering the interplay between stromal cells and FL cells provides potential new therapeutic targets with the aim to mobilize malignant cells outside their protective microenvironment and increase their sensitivity to conventional treatment. PMID:22973275

  5. The heterogeneity of follicular lymphomas: from early development to transformation.

    PubMed

    Xerri, Luc; Dirnhofer, Stephan; Quintanilla-Martinez, Leticia; Sander, Birgitta; Chan, John K C; Campo, Elias; Swerdlow, Steven H; Ott, German

    2016-02-01

    Follicular lymphoma (FL) is a lymphoma composed of germinal center B cells, i.e., centroblasts and centrocytes, that almost always show at least a focal follicular growth pattern. Most cases have a characteristic CD5-, CD10+, BCL6+, and BCL2+ immunophenotype, and 85 % of cases exhibit the hallmark translocation t(14;18)(q32;q21) involving BCL2 and IGH. Although the typical clinicopathological findings of FL are well recognized, cases with unusual clinical, morphologic, immunophenotypic, and genetic features may pose problems in diagnosis and nomenclature. In the slide workshop organized by the European Association for Haematopathology (EAHP) and the Society for Hematopathology (SH) held in Istanbul, Turkey, unusual variants of FL were discussed based on the submitted cases, including early lesions, localized extranodal presentation, uncommon immunophenotype, rare genetic alterations, diffuse variant, and marginal zone differentiation. Interesting features such as blastoid morphology and unusual progression forms were presented, aiming to understand the genetic basis of transformation. In this report, novel findings and diagnostic challenges emerging from the submitted cases will be highlighted, and new terminologies for some of these lesions are proposed. PMID:26481245

  6. Randomized controlled trials in relapsed/refractory follicular lymphoma: a systematic review and meta-analysis.

    PubMed

    Police, Rachel L; Trask, Peter C; Wang, Jianmin; Olivares, Robert; Khan, Shahnaz; Abbe, Adeline; Colosia, Ann; Njue, Annete; Sherril, Beth; Ruiz-Soto, Rodrigo; Kaye, James A; Hamadani, Mehdi

    2016-10-01

    This systematic literature review evaluated the clinical efficacy and safety of interventions used in relapsed/refractory follicular lymphoma. Primary efficacy outcomes were objective response rate, progression-free survival and overall survival. Safety endpoints were grade 3/4 toxicities, serious adverse events and withdrawals or deaths due to toxicity. Studies were selected if they were randomized controlled trials reporting on the efficacy or safety of treatments for relapsed or refractory follicular lymphoma, and if outcomes were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 10 randomized controlled trials of treatments for relapsed/refractory follicular lymphoma. The most prominent drug investigated (alone or in combination) was rituximab. Most trials did not report median overall survival. Two trials reported median event-free survival (range, 1.2-23.2 months). Six of ten trials reported objective response rate (range, 9-93%). Meta-analysis showed only one statistically significant result: rituximab + bortezomib yielded a significantly higher objective response rate than rituximab monotherapy (relative risk, 1.28; 95% confidence interval, 1.11-1.47). Otherwise, there were no discernable differences in overall survival or progression-free survival, partly due to insufficient reporting of results in the clinical trials. The relatively small number of randomized controlled trials, few overlapping treatment arms, and variability in the randomized controlled trial features and in the endpoints studied complicate the formal comparison of therapies for relapsed/refractory follicular lymphoma. Additional well-designed randomized controlled trials are needed to fully understand the relative outcomes of older and more recently developed therapies. PMID:26320127

  7. Clinical impact of molecular features in diffuse large B-cell lymphoma and follicular lymphoma.

    PubMed

    Pon, Julia R; Marra, Marco A

    2016-01-14

    Our understanding of the pathogenesis and heterogeneity of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) has been dramatically enhanced by recent attempts to profile molecular features of these lymphomas. In this article, we discuss ways in which testing for molecular features may impact DLBCL and FL management if clinical trials are designed to incorporate such tests. Specifically, we discuss how distinguishing lymphomas on the basis of cell-of-origin subtypes or the presence of other molecular features is prognostically and therapeutically significant. Conversely, we discuss how the molecular similarities of DLBCL and FL have provided insight into the potential of both DLBCL and FL cases to respond to agents targeting alterations they have in common. Through these examples, we demonstrate how the translation of our understanding of cancer biology into improvements in patient outcomes depends on analyzing the molecular correlates of treatment outcomes in clinical trials and in routinely treated patients. PMID:26447189

  8. Radiation therapy for localized duodenal low-grade follicular lymphoma

    PubMed Central

    Harada, Arisa; Oguchi, Masahiko; Terui, Yasuhito; Takeuchi, Kengo; Igarashi, Masahiro; Kozuka, Takuyo; Harada, Ken; Uno, Takashi; Hatake, Kiyohiko

    2016-01-01

    The aim of this study was to evaluate the initial treatment results and toxicities of radiation therapy for patients with early stage low-grade follicular lymphoma (FL) arising from the duodenum. We reviewed 21 consecutive patients with early stage duodenal FL treated with radiation therapy between January 2005 and December 2013 at the Cancer Institute Hospital, Tokyo. The characteristics of patients were: median age 62 years (range, 46–79 years), gender (male, 6; female, 15), clinical stage (I, 20; II1, 1), histological grade (I, 17; II, 4). All patients were treated with radiation therapy alone. The median radiation dose was 30.6 Gy (range, 30.6–39.6) in 17 fractions. The involved-site radiation therapy was delivered to the whole duodenum. The median follow-up time was 43.2 months (range 21.4–109.3). The 3-year overall survival (OS), relapse-free survival (RFS) and local control (LC) rates were 94.7%, 79.3% and 100%, respectively. There were four relapses documented outside the treated volumes: two in the gastrointestinal tract (jejunum, terminal ileum), one in an abdominal lymph node (mesenteric lymph node) and one in the bone marrow. None died of the disease; one death was due to acute myeloid leukemia. No toxicities greater than Grade 1 were observed during treatment and over the follow-up time. The 30.6 Gy of involved-site radiation therapy provided excellent local control with very low toxicities. Radiation therapy could be an effective and safe treatment option for patients with localized low grade FL arising from the duodenum. PMID:27009323

  9. Radiation therapy for localized duodenal low-grade follicular lymphoma.

    PubMed

    Harada, Arisa; Oguchi, Masahiko; Terui, Yasuhito; Takeuchi, Kengo; Igarashi, Masahiro; Kozuka, Takuyo; Harada, Ken; Uno, Takashi; Hatake, Kiyohiko

    2016-07-01

    The aim of this study was to evaluate the initial treatment results and toxicities of radiation therapy for patients with early stage low-grade follicular lymphoma (FL) arising from the duodenum. We reviewed 21 consecutive patients with early stage duodenal FL treated with radiation therapy between January 2005 and December 2013 at the Cancer Institute Hospital, Tokyo. The characteristics of patients were: median age 62 years (range, 46-79 years), gender (male, 6; female, 15), clinical stage (I, 20; II1, 1), histological grade (I, 17; II, 4). All patients were treated with radiation therapy alone. The median radiation dose was 30.6 Gy (range, 30.6-39.6) in 17 fractions. The involved-site radiation therapy was delivered to the whole duodenum. The median follow-up time was 43.2 months (range 21.4-109.3). The 3-year overall survival (OS), relapse-free survival (RFS) and local control (LC) rates were 94.7%, 79.3% and 100%, respectively. There were four relapses documented outside the treated volumes: two in the gastrointestinal tract (jejunum, terminal ileum), one in an abdominal lymph node (mesenteric lymph node) and one in the bone marrow. None died of the disease; one death was due to acute myeloid leukemia. No toxicities greater than Grade 1 were observed during treatment and over the follow-up time. The 30.6 Gy of involved-site radiation therapy provided excellent local control with very low toxicities. Radiation therapy could be an effective and safe treatment option for patients with localized low grade FL arising from the duodenum. PMID:27009323

  10. Elucidation and Pharmacological Targeting of Novel Molecular Drivers of Follicular Lymphoma Progression.

    PubMed

    Bisikirska, Brygida; Bansal, Mukesh; Shen, Yao; Teruya-Feldstein, Julie; Chaganti, Raju; Califano, Andrea

    2016-02-01

    Follicular lymphoma, the most common indolent subtype of non-Hodgkin lymphoma, is associated with a relatively long overall survival rate ranging from 6 to 10 years from the time of diagnosis. However, in 20% to 60% of follicular lymphoma patients, transformation to aggressive diffuse large B-cell lymphoma (DLBCL) reduces median survival to only 1.2 years. The specific functional and genetic determinants of follicular lymphoma transformation remain elusive, and genomic alterations underlying disease advancement have only been identified for a subset of cases. Therefore, to identify candidate drivers of follicular lymphoma transformation, we performed systematic analysis of a B-cell-specific regulatory model exhibiting follicular lymphoma transformation signatures using the Master Regulator Inference algorithm (MARINa). This analysis revealed FOXM1, TFDP1, ATF5, HMGA1, and NFYB to be candidate master regulators (MR) contributing to disease progression. Accordingly, validation was achieved through synthetic lethality assays in which RNAi-mediated silencing of MRs individually or in combination reduced the viability of (14;18)-positive DLBCL (t-DLBCL) cells. Furthermore, specific combinations of small-molecule compounds targeting synergistic MR pairs induced loss of viability in t-DLBCL cells. Collectively, our findings indicate that MR analysis is a valuable method for identifying bona fide contributors to follicular lymphoma transformation and may therefore guide the selection of compounds to be used in combinatorial treatment strategies. PMID:26589882

  11. Follicular Lymphoma Tregs Have a Distinct Transcription Profile Impacting Their Migration and Retention in the Malignant Lymph Node

    PubMed Central

    Hyrien, Ollivier; Burack, W. Richard; Quataert, Sally A.; Baker, Christina M.; Azadniv, Mitra; Welle, Stephen L.; Ansell, Stephen M.; Kim, Minsoo; Bernstein, Steven H.

    2016-01-01

    We have previously shown that regulatory T cells (Tregs) infiltrating follicular lymphoma lymph nodes are quantitatively and qualitatively different than those infiltrating normal and reactive nodes. To gain insight into how such Treg populations differ, we performed RNA sequence (RNAseq) analyses on flow sorted Tregs from all three sources. We identify several molecules that could contribute to the observed increased suppressive capacity of follicular lymphoma nodal tregs, including upregulation of CTLA-4, IL-10, and GITR, all confirmed by protein expression. In addition, we identify, and confirm functionally, a novel mechanism by which Tregs target to and accumulate within a human tumor microenvironment, through the down regulation of S1PR1, SELL (L-selectin) and CCR7, potentially resulting in greater lymph node retention. In addition we identify and confirm functionally the upregulation of the chemokine receptor CXCR5 as well as the secretion of the chemokines CXCL13 and IL-16 demonstrating the unique ability of the follicular derived Tregs to localize and accumulate within not only the malignant lymph node, but also localize and accumulate within the malignant B cell follicle itself. Such findings offer significant new insights into how follicular lymphoma nodal Tregs may contribute to the biology of follicular lymphoma and identify several novel therapeutic targets. PMID:27228053

  12. Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma.

    PubMed

    Liu, Qingyan; Salaverria, Itziar; Pittaluga, Stefania; Jegalian, Armin G; Xi, Liqiang; Siebert, Reiner; Raffeld, Mark; Hewitt, Stephen M; Jaffe, Elaine S

    2013-03-01

    Follicular lymphoma (FL), a common lymphoma in adults, occurs rarely in pediatric and young adult patients. Most pediatric cases have been described as grade 3, but the criteria to distinguish the pediatric variant of FL (PFL) from usual FL (UFL) seen in adults are not well defined. We undertook a study of FL in patients under the age of 30. We identified 63 cases, which were analyzed by morphology, immunohistochemistry, and polymerase chain reaction analysis of IGH@ and IGK@ clonality. These data were correlated with clinical findings including stage, treatment, and outcome. Among the 63 cases, 34 cases were classified as PFL: 22 presenting in lymph nodes, 8 in the Waldeyer ring, and 4 in the testis. Clonal immunoglobulin gene rearrangement was detected in 97% of PFL cases, but fluorescence in situ hybridization analysis showed an absence of the BCL2/IGH@ translocation in all cases tested. Twenty-nine cases were classified as UFL, 28 of which presented in lymph nodes. The nodal PFLs were observed exclusively in male patients in both children and young adults with a median age of 15 years. They showed marked head/neck predilection, blastoid cytologic features with a high proliferation rate, lack of BCL2 protein and t(14;18), low clinical stage at presentation, and good prognosis. PFLs involving the Waldeyer ring were distinguished by MUM1 expression, 50% (3/6) of which carried IRF4 breaks. BCL2 expression was common (63%) in the absence of BCL2/IGH@ translocation. UFLs were more common in female patients, exclusively in young adults (median age, 24 y), with no cases reported in patients under the age of 18. Twenty-five of 29 cases were of grade 1-2, and 4 cases were classified as grade 3A. They exhibited a higher clinical stage at presentation. Eighty-three percent expressed BCL2. Our results indicate that histologic and immunophenotypic criteria can reliably separate PFL and UFL and that UFL is exceptionally rare in the pediatric age group. PFL associated with

  13. Rare case of sclerosing mesenteritis and low grade follicular lymphoma

    PubMed Central

    Shah, Seema; Mahy, Gillian; Roche, Enrico

    2016-01-01

    An unusual case of long standing sclerosing mesenteritis; initially presented with recurrent abdominal pain and a mesenteric mass with surrounding fat oedema and stranding with a pseudocapsule and fat ring sign were clearly visualised on the initial computed tomography scan. Laparotomy showed diffuse thickening at the root of the mesentery and histology from this specimen revealed fat necrosis and reactive lymphoid tissue consistent with sclerosing mesenteritis. Initial treatment with steroids and tamoxifen relieved the symptoms and the mass. He was maintained on tamoxifen. Three years later he developed a recurrence of his symptoms and abdominal mass that responded to a course of steroids. Two years following this, he developed a follicular Hodgkin’s lymphoma. PMID:27099861

  14. Rare case of sclerosing mesenteritis and low grade follicular lymphoma.

    PubMed

    Shah, Seema; Mahy, Gillian; Roche, Enrico

    2016-04-16

    An unusual case of long standing sclerosing mesenteritis; initially presented with recurrent abdominal pain and a mesenteric mass with surrounding fat oedema and stranding with a pseudocapsule and fat ring sign were clearly visualised on the initial computed tomography scan. Laparotomy showed diffuse thickening at the root of the mesentery and histology from this specimen revealed fat necrosis and reactive lymphoid tissue consistent with sclerosing mesenteritis. Initial treatment with steroids and tamoxifen relieved the symptoms and the mass. He was maintained on tamoxifen. Three years later he developed a recurrence of his symptoms and abdominal mass that responded to a course of steroids. Two years following this, he developed a follicular Hodgkin's lymphoma. PMID:27099861

  15. Incidental and Isolated Follicular Lymphoma In Situ and Mantle Cell Lymphoma In Situ Lack Clinical Significance.

    PubMed

    Bermudez, Glenda; González de Villambrosía, Sonia; Martínez-López, Azahara; Batlle, Ana; Revert-Arce, José B; Cereceda Company, Laura; Ortega Bezanilla, César; Piris, Miguel A; Montes-Moreno, Santiago

    2016-07-01

    Follicular lymphoma in situ (FLIS) and mantle cell lymphoma in situ (MCLIS) are histopathologic findings of undetermined clinical significance. We studied a series of 341 consecutive lymph node resection specimens from patients diagnosed with colorectal (201 cases) and breast (140 cases) adenocarcinoma between 1998 and 2000. Incidental and isolated FLIS was identified in 11/341 patients (3.23%), whereas incidental and isolated MCLIS was found in 2/341 patients (0.59%). None of these cases developed overt lymphoma. A second series of 17 cases of FLIS (16 cases) and MCLIS (1 case) from consultation files was analyzed. Five cases with incidental and isolated FLIS were identified. None of these cases developed overt lymphoma. Overall, none of the 16 cases with incidental and isolated FLIS in both series developed overt FL after a median follow-up of 54 months (range, 7 to 187 mo). However, 12 of these cases with a clinical suspicion of lymphoproliferative disorder showed the association (in different lymph nodes) or combination (in the same sample) of FLIS or MCLIS with other lymphoid neoplasms (FL, splenic marginal zone lymphoma, nodal marginal zone lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma). In conclusion, the clinical relevance of FLIS and MCLIS seems to strictly depend on the clinical context. Incidental FLIS or MCLIS seem to have a very low risk for transformation, which recommends careful clinical examination after histopathologic diagnosis and conservative management with follow-up for a limited period of time. PMID:26945339

  16. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses

    PubMed Central

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G.

    2016-01-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  17. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

    PubMed

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

    2016-07-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  18. Primary Follicular Lymphoma of the Duodenum with Erosions as Atypical Macroscopic Features

    PubMed Central

    Takeuchi, Keiko; Iwamuro, Masaya; Imagawa, Atsushi; Kubota, Yoshitsugu; Miyatani, Katsuya; Takata, Katsuyoshi; Okada, Hiroyuki

    2012-01-01

    A 52-year-old Japanese woman who was eventually diagnosed with primary follicular lymphoma of the duodenum showed atypical endoscopic features, namely, erosions with peripheral whitish edematous mucosa. Initial biopsy specimens taken from the erosions revealed insufficient numbers of lymphoma cells for histological diagnosis. Subsequent biopsy specimens from the peripheral mucosa containing the whitish enlarged villi showed infiltration of the lymphoma cells forming lymphoid follicles, which led us to the appropriate diagnosis. This case indicates that endoscopists should take biopsy samples from the peripheral mucosa with whitish enlarged villi rather than erosions in the rare instances that erosions appear as the main macroscopic feature of intestinal follicular lymphoma. PMID:22690224

  19. Diagnosis of follicular lymphoma of the gastrointestinal tract: A better initial diagnostic workup

    PubMed Central

    Iwamuro, Masaya; Kondo, Eisei; Takata, Katsuyoshi; Yoshino, Tadashi; Okada, Hiroyuki

    2016-01-01

    Due to an increasing incidence and more frequent recognition by endoscopists, gastrointestinal follicular lymphoma has been established as a variant of follicular lymphoma. However, due to its rarity, there are no established guidelines on the optimal diagnostic strategy for patients with primary gastrointestinal follicular lymphoma or secondary gastrointestinal involvement of systemic follicular lymphoma. This review offers an overview and pitfalls to avoid during the initial diagnostic workup of this disease entity. Previously reported case reports, case series, and retrospective studies are reviewed and focus on the disease’s endoscopic and histological features, the roles of computed tomography and positron emission tomography scanning, the clinical utility of the soluble interleukin-2 receptor, and the possible pathogenesis. PMID:26819532

  20. Diagnosis of follicular lymphoma of the gastrointestinal tract: A better initial diagnostic workup.

    PubMed

    Iwamuro, Masaya; Kondo, Eisei; Takata, Katsuyoshi; Yoshino, Tadashi; Okada, Hiroyuki

    2016-01-28

    Due to an increasing incidence and more frequent recognition by endoscopists, gastrointestinal follicular lymphoma has been established as a variant of follicular lymphoma. However, due to its rarity, there are no established guidelines on the optimal diagnostic strategy for patients with primary gastrointestinal follicular lymphoma or secondary gastrointestinal involvement of systemic follicular lymphoma. This review offers an overview and pitfalls to avoid during the initial diagnostic workup of this disease entity. Previously reported case reports, case series, and retrospective studies are reviewed and focus on the disease's endoscopic and histological features, the roles of computed tomography and positron emission tomography scanning, the clinical utility of the soluble interleukin-2 receptor, and the possible pathogenesis. PMID:26819532

  1. Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

    ClinicalTrials.gov

    2016-09-08

    Follicular Variant Peripheral T-Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

  2. Magnified endoscopic features of duodenal follicular lymphoma and other whitish lesions.

    PubMed

    Iwamuro, Masaya; Okada, Hiroyuki; Takata, Katsuyoshi; Kawai, Yoshinari; Kawano, Seiji; Nasu, Junichiro; Kawahara, Yoshiro; Tanaka, Takehiro; Yoshino, Tadashi; Yamamoto, Kazuhide

    2015-01-01

    The sensitivity and specificity of magnified endoscopic features for differentiating follicular lymphoma from other diseases with duodenal whitish lesions have never been investigated. Here we compared the magnified endoscopic features of duodenal follicular lymphoma with those of other whitish lesions. We retrospectively reviewed the cases of patients with follicular lymphoma (n=9), lymphangiectasia (n=7), adenoma (n=10), duodenitis (n=4), erosion (n=1), lymphangioma (n=1), and hyperplastic polyp (n=1). The magnified features of the nine follicular lymphomas included enlarged villi (n=8), dilated microvessels (n=5), and opaque white spots of various sizes (n=9). The lymphangiectasias showed enlarged villi, dilated microvessels, and white spots, but the sizes of the white spots were relatively homogeneous and their margin was clear. Observation of the adenoma and duodenitis revealed only whitish villi. Although the lymphangioma was indistinguishable from the follicular lymphomas by magnified features, it was easily diagnosed based on the macroscopic morphology. In conclusion, magnified endoscopic features, in combination with macroscopic features, are useful for differentiating follicular lymphomas from other duodenal diseases presenting whitish lesions. PMID:25703169

  3. Two cases of histiocytic sarcoma with BCL2 translocations and occult or subsequent follicular lymphoma.

    PubMed

    Fernandez-Pol, Sebastian; Bangs, Charles D; Cherry, Athena; Arber, Daniel A; Gratzinger, Dita

    2016-09-01

    Histiocytic sarcoma is rare and difficult to distinguish from histologic mimics such as myeloid sarcoma due to its relatively nonspecific immunoprofile. A subset of histiocytic sarcomas are clonally related to synchronous or metachronous follicular lymphomas. Interestingly, the histiocytic tumor component has been shown to harbor BCL2 gene translocations that are identical to those found in the lymphoma. We present one case of histiocytic sarcoma and initially occult follicular lymphoma in which detection of a BCL2 gene translocation helped support the diagnosis. We also provide follow-up regarding a previously published case of histiocytic sarcoma with IGH/BCL2 fusion gene in which the patient subsequently developed follicular lymphoma and, later, diffuse large B-cell lymphoma. Our findings suggest that BCL2 gene translocations are a recurrent feature of a distinct subset of histiocytic sarcomas that are associated with follicular lymphoma; the follicular lymphoma component may be clinically occult at the time of diagnosis. Testing for an IGH/BCL2 translocation should be considered in the diagnostic workup of difficult-to-characterize neoplasms with histiocytic/monocytic morphology and immunoprofile. PMID:27134111

  4. Composite diffuse large B-cell lymphoma and follicular B-cell lymphoma - case report and review of literature.

    PubMed

    Turbatu, Andrei; Stoian, Marilena; Brezean, Iulian; Stoica, Victor Constantin Ion; Colita, Andrei; Dobrea, Camelia; State, Nicoleta; Ionescu, Cosmin; Ivanescu, Ana-Maria; Oprea, Madalina; Ghimici, Cecilia; Lupu, Anca Roxana

    2014-06-01

    Composite lymphoma refers to the co-occurrence of two or more morphologically and immunophenotypically separate lymphomas in the same topographic site at the time of clinical presentation. It is an infrequent type of lymphoid neoplasm, present in lymphoid tissue and may be due to the existence of two genetically related neoplasms such as transformation of a single lymphoma into another more aggressive lymphoma or be due to the presence of two clonally unrelated lymphomas. This paper is presenting a case of diffuse non-Hodgkin large B-cell lymphoma with areas of low grade and high grade follicular non-Hodgkin B-cell lymphoma in a retroperitoneal lymph node and spleen of an 62 year old woman. Histopathological examination and immunohistochemistry features proved the diagnosis of composite lymphoma. PMID:25705280

  5. Composite Diffuse Large B-Cell Lymphoma and Follicular B-Cell Lymphoma – Case Report and Review of Literature

    PubMed Central

    TURBATU, Andrei; STOIAN, Marilena; BREZEAN, Iulian; STOICA, Victor Constantin Ion; COLITA, Andrei; DOBREA, Camelia; STATE, Nicoleta; IONESCU, Cosmin; IVANESCU, Ana-Maria; OPREA, Madalina; GHIMICI, Cecilia; LUPU, Anca Roxana

    2014-01-01

    Composite lymphoma refers to the co-occurrence of two or more morphologically and immunophenotypically separate lymphomas in the same topographic site at the time of clinical presentation. It is an infrequent type of lymphoid neoplasm, present in lymphoid tissue and may be due to the existence of two genetically related neoplasms such as transformation of a single lymphoma into another more aggressive lymphoma or be due to the presence of two clonally unrelated lymphomas. This paper is presenting a case of diffuse non-Hodgkin large B-cell lymphoma with areas of low grade and high grade follicular non-Hodgkin B-cell lymphoma in a retroperitoneal lymph node and spleen of an 62 year old woman. Histopathological examination and immunohistochemistry features proved the diagnosis of composite lymphoma. PMID:25705280

  6. Identification of MUM1 as a prognostic immunohistochemical marker in follicular lymphoma using computerized image analysis.

    PubMed

    Xerri, Luc; Bachy, Emmanuel; Fabiani, Bettina; Canioni, Danielle; Chassagne-Clément, Catherine; Dartigues-Cuilléres, Peggy; Charlotte, Frédéric; Brousse, Nicole; Rousselet, Marie-Christine; Foussard, Charles; Brice, Pauline; Feugier, Pierre; Morschhauser, Frank; Sonet, Anne; Olive, Daniel; Salles, Gilles

    2014-10-01

    Detection of MUM1+ cells in follicular lymphoma (FL) tissues was previously found to be associated with poor prognosis in a single report, whereas the usefulness of Ki-67 immunostaining remains debated. Our goal was to establish whether these markers have predictive value for patients with FL. We analyzed MUM1 and Ki-67 expression using immunohistochemistry in biopsy samples from 434 patients from the PRIMA randomized trial. The MUM1 prognostic value was then validated in a cohort of 138 patients from the FL2000 randomized trial, using the optimal cutoff value obtained from the PRIMA cohort. The surface of positive staining was quantified using computerized image analysis. In the PRIMA cohort, both high levels of MUM1 positivity (cutoff value of 0.80%) and high levels of Ki-67 positivity (cutoff value of 10.25%) were significantly associated with a shorter progression-free survival (PFS) (P = .004 and P = .007 for MUM1 and Ki-67, respectively). In a multivariate Cox proportional hazards regression model, only MUM1 retained a statistical significance (hazards ratio 1.56; 95% confidence interval, 1.02-2.37; P = .038) after adjustment for the maintenance arm of treatment and the follicular lymphoma international prognostic index score. In the FL2000 cohort, high levels of MUM1 positivity were significantly associated to a shorter PFS (P = .004) and to a trend toward a shorter overall survival (P = .043). This remained significant using a multivariate Cox regression model after adjustment for the follicular lymphoma international prognostic index and the treatment arm for PFS (P = .016). These results show that MUM1 is a strong and robust predictive immunohistochemical marker in patients with FL. PMID:25149549

  7. Array-based DNA methylation profiling in follicular lymphoma

    PubMed Central

    O’Riain, Ciarán; O’Shea, Derville M.; Yang, Youwen; Le Dieu, Rifca; Gribben, John G.; Summers, Karin; Yeboah-Afari, Johnson; Bhaw-Rosun, Leena; Fleischmann, Christina; Mein, Charles A.; Crook, Tim; Smith, Paul; Kelly, Gavin; Rosenwald, Andreas; Ott, German; Campo, Elias; Rimsza, Lisa M.; Smeland, Erlend B.; Chan, Wing C.; Johnson, Natalie; Gascoyne, Randy D.; Reimer, Sandra; Braziel, Rita M.; Wright, George W.; Staudt, Louis M.; Lister, T. Andrew; Fitzgibbon, Jude

    2009-01-01

    Quantitative methylation profiling was performed using the Illumina GoldenGate Assay in untreated Follicular Lymphoma (FL) (164), paired pre- and post-transformation FL (20), benign haematopoietic (24) samples and purified B & T cells from two FL cases. Methylation values allowed separation of untreated FL samples from controls with one exception based primarily on tumour-specific gains of methylation typically occurring within CpG islands. Genes which are targets for epigenetic repression in stem cells by Polycomb Repressor Complex 2 were significantly overrepresented among hypermethylated genes. Methylation profiles were conserved in sequential FL and t-FL biopsies suggesting that widespread methylation represents an early event in lymphomagenesis and may not contribute substantially to transformation. Significant (p<0.05) correlation between FL methylation values and reduced gene expression was demonstrated for up to 28% of loci. Methylation changes occurred predominantly in B cells with variability in the amount of non-malignant tissue between samples preventing conclusive correlation with survival. This represents an important caveat in attributing prognostic relevance to methylation and future studies in cancer will optimally require purified tumour populations to address the impact of methylation on clinical outcome. PMID:19587707

  8. Chemotherapy-free treatment in patients with follicular lymphoma.

    PubMed

    Sarkozy, Clémentine; Salles, Gilles; Bachy, Emmanuel

    2015-04-01

    The outcome of patients with follicular lymphoma (FL) has improved over the last two decades through the introduction of anti-CD20 monoclonal antibodies, usually used in combination with chemotherapy. However, patients with FL still experience multiple relapses, requiring several lines of treatment. Early toxicity of chemotherapy is a significant concern and as the life expectancy of patients with FL is increasing, late toxicities become an increasingly important concern. Progress made in understanding the biology of FL, especially dysregulation of intracellular pathways and immunological antitumor responses, recently allowed for the development of innovative chemo-free therapeutic approaches. In this report, different options such as new anti-CD20 antibodies, antibodies targeting other cell surface antigens, bi-specific antibodies, immunomodulation, idiotype vaccine and other targeted therapies are presented. The article also highlights how, although promising in early phase studies, the cost-effectiveness of new agents will have to be justified in Phase III trials. Furthermore, chemo-free regimen might not mean toxicity-free treatment and monitoring of early and late toxicities is required. PMID:25585961

  9. Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations.

    PubMed

    Louissaint, Abner; Schafernak, Kristian T; Geyer, Julia T; Kovach, Alexandra E; Ghandi, Mahmoud; Gratzinger, Dita; Roth, Christine G; Paxton, Christian N; Kim, Sunhee; Namgyal, Chungdak; Morin, Ryan; Morgan, Elizabeth A; Neuberg, Donna S; South, Sarah T; Harris, Marian H; Hasserjian, Robert P; Hochberg, Ephraim P; Garraway, Levi A; Harris, Nancy Lee; Weinstock, David M

    2016-08-25

    Pediatric-type nodal follicular lymphoma (PTNFL) is a variant of follicular lymphoma (FL) characterized by limited-stage presentation and invariably benign behavior despite often high-grade histological appearance. It is important to distinguish PTNFL from typical FL in order to avoid unnecessary treatment; however, this distinction relies solely on clinical and pathological criteria, which may be variably applied. To define the genetic landscape of PTNFL, we performed copy number analysis and exome and/or targeted sequencing of 26 PTNFLs (16 pediatric and 10 adult). The most commonly mutated gene in PTNFL was MAP2K1, encoding MEK1, with a mutation frequency of 43%. All MAP2K1 mutations were activating missense mutations localized to exons 2 and 3, which encode negative regulatory and catalytic domains, respectively. Missense mutations in MAPK1 (2/22) and RRAS (1/22) were identified in cases that lacked MAP2K1 mutations. The second most commonly mutated gene in PTNFL was TNFRSF14, with a mutation frequency of 29%, similar to that seen in limited-stage typical FL (P = .35). PTNFL was otherwise genomically bland and specifically lacked recurrent mutations in epigenetic modifiers (eg, CREBBP, KMT2D). Copy number aberrations affected a mean of only 0.5% of PTNFL genomes, compared with 10% of limited-stage typical FL genomes (P < .02). Importantly, the mutational profiles of PTNFLs in children and adults were highly similar. Together, these findings define PTNFL as a biologically and clinically distinct indolent lymphoma of children and adults characterized by a high prevalence of MAPK pathway mutations and a near absence of mutations in epigenetic modifiers. PMID:27325104

  10. Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations

    PubMed Central

    Schafernak, Kristian T.; Geyer, Julia T.; Kovach, Alexandra E.; Ghandi, Mahmoud; Gratzinger, Dita; Roth, Christine G.; Paxton, Christian N.; Kim, Sunhee; Namgyal, Chungdak; Morin, Ryan; Morgan, Elizabeth A.; Neuberg, Donna S.; South, Sarah T.; Harris, Marian H.; Hasserjian, Robert P.; Hochberg, Ephraim P.; Garraway, Levi A.; Harris, Nancy Lee; Weinstock, David M.

    2016-01-01

    Pediatric-type nodal follicular lymphoma (PTNFL) is a variant of follicular lymphoma (FL) characterized by limited-stage presentation and invariably benign behavior despite often high-grade histological appearance. It is important to distinguish PTNFL from typical FL in order to avoid unnecessary treatment; however, this distinction relies solely on clinical and pathological criteria, which may be variably applied. To define the genetic landscape of PTNFL, we performed copy number analysis and exome and/or targeted sequencing of 26 PTNFLs (16 pediatric and 10 adult). The most commonly mutated gene in PTNFL was MAP2K1, encoding MEK1, with a mutation frequency of 43%. All MAP2K1 mutations were activating missense mutations localized to exons 2 and 3, which encode negative regulatory and catalytic domains, respectively. Missense mutations in MAPK1 (2/22) and RRAS (1/22) were identified in cases that lacked MAP2K1 mutations. The second most commonly mutated gene in PTNFL was TNFRSF14, with a mutation frequency of 29%, similar to that seen in limited-stage typical FL (P = .35). PTNFL was otherwise genomically bland and specifically lacked recurrent mutations in epigenetic modifiers (eg, CREBBP, KMT2D). Copy number aberrations affected a mean of only 0.5% of PTNFL genomes, compared with 10% of limited-stage typical FL genomes (P < .02). Importantly, the mutational profiles of PTNFLs in children and adults were highly similar. Together, these findings define PTNFL as a biologically and clinically distinct indolent lymphoma of children and adults characterized by a high prevalence of MAPK pathway mutations and a near absence of mutations in epigenetic modifiers. PMID:27325104

  11. CD5-positive follicular lymphoma: clinicopathologic correlations and outcome in 88 cases.

    PubMed

    Li, Yu; Hu, Shimin; Zuo, Zhuang; Hong, Ming; Lin, Pei; Li, Shaoying; Konoplev, Sergej; Wang, Zhen; Khoury, Joseph D; Young, Ken H; Medeiros, L Jeffrey; Yin, C Cameron

    2015-06-01

    Follicular lymphoma is a low-grade B-cell lymphoma of germinal center B-cell origin that typically lacks CD5 expression. We describe the clinicopathologic features of 88 cases of CD5+ follicular lymphoma (53 men, 35 women; median age, 60 years; range, 31-86). Follicular lymphoma was diagnosed initially in lymph nodes in 66 and extranodal sites in 22 patients. Eighty-one patients had lymphadenopathy, 66 had more than one involved site, 46 had bone marrow involvement, and 7 had splenomegaly. Staging information was available for 84 patients: 52 stage IV, 18 stage III, 12 stage II, and 2 stage I. Sixty-one cases were grade 1 or 2 and 27 were grade 3. The median proliferation index (Ki-67) was 30%. CD5 expression was detected by flow cytometry in 69, immunohistochemistry in 8, and both methods in 11 cases. The presence of t(14;18)(q32;q21)/IGH-BCL2 or other BCL2 translocation was detected in 28/44 (64%) cases. A total of 38 (43%) patients also had diffuse large B-cell lymphoma, concurrent with (n=20), subsequent to (n=13), or developing before CD5+ follicular lymphoma (n=5). All patients received chemotherapy; 12 also received stem-cell transplantation. With a median follow-up of 55 months (range, 0.5-207), 15 patients died, 46 were alive with disease, and 20 were in clinical remission. Compared with a matched group of patients with CD5- follicular lymphoma, patients with CD5+ follicular lymphoma more commonly had an International Prognostic Index >2 (35/80 vs 10/99, P<0.001), more often developed diffuse large B-cell lymphoma (38/88 vs 17/99; P<0.001), and had a shorter median progression-free survival (44 vs 89 months, P=0.0042). Higher Ki-67 and International Prognostic Index were identified as poor prognostic factors in both the groups. We conclude that CD5 expression in follicular lymphoma is associated with a higher International Prognostic Index, higher rate of transformation to diffuse large B-cell lymphoma, and shorter progression-free survival. PMID:25743023

  12. Economic burden of follicular non-Hodgkin's lymphoma.

    PubMed

    Foster, Talia; Miller, Jeffrey D; Boye, Mark E; Russell, Mason W

    2009-01-01

    Follicular non-Hodgkin's lymphoma (FNHL), a slow-growing cancer of the immune system, constitutes about 15-30% of all incident non-Hodgkin's lymphoma in developed countries. Its incidence is rising worldwide. Patients can live many years, but FNHL is considered incurable. We systematically reviewed the English-language MEDLINE-indexed and non-indexed economic literature published in the past 10 years on FNHL, identifying 23 primary economic studies. The economic burden of FNHL is significant, but available data are generally limited to retrospective considerations of hospital-based direct treatment costs, with little information available regarding societal cost of illness. Most direct cost information originates from the US, with one estimate of $US36 000 for the per-patient incremental cost of FNHL care during the first year following diagnosis. The most studied treatment is rituximab, which may offer similar overall costs to fludarabine considering higher resource use with fludarabine complications. Nearly all cost-effectiveness models identified by this review evaluated rituximab for relapsed/refractory FNHL responding to chemotherapy induction. Rituximab is supported as a cost-effective addition to standard chemotherapy by two models in the UK and one in the US, as maintenance therapy instead of stem-cell transplant by one UK model, and as maintenance therapy instead of observation alone by one model each in France, Spain and Canada. The UK National Institute for Health and Clinical Excellence updated guidance on rituximab in February 2008, concluding that it is cost effective when added to induction chemotherapy, and when used as maintenance therapy. No studies of per-patient or national indirect costs of illness were identified, with the only study of indirect costs a Canadian survey documenting lost work productivity. Across all study types identified by our review, the most common focus was on the direct costs of rituximab. As new treatments for FNHL come

  13. A Case of Chyloperitoneum Secondary to Follicular Lymphoma and a Review of Prognostic Implications

    PubMed Central

    Taylor, Brice; Taylor, Stephanie Parks

    2016-01-01

    Chyloperitoneum, or chylous ascites, is a rare condition characterized by milky-appearing fluid with elevated triglyceride content and the presence of chylomicrons. Malignancy, specifically lymphoma, is reported to be the predominant cause in Western countries. Previously, the prognosis for patients with chyloperitoneum due to lymphoma has been reported as poor. We present a case of chyloperitoneum and chylothorax due to follicular lymphoma with excellent response to bendamustine and Rituxan. A review of the literature indicates that patients with chyloperitoneum associated with lymphoma generally have a favorable response to contemporary treatment regimens. PMID:27429812

  14. Regression of follicular lymphoma of the duodenum following eradication of H. pylori infection.

    PubMed

    Hayashi, Hiroki; Onishi, Yutaka; Mitsuoka, Hiroshi; Ogura, Takeshi; Maeda, Mitsuo; Nishigami, Takashi; Harada, Masaru

    2013-01-01

    A 64-year-old woman was referred for an examination of the upper gastrointestinal (GI) tract. Endoscopy showed an elevated lesion in the duodenum with central depression and multiple white granules. Biopsy specimens revealed lymphoid follicles composed predominantly of centrocytes with scattered centroblasts. The tumor cells were positive for bcl-2. The patient was diagnosed with follicular lymphoma and underwent antibiotic therapy for Helicobacter pylori (H. pylori) infection. The regression of the lesion was obvious. After 5.5 years of follow-up, there has been no evidence of recurrence. This case suggests that H. pylori eradication therapy is effective for treating follicular lymphoma in the duodenum. PMID:24292749

  15. Follicular lymphoma with leukemic phase at diagnosis: An aggressive disease. Report of seven cases and review of the literature

    PubMed Central

    Beltran, Brady E.; Castillo, Jorge J.; Quiñones, Pilar; Morales, Domingo; Alva, Jose C.; Miranda, Roberto N.; Shah, Bijal D.; Sotomayor, Eduardo M.

    2014-01-01

    Follicular lymphoma FL) is a prevalent subtype of non-Hodgkin lymphoma in the United States and Europe. Although, FL typically presents with nodal involvement, extranodal involvement has been rarely described. There is mounting evidence that leukemic presentation portends a worse prognosis in patients with FL. We describe 7 patients with a pathological diagnosis of FL who presented with a leukemic component. We also present data on patients with leukemic FL reported in the literature. Based on our results, leukemic FL seems to be associated with a worse prognosis. However, larger prospective studies are needed to confirm our findings. PMID:23790442

  16. CD10 delineates a subset of human IL-4 producing follicular helper T cells involved in the survival of follicular lymphoma B cells.

    PubMed

    Amé-Thomas, Patricia; Hoeller, Sylvia; Artchounin, Catherine; Misiak, Jan; Braza, Mounia Sabrina; Jean, Rachel; Le Priol, Jérôme; Monvoisin, Céline; Martin, Nadine; Gaulard, Philippe; Tarte, Karin

    2015-04-01

    In follicular lymphoma (FL), follicular helper T cells (TFH) have been depicted as one of the main components of the malignant B-cell niche and a promising therapeutic target. Although defined by their capacity to sustain FL B-cell growth together with specific gene expression and cytokine secretion profiles, FL-TFH constitute a heterogeneous cell population. However, specific markers reflecting such functional heterogeneity are still lacking. In this study, we demonstrate that CD10 identifies a subset of fully functional germinal center TFH in normal secondary lymphoid organs. Importantly, this subset is amplified in the FL context, unlike in other B-cell lymphomas with a follicular growth pattern. Furthermore, whereas FL-TFH produce high levels of interleukin (IL)-21 and low levels of IL-17 irrespectively of their CD10 expression, CD10(pos) FL-TFH specifically exhibit an IL-4(hi)IFN-γ(lo)TNF-α(hi) cytokine profile associated with a high capacity to sustain directly and indirectly malignant B-cell survival. Altogether, our results highlight the important role of this novel functional subset in the FL cell niche. PMID:25733581

  17. Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients.

    PubMed

    Duarte, Ivison X; Domeny-Duarte, Pollyanna; Wludarski, Sheila C L; Natkunam, Yasodha; Bacchi, Carlos E

    2013-09-01

    Follicular lymphoma is clinically heterogenous, and therefore necessitates the identification of prognostic markers to stratify risk groups and optimize clinical management. It is relatively rare in patients younger than 40 years, and the clinicopathologic characteristics and biological behavior in this age group are poorly understood. In the current study, samples from a cohort of 200 patients between 19 and 40 years were evaluated retrospectively with respect to clinical, histologic, and genetic features. These were then correlated with clinical outcome. The median age at presentation was 35 years with a slight female prepoderance (56%). Most of the cases are presented with nodal disease (90%). Concomitant follicular lymphoma and diffuse large B-cell lymphoma were observed in 7 (4%) patients. Immunohistologic studies showed the expression of CD10 (91%), BCL6 (97%), BCL2 (95%), MUM1/IRF4 (12%), MDM2 (17%), and CD23 (25%). BCL2 rearrangement was present in 74%, and BCL6 in 20%. The estimated overall survival of patients was 13 years (mean). The presence of anemia, elevated lactose dehydrogenase, bone marrow involvement, and high-risk follicular lymphoma international prognostic index correlated with adverse overall survival. Our findings revealed that follicular lymphoma in young adults demonstrate similarities with that of older adults, including the frequency of presentation at various anatomic sites, grade, and adverse prognostic factors. PMID:23599146

  18. Total peroxiredoxin expression is associated with survival in patients with follicular lymphoma.

    PubMed

    Peroja, Pekka; Haapasaari, Kirsi-Maria; Mannisto, Susanna; Miinalainen, Ilkka; Koivunen, Petri; Leppä, Sirpa; Karjalainen-Lindsberg, Marja-Liisa; Kuusisto, Milla Elvi Linnea; Turpeenniemi-Hujanen, Taina; Kuittinen, Outi; Karihtala, Peeter

    2016-05-01

    Redox state-regulating enzymes may have roles in chemoresistance and also in lymphomagenesis, but there have been only a limited number of studies on this topic in lymphomas. Our aim was to assess expression of the redox state-regulating enzymes peroxiredoxins (Prxs) I-VI and thioredoxin (Trx) and the oxidative stress marker nitrotyrosine in follicular lymphomas (FLs). We immunohistochemically assessed Prxs I-VI, Trx and nitrotyrosine in a cohort of 76 histologically confirmed, untreated FLs. We also studied the localisation of Prxs I, II, III, V and VI by means of immunoelectron microscopy (IEM). Immunohistochemistry results were correlated with disease-specific survival (DSS), progression-free survival (PFS), overall survival (OS) and clinical prognostic factors. When all Prx expression intensities were grouped as a single variable, we discovered that high total Prx intensity correlated with favourable DSS (p = 0.024) and OS (p = 0.035) but not with PFS. No deaths due to lymphoma were recorded amongst patients with high total Prx expression during the median follow-up period of 7.6 years. IEM results were in line with earlier ones demonstrating wide subcellular localisation of Prx isoenzymes. In conclusion, our results demonstrate an association between high total Prx expression and prolonged survival and suggest that Prxs may have a protective role in FL that cannot be compensated by other antioxidant mechanisms. PMID:26983700

  19. Long-term follow-up of autologous stem-cell transplantation for follicular and transformed follicular lymphoma.

    PubMed

    Berglund, A; Enblad, G; Carlson, K; Glimelius, B; Hagberg, H

    2000-07-01

    Despite the fact that follicular lymphomas are both chemo- and radiosensitive, the disease is generally non-curable. These lymphomas often undergo transformation to a more malignant state. In order to improve the prognosis, high-dose treatment with stem cell support has been tested, but its role in the treatment of this disease is still unclear. Fourteen men and eight women with a median age of 45 yr (34-59) were treated with high-dose therapy with autologous stem cell transplantation between 1987 and 1996. The patients were selected to undergo intensive therapy because of an estimated short survival (median < 3 yr), even though they had chemosensitive disease and adequate performance status. Eleven patients' lymphomas had transformed, and the other eleven patients had one or more unfavourable prognostic signs such as advanced stage, bulky disease, multiple relapses, or short remission duration. The conditioning regimen has varied over the period, but BEAC (Becenum, etoposide, cytarabine, cyclophosphamide) or etoposide/cyclophosphamide with or without total body irradiation (TBI) was used in most patients. Nine patients had their stem cells purged. After a median follow-up time of 74 months overall survival was 81% and disease-free survival 72%. One toxic procedure-related death occured. There was no difference in outcome between patients with a transformed lymphoma compared to those without transformation. The patients treated with TBI had a significantly worse outcome. Toxicity was also much higher in TBI-treated patients, including four cases of secondary malignancy (three myelodysplastic syndrome (MDS) cases and one patient with breast carcinoma). This retrospective study, with the longest follow-up time so far reported, shows a promising 6-yr DFS of 72% in a group of follicular lymphoma patients with a bad prognosis. The outcome of patients with transformed lymphoma compared to historical controls is especially encouraging. The high incidence of MDS is

  20. Dysregulation of autophagy in human follicular lymphoma is independent of overexpression of BCL-2

    PubMed Central

    McCarthy, Aine; Marzec, Jacek; Clear, Andrew; Petty, Robert D.; Coutinho, Rita; Matthews, Janet; Wilson, Andrew; Iqbal, Sameena; Calaminici, Maria; Gribben, John G.; Jia, Li

    2014-01-01

    Overexpression of the anti-apoptotic protein BCL-2 is characteristic of human follicular lymphoma (FL) and some cases of diffuse large B cell lymphoma (DLBCL). We aimed to determine autophagy status in primary FL and DLBCL samples and the BCL-2+/BCL-2− lymphoma cell lines using both autophagy PCR array and tissue microarray (TMA). A greater number of autophagy machinery genes were up-regulated in the BCL-2+ Su-DHL4 cell line compared with BCL-2− Su-DHL8 cells, at both the basal level and in response to autophagic stress. The autophagy-related gene expression profiles were determined in purified and unpurified malignant human lymph node biopsies. Seven autophagy machinery genes were up-regulated in purified FL B-cells compared with reactive B-cells. Only 2 autophagy machinery genes were up-regulated in DLBCL B-cells. In unpurified tissue biopsies, 20 of 46 genes in FL and 2 of 5 genes in DLBCL with increased expression were autophagy machinery genes. Expression of autophagy substrates p62 and LC3 were determined by TMAs. FL samples showed significantly decreased levels of both p62 and LC3 compared with reactive and DLBCL, indicative of an increased autophagy activity in FL. In summary, these results demonstrate that FL showed increased basal autophagy activity, regardless of overexpression of BCL-2 in this disease. PMID:25362242

  1. Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.

    PubMed

    Gravelle, Pauline; Jean, Christine; Familiades, Julien; Decaup, Emilie; Blanc, Amandine; Bezombes-Cagnac, Christine; Laurent, Camille; Savina, Ariel; Fournié, Jean-Jacques; Laurent, Guy

    2014-01-01

    Lymphomas grow as dense aggregates in patients, but whether this spatial organization affects lymphoma cell biology is unknown. We grew follicular lymphoma (FL) cells in vitro as multicellular aggregates of lymphoma cells to investigate this question. Gene expression analysis revealed that 612 genes were differentially expressed when cells grew in multicellular aggregates of lymphoma cells rather than in suspension. These genes correspond to several GO biological processes, such as hypoxia, activation of NF-κB pathway, and negative regulation of cell cycle, a gene signature also found in the transcriptomes from FL biopsies. Pimonidazole staining, HIF-1A accumulation, and VEGFA release confirmed that cells in multicellular aggregates of lymphoma cells actually respond to hypoxia. In adaptation to such conditions, they also displayed an activated NF-κB pathway and a quiescent status far more frequently than in suspension. When cultured in three dimensions, FL cells display resistance to doxorubicin and bendamustine, two drugs largely used in FL therapy, compared to FL cultured in suspension. Finally, multicellular aggregates of lymphoma cells were also found to be less sensitive to purified natural killer cells. To conclude, our study shows that in FL, spatial organization results in dramatic changes in FL biology, including gene expression, proliferation, drug resistance, and immune escape. PMID:24231431

  2. Morphology and immunology of circulating cells in leukaemic phase of follicular lymphoma.

    PubMed Central

    Melo, J V; Robinson, D S; De Oliveira, M P; Thompson, I W; Lampert, I A; Ng, J P; Galton, D A; Catovsky, D

    1988-01-01

    Ten patients with follicular lymphoma presented with a high white cell count (45-220 x 10(9)/l) which resembled chronic lymphocytic leukaemia (CCL): all had pronounced splenomegaly and, except one, generalised lymphadenopathy. The blood lymphocytes were small with scanty cytoplasm, densely condensed nuclear chromatin, and deep clefts originating in sharp angles from the nuclear surface. CLL cells are larger, have more cytoplasm, a different pattern of chromatin condensation, and may have shallow nuclear indentations or foldings rather than clefts. The circulating follicular lymphoma cells had moderate to strong membrane immunoglobulins (SmIg), low mouse (M)-rosettes, strong reactivity with the monoclonal antibody FMC7, and occasional expression of the CD5-antigen; at least one third of cells in each case were positive with anti-cALLa (J5,CD10). Half the cases were referred as B-CLL but none had the typical B-CLL immunophenotype: weak SmIg, M-rosettes of greater than 50%, CD5 positive, FMC7 and J5 negative. The diagnosis of follicular lymphoma was confirmed by lymph node biopsy in seven of the 10 cases. The overall response to treatment was poor and five patients died within three years of diagnosis. This aggressive form of follicular lymphoma needs to be distinguished from B-CLL as different management is required. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 PMID:3056987

  3. Histological conversion of follicular lymphoma with structural alterations of t(14;18) and immunoglobin genes.

    PubMed

    Raghoebier, S; Broos, L; Kramer, M H; van Krieken, J H; Kluin-Nelemans, J C; van Ommen, G J; Kluin, P

    1995-10-01

    About half of the patients with follicular lymphoma will develop an aggressive B cell lymphoma with morphological changes in growth pattern and cellular morphology. Changes of the immunophenotype, especially of the expression of immunoglobulin (Ig) have been documented less frequently. Multiple tumor samples of two patients with follicular lymphoma who developed tumor progression, were studied by Southern blot analysis for rearrangements of the Ig genes and the oncogenes BCL2 and MYC. In both patients, the general pattern of Ig gene rearrangements, especially of the Ig light-chain genes, and the structure of the t(14;18) breakpoint as assessed by the polymerase chain reaction (PRC) and fine restriction mapping, remained unaltered with time. However, both within the functional Ig heavy-chain allele and around the t(14;18) breakpoint, extensive secondary alterations took place. This indicates clonal evolution rather than the appearance of an independent lymphoma. In the first case with progression from follicular lymphoma to Burkitt's lymphoma 3 years after diagnosis, alterations were especially present 3' of the t(14;18) breakpoint. In the second patient with a change from follicular to diffuse centroblastic lymphoma 4 years after diagnosis, subsequent class switches from IgM to IgG and to defective IgH expression were accompanied by deletion of C mu sequences and a rearrangement of the MYC gene, respectively. Additionally, in both patients alterations in individual restriction sites occurred, which most likely were due to somatic mutations within both the functional IgH and translocated allele. Our data indicate that complex alterations of both the functional and non-functional IgH allele may accompany tumor progression and may erroneously suggest the appearance of independent clones by Southern blot analysis. It remains to be established whether these alterations are causative events or the consequence of genetic instability and clonal evolution. PMID:7564520

  4. Elucidation and pharmacological targeting of novel molecular drivers of follicular lymphoma progression | Office of Cancer Genomics

    Cancer.gov

    Follicular lymphoma (FL), the most common indolent subtype of non-Hodgkin's lymphoma, is associated with a relatively long overall survival rate ranging from 6 to 10 years from time of diagnosis. However, in 20-60% of FL patients, transformation to aggressive diffuse large B-cell lymphoma (DLBCL) reduces median survival to only 1.2 years. The specific functional and genetic determinants of FL transformation remain elusive, and genomic alterations underlying disease advancement have only been identified for a subset of cases.

  5. Follicular variant of peripheral T cell lymphoma with mediastinal involvement in a child: a case report.

    PubMed

    Delas, Audrey; Gaulard, Philippe; Plat, Geneviève; Brousset, Pierre; Laurent, Camille

    2015-03-01

    Peripheral T cell lymphomas are rare in young patients. We report the first case of a follicular variant of peripheral T cell lymphoma not otherwise specified in an 11-year-old boy, who presented with a large mediastinal mass. Microscopic examination of the mediastinal biopsy revealed nodular infiltration of medium- to large-sized atypical lymphocytes. Immunohistochemistry showed expression of follicular helper T cell markers (CD10, PD1, CXCL13, and BCL6) in tumor T cells. Epstein-Barr virus (EBV) was not detected by an in situ hybridization assay for EBV-encoded RNA. Interestingly, fluorescence in situ hybridization detected the presence in the tumor cells of the t(5;9)(q33;q22) translocation, involving ITK and SYK rearrangement. T cell clonality was detected by multiplex PCR analysis of TRG and TRD gene rearrangements. After 4 cycles of systemic chemotherapy, the patient was in complete remission. Although this entity is very rare, our observations show that lymphomas arising from T follicular helper cells may occur in children and that this should be distinguished from other lymphomas, such T-lymphoblastic lymphomas, which require a specific therapeutic approach. PMID:25604350

  6. Chemotherapy plus interferon-alpha2b versus chemotherapy in the treatment of follicular lymphoma.

    PubMed

    Neri, N; Avilés, A; Cleto, S; Díaz, N; Talavera, A; García, E L; Díaz-Maqueo, J C

    2001-10-01

    The best treatment of follicular lymphoma remains to be determined because the long natural history of follicular lymphoma requires mature data for accurate analysis. Although the goal of primary treatment remains durable remission, the sequential application of effective treatments may also result in a prolongation of median survival time. The use of interferon (IFN) with doxorubicin-based chemotherapy has demonstrated an increase of event-free survival but not in overall survival; however, its acute and late cardiac toxicity limits its use. For this reason, we began a controlled clinical trial to assess the efficacy and toxicity of chemotherapy: COPP (cyclophosphamide, vincristine, prednisone, and procarbazine) + IFN alternating every month for six cycles compared to six cycles of chemotherapy. In an intent-to treat analysis, 55 patients were enrolled (median age 61 years). Most cases (91%) with advanced disease were randomly assigned to chemotherapy + IFN (28 cases) or chemotherapy (27 cases). Complete remission was observed in 16 patients: 59% (95% CI, 53-70%) in the chemotherapy arm compared to 20 patients 71% (95% CI, 58-79%) in the chemotherapy + IFN arm; total responses were 74% and 86%, respectively. At a median follow-up of 60 months, event-free survival was 100% for patients treated with chemotherapy + IFN, which was statistically different from patients treated with chemotherapy 70%. At 7 years, median survival has not yet been reached; 72% of patients chemotherapy + IFN remain alive without disease (95% CI, 59-81%), which is not statistically different from 72% (95%CI, 50-73%) in the chemotherapy arm. Non-hematological toxicity was most frequent and severe in the chemotherapy arm; hematological toxicity was similar in both groups. Thus, it appears that chemotherapy + IFN, as described herein, improves event-free survival but the overall survival rates remain unchanged. The use of COPP appears to be better that anthracycline-based chemotherapy because

  7. Germinal center reentries of BCL2-overexpressing B cells drive follicular lymphoma progression

    PubMed Central

    Sungalee, Stéphanie; Mamessier, Emilie; Morgado, Ester; Grégoire, Emilie; Brohawn, Philip Z.; Morehouse, Christopher A.; Jouve, Nathalie; Monvoisin, Céline; Menard, Cédric; Debroas, Guilhaume; Faroudi, Mustapha; Mechin, Violaine; Navarro, Jean-Marc; Drevet, Charlotte; Eberle, Franziska C.; Chasson, Lionel; Baudimont, Fannie; Mancini, Stéphane J.; Tellier, Julie; Picquenot, Jean-Michel; Kelly, Rachel; Vineis, Paolo; Ruminy, Philippe; Chetaille, Bruno; Jaffe, Elaine S.; Schiff, Claudine; Hardwigsen, Jean; Tice, David A.; Higgs, Brandon W.; Tarte, Karin; Nadel, Bertrand; Roulland, Sandrine

    2014-01-01

    It has recently been demonstrated that memory B cells can reenter and reengage germinal center (GC) reactions, opening the possibility that multi-hit lymphomagenesis gradually occurs throughout life during successive immunological challenges. Here, we investigated this scenario in follicular lymphoma (FL), an indolent GC-derived malignancy. We developed a mouse model that recapitulates the FL hallmark t(14;18) translocation, which results in constitutive activation of antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and applied a combination of molecular and immunofluorescence approaches to track normal and t(14;18)+ memory B cells in human and BCL2-overexpressing B cells in murine lymphoid tissues. BCL2-overexpressing B cells required multiple GC transits before acquiring FL-associated developmental arrest and presenting as GC B cells with constitutive activation–induced cytidine deaminase (AID) mutator activity. Moreover, multiple reentries into the GC were necessary for the progression to advanced precursor stages of FL. Together, our results demonstrate that protracted subversion of immune dynamics contributes to early dissemination and progression of t(14;18)+ precursors and shapes the systemic presentation of FL patients. PMID:25384217

  8. Indolent lymphomas in the pediatric population: follicular lymphoma, IRF4/MUM1+ lymphoma, nodal marginal zone lymphoma and chronic lymphocytic leukemia.

    PubMed

    Quintanilla-Martinez, Leticia; Sander, Birgitta; Chan, John K C; Xerri, Luc; Ott, German; Campo, Elias; Swerdlow, Steven H

    2016-02-01

    Indolent lymphomas in the pediatric population were discussed during the 2014 European Association for Haematopathology/Society of Hematopathology workshop in Istanbul, Turkey. This session was focused on pediatric-type follicular lymphoma (FL), and its differential diagnosis with the newly recognized entity of IRF4/MUM1+ lymphomas mainly involving Waldeyer's ring. The differential diagnosis between t(14;18) negative FL grade 1/2 and pediatric-type FL in adults was highlighted. The overlapping pathological and clinical features between FL and nodal marginal zone lymphoma (NMZL) in children and young adults were recognized and morphologic and immunophenotypical criteria helpful for the differential diagnosis were presented. Both pediatric-type FL and NMZL are indolent processes that should be distinguished from atypical lymphoid hyperplasia of the tonsils and lymph nodes. The demonstration of a B cell monoclonal population by molecular studies is strongly recommended for the diagnosis. Recognition of these indolent variants to avoid overtreatment was emphasized. Whereas most indolent lymphomas in the pediatric population show characteristic clinical, pathologic, and genetic features that differ from the adult counterpart, other rare indolent lymphoid tumors such as chronic lymphocytic leukemia (CLL) have similar characteristics. In this report, novel findings, areas of special interest, and diagnostic challenges emerging from the cases submitted to the workshop will be discussed. PMID:26416032

  9. Frequency of CD43 expression in non-Hodgkin lymphoma. A survey of 742 cases and further characterization of rare CD43+ follicular lymphomas.

    PubMed

    Lai, R; Weiss, L M; Chang, K L; Arber, D A

    1999-04-01

    CD43 expression on B cells is an immunophenotypic feature suggestive of malignancy. In the light of its diagnostic importance, we performed a comprehensive survey of CD43 expression in various types of non-Hodgkin lymphoma (NHL) and determined the frequency of its expression in routinely fixed paraffin-embedded tissues. Tissue sections in 742 cases of NHL, pretreated by the heat-induced epitope retrieval technique, were immunostained using an anti-CD43 antibody. Three categories of CD43 positivity were found: (1) more than 90% of T-cell lymphoma, mantle cell lymphoma, B-cell small lymphocytic lymphoma, and Burkitt lymphoma cases were positive; (2) 20% to 40% of nodal and extranodal marginal zone lymphoma (MZL), diffuse large B-cell lymphoma, Burkitt-like B-cell lymphoma, and lymphoplasmacytoid lymphoma cases were positive; and (3) 0% to 6% of primary splenic MZL and various types of follicular lymphoma cases were positive. Most CD43+ follicular lymphomas were predominantly large cell type with focally diffuse areas; their follicular center cell origin in 4 of 8 cases was supported by the presence of CD10 immunoreactivity and/or t(14;18) fusion gene product. CD43 is frequently detectable in a subset of B-NHL, and, thus, it seems to be a highly sensitive marker for these tumors. CD43 also may be a useful marker for classifying B-cell NHLs by virtue of its differential expression in these tumors. PMID:10191768

  10. Adult T-cell leukemia-lymphoma associated with follicular mucinosis.

    PubMed

    Ballester, Leomar Y; Cowen, Edward W; Lee, Chyi-Chia Richard

    2014-11-01

    Follicular mucinosis is frequently associated with follicular mycosis fungoides, but its association with adult T-cell leukemia-lymphoma (ATLL) is extremely rare. We report a case of a 50-year-old female patient with a history of ATLL, after multiple treatments, with residual/recurrent skin tumors in the forehead and legs. Biopsy of a skin tumor from the forehead revealed a perifollicular and intrafollicular atypical lymphoid infiltrate with abundant mucin deposition. Immunohistochemical stains showed that the atypical cells were positive for CD3, CD4, and CD25. Reverse transcription polymerase chain reaction performed on the tissue sections confirmed the presence of human T-cell leukemia virus in the biopsies of skin tumors. To our knowledge, this is only the third reported case of a follicular mucinosis in the setting of ATLL. PMID:24614206

  11. BCL2 protein expression in follicular lymphomas with t(14;18) chromosomal translocations.

    PubMed

    Masir, Noraidah; Campbell, Lisa J; Goff, Lindsey K; Jones, Margaret; Marafioti, Teresa; Cordell, Jacqueline; Clear, Andrew J; Lister, T Andrew; Mason, David Y; Lee, Abigail M

    2009-03-01

    The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein overexpression in most follicular lymphomas. However the expression of BCL2 is not always homogeneous and may demonstrate a variable degree of heterogeneity. This study analysed BCL2 protein expression pattern in 33 cases of t(14;18)-positive follicular lymphomas using antibodies against two different epitopes (i.e. the widely used antibody BCL2/124 and an alternative antibody E17). 16/33 (49%) cases demonstrated strong BCL2 expression. In 10/33 (30%) cases, BCL2 expression was heterogeneous and in some of these, its loss appeared to be correlated with cell proliferation, as indicated by Ki67 expression. Double immunofluorescence labelling confirmed an inverse BCL2/Ki67 relationship, where in 24/28 (86%) cases cellular expression of BCL2 and Ki67 was mutually exclusive. In addition, seven BCL2 'pseudo-negative' cases were identified in which immunostaining was negative with antibody BCL2/124, but positive with antibody E17. Genomic DNA sequencing of these 'pseudo-negative' cases demonstrated eleven mutations in four cases and nine of these were missense mutations. It can be concluded that in follicular lymphomas, despite carrying the t(14;18) translocations, BCL2 protein expression may be heterogeneous and loss of BCL2 could be related to cell proliferation. Secondly, mutations in translocated BCL2 genes appear to be common and may cause BCL2 pseudo-negative immunostaining. PMID:19120369

  12. The utility of IgM, CD21, HGAL and LMO2 in the diagnosis of pediatric follicular lymphoma.

    PubMed

    Karnik, Tejashree; Ozawa, Michael G; Lefterova, Martina; Luna-Fineman, Sandra; Alvarez, Elysia; Link, Michael; Zehnder, James L; Arber, Daniel A; Ohgami, Robert S

    2015-04-01

    Pediatric follicular lymphoma (pFL) is a rare neoplasm with features differing from follicular lymphoma arising in adults. Here, we describe a rare case of pFL that showed morphologic features partially overlapping with progressive transformation of germinal centers and reactive follicular hyperplasia. As typical of pFL, neoplastic B cells within follicles did not express B-cell leukemia/lymphoma 2 (BCL2). However, this case showed additional distinctive abnormal findings, which contributed to the diagnosis: (1) diffuse and uniform staining of immunoglobulin M (IgM) on cells within and outside of follicles, (2) abnormally dim expression of CD21 on follicular dendritic cells, and (3) expression of human germinal center-associated lymphoma (HGAL) and LIM domain only 2 (LMO2) on B cells in interfollicular and follicular areas. This case demonstrates the utility of these abnormal features, which can be seen in adult- or usual-type follicular lymphoma, in the diagnosis of pFL. Further studies are necessary to evaluate the significance of these findings in other cases of pFL. PMID:25701230

  13. Long-term outcome and mortality trends in early-stage, Grade 1-2 follicular lymphoma treated with radiation therapy

    SciTech Connect

    Guadagnolo, Beverly A.; Neuberg, Donna; Ng, Andrea; Mauch, Peter

    2006-03-01

    Purpose: To analyze long-term outcomes and causes of death in patients receiving radiation therapy (RT) for localized, low-grade follicular lymphoma. Methods and Materials: Between 1972 and 2000, 106 patients with Stage I-II, Grade 1-2 follicular lymphoma received RT alone or radiation and chemotherapy (RT/CT). Seventy-four percent had Stage I, and 26% had Stage II disease. Seventy-six percent received RT alone, and 24% received combined RT/CT. Second malignancy rates were compared with an age- and sex-matched population. Results: Median follow-up was 12 years. Median survival time was 19 years. The 5-, 10-, and 15-year overall survival (OS) rates were 93%, 75%, and 62%, respectively. Age {>=}60 was the only significant adverse prognostic factor with respect to OS. There were 35 deaths, 20 of which were attributable to lymphoma. Freedom from treatment failure (FFTF) rates at 5, 10, and 15 years were 72%, 46%, and 39%, respectively. Forty-seven patients (48%) relapsed. Tumor size >3 cm was the only significant adverse factor for FFTF. Observed incidence of second malignancy did not significantly exceed expected incidence. Conclusions: Although patients with early-stage, low-grade follicular lymphoma have long median survival, the leading cause of death remains lymphoma. However, patients receiving RT do not have significantly elevated cumulative incidence of second malignancy.

  14. Prognostic value of interim and end-of-treatment FDG-PET in follicular lymphoma: a systematic review.

    PubMed

    Adams, Hugo J A; Nievelstein, Rutger A J; Kwee, Thomas C

    2016-01-01

    This study aimed to systematically review the prognostic value of interim and end-of-treatment (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in follicular lymphoma during and after first-line therapy. The PubMed/MEDLINE database was searched for relevant original studies. Included studies were methodologically assessed, and their results were extracted and descriptively analyzed. Three studies on the prognostic value of interim FDG-PET and eight studies on the prognostic value of end-of-treatment FDG-PET were included. Overall, studies were of poor methodological quality. In addition, there was incomplete reporting of progression-free survival (PFS) and overall survival (OS) data by several studies, and none of the studies incorporated the Follicular Lymphoma International Prognostic Index (FLIPI) in the OS analyses. Two studies reported no significant difference in PFS between interim FDG-PET positive and negative patients, whereas one study reported a significant difference in PFS between the two groups. Two studies reported no significant difference in OS between interim FDG-PET positive and negative patients. Five studies reported end-of-treatment FDG-PET positive patients to have a significantly worse PFS than end-of-treatment FDG-PET negative patients, and one study reported a non-significant trend towards a worse PFS for end-of-treatment FDG-PET positive patients. Three studies reported end-of-treatment FDG-PET positive patients to have a significantly worse OS than end-of-treatment FDG-PET negative patients. In conclusion, the available evidence does not support the use of interim FDG-PET in follicular lymphoma. Although published studies suggest end-of-treatment FDG-PET to be predictive of PFS and OS, they suffer from numerous biases and failure to correct OS prediction for the FLIPI. PMID:26576560

  15. Is watch and wait still acceptable for patients with low-grade follicular lymphoma?

    PubMed

    Armitage, James O; Longo, Dan L

    2016-06-01

    Follicular lymphoma (FL) represents more than 20% of all non-Hodgkin lymphomas worldwide and approximately 30% of the non-Hodgkin lymphomas diagnosed in the United States. Although occasionally localized at the time of diagnosis, most patients have disseminated disease. However, patients are frequently asymptomatic, and this, in combination with a long median survival, led to the initial studies of observing asymptomatic patients without initial therapy, ie, "watch and wait." Since the initial report of watch and wait as a treatment strategy for patients with low-grade FL, our understanding of the biology of the disease has advanced; multiple active new agents have been introduced into practice, and the survival of patients with low-grade FL has improved. Given these changes, is watch and wait still an acceptable treatment recommendation for a newly diagnosed patient with low-grade FL? PMID:26994147

  16. Diagnostic accuracy of endoscopic biopsies for the diagnosis of gastrointestinal follicular lymphoma: a clinicopathologic study of 48 patients.

    PubMed

    Iwamuro, Masaya; Okada, Hiroyuki; Takata, Katsuyoshi; Nose, Soichiro; Miyatani, Katsuya; Yoshino, Tadashi; Yamamoto, Kazuhide

    2014-04-01

    The purpose of this study was to reveal the diagnostic accuracy of initial pathologic assessment of biopsied samples in patients with gastrointestinal follicular lymphoma lesions. A total of 48 patients with follicular lymphoma (Lugano system stage I: n = 30; II1: n = 4; II2: n = 4; IV: n = 10) with gastrointestinal involvement who underwent endoscopic biopsy were enrolled and retrospectively reviewed. Nine (18.8%) of the 48 patients were not appropriately diagnosed as having follicular lymphoma at the initial biopsy. The initial pathological diagnosis included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (n = 4), necrotic tissue (n = 2), duodenitis (n = 1), or suspected lymphoma of unspecified subtype (n = 2). The reasons for these inappropriate diagnoses were insufficient histopathologic analysis lacking CD10 and BCL2 staining (n = 7) and unsuitable biopsy samples taken from erosions or ulcers that contained scanty lymphoma cells or no lymphoid follicles (n = 2). In conclusion, incomplete histopathologic analysis and unsuitable biopsy samples are pitfalls in the diagnosis of gastrointestinal follicular lymphoma. PMID:24513028

  17. [Therapy-related chronic myelogenous leukemia following RFM therapy in a patient with follicular lymphoma].

    PubMed

    Shibazaki, Mio; Sumi, Masahiko; Takeda, Wataru; Kirihara, Takehiko; Kurihara, Taro; Sato, Keijiro; Ueki, Toshimitsu; Hiroshima, Yuki; Ueno, Mayumi; Ichikawa, Naoaki; Mori, Yuichi; Kobayashi, Hikaru

    2014-08-01

    Therapy-related myelodysplastic syndrome and acute myelogenous leukemia are increasingly being recognized as treatment complications in patients receiving chemotherapy or radiotherapy for previous neoplasms. However, therapy-related chronic myelogenous leukemia is relatively rare. A 61-year-old woman with a history of radiation therapy for breast cancer had previously, in 2007, received 4 courses of chemotherapy (RFM: rituximab, fludarabine, and mitoxantrone) for follicular lymphoma. In 2010, she was diagnosed with chronic-phase chronic myelogenous leukemia (CML) with Philadelphia chromosome but no other cytogenetic anomalies. Although a complete cytogenetic response (CCyR) was achieved with imatinib therapy, she developed leukocytosis with lymphoblasts and lymphoid crisis was diagnosed in January 2013. G-banded karyotyping showed 45, XX, -7, t, (9;22)(q33;q11.2). Unrelated bone marrow stem cell transplantation was performed after she had achieved a CCyR with dasatinib therapy. Polymerase chain reaction detected no major bcr/abl transcript in her bone marrow 42 days after transplantation. The majority of secondary leukemias resulting from the use of cytotoxic drugs can be divided into two well-defined groups depending on whether the patient has received alkylating agents or topoisomerase II inhibitors. However, concerns regarding the leukemogenic potential of fludarabine-based chemotherapy are growing. The potential risk of therapy-related leukemias including CML needs to be considered following fludarabine-based chemotherapy. PMID:25186488

  18. Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma.

    PubMed

    Okosun, Jessica; Wolfson, Rachel L; Wang, Jun; Araf, Shamzah; Wilkins, Lucy; Castellano, Brian M; Escudero-Ibarz, Leire; Al Seraihi, Ahad Fahad; Richter, Julia; Bernhart, Stephan H; Efeyan, Alejo; Iqbal, Sameena; Matthews, Janet; Clear, Andrew; Guerra-Assunção, José Afonso; Bödör, Csaba; Quentmeier, Hilmar; Mansbridge, Christopher; Johnson, Peter; Davies, Andrew; Strefford, Jonathan C; Packham, Graham; Barrans, Sharon; Jack, Andrew; Du, Ming-Qing; Calaminici, Maria; Lister, T Andrew; Auer, Rebecca; Montoto, Silvia; Gribben, John G; Siebert, Reiner; Chelala, Claude; Zoncu, Roberto; Sabatini, David M; Fitzgibbon, Jude

    2016-02-01

    Follicular lymphoma is an incurable B cell malignancy characterized by the t(14;18) translocation and mutations affecting the epigenome. Although frequent gene mutations in key signaling pathways, including JAK-STAT, NOTCH and NF-κB, have also been defined, the spectrum of these mutations typically overlaps with that in the closely related diffuse large B cell lymphoma (DLBCL). Using a combination of discovery exome and extended targeted sequencing, we identified recurrent somatic mutations in RRAGC uniquely enriched in patients with follicular lymphoma (17%). More than half of the mutations preferentially co-occurred with mutations in ATP6V1B2 and ATP6AP1, which encode components of the vacuolar H(+)-ATP ATPase (V-ATPase) known to be necessary for amino acid-induced activation of mTORC1. The RagC variants increased raptor binding while rendering mTORC1 signaling resistant to amino acid deprivation. The activating nature of the RRAGC mutations, their existence in the dominant clone and their stability during disease progression support their potential as an excellent candidate for therapeutic targeting. PMID:26691987

  19. Incidence, risk factors and outcome of histological transformation in follicular lymphoma.

    PubMed

    Conconi, Annarita; Ponzio, Carlotta; Lobetti-Bodoni, Chiara; Motta, Maddalena; Rancoita, Paola M V; Stathis, Anastasios; Moccia, Alden A; Mazzucchelli, Luca; Bertoni, Francesco; Ghielmini, Michele; Cavalli, Franco; Zucca, Emanuele

    2012-04-01

    Histological transformation (HT) into diffuse large B-cell lymphoma (DLBCL) was documented in 37 of the 281 (13%; 95% CI, 9-18) follicular lymphoma (FL) patients treated at our institute from 1979 to 2007. HT occurred at a median of 2·75 years from initial FL diagnosis and HT rate was 15% at 10 years and 26% at 14 years, with a plateau from that point onward. Patients with bulky or extranodal disease, or those diagnosed before 1990 had a significantly higher risk of HT. When initial treatment strategies were taken into account, a reduced HT risk was seen in the patients initially managed with a 'watch and wait' policy, while the risk appeared significantly increased in the small subset of 18 patients initially managed with rituximab plus chemotherapy (P = 0·0005). HT was associated with a significantly shorter cause-specific survival (P = 0·0002). Predictors of survival after HT were the Follicular Lymphoma International Prognostic Index at diagnosis, as well as age and performance status at the time of HT. Our data confirm the adverse clinical outcome of FL after HT. In keeping with previous isolated reports, our findings suggest that there is a subgroup of patients in whom HT may not occur. PMID:22348437

  20. BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma

    PubMed Central

    Correia, Cristina; Schneider, Paula A.; Dai, Haiming; Dogan, Ahmet; Maurer, Matthew J.; Church, Amy K.; Novak, Anne J.; Feldman, Andrew L.; Wu, Xiaosheng; Ding, Husheng; Meng, X. Wei; Cerhan, James R.; Slager, Susan L.; Macon, William R.; Habermann, Thomas M.; Karp, Judith E.; Gore, Steven D.; Kay, Neil E.; Jelinek, Diane F.; Witzig, Thomas E.; Nowakowski, Grzegorz S.

    2015-01-01

    Follicular lymphoma (FL), an indolent neoplasm caused by a t(14;18) chromosomal translocation that juxtaposes the BCL2 gene and immunoglobulin locus, has a variable clinical course and frequently undergoes transformation to an aggressive lymphoma. Although BCL2 mutations have been previously described, their relationship to FL progression remains unclear. In this study, we evaluated the frequency and nature of BCL2 mutations in 2 independent cohorts of grade 1 and 2 FLs, along with the correlation between BCL2 mutations, transformation risk, and survival. The prevalence of BCL2 coding sequence mutations was 12% in FL at diagnosis and 53% at transformation (P < .0001). The presence of these BCL2 mutations at diagnosis correlated with an increased risk of transformation (hazard ratio 3.6; 95% CI, 2.0-6.2; P < .0001) and increased risk of death due to lymphoma (median survival of 9.5 years with BCL2 mutations vs 20.4 years without; P = .012). In a multivariate analysis, BCL2 mutations and high FL international prognostic index were independent risk factors for transformation and death due to lymphoma. Some mutant Bcl-2 proteins exhibited enhanced antiapoptotic capacity in vitro. Accordingly, BCL2 mutations can affect antiapoptotic Bcl-2 function, are associated with increased activation-induced cytidine deaminase expression, and correlate with increased risk of transformation and death due to lymphoma. PMID:25452615

  1. A phase II trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701

    PubMed Central

    Grant, Barbara W.; Jung, Sin-Ho; Johnson, Jeffrey L.; Kostakoglu, Lale; His, Eric; Byrd, John C.; Jones, Jeffrey; Leonard, John P.; Martin, S. Eric; Cheson, Bruce D.

    2013-01-01

    Rituximab combined with chemotherapy has improved the survival of previously untreated patients with follicular lymphoma (FL). Nevertheless, many patients neither want nor can tolerate chemotherapy, leading to interest in biological approaches. Epratuzumab is a humanized anti-CD22 monoclonal antibody with efficacy in relapsed FL. Since both rituximab and epratuzumab have single agent activity in FL, we evaluated the antibody combination as initial treatment of patients with FL. Patients and Methods Fifty-nine untreated patients with FL received epratuzumab 360 mg/m2 with rituximab 375 mg/m2 weekly for four induction doses. This combination was continued as extended induction in weeks 12, 20, 28, and 36. Response assessed by CT was correlated with clinical risk factors, FDG-PET findings at week 3, Fcg polymorphisms, immunohistochemical markers, and statin use. Results Therapy was well-tolerated with toxicities similar to expected with rituximab monotherapy. Fifty-two (88.2%) evaluable patients responded, including 25 complete responses (CR)(42.4%), and 27 partial responses (45.8%). At 3 years follow-up, 60% of patients remain in remission. Follicular Lymphoma International Prognostic Index (FLIPI) risk strongly predicted progression-free survival (p=0.022). Conclusions The high response rate and prolonged time to progression observed with this antibody combination are comparable to those observed after standard chemo-immunotherapies and further support the development of biologic, non-chemotherapeutic approaches for these patients. PMID:23922187

  2. The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin: FIL-FOLL study.

    PubMed

    Rossi, Davide; Bruscaggin, Alessio; La Cava, Piera; Galimberti, Sara; Ciabatti, Elena; Luminari, Stefano; Rigacci, Luigi; Tucci, Alessandra; Pulsoni, Alessandro; Bertoldero, Giovanni; Vallisa, Daniele; Rusconi, Chiara; Spina, Michele; Arcaini, Luca; Angrilli, Francesco; Stelitano, Caterina; Merli, Francesco; Gaidano, Gianluca; Federico, Massimo; Palumbo, Giuseppe A

    2015-04-01

    Though most follicular lymphoma biomarkers rely on tumor features, the host genetic background may also be relevant for outcome. Here we aimed at verifying the contribution of candidate polymorphisms of FCγ receptor, DNA repair and detoxification genes to prognostic stratification of follicular lymphoma treated with immunochemotherapy. The study was based on 428 patients enrolled in the FOLL05 prospective trial that compared three standard-of-care regimens (rituximab-cyclophosphamide-vincristine-prednisone versus rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone versus rituximab-fludarabine-mitoxantrone) for the first line therapy of advanced follicular lymphoma. Polymorphisms were genotyped on peripheral blood DNA samples. The primary endpoint was time to treatment failure. Polymorphisms of FCGR2A and FCGR3A, which have been suggested to influence the activity of rituximab as a single agent, did not affect time to treatment failure in the pooled analysis of the three FOLL05 treatment arms that combined rituximab with chemotherapy (P=0.742, P=0.252, respectively). These results were consistent even when the analysis was conducted by intention to treat, indicating that different chemotherapy regimens and loads did not interact differentially with the FCGR2A and FCGR3A genotypes. The genotype of MLH1, which regulates the genotoxic effect of doxorubicin, significantly affected time to treatment failure in patients in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone arm (P=0.001; q<0.1), but not in arms in which patients did not receive doxorubicin (i.e., the rituximab-cyclophosphamide-vincristine-prednisone and rituximab-fludarabine-mitoxantrone arms). The impact of MLH1 on time to treatment failure was independent after adjusting for the Follicular Lymphoma International Prognostic Index and other potential confounding variables by multivariate analysis. These data indicate that MLH1 genotype is a predictor of failure to benefit from

  3. Large-scale profiling of archival lymph nodes reveals pervasive remodeling of the follicular lymphoma methylome.

    PubMed

    Killian, J Keith; Bilke, Sven; Davis, Sean; Walker, Robert L; Killian, M Scott; Jaeger, Erich B; Chen, Yidong; Hipp, Jason; Pittaluga, Stefania; Raffeld, Mark; Cornelison, Robert; Smith, William I; Bibikova, Marina; Fan, Jian-Bing; Emmert-Buck, Michael R; Jaffe, Elaine S; Meltzer, Paul S

    2009-02-01

    Emerging technologies allow broad profiling of the cancer genome for differential DNA methylation relative to benign cells. Herein, bisulfite-modified DNA from lymph nodes with either reactive hyperplasia or follicular lymphoma (FL) were analyzed using a commercial C/UpG genotyping assay. Two hundred fifty-nine differentially methylated targets (DMT) distributed among 183 unique genes were identified in FL. Comparison of matched formalin-fixed, paraffin-embedded and frozen surgical pathology replicates showed the complete preservation of the cancer methylome among differently archived tissue specimens. Analysis of the DMT profile is consistent with a pervasive epigenomic remodeling process in FL that affects predominantly nonlymphoid genes. PMID:19155300

  4. Primary follicular non-Hodgkin's lymphoma of the ureter: A case report and literature review

    PubMed Central

    DAI, ZHIHONG; LIU, ZHIYU; GAO, YUREN; WANG, LIANG

    2016-01-01

    Ureteral cancer is a rare type of neoplasm, with the most prevalent forms including squamous cell carcinoma, transitional cell carcinoma and adenocarcinoma. Ureteral lymphoma is particularly uncommon, and forming a pre-operative diagnosis of the disease is often difficult. The current study describes the case of a 31-year-old man presenting with a space-occupying lesion located in the left lower ureter. Follicular non-Hodgkin's lymphoma was diagnosed via intraoperative frozen section and post-operative pathological analysis. The affected ureteric segment was excised, and the ureter was repaired by end-to-end anastomosis with insertion of a double-J tube for internal drainage. The patient was followed up for 10 months and presented with no signs of recurrence. The current study affirms the importance of pathological examination in the differential diagnosis of ureteral neoplasms and the selection of an appropriate treatment. PMID:27313721

  5. A General Framework for the Segmentation of Follicular Lymphoma Virtual Slides

    PubMed Central

    Oger, Myriam; Belhomme, Philippe; Gurcan, Metin N.

    2012-01-01

    Follicular Lymphoma (FL) is one of the most common types of non-Hodgkin's Lymphomas in the world. Diagnosis of FLis based on morphological and immunohistochemical characteristics found on tissue sections. Our project's aim is to develop computer-aided analysis tools on virtual slide images (VSI) of lymphoid tissues with the purpose of improving the FL grading performed in malignant follicles. In this paper, we focus on the first step of our work, an automated system for detecting follicles in VSI of lymphoid tissues. To mimic the human expert process, the system works on low-resolution CD20 images and maps the follicle boundaries on high-resolution H&E images. PMID:22717207

  6. Peripheral blood involvement in patients with follicular lymphoma: a rare disease manifestation associated with poor prognosis.

    PubMed

    Sarkozy, Clémentine; Baseggio, Lucile; Feugier, Pierre; Callet-Bauchu, Evelyne; Karlin, Lionel; Seymour, John F; Lebras, Laure; Michallet, Anne-Sophie; Offner, Fritz; Dumas, Olivier; Traverse-Glehen, Alexandra; Ffrench, Martine; Lopez-Guillermo, Armando; Berger, Françoise; Coiffier, Bertrand; Felman, Pascale; Salles, Gilles

    2014-03-01

    Follicular Lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) subtype and its course is heterogeneous. At diagnosis, some patients with FL manifest a detectable leukaemic phase (FL-LP), but this feature has been seldom described and is poorly characterized. Among 499 patients diagnosed with FL in Lyon-Sud hospital, 37 (7·4%) had characteristic FL-LP (by cytological blood smears and flow cytometric analysis). In addition, 91/1135 FL patients from the PRIMA study presented FL-LP at study entry. In order to evaluate the outcome of this Lyon-Sud cohort, FL-LP patients were matched with 111 newly diagnosed FL without LP according to the Follicular Lymphoma International Prognostic Index (FLIPI) score, age and treatment. Presence of FL-LP was associated with shorter progression-free survival (PFS) and overall survival (OS) (P = 0·004 and P = 0·031, respectively). Presence of FL-LP and high FLIPI score remained independent prognostic factors in a Cox model for time to progression (TTP). A number of circulating lymphoma cells (CLC) >4 × 10(9) /l was the most significant predictor for a shorter TTP in this Cox model. The prognostic impact of FL-LP on TTP was validated in the PRIMA cohort (P = 0·0004). In conclusion, FL-LP is a rare event associated with shorter PFS and patients with CLC >4 × 10(9) /l have a poorer outcome. These patients should be monitored carefully to consider alternative therapeutic options. PMID:24274024

  7. Role of Hematopoietic Stem Cell Transplant in the Management of Follicular Lymphoma

    PubMed Central

    Foster, Matthew; Gabriel, Don A.; Shea, Thomas

    2010-01-01

    Despite decades of published data regarding the application of autologous and allogeneic stem cell transplant in patients with follicular lymphoma, there remain no uniform indications for its use in this disease. Autologous transplant has been shown to lead to longer progression-free survival times in randomized trials when compared with postremission interferon-based chemo-immunotherapy. However, the development of rituximab and its use in frontline, salvage, and maintenance therapy complicates the decision to pursue autologous transplant, a modality developed prior to the advent of anti-CD20 monoclonal antibodies. Allogeneic transplant offers the advantages of lymphoma-free grafts and the immunologic graft-versus-lymphoma effect. These factors may confer the possibility of long-term remission, though historically they have been accompanied by high rates of upfront morbidity and mortality, especially in heavily pretreated patients with a poor performance status or chemotherapy-refractory disease. Advances in patient selection, human leukocyte antigen (HLA) matching, conditioning regimens, and supportive care have reduced transplant-related mortality and the incidence of graft-versus-host disease. Recently published data focus on the incorporation of rituximab and radioimmunoconjugates prior to, during, and following autologous transplant. Furthermore, reduced-intensity allogeneic stem cell transplantation has increasingly been used for relapsed follicular lymphoma patients with comorbidities or advanced age. Several recent reports suggest that reduced-intensity regimens may provide a high likelihood of long-term disease-free survival for patients up to 70 years of age with a good performance status, chemotherapy-sensitive disease, and HLA-matched sibling donors. Such patients with relapsed disease should be referred to a transplant center that can enroll them in one of the forthcoming clinical trials that aim to confirm these outcomes. PMID:19561292

  8. A Clinicopathologic Study of Lennert Lymphoma and Possible Prognostic Factors: The Importance of Follicular Helper T-cell Markers and the Association With Angioimmunoblastic T-cell Lymphoma.

    PubMed

    Kurita, Daisuke; Miyoshi, Hiroaki; Yoshida, Noriaki; Sasaki, Yuya; Kato, Seiichi; Niino, Daisuke; Sugita, Yasuo; Hatta, Yoshihiro; Takei, Masami; Makishima, Makoto; Ohshima, Koichi

    2016-09-01

    Lennert lymphoma (LeL) is a variant of peripheral T-cell lymphoma, not otherwise specified. Few clinicopathologic studies have investigated LeL, which is a rare disease. Here, we analyzed the clinicopathologic features of 26 patients with LeL to identify potential prognostic factors. Neoplastic cells positive for CD4, CD8, CD4/CD8, TIA-1, and granzyme B were observed in 21 (80.8%), 4 (15.4%), 1 (3.8%), 4 (15.3%), and 0 (0.0%) patients, respectively. Regarding follicular helper T-cell (TFH) markers, neoplastic cells positive for programmed cell death-1 (PD-1), CXCL13, CD10, and BCL6 were observed in 14 (53.8%), 13 (50.0%), 1 (3.8%), and 0 (0.0%) patients, respectively. Patients with positivity for at least 1 TFH cell marker (PD-1, CXCL13, CD10, and/or BCL6) were defined as being TFH cell marker-positive (n=15) and had a worse prognosis than TFH cell marker-negative patients (n=11) (P=0.011). Clinicopathologic characteristics did not differ significantly between TFH cell marker-positive and marker-negative LeL patients. Moreover, prognosis did not differ significantly between TFH cell marker-positive LeL patients and patients with angioimmunoblastic T-cell lymphoma (AITL) (n=42). Nevertheless, as compared with AITL, TFH cell marker-positive LeL was associated with significantly lower frequencies of B symptoms, skin rash, high-intermediate-risk or high-risk international prognostic index values, expanded follicular dendritic cell meshworks, polymorphic infiltrate, clear cells, and positivity for CD10 and BCL6. Although it may be difficult to definitively distinguish between TFH cell marker-positive LeL and AITL, our results suggest that TFH cell markers are useful for identifying LeL patients who will experience unfavorable outcomes. PMID:27428734

  9. ALLOGENEIC TRANSPLANTS IN FOLLICULAR LYMPHOMA: HIGHER RISK OF DISEASE PROGRESSION AFTER REDUCED INTENSITY COMPARED TO MYELOABLATIVE CONDITIONING

    PubMed Central

    Hari, Parameswaran; Carreras, Jeanette; Zhang, Mei-Jie; Gale, Robert Peter; Bolwell, Brian J.; Bredeson, Christopher N.; Burns, Linda J.; Cairo, Mitchell S.; Freytes, César O.; Goldstein, Steven C.; Hale, Gregory A.; Inwards, David J.; LeMaistre, Charles F.; Maharaj, Dipnarine; Marks, David I.; Schouten, Harry C.; Slavin, Shimon; Vose, Julie M.; Lazarus, Hillard M.; van Besien, Koen

    2008-01-01

    Reduced intensity conditioning (RIC) regimens have been increasingly used for allogeneic hematopoietic stem cell transplantation (HSCT) in Follicular lymphoma (FL). We compared traditional myeloablative conditioning regimens to RIC in FL. Outcomes of HLA-identical sibling HSCT for follicular lymphoma in 208 recipients reported to the Center for International Blood and Marrow Transplant Research between 1997 and 2002 were studied. Conditioning regimens were categorized as myeloablative (N=120) or reduced-intensity (RIC; N=88). Use of RIC regimens increased from <10% of transplants in 1997 to >80% in 2002 signaling a major shift in practice. Patients receiving RIC were older and had a longer interval from diagnosis to transplant. These differences did not correlate with outcomes. Median follow-up of survivors was 50 mo (4–96 mo) after myeloablative conditioning versus 35 mo (4–82 mo) after RIC (p<0.001). At 3 years, overall survival (OS) for the myeloablative and RIC cohorts were 71 (63–79%) and 62 (51–72%; p=0.15) and progression free survival (PFS), 67 (58–75%) and 55 (44–65%; p=0.07) respectively. Lower Karnofsky performance score (KPS) and resistance to chemotherapy were associated with higher treatment related mortality (TRM), lower OS and PFS. On multivariate analysis, an increased risk of lymphoma progression after RIC was observed (RR=2.97, p=0.04) RIC has become the de facto standard in allogeneic HSCT for FL and appears to result in similar long term outcomes. Although disease free survival is similar compared to myeloablative conditioning, an increased risk of late disease progression after RIC is concerning. PMID:18215784

  10. Obatoclax and Bortezomib in Treating Patients With Aggressive Relapsed or Recurrent Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-12-03

    Adult Non-Hodgkin Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma

  11. Interferon alpha 2b as maintenance therapy improves outcome in follicular lymphoma.

    PubMed

    Avilés, Agustin; Neri, Natividad; Huerta-Guzmán, Judith; Pérez, Felipe; Sotelo, León

    2004-11-01

    The role of interferon alpha as maintenance therapy in follicular lymphoma (FL) remains unsolved. We started a controlled clinical trial to assess if interferon alpha 2b could improve outcome, measured with event free survival (EFS) and overall survival (OS) in patients with FL in complete remission after chemotherapy based anthracyclines and adjuvant radiotherapy to sites of initial bulky disease. Three hundred and eighty four patients in complete response after 6 cycles of CEOP-Bleo (cyclophosphamide, epirubicin, vincristine, prednisone and bleomycin, at standard doses), and adjuvant radiotherapy when necessary, were randomized to received Interferon alpha 2b, three times a week for 1 year or no treatment (control group). Median follow up was 9.8 years (range 7.0-15 years); actuarial curves showed that EFS was 64% (95% confidence interval (CI) 56-71%) in patients treated with interferon that was statistically significant to patients in the control group: 35% (95% CI: 28-43%) (p<.01). OS was also statistically significant: 81% in patients treated with interferon (95% CI: 74-93%) and 57% (95% CI: 50-63%) in the control group (p<.001). Toxicity was mild, all patients received the planned dose of interferon on time. The use of aggressive chemotherapy and maintenance therapy with interferon alpha 2b in follicular lymphoma improved outcome; more than 60% of patients remain alive free of disease at longer follow-up. PMID:15512813

  12. Follicular lymphoma grading using cell-graphs and multi-scale feature analysis

    NASA Astrophysics Data System (ADS)

    Oztan, Basak; Kong, Hui; Gürcan, Metin N.; Yener, Bülent

    2012-03-01

    We present a method for the computer-aided histopathological grading of follicular lymphoma (FL) images based on a multi-scale feature analysis. We analyze FL images using cell-graphs to characterize the structural organization of the cells in tissues. Cell-graphs represent histopathological images with undirected and unweighted graphs wherein the cytological components constitute the graph nodes and the approximate adjacencies of the components are represented with edges. Using the features extracted from nuclei- and cytoplasm-based cell-graphs, a classifier defines the grading of the follicular lymphoma images. The performance of this system is comparable to that of our recently developed system that characterizes higher-level semantic description of tissues using model-based intermediate representation (MBIR) and color-textural analysis. When tested with three different classifiers, the combination of cell-graph based features with the MBIR and color-textural features followed by a multi-scale feature selection is shown to achieve considerably higher classification accuracies than any set of these feature sets can achieve separately.

  13. Myeloid cell nuclear differentiation antigen is expressed in a subset of marginal zone lymphomas and is useful in the differential diagnosis with follicular lymphoma.

    PubMed

    Metcalf, Ryan A; Monabati, Ahmad; Vyas, Monika; Roncador, Giovanna; Gualco, Gabriela; Bacchi, Carlos E; Younes, Sheren F; Natkunam, Yasodha; Freud, Aharon G

    2014-08-01

    The diagnosis of marginal zone lymphomas (MZL) is challenged by the lack of specific markers that distinguish them from other low-grade non-Hodgkin B-cell lymphomas. Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein that labels myelomonocytic cells as well as B lymphocytes that localize to the marginal zone areas of splenic white pulp. We evaluated MNDA expression in a large series of B-cell lymphomas to assess the sensitivity and specificity of this antigen for the characterization of MZL. A total of 440 tissue sections containing extramedullary B-cell lymphomas and 216 bone marrow biopsies containing atypical or neoplastic lymphoid infiltrates were stained for MNDA by immunohistochemistry. Among the extramedullary lymphoma cases, approximately 67% of nodal MZL, 61% of extranodal MZL, and 24% of splenic MZL expressed MNDA. MNDA was also infrequently expressed in other B-cell neoplasms including mantle cell lymphoma (6%), chronic lymphocytic leukemia/small lymphocytic lymphoma (13%), follicular lymphoma (FL) (4%), lymphoplasmacytic lymphoma (25%), and diffuse large B-cell lymphoma (3%). In contrast, MNDA was only expressed in 2.3% of all bone marrow biopsies involved by lymphoid infiltrates, including 2 cases of FL and one case of MZL. Collectively, these data support the inclusion of MNDA in the diagnostic evaluation of extramedullary B-cell lymphomas, particularly those in which the differential diagnosis is between low-grade FL and MZL. PMID:24925224

  14. Quantifying Benefit of Autologous Transplantation for Relapsed Follicular Lymphoma Patients via Instrumental Variable Analysis.

    PubMed

    Oh, Danielle H; Li, Haocheng; Duan, Qiuli; Villa, Diego; Peters, Anthea; Chua, Neil; Owen, Carolyn J; Connors, Joseph M; Stewart, Douglas A

    2016-05-01

    The role of autologous stem cell transplantation (ASCT) in patients with relapsed follicular lymphoma (FL) remains controversial because of a lack of proven overall survival (OS) benefit versus nontransplant strategies. We conducted a comparative effectiveness research study involving 3 tertiary Canadian cancer centers to determine whether the ASCT-based approach used at 1 center improved OS relative to non-ASCT approaches used at the other centers. Of 1082 consecutive patients aged 18 to 60 years and diagnosed with FL from 2001 to 2010, the study population included 355 patients who experienced relapse from chemotherapy (center A = 96, center B = 84, center C = 175). Data were analyzed according to the instrumental variable of treatment center to control for confounding factors. The frequency of using ASCT at first or second relapse was significantly different between the centers (A = 58%, B = 7%, C = 5%, P < .001). With a median follow-up of 69.1 months, the actuarial 5-year OS rates after first chemotherapy relapse were 89%, 60%, and 60% for centers A, B, and C respectively (log rank P < .0001). Based on instrumental variable analysis, the use of ASCT at relapse 1 or 2 significantly decreased the risk of death from first relapse (HR .127, P = .004) and from initial diagnosis (HR .116, P = .004). In conclusion, for FL patients who relapse after chemotherapy, these results strongly support more frequent use of ASCT at first or second relapse. PMID:26785331

  15. Cutaneous Spindle-Cell B-Cell Lymphomas: Most are Neoplasms of Follicular Center Cell Origin.

    PubMed

    Charli-Joseph, Yann; Cerroni, Lorenzo; LeBoit, Philip E

    2015-06-01

    Cutaneous lymphomas of both B cells and less commonly T cells can exceptionally exhibit spindle-cell morphology. Less than 30 spindle-cell B-cell lymphomas of the skin have been described, mostly before the adoption of detailed immunohistochemistry, and thus initially interpreted as variants of diffuse large B-cell lymphoma (DLBCL). Furthermore, some authors suggest that cutaneous spindle-cell B-cell lymphomas (cSCBCLs) may behave more aggressively than their conventional morphologic counterparts and may thus merit more aggressive treatment. Herein we describe the largest case series of cSCBCL analyzed to date to characterize their clinicopathologic and immunohistochemical features and clarify their subtype according to the current WHO/EORTC classification scheme. Twenty-four cSCBCLs arose in 18 male and 6 female individuals with a mean age of 55 years, mostly on the head (12/24), trunk (8/24), and lower extremities (4/24). Histopathologic features were similar for all cases. Neoplasms involved the entire dermis and focally the subcutis. The neoplastic infiltrates comprised a mixture of medium-sized, visually prominent spindled cells (15%; up to 85% of the infiltrate) arranged in a fascicular pattern around nodular aggregates and admixed in a random manner between centrocyte/centroblast-like cells within these nodular collections. Immunohistochemical support for a follicular center cell origin was present in 22/24 cases, 1 was consistent with DLBCL-leg type and 1 defied precise classification, best fitting with intermediate-grade DLBCL-other. Our findings reinforce the concept that most cSCBCLs are variants of low-grade B-cell lymphomas of follicle center cell origin and not intermediate-grade variants of DLBCL. PMID:25634743

  16. Characterization of a case of follicular lymphoma transformed into B-lymphoblastic leukemia

    PubMed Central

    2013-01-01

    Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma with an ability to transform into a more aggressive disease, albeit infrequently to B-lymphoblastic leukemia/lymphoma. While t(14;18)(q32;q21) has been associated with approximately 90% cases of FL, that alteration alone is insufficient to cause FL and associated mutations are still being elucidated. The transformation of FL to B-lymphoblastic leukemia generally includes the dysregulation of MYC gene expression, typically through IGH rearrangement. Such cases of “double-hit” leukemia/lymphoma with both BCL2 and MYC translocations warrant further study as they are often not identified early, are associated with a poor prognosis, and are incompletely understood in molecular terms. Here we describe a patient with a diagnosis of FL that transformed to B-lymphoblastic leukemia. Detailed cytogenetic characterization of the transformed specimen using karyotype, fluorescence in situ hybridization, microarray and gene rearrangement analyses revealed a complex karyotype comprised principally of whole chromosome or whole arm copy number gains or losses. Smaller, single-gene copy number alterations identified by microarray were limited in number, but included amplification of a truncated EP300 gene and alterations in NEIL1 and GPHN. Analyses defined the presence of an IGH/BCL2 fusion due to a translocation as well as a MYC/IGH fusion due to an insertion, with both rearrangements involving the same IGH allele. The data illustrate the value in characterizing double-hit lymphoma cases with both traditional and novel technologies in the detailed cytogenetic workup. PMID:23985173

  17. Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma.

    PubMed

    Boland, A; Bagust, A; Hockenhull, J; Davis, H; Chu, P; Dickson, R

    2009-09-01

    This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma (NHL), in accordance with the licensed indication, based upon the evidence submission from Roche Products Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submitted clinical evidence included two randomised controlled trials [European Organisation for Research and Treatment of Cancer (EORTC) and German Low Grade Lymphoma Study Group - Fludarabine, Cyclophosphamide and Mitoxantrone and (GLSG-FCM)] comparing the clinical effects of chemotherapy with or without rituximab in the induction of remission at first or second relapse and the clinical benefits of rituximab maintenance therapy versus the NHS's current clinical practice of observation for follicular lymphoma (FL) patients. Both trials showed that in patients with relapsed FL the addition of rituximab to chemotherapy induction treatment increased overall response rates. Furthermore, rituximab maintenance therapy increased the median length of remission when compared with observation only. Safety data from the two trials showed that while the majority of patients reported some adverse events, the number of patients withdrawing from treatment in the EORTC trial was low, with rates not being reported for the GLSG-FCM trial. The most commonly reported adverse events were blood/bone marrow toxicity, skin rashes and allergies. The ERG reran the manufacturer's economic model after altering several of the assumptions and parameter values in order to recalculate the cost-utility ratios, quality-adjusted life-years (QALYs) and estimates of benefits. The manufacturer reported that maintenance therapy with rituximab was cost-effective compared with observation against commonly applied thresholds, with an incremental

  18. Nodal Follicular Lymphomas: A Clinicopathological Study from a Tertiary Care Centre in South India.

    PubMed

    Supari, Divya; Ananthamurthy, Anuradha

    2016-06-01

    The aim of this study was to assess the distribution of nodal follicular lymphomas (FL) among various subtypes of non- Hodgkin lymphoma and to study their clinico-pathological features. Clinical details, histomorphology including grading & patterns and immunoprofile of 44 cases were studied. Majority of the cases were grade 1 (61 %) FL. BCL2 positivity was higher in low grade FLs (97 %). An associated diffuse large B cell lymphoma component was seen in 18 % and was present only in conjunction with grade 3 FL. Majority of our patients (76 %) had a high FLIPI score and belonged to the high risk group. Our study showed that the incidence of FLs is much lower in the Indian population (14.5 %) when compared to western studies and majority were of low grade. Although there was complete initial response to treatment, relapse was common and was much higher in low grade FLs with diffuse areas on histology, Ann Arbor stage III/IV and FLIPI scores of 3-5. PMID:27065580

  19. Pediatric follicular lymphoma: a report of the first 3 cases from Taiwan and literature review.

    PubMed

    Yang, Sheau-Fang; Chuang, Wen-Yu; Chang, Seng-Tsung; Liu, Hongxiang; Chen, Rong-Long; Chuang, Shih-Sung

    2011-11-01

    Follicular lymphoma (FL) is a common lymphoma entity in adults but is rare in children. As opposed to adult cases, pediatric FL is characterized by a high-grade histology, low-stage disease, a lower frequency of both bcl-2 protein expression and BCL2 gene rearrangement, and a more favorable prognosis. During the authors' previous study of pediatric Burkitt lymphoma, they identified 3 cases of pediatric FL. Here the authors present the first series of pediatric FL from Taiwan. The patients were 2 boys and 1 girl, aged from 7 to 14. The presentation sites were cervical lymph node in 2 and tonsil in 1. All cases showed large neoplastic nodules comprising sheets of centroblasts, corresponding to grade 3b FL. Two of the 3 tumors weakly expressed bcl-2 protein. Fluorescence in situ hybridization for IGH, BCL2, BCL6, CCND1, and MYC loci showed that the only chromosomal translocation was rearranged IGH in 1 case. Two patients were at stage I, and 1 at stage III. All were treated with combination chemotherapy and achieved long-term complete remission. Literature review including the current cases showed that 45% cases of pediatric FL expressed bcl-2 protein and 9% cases carried BCL2 gene rearrangement, suggesting an alternate molecular pathogenesis of pediatric FL as compared to their adult counterparts. PMID:21875318

  20. Human Leukocyte Antigen Class I and II Alleles and Overall Survival in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma

    PubMed Central

    Lu, Yani; Abdou, Amr M.; Cerhan, James R.; Morton, Lindsay M.; Severson, Richard K.; Davis, Scott; Cozen, Wendy; Rothman, Nathaniel; Bernstein, Leslie; Chanock, Stephen; Hartge, Patricia; Wang, Sophia S.

    2011-01-01

    Genetic variation in the 6p21 chromosomal region, including human leukocyte antigen (HLA) genes and tumor necrosis factor (TNF), has been linked to both etiology and clinical outcomes of lymphomas. We estimated the effects of HLA class I (A, B, and C), class II DRB1 alleles, and the ancestral haplotype (AH) 8.1 (HLAA*01-B*08-DRB1*03-TNF-308A) on overall survival (OS) among patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in a population-based study of non-Hodgkin lymphoma. During a median followup of 89 months, 31% (52 of 166) DLBCL and 28% (46 of 165) FL patients died. Using multivariate Cox regression models, we observed statistically significant associations between genetic variants and survival: HLA-Cw*07:01 was associated with poorer OS among DLBCL patients (Hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.01–3.05); HLA-A*01:01 was associated with poorer OS (HR = 2.23, 95% CI = 1.24–4.01), and HLA-DRB1*13 (HR = 0.12, 95% CI = 0.02–0.90) and HLA-B Bw4 (HR = 0.36, 95% CI = 0.20–0.63) with better OS among FL patients. These results support a role for HLA in the prognosis of DLBCL and FL and represent a promising class of prognostic factors that warrants further evaluation. PMID:22125456

  1. Human leukocyte antigen class I and II alleles and overall survival in diffuse large B-cell lymphoma and follicular lymphoma.

    PubMed

    Lu, Yani; Abdou, Amr M; Cerhan, James R; Morton, Lindsay M; Severson, Richard K; Davis, Scott; Cozen, Wendy; Rothman, Nathaniel; Bernstein, Leslie; Chanock, Stephen; Hartge, Patricia; Wang, Sophia S

    2011-01-01

    Genetic variation in the 6p21 chromosomal region, including human leukocyte antigen (HLA) genes and tumor necrosis factor (TNF), has been linked to both etiology and clinical outcomes of lymphomas. We estimated the effects of HLA class I (A, B, and C), class II DRB1 alleles, and the ancestral haplotype (AH) 8.1 (HLAA*01-B*08-DRB1*03-TNF-308A) on overall survival (OS) among patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in a population-based study of non-Hodgkin lymphoma. During a median followup of 89 months, 31% (52 of 166) DLBCL and 28% (46 of 165) FL patients died. Using multivariate Cox regression models, we observed statistically significant associations between genetic variants and survival: HLA-Cw*07:01 was associated with poorer OS among DLBCL patients (Hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.01-3.05); HLA-A*01:01 was associated with poorer OS (HR = 2.23, 95% CI = 1.24-4.01), and HLA-DRB1*13 (HR = 0.12, 95% CI = 0.02-0.90) and HLA-B Bw4 (HR = 0.36, 95% CI = 0.20-0.63) with better OS among FL patients. These results support a role for HLA in the prognosis of DLBCL and FL and represent a promising class of prognostic factors that warrants further evaluation. PMID:22125456

  2. A Case of Fulminant Hepatitis due to Echovirus 9 in a Patient on Maintenance Rituximab Therapy for Follicular Lymphoma

    PubMed Central

    Thomson, S. J.; Legg, Joanne; Narat, Santosh

    2015-01-01

    Rituximab is a CD20 monoclonal antibody commonly used in the treatment of haematological malignancies. It causes lymphopenia with subsequent compromised humoral immunity resulting in an increased risk of infection. A number of infections and viral reactivations have been described as complicating Rituximab therapy. We report an apparently unique case of echovirus 9 (an enterovirus) infection causing an acute hepatitis and significant morbidity in an adult patient on maintenance treatment of Rituximab for follicular lymphoma. We also describe potential missed opportunities to employ more robust screening for viral infections which may have prevented delays in the appropriate treatment and thus may have altered the patient's clinical course. We also make suggestions for lowering the threshold of viral testing in similar patients in the future. PMID:26106492

  3. Software-Automated Counting of Ki-67 Proliferation Index Correlates With Pathologic Grade and Disease Progression of Follicular Lymphomas

    PubMed Central

    Samols, Mark A.; Smith, Nathan E.; Gerber, Jonathan M.; Vuica-Ross, Milena; Gocke, Christopher D.; Burns, Kathleen H.; Borowitz, Michael J.; Cornish, Toby C.; Duffield, Amy S.

    2014-01-01

    Objectives To examine the accuracy of software-assisted measurement of the Ki-67 proliferation index (PI) and its correlation with the grade and clinical progression of follicular lymphoma (FL). Methods High-power field equivalents were extracted from H&E- and Ki-67–immunostained slides of FL, and a nuclear quantitation algorithm was used to calculate a PI. Representative fields were manually counted for validation with close agreement. Results The PI was significantly higher in World Health Organization grade 3 FL than grade 1 to 2 FL. Disease progression, as defined by subsequent treatment with radiation or cytotoxic chemotherapy, was also significantly associated with elevated PI but not pathologic grade. Conclusions These data show that software-automated quantitation of Ki-67 can provide both a useful adjunct to pathologic grade in FL and improved prognostic information for patients. PMID:24045557

  4. DNA rearrangement in human follicular lymphoma can involve the 5' or the 3' region of the bcl-2 gene

    SciTech Connect

    Tsujimoto, Y.; Bashir, M.M.; Givol, I.; Cossman, J.; Jaffe, E.; Croce, C.M.

    1987-03-01

    In most human lymphomas, the chromosome translocation t(14;18) occurs within two breakpoint clustering regions on chromosome 18, the major one at the 3' untranslated region of the bcl-2 gene and the minor one at 3' of the gene. Analysis of a panel of follicular lymphoma DNAs using probes for the first exon of the bcl-2 gene indicates that DNA rearrangements may also occur 5' to the involved bcl-2 gene. In this case the IgH locus and the bcl-2 gene are found in an order suggesting that an inversion also occurred during the translocation process. The coding region of the bcl-2 gene, however, are left intact in all cases of follicular lymphoma studied to date.

  5. Early Stage W.H.O. Grade I and II Follicular Lymphoma Treated with Radiation Therapy Alone

    PubMed Central

    Ahmed, Naseer; Owen, Timothy E.; Rubinger, Morel; Williams, Gaynor; Nugent, Zoann; Ahmed, Shahida; Cooke, Andrew

    2013-01-01

    Objectives This retrospective study was undertaken to evaluate the outcome of patients with stage I or II (limited stage), grade I–II follicular non-Hodgkin’s lymphoma (FL) treated with radiation therapy (RT) alone as initial management. Methods Patients with stage I or II and pathologically confirmed WHO grade I or II FL treated initially with RT alone between 1982 and 2008 were identified from a population based cancer registry. Results Forty patients with a mean age 61.3 years at diagnosis were identified. The median follow up was 6.9 years from the end of radiation therapy. Stage was I (n = 26) and II (n = 14). None had B symptoms. The Follicular Lymphoma International Prognostic Index (FLIPI) was low risk in 26 patients and intermediate risk in 5. Doses ranged from 15 Gy to 48 Gy, with a median dose of 35 Gy. All patients achieved a complete clinical response (CR). 5 and 10 year overall survival (OS) was 86% and 59%, progression free survival (PFS) 67% and 54%. Age ≥60 at diagnosis was associated with reduced OS, p = 0.029, but did not affect PFS. No other clinical features including grade or FLIPI were significant for outcomes. Local failure was uncommon occurring in 8% (3/40) although this was 21% (3/14) of all recurrences. Conclusions OS and PFS outcomes for radiation alone in limited stage low grade FL patients from this single institution study are consistent with previously published data. No predictors were prognostic for PFS. A dose of ≤35 Gy may be appropriate. In this highly selected homogeneous group the FLIPI loses discriminating ability. Local control is excellent, and a majority of patients are free of disease after 5 years. PMID:23762303

  6. Follicular Lymphoma Showing Avid Uptake on 68Ga PSMA-HBED-CC PET/CT.

    PubMed

    Kanthan, Gowri L; Coyle, Luke; Kneebone, Andrew; Schembri, Geoffrey Paul; Hsiao, Edward

    2016-06-01

    Ga prostate-specific membrane antigen (PSMA) PET/CT is a new imaging technique that is significantly more sensitive to prostate cancer lesions than other conventional imaging modalities. Various other benign and malignant neoplasms may also express PSMA and show uptake on PSMA PET/CT scan. We report a case of 66-year-old man who had a PSMA PET/CT scan for restaging of prostate carcinoma. A PSMA-avid left femoral lymph node was identified. Subsequent biopsy confirmed the diagnosis of follicular lymphoma. It is important to be aware of this possibility to avoid scan misinterpretation. Biopsy of any atypical or clinically unexpected lesions should be considered. PMID:26914565

  7. Analysis of dendritic cell subpopulations in follicular lymphoma with respect to the tumor immune microenvironment.

    PubMed

    Chevalier, Nina; Mueller, Michael; Mougiakakos, Dimitrios; Ihorst, Gabriele; Marks, Reinhard; Schmitt-Graeff, Annette; Veelken, Hendrik

    2016-09-01

    The immune cell composition of the follicular lymphoma (FL) tumor microenvironment is increasingly recognized as an important determinant for clinical outcome. Here, we explored frequency and distribution of dendritic cell (DC) subtypes in relation to regulatory T cells (Treg) by immunohistochemistry in lymph node biopsies from patients with de novo FL. We found that neoplastic follicles contained lower DC and higher Treg frequencies than hyperplastic follicles in control lymph nodes. Treg numbers particularly correlated with the subset of conventional CD11c(+ )DCs. Additionally, both a high intra- to interfollicular ratio of CD11c(+ )DCs and increased intrafollicular Treg frequencies were associated with decreased overall survival. This suggests that functional interactions between these cells may be relevant for FL progression/recurrence. The presence of CD11c(+ )DCs in the tumor microenvironment may assist tumor infiltration by Tregs, thus contributing to the suppression of an otherwise beneficial T-cell-dominated FL microenvironment. PMID:26757600

  8. Bcl-2/IgH expression in minimal bone marrow infiltration by follicular lymphoma cells.

    PubMed

    Che, Yi-Qun; Liu, Peng; Wang, Yue; Zhang, Chang-Gong; Han, Ya-Ling; Shen, Di; Zhang, Ying; Zheng, Cui-Ling; Qi, Jun; Wang, Qing-Tao

    2012-02-01

    The purpose of this study was to investigate the roles of bcl-2 chromosomal translocation and Bcl-2 protein expression in follicular lymphoma (FL) minimal bone marrow (BM) infiltration. We identified the same bcl-2/IgH fusion gene in paraffin-embedded lymph node (LN) samples and BM samples using immunohistochemistry (IHC), immunocytochemistry (ICC), cytologic morphology and fluorescence in situ hybridization (FISH). The presence of the Bcl-2/IgH fusion gene in the BM samples and paraffin-embedded LN samples from 56 patients with follicular lymphomas was detected using FISH. The Bcl-2 protein levels in BM and paraffin-embedded tissues were quantified using ICC and IHC, respectively. Approximately 78.6% (44/56) of the paraffin‑embedded LN tissue sections that underwent FISH analysis had a bcl-2/IgH translocation. The primary lesion was also positive for the bcl-2/IgH fusion gene, as were the BM minimal infiltrates. The bcl-2/IgH rearrangement occurred in 88.6% (39/44) of the BM specimens. The bcl-2/IgH recombination rate in stage III/IV cancers was significantly different to that observed in stage I/II cancers (p=0.041). In 59% (23/39) of the cases with t(14;18), Bcl-2 was found to be present as assessed by ICC. Positive Bcl-2 ICC staining and the t(14;18) translocation (as detected using FISH) were positively correlated (p=0.028). We then applied the FISH method to slides that had previously been morphologically evaluated using Wright-Giemsa staining; any slides with at least one abnormal cell were subjected to FISH analysis following staining. The assessment of bcl-2/IgH translocation status may contribute to the better detection of minimal BM infiltration by FL cells. Utilizing FISH and cytologic morphology techniques allows for earlier and more accessible BM examination. PMID:22052344

  9. Vorinostat in Treating Patients With Low-Grade Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2016-06-10

    Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma

  10. Partial lack of BCL2 in follicular lymphoma: An unusual immunohistochemical staining pattern explained by ongoing BCL2 mutation.

    PubMed

    van den Brand, Michiel; Garcia-Garcia, Mar; Mathijssen, Janneke J M; Colomo, Lluis; Groenen, Patricia J T A; Serrano, Sergio; van Krieken, J Han J M

    2016-02-01

    Follicular lymphomas are characterized by overexpression of BCL2 which, in the large majority of cases, is due to a t(14;18) translocation which juxtaposes the BCL2 locus to the immunoglobulin heavy chain locus (IGH). Here, we report partial absence of BCL2 immunohistochemical staining in a case of FL, due to a mutation in the part of BCL2 that encodes the epitope for the most frequently used antibody against BCL2. This finding shows that mutations in BCL2 occur in an ongoing process in follicular which can give rise to unusual immunohistochemical staining patterns. PMID:26725534

  11. Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma

    PubMed Central

    Wang, Jun; Araf, Shamzah; Wilkins, Lucy; Castellano, Brian M.; Escudero-Ibarz, Leire; Al Seraihi, Ahad Fahad; Richter, Julia; Bernhart, Stephan H.; Efeyan, Alejo; Iqbal, Sameena; Matthews, Janet; Clear, Andrew; Guerra-Assunção, José Afonso; Bödör, Csaba; Quentmeier, Hilmar; Mansbridge, Christopher; Johnson, Peter; Davies, Andrew; Strefford, Jonathan C.; Packham, Graham; Barrans, Sharon; Jack, Andrew; Du, Ming-Qing; Calaminici, Maria; Lister, T. Andrew; Auer, Rebecca; Montoto, Silvia; Gribben, John G.; Siebert, Reiner; Chelala, Claude; Zoncu, Roberto; Sabatini, David M.; Fitzgibbon, Jude

    2015-01-01

    Follicular lymphoma is an incurable B-cell malignancy1 characterized by the t(14;18) and mutations in one or more components of the epigenome2,3. Whilst frequent gene mutations in signaling pathways, including JAK-STAT, NOTCH and NF-κB, have also been defined2-7, the spectrum of these mutations typically overlap with the closely-related diffuse large B cell lymphoma (DLBCL)6-13. A combination of discovery exome and extended targeted sequencing revealed recurrent somatic mutations in RRAGC uniquely enriched in FL patients (17%). More than half of the mutations preferentially co-occurred with ATP6V1B2 and ATP6AP1 mutations, components of the vacuolar H+-adenosine triphosphate ATPase (v-ATPase) known to be necessary for amino acid-induced mTORC1 activation. The RagC mutants increased raptor binding whilst rendering mTORC1 signaling resistant to amino acid deprivation. Collectively, the activating nature of the RRAGC mutations, their existence within the dominant clone and stability during disease progression supports their potential as an excellent candidate to be therapeutically exploited. PMID:26691987

  12. Disease, treatment, and outcome differences between men and women with follicular lymphoma in the United States.

    PubMed

    Nabhan, Chadi; Zhou, Xiaolei; Day, Bann-Mo; Dawson, Keith; Zelenetz, Andrew D; Friedberg, Jonathan W; Cerhan, James R; Link, Brian K; Flowers, Christopher R

    2016-08-01

    We aimed to comprehensively study sex differences in disease and patients' characteristics, treatment and outcomes in patients with follicular lymphoma (FL) in the United States (USA) utilizing the National LymphoCare Study registry (2004-2014). Among evaluable males (n = 1277) and females (n = 1375) with FL, females less commonly received anthracyclines and were more likely to receive rituximab monotherapy. Overall response rates were comparable between sex groups. With a median follow-up of 8.1 years, male sex emerged as an adverse factor for PFS (HR, 0.84, 95% CI, 0.72-0.97). Lymphoma-related mortality (HR, 0.46; 0.23-0.93) and overall survival (HR, 0.63; 0.41-0.97) favored females aged ≤60 years. There are subtle differences in outcomes between male and female FL patients diagnosed and treated in the contemporary era. These data represent the largest prospective analysis of FL patients in the USA based on sex and can aid design of clinical trials for this disease. Am. J. Hematol. 91:770-775, 2016. © 2016 Wiley Periodicals, Inc. PMID:27124800

  13. PET Scans for Staging and Restaging in Diffuse Large B-Cell and Follicular Lymphomas.

    PubMed

    Barrington, Sally F; Mikhaeel, N George

    2016-06-01

    Positron emission tomography (PET)-CT was recommended in updated international guidelines for staging/restaging of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). In FL, PET was previously regarded as a research application only. This review concentrates on new publications related to PET in these diseases. In DLBCL, PET appears appropriate for staging using prognostic indices established with CT and baseline PET parameters, e.g. metabolic tumour volume, are prognostic of outcome. Early complete metabolic response (CMR) predicts end-of-treatment CMR with excellent prognosis. Patients without CMR at interim should not have treatment altered, but have a worse prognosis, and patients with other high risk features may need closer monitoring. The end-of-treatment scan is confirmed as the standard for remission assessment using Deauville criteria, which are also predictive for patients undergoing ASCT. In FL, PET is more sensitive for staging than CT but misses bone marrow involvement. PET-CT identifies patients at risk of progression after induction chemotherapy better than CT. PMID:27095319

  14. Clinical features of patients with nodal marginal zone lymphoma compared to follicular lymphoma: similar presentation, but differences in prognostic factors and rate of transformation.

    PubMed

    van den Brand, Michiel; van der Velden, Walter J F M; Diets, Illja J; Ector, Geneviève I C G; de Haan, Anton F J; Stevens, Wendy B C; Hebeda, Konnie M; Groenen, Patricia J T A; van Krieken, Han J M

    2016-07-01

    Nodal marginal zone lymphoma (NMZL) is a rare type of B-cell non-Hodgkin lymphoma. This study assessed the clinical features of 56 patients with NMZL in comparison to 46 patients with follicular lymphoma (FL). Patients with NMZL and FL had a largely similar clinical presentation, but patients with FL had a higher disease stage at presentation, more frequent abdominal lymphadenopathy and bone marrow involvement, and showed more common transformation into diffuse large B-cell lymphoma (DLBCL) during the course of disease. Overall survival and event-free survival were similar for patients with NMZL and FL, but factors associated with worse prognosis differed between the two groups. Transformation into DLBCL was associated with a significantly poorer outcome in both groups, but the phenotypes were different: DLBCL arising in FL was mainly of germinal center B-cell phenotype, whereas DLBCL arising in NMZL was mainly of non-germinal center B-cell phenotype. PMID:26694256

  15. Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement.

    PubMed

    Louissaint, Abner; Ackerman, Adam M; Dias-Santagata, Dora; Ferry, Judith A; Hochberg, Ephraim P; Huang, Mary S; Iafrate, A John; Lara, Daniel O; Pinkus, Geraldine S; Salaverria, Itziar; Siddiquee, Zakir; Siebert, Reiner; Weinstein, Howard J; Zukerberg, Lawrence R; Harris, Nancy Lee; Hasserjian, Robert P

    2012-09-20

    Pediatric follicular lymphoma (PFL) is a variant of follicular lymphoma (FL) presenting as localized lymphadenopathy in children. Unlike conventional adult FL, PFL typically does not recur or progress. Clear diagnostic criteria for PFL are lacking, and it is uncertain whether this indolent lymphoma is defined by age or may occur in adults. We analyzed 27 FL in patients < 40 years of age and found that all 21 cases that lacked a BCL2 gene abnormality (BCL2-N; P < .0001) and had > 30% Ki67 fraction (high proliferation index, HPI; P = .0007) were stage I and did not progress or recur; in comparison, all 6 cases with BCL2 rearrangement and/or PI < 30% were stage III/IV, and 5 of 6 recurred or progressed. In a separate cohort of 58 adult FL (≥ 18 years of age), all 13 BCL2-N/HPI cases were stage I, and none progressed or relapsed, whereas 11 of 15 stage I cases with BCL2 gene abnormality and/or LPI relapsed or progressed (P = .0001). The adult and pediatric BCL2-N/HPI FL cases had similar morphologic features. Our results confirm the highly indolent behavior of PFL and suggest that these are characterized by HPI and absence of BCL2 gene abnormality. PFL-like cases also occur in adults and are associated with indolent behavior in this patient population. PMID:22855608

  16. Double-hit and triple-hit lymphomas arising from follicular lymphoma following acquisition of MYC: report of two cases and literature review.

    PubMed

    Xu, Xiaoxiao; Zhang, Le; Wang, Yafei; Zhang, Qing; Zhang, Lianyu; Sun, Baocun; Zhang, Yizhuo

    2013-01-01

    Double-hit or triple-hit B-cell lymphomas (DHL and THL) are rare subtype lymphomas usually associated with poor prognosis. It is defined by two or three recurrent chromosome translocations; MYC/8q24 loci, usually in combination with the t (14; 18) (q32; q21) bcl-2 gene or/and BCL6/3q27 chromosomal translocation. DHL was often observed both in de-novo diffuse large B cell lymphomas (DLBCL). It is otherwise unclassifiable, showing features intermediate that of large B-cell lymphoma and Burkitt lymphoma. Here, we present two follicular lymphoma patients; one transformed to THL, another transformed to DHL. Both cases revealed aggressive clinical courses with poor prognosis and associated with acquisition of c-Myc gene (MYC) and central nervous system (CNS) involvement. We reviewed the related literature, correlated the immunophenotype and clinical manifestations such as response to therapy and prognosis. Although the incidence of DHT and THL is low, cytogenetic and FISH analyses should be included when B-cell lymphoma patients experience relapse or refractory course of disease. We concluded that c-Myc may contribute to aggressive transformation, and more mechanism-based therapy should be explored. PMID:23573328

  17. [Follicular and mantle cell lymphoma diagnosed in biopsies of gastroenterocolic region].

    PubMed

    Plank, Lukáš; Balhárek, Tomáš; Szépe, Peter

    2016-01-01

    The authors present a retrospective analysis of follicular lymphomas (FL) and mantle cell lymphomas (MCL) diagnosed according to the WHO classification (2008) in consecutive biopsies of GI organs in a period of 11 years. The series includes 18 patients with FL verified in 22 biopsies and 44 patients with MCL diagnosed in 54 biopsies. FL represented always a solitary tumor, most often - up to ¾ of all the cases - of a small intestine, more often in its jejunoileal than duodenal parts. The biopsies were obtained almost equally by endoscopical approach, they were usually mucosal and rarely polypectomic, as well as by surgical resections (54,5 % and 45,5 % of the cases respectively). FL of grade 3 was identified in approximately 11 % of the cases, while majority of the patients showed FL of grade 1 or 2. Only 2 patients with duodenal FL relapsed and bioptically verified recidives did not show signs of a high grade transformation. Although it was difficult to identify a nodular growth pattern in more common small biopsies, a typical histomorphology and phenotype mostly allowed the FL diagnosis in the majority of the cases. The FL diagnosis had to be supported by detection of BCL2 translocation only in one case. MCL appeared most often in the stomach and large intestine, the small intestinal cases represented less than 23 %. In ¼ of the patients the lymphoma was multifocal and manifested as lymphomatoid polyposis affecting most often both large and small intestine. In a majority of the MCL patients, the diagnosis was done in mucosal and polypectomic endoscopic biopsies, surgical intervention and resection was recorded in less than 10 % of the cases. Most of the patients showed conventional "centrocytic" MCL morphology and approximately ¼ of the cases showed blastoid MCL. The rebiopsies of 9 patients revealed a relaps of the disease which was locoidentical in 5 of them; in other 4 patients the biopsies documented a dissemination to other GI organs. The blastic

  18. Localized beta dosimetry of sup 131 I -labeled antibodies in follicular lymphoma

    SciTech Connect

    Hui, T.E.; Fisher, D.R. ); Press, O.W.; Eary, J.F. ); Weinstein, J.N. ); Badger, C.C.; Bernstein, I.D. )

    1992-01-01

    The purpose of this study is to assess the multicellular dosimetry of {sup 131}I -labeled antibody in follicular lymphoma based on histological measurements on human tumor biopsy tissue. Photomicrographs of lymph node specimens were analyzed by first-order treatment to determine the mean values and statistical variations of the radii of follicles (260{plus minus}90 {mu}m), interfollicular distances (740{plus minus}160 {mu}m), and the number density of follicles (60{plus minus}18 in a volume of (2{times}1480 {mu}m){sup 3}). Based on these measurements, two geometrical models were developed for localized beta dosimetry. The first, a regular cubic lattice model, assumes no variation in follicular radius of follicles and interfollicular distance. The second, a randomized distribution model, is a more complicated but more realistic representation of observed histological specimens. In this model, Monte Carlo methods were used to reconstruct the spatial distribution of follicles by simulating the distribution of the radii of follicles, interfollicular distances, and the number density of follicles. Dose calculations were performed using Berger's point kernels for absorbed-dose distribution for beta particles in water, assuming the {sup 131}I -labeled antibodies as point sources. It was assumed that the activity concentration of the labeled antibody within the follicles was ten times the activity concentration in the interfollicular spaces. The spatial distribution of localized dose was calculated for a tumor having an average dose of 40 Gy. The localized dose was found to be highly nonuniform, ranging from 20 to 90 Gy, and varying by a factor of about 2 from the average tumor dose.

  19. Role of consolidation with yttrium-90 ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma

    PubMed Central

    Sánchez Ruiz, Antonio C.; de la Cruz-Merino, Luis

    2014-01-01

    Non-Hodgkin’s lymphoma (NHL) accounts for 4% of all cancers diagnosed in the United States. Follicular lymphoma (FL) is the most common type of indolent NHL with a survival from 5 to 15 years. Although it is very sensitive to chemotherapy and radiotherapy, relapses are the main cause of therapeutic failure, and currently there is no consensus on the first-line treatment and optimal therapeutic strategies for patients with FL. Immediate treatment offers any survival benefit for asymptomatic and more indolent disease. In order to improve outcomes in FL, extend the remission, postpone the need for chemotherapy and improve OS, maintenance therapies with rituximab and consolidation treatments represent very attractive strategies. 90Y-ibritumomab tiuxetan (90Y-IT, Zevalin®) is approval as consolidation therapy in previously untreated FL patients who achieve response to first-line chemotherapy. Consolidation therapy with 90Y-IT after initial induction treatment has shown improved activity compared with induction chemotherapy alone, even in patients previously treated with rituximab, in one phase III and several phase II trials, improving progression-free survival (PFS) and rate of conversion from partial response (PR) to complete response (CR). The phase III international FIT trial shows an improvement in PFS that is maintained after a median follow up of 7.3 years. Several phase II trials show high rate of conversion from PR to CR and a significant improvement in PFS. Treatment is feasible and well tolerated although myelodysplastic syndrome cases has been observed in some trials. 90Y-IT should be considered for the initial treatment of FL in patients who are unable to tolerate standard chemotherapy, e.g., elderly or frail patients and otherwise in high-risk patients who achieve a PR or CR due to improvements in CR rate and PFS. PMID:24883180

  20. Clinicogenetic risk models predict early progression of follicular lymphoma after first-line immunochemotherapy.

    PubMed

    Jurinovic, Vindi; Kridel, Robert; Staiger, Annette M; Szczepanowski, Monika; Horn, Heike; Dreyling, Martin H; Rosenwald, Andreas; Ott, German; Klapper, Wolfram; Zelenetz, Andrew D; Barr, Paul M; Friedberg, Jonathan W; Ansell, Stephen; Sehn, Laurie H; Connors, Joseph M; Gascoyne, Randy D; Hiddemann, Wolfgang; Unterhalt, Michael; Weinstock, David M; Weigert, Oliver

    2016-08-25

    Follicular lymphoma (FL) is a clinically and molecularly heterogeneous disease. Posttreatment surrogate end points, such as progression of disease within 24 months (POD24) are promising predictors for overall survival (OS) but are of limited clinical value, primarily because they cannot guide up-front treatment decisions. We used the clinical and molecular data from 2 independent cohorts of symptomatic patients in need of first-line immunochemotherapy (151 patients from a German Low-Grade Lymphoma Study Group [GLSG] trial and 107 patients from a population-based registry of the British Columbia Cancer Agency [BCCA]) to validate the predictive utility of POD24, and to evaluate the ability of pretreatment risk models to predict early treatment failure. POD24 occurred in 17% and 23% of evaluable GLSG and BCCA patients, with 5-year OS rates of 41% (vs 91% for those without POD24, P < .0001) and 26% (vs 86%, P < .0001), respectively. The m7-FL International Prognostic Index (m7-FLIPI), a prospective clinicogenetic risk model for failure-free survival, had the highest accuracy to predict POD24 (76% and 77%, respectively) with an odds ratio of 5.82 in GLSG (P = .00031) and 4.76 in BCCA patients (P = .0052). A clinicogenetic risk model specifically designed to predict POD24, the POD24-PI, had the highest sensitivity to predict POD24, but at the expense of a lower specificity. In conclusion, the m7-FLIPI prospectively identifies the smallest subgroup of patients (28% and 22%, respectively) at highest risk of early failure of first-line immunochemotherapy and death, including patients not fulfilling the POD24 criteria, and should be evaluated in prospective trials of precision medicine approaches in FL. PMID:27418643

  1. [Lymphomas].

    PubMed

    Lohri, Andreas

    2016-01-01

    Although malignant lymphoma is split in over 60 distinct entities, four of them, diffuse large B cell lymphoma, follicular-, Hodgkin's- and mantle cell lymphoma constitute more than half of all new cases. A recent major revision of the Ann Arbor staging system restricts the suffix “A” and “B” just to Hodgkin's lymphoma. Bone marrow exams are abandonned in Hodgkin's and restricted in DLBCL. PET exams at different time points are crucial. PET guided therapy will lead to a reduction of the use of chemo- and radiation therapy. Many new targeted drugs have been introduced. Their therapeutic index is impressive as is their price tag. The radiation and chemotherapy free treatment of malignant lymphoma is within reach. PMID:26732717

  2. Frequent disruption of the RB pathway in indolent follicular lymphoma suggests a new combination therapy.

    PubMed

    Oricchio, Elisa; Ciriello, Giovanni; Jiang, Man; Boice, Michael H; Schatz, Jonathan H; Heguy, Adriana; Viale, Agnes; de Stanchina, Elisa; Teruya-Feldstein, Julie; Bouska, Alyssa; McKeithan, Tim; Sander, Chris; Tam, Wayne; Seshan, Venkatraman E; Chan, Wing-Chung; Chaganti, R S K; Wendel, Hans-Guido

    2014-06-30

    Loss of cell cycle controls is a hallmark of cancer and has a well-established role in aggressive B cell malignancies. However, the role of such lesions in indolent follicular lymphoma (FL) is unclear and individual lesions have been observed with low frequency. By analyzing genomic data from two large cohorts of indolent FLs, we identify a pattern of mutually exclusive (P = 0.003) genomic lesions that impair the retinoblastoma (RB) pathway in nearly 50% of FLs. These alterations include homozygous and heterozygous deletions of the p16/CDKN2a/b (7%) and RB1 (12%) loci, and more frequent gains of chromosome 12 that include CDK4 (29%). These aberrations are associated with high-risk disease by the FL prognostic index (FLIPI), and studies in a murine FL model confirm their pathogenic role in indolent FL. Increased CDK4 kinase activity toward RB1 is readily measured in tumor samples and indicates an opportunity for CDK4 inhibition. We find that dual CDK4 and BCL2 inhibitor treatment is safe and effective against available models of FL. In summary, frequent RB pathway lesions in indolent, high-risk FLs indicate an untapped therapeutic opportunity. PMID:24913233

  3. Outcomes following watchful waiting for stage II-IV follicular lymphoma patients in the modern era.

    PubMed

    Nastoupil, Loretta J; Sinha, Rajni; Byrtek, Michelle; Ziemiecki, Ryan; Zhou, Xiaolei; Taylor, Michael; Friedberg, Jonathan W; Link, Brian K; Cerhan, James R; Dawson, Keith; Flowers, Christopher R

    2016-03-01

    To examine the effectiveness of an initial management strategy of watchful waiting for follicular lymphoma (FL) in clinical practice, we compared outcomes for patients diagnosed 2004-2007 in the United States initially managed with watchful waiting with outcomes following initial rituximab monotherapy and chemoimmunotherapy. In total, 1754 stage II-IV patients in the National LymphoCare Study underwent watchful waiting (n = 386), rituximab monotherapy (n = 296) or rituximab plus chemotherapy (n = 1072) as initial management strategy. Female patients and those who received treatment in the Northeast or in an academic setting more commonly underwent watchful waiting versus initial chemoimmunotherapy; whereas patients with grade 3 histology, anaemia, elevated lactate dehydrogenase, extranodal involvement, B symptoms or performance status ≥1 more commonly received chemoimmunotherapy. Although time to new treatment and progression-free survival following first- and second-line therapy were improved with chemoimmunotherapy, and time to chemotherapy was improved with rituximab monotherapy, there were no differences in overall survival between watchful waiting and chemoimmunotherapy or rituximab monotherapy. With 8-year overall survival estimates of 74%, initial management with watchful waiting in the context of sequential therapy remains a viable option for FL patients in the modern era. This trial was registered at www.clinicaltrials.gov (NCT00097565). PMID:26729445

  4. Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas.

    PubMed

    Heinzelmann, F; Bethge, W; Beelen, D W; Engelhard, M; Kröger, N; Dreger, P; Niederwieser, D; Finke, J; Bunjes, D; Tischer, J; Kobbe, G; Holler, E; Bornhäuser, M; Stelljes, M; Baurmann, H; Müller, A; Haubitz, I; Schrezenmeier, H; Müller, C; Ottinger, H

    2016-05-01

    Allogeneic hematopoietic cell transplantation (HCT) offers the chance of cure for patients with non-transformed follicular lymphoma (FL), but is associated with the risk of non-relapse mortality (NRM). The aim of this study was to identify subgroups of FL patients who benefit from HCT. The European Society for Blood and Marrow Transplantation (EBMT) Minimum-Essential-A Data of 146 consecutive patients who received HCT for FL between 1998 and 2008 were extracted from the database of the German Registry 'DRST'. Diagnosis of FL was verified by contact with the reference pathologists. Estimated 1-, 2- and 5-year overall survivals (OS) were 67%, 60% and 53%, respectively. Day 100 NRM was 15%. Thirteen out of 33 patients (40%) with treatment-refractory disease (RD) at the time of transplantation survived long term. Univariate statistical analysis suggested limited chronic GvHD, donor age ⩽42 years and TBI-based conditioning in treatment refractory patients to correlate with favorable OS. Independent prognostic factors for OS were treatment-sensitive disease and limited chronic GvHD for the whole cohort, and additionally TBI-based conditioning for the treatment refractory subgroup. In contrast, patient age ⩾55 years had no impact on outcome. Thus, HCT for FL is associated with acceptable NRM, and offers a substantial chance of cure for patients with RD or advanced age. Donors ⩽42 years should be preferred if available. PMID:26855152

  5. [Primary gastrointestinal follicular lymphoma of the small intestine with massive hemorrhage: a report of three cases].

    PubMed

    Sato, Akiyasu; Tsujimura, Hideki; Sugiyama, Takahiro; Maruyama, Satoshi; Yamada, Shuhei; Ono, Keiko; Wang, Xiaofei; Sugawara, Takeaki; Ise, Mikiko; Itami, Makiko; Kumagai, Kyouya

    2016-03-01

    Primary gastrointestinal follicular lymphoma (FL) has an indolent clinical presentation and many of cases are diagnosed incidentally during routine endoscopic examinations. Herein, we present 3 cases with FL of the small intestine developed massive intestinal hemorrhage that necessitated blood transfusion. In all three patients, upper and lower endoscopic examinations failed to detect the bleeding sites. Eventually, video capsule endoscopies identified ulcerative lesions in the jejunum and biopsies using single- or double-balloon endoscopy confirmed the FL diagnosis in our three cases. The respective clinical stages according to the Lugano system were I, II-1 and II-1. PET-CT did not play a significant role in identifying the gastrointestinal lesions. Two patients received rituximab monotherapy and achieved a complete response. The other remains under observation after termination of antiplatelet drug therapy. Generally, the macroscopic appearance of multiple whitish nodules and the absence of symptoms represent the typical clinical picture of gastrointestinal FL. However, this study demonstrates that patients with ulcerative lesions may be at risk for massive bleeding. Further discussion is required to determine the optimal indications for total endoscopic examination of the small intestine. PMID:27076249

  6. Is There a Best Initial Treatment for a New Patient With Low Grade Follicular Lymphoma.

    PubMed

    Jacobson, Caron A; Freedman, Arnold S

    2016-06-01

    The treatment landscape for newly diagnosed follicular lymphoma (FL) has dramatically changed over the past decade, first with the advent of rituximab and then with the activity of old and new drugs, like bendamustine and lenalidomide, in this disease. The efficacy and tolerability of rituximab has led to a paradigm shift for the management of patients with low volume FL for many oncologists. Despite the lack of a survival benefit seen with this approach, many now use this single agent in patients who had historically been observed. Likewise, its use as maintenance therapy following successful front-line induction therapy of patients with symptomatic FL, with either rituximab alone or specific chemoimmunotherapy regimens, has improved remission duration and widely been adopted. As newer chemoimmunotherapy regimens, like bendamustine and rituximab, have superior outcomes with improved tolerability, upfront treatment options are redefined and questions emerge: whom do maintenance strategies benefit, and what is the optimal sequencing of therapies? Finally, as newer targeted and potentially better tolerated therapies demonstrate efficacy in the relapsed setting, their use, both in combination with and in place of chemotherapy, is being explored. The promising regimen of lenalidomide with rituximab is being compared with chemoimmunotherapy in a randomized fashion. Cure remains elusive, however, in advanced stage disease and so safety and tolerability, in addition to efficacy, remain important endpoints. PMID:26995595

  7. T cells raised against allogeneic HLA-A2/CD20 kill primary follicular lymphoma and acute lymphoblastic leukemia cells.

    PubMed

    Abrahamsen, Ingerid Weum; Kjellevoll, Synneva; Greve-Isdahl, Margrethe; Mensali, Nadia; Wälchli, Sébastien; Kumari, Shraddha; Loland, Beate Fossum; Egeland, Torstein; Kolstad, Arne; Olweus, Johanna

    2012-04-15

    T cells mediating a graft-versus-leukemia/lymphoma effects without causing graft-versus-host disease would greatly improve the safety and applicability of hematopoietic stem cell transplantation. We recently demonstrated that highly peptide- and HLA-specific T cells can readily be generated against allogeneic HLA-A*02:01 in complex with a peptide from the B cell-restricted protein CD20. Here, we show that such CD20-specific T cells can easily be induced from naïve precursors in cord blood, demonstrating that they do not represent cross-reactive memory cells. The cells displayed high avidity and mediated potent cytotoxic effects on cells from patients with the CD20(pos) B cell malignancies follicular lymphoma (FL) and acute lymphoblastic leukemia (ALL). However, the cytotoxicity was consistently lower for cells from two of the ALL patients. The ALL cells that were less efficiently killed did not display lower surface expression of CD20 or HLA-A*02:01, or mutations in the CD20 sequence. Peptide pulsing fully restored the levels of cytotoxicity, indicating that they are indeed susceptible to T cell-mediated killing. Adoptive transfer of CD20-specific T cells to an HLA-A*02:01(pos) patient requires an HLA-A*02:01(neg) , but otherwise HLA identical, donor. A search clarified that donors meeting these criteria can be readily identified even for patients with rare haplotypes. The results bear further promise for the clinical utility of CD20-specific T cells in B cell malignancies. PMID:21630262

  8. Isotype-switched follicular lymphoma displays dissociation between activation-induced cytidine deaminase expression and somatic hypermutation.

    PubMed

    Scherer, Florian; Navarrete, Marcelo A; Bertinetti-Lapatki, Cristina; Boehm, Joachim; Schmitt-Graeff, Annette; Veelken, Hendrik

    2016-01-01

    In B-cells, activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. AID introduces mutations in immunoglobulin variable regions (IGV) during B-cell receptor affinity maturation, but may also introduce aberrant mutations into non-immunoglobulin genes, most commonly BCL6. Follicular lymphoma (FL) B-cells constitutively express AID and undergo CSR, SHM and aberrant SHM. We have studied AID expression, the presence of SHM mutations, CSR, and aberrant SHM in BCL6 in a cohort of 75 FL patients. Whereas IgM-expressing (non-switched) FL were characterized by an expected positive correlation between AID and IGV and BCL6 mutations, isotype-switched FL showed dissociation between AID expression and aberrant SHM, and inverse correlation between SHM and AID expression. Our results unveil two manifest biological subgroups of FL and indicate that the specific dissociation between AID and SHM after isotype switch may correlate with the clinical outcome of this heterogeneous disease. PMID:25860234

  9. Follicular lymphoma transforming into anaplastic diffuse large B-cell lymphoma of oral cavity: A case report with review of literature

    PubMed Central

    Mittal, Megha; Puri, Abhiney; Nangia, Rajat; Sachdeva, Alisha

    2015-01-01

    Follicular lymphoma (FL) is a common form of non-Hodgkin's lymphoma (NHL) with the ability to transform into a more aggressive disease, frequently to B cell-lymphoblastic lymphoma. Diffuse large B-cell lymphoma (DLBCL) is a subtype of NHL, which is characterized by diffuse proliferation of large neoplastic B-lymphocytes. It accounts for 30% of all NHL and its occurrence in the mandible is very rare. It is often seen in young adults, but in the present case, a 50-year-old male patient presented with painless swelling in left lower jaw since 25 days following extraction of left lower molar teeth. There was a history of fever and submandibular lymph nodes were enlarged. On incisional biopsy, features of NHL-like lesion were observed and confirmed by immunohistochemistry using CD20, bcl-2, CD10, CD3, CD5, Ki67 markers to be FL (3A) lymphoma transforming into DLBCL. This is a very uncommon presentation. PMID:26980969

  10. Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas.

    PubMed

    Martin-Guerrero, Idoia; Salaverria, Itziar; Burkhardt, Birgit; Szczepanowski, Monika; Baudis, Michael; Bens, Susanne; de Leval, Laurence; Garcia-Orad, Africa; Horn, Heike; Lisfeld, Jasmin; Pellissery, Shoji; Klapper, Wolfram; Oschlies, Ilske; Siebert, Reiner

    2013-08-01

    Pediatric follicular lymphoma is a rare disease that differs genetically and clinically from its adult counterpart. With the exception of pediatric follicular lymphoma with IRF4-translocation, the genetic events associated with these lymphomas have not yet been defined. We applied array-comparative genomic hybridization and molecular inversion probe assay analyses to formalin-fixed paraffin-embedded tissues from 18 patients aged 18 years and under with IRF4 translocation negative follicular lymphoma. All evaluable cases lacked t(14;18). Only 6 of 16 evaluable cases displayed chromosomal imbalances with gains or amplifications of 6pter-p24.3 (including IRF4) and deletion and copy number neutral-loss of heterozygosity in 1p36 (including TNFRSF14) being most frequent. Sequencing of TNFRSF14 located in the minimal region of loss in 1p36.32 showed nine mutations in 7 cases from our series. Two subsets of pediatric follicular lymphoma were delineated according to the presence of molecular alterations, one with genomic aberrations associated with higher grade and/or diffuse large B-cell lymphoma component and more widespread disease, and another one lacking genetic alterations associated with more limited disease. PMID:23445872

  11. Identification of follicular lymphoma by polymerase chain reaction amplification of the t(14;18) translocation: An improved method for staging of malignancy and detection of minimal residual disease

    SciTech Connect

    La Spada, A.R.; Lakey, C.; Hanke, D.C.

    1994-09-01

    60 to 85% of follicular non-Hodgkin`s lymphomas have a reciprocal translocation between chromosomes 14 and 18 (t(14q21;18q32)). As a result of this translocation, the joining region of the immunoglobulin heavy chain gene (J{sub H}) on chromosome 14 is juxtaposed to the bcl-2 gene on chromosome 18. Polymerase chain reaction (PCR) amplification across the translocation breakpoint may be used to detect follicular lymphoma cells in the peripheral blood and bone marrow, as morphological examination for lymphoma cells is extremely insensitive. We performed PCR assays with a universal J{sub H} primer and pairs of major breakpoint region (MBR) primers or minor cluster region (MCR) primers from the bcl-2 gene. PCR products were then visualized on ethidium-stained agarose gels, along with size markers and appropriate positive and negative controls. We began by comparing the PCR assay to Southern blot analysis and found that Southern blot analysis detected 9 translocations in 24 follicular lymphomas (37.5%), while PCR amplification detected 13 (58.3%), making it the more sensitive technique. By using adjacent MBR and MCR primer pairs in the PCR assay, we were also able to attain very high specificities (>95%). As detection of minimal residual disease after therapy is likely important for the prognosis and further management of these patients, we decided to use our PCR assay to evaluate peripheral blood stem cell preparations from patients undergoing autologous bone marrow transplantation. Of the 26 patients analyzed thus far, 4 (15%) have been found positive for MBR translocations. These results indicate that PCR amplification of the t(14;18) translocation is a sensitive and specific method for detection of follicular lymphoma cells, and therefore has potential application as a tool not only for the staging but also for the management of this malignancy.

  12. Rituximab and Dexamethasone in Treating Patients With Low-Grade Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2011-08-11

    Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  13. The Value of PET/CT in Detecting Bone Marrow Involvement in Patients With Follicular Lymphoma.

    PubMed

    Perry, Chava; Lerman, Hedva; Joffe, Erel; Sarid, Nadav; Amit, Odelia; Avivi, Irit; Kesler, Mikhail; Ben-Ezra, Jonathan; Even-Sapir, Einat; Herishanu, Yair

    2016-03-01

    Follicular lymphoma (FL) is the 2nd most common type of lymphoma diagnosed in the Western World. Bone marrow (BM) involvement is an adverse prognostic factor in FL, routinely assessed by an arbitrary biopsy of the iliac crest. This study was aimed to investigate the role of positron emission tomography/computed tomography (PET/CT) in identifying BM involvement by FL. In this retrospective, single-center study we reviewed the records of consecutive patients with FL at diagnosis or relapse who underwent staging/restaging workup visual assessment of BM uptake was categorized as either normal, diffusely increased, or focally increased. Quantitative BM fluorine-18-fluro-deoxyglucose (FDG) uptake was measured using mean standardized uptake value (BM-SUVmean). The diagnosis of BM involvement was based on either BM histological findings or disappearance of increased uptake at end-treatment PET/CT in patients who responded to treatment. Sixty eight cases with FL were included. Sixteen (23.5%) had BM involvement, 13 (19.1%) had a biopsy proven involvement, and 3 (4.4%) had a negative BM biopsy, but increased medullary uptake that normalized post-treatment. BM FDG uptake in these patients was diffuse in 8 (50%) and focal in 8 (50%). Focal increased uptake was indicative of BM involvement; however, diffuse uptake was associated with 17 false positive cases (32.7%). Overall, visual assessment of BM involvement had a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 48.5%. On a quantitative assessment, BM-SUVmean was significantly higher in patients with BM involvement (SUVmean of 3.7 [1.7-6] vs 1.4 [0.4-2.65], P < 0.001). On receiver operator curve (ROC) analysis, BM-SUVmean > 2.7 had a PPV of 100% for BM involvement (sensitivity of 68%), while BM-SUVmean < 1.7 had an NPV of 100% (specificity of 73%). Visual assessment of PET/CT is appropriate for ruling out BM involvement by FL. Although focal increased uptake indicates marrow

  14. Somatic mutation of EZH2 (Y641) in follicular and diffuse large B-cell lymphomas of germinal center origin | Office of Cancer Genomics

    Cancer.gov

    Morin et al. describe recurrent somatic mutations in EZH2, a polycomb group oncogene. The mutation, found in the SET domain of this gene encoding a histone methyltransferase, is found only in a subset of lymphoma samples. Specifically, EZH2 mutations are found in about 12% of follicular lymphomas (FL) and almost 23% of diffuse large B-cell lymphomas (DLBCL) of germinal center origin. This paper goes on to demonstrate that altered EZH2 proteins, corresponding to the most frequent mutations found in human lymphomas, have reduced activity using in vitro histone methylation assays.

  15. Coexistence of follicular lymphoma and an unclassifiable myeloproliferative neoplasm in a treatment-naïve patient: A case report

    PubMed Central

    JEONG, GYEONGMIN; KIM, JINHYONG; HAN, SEEUN; LEE, JONGMIN; PARK, KYUNGHYE; PAK, CHUIYONG; LIM, JI-HUN; CHA, HEE JEONG; KIM, HAWK; JO, JAE-CHEOL

    2016-01-01

    Myeloproliferative neoplasms are associated with lymphoproliferative diseases following the administration of cytotoxic drugs or exposure to radiation, but are rare prior to therapy. The present study reports the case of a 61-year-old female with a history of transient ischemic attack. The patient, who presented with a palpable mass in the epitrochlear area of the left arm, was simultaneously diagnosed with follicular lymphoma and an unclassifiable myeloproliferative neoplasm. Excisional lymph node biopsy revealed stage I follicular lymphoma (grade 1). Laboratory findings demonstrated leukocytosis, erythrocytosis, thrombocytosis and decreased erythropoietin. Biopsy of the bone marrow revealed hypercellularity, with predominance of erythroid cells, and large polylobated megakaryocytes with increased mitotic figures, but no evidence of lymphomatous infiltration. The janus kinase 2 V617F mutation was also detected in the cells derived from the bone marrow specimen. Following local excision of the lymph node in the left epitrochlear area, radiation was delivered to the involved field, at a dose of 24 Gy in 12 fractions. The patient was started on hydroxyurea (1 g twice per day, orally) 2 weeks subsequent to radiotherapy, and was administered 500 mg twice per day as maintenance therapy. At the six-month follow-up, the white blood cell count, hemoglobin levels and platelet count had reduced, and the patient was in a healthy condition. A computed tomography scan of the neck, chest and abdomen indicated no abnormalities. To the best of our knowledge, the present study is the first case report of follicular lymphoma coexisting with an unclassifiable myeloproliferative neoplasm in a previously healthy patient. Molecular and genetic studies are required to further evaluate this infrequent disease association. PMID:26893762

  16. Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With Stage III or Stage IV Low-Grade Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-02-26

    Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Small Lymphocytic Lymphoma

  17. Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-25

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

  18. Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations.

    PubMed

    Siddiqi, Imran N; Friedman, Julia; Barry-Holson, Keegan Q; Ma, Charles; Thodima, Venkata; Kang, Irene; Padmanabhan, Raghavendra; Dias, Lizalynn M; Kelly, Kevin R; Brynes, Russell K; Kamalakaran, Sitharthan; Houldsworth, Jane

    2016-06-01

    A predominantly diffuse growth pattern and CD23 co-expression are uncommon findings in nodal follicular lymphoma and can create diagnostic challenges. A single case series in 2009 (Katzenberger et al) proposed a unique morphologic variant of nodal follicular lymphoma, characterized by a predominantly diffuse architecture, lack of the t(14;18) IGH/BCL2 translocation, presence of 1p36 deletion, frequent inguinal lymph node involvement, CD23 co-expression, and low clinical stage. Other studies on CD23+ follicular lymphoma, while associating inguinal location, have not specifically described this architecture. In addition, no follow-up studies have correlated the histopathologic and cytogenetic/molecular features of these cases, and they remain a diagnostic problem. We identified 11 cases of diffuse, CD23+ follicular lymphoma with histopathologic features similar to those described by Katzenberger et al. Along with pertinent clinical information, we detail their histopathology, IGH/BCL2 translocation status, lymphoma-associated chromosomal gains/losses, and assessment of mutations in 220 lymphoma-associated genes by massively parallel sequencing. All cases showed a diffuse growth pattern around well- to ill-defined residual germinal centers, uniform CD23 expression, mixed centrocytic/centroblastic cytology, and expression of at least one germinal center marker. Ten of 11 involved inguinal lymph nodes, 5 solely. By fluorescence in situ hybridization analysis, the vast majority lacked IGH/BCL2 translocation (9/11). Deletion of 1p36 was observed in five cases and included TNFRSF14. Of the six cases lacking 1p36 deletion, TNFRSF14 mutations were identified in three, highlighting the strong association of 1p36/TNFRSF14 abnormalities with this follicular lymphoma variant. In addition, 9 of the 11 cases tested (82%) had STAT6 mutations and nuclear P-STAT6 expression was detectable in the mutated cases by immunohistochemistry. The proportion of STAT6 mutations is higher than

  19. Follicular B Lymphomas Generate Regulatory T Cells via the ICOS/ICOSL Pathway and Are Susceptible to Treatment by Anti-ICOS/ICOSL Therapy.

    PubMed

    Le, Kieu-Suong; Thibult, Marie-Laure; Just-Landi, Sylvain; Pastor, Sonia; Gondois-Rey, Françoise; Granjeaud, Samuel; Broussais, Florence; Bouabdallah, Reda; Colisson, Renaud; Caux, Christophe; Ménétrier-Caux, Christine; Leroux, Dominique; Xerri, Luc; Olive, Daniel

    2016-08-15

    The prognosis of follicular lymphoma (FL) patients is suspected to be influenced by tumor-infiltrating regulatory T cells (Treg). The mechanism of Treg enrichment in FL and their impact on malignant FL B cells remains to be elucidated. We analyzed 46 fresh lymph node biopsy samples, including FL (n = 20), diffuse large B-cell lymphoma (n = 10), classical Hodgkin lymphoma (n = 9), and reactive lymphadenitis (n = 7). Using multicolor flow cytometry and cell sorting, we observed an accumulation of CD25(high)CD127(low/neg) Tregs in FL tissues. These Tregs comprised activated ICOS(+) Tregs that were able to suppress not only conventional T cells, but also FL B cells. These FL B cells were able to express ICOSL in vitro and to generate CD25(high)FoxP3(high) Tregs expressing ICOS. Treg generation was associated with ICOS/ICOSL engagement and was abrogated by antagonist anti-ICOS and anti-ICOSL antibodies. Interactions between Tregs and FL B cells resulted in ICOSL downregulation on FL B cells. Our results highlight a key role for Tregs in FL pathogenesis and suggest that targeting the ICOS/ICOSL pathway may be a promising immunotherapy for FL treatment. Cancer Res; 76(16); 4648-60. ©2016 AACR. PMID:27246829

  20. Indications for hematopoietic stem cell transplantation in patients with follicular lymphoma: a consensus project of the EBMT-Lymphoma Working Party.

    PubMed

    Montoto, Silvia; Corradini, Paolo; Dreyling, Martin; Ghielmini, Michele; Kimby, Eva; López-Guillermo, Armando; Mackinnon, Stephen; Marcus, Robert E; Salles, Gilles; Schouten, Harry C; Sureda, Anna; Dreger, Peter

    2013-07-01

    The aim of this project was to define indications for hematopoietic stem cell transplantation in follicular lymphoma in Europe. In the absence of evidence-based data, a RAND-modified Delphi procedure was used by an expert panel. After pre-defining statements, these were individually/anonymously scored by each participant using a 9-point scale. Consensus was reached that: 1) high-dose therapy with autologous stem cell rescue is not an appropriate option to consolidate first remission in patients responding to immuno-chemotherapy outside clinical trials; 2) in patients with first chemo-sensitive relapse, high-dose therapy with autologous stem cell rescue is an appropriate option to consolidate remission, especially in patients with a short response after immuno-chemotherapy or with high-risk FLIPI; 3) high-dose therapy with autologous stem cell rescue is also appropriate in second/subsequent chemo-sensitive relapses; 4) allotransplant (preferably a reduced intensity conditioning-allotransplant) should be considered at relapse after high-dose therapy with autologous stem cell rescue. No consensus was reached on the role of high-dose therapy with autologous stem cell rescue in low-risk first relapse, or on when an allotransplant should be preferred over high-dose therapy with autologous stem cell rescue. In the absence of evidence-based data, the consensus method used was a valuable tool to define indications for hematopoietic stem cell transplant in follicular lymphoma. PMID:23813647

  1. Medical History, Lifestyle, Family History, and Occupational Risk Factors for Follicular Lymphoma: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

    PubMed Central

    Vajdic, Claire M.; Morton, Lindsay M.; de Roos, Anneclaire J.; Skibola, Christine F.; Boffetta, Paolo; Cerhan, James R.; Flowers, Christopher R.; de Sanjosé, Silvia; Monnereau, Alain; Cocco, Pierluigi; Kelly, Jennifer L.; Smith, Alexandra G.; Weisenburger, Dennis D.; Clarke, Christina A.; Blair, Aaron; Bernstein, Leslie; Zheng, Tongzhang; Miligi, Lucia; Clavel, Jacqueline; Benavente, Yolanda; Chiu, Brian C. H.

    2014-01-01

    Background Follicular lymphoma (FL) has been linked with cigarette smoking and, inconsistently, with other risk factors. Methods We assessed associations of medical, hormonal, family history, lifestyle, and occupational factors with FL risk in 3530 cases and 22639 controls from 19 case–control studies in the InterLymph consortium. Age-, race/ethnicity-, sex- and study-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. Results Most risk factors that were evaluated showed no association, except for a few modest or sex-specific relationships. FL risk was increased in persons: with a first-degree relative with non-Hodgkin lymphoma (OR = 1.99; 95% CI = 1.55 to 2.54); with greater body mass index as a young adult (OR = 1.15; 95% CI = 1.04 to 1.27 per 5kg/m2 increase); who worked as spray painters (OR = 2.66; 95% CI = 1.36 to 5.24); and among women with Sjögren syndrome (OR = 3.37; 95% CI = 1.23 to 9.19). Lower FL risks were observed in persons: with asthma, hay fever, and food allergy (ORs = 0.79–0.85); blood transfusions (OR = 0.78; 95% CI = 0.68 to 0.89); high recreational sun exposure (OR = 0.74; 95% CI = 0.65 to 0.86, fourth vs first quartile); who worked as bakers or millers (OR = 0.51; 95% CI = 0.28 to 0.93) or university/higher education teachers (OR = 0.58; 95% CI = 0.41 to 0.83). Elevated risks specific to women included current and longer duration of cigarette use, whereas reduced risks included current alcohol use, hay fever, and food allergies. Other factors, including other autoimmune diseases, eczema, hepatitis C virus seropositivity, hormonal drugs, hair dye use, sun exposure, and farming, were not associated with FL risk. Conclusions The few relationships observed provide clues suggesting a multifactorial etiology of FL but are limited in the extent to which they explain FL occurrence. PMID:25174024

  2. RIT with Y90-Ibritumomab Tiuxetan in Follicular Non-Hodgkin Lymphoma: Evaluation of Recent Outcomes in a Single Institution

    PubMed Central

    Andrade Campos, Marcio Miguel; Montes Limón, Anel E.; Grasa, Jose María; Lievano, Paola; Baringo, Teresa; Giraldo, Pilar

    2012-01-01

    Background. Based on historical data we reviewed our hospital clinical database to analyse our updated information and therapy outcomes of follicular non-Hodgkin lymphoma (F-NHL) patients treated with 90Y-Ibritumomab tiuxetan. Patients and Methods. Between 2005 and 2011, 56 F-NHL patients were included in a clinical protocol conducted by a multidisciplinary team and treated in the same centre. All patients received 0.3 or 0.4 mCi/kg IV (88%) of 90Y-IT; response evaluation was performed 12 weeks after. Results. M/F 44.6%/55.4%, mean age 61.45 years (30–85); ECOG 0-1 96.9%. According to FLIPI score, distribution were good: 58.5%, intermediate: 29.2%, and poor: 12.3%. Previous therapies: >2: 40% (26). ORR was 94.6% (53/56). CR: 85.7%; CR according to previous disease: relapsed disease: 90% (27/30), refractory disease: 42.85% (3/7), consolidation with CR: 92.85% (13/14), and consolidation with PR: 100% (5/5). Global PR and NR were 8.9% (5) and 5.3% (3), respectively. Mean OS 63.86 months with a mean follow-up time of 57 months (2–73). Mean TTP: 52.65 months (95% CI: 43.83–61.48). Median OS and TTP were not achieved. No hospital submissions or deaths were registered. Conclusions. This study confirms the safety and high efficacy of 90Y-IT in F-NHL patients, RIT in early stage of disease could improve outcomes. PMID:23049552

  3. A case of t(14; 18)-negative follicular lymphoma with atypical immunophenotype: usefulness of immunoarchitecture of Ki67, CD79a and follicular dendritic cell meshwork in making the diagnosis.

    PubMed

    Wong, Yin- Ping; Abdul-Rahman, Faridah; Samsudin, Aamad Toha; Masir, Noraidah

    2014-08-01

    Follicular lymphoma is characterised by the t(14;18)(q32;q21) chromosomal translocation causing BCL2 protein overexpression. A proportion of follicular lymphomas do not carry the t(14;18) translocation and lacked BCL2 protein expression. We describe a case of a BCL2 protein- and t(14;18)-negative follicular lymphoma that caused diagnostic difficulty. The usefulness of several immunomarkers including Ki67, CD79a and CD21 in aiding the diagnosis is discussed. The patient is a 51-year-old male who presented with gradually enlarging lymphadenopathy. Histopathological examination of the lymph node showed complete architectural effacement by neoplastic follicles containing expanded CD21-positive follicular dendritic cell meshwork. The neoplastic cells expressed pan-B cell markers (CD20, CD79a) and germinal centre marker (BCL6) but not BCL2 and CD10. Of interest are the staining patterns of Ki67 and CD79a. We observed that the Ki67- positive proliferating cells were evenly distributed within the neoplastic follicles without zonation. In addition, CD79a was homogeneously strong within the neoplastic follicles. These staining patterns were distinctly different from that observed in reactive lymphoid follicles. Fluorescent insitu hybridisation (FISH) analysis however showed absence of BCL2 gene rearrangement. Despite the atypical immunophenotype and lack of BCL2 gene rearrangement, the diagnosis of follicular lymphoma was made based on careful observation of the morphology as well as immunoarchitecture of the Ki67, CD79a and CD21 markers. PMID:25194535

  4. Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma

    PubMed Central

    Bachy, Emmanuel; Houot, Roch; Morschhauser, Franck; Sonet, Anne; Brice, Pauline; Belhadj, Karim; Cartron, Guillaume; Audhuy, Bruno; Fermé, Christophe; Feugier, Pierre; Sebban, Catherine; Delwail, Vincent; Maisonneuve, Hervé; Le Gouill, Steven; Lefort, Sophie; Brousse, Nicole; Foussard, Charles; Salles, Gilles

    2013-01-01

    Anti-CD20-containing chemotherapy regimens have become the standard of care for patients with follicular lymphoma needing cytotoxic therapy. Four randomized trials demonstrated a clinical benefit for patients treated with rituximab. However, no long-term follow up (i.e. > 5 years) of these trials is yet available. Between May 2000 and May 2002, 358 newly diagnosed patients with high tumor burden follicular lymphoma were randomized to receive cyclophosphamide, adriamycin, etoposide and prednisolone plus interferon-α2a or a similar chemotherapy-based regimen plus rituximab, and outcome was up-dated. With a median follow up of 8.3 years, addition of rituximab remained significantly associated with prolonged event-free survival (primary end point) (P=0.0004) with a trend towards a benefit for overall survival (P=0.076). The Follicular Lymphoma International Prognostic Index score was strongly associated with outcome for both event-free and overall survival in univariate analysis and its prognostic value remained highly significant after adjusting for other significant covariates in multivariate models (P<0.0001 and P=0.001, respectively). Considering long-term toxicity, the addition of rituximab in the first-line setting was confirmed as safe with regards to development of secondary malignancies. Long-term follow up of patients with follicular lymphoma treated in the FL2000 study confirms the sustained clinical benefit of rituximab without long-term toxicity. This study was registered at ClinicalTrials.gov (Identifier:00136552). PMID:23645690

  5. Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma.

    PubMed

    Bachy, Emmanuel; Houot, Roch; Morschhauser, Franck; Sonet, Anne; Brice, Pauline; Belhadj, Karim; Cartron, Guillaume; Audhuy, Bruno; Fermé, Christophe; Feugier, Pierre; Sebban, Catherine; Delwail, Vincent; Maisonneuve, Hervé; Le Gouill, Steven; Lefort, Sophie; Brousse, Nicole; Foussard, Charles; Salles, Gilles

    2013-07-01

    Anti-CD20-containing chemotherapy regimens have become the standard of care for patients with follicular lymphoma needing cytotoxic therapy. Four randomized trials demonstrated a clinical benefit for patients treated with rituximab. However, no long-term follow up (i.e. > 5 years) of these trials is yet available. Between May 2000 and May 2002, 358 newly diagnosed patients with high tumor burden follicular lymphoma were randomized to receive cyclophosphamide, adriamycin, etoposide and prednisolone plus interferon-α2a or a similar chemotherapy-based regimen plus rituximab, and outcome was up-dated. With a median follow up of 8.3 years, addition of rituximab remained significantly associated with prolonged event-free survival (primary end point) (P=0.0004) with a trend towards a benefit for overall survival (P=0.076). The Follicular Lymphoma International Prognostic Index score was strongly associated with outcome for both event-free and overall survival in univariate analysis and its prognostic value remained highly significant after adjusting for other significant covariates in multivariate models (P<0.0001 and P=0.001, respectively). Considering long-term toxicity, the addition of rituximab in the first-line setting was confirmed as safe with regards to development of secondary malignancies. Long-term follow up of patients with follicular lymphoma treated in the FL2000 study confirms the sustained clinical benefit of rituximab without long-term toxicity. PMID:23645690

  6. Fludarabine-Mitoxantrone-Rituximab regimen in untreated indolent non-follicular non-Hodgkin's lymphoma: experience on 143 patients.

    PubMed

    Zinzani, Pier Luigi; Pellegrini, Cinzia; Broccoli, Alessandro; Gandolfi, Letizia; Stefoni, Vittorio; Casadei, Beatrice; Maglie, Roberto; Argnani, Lisa; Pileri, Stefano

    2015-09-01

    Indolent non-follicular lymphomas (inFLs) are generally regarded as incurable, apart from extranodal mucosa-associated lymphatic tissue lymphomas, which can be partially cured by surgery, local radiotherapy, or antibiotic treatment. The aim of the present study was to test the degree of effectiveness and the safety of the regimen containing fludarabine, mitoxantrone, and rituximab (FMR) in inFL patients considering all the different entities belonging to this group. An observational retrospective study was conducted on 143 inFL patients providing that their first chemoimmunotherapy performed was FMR regimen and diagnosis from September 2000 to March 2011. There were 32 small lymphocytic lymphomas and 111 marginal zone lymphomas. At the end of treatment, overall response rate was 96.5% with 88% of complete responses (CR) and 8.5% of partial responses. With a median follow-up of 48 months, 10 out of 125 (8%) CR patients had disease relapse, yielding an estimated 9-year disease-free survival (DFS) of 74.9% and an estimated 10-year overall survival of 92.8%. The estimated 9-year progression free survival was 70.5%. The 10 relapsed patients showed lymphoma recurrence within 52 months: after this time, the DFS curve presented a plateau configuration. Only two (1.4%) patients developed a secondary hematological neoplasia. This study showed promising findings for the use of a fludarabine-based regimen in combination with rituximab in the front-line treatment of symptomatic inFL with a noteworthy high percentage of CR associated to an interesting long-term DFS and favorable acute and long-term safety profile. PMID:24986783

  7. Monoclonal Antibody Therapy and Peripheral Stem Cell Transplant in Treating Patients With Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-08

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2

  8. Statin use is safe and does not impact prognosis in patient with de novo follicular lymphoma treated with immunochemotherapy: An exploratory analysis of the PRIMA cohort study.

    PubMed

    Bachy, Emmanuel; Estell, Jane A; Van de Neste, Eric; Bouabdallah, Réda; Bargay, Joan; Delmer, Alain; Gelas-Dore, Bénédicte; Gomes da Silva, Maria; Fitoussi, Olivier; Belada, David; Maisonneuve, Hervé; Intragumtornchai, Tanin; Lamy, Thierry; Dartigues, Peggy; Seymour, John Francis; Salles, Gilles

    2016-06-01

    An adverse prognostic impact of statin use in lymphoma was first suspected from in vitro data showing an impairment of anti-CD20 antibody binding. However, further clinical studies suggested an improved outcome associated with their use in hematological malignancies. In particular, a survival benefit was reported for patients with follicular lymphoma on statins. Our objective was to assess the outcome of follicular lymphoma patients treated in the PRIMA study with immunochemotherapy according to the use of statins. Among the 1,217 patients enrolled in the PRIMA study, 1,135 were included in the present study. Concomitant treatments at registration were available for all patients. Among those 1,135 patients, 119 were on statins (10.5%) at diagnosis. Adverse events frequencies, event-free survival (EFS), time to next lymphoma treatment (TTNLT), time to next chemotherapy (TTNCT), and overall survival (OS) were evaluated according to the use of statins. The rates of overall and specific cardiovascular adverse events between the two groups of patients were comparable both during induction and maintenance. Outcome in terms of response rates or EFS, TTNLT, TTNCT, and OS were similar regardless of the use of statins (P = 0.57, P = 0.85, P = 0.30, and P = 0.43, respectively) in univariate analysis and after further adjustments for potential confounding factors in multivariate analysis. In conclusion, statin use does not impact the prognosis of patients with follicular lymphoma treated with immunochemotherapy. PMID:26799234

  9. NK Cell Activation in the Antitumor Response Induced by IFN-α Dendritic Cells Loaded with Apoptotic Cells from Follicular Lymphoma Patients.

    PubMed

    Lapenta, Caterina; Donati, Simona; Spadaro, Francesca; Castaldo, Paolo; Belardelli, Filippo; Cox, Maria C; Santini, Stefano M

    2016-08-01

    Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma. This malignancy is considered virtually incurable, with high response rates to therapy but frequent relapses. We investigated the ability of monocyte-derived dendritic cells generated in the presence of IFN-α and GM-CSF (IFN-DC) and loaded with apoptotic lymphoma cells to activate immune responses against FL cells, with the ultimate goal of designing novel patient-specific vaccination strategies for the treatment of FL. In this article, we show that apoptotic tumor cell-loaded IFN-DC from FL patients, which were cultured for 2 wk with autologous lymphocytes, led to Th1 response skewing, based on significantly higher levels of IFN-γ production and a remarkable increase in CD8(+) and NK cell frequency, consistent with the detection of enhanced cytotoxic effector function toward autologous FL cells. IFN-DC were found to promote efficient NK cell activation, increased expression of cytotoxicity receptors, and extensive IFN-γ production in the virtual absence of IL-10. Moreover, direct recognition and killing of primary autologous lymphoma cells by activated NK cells from FL patients was also demonstrated. A critical role was demonstrated for MHC class I-related chain A and B and membrane-bound IL-15 in IFN-DC-mediated NK cell activation and early IFN-γ production. The overall results indicate that IFN-DC loaded with autologous apoptotic FL cells represent a valuable tool for improving the potency of therapeutic cancer vaccines through the efficient induction of NK cell activation and promotion of CD8(+) T cell antitumor immunity. PMID:27357153

  10. Disseminated juvenile xanthogranuloma associated with follicular lymphoma in an adult: successful treatment with chemotherapy and rituximab. A review of the literature.

    PubMed

    Narváez-Moreno, B; Pulpillo-Ruiz, Á; De Zulueta-Dorado, T; Conejo-Mir, J

    2013-04-01

    Juvenile xanthogranuloma is a non-Langerhans cell histiocytosis that typically affects children, but several cases have been reported in adults, some in connection with hematologic malignancies. We present the case of a 61-year-old woman with multiple xanthogranulomas who developed a follicular lymphoma after 4 years of follow-up. After 6 months of treatment with chemotherapy and rituximab, the cutaneous lesions disappeared and the patient achieved remission from lymphoma. We highlight this case because xanthogranuloma is a rare disorder that is difficult to diagnose in adults and also because this is the first report of an association between xanthogranuloma and follicular lymphoma. Excellent response was achieved with chemotherapy and rituximab. Finally, given the possible association between xanthogranulomas and hematologic diseases, these lesions may be a cutaneous manifestation of an occult malignancy. PMID:22681714

  11. Agatolimod Sodium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Recurrent or Refractory Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-01-04

    Adult Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  12. Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

    ClinicalTrials.gov

    2016-06-08

    HIV Infection; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Plasmablastic Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Follicular Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  13. Low NK cell counts in peripheral blood are associated with inferior overall survival in patients with follicular lymphoma

    PubMed Central

    Shafer, Danielle; Smith, Mitchell R.; Borghaei, Hossein; Millenson, Michael M.; Li, Tianyu; Litwin, Samuel; Anad, Rachna; Al-Saleem, Tahseen

    2013-01-01

    Host immune responses influence follicular lymphoma (FL) outcomes. To test our hypothesis that immune cells in blood reflect that response, we assessed by peripheral blood flow cytometry in 75 untreated FL patients the absolute counts of: lymphocytes (ALC), CD4+T (ACD4C), CD8+T (ACD8C) and natural killer (ANKC) cells. Low ANKC was the only parameter associated with inferior overall survival by univariate analysis (p= 0.02), and trended to significance in multivariable analysis with ACD4C (p= 0.08). Five (24%) patients with low initial ANKC died, while none with normal/high ANKC have died Conclusions: Evaluation of blood ANKC may be a useful indicator of outcome in previously untreated FL patients. PMID:23968916

  14. Anti-CD22 CAR-T Therapy for CD19-refractory or Resistant Lymphoma Patients

    ClinicalTrials.gov

    2016-08-22

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Stage III/IV Adult Diffuse Large Cell Lymphoma; Stage III/IV Follicular Lymphoma; Stage III/IV Mantle Cell Lymphoma

  15. Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma

    PubMed Central

    Schuster, Stephen J.; Neelapu, Sattva S.; Gause, Barry L.; Janik, John E.; Muggia, Franco M.; Gockerman, Jon P.; Winter, Jane N.; Flowers, Christopher R.; Nikcevich, Daniel A.; Sotomayor, Eduardo M.; McGaughey, Dean S.; Jaffe, Elaine S.; Chong, Elise A.; Reynolds, Craig W.; Berry, Donald A.; Santos, Carlos F.; Popa, Mihaela A.; McCord, Amy M.; Kwak, Larry W.

    2011-01-01

    Purpose Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) –specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial. Patients and Methods Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control. Results Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients. Conclusion Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other

  16. Collision tumor consisting of primary follicular lymphoma and adenocarcinoma in the cecum: A case report and literature review

    PubMed Central

    KUS, TULAY; AKTAS, GOKMEN; KALENDER, MEHMET EMIN; SARI, IBRAHIM; ULKER, ESRA; CAMCI, CELALETDIN

    2016-01-01

    The present study reports the case of a collision tumor consisting of follicular lymphoma (FL) and adenocarcinoma in the cecum of a 73-year-old man. To the best of our knowledge, the present study is the 11th case of a collision tumor consisting of colon adenocarcinoma and lymphoma to be reported in the literature, and the first case of cecum adenocarcinoma with low grade FL in the same segment of the cecum and the same regional lymph node to be reported. The present study reviewed the literature to determine treatment options for patients with collision tumors. The present patient was administered with adjuvant chemotherapy for T3N1M0 colon cancer following surgery, due to the dominance of colon adenocarcinoma in the collision tumor. Following the completion of treatment, progression of the untreated FL was observed. In the literature, patients with collision tumors are administered with chemotherapy for stage IV FL, and following the completion of treatment patients have presented with a recurrence of early stage colon adenocarcinoma. The recommended treatment for collision tumors is dependent on the dominant tumor; however, the treatment options for collision tumors in the literature appeared to exacerbate the other tumor. The characteristics of the tumors altered following chemotherapy, and immunological alterations in the tumors due to chemotherapy appear to have contributed to the exacerbation of the tumors. Therefore, patients with early-stage tumors should be considered at risk of recurrence of other malignancies, which are present in collision tumors. PMID:27073555

  17. Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma

    PubMed Central

    Schneider, Dunja; Dühren-von Minden, Marcus; Alkhatib, Alabbas; Setz, Corinna; van Bergen, Cornelis A. M.; Benkißer-Petersen, Marco; Wilhelm, Isabel; Villringer, Sarah; Krysov, Sergey; Packham, Graham; Zirlik, Katja; Römer, Winfried; Buske, Christian; Stevenson, Freda K.; Veelken, Hendrik

    2015-01-01

    B-cell antigen receptor (BCR) expression is a key feature of most B-cell lymphomas, but the mechanisms of BCR signal induction and the involvement of autoantigen recognition remain unclear. In follicular lymphoma (FL) B cells, BCR expression is retained despite a chromosomal translocation that links the antiapoptotic gene BCL2 to the regulatory elements of immunoglobulin genes, thereby disrupting 1 heavy-chain allele. A remarkable feature of FL-BCRs is the acquisition of potential N-glycosylation sites during somatic hypermutation. The introduced glycans carry mannose termini, which create potential novel binding sites for mannose-specific lectins. Here, we investigated the effect of N-linked variable-region glycosylation for BCR interaction with cognate antigen and with lectins of different origins. N-glycans were found to severely impair BCR specificity and affinity to the initial cognate antigen. In addition, we found that lectins from Pseudomonas aeruginosa and Burkholderia cenocepacia bind and stimulate FL cells. Human exposure to these bacteria can occur by contact with soil and water. In addition, they represent opportunistic pathogens in susceptible hosts. Understanding the role of bacterial lectins might elucidate the pathogenesis of FL and establish novel therapeutic approaches. PMID:25784678

  18. High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells.

    PubMed

    Myklebust, June H; Irish, Jonathan M; Brody, Joshua; Czerwinski, Debra K; Houot, Roch; Kohrt, Holbrook E; Timmerman, John; Said, Jonathan; Green, Michael R; Delabie, Jan; Kolstad, Arne; Alizadeh, Ash A; Levy, Ronald

    2013-02-21

    Defects in T-cell function in patients with cancer might influence their capacity to mount efficient antitumor immune responses. Here, we identified highly reduced IL-4-, IL-10-, and IL-21-induced phosphorylation of STAT6 and STAT3 in tumor-infiltrating T cells (TILs) in follicular lymphoma (FL) tumors, contrasting other non-Hodgkin lymphoma TILs. By combining phospho-protein-specific flow cytometry with several T-cell markers, we identified that CD4(+)CD45RO(+)CD62L(-) FL TILs were largely nonresponsive to cytokines, in contrast to the corresponding autologous peripheral blood subset. We observed differential expression of the inhibitory receptor PD-1 in FL TILs and peripheral blood T cells. Furthermore, CD4(+)PD-1(hi) FL TILs, containing T(FH) and non-T(FH) cells, had lost their cytokine responsiveness, whereas PD-1 TILs had normal cytokine signaling. However, this phenomenon was not tumor specific, because tonsil T cells were similar to FL TILs. FL tumor cells were negative for PD-1 ligands, but PD-L1(+) histiocytes were found within the T cell-rich zone of the neoplastic follicles. Disruption of the microenvironment and in vitro culture of FL TILs could restore cytokine signaling in the PD-1(hi) subset. Because FL TILs in vivo probably receive suppressive signals through PD-1, this provides a rationale for testing PD-1 Ab in combination with immunotherapy in patients with FL. PMID:23297127

  19. A rare combination of an endocrine tumour of the common bile duct and a follicular lymphoma of the ampulla of Vater: a case report and review of the literature

    PubMed Central

    2011-01-01

    Carcinoid tumours of the common bile duct represent an extremely rare entity. Similarly, primary follicular lymphomas of the ampulla of Vater constitute an infrequent neoplasia. Herein, we report the first case of a synchronous development of a carcinoid tumour of the common bile duct and an ampullary follicular lymphoma that was treated surgically with a Whipple's procedure, due to inability to establish definitive preoperative diagnosis despite the extensive diagnostic investigation. PMID:21232154

  20. External Beam Radiotherapy Followed by {sup 90}Y Ibritumomab Tiuxetan in Relapsed or Refractory Bulky Follicular Lymphoma

    SciTech Connect

    Burdick, Michael J.; Neumann, Donald; Pohlman, Brad; Reddy, Chandana A.; Tendulkar, Rahul D.; Macklis, Roger

    2011-03-15

    Purpose: We combined external beam radiotherapy (EBRT) with yttrium-90 ibritumomab tiuxetan ({sup 90}Y-IT) in an attempt to improve therapeutic response in patients with relapsed or refractory bulky follicular lymphoma (RRBFL). Methods and Materials: Between February 2006 and September 2007, 11 patients with RRBFL were treated with EBRT followed by {sup 90}Y-IT. Bulky disease (BD) was defined as >5 cm. EBRT was delivered to BD as 2,400 cGy in eight fractions using computed tomography (CT)-based planning. BD was contoured as the gross tumor volume. A planning margin of 1 to 2 cm was added depending on anatomical location. After recovery of complete blood counts (CBC), {sup 90}Y-IT was administered at a dose of 0.3 or 0.4 mCi/kg depending on platelet counts. Hematologic toxicity was monitored through weekly CBC. Response was measured by positron emission tomography/CT or CT 3-4 months after {sup 90}Y-IT. Results: Only 2 patients required prolonged breaks between EBRT and {sup 90}Y-IT. The median time after {sup 90}Y-IT for platelets to recover to >100,000/ml was 55 days (range, 41-128 days). Platelet counts for 1 patient, who had received 4 previous chemotherapy regimens, never reached 100,000/ml. The complete and overall responses to combined therapy as measured 3-4 months after {sup 90}Y-IT were 64%. No patients relapsed within the EBRT field. With a median follow-up of 36.1 months, 6 patients have relapsed, 2 of whom have died. Median progression-free survival was 17.5 months. Conclusions: In contrast to prior failure analysis data for RRBFL patients treated with {sup 90}Y-IT alone, a brief course of EBRT prevented relapse in sites of BD. EBRT used to pretreat bulky sites may improve clinical outcomes and potentially extend survival when combined with {sup 90}Y-IT.

  1. IMPACT OF PRETRANSPLANT CONDITIONING REGIMENS ON OUTCOMES OF ALLOGENEIC TRANSPLANTATION FOR CHEMOTHERAPY-UNRESPONSISVE DIFFUSE LARGE B-CELL LYMPHOMA AND GRADE-III FOLLICULAR LYMPHOMA

    PubMed Central

    Hamadani, Mehdi; Saber, Wael; Ahn, Kwang Woo; Carreras, Jeanette; Cairo, Mitchell S.; Fenske, Timothy S.; Gale, Robert Peter; Gibson, John; Hale, Gregory A.; Hari, Parameswaran N.; Hsu, Jack W.; Inwards, David J.; Kamble, Rammurti T.; Klein, Anderas; Maharaj, Dipnarine; Marks, David I.; Rizzieri, David A.; Savani, Bipin N.; Schouten, Harry C.; Waller, Edmund K.; Wirk, Baldeep; Laport, Ginna G.; Montoto, Silvia; Maloney, David G.; Lazarus, Hillard M.

    2013-01-01

    Patients with chemorefractory non-Hodgkin lymphomas (NHL) generally have a poor prognosis. We used the observational database of the CIBMTR to study the outcome of 533 patients with refractory diffuse large B-cell lymphoma (DLBCL) or grade-III follicular lymphoma (FL-III) who underwent allogeneic transplantation (allo-HCT) using either myeloablative (MA; N=307) or reduced intensity/non-myeloablative conditioning (RIC/NST; N=226), between 1998-2010. We analyzed non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Only 45% of the patients at transplant had a Karnofsky performance score of ≥90%. Median follow-up of surviving patients after MA and RIC/NST allo-HCT is 35 months and 30 months, respectively. At 3years, MA allo-HCT was associated with a higher NRM compared to RIC/NST (53% vs. 42%; p=0.03), similar PFS (19% vs. 23%; p=0.40), and lower OS (19% vs. 28%; p=0.02), respectively. On multivariate analysis, FL-III histology was associated with lower NRM (relative-risk [RR]=0.52), reduced risk of relapse/progression (RR=0.42), superior PFS (RR=0.51) and OS (RR=0.53), while MA conditioning was associated with reduced risk of relapse/progression (RR=0.66). Despite a refractory state, a small subset of DLBCL and FL-III patients can attain durable remissions after allo-HCT. Conditioning regimen intensity was not associated with PFS and OS despite a higher risk of relapse/progression with RIC/NST allo-HCT. PMID:23380340

  2. Alisertib With and Without Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-15

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  3. Lenalidomide and Blinatumomab in Treating Patients With Relapsed Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-09-09

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Mediastinal Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma

  4. Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma

    ClinicalTrials.gov

    2016-04-25

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  5. Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, MCL, or Indolent Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2016-04-05

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  6. Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-12-13

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

  7. Lenalidomide and Temsirolimus in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-06-24

    AIDS-Related Hodgkin Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Waldenstrom Macroglobulinemia

  8. Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2016-04-26

    B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma,; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

  9. Fenretinide and Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2014-09-30

    Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Stage II Marginal Zone Lymphoma; Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult

  10. Germline variation in complement genes and event-free survival in follicular and diffuse large B-cell lymphoma.

    PubMed

    Charbonneau, Bridget; Maurer, Matthew J; Fredericksen, Zachary S; Zent, Clive S; Link, Brian K; Novak, Anne J; Ansell, Stephen M; Weiner, George J; Wang, Alice H; Witzig, Thomas E; Dogan, Ahmet; Slager, Susan L; Habermann, Thomas M; Cerhan, James R

    2012-09-01

    The complement pathway plays a central role in innate immunity, and also functions as a regulator of the overall immune response. We evaluated whether polymorphisms in complement genes are associated with event-free survival (EFS) in follicular lymphoma (FL) and diffuse large B-cell (DLBCL) lymphoma. We genotyped 167 single nucleotide polymorphisms (SNPs) from 30 complement pathway genes in a prospective cohort study of newly diagnosed FL (N = 107) and DLBCL (N = 82) patients enrolled at the Mayo Clinic from 2002 to 2005. Cox regression was used to estimate hazard ratios (HRs) for individual SNPs with EFS, adjusting for FLIPI or IPI and treatment. For gene-level analyses, we used a principal components based gene-level test. In gene-level analyses for FL EFS, CFH (P = 0.009), CD55 (P = 0.006), CFHR5 (P = 0.01), C9 (P = 0.02), CFHR1 (P = 0.03), and CD46 (P = 0.03) were significant at P < 0.05, and these genes remained noteworthy after accounting for multiple testing (q < 0.15). SNPs in CFH, CFHR1, and CFHR5 showed stronger associations among patients receiving any rituximab, while SNPs from CD55 and CD46 showed stronger associations among patients who were observed. For DLBCL, only CLU (P = 0.001) and C7 (P = 0.03) were associated with EFS, but did not remain noteworthy after accounting for multiple testing (q>0.15). Genes from the regulators of complement activation (CFH, CD55, CFHR1, CFHR5, CD46) at 1q32-q32.1, along with C9, were associated with FL EFS after adjusting for clinical variables, and if replicated, these findings add further support for the role of host innate immunity in FL prognosis. PMID:22718493

  11. 506U78 in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or T-cell Lymphoma

    ClinicalTrials.gov

    2013-01-22

    Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  12. Alvocidib, Fludarabine Phosphate, and Rituximab in Treating Patients With Lymphoproliferative Disorders or Mantle Cell Lymphoma

    ClinicalTrials.gov

    2013-06-03

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Splenic Marginal Zone Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Untreated Hairy Cell Leukemia; Waldenström Macroglobulinemia

  13. Safety and efficacy of (90) yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients. An Italian cooperative study.

    PubMed

    Ibatici, Adalberto; Pica, Gian Matteo; Nati, Sandro; Vitolo, Umberto; Botto, Barbara; Ciochetto, Chiara; Petrini, Mario; Galimberti, Sara; Ciabatti, Elena; Orciuolo, Enrico; Zinzani, Pier Luigi; Cascavilla, Nicola; Guolo, Fabio; Fraternali Orcioni, Giulio; Carella, Angelo M

    2014-03-01

    (90) Yttrium ((90) Y)-Ibritumomab-Tiuxetan combines the targeting advantage of a monoclonal antibody with the radiosensitivity of Follicular Lymphoma (FL). Previous studies showed that 90Y-IT is safe and effective in relapsed/refractory indolent FL, irrespective of prior treatment with rituximab. This multicentre trial aimed to evaluate the safety and the efficacy of "upfront" single-agent ((90) Y)-Ibritumomab-Tiuxetan in advanced-stage FL. The primary objective was the incidence of responses in terms of complete (CR) and partial remission (PR). Fifty patients with stage II "bulky", III or IV FL received a single treatment course with ((90) Y)-Ibritumomab-Tiuxetan as initial therapy. The median age was 60 years. Bone marrow involvement (<25%) was observed in 24 patients (48%) and 7 (14%) had an elevated lactate dehydrogenase level. The overall response (ORR) and CR rates were 94% and 86%, respectively with a median follow-up of 38·8 months. The median progression-free survival (PFS) was not reached, whereas the 3-year estimated PFS and overall survival (OS) rate was 63·4% and 90%, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 30% and 26% of patients respectively; none experienced grade 3/4 non-haematological toxicity. No cases of secondary haematological malignancies were observed. ((90) Y)-Ibritumomab-Tiuxetan was demonstrated to be highly effective and safe as first-line treatment for advanced-stage FL. PMID:24344981

  14. S(mu) mutation patterns suggest different progression pathways in follicular lymphoma: early direct or late from FL progenitor cells.

    PubMed

    Ruminy, Philippe; Jardin, Fabrice; Picquenot, Jean-Michel; Parmentier, Françoise; Contentin, Nathalie; Buchonnet, Gérard; Tison, Sandrine; Rainville, Vinciane; Tilly, Hervé; Bastard, Christian

    2008-09-01

    Follicular lymphoma (FL) is a B-cell malignancy characterized by the t(14;18) translocation. Although sensitive to treatment, the disease remains incurable and the reason why tumor cells invariably evade treatment, leading to clinical relapse, is still unknown. Here, we tracked the clonal history of tumor cells by studying mutations introduced by activation-induced cytidine deaminase on the switch mu region of the der(14)t(14;18) during the early phase of the class-switch recombination (CSR) process. We observed frequent intraclonal variations, suggesting that CSR often remains active after the acquisition of the fully transformed phenotype. However, mutations only rarely accumulated over time, but instead showed complex evolutionary scenarios and 2 different progression pathways. The first pathway was a direct and rapid evolution from the dominant clone. The second was indirect, arising from earlier subclones usually after years of remission. A better understanding of these mechanisms might influence the future choice of treatment strategies. PMID:18515657

  15. Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma.

    PubMed

    Tusé, Daniel; Ku, Nora; Bendandi, Maurizio; Becerra, Carlos; Collins, Robert; Langford, Nyla; Sancho, Susana Inogés; López-Díaz de Cerio, Ascensión; Pastor, Fernando; Kandzia, Romy; Thieme, Frank; Jarczowski, Franziska; Krause, Dieter; Ma, Julian K-C; Pandya, Shan; Klimyuk, Victor; Gleba, Yuri; Butler-Ransohoff, John E

    2015-01-01

    We report the first evaluation of plant-made conjugate vaccines for targeted treatment of B-cell follicular lymphoma (FL) in a Phase I safety and immunogenicity clinical study. Each recombinant personalized immunogen consisted of a tumor-derived, plant-produced idiotypic antibody (Ab) hybrid comprising the hypervariable regions of the tumor-associated light and heavy Ab chains, genetically grafted onto a common human IgG1 scaffold. Each immunogen was produced in Nicotiana benthamiana plants using twin magnICON vectors expressing the light and heavy chains of the idiotypic Ab. Each purified Ab was chemically linked to the carrier protein keyhole limpet hemocyanin (KLH) to form a conjugate vaccine. The vaccines were administered to FL patients over a series of ≥6 subcutaneous injections in conjunction with the adjuvant Leukine (GM-CSF). The 27 patients enrolled in the study had previously received non-anti-CD20 cytoreductive therapy followed by ≥4 months of immune recovery prior to first vaccination. Of 11 patients who became evaluable at study conclusion, 82% (9/11) displayed a vaccine-induced, idiotype-specific cellular and/or humoral immune response. No patients showed serious adverse events (SAE) related to vaccination. The fully scalable plant-based manufacturing process yields safe and immunogenic personalized FL vaccines that can be produced within weeks of obtaining patient biopsies. PMID:26425548

  16. Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma

    PubMed Central

    Tusé, Daniel; Ku, Nora; Bendandi, Maurizio; Becerra, Carlos; Collins, Robert; Langford, Nyla; Sancho, Susana Inogés; López-Díaz de Cerio, Ascensión; Pastor, Fernando; Kandzia, Romy; Thieme, Frank; Jarczowski, Franziska; Krause, Dieter; Ma, Julian K.-C.; Pandya, Shan; Klimyuk, Victor; Gleba, Yuri; Butler-Ransohoff, John E.

    2015-01-01

    We report the first evaluation of plant-made conjugate vaccines for targeted treatment of B-cell follicular lymphoma (FL) in a Phase I safety and immunogenicity clinical study. Each recombinant personalized immunogen consisted of a tumor-derived, plant-produced idiotypic antibody (Ab) hybrid comprising the hypervariable regions of the tumor-associated light and heavy Ab chains, genetically grafted onto a common human IgG1 scaffold. Each immunogen was produced in Nicotiana benthamiana plants using twin magnICON vectors expressing the light and heavy chains of the idiotypic Ab. Each purified Ab was chemically linked to the carrier protein keyhole limpet hemocyanin (KLH) to form a conjugate vaccine. The vaccines were administered to FL patients over a series of ≥6 subcutaneous injections in conjunction with the adjuvant Leukine (GM-CSF). The 27 patients enrolled in the study had previously received non-anti-CD20 cytoreductive therapy followed by ≥4 months of immune recovery prior to first vaccination. Of 11 patients who became evaluable at study conclusion, 82% (9/11) displayed a vaccine-induced, idiotype-specific cellular and/or humoral immune response. No patients showed serious adverse events (SAE) related to vaccination. The fully scalable plant-based manufacturing process yields safe and immunogenic personalized FL vaccines that can be produced within weeks of obtaining patient biopsies. PMID:26425548

  17. Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience

    PubMed Central

    Tan, Daryl; Horning, Sandra J.; Hoppe, Richard T.; Levy, Ronald; Rosenberg, Saul A.; Sigal, Bronislava M.; Warnke, Roger A.; Natkunam, Yasodha; Han, Summer S.; Yuen, Alan; Plevritis, Sylvia K.

    2013-01-01

    Recent studies report an improvement in overall survival (OS) of patients with follicular lymphoma (FL). Previously untreated patients with grade 1 to 2 FL treated at Stanford University from 1960-2003 were identified. Four eras were considered: era 1, pre-anthracycline (1960-1975, n = 180); era 2, anthracycline (1976-1986, n = 426); era 3, aggressive chemotherapy/purine analogs (1987-1996, n = 471); and era 4, rituximab (1997-2003, n = 257). Clinical characteristics, patterns of care, and survival were assessed. Observed OS was compared with the expected OS calculated from Berkeley Mortality Database life tables derived from population matched by gender and age at the time of diagnosis. The median OS was 13.6 years. Age, gender, and stage did not differ across the eras. Although primary treatment varied, event-free survival after the first treatment did not differ between eras (P = .17). Median OS improved from 11 years in eras 1 and 2 to 18.4 years in era 3 and has not yet been reached for era 4 (P < .001), with no suggestion of a plateau in any era. These improvements in OS exceeded improvements in survival in the general population during the same period. Several factors, including better supportive care and effective therapies for relapsed disease, are likely responsible for this improvement. PMID:23777769

  18. Study of BKM120 & Rituximab in Patients With Relapsed or Refractory Indolent B-Cell Lymphoma

    ClinicalTrials.gov

    2016-06-14

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  19. Differential Expression of Bcl-2 Family Proteins Determines the Sensitivity of Human Follicular Lymphoma Cells to Dexamethasone-mediated and Anti-BCR-mediated Apoptosis.

    PubMed

    Adem, Jemal; Ropponen, Antti; Eeva, Jonna; Eray, Mine; Nuutinen, Ulla; Pelkonen, Jukka

    2016-01-01

    Bcl-2 family comprises proapoptotic and antiapoptotic proteins. The balance between these proteins is critical for the survival of the cells. Overexpression of the antiapoptotic protein, Bcl-2, is the hallmark of follicular lymphoma (FL). High expression of Bcl-2 provides survival advantage and may facilitate chemotherapeutic resistance in FL. In the present study, we examined expression profile of Bcl-2 family proteins such as Bcl-2, Bcl-xL, and Bim in human FL cell lines, HF1A3 and HF28. We assessed the correlation between the expression levels of these proteins and cells' sensitivity to dexamethasone (Dex)-mediated and B-cell receptor (BCR)-mediated apoptosis. Here, we show that Dex and anti-BCR-induced synergistic apoptosis which correlated with significant downregulation of Bcl-xL, inhibition of ERK1/2 phosphorylation and accumulation of nonphosphorylated Bim. However, HF28 cells were less sensitive than HF1A3 cells to Dex-induced and anti-BCR-induced apoptosis due to high Bcl-2 protein level. It is interesting to note that, a Bcl-2-specific inhibitor, ABT-199, sensitized HF28 cells to Dex-induced or anti-BCR-induced apoptosis. In addition, overexpression of Bcl-xL prevented Dex-mediated, anti-BCR-mediated, and ABT-199-mediated apoptosis, indicating that mitochondria were involved. In conclusion, these data show that the expression levels of Bcl-2 family proteins may serve to predict tumor response to BH3 mimetics and the sensitivity of FL cells to Dex-induced and anti-BCR-induced apoptosis. Moreover, our results show that BCR-targeted apoptosis might have therapeutic benefit against FL and B-cell lymphomas. PMID:26641257

  20. Impact of [{sup 18}F] Fluorodeoxyglucose Positron Emission Tomography on Staging and Management of Early-Stage Follicular Non-Hodgkin Lymphoma

    SciTech Connect

    Wirth, Andrew Foo, Marcus; Seymour, John F.; MacManus, Michael P.; Hicks, Rodney J.

    2008-05-01

    Purpose: Accurate staging is critical to select patients with early-stage (I-II) follicular lymphoma (ESFL) suitable for involved-field radiotherapy (IFRT) and to define the radiotherapy portal. We evaluated the impact of fluorodeoxyglucose (FDG) PET on staging, treatment, and outcome for patients with ESFL on conventional staging. Methods and Materials: Forty-two patients with untreated ESFL (World Health Organization Grade I-IIIa, or 'low grade') following a minimum of physical examination, computerized tomography, and bone marrow examination (conventional assessment) and who had staging PET from June 1997 to June 2006 were studied retrospectively. Stage allocation was based on routine imaging reports. Disease sites, stage, and management plan were recorded based on conventional assessment or conventional assessment plus PET. Results: FDG avidity was demonstrated in 97% of patients in whom disease was evident on conventional assessment after biopsy. PET findings suggested a change of stage or management in 19 patients: 13 (31%) who were upstaged to Stage III-IV, altering ideal management from IFRT to systemic therapy, and 6 (14%) who had the involved field enlarged, including 4 upstaged from Stage I to II. Of these 19 cases, PET findings were considered true positive in 8 patients, indeterminate in 10, and false positive in only 1 patient. Conclusions: Our data confirm that ESFL is usually FDG-avid. In routine practice, PET has the potential to upstage and thereby alter management in a high proportion of patients with apparent ESFL.

  1. Radioimmunotherapy Combined with Maintenance Anti-CD20 Antibody May Trigger Long-Term Protective T Cell Immunity in Follicular Lymphoma Patients

    PubMed Central

    Buchegger, Franz; Larson, Steven M.; Mach, Jean-Pierre; Dietrich, Pierre-Yves; Cairoli, Anne; Prior, John O.; Romero, Pedro; Speiser, Daniel E.

    2013-01-01

    Growing evidence suggests that the patient's immune response may play a major role in the long-term efficacy of antibody therapies of follicular lymphoma (FL). Particular long-lasting recurrence free survivals have been observed after first line, single agent rituximab or after radioimmunotherapy (RIT). Rituximab maintenance, furthermore, has a major efficacy in prolonging recurrence free survival after chemotherapy. On the other hand, RIT as a single step treatment showed a remarkable capacity to induce complete and partial remissions when applied in recurrence and as initial treatment of FL or given for consolidation. These clinical results strongly suggest that RIT combined with rituximab maintenance could stabilize the high percentages of patients with CR and PR induced by RIT. While the precise mechanisms of the long-term efficacy of these 2 treatments are not elucidated, different observations suggest that the patient's T cell immune response could be decisive. With this review, we discuss the potential role of the patient's immune system under rituximab and RIT and argue that the T cell immunity might be particularly promoted when combining the 2 antibody treatments in the early therapy of FL. PMID:24371449

  2. Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-08-10

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma

  3. Safety, Tolerability, and Pharmacokinetics of Idelalisib in Japanese Adults With Relapsed or Refractory Indolent B-Cell Non-Hodgkin Lymphomas or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2016-05-16

    Chronic Lymphocytic Leukemia; Indolent Non-Hodgkin Lymphoma; Follicular Lymphoma; Small Lymphocytic Lymphoma; Lymphoplasmacytic Lymphoma (With or Without Waldenstrom Macroglobulinemia); Marginal Zone Lymphoma

  4. Oblimersen Sodium and Rituximab in Treating Patients With Recurrent B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2014-05-13

    Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  5. The long term follow-up of early stage follicular lymphoma treated with radiotherapy, chemotherapy or combined modality treatment.

    PubMed

    Sancho, Juan-Manuel; García, Olga; Mercadal, Santiago; Pomares, Helena; Fernández-Alvarez, Rubén; González-Barca, Eva; Tapia, Gustavo; González-García, Esther; Moreno, Miriam; Domingo-Domènech, Eva; Sorigué, Marc; Navarro, José-Tomás; Motlló, Cristina; Fernández-de-Sevilla, Alberto; Feliu, Evarist; Ribera, Josep-Maria

    2015-08-01

    Local (involved-field or recently involved-site) radiotherapy is the standard therapy in limited-stage follicular lymphoma (FL). We retrospectively analyzed the value of chemotherapy in 130 patients with limited-stage FL (46 treated with radiotherapy alone [RT group], 30 with radiotherapy plus chemotherapy [COMBINED group] and 43 with chemotherapy alone [CHEMO group], 11 were managed with observation). Ninety-six percent of patients responded (RT 98%, COMBINED 100%, CHEMO 91%, p=0.179), and 37% (40/107) of patients in complete response relapsed (RT 42%, COMBINED 27%, CHEMO 41%, p=0.371). Progression-free survival (PFS) and overall survival (OS) probabilities at 10 years were similar in RT, COMBINED and CHEMO patients (PFS 41%, 61% and 39% [p=0.167], and OS 77%, 81% and 72% [p=0.821], respectively), while the COMBINED group showed a trend to better time-to-progression (TTP 43%, 72% and 47% [p=0.055]). On multivariate analysis, only a FLIPI score ≥2 showed a trend to influence PFS (HR 2.1 [95% confidence interval 0.9-4.6], p=0.067), and OS (HR 2.4 [0.9-6.5], p=0.084), while patients treated with radiotherapy plus chemotherapy (COMBINED group) showed a significantly better TTP compared with those receiving only RT (HR 0.3 [0.1-0.8], p=0.024). In our study no benefit was observed in survival with the use of systemic therapy compared with local radiotherapy. PMID:26122511

  6. Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma.

    PubMed

    Klyuchnikov, E; Bacher, U; Woo Ahn, K; Carreras, J; Kröger, N M; Hari, P N; Ku, G H; Ayala, E; Chen, A I; Chen, Y-B; Cohen, J B; Freytes, C O; Gale, R P; Kamble, R T; Kharfan-Dabaja, M A; Lazarus, H M; Martino, R; Mussetti, A; Savani, B N; Schouten, H C; Usmani, S Z; Wiernik, P H; Wirk, B; Smith, S M; Sureda, A; Hamadani, M

    2016-01-01

    Grade 3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade 3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs autologous hematopoietic cell transplantation (auto-HCT) in the rituximab era. A total of 197 patients undergoing first reduced-intensity conditioning (RIC) allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naive patients were excluded. Allo-HCT recipients were younger, more heavily pretreated and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, PFS and overall survival (OS) for auto-HCT vs allo-HCT groups were 4% vs 27% (P<0.001), 61% vs 20% (P<0.001), 36% vs 51% (P=0.07) and 59% vs 54% (P=0.7), respectively. On multivariate analysis, auto-HCT was associated with reduced risk of NRM (relative risk (RR)=0.20; P=0.001). Within the first 11 months post HCT, auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11 months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; P=0.003) and inferior PFS (RR=3.2; P=0.005). In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.42; P=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; P=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors. PMID:26437062

  7. Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma

    PubMed Central

    Klyuchnikov, Evgeny; Bacher, Ulrike; Ahn, Kwang Woo; Carreras, Jeanette; Kröger, Nicolaus M.; Hari, Parameswaran N.; Ku, Grace H.; Ayala, Ernesto; Chen, Andy I.; Chen, Yi-Bin; Cohen, Jonathon B.; Freytes, César O.; Gale, Robert Peter; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed A.; Lazarus, Hillard M.; Martino, Rodrigo; Mussetti, Alberto; Savani, Bipin N.; Schouten, Harry C.; Usmani, Saad Z.; Wiernik, Peter H.; Wirk, Baldeep; Smith, Sonali M.; Sureda, Anna; Hamadani, Mehdi

    2015-01-01

    Grade-3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade-3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. A total of 197 patients undergoing first RIC allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naïve patients were excluded. Allo-HCT recipients were younger; more heavily pretreated, and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS) and overall survival (OS) for auto-HCT vs. allo-HCT groups were 4% vs. 27% (p<0.001); 61% vs. 20% (p<0.001); 36% vs. 51% (p=0.07) and 59% vs. 54% (p=0.7), respectively. On multivariate analysis auto-HCT was associated with reduced risk of NRM (RR=0.20; p=0.001). Within the first 11months post-HCT auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; p=0.003) and inferior PFS (RR=3.2; p=0.005). In the first 24 months post-HCT, auto-HCT was associated with improved OS (RR=0.42; p=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; p=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors. PMID:26437062

  8. Lectin binding to surface Ig variable regions provides a universal persistent activating signal for follicular lymphoma cells.

    PubMed

    Linley, Adam; Krysov, Sergey; Ponzoni, Maurilio; Johnson, Peter W; Packham, Graham; Stevenson, Freda K

    2015-10-15

    The vast majority of cases of follicular lymphoma (FL), but not normal B cells, acquire N-glycosylation sites in the immunoglobulin variable regions during somatic hypermutation. Glycans added to sites are unusual in terminating at high mannoses. We showed previously that the C-type lectins, dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) and mannose receptor, bound to FL surface immunoglobulin (sIg), generating an intracellular Ca(2+) flux. We have now mapped further intracellular pathways activated by DC-SIGN in a range of primary FL cells with detection of phosphorylated ERK1/2, AKT, and PLCγ2. The SYK inhibitor (tamatinib) or the BTK inhibitor (ibrutinib) each blocked phosphorylation. Activation by DC-SIGN occurred in both IgM(+) and IgG(+) cases and led to upregulation of MYC expression, with detection in vivo observed in lymph nodes. Unlike cells of chronic lymphocytic leukemia, FL cells expressed relatively high levels of sIg, unchanged by long-term incubation in vitro, indicating no antigen-mediated downregulation in vivo. In contrast, expression of CXCR4 increased in vitro. Engagement of sIg in FL cells or normal B cells by anti-Ig led to endocytosis in vitro as expected, but DC-SIGN, even when cross-linked, did not lead to significant endocytosis of sIg. These findings indicate that lectin binding generates signals via sIg but does not mediate endocytosis, potentially maintaining a supportive antigen-independent signal in vivo. Location of DC-SIGN in FL tissue revealed high levels in sinusoidlike structures and in some colocalized mononuclear cells, suggesting a role for lectin-expressing cells at this site. PMID:26194765

  9. Prediction of high risk for death in patients with follicular lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in first-line chemotherapy.

    PubMed

    Murakami, Satsuki; Kato, Harumi; Higuchi, Yusuke; Yamamoto, Kazuhito; Yamamoto, Hideyuki; Saito, Toko; Taji, Hirofumi; Yatabe, Yasushi; Nakamura, Shigeo; Kinoshita, Tomohiro

    2016-08-01

    Risk stratification of patients with relapsed and refractory follicular lymphoma (FL) remains challenging. Recently, much attention has been paid to the impact of early progression of disease within 2 years of diagnosis (early POD) on subsequent survival. The aim of this study was to clarify the clinical features and prognostic factors of patients with FL who experienced early POD. Data were available for 94 patients diagnosed with FL (clinical stage II-IV) who had received immunochemotherapy. Early POD was seen in 20 % of these patients. The Cox proportional hazards model showed worse overall survival (OS) in the patients with early POD compared with those without early POD (5-year OS rates 48 % vs. 96 %, P < 0.0001). In multivariate analysis, early POD (P = 0.003) and poor performance status (P = 0.006) remained a significant factor for subsequent OS. In Follicular Lymphoma International Prognostic Index (FLIPI)- and Follicular Lymphoma International Prognostic Index-2 (FLIPI2)-adjusted Cox regression analysis, early POD was associated with markedly reduced OS with a hazard ratio of 11.2 [95 % confidence interval (CI) 3.13-40.3, P < 0.001] and 13.5 (95 % CI 3.22-56.3, P < 0.003), respectively. Among patients who had early POD, high levels of serum lactate dehydrogenase (LDH) both at the time of initial diagnosis and first progression could be associated with worse survival (2-year OS rates 33 vs. 92 %, P < 0.0001). Evaluation of LDH levels at the time of initial diagnosis and first progression may be important to define patients who were associated with worse prognosis. Risk stratification of patients with early POD could lead to improved clinical outcomes for FL patients. Further research is needed to investigate its value for decision making. PMID:27220639

  10. Vaccine Therapy With or Without Cryosurgery in Treating Patients With Residual, Relapsed, or Refractory B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-04-19

    Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Adult Diffuse Mixed Cell Lymphoma; Adult Diffuse Small Cleaved Cell Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; Adult Immunoblastic Large Cell Lymphoma; Adult Lymphoblastic Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia With Nodal Disease

  11. Study of Alisertib (MLN8237) in Adults With Aggressive Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-11-15

    Diffuse Large B-cell Lymphoma; Mantle Cell Lymphoma; Burkitt's Lymphoma; Precursor B-lymphoblastic Leukemia/Lymphoma; T-cell Lymphoma, Excluding Primary Cutaneous T-cell Lymphoma; Transformed Follicular Lymphoma With ≥ 50% Diffuse Large Cell Component

  12. Ixazomib Citrate and Rituximab in Treating Patients With Indolent B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-06-01

    Chronic Lymphocytic Leukemia; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

  13. Panobinostat in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-04-18

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  14. Genetically Engineered Lymphocyte Therapy in Treating Patients With Lymphoma That is Resistant or Refractory to Chemotherapy

    ClinicalTrials.gov

    2015-09-27

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  15. Radioimmunotherapy in relapsed follicular lymphoma previously treated by autologous bone marrow transplant: a report of eight new cases and literature review.

    PubMed

    Peyrade, Frederic; Triby, Caroline; Slama, Bohane; Fontana, Xavier; Gressin, Remy; Broglia, Jean-Marc; Lepeu, Gerard; Carrier, Patricia; Peyrottes, Isabelle; Darcourt, Jacques; Bondiau, Pierre-Yves; Thyss, Antoine

    2008-09-01

    Multicenter, retrospective study of standard-dose RIT in eight heavily pre-treated patients with CD20-positive follicular lymphoma who had relapsed after previous autologous bone marrow transplantation (ABMT). Patients underwent nine courses of (90)Y-ibritumomab tiuxetan (0.3 or 0.4 mCi/kg body weight). Responses included five CR, two PR, one SD and one PD. Median DFS was 12 months with median follow-up of 17 months and 1-year OS was 83% (7/8 patients). Grade 4 thrombocytopenia occurred in 7/9 treatments, with no episodes of bleeding, and only two patients received a platelet transfusion. One patient, who had 20% bone marrow involvement at the time of relapse diagnosis, presented with Grade 4 thrombocytopenia and Grade 4 neutropenia and died of septic shock 6 months after RIT. One other case of Grade 4 neutropenia, without a serious infectious syndrome, was observed. Standard-dose RIT seems feasible and potentially effective after ABMT in correctly selected patients with follicular lymphoma. PMID:18661403

  16. Clinical outcome of patients with follicular lymphoma receiving chemoimmunotherapy in the PRIMA study is not affected by FCGR3A and FCGR2A polymorphisms.

    PubMed

    Ghesquières, Hervé; Cartron, Guillaume; Seymour, John Francis; Delfau-Larue, Marie-Hélène; Offner, Fritz; Soubeyran, Pierre; Perrot, Aurore; Brice, Pauline; Bouabdallah, Réda; Sonet, Anne; Dupuis, Jehan; Casasnovas, Olivier; Catalano, John Vincent; Delmer, Alain; Jardin, Fabrice; Verney, Aurélie; Dartigues, Peggy; Salles, Gilles

    2012-09-27

    In patients with follicular lymphoma treated with single-agent rituximab, single nucleotide polymorphisms in the FCGR3A gene are known to influence response and progression-free survival. The prognostic role of FCGR3A and FCGR2A polymorphisms in patients with follicular lymphoma treated with rituximab and chemotherapy combination remains controversial and has not been evaluated in the context of rituximab maintenance. FCGR3A and FCGR2A single nucleotide polymorphisms were evaluated in, respectively, 460 and 455 patients treated in the PRIMA study to investigate whether these were associated with response rate and patient outcome after rituximab chemotherapy induction and 2-year rituximab maintenance. In this representative patient cohort, complete and unconfirmed complete responses after rituximab chemotherapy were observed in 65%, 67%, 66% (P = .86) and 60%, 72%, 66% (P = .21) of FCGR3A VV, VF, FF and FCGR2A HH, HR, RR carriers, respectively. After 2 years of rituximab maintenance (or observation), response rates did not differ among the different genotypes. Progression-free survival measured from either treatment initiation or randomization to observation or maintenance was not influenced by these polymorphisms. These data indicate that FCGR3A and FCGR2A polymorphisms do not influence response rate and outcome when rituximab is combined with chemotherapy or used as maintenance treatment. The PRIMA study is registered at www.clinicaltrials.gov as NCT00140582. PMID:22885164

  17. Rituximab maintenance after autologous stem cell transplantation prolongs response duration in non-naive rituximab follicular lymphoma patients: a single institution experience.

    PubMed

    Bourcier, J; Gastinne, T; Leux, C; Moreau, A; Bossard, C; Mahé, B; Blin, N; Dubruille, V; Touzeau, C; Voldoire, M; Guillaume, T; Peterlin, P; Gallas, P; Garnier, A; Maisonneuve, H; Moreau, P; Juge-Morineau, N; Jardel, H; Chevallier, P; Moreau, P; Le Gouill, S

    2016-08-01

    We retrospectively evaluated the role of rituximab (R) in maintenance treatment after autologous stem cell transplantation performed in patients with relapsed follicular lymphoma. We compared the outcome of 67 follicular lymphoma (FL) patients according to the use of rituximab maintenance (RM) or not. All patients received rituximab plus chemotherapy before autologous stem-cell transplantation (ASCT). Patients received median of two lines of prior therapy. The RM schedule was one injection of rituximab every 3 months for 2 years. Median follow-up is 4.6 years. The 3-year progression-free survival (PFS) after ASCT was 86 % with RM vs. 46 % without (p = 0.0045). Median is not reached in the RM arm vs. 31 months in non-RM arm. The 3-year OS was 96 % with RM vs. 78 % without (p = 0.059). The present monocentric study shows that 2 years of RM after ASCT significantly increases response duration for non-naive rituximab relapsed FL patients compared with observation. PMID:27297970

  18. Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8+ T cells

    PubMed Central

    Liu, Xiao; Venkataraman, Girish; Lin, Jiaying; Kiyotani, Kazuma; Smith, Sonali; Montoya, Magdeline; Nakamura, Yusuke; Kline, Justin

    2015-01-01

    The immune microenvironment in follicular lymphoma (FL) plays an important role in controlling disease characteristics. To characterize the T-cell receptor (TCR) repertoire in follicular lymphoma (FL) tissues, we applied a next-generation sequencing platform and deeply sequenced TCR cDNAs of T-cell subset populations present in pretreatment FL biopsy specimens. T regulatory cell (Treg) TCRs in FL tissues revealed a highly oligoclonal expansion compared to those in control lymph nodes. Furthermore, an inverse correlation was observed between the diversity of Treg and CD8+ TCRs in FL specimens. Interestingly, a tumor from an FL patient, who had not received anticancer treatment for more than 10 years, was found to have missense mutations in the peptide-binding domain of both human leukocyte antigen (HLA) class I and II molecules, which might have presented tumor-specific antigens and enhanced host immune responses. Although further verification is required, our data suggest that the T-cell repertoire is skewed and restricted in FL and support the evolving understanding of the microenvironment in this disease. PMID:26155390

  19. Cilengitide (EMD 121974) in Treating Patients With Advanced Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-01-23

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2

  20. Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene.

    PubMed

    Schmidt, Janine; Gong, Shunyou; Marafioti, Teresa; Mankel, Barbara; Gonzalez-Farre, Blanca; Balagué, Olga; Mozos, Ana; Cabeçadas, José; van der Walt, Jon; Hoehn, Daniela; Rosenwald, Andreas; Ott, German; Dojcinov, Stefan; Egan, Caoimhe; Nadeu, Ferran; Ramis-Zaldívar, Joan Enric; Clot, Guillem; Bárcena, Carmen; Pérez-Alonso, Vanesa; Endris, Volker; Penzel, Roland; Lome-Maldonado, Carmen; Bonzheim, Irina; Fend, Falko; Campo, Elias; Jaffe, Elaine S; Salaverria, Itziar; Quintanilla-Martinez, Leticia

    2016-08-25

    Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14:18)(-) FL in adults were investigated. Morphologically, PTFL cases had follicular growth pattern without diffuse areas and characteristic immunophenotype. All cases showed monoclonal immunoglobulin (IG) rearrangement. PTFL displays low genomic complexity when compared with t(14;18)(-) FL (mean, 0.77 vs 9 copy number alterations per case; P <001). Both groups presented 1p36 alterations including TNFRSF14, but copy-number neutral loss of heterozygosity (CNN-LOH) of this locus was more frequently observed in PTFL (40% vs 9%; P =075). TNFRSF14 was the most frequently affected gene in PTFL (21 mutations and 2 deletions), identified in 54% of cases, followed by KMT2D mutations in 16%. Other histone-modifying genes were rarely affected. In contrast, t(14;18)(-) FL displayed a mutational profile similar to t(14;18)(+) FL. In 8 PTFL cases (19%), no genetic alterations were identified beyond IG monoclonal rearrangement. The genetic landscape of PTFL suggests that TNFRSF14 mutations accompanied by CNN-LOH of the 1p36 locus in over 70% of mutated cases, as additional selection mechanism, might play a key role in the pathogenesis of this disease. The genetic profiles of PTFL and t(14;18)(-) FL in adults indicate that these are two different disorders. PMID:27257180

  1. Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)

    ClinicalTrials.gov

    2016-07-04

    Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom Macroglobulinemia

  2. Rituximab Extended Schedule or Re-Treatment Trial for Low–Tumor Burden Follicular Lymphoma: Eastern Cooperative Oncology Group Protocol E4402

    PubMed Central

    Kahl, Brad S.; Hong, Fangxin; Williams, Michael E.; Gascoyne, Randy D.; Wagner, Lynne I.; Krauss, John C.; Habermann, Thomas M.; Swinnen, Lode J.; Schuster, Stephen J.; Peterson, Christopher G.; Sborov, Mark D.; Martin, S. Eric; Weiss, Matthias; Ehmann, W. Christopher; Horning, Sandra J.

    2014-01-01

    Purpose In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Patients and Methods Eligible patients with previously untreated low–tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). Results A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. Conclusion In low–tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy. PMID:25154829

  3. Chlorambucil-rituximab as first-line therapy in patients affected by follicular non-Hodgkin's lymphoma: a retrospective single-centre study.

    PubMed

    Martinelli, Giovanni; Montoro, Juan; Vanazzi, Anna; Andreola, Giovanna; Liptrott, Sarah; Radice, Davide; Negri, Mara; Preda, Lorenzo; Pruneri, Giancarlo; Laszlo, Daniele

    2015-12-01

    Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, has been shown to be active in newly diagnosed and relapsed patients with follicular lymphoma (FL), both as monotherapy and in combination with chemotherapy. Many studies suggest that the prognosis of patients with FL may improve when it is used in combination with chemotherapy. Despite these advances, the disease remains essentially incurable with standard therapy, and novel approaches to treatment are needed because optimal therapy is not defined. The combination of chlorambucil-rituximab is one of several standard treatment options for FL. Here, we considered data arising from 75 patients with newly diagnosed FL at the European Institute of Oncology treated with the combination of rituximab plus chlorambucil. The aim of this study was to evaluate the efficacy and safety of chlorambucil and rituximab, delivered 6 mg/m(2) /day orally for 6 weeks and 375 mg/m(2) in a standard 4-weekly schedule, respectively. Patients responding to the induction therapy received a prolonged therapy with four additional cycles of chlorambucil plus rituximab. Seventy-one patients (94.6%) completed the treatment; four patients discontinued treatment because of grade 3-4 hematological toxicity. The overall response rate was 97.3% including 74.7% of complete responses. Only two patients had a stable disease at revaluation after treatment. With a median follow-up of 57 months, 72 patients (96%) are alive. Median event-free survival (EFS) and median overall survival (OS) were not reached; 5-year OS rate was 98.4%. The 5-year EFS was 71.3%. By univariate and multivariate analyses, elevated beta-2 microglobulin levels and partial responses to therapy were correlated with worse EFS. These results suggest that the combination of chlorambucil and rituximab is an active and safe regimen in patients with newly diagnosed FL, principally in those with low tumour burden and favourable prognostic factors. PMID

  4. Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-02-16

    Follicular Lymphoma; Marginal Zone Lymphoma; Mantle Cell Lymphoma; Small Lymphocytic Lymphoma; Lymphoplasmacytic Lymphoma; Low Grade B-cell Lymphoma, Not Otherwise Specified; Diffuse Large B-cell Lymphoma; Peripheral T-cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Anaplastic Large-cell Lymphoma

  5. Sorafenib in Treating Patients With Metastatic or Unresectable Solid Tumors, Multiple Myeloma, or Non-Hodgkin's Lymphoma With or Without Impaired Liver or Kidney Function

    ClinicalTrials.gov

    2013-01-04

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  6. Radiolabeled Monoclonal Antibody Plus Rituximab With and Without Filgrastim and Interleukin-11 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2015-11-04

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  7. Interleukin-2 or Observation Following Radiation Therapy, Combination Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With Recurrent Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-02-27

    Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma

  8. Genetically Engineered Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Indolent B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2014-08-04

    B-cell Chronic Lymphocytic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  9. Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

    ClinicalTrials.gov

    2016-06-15

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

  10. Bryostatin 1 Plus Vincristine in Treating Patients With Progressive or Relapsed Non-Hodgkin's Lymphoma After Bone Marrow or Stem Cell Transplantation

    ClinicalTrials.gov

    2013-01-09

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

  11. Ixabepilone in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2014-05-07

    Anaplastic Large Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma

  12. Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-04-18

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  13. Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas

    ClinicalTrials.gov

    2016-08-24

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Chronic Lymphocytic

  14. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Lymphoma or Leukemia

    ClinicalTrials.gov

    2013-01-31

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  15. Vorinostat and Combination Chemotherapy With Rituximab in Treating Patients With HIV-Related Diffuse Large B-Cell Non-Hodgkin Lymphoma or Other Aggressive B-Cell Lymphomas

    ClinicalTrials.gov

    2016-09-08

    AIDS-Related Diffuse Large Cell Lymphoma; AIDS-Related Plasmablastic Lymphoma; AIDS-Related Primary Effusion Lymphoma; Grade 3b Follicular Lymphoma; HIV Infection; Plasmablastic Lymphoma; Primary Effusion Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  16. Validation of various adaptive threshold methods of segmentation applied to follicular lymphoma digital images stained with 3,3’-Diaminobenzidine&Haematoxylin

    PubMed Central

    2013-01-01

    The comparative study of the results of various segmentation methods for the digital images of the follicular lymphoma cancer tissue section is described in this paper. The sensitivity and specificity and some other parameters of the following adaptive threshold methods of segmentation: the Niblack method, the Sauvola method, the White method, the Bernsen method, the Yasuda method and the Palumbo method, are calculated. Methods are applied to three types of images constructed by extraction of the brown colour information from the artificial images synthesized based on counterpart experimentally captured images. This paper presents usefulness of the microscopic image synthesis method in evaluation as well as comparison of the image processing results. The results of thoughtful analysis of broad range of adaptive threshold methods applied to: (1) the blue channel of RGB, (2) the brown colour extracted by deconvolution and (3) the ’brown component’ extracted from RGB allows to select some pairs: method and type of image for which this method is most efficient considering various criteria e.g. accuracy and precision in area detection or accuracy in number of objects detection and so on. The comparison shows that the White, the Bernsen and the Sauvola methods results are better than the results of the rest of the methods for all types of monochromatic images. All three methods segments the immunopositive nuclei with the mean accuracy of 0.9952, 0.9942 and 0.9944 respectively, when treated totally. However the best results are achieved for monochromatic image in which intensity shows brown colour map constructed by colour deconvolution algorithm. The specificity in the cases of the Bernsen and the White methods is 1 and sensitivities are: 0.74 for White and 0.91 for Bernsen methods while the Sauvola method achieves sensitivity value of 0.74 and the specificity value of 0.99. According to Bland-Altman plot the Sauvola method selected objects are segmented without

  17. The potential benefit of allogeneic over autologous transplantation in patients with very early relapsed and refractory follicular lymphoma with prior remission duration of ≤12 months.

    PubMed

    Lunning, Matthew A; Migliacci, Jocelyn C; Hilden, Patrick; Devlin, Sean M; Castro-Malaspina, Hugo; Giralt, Sergio; Perales, Miguel-Angel; Zelenetz, Andrew D; Moskowitz, Craig H; Sauter, Craig S

    2016-04-01

    Early relapsed or refractory follicular lymphoma (FL) warrants consolidation with transplantation, though graft source modality remains controversial. We analysed the outcomes of 44 patients transplanted with either autologous or allogeneic graft sources in the post-rituximab era. No difference in event-free (EFS) or overall survival (OS) was observed between allogeneic (81% and 81%) and autologous transplantation (64% and 70%) at 3 years. There was a significant difference in EFS between allogeneic and autologous transplantation patients with previous remission duration of ≤12 months (80% and 42% at 3 years, P < 0·015). Very early relapsed FL may warrant consideration of allogeneic over autologous transplantation in the appropriate setting. PMID:26847389

  18. 17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-01-24

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenstr

  19. An Open-Label, Multicenter, Phase 1/2 Study of E7438 (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas

    ClinicalTrials.gov

    2016-09-01

    B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

  20. Elimination of bcl-2-IgH-positive follicular lymphoma cells from blood transplants with high recovery of hematopoietic progenitors by the miltenyi CD34+ cell sorting system.

    PubMed

    Di Nicola, M; Siena, S; Corradini, P; Bregni, M; Milanesi, M; Magni, M; Ruffini, P A; Ravagnani, F; Tarella, C; Gianni, A M

    1996-12-01

    Contamination of autologous blood cell transplants with cells of follicular non-Hodgkin's lymphoma (F-NHL) may contribute to relapse of the malignancy after potentially curative high doses of chemotherapy and radiotherapy. In an attempt to circumvent this limitation, we have evaluated various techniques of selection of CD34+ cells to eliminate malignant cells from blood cell transplants of five patients with F-NHL undergoing high-dose sequential therapy. The contamination of F-NHL cells was evaluated using a nested PCR assay for the detection of bcl-2-IgH rearrangement with a sensitivity of one F-NHL cell in 10(5) normal cells. In two experiments with blood cell transplant fractions of 0.5 x 10(9) nucleated cells, negative selection of CD34+ cells by removal of B cells and other mature cells that naturally adhere to nylon wool fibers decreased the number of CD19+ B cells detectable by flow cytometry but failed to eliminate bcl-2-IgH-positive F-NHL cells detectable by PCR. In contrast, positive selection of CD34+ cells by the Miltenyi MiniMACS high gradient magnetic cell sorting system in five separate experiments resulted in: (1) the elimination of F-NHL cells in four out of five cases as detected both flow cytometry and bclk-2-IgH PCR; (2) a highly purified population of hematopoietic progenitors comprising 90.8% +/- 2.3% CD34+ cells; and (3) the recovery of 77.9% +/- 3.2% CD34+ cells. These favorable results were confirmed on a large-scale with a blood cell transplant comprising 5.8 x 10(9) nucleated cells in which positive selection of CD34+ cells by the Miltenyi SuperMACS system resulted in: (1) the elimination of F-NHL cells as detected both by flow cytometry and bcl-2-IgH PCR; (2) a highly purified population of hematopoietic progenitors comprising 94.6% CD34+ cells; and (3) the recovery of 62.7% CD34+ cells. These results, attained with the newly available Super MACS system, compare favorable with previous techniques because they show the feasibility of

  1. Interleukin-12 in Treating Patients With Previously Treated Non-Hodgkin's Lymphoma or Hodgkin's Disease

    ClinicalTrials.gov

    2015-04-14

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  2. [Specifics of histopathological and genetical diagnosis and classification of lymphomas in children and adolescents].

    PubMed

    Klapper, W; Oschlies, I

    2012-04-01

    Malignant lymphoma along with leukemias account for nearly half of all malignancies arising in childhood and adolescence. The correct tissue-based histopathological diagnosis of lymphomas results from a close interdisciplinary exchange between pediatric oncologists and hematopathologists. We describe here relevant features of lymphoma subtypes arising in the young age group, Burkitt lymphoma, precursor/lymphoblastic lymphomas, anaplastic large cell lymphoma and diffuse large B-cell lymphoma as well as primary mediastinal B-cell lymphoma and the rare pediatric follicular lymphomas. Special focus is put on specific diagnostic difficulties as well as new insights into biological features of pediatric lymphomas in comparison with their adult counterpart. In addition the relevance of newly defined lymphoma entities of the WHO-classification 2008, e.g. greyzone lymphomas, will be discussed for the young age group. PMID:22513791

  3. Radiotherapy Compared to Other Strategies in the Treatment of Stage I/II Follicular Lymphoma: A Study of 404 Patients with a Median Follow-Up of 15 Years

    PubMed Central

    Barzenje, Dlawer Abdulla; Kolstad, Arne; Holte, Harald

    2015-01-01

    Purpose To investigate outcome for patients with follicular lymphoma (FL) stage I-II treated at a population-based referral institution with a median follow-up of 15 years. Overall and cause-specific survival was compared to that of a sex, age and residency matched individuals from normal population. Material and Methods 404 patients with early stage FL treated between 1980 and 2005 were retrospectively analyzed. Two of three patients had stage I disease. Based on clinical characteristics, first line treatments were radiotherapy (RT) (48% of patients), chemotherapy (CT) (16%), combined chemo-and radiotherapy (CRT) (16%) or observation (OBS) (15%). Survival was modeled with Kaplan-Meier methodology. Multivariate analyses were performed with the Cox model. Results Fifteen years overall survival (OS), progression free survival (PFS) and time to next treatment (TNT) were 50% (95% confidence interval [CI]: 45–55), 42% (95% CI: 36–47) and 48% (95% CI, 42–54), respectively. For patients treated with RT 97% achieved a complete remission, and 15 year OS, PFS and TNT were 57% (95% CI, 50–64), 46% (95% CI, 39–54) and 49% (95% CI, 42–57), respectively. Relapse rate after RT and CRT was 49% and 36%, respectively. Only 2% of patients who received RT or CRT relapsed inside the radiation field and 5% had isolated near-field relapse. No statistical differences were found between treatment groups regarding death from cardiovascular disease or incidence of second cancer. Compared to a matched normal population, non-lymphoma cancer mortality was higher among patients given RT, hazard ratio 1.66 (95% CI: 1.14–2.42; P<0.01). Compared to other treatment modalities, patients selected for observation without treatment did not have inferior outcome. Conclusions A differentiated treatment strategy in early stage FL results in long term survival for the majority of patients. OBS is a valid initial choice for selected patients without lymphoma-related symptoms. PMID:26147646

  4. Genetically Engineered Lymphocyte Therapy in Treating Patients With B-Cell Leukemia or Lymphoma That is Resistant or Refractory to Chemotherapy

    ClinicalTrials.gov

    2015-07-31

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  5. High resolution copy number analysis of IRF4 translocation-positive diffuse large B-cell and follicular lymphomas.

    PubMed

    Salaverria, Itziar; Martin-Guerrero, Idoia; Burkhardt, Birgit; Kreuz, Markus; Zenz, Thorsten; Oschlies, Ilske; Arnold, Norbert; Baudis, Michael; Bens, Susanne; García-Orad, Africa; Lisfeld, Jasmin; Schwaenen, Carsten; Szczepanowski, Monika; Wessendorf, Swen; Pfreundschuh, Michael; Trümper, Lorenz; Klapper, Wolfram; Siebert, Reiner

    2013-02-01

    Translocations affecting chromosome subband 6p25.3 containing the IRF4 gene have been recently described as characteristic alterations in a molecularly distinct subset of germinal center B-cell-derived lymphomas. Secondary changes have yet only been described in few of these lymphomas. Here, we performed array-comparative genomic hybridization and molecular inversion probe microarray analyses on DNA from 12 formalin-fixed paraffin-embedded and two fresh-frozen IRF4 translocation-positive lymphomas, which together with the previously published data on nine cases allowed the extension of copy number analyses to a total of 23 of these lymphomas. All except one case carried chromosomal imbalances, most frequently gains in Xq28, 11q22.3-qter, and 7q32.1-qter and losses in 6q13-16.1, 15q14-22.31, and 17p. No recurrent copy-neutral losses of heterozygosity were observed. TP53 point mutations were detected in three of six cases with loss of 17p. Overall this study unravels a recurrent pattern of secondary genetic alterations in IRF4 translocation-positive lymphomas. PMID:23073988

  6. FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2014-01-06

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell

  7. Panobinostat and Everolimus in Treating Patients With Recurrent Multiple Myeloma, Non-Hodgkin Lymphoma, or Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-04-19

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; Waldenström Macroglobulinemia

  8. Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group.

    PubMed

    Provencio, Mariano; Cruz Mora, Miguel Á; Gómez-Codina, José; Quero Blanco, Cristina; Llanos, Marta; García-Arroyo, Francisco R; de la Cruz, Luis; Gumá Padró, Josep; Delgado Pérez, Juan R; Sánchez, Antonio; Alvarez Cabellos, Ruth; Rueda, Antonio

    2014-01-01

    Relapse is the main cause of therapeutic failure in follicular lymphoma (FL). We set out to evaluate the role of consolidation with Yttrium-90 ibritumomab tiuxetan in patients with intermediate- and high-risk FL after four cycles of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and two cycles of CHOP. Thirty patients were included. The overall response rate after consolidation therapy was 93%. Of the 18 patients who presented with a partial response after induction treatment, 11 had a complete response after consolidation treatment. The complete clinical response rate was 76.6%. The most important grade 3-4 toxicity was hematological, with 46% thrombopenia and 56% neutropenia. With a median follow-up of 26 months, the means for progression-free survival and overall survival were not reached. Our data support consolidation with Yttrium-90 ibritumomab tiuxetan as an effective treatment, which provides long progression-free and overall survival, in first line after a response to induction treatment in patients with intermediate- and high-risk FL. PMID:23573825

  9. Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-06-03

    Anaplastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  10. Radiation therapy for orbital lymphoma

    SciTech Connect

    Zhou Ping . E-mail: pzhou@partners.org; Ng, Andrea K.; Silver, Barbara; Li Sigui; Hua Ling; Mauch, Peter M.

    2005-11-01

    Purpose: To describe radiation techniques and evaluate outcomes for orbital lymphoma. Methods and Materials: Forty-six patients (and 62 eyes) with orbital lymphoma treated with radiotherapy between 1987 and 2003 were included. The majority had mucosa-associated lymphoid tissue (48%) or follicular (30%) lymphoma. Seventeen patients had prior lymphoma at other sites, and 29 had primary orbital lymphoma. Median follow-up was 46 months. Results: The median dose was 30.6 Gy; one-third received <30 Gy. Electrons were used in 9 eyes with disease confined to the conjunctiva or eyelid, and photons in 53 eyes with involvement of intraorbital tissues to cover entire orbit. Local control rate was 98% for all patients and 100% for those with indolent lymphoma. Three of the 26 patients with localized primary lymphoma failed distantly, resulting in a 5-year freedom-from-distant-relapse rate of 89%. The 5-year disease-specific and overall survival rates were 95% and 88%, respectively. Late toxicity was mainly cataract formation in patients who received radiation without lens block. Conclusions A dose of 30 Gy is sufficient for indolent orbital lymphoma. Distant relapse rate in patients with localized orbital lymphoma was lower than that reported for low-grade lymphoma presenting in other sites. Orbital radiotherapy can be used for salvage of recurrent indolent lymphoma.

  11. Detection and quantification of MBR/JH2 t(14;18) BCL-2 gene rearrangement in follicular lymphoma using a combined real-time polymerase chain reaction assay.

    PubMed

    Csernák, Erzsébet; Tóth, Erika; Melegh, Zsombor; Schneider, Tamás; Rosta, András; Szentirmay, Zoltán

    2006-06-01

    We report our experience with a new real-time polymerase chain reaction (PCR) assay applicable for simultaneous quantification and characterization of MBR/JH translocation in follicular lymphomas. This technique, which combines amplification with the FRET probe with SYBR Green I melting curve analysis, allows efficient detection of tumor cells in bone marrow or peripheral blood and their comparison with the original neoplastic clone. PMID:16704964

  12. Rituximab and Interleukin-12 in Treating Patients With B-Cell Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-08-23

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

  13. Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-08-11

    Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom's Macroglobulinaemia; Lymphoma,T-cell Cutaneous; Lymphoma, T-Cell, Peripheral

  14. Clinical and Pathologic Studies in Non-Hodgkin's Lymphoma Patients Receiving Antibody Treatment

    ClinicalTrials.gov

    2011-05-31

    Lymphoma, Non-Hodgkin; Lymphomas: Non-Hodgkin; Lymphomas: Non-Hodgkin Cutaneous Lymphoma; Lymphomas: Non-Hodgkin Diffuse Large B-Cell; Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell; Lymphomas: Non-Hodgkin Mantle Cell; Lymphomas: Non-Hodgkin Marginal Zone; Lymphomas: Non-Hodgkin Peripheral T-Cell; Lymphomas: Non-Hodgkin Waldenstr Macroglobulinemia

  15. Oblimersen and Gemcitabine in Treating Patients With Advanced Solid Tumor or Lymphoma

    ClinicalTrials.gov

    2013-01-24

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

  16. Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas

    ClinicalTrials.gov

    2015-04-28

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Epstein-Barr Virus Infection; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis

  17. Long-term efficacy of (90)Y ibritumomab tiuxetan therapy in follicular non-Hodgkin lymphoma and health-related quality of life.

    PubMed

    Andrade-Campos, Marcio Miguel; Montes-Limón, Anel E; Soro-Alcubierre, Gloria; Grasa, José María; Lopez-Gómez, Luis; Baringo, Teresa; Giraldo, Pilar

    2014-12-01

    The aim of this study was to analyze the outcomes of 37 follicular lymphoma (FL) patients treated with (90)ytrium ibritumomab tiuxetan (90Y-IT), outside of clinical trial, according to protocol ISCRTN36210045, after ≥5 years follow-up to February 2014. Health-related quality of life (HRQoL) was evaluated with the SF-36, Spanish version, and compared with the general population of Spain. Patients had a mean age of 61.9 (range, 30-85) years and included 18 males. FLIPI, low: 25 (67.6 %), intermedium 9 (24.3 %), and low 3 (8.1 %). Previous therapy schedules >2: 48.6 % The median follow-up was 66 months, mean Time to Relapse (TTR) 71.3 months (58.8-83.8) median not reached. Thirty-four patients achieved complete response (91.8 %), and three no response. Mean overall survival: 82.3 months (71.6-92.9). Four patients presented with concomitant tumors (colon, breast, prostate, lung) after radioimmunotherapy, and three developed second primary neoplasms (esophagus, renal, and myelodysplastic syndrome in a relapsed patient who received fludarabine). Four of 10 deaths were related to lymphoma progression. Hematological toxicities were mild and easily managed. No patients required hospitalization. Negative scores were obtained in the physical and emotional roles items; however, the perception of general health and vitality were better than in the general population, with the best outcomes in non-relapsed patients. Radioimmunotherapy with 90Y-IT was safe and effective as long-term therapy in patients with FL. Early use of radioimmunotherapy could offer good, sustained responses with low toxicity over the long term and acceptable HRQoL. PMID:24985089

  18. Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

    ClinicalTrials.gov

    2016-06-02

    Recurrent Chronic Lymphocytic Leukemia; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Richter Syndrome; Waldenstrom Macroglobulinemia

  19. Iodine I 131 Tositumomab, Etoposide and Cyclophosphamide Followed by Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2014-08-04

    Anaplastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  20. Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma

    ClinicalTrials.gov

    2016-08-22

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  1. Localization of collagen modifying enzymes on fibroblastic reticular cells and follicular dendritic cells in non-neoplastic and neoplastic lymphoid tissues.

    PubMed

    Ohe, Rintaro; Aung, Naing Ye; Meng, Hongxue; Kabasawa, Takanobu; Suto, Aya; Tamazawa, Nobuyuki; Yang, Suran; Kato, Tomoya; Yamakawa, Mitsunori

    2016-07-01

    The aim of this study was to evaluate the localization of collagen modifying enzymes (CMEs) on fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs) in non-neoplastic lymphoid tissues and various malignant lymphomas. The expression of prolyl 4-hydroxylase 1 (P4H1), lysyl hydroxylase 3 (LH3), and protein disulfide isomerase (PDI) was frequently observed on FRCs and FDCs in the germinal center (GC), except for the mantle zone. The expression of CMEs was lower in most lymphomas than in their respective postulated normal counterparts. The ratio of transglutaminase II(+) FRCs/CD35(+) FDCs was also lower in follicular lymphomas (FL) than in other lymphomas. The mRNAs of some CMEs (P4H1, prolyl 4-hydroxylase 3, LH3, and heat shock protein 47) were confirmed in almost all lymphomas. These results indicate that lymphoma cell proliferation suppresses/decreases the number of CMEs expressing FRCs and FDCs in most lymphomas. PMID:26700650

  2. Localization of collagen modifying enzymes on fibroblastic reticular cells and follicular dendritic cells in non-neoplastic and neoplastic lymphoid tissues

    PubMed Central

    Ohe, Rintaro; Aung, Naing Ye; Meng, Hongxue; Kabasawa, Takanobu; Suto, Aya; Tamazawa, Nobuyuki; Yang, Suran; Kato, Tomoya; Yamakawa, Mitsunori

    2016-01-01

    Abstract The aim of this study was to evaluate the localization of collagen modifying enzymes (CMEs) on fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs) in non-neoplastic lymphoid tissues and various malignant lymphomas. The expression of prolyl 4-hydroxylase 1 (P4H1), lysyl hydroxylase 3 (LH3), and protein disulfide isomerase (PDI) was frequently observed on FRCs and FDCs in the germinal center (GC), except for the mantle zone. The expression of CMEs was lower in most lymphomas than in their respective postulated normal counterparts. The ratio of transglutaminase II+ FRCs/CD35+ FDCs was also lower in follicular lymphomas (FL) than in other lymphomas. The mRNAs of some CMEs (P4H1, prolyl 4-hydroxylase 3, LH3, and heat shock protein 47) were confirmed in almost all lymphomas. These results indicate that lymphoma cell proliferation suppresses/decreases the number of CMEs expressing FRCs and FDCs in most lymphomas. PMID:26700650

  3. Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma

    PubMed Central

    Nambiar, Mridula; Goldsmith, G.; Moorthy, Balaji T.; Lieber, Michael R.; Joshi, Mamata V.; Choudhary, Bibha; Hosur, Ramakrishna V.; Raghavan, Sathees C.

    2011-01-01

    The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Most breaks on chromosome 18 are located at the 3′-UTR of the BCL2 gene and are mainly clustered in the major breakpoint region (MBR). Recently, we found that the BCL2 MBR has a non-B DNA character in genomic DNA. Here, we show that single-stranded DNA modeled from the template strand of the BCL2 MBR, forms secondary structures that migrate faster on native PAGE in the presence of potassium, due to the formation of intramolecular G-quadruplexes. Circular dichroism shows evidence for a parallel orientation for G-quadruplex structures in the template strand of the BCL2 MBR. Mutagenesis and the DMS modification assay confirm the presence of three guanine tetrads in the structure. 1H nuclear magnetic resonance studies further confirm the formation of an intramolecular G-quadruplex and a representative model has been built based on all of the experimental evidence. We also provide data consistent with the possible formation of a G-quadruplex structure at the BCL2 MBR within mammalian cells. In summary, these important features could contribute to the single-stranded character at the BCL2 MBR, thereby contributing to chromosomal fragility. PMID:20880994

  4. Intensified therapy followed by autologous stem-cell transplantation (ASCT) versus conventional therapy as first-line treatment of follicular lymphoma: a meta-analysis.

    PubMed

    Wang, Baohong; Ren, Cuiai; Zhang, Weide; Ma, Xiaoyan; Xia, Bingsen; Sheng, Zhixin

    2013-03-01

    There are two different international standards for the treatment of follicular lymphoma (FL): intensified therapy followed by autologous stem-cell transplantation (ASCT) and conventional therapy in the first-line setting. However, their role remains unclear. Our aim was to define the treatment effect of intensified therapy followed by ASCT compared with conventional therapy as first-line treatment of patients with FL in terms of overall survival (OS) and event-free survival (EFS). We searched for randomised controlled trials in Medline, Embase, the Cochrane controlled trials register and the Science Citation Index (1985 to June 2011). Effect measures used were hazard ratios (HR) for OS, EFS and secondary tumour rate. Two independent review authors extracted data and assessed quality of trials. Four trials were identified, covering a total of 941 subjects. The random-effects summary HR by comparing the treatment effect on OS between intensified and conventional therapy was 0.95 [0.70, 1.30] (p = 0.75), indicating that no additional survival benefit was derived from the intensified therapy followed by ASCT. A significant benefit of intensified therapy followed by ASCT as first-line treatment was detected in terms of EFS: the random-effects summary HR (intensified versus conventional therapy) was 0.59 [0.44, 0.79] (p < 0.001). This meta-analysis showed that despite its superior EFS, intensified therapy followed by ASCT does not improve the OS compared with conventional therapy. PMID:22488650

  5. Children and adolescents with follicular lymphoma have an excellent prognosis with either limited chemotherapy or with a "Watch and wait" strategy after complete resection.

    PubMed

    Attarbaschi, Andishe; Beishuizen, Auke; Mann, Georg; Rosolen, Angelo; Mori, Tetsuya; Uyttebroeck, Anne; Niggli, Felix; Csoka, Monika; Krenova, Zdenka; Mellgren, Karin; Kabickova, Edita; Chiang, Alan Ks; Reiter, Alfred; Williams, Denise; Burkhardt, Birgit

    2013-11-01

    Data on clinical features and outcome in pediatric follicular lymphoma (pFL) are scarce. The aim of this retrospective study including 13 EICNHL and/or i-BFM study group members was to assess clinical characteristics and course in a series of 63 pFL patients. pFL was found to be associated with male gender (3:1), older age (72 % ≥10 years old), low serum LDH levels (<500 U/l in 75 %), grade 3 histology (in 88 %), and limited disease (87 % stage I/II disease), mostly involving the peripheral lymph nodes. Forty-four out of sixty-three patients received any polychemotherapy and 1/63 rituximab only, while 17/63 underwent a "watch and wait" strategy. Of 36 stage I patients, 30 had complete resections. Only one patient relapsed; 2-year event-free survival and overall survival were 94 ± 5 and 100 %, respectively, after a median follow-up of 2.2 years. Conclusively, treatment outcome in pFL seems to be excellent with risk-adapted chemotherapy or after complete resection and an observational strategy only. PMID:23665980

  6. Lymphoma

    MedlinePlus

    ... doctors don't know why a person gets non-Hodgkin lymphoma. You are at increased risk if you have ... immune system or have certain types of infections. Non-Hodgkin lymphoma can cause many symptoms, such as Swollen, painless ...

  7. CCI-779 in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2014-05-07

    B-cell Chronic Lymphocytic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Malignant Neoplasm; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  8. Obatoclax Mesylate, Rituximab, and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2013-06-05

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma

  9. CD43 expression in B cell lymphoma.

    PubMed Central

    Treasure, J.; Lane, A.; Jones, D. B.; Wright, D. H.

    1992-01-01

    AIMS: To determine the expression of CD43 in frozen sections in a range of B cell lymphomas. METHODS: The monoclonal antibody WR14, clustered provisionally in the Fourth Leucocyte Typing Workshop as a CD43 reagent, was investigated by epitope blocking studies on formalin fixed reactive lymph node tissue, using the established CD43 antibody MT1, to validate its use as a CD43 reagent. CD43 expression was studied in 131 immunophenotypically defined B cell lymphomas, including lymphocytic lymphoma (Lc, n = 13), centrocytic lymphoma (Cc, n = 14), and a range of follicle centre cell lymphomas (FCC) including centroblastic/centrocytic follicular (CbCcF, n = 48), centroblastic diffuse (CbD, n = 39), centroblastic/centrocytic diffuse (CbCcD, n = 4), centroblastic follicular and diffuse (Cb FD, n = 3) and centroblastic/centrocytic follicular and diffuse (CbCc FD, n = 1). Nine lymphomas of mucosa associated lymphoid tissue (MALT) were also examined. RESULTS: Epitope blocking studies showed that WR14 is a CD43 reagent that binds to an epitope identical with or close to that recognised by MT1. Eleven of 13 (84%) cases of Lc and 11 of 14 (78%) cases of Cc expressed CD43; 87 of 95 (91%) cases of FCC did not. All eight low grade lymphomas of MALT were negative. One high grade lymphoma, transformed from a low grade MALT lymphoma, was positive for CD43. The expression of CD43 by tumours of B cell lineage was associated with the expression of CD5 (p < 0.001) although either antigen could occasionally be found in the absence of the other. CONCLUSION: CD43 reagents can be used in conjunction with CD5 antibodies for the immunophenotypic discrimination of follicle centre cell lymphomas from non-follicle centre cell lymphomas. Images PMID:1280654

  10. Lenalidomide And Rituximab as Maintenance Therapy in Treating Patients With B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-11-25

    Adult Non-Hodgkin Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent

  11. Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia or B-Cell Prolymphocytic Leukemia

    ClinicalTrials.gov

    2016-07-29

    Post-transplant Lymphoproliferative Disorder; B-Cell Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Recurrent Lymphoplasmacytic Lymphoma

  12. Lymphoma

    MedlinePlus

    ... group of blood cancers that develop in the lymphatic system. The two main types are Hodgkin lymphoma and ... Is a type of cancer that affects the lymphatic system Generally develops in the lymph nodes and lymphatic ...

  13. Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction

    ClinicalTrials.gov

    2014-02-21

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage

  14. Bortezomib may be safely combined with Y-90-ibritumomab tiuxetan in patients with relapsed/refractory follicular non-Hodgkin lymphoma: a phase I trial of combined induction therapy and bortezomib consolidation.

    PubMed

    Roy, Rupali; Evens, Andrew M; Patton, David; Gallot, Lillia; Larson, Annette; Rademaker, Alfred; Cilley, Jeffrey; Spies, Stewart; Variakojis, Daina; Gordon, Leo I; Winter, Jane N

    2013-03-01

    Preclinical studies suggest that bortezomib, through inhibition of nuclear factor-κB (NF-κB) activation, may enhance the effects of radioimmunotherapy. This phase I trial was designed to determine the maximum tolerated dose (MTD) of weekly bortezomib induction combined with Y-90-ibritumomab tiuxetan followed at the time of count recovery by weekly bortezomib consolidation in patients with relapsed/refractory follicular or transformed non-Hodgkin lymphoma. Grade 3 or 4 toxicities were observed in eight of nine treated patients, and all but one of these toxicities were hematologic. One patient had grade 3 cardiotoxicity. A dose limiting toxicity (DLT) of grade 4 thrombocytopenia was observed in two of three patients treated with bortezomib at 1.6 mg/m(2), resulting in a MTD of 1.3 mg/m(2). The overall response rate was 89% (two complete response [CR], six partial response [PR], one stable disease [SD]), with a median progression-free survival of 6.5 months (range: 3-22.5+ months). A phase II trial at the MTD is under way to better define the toxicity and effectiveness of this regimen. PMID:22906230

  15. Genetic Testing Plus Irinotecan in Treating Patients With Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-01-23

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic

  16. AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma

    ClinicalTrials.gov

    2016-03-16

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large

  17. Bendamustine Hydrochloride, Etoposide, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma

    ClinicalTrials.gov

    2016-03-08

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  18. Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

    ClinicalTrials.gov

    2014-09-02

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Waldenström Macroglobulinemia

  19. 3-AP and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-09-27

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T

  20. Lenalidomide as Maintenance Therapy After Combination Chemotherapy With or Without Rituximab and Stem Cell Transplant in Treating Patients With Persistent or Recurrent Non-Hodgkin Lymphoma That is Resistant to Chemotherapy

    ClinicalTrials.gov

    2014-12-02

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  1. High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution

    PubMed Central

    Carlotti, Emanuela; Wrench, David; Rosignoli, Guglielmo; Marzec, Jacek; Sangaralingam, Ajanthah; Hazanov, Lena; Michaeli, Miri; Hallam, Simon; Chaplin, Tracy; Iqbal, Sameena; Calaminici, Maria; Young, Bryan; Mehr, Ramit; Campbell, Peter; Fitzgibbon, Jude; Gribben, John G.

    2015-01-01

    Understanding the dynamics of evolution of Follicular Lymphoma (FL) clones during disease progression is important for monitoring and targeting this tumor effectively. Genetic profiling of serial FL biopsies and examples of FL transmission following bone marrow transplant suggest that this disease may evolve by divergent evolution from a common ancestor cell. However where this ancestor cell resides and how it evolves is still unclear. The analysis of the pattern of somatic hypermutation of the immunoglobulin gene (Ig) is traditionally used for tracking the physiological clonal evolution of B cells within the germinal center and allows to discriminate those cells that have just entered the germinal center and display features of ancestor cells from those B cells that keep re-circulating across different lymphoid organs. Here we investigated the pattern of somatic hypermutation of the heavy chain of the immunoglobulin gene (IgH-VH) in 4 flow-sorted B cells subpopulations belonging to different stages of differentiation, from sequential lymph node biopsies of cases displaying diverse patterns of evolution, using the GS-FLX Titanium sequencing platform. We observed an unexpectedly high level of clonality, with hundreds of distinct tumor subclones in the different subpopulations from the same sample, the majority detected at a frequency <10−2. By using a lineage trees analysis we observed in all our FL and t-FL cases that the oligoclonal FL population was trapped in a narrow intermediate stage of maturation that maintains the capacity to undergo SHM, but was unable to further differentiate. The presence of such a complex architecture highlights challenges currently encountered in finding a cure for this disease. PMID:26325507

  2. Collection of hematopoietic stem cells after previous radioimmunotherapy is feasible and does not impair engraftment after autologous stem cell transplantation in follicular lymphoma.

    PubMed

    Derenzini, Enrico; Stefoni, Vittorio; Maglie, Roberto; Casadei, Beatrice; Pellegrini, Cinzia; Broccoli, Alessandro; Stefani, Giulia; Fanti, Stefano; Motta, Maria Rosa; Narducci, Riccardo; Argnani, Lisa; Zinzani, Pier Luigi

    2013-12-01

    Major concerns about radioimmunotherapy (RIT) administration early in the course of follicular lymphoma (FL) are long-term toxicity and the theoretical impairment of hematopoietic stem cell (HSC) harvest, but few data are available about mobilization rates after RIT. This study evaluates the impact of prior therapy with RIT (yttrium-90 ibritumomab tiuxetan) and different chemotherapy regimens in all FL patients (N = 103) attempting HSC mobilization at our institution over the last 7 years. Sixty-nine patients received R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone) or CHOP-like regimens, 21 patients received R-FM (rituximab-fludarabine-mitoxantrone), and 13 patients received RIT before HSC mobilization. Median CD34+ cell yield at first mobilization was 7.2 × 10(6)/kg in the R-CHOP group versus 4.3 in the R-FM group versus 1.7 in the RIT group (P = .02 R-CHOP versus R-FM; P < .0001 R-CHOP versus RIT; P < .02 R-FM versus RIT). Although 8 of 13 patients initially failed to collect enough HSC after RIT, a second and/or salvage harvest was successfully performed in 7 patients, with 10 of 13 patients (77%) finally undergoing autologous stem cell transplantation (ASCT). No differences in engraftment kinetics were observed between the three groups (R-CHOP versus R-FM versus RIT). Although mobilization was significantly impaired in patients previously treated with RIT, a salvage HSC harvest and ASCT after RIT were safe and feasible in most patients. PMID:24055654

  3. Intranodular clusters of activated cells with T follicular helper phenotype in nodular lymphocyte predominant Hodgkin lymphoma: a pilot study of 32 cases from Finland.

    PubMed

    Nathwani, Bharat N; Vornanen, Martine; Winkelmann, Ria; Kansal, Rina; Doering, Claudia; Hartmann, Sylvia; Hansmann, Martin L

    2013-09-01

    In nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), little is known about the presence of intranodular clusters of cytologically activated lymphoid cells producing a moth-eaten pattern histologically. This pilot study of 32 NLPHL cases from Finland ascertained (1) the frequency of the intranodular clusters of activated lymphoid cells, (2) the immunophenotype of the activated cells, (3) the size and immunophenotype of the rosetting cells, and (4) the clinical significance of the activated cells. Histologically, intranodular clusters of activated cells produced a moth-eaten pattern in 100% (32 cases; subtle in 62.5%, overt in 37.5%). In immunostains, activated cells in subtle clusters (20 cases) were very difficult to identify. Twelve cases had overt clusters of activated cells, which were positive with CD3, CD4, PD1, CXCL13 (T follicular helper [T(FH)] phenotype), but rarely with Ki-67 and BCL2. Most activated rosetting cells had the same immunophenotype as the nonrosetting cells, except for CXCL13. Clinical presentation for all 32 Finnish patients was distinctive: 97% men, 97% with peripheral lymphadenopathy and 35.5% with stage III/IV disease. Only 22% relapsed; 97% were in remission. There was no significant clinical difference between cases with overt and subtle clusters. Intranodular activated TFH cells in NLPHL appeared to be nonproliferating and not long-living, and they were not associated with any adverse clinical outcome. Although most activated cells were TFH cells, it seemed that they were unable to increase the number of malignant cells. The pathogenetic role of the intranodular activated TFH and the small T cells in NLPHL needs further investigation. PMID:23684509

  4. High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution.

    PubMed

    Carlotti, Emanuela; Wrench, David; Rosignoli, Guglielmo; Marzec, Jacek; Sangaralingam, Ajanthah; Hazanov, Lena; Michaeli, Miri; Hallam, Simon; Chaplin, Tracy; Iqbal, Sameena; Calaminici, Maria; Young, Bryan; Mehr, Ramit; Campbell, Peter; Fitzgibbon, Jude; Gribben, John G

    2015-01-01

    Understanding the dynamics of evolution of Follicular Lymphoma (FL) clones during disease progression is important for monitoring and targeting this tumor effectively. Genetic profiling of serial FL biopsies and examples of FL transmission following bone marrow transplant suggest that this disease may evolve by divergent evolution from a common ancestor cell. However where this ancestor cell resides and how it evolves is still unclear. The analysis of the pattern of somatic hypermutation of the immunoglobulin gene (Ig) is traditionally used for tracking the physiological clonal evolution of B cells within the germinal center and allows to discriminate those cells that have just entered the germinal center and display features of ancestor cells from those B cells that keep re-circulating across different lymphoid organs. Here we investigated the pattern of somatic hypermutation of the heavy chain of the immunoglobulin gene (IgH-VH) in 4 flow-sorted B cells subpopulations belonging to different stages of differentiation, from sequential lymph node biopsies of cases displaying diverse patterns of evolution, using the GS-FLX Titanium sequencing platform. We observed an unexpectedly high level of clonality, with hundreds of distinct tumor subclones in the different subpopulations from the same sample, the majority detected at a frequency <10-2. By using a lineage trees analysis we observed in all our FL and t-FL cases that the oligoclonal FL population was trapped in a narrow intermediate stage of maturation that maintains the capacity to undergo SHM, but was unable to further differentiate. The presence of such a complex architecture highlights challenges currently encountered in finding a cure for this disease. PMID:26325507

  5. PXD101 and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-05-01

    Adult Grade III Lymphomatoid Granulomatosis; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin

  6. Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2016-03-21

    B-cell Chronic Lymphocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  7. MORAb-004 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2016-01-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  8. Bortezomib and Filgrastim in Promoting Stem Cell Mobilization in Patients With Non-Hodgkin Lymphoma or Multiple Myeloma Undergoing Stem Cell Transplant

    ClinicalTrials.gov

    2016-04-19

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular

  9. TLR9 Agonist SD-101, Ipilimumab, and Radiation Therapy in Treating Patients With Low-Grade Recurrent B-cell Lymphoma

    ClinicalTrials.gov

    2016-04-23

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

  10. Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-05-06

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  11. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  12. SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-11

    Adult Grade III Lymphomatoid Granulomatosis; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  13. Stage I/II follicular lymphoma: spread of bcl-2/IgH+ cells in blood and bone marrow from primary site of disease and possibility of clearance after involved field radiotherapy.

    PubMed

    Pulsoni, Alessandro; Starza, Irene Della; Frattarelli, Natalia; Ghia, Emanuela; Carlotti, Emanuela; Cavalieri, Elena; Matturro, Angela; Tempera, Settimio; Rambaldi, Alessandro; Foà, Robin

    2007-05-01

    Stage I/IIA follicular lymphoma (FL) is considered a localised disease that can be adequately treated with radiotherapy alone. Bone marrow (BM) and peripheral blood (PB) involvement in FL was investigated by polymerase chain reaction (PCR) in a series of 24 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy. Despite the limited stage, Bcl-2/IgH+ cells were found at diagnosis in PB and/or BM of 16 patients (66.6%). After treatment, in 9/15 Bcl-2/IgH positive evaluable patients, a disappearance of Bcl-2/IgH+ cells was observed, which persisted after a median follow-up of 43.5 months (range 11-70) in all but one patient. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl-2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000. Patients with Bcl-2/IgH+ cells at diagnosis or after treatment had a higher likelihood of relapse. Thus, despite a negative BM biopsy, the majority of localised FL Bcl-2/IgH+ cells were found in the PB and BM. Lymphoma cells can reversibly spread from the affected lymph node to PB and BM and, in a proportion of cases, durably disappear after irradiation. The possibility of a persistent lymphoma cell clearance is proportional to the amount of cells detected at presentation by quantitative PCR. PMID:17408460

  14. Thyroid-specific ablation of the Carney complex gene, PRKAR1A, results in hyperthyroidism and follicular thyroid cancer.

    PubMed

    Pringle, Daphne R; Yin, Zhirong; Lee, Audrey A; Manchanda, Parmeet K; Yu, Lianbo; Parlow, Alfred F; Jarjoura, David; La Perle, Krista M D; Kirschner, Lawrence S

    2012-06-01

    Thyroid cancer is the most common endocrine malignancy in the population, and the incidence of this cancer is increasing at a rapid rate. Although genetic analysis of papillary thyroid cancer (PTC) has identified mutations in a large percentage of patients, the genetic basis of follicular thyroid cancer (FTC) is less certain. Thyroid cancer, including both PTC and FTC, has been observed in patients with the inherited tumor predisposition Carney complex, caused by mutations in PRKAR1A. In order to investigate the role of loss of PRKAR1A in thyroid cancer, we generated a tissue-specific knockout of Prkar1a in the thyroid. We report that the resulting mice are hyperthyroid and developed follicular thyroid neoplasms by 1 year of age, including FTC in over 40% of animals. These thyroid tumors showed a signature of pathway activation different from that observed in other models of thyroid cancer. In vitro cultures of the tumor cells indicated that Prkar1a-null thyrocytes exhibited growth factor independence and suggested possible new therapeutic targets. Overall, this work represents the first report of a genetic mutation known to cause human FTC that exhibits a similar phenotype when modeled in the mouse. In addition to our knowledge of the mechanisms of human follicular thyroid tumorigenesis, this model is highly reproducible and may provide a viable mechanism for the further clinical development of therapies aimed at FTC. PMID:22514108

  15. Tanespimycin and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2014-02-21

    Adult Grade III Lymphomatoid Granulomatosis; AIDS-related Peripheral/Systemic Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous

  16. MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

    ClinicalTrials.gov

    2014-05-22

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  17. MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-01-23

    Adult Grade III Lymphomatoid Granulomatosis; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  18. Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors.

    PubMed

    Klyuchnikov, Evgeny; Bacher, Ulrike; Kröger, Nicolaus M; Hari, Parameswaran N; Ahn, Kwang Woo; Carreras, Jeanette; Bachanova, Veronika; Bashey, Asad; Cohen, Jonathon B; D'Souza, Anita; Freytes, César O; Gale, Robert Peter; Ganguly, Siddhartha; Hertzberg, Mark S; Holmberg, Leona A; Kharfan-Dabaja, Mohamed A; Klein, Andreas; Ku, Grace H; Laport, Ginna G; Lazarus, Hillard M; Miller, Alan M; Mussetti, Alberto; Olsson, Richard F; Slavin, Shimon; Usmani, Saad Z; Vij, Ravi; Wood, William A; Maloney, David G; Sureda, Anna M; Smith, Sonali M; Hamadani, Mehdi

    2015-12-01

    This study was conducted to compare long-term outcomes in patients with refractory/relapsed grades 1 and 2 follicular lymphoma (FL) after allogeneic (allo) versus autologous (auto) hematopoietic cell transplantation (HCT) in the rituximab era. Adult patients with relapsed/refractory grades 1 and 2 FL undergoing first reduced-intensity allo-HCT or first autograft during 2000 to 2012 were evaluated. A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger and more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto-HCT versus allo-HCT groups for nonrelapse mortality (NRM) were 5% versus 26% (P < .0001); relapse/progression: 54% versus 20% (P < .0001); progression-free survival (PFS): 41% versus 58% (P < .001), and overall survival (OS): 74% versus 66% (P = .05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months after HCT (relative risk [RR], 4.4; P < .0001) and worse PFS (RR, 2.9; P < .0001) beyond 11 months after HCT. In the first 24 months after HCT, auto-HCT was associated with improved OS (RR, .41; P < .0001), but beyond 24 months, it was associated with inferior OS (RR, 2.2; P = .006). A landmark analysis of patients alive and progression-free at 2 years after HCT confirmed these observations, showing no difference in further NRM between both groups, but there was significantly higher risk of relapse/progression (RR, 7.3; P < .0001) and inferior PFS (RR, 3.2; P < .0001) and OS (RR, 2.1; P = .04) after auto-HCT. The 10-year cumulative incidences of second hematological malignancies after allo-HCT and auto-HCT were 0% and 7%, respectively. Auto-HCT and reduced-intensity-conditioned allo-HCT as first transplantation approach can provide durable disease control in grades 1 and 2 FL patients. Continued disease relapse risk after auto-HCT translates into improved PFS and OS after allo-HCT in long-term survivors. PMID

  19. Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant

    ClinicalTrials.gov

    2015-08-12

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult

  20. Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study

    PubMed Central

    Casulo, Carla; Byrtek, Michelle; Dawson, Keith L.; Zhou, Xiaolei; Farber, Charles M.; Flowers, Christopher R.; Hainsworth, John D.; Maurer, Matthew J.; Cerhan, James R.; Link, Brian K.; Zelenetz, Andrew D.; Friedberg, Jonathan W.

    2015-01-01

    Purpose Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death. Patients and Methods In total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility. Results Of 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index–adjusted hazard ratio, 19.8). Conclusion In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials. PMID:26124482

  1. Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

    ClinicalTrials.gov

    2016-07-12

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  2. PXD101 and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-05-15

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV

  3. Iodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2014-08-04

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  4. Follicular mucinosis - Case report*

    PubMed Central

    Passos, Paola C. Vieira da Rosa; Zuchi, Manuela Ferrasso; Fabre, Andréa Buosi; Martins, Luis Eduardo A. Machado

    2014-01-01

    Follicular mucinosis, also known as alopecia mucinosa, is a cutaneous mucinosis histologically characterized by accumulation of dermal type mucin in the pilosebaceous follicle and sebaceous glands. It presents in two forms, a primary or idiopathic form and a secondary form associated with various benign or malignant processes. Among the malignant processes, the main association is with mycosis fungoides. The frequent overlap of clinical, histopathological, immunohistochemical and molecular biology characteristics makes the correct classification of these conditions difficult, therefore a long follow-up of all cases is recommended. We report the case of an adolescent with disseminated lesions and discuss the difficulty of early identification of secondary follicular mucinosis associated with cutaneous lymphoma. PMID:24770517

  5. Vorinostat and Lenalidomide in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2010-12-08

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-Cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  6. 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

    ClinicalTrials.gov

    2013-02-06

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chondrosarcoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Nodal Marginal Zone B-cell Lymphoma; Ovarian Sarcoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Uterine Sarcoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small

  7. Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection

    ClinicalTrials.gov

    2015-08-18

    Adult B Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; HIV Infection; Intraocular Lymphoma; Multicentric Angiofollicular Lymphoid Hyperplasia; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Plasma Cell Myeloma; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  8. CPI-613, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-26

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  9. Promising results in treating lymphoma in young people

    Cancer.gov

    Patients with a type of cancer known as primary mediastinal B-cell lymphoma who received infusions of chemotherapy, but who did not have radiation therapy to an area of the thorax known as the mediastinum, had excellent outcomes, according to clinical tri

  10. miRNAs with the potential to distinguish follicular thyroid carcinomas from benign follicular thyroid tumors: results of a meta-analysis.

    PubMed

    Stokowy, T; Wojtaś, B; Fujarewicz, K; Jarząb, B; Eszlinger, M; Paschke, R

    2014-03-01

    The detection of somatic mutations in indeterminate or follicular proliferation fine-needle aspiration cytologies (FNACs) is able to clarify only a subgroup of those FNACs. Therefore, further markers to differentiate this problematic FNAC category by the identification of mutation negative thyroid cancers and benign nodules are urgently needed. Our objective was to evaluate previously published miRNA markers and discover novel ones from all publicly available miRNA expression profiling data sets. By literature review and data repository search we gathered 3 data sets describing human miRNA expression profiles of follicular thyroid cancer (FTC) and follicular adenoma (FA) samples. Literature review summarized 27 previously published miRNAs, which were validated in the 3 available data sets. By means of uniform statistical analysis 6 further miRNAs were identified and tested in an independent, previously published microarray data set. Meta-analysis confirmed 7 out of 27 previously published, and 4 out of 6 de novo identified miRNAs. The low confirmation rate of previously published miRNA markers was induced by low numbers of samples in the analyzed studies and high false discovery rates that were higher than 0.2. Finally, miR-637, miR-181c-3p, miR-206, and miR-7-5p were discovered as de novo potential FTC markers and validated in at least one independent, previously published data set. Two out of these new identified miRNAs (miR-7-5p and miR-206) were validated by qPCR in an independent sample set of 32 FTC and 46 FA samples. Especially miR-7-5p was able to differentiate benign and malignant thyroid tumors in several datasets. PMID:24446156

  11. Bortezomib and Fludarabine With or Without Rituximab in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-09-27

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hematopoietic/Lymphoid Cancer; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  12. Treatment results in advanced stage Hodgkin's lymphoma: A retrospective study

    PubMed Central

    Jain, H; Sengar, M; Nair, R; Menon, H; Laskar, S; Shet, T; Gujral, S; Sridhar, E

    2015-01-01

    Background: Hodgkin's lymphoma displays distinct epidemiological attributes in Asian population thus making it relevant to study whether there are any differences in treatment outcomes too when treated with current standard of care. Aim: To evaluate the treatment outcomes of de-novo advanced stage HL in adults. Materials and Methods: This retrospective study included de-novo advanced stage HL patients (≥15 years) registered at our center from January 2004 to December 2007. Treatment outcomes were measured in terms of response rates, overall survival (OS) and progression-free survival (PFS). Overall and PFS were calculated with Kaplan-Meier methodology and Cox-proportional hazards model was used for multivariate analysis to identify prognostic factors. Results: There were 125 patients (males 77%) who received minimum one cycle of chemotherapy with median age of 32 years (Range 15-65 years). Stage IV disease was seen in (46 patients) 37%; 75% (94 patients) patients had B symptoms. International prognostic score (IPS) ≤4 was seen in 95/112 (85%) patients. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy was given to 94%. Radiation to residual/bulky sites was given to 36% (45 patients). Response data was available for 112 patients; complete response in 76%; partial response in 10 % and progressive disease in 3 patients. Nineteen deaths (progressive disease-7, toxicity-8, unrelated cause-4) were observed. At median follow-up of 28 months, estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate analysis, IPS and response to treatment were significant factors for both OS and PFS. Conclusions: The treatment outcomes in this study are comparable with the published literature with limited follow-up data. PMID:25766339

  13. Rituximab, Romidepsin, and Lenalidomide in Treating Patients With Recurrent or Refractory B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-01-07

    B-cell Adult Acute Lymphoblastic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  14. Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-29

    Adult Grade III Lymphomatoid Granulomatosis; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  15. Follicular dermographism.

    PubMed

    Shelley, W B; Shelley, E D

    1983-09-01

    Four patients who complained of an inexplicable pruritus of several weeks to several years in duration are presented. General medical studies were unremarkable and the skin was normal except for erythematous papular lesions at sites recently scratched. The skin changes could be reproduced by multiple firm strokes with the broad edge of a tongue blade. The transitory, discrete, follicular, urticarial papules so elicited have been labeled by us as follicular dermographism. It is an entity to be distinguished from cholinergic and aquagenic urticaria. We postulate that follicular dermographism occurs during periods of transient antigenemia. At such times, the frictional force of scratching or the tongue blade test releases antigen from the blood stream to trigger focal urticaria at sites of high density mast cells, namely around the hair follicle. Hydroxyzine is an effective therapy. PMID:6627988

  16. Brentuximab Vedotin in Treating Patients With Relapsed or Refractory CD30+ Lymphoma

    ClinicalTrials.gov

    2016-06-01

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  17. Salvia Hispanica Seed in Reducing Risk of Disease Recurrence in Patients With Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-08-26

    Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult T-Cell Leukemia/Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; B Lymphoblastic Leukemia/Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; Burkitt Leukemia; Central Nervous System Lymphoma; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Diffuse Large B-Cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Hepatosplenic T-Cell Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Mycosis Fungoides; Nasal Type Extranodal NK/T-Cell Lymphoma; Nodal Marginal Zone Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Post-Transplant Lymphoproliferative Disorder; Primary Cutaneous Anaplastic Large Cell Lymphoma; Primary Effusion Lymphoma; Sezary Syndrome; Splenic Marginal Zone Lymphoma; Subcutaneous Panniculitis-Like T-Cell Lymphoma; Systemic Anaplastic Large Cell Lymphoma; T Lymphoblastic Leukemia/Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  18. Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma

    ClinicalTrials.gov

    2014-02-14

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV

  19. Blood Sample Markers of Reproductive Hormones in Assessing Ovarian Reserve in Younger Patients With Newly Diagnosed Lymphomas

    ClinicalTrials.gov

    2016-06-06

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Small Intestine Lymphoma; Splenic Marginal Zone

  20. Orbital marginal zone B-cell lymphoma of Malt: Radiotherapy results and clinical behavior

    SciTech Connect

    Suh, Chang-Ok . E-mail: cosuh317@yumc.yonsei.ac.kr; Shim, Su Jung; Lee, Sang-wook; Yang, Woo Ick; Lee, Sang Yeul; Hahn, Jee Sook

    2006-05-01

    Purpose: To elucidate the clinical behavior and treatment outcome of low-grade primary orbital lymphoma arising from mucosa-associated lymphoid tissue (Malt). Methods and Materials: Forty-eight patients with pathologically confirmed marginal zone B-cell lymphoma of MALT were treated with radiotherapy (RT). Thirty-eight patients (79.1%) received thorough staging workup studies including bone marrow biopsy. Radiation doses ranged from 5.4 to 30.6 Gy (median, 30.6 Gy). Median follow-up period was 70 months. Results: Only 2 patients revealed extraorbital lymphoma involvement (bone marrow, skin). Forty-six of 52 eye lesions showed complete response to RT. Six lesions demonstrated a partial response and showed gradual regression during the follow-up period of 39-72 months. Three patients experienced local recurrences at 34, 48, and 52 months after RT, which seemed to be related to improper use of the lens shield. Salvage re-RT was successful. The 10-year actuarial relapse-free survival, cause-specific survival, and overall survival rates were 93.1%, 97.9%, and 86.9%, respectively. Conclusion: Most of the MALT lymphoma of the orbit was localized at diagnosis and extraorbital relapse rarely occurred. Therefore, extensive staging workup at the time of diagnosis and follow-up studies to detect distant relapse may not be obligatory. Low-dose RT alone with proper lens shielding is the optimum treatment modality for orbital MALT lymphoma.

  1. Membrane-associated signaling in human B-lymphoma lines

    SciTech Connect

    Tauzin, Sebastien; Ding, Heidrun; Burdevet, Dimitri; Borisch, Bettina; Hoessli, Daniel C.

    2011-01-15

    In B-non-Hodgkin lymphomas, Lyn and Cbp/PAG constitute the core of an oncogenic signalosome that captures the Phosphatidylinositol-3-kinase, the Spleen tyrosine kinase and the Signal transducer and activator of transcription-3 to generate pro-survival and proliferative signals. Lymphoma lines corresponding to follicular, mantle-cell and Burkitt-derived lymphomas display type-specific signalosome organizations that differentially activate PI3K, Syk and STAT3. In the follicular lymphoma line, PI3K, Syk and STAT3 were optimally activated upon association with the Lyn-Cbp/PAG signalosome, while in the Burkitt lymphoma-derived line, the association with Cbp/PAG and activation of PI3K were interfered with by the latent membrane proteins encoded by the Epstein-Barr virus. In the Jeko-1 mantle-cell line, a weak association of Syk with the Lyn-Cbp/PAG signalosome resulted in poor activation of Syk, but in those cells, as in the follicular and Burkitt-derived lines, efficient apoptosis induction by the Syk inhibitor R406 indicated that Syk is nonetheless an important prosurvival element and therefore a valuable therapeutic target. In all configurations described herein is the Lyn-Cbp/PAG signalosome independent of external signals and provides efficient means of activation for its associated lipid and protein kinases. In follicular and Burkitt-derived lines, Syk appears to be activated following binding to Cbp/PAG and no longer requires B-cell receptor-associated activation motifs for activation. Assessment of the different modalities of Lyn-Cbp/PAG signalosome organization could help in selecting the appropriate combination of kinase inhibitors to eliminate a particular type of lymphoma cells.

  2. Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults.

    PubMed

    Salaverria, Itziar; Philipp, Claudia; Oschlies, Ilske; Kohler, Christian W; Kreuz, Markus; Szczepanowski, Monika; Burkhardt, Birgit; Trautmann, Heiko; Gesk, Stefan; Andrusiewicz, Miroslaw; Berger, Hilmar; Fey, Miriam; Harder, Lana; Hasenclever, Dirk; Hummel, Michael; Loeffler, Markus; Mahn, Friederike; Martin-Guerrero, Idoia; Pellissery, Shoji; Pott, Christiane; Pfreundschuh, Michael; Reiter, Alfred; Richter, Julia; Rosolowski, Maciej; Schwaenen, Carsten; Stein, Harald; Trümper, Lorenz; Wessendorf, Swen; Spang, Rainer; Küppers, Ralf; Klapper, Wolfram; Siebert, Reiner

    2011-07-01

    The prognosis of germinal center-derived B-cell (GCB) lymphomas, including follicular lymphoma and diffuse large-B-cell lymphoma (DLBCL), strongly depends on age. Children have a more favorable outcome than adults. It is not known whether this is because of differences in host characteristics, treatment protocols, or tumor biology, including the presence of chromosomal alterations. By screening for novel IGH translocation partners in pediatric and adult lymphomas, we identified chromosomal translocations juxtaposing the IRF4 oncogene next to one of the immunoglobulin (IG) loci as a novel recurrent aberration in mature B-cell lymphoma. FISH revealed 20 of 427 lymphomas to carry an IG/IRF4-fusion. Those were predominantly GCB-type DLBCL or follicular lymphoma grade 3, shared strong expression of IRF4/MUM1 and BCL6, and lacked PRDM1/BLIMP1 expression and t(14;18)/BCL2 breaks. BCL6 aberrations were common. The gene expression profile of IG/IRF4-positive lymphomas differed from other subtypes of DLBCL. A classifier for IG/IRF4 positivity containing 27 genes allowed accurate prediction. IG/IRF4 positivity was associated with young age and a favorable outcome. Our results suggest IRF4 translocations to be primary alterations in a molecularly defined subset of GCB-derived lymphomas. The probability for this subtype of lymphoma significantly decreases with age, suggesting that diversity in tumor biology might contribute to the age-dependent differences in prognosis of lymphoma. PMID:21487109

  3. Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma☆

    PubMed Central

    Gualco, Gabriela; Weiss, Lawrence M.; Bacchi, Carlos E.

    2009-01-01

    Summary Immunohistochemical determination of p63 protein is frequently used in the pathologic diagnosis of nonhematological solid tumors. In malignant hematological disease, p63 expression has been reported in 22% of follicular lymphoma, about 35% of diffuse large B-cell lymphoma, 23% of chronic lymphocytic leukemia, and in some cases of blast crisis of chronic myelogenous leukemia. Anaplastic large cell lymphoma is a rare disease that accounts for less than 5% of all cases of non-Hodgkin's lymphoma. There is little information concerning p63 expression in this specific type of lymphoma. In some cases, the morphological and phenotypic features between anaplastic large cell lymphoma and classical Hodgkin's lymphoma are similar, making this differential diagnosis challenging. We studied p63 expression using a tissue microarray approach in 154 cases of anaplastic large cell lymphoma, including 38% anaplastic large cell kinase positive and 62% anaplastic large cell kinase negative, and 58 Hodgkin's lymphoma cases. Sixty-eight cases of anaplastic large cell lymphoma (44%) showed p63 nuclear positivity (41% of anaplastic large cell kinase positive and 47% of anaplastic large cell kinase negative). Of 130 cases of systemic-anaplastic large cell lymphoma, 42% showed p63 positivity. The neoplastic cells expressed p63 in 38% of the cases of CD45-negative/anaplastic large cell kinase–negative null cell–type anaplastic large cell lymphoma, a subgroup that offers the most difficulties in the differential diagnosis with classical Hodgkin's lymphoma. In contrast, none of the cases of classical Hodgkin's lymphoma demonstrated any p63 expression. These results demonstrate that p63 protein expression is frequently expressed in a subset of anaplastic large cell lymphoma cases and may be used as a potential tool in the differential diagnosis between anaplastic large cell lymphoma and classical Hodgkin's lymphoma. PMID:18620733

  4. A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2

    PubMed Central

    Lavik, Andrew R.; Greenberg, Edward; Choudhary, Yuvraj; Smith, Mitchell R.; McColl, Karen S.; Pink, John; Reu, Frederic J.; Matsuyama, Shigemi; Distelhorst, Clark W.

    2015-01-01

    Bcl-2 inhibits apoptosis by two distinct mechanisms but only one is targeted to treat Bcl-2-positive malignancies. In this mechanism, the BH1-3 domains of Bcl-2 form a hydrophobic pocket, binding and inhibiting pro-apoptotic proteins, including Bim. In the other mechanism, the BH4 domain mediates interaction of Bcl-2 with inositol 1,4, 5-trisphosphate receptors (IP3Rs), inhibiting pro-apoptotic Ca2+ signals. The current anti-Bcl-2 agents, ABT-263 (Navitoclax) and ABT-199 (Venetoclax), induce apoptosis by displacing pro-apoptotic proteins from the hydrophobic pocket, but do not inhibit Bcl-2-IP3R interaction. Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP3 Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP3R interaction and thus inducing Ca2+-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton’s tyrosine kinase inhibitor Ibrutinib. Moreover, combining BIRD-2 with ABT-263 or ABT-199 enhances apoptosis induction compared to single agent treatment. Overall, these findings provide strong rationale for developing novel therapeutic agents that mimic the action of BIRD-2 in targeting the BH4 domain of Bcl-2 and disrupting Bcl-2-IP3R interaction. PMID:26317541

  5. A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2.

    PubMed

    Lavik, Andrew R; Zhong, Fei; Chang, Ming-Jin; Greenberg, Edward; Choudhary, Yuvraj; Smith, Mitchell R; McColl, Karen S; Pink, John; Reu, Frederic J; Matsuyama, Shigemi; Distelhorst, Clark W

    2015-09-29

    Bcl-2 inhibits apoptosis by two distinct mechanisms but only one is targeted to treat Bcl-2-positive malignancies. In this mechanism, the BH1-3 domains of Bcl-2 form a hydrophobic pocket, binding and inhibiting pro-apoptotic proteins, including Bim. In the other mechanism, the BH4 domain mediates interaction of Bcl-2 with inositol 1,4, 5-trisphosphate receptors (IP3Rs), inhibiting pro-apoptotic Ca2+ signals. The current anti-Bcl-2 agents, ABT-263 (Navitoclax) and ABT-199 (Venetoclax), induce apoptosis by displacing pro-apoptotic proteins from the hydrophobic pocket, but do not inhibit Bcl-2-IP3R interaction. Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP3 Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP3R interaction and thus inducing Ca2+-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton's tyrosine kinase inhibitor Ibrutinib. Moreover, combining BIRD-2 with ABT-263 or ABT-199 enhances apoptosis induction compared to single agent treatment. Overall, these findings provide strong rationale for developing novel therapeutic agents that mimic the action of BIRD-2 in targeting the BH4 domain of Bcl-2 and disrupting Bcl-2-IP3R interaction. PMID:26317541

  6. Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry

    PubMed Central

    Mariette, Xavier; Tubach, Florence; Bagheri, Haleh; Bardet, Michel; Berthelot, Jean-Marie; Gaudin, Philippe; Heresbach, Denis; Martin, Antoine; Schaeverbeke, Thierry; Salmon, Dominique; Lemann, Marc; Hermine, Olivier; Raphael, Martine; Ravaud, Philippe

    2010-01-01

    Objective To describe cases of lymphoma associated with anti-TNF therapy, identify risk factors, estimate the incidence and compare risks for different anti-TNF agents. Methods We designed a national prospective registry (RATIO) from 2004 to 2006, for collecting all cases of lymphoma in French patients receiving anti-TNF therapy, whatever the indication. We conducted a case-control analysis including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population used as reference.. Results We collected 38 cases of lymphoma, 31 non-Hodgkin’s lymphoma (NHL) (26 B-cell and 5 T-cell), 5 Hodgkin’s lymphoma (HL) and 2 Hodgkin’s-like lymphoma. Epstein-Barr virus (EBV) was detected in 2 of 2 Hodgkin’s-like lymphoma, 3 of 5 HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: SIR = 4.1 (2.3–7.1) and 3.6 (2.3–5.6) versus 0.9 (0.4– 1.8). The exposure to adalimumab or infliximab versus etanercept was an independent risk factor for lymphoma in the case-control study: odds ratio=4.7 (1.3– 17.7) and 4.1 (1.4–12.5), respectively. The sex and age- adjusted incidence rate of lymphoma was 42.1 per 100,000 patient-years. The standardized incidence ratio (SIR) was 2.4 (95% confidence interval [CI] 1.7–3.2). Conclusion Some lymphomas associated with immunosuppression may occur in patients receiving anti TNF therapy, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy. PMID:19828563

  7. Subtype distribution of lymphomas in Southwest China: Analysis of 6,382 cases using WHO classification in a single institution

    PubMed Central

    2011-01-01

    Background The subtype distribution of lymphoid neoplasms in Southwest China was analyzed according to WHO classifications. This study aims to analyze subtype distribution of lymphomas in southwest China. Methods Lymphoid neoplasms diagnosed within 9 years in a single institution in Southwest China were analyzed according to the WHO classification. Results From January 2000 to December 2008, a total number of 6,382 patients with lymphoma were established, of which mature B-cell neoplasms accounted for 56%, mature T- and NK-cell neoplasms occupied 26%, and precursor lymphoid neoplasms and Hodgkin lymphomas were 5% and 13%, respectively. Mixed cellularity (76%) was the major subtype of classical Hodgkin lymphoma; and the bimodal age distribution was not observed. The top six subtypes of non-Hodgkin lymphoma were as follows: diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, nasal type, extranodal marginal zone lymphoma of mucosa associated lymphoid tissue, follicular lymphoma, precursor lymphoid neoplasms, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Extranodal lymphomas comprised about half of all cases, and most frequently involved Waldeyer's ring, gastrointestinal tract, sinonasal region and skin. Conclusions The lymphoid neoplasms of Southwest China displayed some epidemiologic features similar to those reported in literature from western and Asian countries, as well as other regions of China, whereas some subtypes showed distinct features. The high frequency of mature T/NK cell neoplasms and extranodal lymphomas, especially for extranodal NK/T-cell lymphoma, nasal type, is the most outstanding characteristic of this series. PMID:21854649

  8. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402.

    PubMed

    Williams, Michael E; Hong, Fangxin; Gascoyne, Randy D; Wagner, Lynne I; Krauss, John C; Habermann, Thomas M; Swinnen, Lode J; Schuster, Stephen J; Peterson, Christopher G; Sborov, Mark D; Martin, S Eric; Weiss, Matthias; Ehmann, W Christopher; Horning, Sandra J; Kahl, Brad S

    2016-06-01

    The rituximab extended schedule or retreatment trial (RESORT; E4402) was a phase 3 randomized prospective trial comparing maintenance rituximab (MR) versus a retreatment (RR) dosing strategy in asymptomatic, low tumour burden indolent lymphoma. A planned exploratory sub-study compared the two strategies for small lymphocytic (SLL) and marginal zone lymphomas (MZL). Patients responding to rituximab weekly × 4 were randomized to MR (single dose rituximab every 3 months until treatment failure) or RR (rituximab weekly × 4) at the time of each progression until treatment failure. The primary endpoint was time to treatment failure (TTTF). Patients with SLL (n = 57), MZL (n = 71) and unclassifiable small B-cell lymphoma (n = 3) received induction rituximab. The overall response rate (ORR) was 40% [95% confidence interval (CI) 31-49%; SLL ORR 22·8%; MZL ORR 52·1%]; all 52 responders were randomized. At a median of 4·3 years from randomization, treatment failure occurred in 18/23 RR and 15/29 MR. The median TTTF was 1·4 years for RR and 4·8 years for MR (P = 0·012); median time to first cytotoxic therapy was 6·3 years for RR and not reached for MR (P = 0·0002). Survival did not differ (P = 0·72). In low tumour burden SLL and MZL patients responding to rituximab induction, MR significantly improved TTTF as compared with RR. PMID:26970533

  9. Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant

    ClinicalTrials.gov

    2014-04-03

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  10. Veliparib, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory Lymphoma, Multiple Myeloma, or Solid Tumors

    ClinicalTrials.gov

    2015-10-14

    Adult B Acute Lymphoblastic Leukemia; Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult Solid Neoplasm; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Plasma Cell Myeloma; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  11. Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

    ClinicalTrials.gov

    2015-11-23

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  12. Rationale for and Preliminary Results of Proton Beam Therapy for Mediastinal Lymphoma

    SciTech Connect

    Li Jing; Dabaja, Bouthaina; Reed, Valerie; Allen, Pamela K.; Cai, Haihong; Amin, Mayankkumar V.; Garcia, John A.; Cox, James D.

    2011-09-01

    Purpose: To evaluate the potential of three-dimensional proton beam therapy (3D-PBT) for reducing doses to normal structures in patients with mediastinal lymphomas compared with conventional photon radiation therapy (RT). Methods and Materials: We treated 10 consecutive patients with mediastinal masses from lymphomas with 3D-PBT between July 2007 and February 2009 to 30.6-50.4 cobalt-Gray equivalents (CGE). Of those patients, 7 had primary refractory or recurrent disease, and 8 had Hodgkin lymphoma. Dosimetric endpoints were compared with those from conventional RT plans. Results: PBT delivered lower mean doses to the lung (6.2 vs. 9.5 Gy), esophagus (9.5 vs. 22.3 Gy), and heart (8.8 vs. 17.7 Gy) but not the breasts (5.9 vs. 6.1 Gy) than did conventional RT. Percentages of lung, esophagus, heart, and coronary artery (particularly the left anterior descending artery) volumes receiving radiation were consistently lower in the 3D-PBT plans over a wide range of radiation doses. Of the 7 patients who had residual disease on positron emission tomography before PBT, 6 (86%) showed a complete metabolic response. Conclusions: In patients with mediastinal lymphomas, 3D-PBT produced significantly lower doses to the lung, esophagus, heart, and coronary arteries than did the current conventional RT. These lower doses would be expected to reduce the risk of late toxicities in these major organs.

  13. [In situ lymphoma and other early stage malignant non-Hodgkin lymphomas].

    PubMed

    Quintanilla-Martínez, L; Adam, P; Fend, F

    2013-05-01

    The increasing use of immunohistochemical and molecular investigations of lymphatic tissues results in more frequent detection of early lymphoid proliferations. These show some but not all features of malignant lymphomas without fulfilling the diagnostic criteria for the diagnosis of lymphoid malignancy. In addition to well-known premalignant B-cell proliferations, such as monoclonal gammopathy of unknown significance (MGUS) and monoclonal B-cell lymphocytosis (MBL), so-called in situ lymphomas have recently been described with minimal infiltrates of clonal B-cells in morphologically reactive lymphoid tissues which show the phenotypic and genetic features of specific B-cell lymphoma subtypes and often show a characteristic topographical distribution. This article addresses a group of clonal lymphoproliferations with usually localized disease and excellent clinical prognosis, such as pediatric follicular lymphoma and nodal marginal zone lymphoma. Another group of early lesions not addressed in this review are virally induced lymphoproliferations which represent a grey zone between purely reactive lesions and malignant lymphomas and may pose significant diagnostic as well as clinical problems. In this review diagnostic criteria for early or in situ lesions and their distinction from partial infiltration by malignant lymphoma are described. PMID:23459785

  14. Obinutuzumab for the treatment of indolent lymphoma.

    PubMed

    Edelmann, Jennifer; Gribben, John G

    2016-08-01

    Obinutuzumab is a humanized, type II anti-CD20 monoclonal antibody designed for strong induction of direct cell death and antibody-dependent cell-mediated cytotoxicity. The Phase III GADOLIN trial tested the clinical efficacy of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy in rituximab-refractory indolent non-Hodgkin lymphoma versus treatment with bendamustine alone. It demonstrated significantly longer progression-free survival for the obinutuzumab-containing regimen in this difficult to treat patient group. Based on the results of this trial, US FDA approval was most recently granted for obinutuzumab in the treatment of follicular lymphoma that has relapsed after or was refractory to a rituximab-containing regimen. This article summarizes the available data on chemistry, pharmacokinetics, clinical efficacy and safety of obinutuzumab in the treatment of indolent non-Hodgkin lymphoma. PMID:27117452

  15. Ipilimumab and Local Radiation Therapy in Treating Patients With Recurrent Melanoma, Non-Hodgkin Lymphoma, Colon, or Rectal Cancer

    ClinicalTrials.gov

    2013-11-19

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Colon Cancer; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Melanoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Rectal Cancer; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  16. Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-06-02

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  17. Rationale and Design of the International Lymphoma Epidemiology Consortium (InterLymph) Non-Hodgkin Lymphoma Subtypes Project

    PubMed Central

    Morton, Lindsay M.; Sampson, Joshua N.; Cerhan, James R.; Turner, Jennifer J.; Vajdic, Claire M.; Wang, Sophia S.; Smedby, Karin E.; de Sanjosé, Silvia; Monnereau, Alain; Benavente, Yolanda; Bracci, Paige M.; Chiu, Brian C. H.; Skibola, Christine F.; Zhang, Yawei; Mbulaiteye, Sam M.; Spriggs, Michael; Robinson, Dennis; Norman, Aaron D.; Kane, Eleanor V.; Spinelli, John J.; Kelly, Jennifer L.; Vecchia, Carlo La; Dal Maso, Luigino; Maynadié, Marc; Kadin, Marshall E.; Cocco, Pierluigi; Costantini, Adele Seniori; Clarke, Christina A.; Roman, Eve; Miligi, Lucia; Colt, Joanne S.; Berndt, Sonja I.; Mannetje, Andrea; de Roos, Anneclaire J.; Kricker, Anne; Nieters, Alexandra; Franceschi, Silvia; Melbye, Mads; Boffetta, Paolo; Clavel, Jacqueline; Linet, Martha S.; Weisenburger, Dennis D.; Slager, Susan L.

    2014-01-01

    Background Non-Hodgkin lymphoma (NHL), the most common hematologic malignancy, consists of numerous subtypes. The etiology of NHL is incompletely understood, and increasing evidence suggests that risk factors may vary by NHL subtype. However, small numbers of cases have made investigation of subtype-specific risks challenging. The International Lymphoma Epidemiology Consortium therefore undertook the NHL Subtypes Project, an international collaborative effort to investigate the etiologies of NHL subtypes. This article describes in detail the project rationale and design. Methods We pooled individual-level data from 20 case-control studies (17471 NHL cases, 23096 controls) from North America, Europe, and Australia. Centralized data harmonization and analysis ensured standardized definitions and approaches, with rigorous quality control. Results The pooled study population included 11 specified NHL subtypes with more than 100 cases: diffuse large B-cell lymphoma (N = 4667), follicular lymphoma (N = 3530), chronic lymphocytic leukemia/small lymphocytic lymphoma (N = 2440), marginal zone lymphoma (N = 1052), peripheral T-cell lymphoma (N = 584), mantle cell lymphoma (N = 557), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (N = 374), mycosis fungoides/Sézary syndrome (N = 324), Burkitt/Burkitt-like lymphoma/leukemia (N = 295), hairy cell leukemia (N = 154), and acute lymphoblastic leukemia/lymphoma (N = 152). Associations with medical history, family history, lifestyle factors, and occupation for each of these 11 subtypes are presented in separate articles in this issue, with a final article quantitatively comparing risk factor patterns among subtypes. Conclusions The International Lymphoma Epidemiology Consortium NHL Subtypes Project provides the largest and most comprehensive investigation of potential risk factors for a broad range of common and rare NHL subtypes to date. The analyses contribute to our understanding of the multifactorial nature of NHL

  18. Radioimmunodetection of non-Hodgkin`s lymphoma with radiolabelled LL2 monoclonal antibody. Preliminary results

    SciTech Connect

    Gasparini, M.; Buraggi, G.L.; Tondini, C.

    1994-05-01

    Radioimmunodetection (RAID) with 99m technetium labelled B cell lymphoma monoclonal antibody (MAb) (IMMU-LL2 Fab`, Immunomedics, Inc., Morris Plains, N.J.) was investigated in 8 patients (5 female and 3 male; age range 20-72 years) with histologically proven non-Hodgkin`s lymphoma (NHL). Of the 8 lymphomas, 5 were intermediate grade and 3 low grade. Whole body images with multiple planar views were obtained at 30 min, 4-6 and 24 hours after the I.V. injection of 1 mg LL2-Fab` labelled with 20-25 mCi (740-925 MBq) {sup 99}Tc. SPECT of chest or abdomen was performed at 5-8 hours after injection in all patients. No adverse reactions were observed in any patient after MAb infusion and no appreciable changes were seen in the blood counts, renal and liver function tests. A total of 17 of 18 (94.4%) lymphoma lesions were detected by RAID. All the tumor localizations were confirmed by clinical examination and with other imaging techniques, such as CT scan, MRI or gallium scan. In this series of patients no false positive results were noted and only 1 false negative resulted in a patient who had a mediastinal bulky disease. As regard the biodistribution of the immunoreagent we can make the following conclusions: (1) no appreciable bone marrow activity was seen, (2) splenic targeting was demonstrated in all patients, (3) tumor-to-non tumor ratios ranged from 1.2 to 2.8 as measured by ROI technique, (4) no difference of uptake was noted for different tumor grades. The images performed 24 hours after injection did not detect new lesions, but areas of doubtful uptake were seen as positive focal areas in the delayed scan. In these preliminary results the LL2-Fab` MAb seems to be useful for detection, staging and follow up of NHL patients.

  19. Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2015-06-30

    Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult Hepatocellular Carcinoma; Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult Solid Neoplasm; Adult T Acute Lymphoblastic Leukemia; Advanced Adult Hepatocellular Carcinoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Localized Non-Resectable Adult Liver Carcinoma; Localized Resectable Adult Liver Carcinoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Progressive Hairy Cell Leukemia Initial Treatment; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Liver Carcinoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Small Lymphocytic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult

  20. Radioimmunotherapy of Non-Hodgkin’s Lymphoma: From the ‘Magic Bullets’ to ‘Radioactive Magic Bullets’

    PubMed Central

    Chamarthy, Murthy R.; Williams, Scott C.; Moadel, Renee M.

    2011-01-01

    Radioimmunotherapy (RIT) of lymphoma with Zevalin and Bexxar was approved by FDA in 2002 and 2003, respectively, for the treatment of relapsed or refractory CD20+ follicular B-cell non-Hodgkin´s lymphoma. In 2009, Zevalin was also approved for consolidation therapy in patients with follicular non-Hodgkin’s lymphoma that achieve a partial or complete response to first-line chemotherapy. For follicular lymphoma patients, the overall response and progression-free survival rates have significantly improved since the implementation of RIT. The predominant complication of RIT is hematological toxicity that is usually manageable. There are ongoing trials to further define the expanding role of RIT as first line or concomitant therapy in the treatment of lymphoma as well as for certain antibiotic resistant infections and aggressive malignancies. There is also growing interest in the development of newer protocols for increased and more uniform dose delivery resulting in better outcomes and improved patient survival. This review will primarily focus on the role of RIT in treatment of non-Hodgkin’s lymphoma, which is of established clinical utility and FDA approved. The mechanism of RIT, available radionuclides and pharmacokinetics, therapy administration, clinical utility and toxicities, and future directions would be discussed. PMID:22180677

  1. B-cell lymphomas with concurrent MYC and BCL2 abnormalities other than translocations behave similarly to MYC/BCL2 double-hit lymphomas.

    PubMed

    Li, Shaoying; Seegmiller, Adam C; Lin, Pei; Wang, Xuan J; Miranda, Roberto N; Bhagavathi, Sharathkumar; Medeiros, L Jeffrey

    2015-02-01

    Large B-cell lymphomas with IGH@BCL2 and MYC rearrangement, known as double-hit lymphoma (DHL), are clinically aggressive neoplasms with a poor prognosis. Some large B-cell lymphomas have concurrent abnormalities of MYC and BCL2 other than coexistent translocations. Little is known about patients with these lymphomas designated here as atypical DHL. We studied 40 patients of atypical DHL including 21 men and 19 women, with a median age of 60 years. Nine (23%) patients had a history of B-cell non-Hodgkin lymphoma. There were 30 diffuse large B-cell lymphoma (DLBCL), 7 B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma, and 3 DLBCL with coexistent follicular lymphoma. CD10, BCL2, and MYC were expressed in 28/39 (72%), 33/35 (94%), and 14/20 (70%) cases, respectively. Patients were treated with standard (n=14) or more aggressive chemotherapy regimens (n=17). We compared the atypical DHL group with 76 patients with DHLand 35 patients with DLBCL lacking MYC and BCL2 abnormalities. The clinicopathologic features and therapies were similar between patients with atypical and typical DHL. The overall survival of patients with atypical double-hit lymphoma was similar to that of patients with double-hit lymphoma (P=0.47) and significantly worse than that of patients with DLBCL with normal MYC and BCL2 (P=0.02). There were some minor differences. Cases of atypical double-hit lymphoma more often have DLBCL morphology (P<0.01), less frequently expressed CD10 (P<0.01), and patients less often had an elevated serum lactate dehydrogenase level (P=0.01). In aggregate, these results support expanding the category of MYC/BCL2 DHL to include large B-cell lymphomas with coexistent MYC and BCL2 abnormalities other than concurrent translocations. PMID:25103070

  2. Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and High-Dose Rituximab for Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma: A Phase Two Multicenter Trial from the Blood and Marrow Transplant Clinical Trials Network.

    PubMed

    Laport, Ginna G; Wu, Juan; Logan, Brent; Bachanova, Veronika; Hosing, Chitra; Fenske, Timothy; Longo, Walter; Devine, Steven M; Nademanee, Auayporn; Gersten, Iris; Horowitz, Mary; Lazarus, Hillard M; Riches, Marcie L

    2016-08-01

    Allogeneic (allo) hematopoietic cell transplantation (HCT) can induce long-term remissions in chemosensitive relapsed follicular lymphoma (FL). The Blood and Marrow Transplant Clinical Trials Network conducted a multicenter phase 2 trial to examine the efficacy of alloHCT using reduced-intensity conditioning with rituximab (RTX) in multiply relapsed, chemosensitive FL. The primary endpoint was 2-year progression-free survival (PFS). The conditioning regimen consisted of fludarabine, cyclophosphamide, and high-dose RTX (FCR), in which 3 of the 4 doses of RTX were administered at a dose of 1 gm/m(2). Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus and methotrexate. Sixty-five patients were enrolled and 62 were evaluable. Median age was 55 years (range, 29 to 74). This group was heavily pretreated: 77% had received ≥ 3 prior regimens, 32% had received ≥ 5 prior regimens, and 11% had received prior autologous HCT. Donors were HLA-matched siblings (n = 33) or HLA-matched unrelated adults (n = 29). No graft failures occurred. The overall response rate after HCT was 94% with 90% in complete remission (CR), including 24 patients not in CR before alloHCT. With a median follow-up of 47 months (range, 30 to 73), 3-year PFS and overall survival rates were 71% (95% confidence interval, 58% to 81%) and 82% (95% confidence interval, 70% to 90%), respectively. Three-year cumulative incidences of relapse/progression and nonrelapse mortality were 13% and 16%, respectively. Two-year cumulative incidences of grades 2 to 4 and grades 3 or 4 acute GVHD were 27% and 10%, respectively, and extensive chronic GVHD incidence was 55%. Serum RTX concentrations peaked at day +28 and remained detectable as late as 1 year in 59% of patients with available data. In conclusion, alloHCT with FCR conditioning confers high CR rates, a low incidence of relapse/progression, and excellent survival probabilities in heavily pretreated FL patients. PMID:27118571

  3. Disruption of CD8+ Treg activity results in expansion of T follicular helper cells and enhanced antitumor immunity.

    PubMed

    Alvarez Arias, Diana A; Kim, Hye-Jung; Zhou, Penghui; Holderried, Tobias A W; Wang, Xuan; Dranoff, Glenn; Cantor, Harvey

    2014-03-01

    Tumor growth is associated with the inhibition of host antitumor immune responses that can impose serious obstacles to cancer immunotherapy. To define the potential contribution of Qa-1-restricted CD8 regulatory T cells (Treg) to the development of tumor immunity, we studied B6.Qa-1 D227K mice that harbor a point mutation in the MHC class Ib molecule Qa-1 that impairs CD8 Treg suppressive activity. Here, we report that the growth of B16 melanoma is substantially delayed in these Qa-1-mutant mice after therapeutic immunization with B16 melanoma cells engineered to express granulocyte macrophage colony-stimulating factor compared with Qa-1 B6-WT controls. Reduced tumor growth is associated with enhanced expansion of follicular T helper cells, germinal center B cells, and high titers of antitumor autoantibodies, which provoke robust antitumor immune responses in concert with tumor-specific cytolytic T cells. Analysis of tumor-infiltrating T cells revealed that the Qa-1 DK mutation was associated with an increase in the ratio of CD8(+) T effectors compared with CD8 Tregs. These data suggest that the CD8(+) T effector-Treg ratio may provide a useful prognostic index for cancer development and raise the possibility that depletion or inactivation of CD8 Tregs represents a potentially effective strategy to enhance antitumor immunity. PMID:24778317

  4. Limited Chemotherapy and Shrinking Field Radiotherapy for Osteolymphoma (Primary Bone Lymphoma): Results From the Trans-Tasman Radiation Oncology Group 99.04 and Australasian Leukaemia and Lymphoma Group LY02 Prospective Trial;Bone; Lymphoma; Radiotherapy; Chemotherapy; Clinical trial

    SciTech Connect

    Christie, David; Dear, Keith; Le, Thai; Barton, Michael; Wirth, Andrew; Porter, David; Roos, Daniel; Pratt, Gary

    2011-07-15

    Purpose: To establish benchmark outcomes for combined modality treatment to be used in future prospective studies of osteolymphoma (primary bone lymphoma). Methods and Materials: In 1999, the Trans-Tasman Radiation Oncology Group (TROG) invited the Australasian Leukemia and Lymphoma Group (ALLG) to collaborate on a prospective study of limited chemotherapy and radiotherapy for osteolymphoma. The treatment was designed to maintain efficacy but limit the risk of subsequent pathological fractures. Patient assessment included both functional imaging and isotope bone scanning. Treatment included three cycles of CHOP chemotherapy and radiation to a dose of 45 Gy in 25 fractions using a shrinking field technique. Results: The trial closed because of slow accrual after 33 patients had been entered. Accrual was noted to slow down after Rituximab became readily available in Australia. After a median follow-up of 4.3 years, the five-year overall survival and local control rates are estimated at 90% and 72% respectively. Three patients had fractures at presentation that persisted after treatment, one with recurrent lymphoma. Conclusions: Relatively high rates of survival were achieved but the number of local failures suggests that the dose of radiotherapy should remain higher than it is for other types of lymphoma. Disability after treatment due to pathological fracture was not seen.

  5. Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

    ClinicalTrials.gov

    2015-10-30

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

  6. Prognostic factors and treatment results of pediatric Hodgkin's lymphoma: A single center experience.

    PubMed

    Büyükkapu-Bay, Sema; Çorapçıoğlu, Funda; Aksu, Görkem; Anık, Yonca; Demir, Hakan; Erçin, Cengiz

    2015-01-01

    The aim of this study was to assess the demographic, clinic data, prognostic factors and treatment/follow-up results of children who were diagnosed with Hodgkin lymphoma and followed in our center of Pediatric Oncology, Kocaeli University Medical Faculty, Kocaeli, Turkey, for 10 years. This retrospective study evaluated 41 patients with Hodgkin lymphoma who were younger than 18 years-old. All patients were treated with risked adapted ABVD (Adriamycin, Bleomycin, Vincristine, Dacarbazine) chemotherapy and also received involved field radiotherapy. Thirty-two patients (78%) were males and 9 (22%) were females, with a mean age of 10.7±4.0 years. The histopathological diagnosis was mixed cellular type in 51.2% of the patients. B symptoms (unexplained fever, unexplained weight loss, drenching night sweats) were present in 53.7% of the patients and 36.6% of the patients were at advanced stage at the time of the diagnosis. The 3-year overall and event-free survival rates were 88% and 5-year overall and event-free survival rates were 88%, 78%. Age, stage, treatment risk groups, presence of B symptoms and hematological parameters had no significant effect on overall and event-free survival in univariate analysis while bulky disease was the only significant factor on overall survival. Our treatment policy was succesful regarding the similar survival rates in the treatment risk groups, however novel treatment strategies adopting the early response with the reduction of adverse effects are planned in the near future. PMID:27186698

  7. Follicular disorders of the face.

    PubMed

    Sardana, Kabir

    2014-01-01

    Follicular disorders are possibly a commonly seen, though rarely reported, group of disorders, which are localized around follicles and appendages and clinically present as small papules. Classically, clinicopathological follicular plugging is seen in the "true" follicular disorders, which are appropriately referred to as follicular keratosis. Another subtype is folliculitis (infectious or noninfectious) and the follicular mimickers that clinically resemble "true" follicular disorders without the follicular keratoses. Acne vulgaris has an amalgamation of all the above lesion types. Our review is aimed at describing all the follicular disorders and gives an algorithm for diagnosing the common follicular disorders. PMID:25441478

  8. Bilateral follicular cysts in a water buffalo.

    PubMed

    Khan, F A; Nabi, S U; Pande, Megha; Das, G K; Sarkar, M

    2011-03-01

    The present short communication puts on record a case of bilateral, multiple follicular cysts in a water buffalo along with a detailed description of its ovarian biometry and follicular fluid composition. The ovarian weight and biometrical parameters were much higher than in normal cycling buffaloes. A total of three follicular cysts were observed, two on the right ovary and one on the left ovary, measuring 4.9, 3.0 and 2.6 cm yielding 21, 9 and 5 ml of follicular fluid, respectively. The cystic fluid was deep yellow in colour with a viscous consistency. The follicular fluid concentrations of glucose, total protein, cholesterol, acid phosphatase, calcium, phosphorus and progesterone in all the cysts were within the range reported previously in normal buffalo follicular fluid; however, the alkaline phosphatase concentration in cyst 1 and total bilirubin concentration in cysts 1 and 2 were higher than the values in normal follicular fluid. In contrast, the levels of urea nitrogen in cysts 1 and 3, and oestradiol in cyst 3 were lower than the normal values. All the three follicles had an oestradiol to progesterone ratio less than 1. The results of our study suggest that follicular cysts in buffalo are oestrogenically inactive and have an altered concentration of certain biochemical and hormonal constituents. PMID:21086160

  9. Primary gastrointestinal lymphomas - A study of 81 Cases from a Tertiary Healthcare Centre.

    PubMed

    Shirsat, H S; Vaiphei, K

    2014-01-01

    Purpose: Retrospective analysis of 81 routinely diagnosed gastrointestinal (GI) lymphoma to illustrate clinicopathological and immunohistochemical characteristics with predisposing condition. Materials and Methods: Age, sex, site, tumour stage, associated pathological features like lympho-epithelial lesion (LEL), atrophic gastritis (AG), intestinal metaplasia (IM) and enteropathy changes were analysed. Requisite immunohistochemical panel was applied wherever needed. Results: There were 55 male and 26 female patients with median age of 54.5 years. Site wise distributions were stomach 40, small intestine 22, colon 4, cecum 2, ileocecum 3, esophagus 1 and multiple sites 9. Histological subtypes were mucosa associated lymphoid tissue lymphoma (MALTOMA) 48, diffuse large B cell lymphoma (DLBL) 21, T cell lymphoma 9 [5 anaplastic large cell lymphoma (ALCL) and 4 enteropathy associated T cell lymphoma (EATL)], immunoproliferative small intestinal disease (IPSID) 2 and follicular lymphoma 1. LEL was present in 31 cases. Of the 19 AG, 8 had associated IM, and 1 case each had associated H Pylori infection and neuroendocrine tumor. Enteropathy was observed in 4 EATL, and one case each of DLBL and high grade MALTOMA. Giardia infection was present in 1 low grade duodenal MALTOMA. Of the 24 resected specimens, 16 were stage IE, 7 stage IIE and 1 stage IV (Mushoff's staging). Conclusion: Primary GI lymphoma was frequently observed in 6 th decade of life with male preponderance. Stomach was the commonest site and high grade MALTOMA being the commonest histological variant. Isolated colonic involvement and intestinal perforations were not infrequent. Rare variants like ALCL and follicular lymphomas were also observed. PMID:25494124

  10. Follicular occlusion tetrad.

    PubMed

    Vasanth, Vani; Chandrashekar, Byalakere Shivanna

    2014-10-01

    Follicular occlusion tetrad is a symptom complex consisting of four conditions having a similar pathophysiology. It includes Hidradenitis suppurativa, acne conglobata, dissecting cellulitis of the scalp and pilonidal sinus. The exact pathogenesis of this group of disease is unknown but evidence suggests that they share the same pathological process initiated by follicular occlusion in apocrine gland bearing areas. Though each of these conditions is commonly encountered singly, follicular occlusion tetrad as a symptom complex has been rarely reported in the literature. PMID:25396138

  11. Follicular occlusion tetrad

    PubMed Central

    Vasanth, Vani; Chandrashekar, Byalakere Shivanna

    2014-01-01

    Follicular occlusion tetrad is a symptom complex consisting of four conditions having a similar pathophysiology. It includes Hidradenitis suppurativa, acne conglobata, dissecting cellulitis of the scalp and pilonidal sinus. The exact pathogenesis of this group of disease is unknown but evidence suggests that they share the same pathological process initiated by follicular occlusion in apocrine gland bearing areas. Though each of these conditions is commonly encountered singly, follicular occlusion tetrad as a symptom complex has been rarely reported in the literature. PMID:25396138

  12. Follicular Lymphoma in Adults (Beyond the Basics)

    MedlinePlus

    ... the Licensed Materials from any location via the Internet. b. STANDALONE WORKSTATION: A standalone subscription permits multiple ... computer. A Standalone Workstation license does not include Internet access to the Licensed Materials. c. INSTITUTIONAL SUBSCRIPTION: ...

  13. T follicular regulatory cells.

    PubMed

    Sage, Peter T; Sharpe, Arlene H

    2016-05-01

    Pathogen exposure elicits production of high-affinity antibodies stimulated by T follicular helper (Tfh) cells in the germinal center reaction. Tfh cells provide both costimulation and stimulatory cytokines to B cells to facilitate affinity maturation, class switch recombination, and plasma cell differentiation within the germinal center. Under normal circumstances, the germinal center reaction results in antibodies that precisely target foreign pathogens while limiting autoimmunity and excessive inflammation. In order to have this degree of control, the immune system ensures Tfh-mediated B-cell help is regulated locally in the germinal center. The recently identified T follicular regulatory (Tfr) cell subset can migrate to the germinal center and inhibit Tfh-mediated B-cell activation and antibody production. Although many aspects of Tfr cell biology are still unclear, recent data have begun to delineate the specialized roles of Tfr cells in controlling the germinal center reaction. Here we discuss the current understanding of Tfr-cell differentiation and function and how this knowledge is providing new insights into the dynamic regulation of germinal centers, and suggesting more efficacious vaccine strategies and ways to treat antibody-mediated diseases. PMID:27088919

  14. Spontaneous rupture of the spleen as a result of primary splenic lymphoma

    PubMed Central

    Mohammed, Ahmed M.A.; Majid, Zulqarnain I.; Villatoro, Eduardo A.

    2016-01-01

    Spontaneous rupture of the spleen is a true surgical emergency that requires immediate management to prevent rapid exsanguination. It occurs mostly as a result of splenic infiltration by infectious or haematological diseases. We present a case of a 79-year-old male who was admitted to our emergency department with 3 days history of feeling unwell, abdominal pain, and dizziness, with no history of trauma. He was hypotensive, but all other observations were within normal limits. Examination revealed abdominal tenderness, mainly on the left side, with no palpable organs or masses. Computed tomography scan showed an abnormal spleen with signs of intraabdominal bleeding; emergency splenectomy was performed successfully. Histological examination showed infiltration of the spleen by diffuse large B cell lymphoma, which was later confirmed to be primary. The patient went through an uneventful post-operative recovery, and remains disease free so far. PMID:26724327

  15. Primary renal lymphoma: long-term results of two patients treated with a chemotherapy + rituximab protocol.

    PubMed

    Vázquez-Alonso, F; Puche-Sanz, I; Sánchez-Ramos, C; Flores-Martín, J; Vicente-Prados, J; Cózar-Olmo, J M

    2012-01-01

    Primary renal lymphoma (PRL) is a rare disease of which the etiology and pathogenesis remain controversial, and there is currently no standard treatment for it. We present the results of a long-term followup of two patients who were diagnosed with PRL and treated with cyclophosphamide, adriamycin, vincristine, prednisolone and rituximab (CHOP + R) regimen. Both patients reached a complete response, and there is no evidence of recurrence after 4.5- and 5-year followup periods. Based on our experience and other recently published studies, we recommend the combination of CHOP + rituximab as the elective treatment for this disease. To our knowledge, this is the longest followup period with a complete response that has been reported with this modality of treatment. PMID:22997596

  16. Follicular Helper T Cells in Autoimmunity.

    PubMed

    Scherm, Martin G; Ott, Verena B; Daniel, Carolin

    2016-08-01

    The development of multiple disease-relevant autoantibodies is a hallmark of autoimmune diseases. In autoimmune type 1 diabetes (T1D), a variable time frame of autoimmunity precedes the clinically overt disease. The relevance of T follicular helper (TFH) cells for the immune system is increasingly recognized. Their pivotal contribution to antibody production by providing help to germinal center (GC) B cells facilitates the development of a long-lived humoral immunity. Their complex differentiation process, involving various stages and factors like B cell lymphoma 6 (Bcl6), is strictly controlled, as anomalous regulation of TFH cells is connected with immunopathologies. While the adverse effects of a TFH cell-related insufficient humoral immunity are obvious, the role of increased TFH frequencies in autoimmune diseases like T1D is currently highlighted. High levels of autoantigen trigger an excessive induction of TFH cells, consequently resulting in the production of autoantibodies. Therefore, TFH cells might provide promising approaches for novel therapeutic strategies. PMID:27324759

  17. Oral clofarabine for relapsed/refractory non-Hodgkin lymphomas: Results of a phase 1 study

    PubMed Central

    Abramson, J.S.; Takvorian, R.W.; Fisher, D.C.; Feng, Y.; Jacobsen, E.D.; Brown, J.R.; Barnes, J.A.; Neuberg, D.S.; Hochberg, E.P.

    2015-01-01

    We conducted a phase 1 trial evaluating the oral nucleoside analogue clofarabine in patients with relapsed/refractory non-Hodgkin lymphoma. Patients were treated once daily on days 1 through 21 of a 28 day cycle for a maximum of 6 cycles. The study was conducted with a 3+3 design with ten additional patients treated at the recommended phase 2 dose. Thirty patients were enrolled including indolent B-cell lymphomas (21), mantle cell (6), and diffuse large B-cell lymphoma (3). The primary toxicities were hematologic including grade 3–4 neutropenia (53%) and thrombocytopenia (27%). Three mg was determined to be the recommended phase 2 dose. Tumor volume was reduced in 70% of patients, and the overall response rate was 47% including 27% complete remissions. Responses were seen in indolent B-cell lymphomas and mantle cell lymphoma. At a median follow-up of 17 months, 68% of responding patients remain in ongoing remission. Oral clofarabine was well tolerated with encouraging efficacy in indolent B-cell lymphomas and mantle cell lymphomas, warranting further investigation. PMID:23289359

  18. Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

    PubMed Central

    Fayad, Luis; Offner, Fritz; Smith, Mitchell R.; Verhoef, Gregor; Johnson, Peter; Kaufman, Jonathan L.; Rohatiner, Ama; Advani, Anjali; Foran, James; Hess, Georg; Coiffier, Bertrand; Czuczman, Myron; Giné, Eva; Durrant, Simon; Kneissl, Michelle; Luu, Kenneth T.; Hua, Steven Y.; Boni, Joseph; Vandendries, Erik; Dang, Nam H.

    2013-01-01

    Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20+/CD22+ B-cell non-Hodgkin lymphoma (NHL). Patients and Methods A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles. Results In all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. Conclusion R-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20+/CD22+ B-cell NHL. PMID:23295790

  19. Lymphoma in acquired generalized lipodystrophy.

    PubMed

    Brown, Rebecca J; Chan, Jean L; Jaffe, Elaine S; Cochran, Elaine; DePaoli, Alex M; Gautier, Jean-Francois; Goujard, Cecile; Vigouroux, Corinne; Gorden, Phillip

    2016-01-01

    Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression. PMID:25864863

  20. Rare gastrointestinal lymphomas: The endoscopic investigation

    PubMed Central

    Vetro, Calogero; Bonanno, Giacomo; Giulietti, Giorgio; Romano, Alessandra; Conticello, Concetta; Chiarenza, Annalisa; Spina, Paolo; Coppolino, Francesco; Cunsolo, Rosario; Raimondo, Francesco Di

    2015-01-01

    Gastrointestinal lymphomas represent up to 10% of gastrointestinal malignancies and about one third of non-Hodgkin lymphomas. The most prominent histologies are mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma. However, the gastrointestinal tract can be the site of rarer lymphoma subtypes as a primary or secondary localization. Due to their rarity and the multifaceted histology, an endoscopic classification has not been validated yet. This review aims to analyze the endoscopic presentation of rare gastrointestinal lymphomas from disease diagnosis to follow-up, according to the involved site and lymphoma subtype. Existing, new and emerging endoscopic technologies have been examined. In particular, we investigated the diagnostic, prognostic and follow-up endoscopic features of T-cell and natural killer lymphomas, lymphomatous polyposis and mantle cell lymphoma, follicular lymphoma, plasma cell related disease, gastrointestinal lymphomas in immunodeficiency and Hodgkin’s lymphoma of the gastrointestinal tract. Contrarily to more frequent gastrointestinal lymphomas, data about rare lymphomas are mostly extracted from case series and case reports. Due to the data paucity, a synergism between gastroenterologists and hematologists is required in order to better manage the disease. Indeed, clinical and prognostic features are different from nodal and extranodal or the bone marrow (in case of plasma cell disease) counterpart. Therefore, the approach should be based on the knowledge of the peculiar behavior and natural history of disease. PMID:26265987

  1. Phase 1 dose-escalation study of IV ixazomib, an investigational proteasome inhibitor, in patients with relapsed/refractory lymphoma.

    PubMed

    Assouline, S E; Chang, J; Cheson, B D; Rifkin, R; Hamburg, S; Reyes, R; Hui, A-M; Yu, J; Gupta, N; Di Bacco, A; Shou, Y; Martin, P

    2014-01-01

    Ixazomib is an investigational proteasome inhibitor that has shown preclinical activity in lymphoma models. This phase 1 study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics and preliminary activity of intravenous (IV) ixazomib in relapsed/refractory lymphoma patients who had received ⩾ 2 prior therapies. Thirty patients with a range of histologies received ixazomib 0.125-3.11 mg/m(2) on days 1, 8 and 15 of 28-day cycles. Patients received a median of two cycles (range 1-36). MTD was determined to be 2.34 mg/m(2). Most common drug-related adverse events (AEs) included fatigue (43%), diarrhea (33%), nausea, vomiting and thrombocytopenia (each 27%). Drug-related grade ⩾ 3 AEs included neutropenia (20%), thrombocytopenia (13%) and diarrhea (10%). Drug-related peripheral neuropathy occurred in four (13%) patients; no grade ⩾ 3 events were reported. Plasma exposure increased dose proportionally from 0.5-3.11 mg/m(2); terminal half-life was 4-12 days after multiple dosing. Of 26 evaluable patients, five achieved responses: 4/11 follicular lymphoma patients (one complete and three partial responses) and 1/4 peripheral T-cell lymphoma patients (partial response). Sustained responses were observed with ⩾ 32 cycles of treatment in two heavily pretreated follicular lymphoma patients. Results suggest weekly IV ixazomib is generally well tolerated and may be clinically active in relapsed/refractory lymphoma. PMID:25325301

  2. Phase 1 dose-escalation study of IV ixazomib, an investigational proteasome inhibitor, in patients with relapsed/refractory lymphoma

    PubMed Central

    Assouline, S E; Chang, J; Cheson, B D; Rifkin, R; Hamburg, S; Reyes, R; Hui, A-M; Yu, J; Gupta, N; Di Bacco, A; Shou, Y; Martin, P

    2014-01-01

    Ixazomib is an investigational proteasome inhibitor that has shown preclinical activity in lymphoma models. This phase 1 study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics and preliminary activity of intravenous (IV) ixazomib in relapsed/refractory lymphoma patients who had received ⩾2 prior therapies. Thirty patients with a range of histologies received ixazomib 0.125−3.11 mg/m2 on days 1, 8 and 15 of 28-day cycles. Patients received a median of two cycles (range 1−36). MTD was determined to be 2.34 mg/m2. Most common drug-related adverse events (AEs) included fatigue (43%), diarrhea (33%), nausea, vomiting and thrombocytopenia (each 27%). Drug-related grade ⩾3 AEs included neutropenia (20%), thrombocytopenia (13%) and diarrhea (10%). Drug-related peripheral neuropathy occurred in four (13%) patients; no grade ⩾3 events were reported. Plasma exposure increased dose proportionally from 0.5−3.11 mg/m2; terminal half-life was 4−12 days after multiple dosing. Of 26 evaluable patients, five achieved responses: 4/11 follicular lymphoma patients (one complete and three partial responses) and 1/4 peripheral T-cell lymphoma patients (partial response). Sustained responses were observed with ⩾32 cycles of treatment in two heavily pretreated follicular lymphoma patients. Results suggest weekly IV ixazomib is generally well tolerated and may be clinically active in relapsed/refractory lymphoma. PMID:25325301

  3. B-cell non-Hodgkin lymphoma linked to Coxiella burnetii.

    PubMed

    Melenotte, Cléa; Million, Matthieu; Audoly, Gilles; Gorse, Audrey; Dutronc, Hervé; Roland, Gauthier; Dekel, Michal; Moreno, Asuncion; Cammilleri, Serge; Carrieri, Maria Patrizia; Protopopescu, Camelia; Ruminy, Philippe; Lepidi, Hubert; Nadel, Bertrand; Mege, Jean-Louis; Xerri, Luc; Raoult, Didier

    2016-01-01

    Bacteria can induce human lymphomas, whereas lymphoproliferative disorders have been described in patients with Q fever. We observed a lymphoma in a patient with Q fever that prompted us to investigate the association between the 2 diseases. We screened 1468 consecutive patients of the 2004 to 2014 French National Referral Center for Q fever database. The standardized incidence ratios (SIRs) of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were calculated comparatively to the 2012 Francim Registry. The presence of Coxiella burnetii was tested using immunofluorescence and fluorescence in situ hybridization using a specific 16S ribosomal RNA probe and genomic DNA probe. Seven patients (0.48%) presented mature B-cell lymphoma consisting of 6 DLBCL and 1 FL. An excess risk of DLBCL and FL was found in Q fever patients compared with the general population (SIR [95% confidence interval], 25.4 [11.4-56.4] and 6.7 [0.9-47.9], respectively). C burnetii was detected in CD68(+) macrophages within both lymphoma and lymphadenitis tissues but localization in CD123(+) plasmacytoid dendritic cells (pDCs) was found only in lymphoma tissues. Q fever patients with persistent focalized infection were found more at risk of lymphoma (hazard ratio, 9.35 [1.10-79.4]). Interleukin-10 (IL10) overproduction (P = .0003) was found in patients developing lymphoma. These results suggest that C burnetii should be added to the list of bacteria that promote human B-cell non-Hodgkin lymphoma, possibly by the infection of pDCs and IL10 overproduction. Screening for early lymphoma diagnosis should be considered in the management of patients with Q fever, especially those with persistent focalized infections. PMID:26463422

  4. Expression of Mitochondria-Associated Genes (PPARGC1A, NRF-1, BCL-2 and BAX) in Follicular Development and Atresia of Goat Ovaries.

    PubMed

    Zhang, G; Wan, Y; Zhang, Y; Lan, S; Jia, R; Wang, Z; Fan, Y; Wang, F

    2015-06-01

    Most follicles undergo atresia during the developmental process. Follicular atresia is predominantly regulated by apoptosis of granulosa cells, but the mechanism underlying apoptosis via the mitochondria-dependent apoptotic pathway is unclear. We aimed to investigate whether the mitochondria-associated genes peroxisome proliferator-activated receptor-gamma, coactivator1-alpha (PPARGC1A), nuclear respiratory factor-1 (NRF-1), B-cell CLL/lymphoma 2 (BCL-2) and BCL2-associated X protein (BAX) played a role in follicular atresia through this pathway. The four mitochondria-associated proteins (PGC-1α, which are encoded by the PPARGC1A gene, NRF-1, BCL-2 and BAX) mainly expressed in granulosa cells. The mRNA and protein levels of PPARGC1A/PGC-1α and NRF-1 in granulosa cells increased with the follicular development. These results showed that these genes may play a role in the regulation of the follicular development. In addition, compared with healthy follicles, the granulosa cell in atretic follicles had a reduced expression of NRF-1, increased BAX expression and increased ratio of BAX to BCL-2 expression. These results suggested that changes of the mitochondria-associated gene expression patterns in granulosa cells may lead to follicular atresia during goat follicle development. PMID:25779891

  5. Burkitt lymphoma

    MedlinePlus

    ... lymphoma is a very fast growing form of non-Hodgkin lymphoma . Causes Burkitt lymphoma was first discovered in children ... CT scan References National Cancer Institute: PDQ Adult Non-Hodgkin Lymphoma Treatment. Bethesda, MD: National Cancer Institute. Date last ...

  6. The role of mitoxantrone in non-Hodgkin's lymphoma.

    PubMed

    Armitage, James O

    2002-04-01

    The development of doxorubicin was an important advance in the treatment of patients with non-Hodgkin's lymphoma (NHL). Alternatives to doxorubicin, such as mitoxantrone (Novantrone), have less nonhematologic toxicity and could offer a therapeutic advantage in some situations if similar antilymphoma activity exists. Several combination regimens that include mitoxantrone have been shown to be active. These include mitoxantrone/ifosfamide (Ifex) and mitoxantrone/etoposide combinations as salvage therapy for aggressive lymphomas. Mitoxantrone in combination with fludarabine (Fludara) for the treatment of newly diagnosed follicular lymphomas and in combination with fludarabine and dexamethasone for relapsed/refractory follicular lymphomas has produced high complete response rates. Other evolving uses of mitoxantrone include combination therapy with cladribine (Leustatin) or rituximab (Rituxan), and as part of conditioning regimens for hematopoietic stem cell transplantation. In diffuse aggressive lymphoma, mitoxantrone, 10 mg/m2, substituted for doxorubicin, 50 mg/m2, results in a poorer response when CNOP (cyclophosphamide [Cytoxan, Neosar], mitoxantrone [Novantrone], vincristine [Oncovin], prednisone) is compared to CHOP (cyclophosphamide, doxorubicin HCl vincristine, prednsione); however, increasing the mitoxantrone dose to 12 mg/m2 in either the CNOP or CMP-BOP (cyclophosphamide, mitoxantrone, procarbazine [Matulane], bleomycin [Blenoxane], vincristine, prednisone) regimens yields results comparable to those achieved with the doxorubicin-containing regimen. Comparable results have also been observed when 10 mg/M2 of mitoxantrone was substituted for 45 mg/M2 of doxorubicin in the m-BACOD (methorexate, bleomycin, doxorubicin [Adriamycin], cyclophosphamide, vincristine, dexamethasone) regimen. Mitoxantrone is active in NHL, and combinations including mitoxantrone can be used effectively and may provide an advantage in the elderly. PMID:12017536

  7. Activity of BKM120 and BEZ235 against Lymphoma Cells

    PubMed Central

    Civallero, Monica; Cosenza, Maria; Pozzi, Samantha; Bari, Alessia; Ferri, Paola; Sacchi, Stefano

    2015-01-01

    Non-Hodgkin lymphomas encompass a heterogeneous group of cancers, with 85–90% arising from B lymphocytes and the remainder deriving from T lymphocytes or NK lymphocytes. These tumors are molecularly and clinically heterogeneous, showing dramatically different responses and outcomes with standard therapies. Deregulated PI3K signaling is linked to oncogenesis and disease progression in hematologic malignancies and in a variety of solid tumors and apparently enhances resistance to antineoplastic therapy, resulting in a poor prognosis. Here, we have evaluated and compared the effects of the pan-PI3K inhibitor BKM120 and the dual PI3K/mTOR inhibitor BEZ235 on mantle, follicular, and T-cell lymphomas. Our results suggest that BKM120 and BEZ235 can effectively inhibit lymphoma cell proliferation by causing cell cycle arrest and can lead to cell death by inducing apoptosis and autophagy mediated by ROS accumulation. Despite great advances in lymphoma therapy after the introduction of monoclonal antibodies, many patients still die from disease progression. Therefore, novel treatment approaches are needed. BKM120 and BEZ235 alone and in combination are very effective against lymphoma cells in vitro. If further studies confirm their effectiveness in animal models, they may be promising candidates for development as new drugs. PMID:26557706

  8. Proteomic analysis of mare follicular fluid during late follicle development

    PubMed Central

    2011-01-01

    Background Follicular fluid accumulates into the antrum of follicle from the early stage of follicle development. Studies on its components may contribute to a better understanding of the mechanisms underlying follicular development and oocyte quality. With this objective, we performed a proteomic analysis of mare follicular fluid. First, we hypothesized that proteins in follicular fluid may differ from those in the serum, and also may change during follicle development. Second, we used four different approaches of Immunodepletion and one enrichment method, in order to overcome the masking effect of high-abundance proteins present in the follicular fluid, and to identify those present in lower abundance. Finally, we compared our results with previous studies performed in mono-ovulant (human) and poly-ovulant (porcine and canine) species in an attempt to identify common and/or species-specific proteins. Methods Follicular fluid samples were collected from ovaries at three different stages of follicle development (early dominant, late dominant and preovulatory). Blood samples were also collected at each time. The proteomic analysis was carried out on crude, depleted and enriched follicular fluid by 2D-PAGE, 1D-PAGE and mass spectrometry. Results Total of 459 protein spots were visualized by 2D-PAGE of crude mare follicular fluid, with no difference among the three physiological stages. Thirty proteins were observed as differentially expressed between serum and follicular fluid. Enrichment method was found to be the most powerful method for detection and identification of low-abundance proteins from follicular fluid. Actually, we were able to identify 18 proteins in the crude follicular fluid, and as many as 113 in the enriched follicular fluid. Inhibins and a few other proteins involved in reproduction could only be identified after enrichment of follicular fluid, demonstrating the power of the method used. The comparison of proteins found in mare follicular fluid

  9. Benign follicular tumors*

    PubMed Central

    Tellechea, Oscar; Cardoso, José Carlos; Reis, José Pedro; Ramos, Leonor; Gameiro, Ana Rita; Coutinho, Inês; Baptista, António Poiares

    2015-01-01

    Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients. PMID:26734858

  10. Breast Implant–associated Anaplastic Large Cell Lymphoma: Updated Results from a Structured Expert Consultation Process

    PubMed Central

    Predmore, Zachary S.; Mattke, Soeren; van Busum, Kristin; Gidengil, Courtney A.

    2015-01-01

    Background: Despite increased cases published on breast implant–associated anaplastic large cell lymphoma (BIA-ALCL), important clinical issues remain unanswered. We conducted a second structured expert consultation process to rate statements related to the diagnosis, management, and surveillance of this disease, based on their interpretation of published evidence. Methods: A multidisciplinary panel of 12 experts was selected based on nominations from national specialty societies, academic department heads, and recognized researchers in the United States. Results: Panelists agreed that (1) this disease should be called “BIA-ALCL”; (2) late seromas occurring >1 year after breast implantation should be evaluated via ultrasound, and if a seroma is present, the fluid should be aspirated and sent for culture, cytology, flow cytometry, and cell block to an experienced hematopathologist; (3) surgical removal of the affected implant and capsule (as completely as possible) should occur, which is sufficient to eradicate capsule-confined BIA-ALCL; (4) surveillance should consist of clinical follow-up at least every 6 months for at least 5 years and breast ultrasound yearly for at least 2 years; and (5) BIA-ALCL is generally a biologically indolent disease with a good prognosis, unless it extends beyond the capsule and/or presents as a mass. They firmly disagreed with statements that chemotherapy and radiation therapy should be given to all patients with BIA-ALCL. Conclusions: Our assessment yielded consistent results on a number of key, incompletely addressed issues regarding BIA-ALCL, but additional research is needed to support these statement ratings and enhance our understanding of the biology, treatment, and outcomes associated with this disease. PMID:25674377

  11. Etiologic heterogeneity among non-Hodgkin lymphoma subtypes

    PubMed Central

    Wang, Sophia S.; Cozen, Wendy; Linet, Martha S.; Chatterjee, Nilanjan; Davis, Scott; Severson, Richard K.; Colt, Joanne S.; Vasef, Mohammad A.; Rothman, Nathaniel; Blair, Aaron; Bernstein, Leslie; Cross, Amanda J.; De Roos, Anneclaire J.; Engels, Eric A.; Hein, David W.; Hill, Deirdre A.; Kelemen, Linda E.; Lim, Unhee; Lynch, Charles F.; Schenk, Maryjean; Wacholder, Sholom; Ward, Mary H.; Hoar Zahm, Shelia; Chanock, Stephen J.; Cerhan, James R.; Hartge, Patricia

    2008-01-01

    Understanding patterns of etiologic commonality and heterogeneity for non-Hodgkin lymphomas may illuminate lymphomagenesis. We present the first systematic comparison of risks by lymphoma subtype for a broad range of putative risk factors in a population-based case-control study, including diffuse large B-cell (DLBCL; N = 416), follicular (N = 318), and marginal zone lymphomas (N = 106), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; N = 133). We required at least 2 of 3 analyses to support differences in risk: (1) polytomous logistic regression, (2) homogeneity tests, or (3) dichotomous logistic regression, analyzing all 7 possible pairwise comparisons among the subtypes, corresponding to various groupings by clinical behavior, genetic features, and differentiation. Late birth order and high body mass index (≥ 35) kg/m2) increased risk for DLBCL alone. Autoimmune conditions increased risk for marginal zone lymphoma alone. The tumor necrosis factor G-308A polymorphism (rs1800629) increased risks for both DLBCL and marginal zone lymphoma. Exposure to certain dietary heterocyclic amines from meat consumption increased risk for CLL/SLL alone. We observed no significant risk factors for follicular lymphoma alone. These data clearly support both etiologic commonality and heterogeneity for lymphoma subtypes, suggesting that immune dysfunction is of greater etiologic importance for DLBCL and marginal zone lymphoma than for CLL/SLL and follicular lymphoma. PMID:18796628

  12. Canine lymphoma

    SciTech Connect

    Weller, R.E.

    1986-10-01

    Canine lymphoma has served as the ''workhorse'' for the development of veterinary oncology and as an important animal model for human non-Hodgkins lymphomas. Significant advances have been achieved in understanding the biological behavior of the disease and in its treatment. Although it is unlikely that a cure for lymphoma will be achieved, owners should be encouraged to treat their pets, provided they understand that only prolonged remissions and survivals are likely to result. Cooperative studies, employing large numbers of dogs, are needed to optimize and refine the classification scheme to provide a system with diagnostic and prognostic correlates and derive maximum benefit from therapeutic regimens. Such studies need to be prospective in nature, with a solid statistical base incorporated into their design. Rather than being content with what we have accomplished to date in treatment of canine lymphoma, the opportunity exists for the veterinary profession to make further significant contributions to the understanding and treatment of lymphoma in the dog. 10 refs., 4 tabs.

  13. Expression of programmed death-1 in primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma, cutaneous pseudo-T-cell lymphoma, and other types of cutaneous T-cell lymphoma.

    PubMed

    Cetinözman, Fatma; Jansen, Patty M; Willemze, Rein

    2012-01-01

    In this study we investigated whether programmed death-1 (PD-1) could serve as a useful diagnostic marker to differentiate between primary cutaneous CD4 small/medium-sized pleomorphic T-cell lymphoma (PCSM-TCL) and cutaneous pseudo-T-cell lymphomas on the one hand and other types of cutaneous T-cell lymphomas (CTCLs) on the other. Formalin-fixed, paraffin-embedded skin biopsies from 26 patients with PCSM-TCL or pseudo-T-cell lymphoma, including 1 patient with a lymphomatoid drug eruption, and 52 skin biopsies from other types of CTCLs were stained for PD-1. In addition, PD-1-positive cases were stained with antibodies against BCL6, CXCL13, and CD10 to determine a possible relationship with follicular helper T (TFH) cells. In all 26 cases of PCSM-TCL or pseudo-T-cell lymphoma, the medium-sized to large-sized atypical T cells consistently expressed PD-1, BCL6, and CXCL13 but not CD10. PD-1 expression was found in only 2 of 21 cases of mycosis fungoides and in only 2 of 16 cases of cutaneous peripheral T-cell lymphoma, unspecified. All 4 patients with an aggressive epidermotropic cytotoxic CD8 CTCL and all 11 cases with a primary cutaneous CD30 lymphoproliferative disorder were negative for PD-1. In conclusion, PD-1 is typically expressed by atypical cells in PCSM-TCL and pseudo-T-cell lymphoma but is not expressed or is rarely expressed in other types of CTCLs. Therefore, it may serve as a suitable adjunct in differential diagnosis. Our results demonstrate that the atypical cells in PCSM-TCL and pseudo-T-cell lymphomas share a common TFH phenotype and support the view that most cases classified nowadays as PCSM-TCL are identical to cutaneous pseudo-T-cell lymphomas described previously. PMID:21989349

  14. Association between simian virus 40 and non-Hodgkin lymphoma

    NASA Technical Reports Server (NTRS)

    Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.

    2002-01-01

    BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.

  15. Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach: results of a controlled clinical trial.

    PubMed

    Avilés, Agustin; Nambo, María Jesús; Neri, Natividad; Talavera, Alejandra; Cleto, Sergio

    2005-01-01

    Treatment of patients with early stage gastric mucosa-associated lymphoid tissue (MALT) remains undefined. We began a controlled clinical trial to evaluate efficacy and toxicity of the most common therapies. Two hundred and forty-one patients with gastric low-grade MALT lymphoma in early stage (IE and IIE) were randomized to surgery (80 cases), radiotherapy (78 cases), and chemotherapy (83 cases). With a median follow-up of 7.5 yr, actuarial curves at 10 yr showed that event-free survival was 52% in patients treated with surgery, 52% in radiotherapy arm, and 87% in the chemotherapy group (p < 0.01). However, overall survival did not showed any statistical differences: 80%, 75% and 87%, respectively (p = 0.4). Acute and late toxicities were mild. No death-related treatments were observed. No clear differences were observed between the most common therapies in patients with primary gastric MALT lymphoma in early stages, probably because this type of lymphoma has an high response rate to salvage treatment after failure to local treatment (surgery and radiotherapy). Thus considered, chemotherapy alone is an effective and safe therapeutic approach in this setting of patients. Surgery or radiotherapy will be reserved to patients that are not candidates for chemotherapy. PMID:15750197

  16. Clinical features and treatment results in children with anaplastic large cell lymphoma.

    PubMed

    Ataş, Erman; Kutluk, M Tezer; Akyüz, Canan; Kale, Gülsev; Varan, Ali; Yalçın, Bilgehan; Aydın, Burça; Büyükpamukçu, Münevver

    2015-01-01

    Anaplastic large cell lymphoma (ALCL) tends to have frequent relapse and good response to salvage chemotherapy. The frequency of ALCL among 1486 Non-Hodgkin's lymphoma (NHL) cases followed-up since 1972 was 1.5%, however, the percentage was 9.3% in cases diagnosed after 2000. Event-free survival (EFS) and overall survival (OS) rates for 23 children were 32.2% and 72.8% at 3 years, respectively. Disseminated diseases, no response to first line treatment, anaplastic lymphoma kinase (ALK) negativity were found as significant predictors on survival of ALCL. The proper diagnosis and early referral is essential in these children for a better survival rate. The children with ALK negative status should be monitored carefully because of the poor prognostic factors, and treated differently. The survival rates in this study are need of further improvement since the survival rates with current protocols are achievable at a level more than 80%. This is mainly related with late referral of those children with advanced disease. PMID:27411412

  17. Mature B-cell lymphoma and leukemia in children and adolescents-review of standard chemotherapy regimen and perspectives.

    PubMed

    Worch, Jennifer; Rohde, Marius; Burkhardt, Birgit

    2013-09-01

    Mature B-cell non-Hodgkin lymphoma (B-NHL) comprises more than 50% of all non-Hodgkin lymphoma (NHL) in children and adolescents. Many B-NHL subtypes frequently observed in adults are rarely diagnosed in children and adolescents. In this age group, Burkitt lymphoma (BL), Burkitt leukemia or FAB L3 leukemia (B-AL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMLBL), follicular lymphoma (FL), and aggressive mature B-NHL not further classifiable (B-NHL nfc) are the most common subtypes. Diverse clinical trials demonstrated similar results of current combination chemotherapy regimens succeeding in overall survival rates of more than 80%. However, treatment-related toxicity and the poor prognosis of relapse are serious concerns. Furthermore, specific histological B-NHL subtypes are rare in children and optimal treatment is not established. New treatment modalities are urgently needed for these patient groups. Rituximab, a monoclonal antibody that is already established in the treatment of adults with mature B-NHL, demonstrated promising results in pediatric patients. The definitive role of rituximab in the treatment of children and adolescents with B-NHL needs to be evaluated in prospective controlled clinical trials. This review provides a comprehensive overview of chemotherapy regimens and the perspectives for children and adolescents with mature B-cell lymphoma and leukemia. PMID:23570584

  18. Pathogenesis of AIDS lymphomas.

    PubMed

    Herndier, B G; Kaplan, L D; McGrath, M S

    1994-08-01

    The AIDS-associated lymphomas represent a heterogeneous set of disease processes. The largest histologic subset of lymphomas is the large-cell lymphomas, which represent a spectrum of disease processes ranging from monomorphic monoclonal B-cell proliferations to very polymorphic and polyclonal mixtures of B cells, T cells and macrophages. The next most frequent class of systemic lymphoma are the small non-cleaved cell or Burkitt's-like lymphomas. These are relatively monomorphic, monoclonal malignant B-cell proliferations. The final subset of lymphomas, which are likely to become more common as the AIDS epidemic progresses, are the primary CNS lymphomas, which are expansions of EBV-immortalized B cells. The high incidence of tumor-associated EBV in the CNS lymphomas makes these lesions somewhat analogous to an opportunistic EBV infection. In HIV disease there is a long lag after infection before the appearance of clinical manifestations of impaired T-cell immunity. During this period, both appropriate B-cell proliferation in response to antigen (including the ubiquitous HIV) and abnormal B-cell proliferation (autoimmune, dysregulated) occur as the follicular architecture is disrupted by the virus and potential APC are exposed and/or infected with HIV. The destruction of FDC or the involution of their processes could interfere with the elimination by apoptosis of low-avidity B-cell clones. Antigen-competent B cells with pre-existing chromosomal translocations such as the t(8;14) (c-myc, IgH) would have a selective growth advantage in this setting. Figure 9 shows a schematic representation of prelymphomatous and lymphomagenic events as they are projected to occur. A similar pathogenetic scheme has been postulated for follicular B-cell lymphomas: PCR studies have demonstrated that a pool of t(14;18) (IgH;bcl-2) B-cells are present in lymph nodes featuring follicular hyperplasia. In response to antigen (the evidence favoring antigen drive is extensive hypersomatic

  19. [Results of immuno-chemotherapeutic treatment of patients with diffuse large B-cell lymphoma].

    PubMed

    Schneider, Tamás; Molnár, Zsuzsanna; Deák, Beáta; Várady, Erika; Tóth, Erika; Csomor, Judit; Matolcsy, András; Lovey, József; Lengyel, Zsolt; Petri, Klára; Gaudi, István; Rosta, András

    2009-11-01

    Treatment with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) has been considered as the standard therapy for diffuse large B-cell lymphoma (DLBCL) for more than 20 years. CHOP treatment in combination with targeted immunotherapy, rituximab (R-CHOP), resulted in significant improvements in the treatment of this group of patients. In this study, efficacy of R-CHOP and R-CHOP-like treatments was analysed. Results were compared to the data of historical patients only receiving CHOP treatment or CHOP-like treatment. Between September 2002 and April 2005, 140 newly diagnosed, untreated DLBCL patients started to receive R-CHOP treatment in a single centre. The eligibility criteria included advanced stage (clinical stages III-IV), or large tumour size (>7 cm) and/or symptom B or extranodal manifestation in the case of clinical stages I-II. The results were compared to the data of 130 patients only receiving CHOP treatment in the past. In the patients receiving R-CHOP, the therapeutic outcomes were superior for all parameters. During an average follow-up period of 44 or 52 months, the overall remission rate was 73.6% in the R-CHOP group in comparison with 47.7% in the CHOP group. The 5-year overall survival was 68.6% vs. 41.0% (RR: 0.4293, CI: 0.2963-0.6221; p < 0.0001), the event-free survival was 59.8% vs. 33.5% (RR: 0.5038, CI: 0.3606-0.7038; p < 0.0001) and the progression-free survival was 64.4% vs. 37.6% (RR: 0.4915, CI: 0.3442-0.7019; p < 0.0001). Since prognostic parameters were more favourable in the R-CHOP group, patient groups were also compared using the International Prognostic Index score. Again, significant differences were revealed by the subgroup analyses. The 5-year overall survival was 74.4% vs. 47.9% (RR: 0.4475, CI: 0.2418-0.8285; p = 0.0084) and 52.0% vs. 28.8% (RR: 0.4989, CI: 0.3098-0.8035; p = 0.003) in the group with good prognosis and in the group with poor prognosis, respectively. In the group with very good prognosis, the

  20. Conjunctival lymphoma: Results and treatment with a single anterior electron field. A lens sparing approach

    SciTech Connect

    Dunbar, S.F.; Linggood, R.M.; Doppke, K.P.; Duby, A.; Wang, C.C. )

    1990-08-01

    Lymphoma of the conjunctiva is rare. It presents in older patients as a mass lesion and usually remains localized. Surgery is limited to biopsy, and radiation therapy is the definitive treatment of choice. The entire conjunctiva is treated. Relatively high doses (approximately 30 Gy) are required for local control, which may lead to cataract formation. Twelve patients with conjunctival lymphoma were treated at the Massachusetts General Hospital between 1979 and 1988. Ten of 12 patients presented with a unilateral lesion; 2 of 12 with bilateral lesions. Two of 12 patients were found to have systemic disease at the time of presentation. One patient developed conjunctival lymphoma 5 years after the diagnosis of generalized disease. Using electron beam, all patients were treated with a single anterior circular field to total doses ranging from 24 Gy to 30 Gy delivered in 8 to 16 fractions over 9 to 20 days. In all cases, the lens was shielded by a specially designed plastic contact lens bearing a 12 mm diameter lead shield. The lens dose was determined at varying depths beneath the shield for 6 MeV and 9 MeV electron beams and ranged from a minimum of 5% to an absolute maximum of 18% of the total dose delivered to the tumor. Local control was maintained in all patients with follow-up to 9 1/2 years. One patient relapsed distantly 3 years after treatment. One of 12 patients died of systemic disease 4 years after treatment of the ocular lesion. Two patients developed cataracts 4 and 5 years after treatment; one had bilateral cataract, although only one eye had been treated. Both patients were over 75 years old. In both cases, the cataracts were felt to be senile cataracts which are ophthalmologically and radiographically distinguishable from radiation induced lesions.

  1. Management of Indolent Lymphoma: Where Are We Now and Where Are We Going

    PubMed Central

    Lunning, Matthew; Vose, Julie M.

    2013-01-01

    Summary Indolent lymphoma comprises a unique and challenging subset of non-Hodgkin lymphoma (NHL). While definitions of indolence will vary, the most common indolent NHL subtypes include follicular lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma. Patients with indolent NHL (iNHL) excluding those with rare localized presentations are often met with an incurable but highly treatable NHL. In the rituximab era, response rates are approaching 90% with rituximab plus chemotherapy and time to next treatment are beginning to be measured in years. As a result of a prolonged natural history, we are encountering a gridlock of novel regimens and agents that appropriately fill peer-reviewed journals. In this review, we tackle a spectrum of topics in the management of indolent lymphoma including the initial approach to the newly diagnosed patient, approaches to first cytotoxic chemotherapy, maintenance and consolidation techniques, as well as highlight promising treatments on the horizon in iNHL. Clinicians continue to face tough choices in the management of iNHL. Through well-thought out clinical trials and peer-reviewed vetting of data we will continue to determine how to best manage the clinical continuum that is iNHL. PMID:23063143

  2. Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States.

    PubMed

    Hopp, Lydia; Löffler-Wirth, Henry; Binder, Hans

    2015-01-01

    Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12. PMID:26371046

  3. Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States

    PubMed Central

    Hopp, Lydia; Löffler-Wirth, Henry; Binder, Hans

    2015-01-01

    Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt’s lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12. PMID:26371046

  4. Down-Regulation of CD9 Expression and its Correlation to Tumor Progression in B Lymphomas

    PubMed Central

    Yoon, Sun-Ok; Zhang, Xin; Freedman, Arnold S.; Zahrieh, David; Lossos, Izidore S.; Li, Li; Choi, Yong Sung

    2010-01-01

    Histological transformation, a pivotal event in the natural history of cancers including lymphomas, is typically associated with more aggressive clinical behavior. L3055, a B lymphoma cell line of germinal center (GC) origin, is dependent on follicular dendritic cells (FDCs) for survival and proliferation, similar to GC-B cells. However, L3055 cells become less FDC-dependent after prolonged culture, which is analogous to transformation in vivo. Comparison of two L3055 subclones (i.e., the FDC-dependent indolent clone 12 and the FDC-independent aggressive clone 33) by DNA microarray revealed that CD9 was the most differentially expressed gene (P = 0.05). L3055-12 expresses high levels of CD9 while L3055-33 does not. Reduced levels or loss of CD9 expression is also observed in other CD9-positive B lymphoma cell lines. The resultant CD9-negative cells grow faster than CD9-positive cells due to their greater resistance to apoptosis. Furthermore, CD9-negative cells are less dependent on FDCs for their survival and growth compared with CD9-positive cells. CD9 down-regulation in B lymphomas appears to be controlled epigenetically, mainly through histone modifications. These findings imply that CD9 is inversely correlated with B lymphoma progression, and CD9 inactivation may play an important role in B lymphoma transformation. PMID:20566742

  5. Leukemia and non-Hodgkin's lymphoma and residential proximity to industrial plants

    SciTech Connect

    Linos, A.; Blair, A.; Gibson, R.W.; Everett, G.; Van Lier, S.; Cantor, K.P.; Schuman, L.; Burmeister, L. )

    1991-03-01

    The risks of developing leukemia and non-Hodgkin's lymphoma from living near industrial facilities were evaluated among men from Iowa and Minnesota in a population-based, case-control study. We found a statistically significant increase in the risk of developing non-Hodgkin's lymphoma (RR = 1.4) and a slight, nonsignificant excess for leukemia (RR = 1.2) among individuals who lived .8-3.2 km (1/2-2 miles) from a factory. Risks were greater for certain histologic types: follicular lymphoma (RR = 1.5), acute lymphocytic leukemia (RR = 5.4), and acute myelocytic leukemia (RR = 2.2). For non-Hodgkin's lymphoma (but not for leukemia), the relative risks for those living within .8 km (1/2 mile) of a factory were similar or slightly larger than for those living .8-3.2 km (1/2-2 miles) from a factory. Risks did not increase with duration of residence near a factory. The elevated risks of non-Hodgkin's lymphoma were particularly associated with residing near stone, clay, or glass industry facilities. The risk of developing leukemia was greater among persons who resided near chemical and petroleum plants. These preliminary findings raise the possibility that general environmental exposure associated with certain industrial activities may elevate the risk of developing leukemia and non-Hodgkin's lymphoma. Evaluation of data on proximity to industrial plants from studies in other geographic locations is needed to determine whether our results represent a meaningful association.

  6. Histopathology and immunohistochemistry of peripheral T cell lymphomas: a proposal for their classification.

    PubMed Central

    Suchi, T; Lennert, K; Tu, L Y; Kikuchi, M; Sato, E; Stansfeld, A G; Feller, A C

    1987-01-01

    Based on the results of histological and immunohistochemical observations of a large number of peripheral T cell lymphomas from China, England, Germany and Japan, histological and cytological morphology were correlated with immunophenotype, aetiological association with HTLV-1, and clinical behaviour to produce a working classification of the T cell lymphomas. This classification, based mainly on cytological criteria, divides the peripheral T cell lymphomas into tumours of low grade and high grade malignancy. Adult T cell lymphoma/leukaemia (ATLL) is caused by HTLV-1 and belongs chiefly to the high grade category. Some tumours are characterised by an admixture of other cells (epithelioid cells, follicular dendritic cells, etc) and structures (high endothelial venules, follicles), which may indicate the secretion of lymphokines by the tumour cells. Clear cells seem to be specific for T cell lymphomas and may occur in various types of peripheral T cell lymphoma. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 Fig 8 Fig 9 Fig 10 Fig 11 Fig 12 Fig 13 Fig 14 Fig 15 PMID:3312308

  7. Lectin-like transcript 1 is a marker of germinal center-derived B-cell non-Hodgkin's lymphomas dampening natural killer cell functions

    PubMed Central

    Germain, Claire; Guillaudeux, Thierry; Galsgaard, Elisabeth D; Hervouet, Catherine; Tekaya, Nedra; Gallouet, Anne-Sophie; Fassy, Julien; Bihl, Franck; Poupon, Gwenola; Lazzari, Anne; Spee, Pieter; Anjuère, Fabienne; Pangault, Céline; Tarte, Karin; Tas, Patrick; Xerri, Luc; Braud, Veronique M

    2015-01-01

    Non-Hodgkin's lymphomas (NHLs) are malignant neoplasms which are clinically and biologically diverse. Their incidence is constantly increasing and despite treatment advances, there is a need for novel targeted therapies. Here, we identified Lectin-like transcript 1 (LLT1) as a biomarker of germinal center (GC)-derived B-cell NHLs. LLT1 identifies GC B cells in reactive tonsils and lymph nodes and its expression is maintained in B-cell NHLs which derive from GC, including Burkitt lymphoma (BL), follicular lymphoma (FL), and GC-derived diffuse large B-cell lymphoma (DLBCL). We further show that LLT1 expression by tumors dampens natural killer (NK) cell functions following interaction with its receptor CD161, uncovering a potential immune escape mechanism. Our results pinpoint LLT1 as a novel biomarker of GC-derived B-cell NHLs and as a candidate target for innovative immunotherapies. PMID:26405582

  8. Brentuximab vedotin for treatment of relapsed or refractory malignant lymphoma: results of a systematic review and meta-analysis of prospective studies

    PubMed Central

    Chen, Runzhe; Wang, Fei; Zhang, Hongming; Chen, Baoan

    2015-01-01

    Background Recently, brentuximab vedotin has become a promising therapeutic approach for CD30-positive hematological malignancies, but its role in other relapsed or refractory malignant lymphoma needs to be proven. Brentuximab vedotin was demonstrated effective, but no study has summarized the concrete effect of brentuximab vedotin in malignant lymphoma. To truly know the role of brentuximab vedotin, we performed a systematic review of the literature and a meta-analysis of all known prospective trials, to assess the value of brentuximab vedotin for patients with relapsed and refractory malignant lymphoma. Methods and materials This was a systematic review of publications indexed in the PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ISI Web of Knowledge performed on February 10, 2015. Six studies, including 302 patients were identified. Meta-analyses were carried out to calculate the objective response rate (ORR), complete response rate (CRR), and partial response rate (PRR) of brentuximab vedotin for malignant lymphoma. Results In patients with malignant lymphoma, ORR was 0.61, CRR was 0.38, and PRR was 0.51. High heterogeneity between studies was observed, and funnel plots were not symmetrical, which means that publication bias existed. Brentuximab vedotin was generally well-tolerated by patients reported in the included studies; adverse effects also occurred, but they were considered manageable. Conclusion Our analysis revealed a promising benefit of brentuximab vedotin in the treatment of relapsed and refractory malignant lymphoma. Larger sample of randomized controlled clinical trials are needed in the future. PMID:25945039

  9. Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis

    PubMed Central

    Weissmann, Marina; Arvatz, Gil; Horowitz, Netanel; Feld, Sari; Naroditsky, Inna; Zhang, Yi; Ng, Mary; Hammond, Edward; Nevo, Eviatar; Vlodavsky, Israel; Ilan, Neta

    2016-01-01

    Heparanase is an endoglycosidase that cleaves heparan sulfate side chains of proteoglycans, resulting in disassembly of the extracellular matrix underlying endothelial and epithelial cells and associating with enhanced cell invasion and metastasis. Heparanase expression is induced in carcinomas and sarcomas, often associating with enhanced tumor metastasis and poor prognosis. In contrast, the function of heparanase in hematological malignancies (except myeloma) was not investigated in depth. Here, we provide evidence that heparanase is expressed by human follicular and diffused non-Hodgkin's B-lymphomas, and that heparanase inhibitors restrain the growth of tumor xenografts produced by lymphoma cell lines. Furthermore, we describe, for the first time to our knowledge, the development and characterization of heparanase-neutralizing monoclonal antibodies that inhibit cell invasion and tumor metastasis, the hallmark of heparanase activity. Using luciferase-labeled Raji lymphoma cells, we show that the heparanase-neutralizing monoclonal antibodies profoundly inhibit tumor load in the mouse bones, associating with reduced cell proliferation and angiogenesis. Notably, we found that Raji cells lack intrinsic heparanase activity, but tumor xenografts produced by this cell line exhibit typical heparanase activity, likely contributed by host cells composing the tumor microenvironment. Thus, the neutralizing monoclonal antibodies attenuate lymphoma growth by targeting heparanase in the tumor microenvironment. PMID:26729870

  10. Polymyalgia Rheumatica Revealing a Lymphoma: A Two-Case Report.

    PubMed

    Verhoeven, Frank; Guillot, Xavier; Chouk, Mickaël; Prati, Clément; Wendling, Daniel

    2016-01-01

    Introduction. Polymyalgia rheumatica (PMR) is one of the most common inflammatory rheumatism types in elderly population. The link between cancer and PMR is a matter of debate. Methods. We report two cases of PMR leading to the diagnosis of lymphoma and the growing interest of PET-TDM in this indication. Results. A 84-year-old man known for idiopathic neutropenia presented an inflammatory arthromyalgia of the limb girdle since one month. Blood exams highlighted the presence of a monoclonal B cell clone. Bone marrow concluded to a B cell lymphoma of the marginal zone. He was successfully treated with 0.3 mg/kg/d of prednisone, and response was sustained after 6 months. A 73-year-old man known for prostatic neoplasia in remission for 5 years presented arthromyalgia of the limb girdle since one month. PET-CT revealed bursitis of the hips and the shoulders, no prostatic cancer recurrence, and a metabolically active iliac lymphadenopathy whose pathologic exam concluded to a low grade follicular lymphoma. He was successfully treated with 0.3 mg/kg/d of prednisone. Conclusion. These observations may imply that lymphoma is sometimes already present when PMR is diagnosed and PET-CT is a useful tool in the initial assessment of PMR to avoid missing neoplasia. PMID:27597921

  11. Non-Hodgkin lymphoma in Southern Africa: review of 487 cases from The International Non-Hodgkin Lymphoma Classification Project.

    PubMed

    Perry, Anamarija M; Perner, Yvonne; Diebold, Jacques; Nathwani, Bharat N; MacLennan, Kenneth A; Müller-Hermelink, Hans K; Bast, Martin; Boilesen, Eugene; Armitage, James O; Weisenburger, Dennis D

    2016-03-01

    Comparative data on the distribution of non-Hodgkin lymphoma (NHL) subtypes in Southern Africa (SAF) is scarce. In this study, five expert haematopathologists classified 487 consecutive cases of NHL from SAF using the World Health Organization classification, and compared the results to North America (NA) and Western Europe (WEU). Southern Africa had a significantly lower proportion of low-grade (LG) B-NHL (34·3%) and a higher proportion of high-grade (HG) B-NHL (51·5%) compared to WEU (54·5% and 36·4%) and NA (56·1% and 34·3%). High-grade Burkitt-like lymphoma was significantly more common in SAF (8·2%) than in WEU (2·4%) and NA (2·5%), most likely due to human immunodeficiency virus infection. When SAF patients were divided by race, whites had a significantly higher frequency of LG B-NHL (60·4%) and a lower frequency of HG B-NHL (32·7%) compared to blacks (22·5% and 62·6%), whereas the other races were intermediate. Whites and other races had a significantly higher frequency of follicular lymphoma and a lower frequency of Burkitt-like lymphoma compared to blacks. The median ages of whites with LG B-NHL, HG B-NHL and T-NHL (64, 56 and 67 years) were significantly higher than those of blacks (55, 41 and 34 years). Epidemiological studies are needed to better understand these differences. PMID:26898194

  12. Prognostic value of FDG-PET in Hodgkin lymphoma for posttreatment evaluation. Long term follow-up results.

    PubMed

    Molnar, Z; Simon, Z; Borbenyi, Z; Deak, B; Galuska, L; Keresztes, K; Miltenyi, Z; Marton, I; Rosta, A; Schneider, T; Tron, L; Varady, E; Illes, A

    2010-01-01

    Determining the viability of residual tumor masses is a great challenge after primary treatment of Hodgkin lymphoma. FDG-PET may play a crucial role in this procedure. In this study, files of 128 Hodgkin lymphoma patients were reviewed, who were treated in three Hungarian hematology centers between January 1995 and February 2005. CT scan showed residual tumor mass by all of them. Their median follow-up was 75.5 months from PET examination. The number of true-positive, true-negative, false-positive, false-negative subjects were 29, 83, 10, 6, respectively. Sensitivity of post-treatment FDG-PET was 83 %, specificity 93 %, positive predictive value 74 %, negative predictive value 93 %, and accuracy 88 %. The difference between the event free survival of PET positive and negative cases is highly significant (p=0.0000), according to the Mantel-Cox test. Our results in the largest cohort of patients, in accordance with literature, clearly indicates that patients with negative FDG-PET results are unlikely to progress or relapse during the longest follow-up. PMID:20429626

  13. Follicular thyroid carcinoma.

    PubMed

    Haigh, Philip I

    2002-08-01

    Follicular carcinomas are rare thyroid malignancies that are difficult to diagnose preoperatively. Fine needle aspiration is an excellent diagnostic tool and should be the initial step in managing the solitary thyroid nodule. Follicular carcinoma cannot be diagnosed with certainty by cytologic features alone; the diagnosis rests on the histologic findings of blood vessel or tumor capsule invasion. Surgical resection is the primary option for treatment. The extent of thyroidectomy for optimal survival outcome has not been determined scientifically. The outcome is excellent in minimally invasive follicular carcinoma with lobectomy and isthmusectomy; it is difficult to argue that total thyroidectomy is necessary. In a low risk prognostic group, for tumors other than minimally invasive carcinoma, lobectomy and isthmusectomy or total thyroidectomy can be justified. However, if total thyroidectomy can be done safely with a minimum of complications, then it has definite advantages for staging, postoperative surveillance, treatment, and possibly a lower recurrence rate and better survival rate. For all patients at high risk of recurrence, total thyroidectomy is preferred. PMID:12074771

  14. Pediatric lymphomas in Brazil

    PubMed Central

    Gualco, Gabriela; Klumb, Claudete E; Barber, Glen N; Weiss, Lawrence M; Bacchi, Carlos E

    2010-01-01

    OBJECTIVE: This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. METHODS: A retrospective analyses of diagnosed pediatric lymphoma cases in a 10‐year period was performed. We believe that it represents the largest series of pediatric lymphomas presented from Brazil. RESULTS: Non‐Hodgkin lymphomas represented 68% of the cases, including those of precursor (36%) and mature (64%) cell origin. Mature cell lymphomas comprised 81% of the B‐cell phenotype and 19% of the T‐cell phenotype. Hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. The geographic distribution showed 38.4% of the cases in the Southeast region, 28.7% in the Northeast, 16.1% in the South, 8.8% in the North, and 8% in the Central‐west region. The distribution by age groups was 15–18 years old, 33%; 11–14 years old, 26%; 6–10 years old, 24%; and 6 years old or younger, 17%. Among mature B‐cell lymphomas, most of the cases were Burkitt lymphomas (65%), followed by diffuse large B‐cell lymphomas (24%). In the mature T‐cell group, anaplastic large cell lymphoma, ALK‐positive was the most prevalent (57%), followed by peripheral T‐cell lymphoma, then not otherwise specified (25%). In the group of classic Hodgkin lymphomas, the main histological subtype was nodular sclerosis (76%). Nodular lymphocyte predominance occurred more frequently than in other series. CONCLUSION: Some of the results found in this study may reflect the heterogeneous socioeconomical status and environmental factors of the Brazilian population in different regions. PMID:21340214

  15. Follicular dendritic cells in health and disease

    PubMed Central

    El Shikh, Mohey Eldin M.; Pitzalis, Costantino

    2012-01-01

    Follicular dendritic cells (FDCs) are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B-cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags) in the form of highly immunogenic immune complexes (ICs) consisting of Ag plus specific antibody (Ab) and/or complement proteins. FDCs multimerize Ags and present them polyvalently to B-cells in periodically arranged arrays that extensively crosslink the B-cell receptors for Ag (BCRs). FDC-FcγRIIB mediates IC periodicity, and FDC-Ag presentation combined with other soluble and membrane bound signals contributed by FDCs, like FDC-BAFF, -IL-6, and -C4bBP, are essential for the induction of the germinal center (GC) reaction, the maintenance of serological memory, and the remarkable ability of FDC-Ags to induce specific Ab responses in the absence of cognate T-cell help. On the other hand, FDCs play a negative role in several disease conditions including chronic inflammatory diseases, autoimmune diseases, HIV/AIDS, prion diseases, and follicular lymphomas. Compared to other accessory immune cells, FDCs have received little attention, and their functions have not been fully elucidated. This review gives an overview of FDC structure, and recapitulates our current knowledge on the immunoregulatory functions of FDCs in health and disease. A better understanding of FDCs should permit better regulation of Ab responses to suit the therapeutic manipulation of regulated and dysregulated immune responses. PMID:23049531

  16. Follicular dendritic cells in health and disease.

    PubMed

    El Shikh, Mohey Eldin M; Pitzalis, Costantino

    2012-01-01

    Follicular dendritic cells (FDCs) are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B-cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags) in the form of highly immunogenic immune complexes (ICs) consisting of Ag plus specific antibody (Ab) and/or complement proteins. FDCs multimerize Ags and present them polyvalently to B-cells in periodically arranged arrays that extensively crosslink the B-cell receptors for Ag (BCRs). FDC-FcγRIIB mediates IC periodicity, and FDC-Ag presentation combined with other soluble and membrane bound signals contributed by FDCs, like FDC-BAFF, -IL-6, and -C4bBP, are essential for the induction of the germinal center (GC) reaction, the maintenance of serological memory, and the remarkable ability of FDC-Ags to induce specific Ab responses in the absence of cognate T-cell help. On the other hand, FDCs play a negative role in several disease conditions including chronic inflammatory diseases, autoimmune diseases, HIV/AIDS, prion diseases, and follicular lymphomas. Compared to other accessory immune cells, FDCs have received little attention, and their functions have not been fully elucidated. This review gives an overview of FDC structure, and recapitulates our current knowledge on the immunoregulatory functions of FDCs in health and disease. A better understanding of FDCs should permit better regulation of Ab responses to suit the therapeutic manipulation of regulated and dysregulated immune responses. PMID:23049531

  17. Segmentation of follicular regions on H&E slides using a matching filter and active contour model

    NASA Astrophysics Data System (ADS)

    Belkacem-Boussaid, Kamel; Prescott, Jeffrey; Lozanski, Gerard; Gurcan, Metin N.

    2010-03-01

    Follicular Lymphoma (FL) accounts for 20-25% of non-Hodgkin lymphomas in the United States. The first step in follicular lymphoma grading is the identification of follicles. The goal of this paper is to develop a technique to segment follicular regions in H&E stained images. The method is based on a robust active contour model, which is initialized by a seed point selected inside the follicle manually by the user. The novel aspect of this method is the introduction of a matched filter for the flattening of background in the L channel of the Lab color space. The performance of the algorithm was tested by comparing it against the manual segmentations of trained readers using the Zijbendos similarity index. The mean accuracy of the final segmentation compared to the manual ground truth was 0.71 with a standard deviation of 0.12.

  18. Clinical Significance of sIL-2R Levels in B-Cell Lymphomas

    PubMed Central

    Yoshida, Noriaki; Oda, Miyo; Kuroda, Yoshiaki; Katayama, Yuta; Okikawa, Yoshiko; Masunari, Taro; Fujiwara, Megumu; Nishisaka, Takashi; Sasaki, Naomi; Sadahira, Yoshito; Mihara, Keichiro; Asaoku, Hideki; Matsui, Hirotaka; Seto, Masao; Kimura, Akiro; Arihiro, Koji; Sakai, Akira

    2013-01-01

    Elevated soluble interleukin-2 receptor (sIL-2R) in sera is observed in patients with malignant lymphoma (ML). Therefore, sIL-2R is commonly used as a diagnostic and prognostic marker for ML, but the mechanisms responsible for the increase in sIL-2R levels in patients with B-cell lymphomas have not yet been elucidated. We first hypothesized that lymphoma cells expressing IL-2R and some proteinases such as matrix metalloproteinases (MMPs) in the tumor microenvironment can give rise to increased sIL-2R in sera. However, flow cytometric studies revealed that few lymphoma cells expressed IL-2R α chain (CD25) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and most CD25-expressing cells in the tumor were T-cells. Distinct correlations between CD25 expression on B-lymphoma cells and sIL-2R levels were not observed. We then confirmed that MMP-9 plays an important role in producing sIL-2R in functional studies. Immunohistochemical (IHC) analysis also revealed that MMP-9 is mainly derived from tumor-associated macrophages (TAMs). We therefore evaluated the number of CD68 and CD163 positive macrophages in the tumor microenvironment using IHC analysis. A positive correlation between the levels of sIL-2R in sera and the numbers of CD68 positive macrophages in the tumor microenvironment was confirmed in FL and extranodal DLBCL. These results may be useful in understanding the pathophysiology of B-cell lymphomas. PMID:24236041

  19. Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells.

    PubMed

    Ise, Wataru; Inoue, Takeshi; McLachlan, James B; Kometani, Kohei; Kubo, Masato; Okada, Takaharu; Kurosaki, Tomohiro

    2014-08-12

    In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of follicular helper T (TFH) cell differentiation; however, its activation mechanisms and role in memory responses remain unclear. Here we demonstrate that survival of CXCR5(+) TFH memory cells, and thus subsequent recall antibody response, require Bcl6 expression. Furthermore, we show that, upon rechallenge with soluble antigen Bcl6 in memory TFH cells is rapidly induced in a dendritic cell-independent manner and that peptide:class II complexes (pMHC) on cognate memory B cells significantly contribute to this induction. Given the previous evidence that antigen-specific B cells residing in the follicles acquire antigens within minutes of injection, our results suggest that memory B cells present antigens to the cognate TFH memory cells, thereby contributing to rapid Bcl6 reexpression and differentiation of the TFH memory cells during humoral memory responses. PMID:25071203

  20. Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells

    PubMed Central

    Ise, Wataru; Inoue, Takeshi; McLachlan, James B.; Kometani, Kohei; Kubo, Masato; Okada, Takaharu; Kurosaki, Tomohiro

    2014-01-01

    In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of follicular helper T (TFH) cell differentiation; however, its activation mechanisms and role in memory responses remain unclear. Here we demonstrate that survival of CXCR5+ TFH memory cells, and thus subsequent recall antibody response, require Bcl6 expression. Furthermore, we show that, upon rechallenge with soluble antigen Bcl6 in memory TFH cells is rapidly induced in a dendritic cell-independent manner and that peptide:class II complexes (pMHC) on cognate memory B cells significantly contribute to this induction. Given the previous evidence that antigen-specific B cells residing in the follicles acquire antigens within minutes of injection, our results suggest that memory B cells present antigens to the cognate TFH memory cells, thereby contributing to rapid Bcl6 reexpression and differentiation of the TFH memory cells during humoral memory responses. PMID:25071203

  1. [Exposure to animals and non-Hodgkin lymphomas: pilot analysis about 261 cases].

    PubMed

    Jeanne, Aurélie; Aras, Myriam; Eisinger, François; Bellagamba, Gauthier; Garciaz, Sylvain; Lehucher-Michel, Marie-Pascale; Bouabdallah, Réda

    2014-03-01

    This study investigated a possible link between the occupational or domestic exposure to animals and a histological subgroup of non-Hodgkin lymphomas (LNH) (diffuse large B-cell lymphomas [LDGCB], follicular lymphomas [LF], indolent non-follicular LNH [LNHINF] and T-cell LNH). This retrospective, descriptive study was carried out over one year in a regional cancer research center. Data on occupational and domestic exposures to animals, from patients treated for a LNH, was collected via a questionnaire. Among the 261 participants, 73.9% reported they had been exposed to animals, 5% were exposed at work, whereas 72.4% were exposed in a domestic setting. The occupational exposure tended to be more frequent in the subgroup of patients with a LF (P = 0.06). The domestic exposure was less frequent (P = 0.04) in patients with LDGCB (63.0%) than in patients with a small cell LNH B (LF and LNHINF) (76.0%). Although there was no obvious link between occupational or domestic exposure to animals and one of the four histological subgroups of LNH, domestic exposure seemed less common among LDGCB patients. These results need to be confirmed by further studies. PMID:24691187

  2. Autonomic neuropathy resulting in recurrent laryngeal nerve palsy in an HIV patient with Hodgkin lymphoma receiving vinblastine and antiretroviral therapy.

    PubMed

    Cherif, S; Danino, S; Yoganathan, K

    2015-03-01

    Hoarseness of voice due to vocal cord paresis as a result of recurrent laryngeal nerve palsy has been well recognised. Recurrent laryngeal nerve palsy is commonly caused by compression due to tumour or lymph nodes or by surgical damage. Vinca alkaloids are well known to cause peripheral neuropathy. However, vinca alkaloids causing recurrent laryngeal nerve palsy has been reported rarely in children. We report a case of an adult patient with HIV who developed hoarseness of voice due to vocal cord paralysis during vinblastine treatment for Hodgkin lymphoma. Mediastinal and hilar lymph node enlargement in such patients may distract clinicians from considering alternative causes of recurrent laryngeal nerve palsy, with potential ensuing severe or even life-threatening stridor. PMID:24828552

  3. PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

    PubMed

    Barrington, Sally F; Kirkwood, Amy A; Franceschetto, Antonella; Fulham, Michael J; Roberts, Thomas H; Almquist, Helén; Brun, Eva; Hjorthaug, Karin; Viney, Zaid N; Pike, Lucy C; Federico, Massimo; Luminari, Stefano; Radford, John; Trotman, Judith; Fosså, Alexander; Berkahn, Leanne; Molin, Daniel; D'Amore, Francesco; Sinclair, Donald A; Smith, Paul; O'Doherty, Michael J; Stevens, Lindsey; Johnson, Peter W

    2016-03-24

    International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice. PMID:26747247

  4. Fludarabine: a review of its use in non-Hodgkin's lymphoma.

    PubMed

    Anderson, Vanessa R; Perry, Caroline M

    2007-01-01

    Fludarabine (Fludara), a purine nucleoside analogue, has been extensively evaluated in the treatment of a number of lymphoproliferative malignancies, including various types of non-Hodgkin's lymphoma. Clinical studies have shown that fludarabine (alone, and particularly as a component of combination therapy) can result in high overall and complete response in adults with various types of non-Hodgkin's lymphoma, including follicular lymphoma. As mono- or combination therapy, intravenous fludarabine is as effective as several other standard treatment regimens in treatment-naive patients and is also effective in patients with recurrent or refractory disease. The efficacy of fludarabine therapy is improved with the use of rituximab, as part of the initial therapeutic regimen or as maintenance therapy, and deserves consideration. The once-daily oral formulation was effective in the treatment of patients with relapsed indolent B-cell non-Hodgkin's lymphoma; however, further studies are required to confirm its role and establish its efficacy relative to that of standard treatment in this patient population. Fludarabine has generally acceptable tolerability; however, it is associated with haematological adverse events, including myelosuppression. Fludarabine, therefore, provides a highly effective first- or second-line option in the treatment of non-Hodgkin's lymphoma. PMID:17661532

  5. Applying Enhancement Filters in the Pre-processing of Images of Lymphoma

    NASA Astrophysics Data System (ADS)

    Henrique Silva, Sérgio; Zanchetta do Nascimento, Marcelo; Alves Neves, Leandro; Ramos Batista, Valério

    2015-01-01

    Lymphoma is a type of cancer that affects the immune system, and is classified as Hodgkin or non-Hodgkin. It is one of the ten types of cancer that are the most common on earth. Among all malignant neoplasms diagnosed in the world, lymphoma ranges from three to four percent of them. Our work presents a study of some filters devoted to enhancing images of lymphoma at the pre-processing step. Here the enhancement is useful for removing noise from the digital images. We have analysed the noise caused by different sources like room vibration, scraps and defocusing, and in the following classes of lymphoma: follicular, mantle cell and B-cell chronic lymphocytic leukemia. The filters Gaussian, Median and Mean-Shift were applied to different colour models (RGB, Lab and HSV). Afterwards, we performed a quantitative analysis of the images by means of the Structural Similarity Index. This was done in order to evaluate the similarity between the images. In all cases we have obtained a certainty of at least 75%, which rises to 99% if one considers only HSV. Namely, we have concluded that HSV is an important choice of colour model at pre-processing histological images of lymphoma, because in this case the resulting image will get the best enhancement.

  6. Imbalanced Matriptase Pericellular Proteolysis Contributes to the Pathogenesis of Malignant B-Cell Lymphomas

    PubMed Central

    Chou, Feng-Pai; Chen, Ya-Wen; Zhao, Xianfeng F.; Xu-Monette, Zijun Y.; Young, Ken H.; Gartenhaus, Ronald B.; Wang, Jehng-Kang; Kataoka, Hiroaki; Zuo, Annie H.; Barndt, Robert J.; Johnson, Michael; Lin, Chen-Yong

    2014-01-01

    Membrane-associated serine protease matriptase is widely expressed by epithelial/carcinoma cells in which its proteolytic activity is tightly controlled by the Kunitz-type protease inhibitor, hepatocyte growth factor activator inhibitor (HAI-1). We demonstrate that, although matriptase is not expressed in lymphoid hyperplasia, roughly half of the non-Hodgkin B-cell lymphomas analyzed express significant amounts of matriptase. Furthermore, a significant proportion of these tumors express matriptase in the absence of HAI-1. Aggressive Burkitt lymphoma was more likely than indolent follicular lymphoma to express matriptase alone (86% versus 36%). In the absence of significant HAI-1 expression, the lymphoma cells activate and shed active matriptase when the cells are stimulated with mildly acidic buffer or the hypoxia-mimicking agent, CoCl2. The shed active matriptase can initiate pericellular proteolytic cascades by activating urokinase-type plasminogen activator on the cell surface of monocytes, and it can activate prohepatocyte growth factor. In addition, matriptase knockdown suppressed proliferation and colony-forming ability of neoplastic B cells in culture and growth as tumor xenografts in mice. Furthermore, exogenous expression of HAI-1 significantly suppressed proliferation of neoplastic B cells. These studies suggest that dysregulated pericellular proteolysis as a result of unregulated matriptase expression with limited HAI-1 may contribute to the pathological characteristics of several human B-cell lymphomas through modulation of the tumor microenvironment and enhanced tumor growth. PMID:24070417

  7. Follicular Helper T Cells.

    PubMed

    Vinuesa, Carola G; Linterman, Michelle A; Yu, Di; MacLennan, Ian C M

    2016-05-20

    Although T cell help for B cells was described several decades ago, it was the identification of CXCR5 expression by B follicular helper T (Tfh) cells and the subsequent discovery of their dependence on BCL6 that led to the recognition of Tfh cells as an independent helper subset and accelerated the pace of discovery. More than 20 transcription factors, together with RNA-binding proteins and microRNAs, control the expression of chemotactic receptors and molecules important for the function and homeostasis of Tfh cells. Tfh cells prime B cells to initiate extrafollicular and germinal center antibody responses and are crucial for affinity maturation and maintenance of humoral memory. In addition to the roles that Tfh cells have in antimicrobial defense, in cancer, and as HIV reservoirs, regulation of these cells is critical to prevent autoimmunity. The realization that follicular T cells are heterogeneous, comprising helper and regulatory subsets, has raised questions regarding a possible division of labor in germinal center B cell selection and elimination. PMID:26907215

  8. Prospective Coronary Heart Disease Screening in Asymptomatic Hodgkin Lymphoma Patients Using Coronary Computed Tomography Angiography: Results and Risk Factor Analysis

    SciTech Connect

    Girinsky, Theodore; M’Kacher, Radhia; Koscielny, Serge; Elfassy, Eric; Raoux, François; Carde, Patrice; Santos, Marcos Dos; Margainaud, Jean-Pierre; Sabatier, Laure; Paul, Jean-François

    2014-05-01

    Purpose: To prospectively investigate the coronary artery status using coronary CT angiography (CCTA) in patients with Hodgkin lymphoma treated with combined modalities and mediastinal irradiation. Methods and Materials: All consecutive asymptomatic patients with Hodgkin lymphoma entered the study during follow-up, from August 2007 to May 2012. Coronary CT angiography was performed, and risk factors were recorded along with leukocyte telomere length (LTL) measurements. Results: One hundred seventy-nine patients entered the 5-year study. The median follow-up was 11.6 years (range, 2.1-40.2 years), and the median interval between treatment and the CCTA was 9.5 years (range, 0.5-40 years). Coronary artery abnormalities were demonstrated in 46 patients (26%). Coronary CT angiography abnormalities were detected in nearly 15% of the patients within the first 5 years after treatment. A significant increase (34%) occurred 10 years after treatment (P=.05). Stenoses were mostly nonostial. Severe stenoses were observed in 12 (6.7%) of the patients, entailing surgery with either angioplasty with stent placement or bypass grafting in 10 of them (5.5%). A multivariate analysis demonstrated that age at treatment, hypertension, and hypercholesterolemia, as well as radiation dose to the coronary artery origins, were prognostic factors. In the group of patients with LTL measurements, hypertension and LTL were the only independent risk factors. Conclusions: The findings suggest that CCTA can identify asymptomatic individuals at risk of acute coronary artery disease who might require either preventive or curative measures. Conventional risk factors and the radiation dose to coronary artery origins were independent prognostic factors. The prognostic value of LTL needs further investigation.

  9. Incidental Lymphoma Discovered During Surveillance for Low-Grade Upper Tract Urothelial Carcinoma Treated Ureteroscopically: A Case Report Series.

    PubMed

    Hubosky, Scott G; Healy, Kelly A; Raval, Amar J; Lallas, Costas D; Filicko-O'Hara, Joanne; Bagley, Demetrius H

    2016-01-01

    Two cases of incidentally found follicular lymphoma during surveillance for ureteroscopically treated upper tract urothelial carcinoma with cross-sectional imaging are described. Multiple independent primary malignancies should be considered in this population. PMID:27579404

  10. Incidental Lymphoma Discovered During Surveillance for Low-Grade Upper Tract Urothelial Carcinoma Treated Ureteroscopically: A Case Report Series

    PubMed Central

    Healy, Kelly A.; Raval, Amar J.; Lallas, Costas D.; Filicko-O'Hara, Joanne; Bagley, Demetrius H.

    2016-01-01

    Abstract Two cases of incidentally found follicular lymphoma during surveillance for ureteroscopically treated upper tract urothelial carcinoma with cross-sectional imaging are described. Multiple independent primary malignancies should be considered in this population. PMID:27579404

  11. [Cutaneous lymphoma].

    PubMed

    Beyeler, M; Burg, G; Dummer, R

    2004-10-01

    Cutaneous lymphomas are uncommon. They must be distinguished from secondary skin manifestations of primary nodal lymphomas. Primary cutaneous lymphomas are divided into B-cell- and T-cell cutaneous lymphoma and commonly have good prognosis. Therapy is based on the stage of the disease. Since cure is not possible, the aim of treatment is to control the disease and reduce symptoms. A variety of new and promising therapeutic modalities have been introduced in recent years. PMID:15349694

  12. Comprehensive genomic profiling of orbital and ocular adnexal lymphomas identifies frequent alterations in MYD88 and chromatin modifiers: new routes to targeted therapies.

    PubMed

    Cani, Andi K; Soliman, Moaaz; Hovelson, Daniel H; Liu, Chia-Jen; McDaniel, Andrew S; Haller, Michaela J; Bratley, Jarred V; Rahrig, Samantha E; Li, Qiang; Briceño, César A; Tomlins, Scott A; Rao, Rajesh C

    2016-07-01

    Non-Hodgkin lymphoma of the orbit and ocular adnexa is the most common primary orbital malignancy. Treatments for low- (extra-nodal marginal zone and follicular lymphomas) and high-grade (diffuse large B-cell lymphoma) are associated with local and vision-threatening toxicities. High-grade lymphomas relapse frequently and exhibit poor survival rates. Despite advances in genomic profiling and precision medicine, orbital and ocular adnexal lymphomas remain poorly characterized molecularly. We performed targeted next-generation sequencing (NGS) profiling of 38 formalin-fixed, paraffin-embedded orbital and ocular adnexal lymphomas obtained from a single-center using a panel targeting near-term, clinically relevant genes. Potentially actionable mutations and copy number alterations were prioritized based on gain- and loss-of-function analyses, and catalogued, approved, and investigational therapies. Of 36 informative samples, including marginal zone lymphomas (n=20), follicular lymphomas (n=9), and diffuse large B-cell lymphomas (n=7), 53% harbored a prioritized alteration (median=1, range 0-5/sample). MYD88 was the most frequently altered gene in our cohort, with potentially clinically relevant hotspot gain-of-function mutations identified in 71% of diffuse large B-cell lymphomas and 25% of marginal zone lymphomas. Prioritized alterations in epigenetic modulators were common and included gain-of-function EZH2 and loss-of-function ARID1A mutations (14% of diffuse large B-cell lymphomas and 22% of follicular lymphomas contained alterations in each of these two genes). Single prioritized alterations were also identified in the histone methyltransferases KMT2B (follicular lymphoma) and KMT3B (diffuse large B-cell lymphoma). Loss-of-function mutations and copy number alterations in the tumor suppressors TP53 (diffuse large B-cell and follicular lymphoma), CDKN2A (diffuse large B-cell and marginal zone lymphoma), PTEN (diffuse large B-cell lymphoma), ATM (diffuse large B

  13. Recent advances in post autologous transplantation maintenance therapies in B-cell non-Hodgkin lymphomas

    PubMed Central

    Epperla, Narendranath; Fenske, Timothy S; Hari, Parameswaran N; Hamadani, Mehdi

    2015-01-01

    Lymphomas constitute the second most common indication for high dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT). The intent of administering HDT in these heterogeneous disorders varies from cure (e.g., in relapsed aggressive lymphomas) to disease control (e.g., most indolent lymphomas). Regardless of the underlying histology or remission status at transplantation, disease relapse remains the number one cause of post auto-HCT therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at prevention of post auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. In relapsed, chemosensitive diffuse large B-cell lymphoma (DLBCL), although post auto-HCT maintenance rituximab seems to be safe and feasible, it does not provide improved survival outcomes and is not recommended. The preliminary results with anti- programmed death -1 (PD-1) antibody therapy as post auto-HCT maintenance in DLBCL is promising but requires randomized validation. Similarly in follicular lymphoma, maintenance therapies including rituximab following auto-HCT should be considered investigational and offered only on a clinical trial. Rituximab maintenance results in improved progression-free survival but has not yet shown to improve overall survival in mantle cell lymphoma (MCL), but given the poor prognosis with post auto-HCT failure in MCL, maintenance rituximab can be considered on a case-by-case basis. Ongoing trials evaluating the efficacy of post auto-HCT maintenance with novel compounds (e.g., immunomodulators, PD-1 inhibitors, proteasome inhibitors and bruton’s tyrosine kinase inhibitors) will likely change the practice landscape in the near future for B cell non-Hodgkin lymphomas patients following HDT and auto-HCT. PMID:26421260

  14. Follicular Dendritic Cell Sarcoma Mediastinum - a case report.

    PubMed

    Bushan, Kirti

    2014-12-01

    Follicular dendritic cell tumor (FDCT) are extremely rare difficult to diagnose category tumors.There has been a considerable controversy in medical community regarding precise classification and optimal management of this tumor with some treating it as a form of non Hodgkins lymphoma and some as soft tissue sarcomas.The number of published cases are still low and documentation too heterogenous to give statistically ified therapeutic recommendation of these tumors.This case report aims to highlight various aspects of diagnosing and treating this rare entity. PMID:25767341

  15. Signet-ring Cell Lymphoma-a Case Report.

    PubMed

    Masir, N; Cheong, S K; Noordin, K

    2001-01-01

    A case of signet-ring cell lymphoma diagnosed initially by fine needle aspiration cytology is reported. This rare tumor is a variant of follicular lymphoma, which closely resembles metastatic adenocarcinoma and other tumors which exhibit signet-ring cell appearance. Correct diagnosis can be achieved by careful morphologic analysis together with positive reactivity with lymphoid markers. The cytohistologic, immunohistochemical and electron microscopic features are described, and the differ ential diagnostic considerations are discussed in the report. PMID:27420125

  16. Bob1 limits cellular frequency of T-follicular helper cells.

    PubMed

    Yamashita, Keiji; Kawata, Koji; Matsumiya, Hiroshi; Kamekura, Ryuta; Jitsukawa, Sumito; Nagaya, Tomonori; Ogasawara, Noriko; Takano, Ken-Ichi; Kubo, Terufumi; Kimura, Sachiko; Shigehara, Katsunori; Himi, Tetsuo; Ichimiya, Shingo

    2016-06-01

    T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B-cell lymphoma-6 and Blimp-1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique mechanisms to establish Tfh-cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1. Bob1 of Tfh cells was dispensable for the expression of B-cell lymphoma-6 and the functional property of the cells for B cell help. However, upon initial immunization of foreign antigens, the percentages of Tfh cells in Bob1(-/-) mice were much higher than those in wild-type (WT) mice. In addition, expansion of Tfh cells within Bob1(-/-) CD4(+) T cells transferred into WT mice revealed that the high frequency of Tfh cells was caused by a T-cell-intrinsic mechanism. These findings were further supported by the results of in vitro studies demonstrating that Bob1(-/-) Tfh cells had greater proliferative activity in response to stimuli by CD3/CD28 monoclonal antibody and were also refractory to CD3-induced cell death in comparison to WT Tfh cells. These results suggest that Tfh cells harbor a Bob1-related mechanism to restrict numerical frequency against stimulation of TCRs. PMID:27080143

  17. Results of the L5178Y mouse lymphoma assay and the Balb/3t3 cell in vitro transformation assay for eight phthalate esters.

    PubMed

    Barber, E D; Cifone, M; Rundell, J; Przygoda, R; Astill, B D; Moran, E; Mulholland, A; Robinson, E; Schneider, B

    2000-01-01

    Eight phthalate esters, with alcohol chain lengths of 1-11 carbon atoms and with various degrees of branching, were tested in vitro in the L5178Y mouse lymphoma mammalian cell mutation assay and in the Balb/3T3 cell transformation assay. The tests were performed as part of a voluntary testing agreement between the Chemical Manufacturers Association's Phthalate Esters Panel and the United States Environmental Protection Agency (US EPA). The esters tested were: dimethyl phthalate (DMP), di-n-butyl phthalate (DBP), butyl benzyl phthalate (BBP), di-¿n-hexyl, n-octyl, n-decyl¿ phthalate (610P), di-isononyl phthalate (DINP), di-¿heptyl, nonyl, undecyl¿ phthalate (711P), di-isodecyl phthalate (DIDP) and di-undecyl phthalate (DUP). Both DMP and DBP were found to produce significant increases in the mutant frequency in the mouse lymphoma assay in the presence but not in the absence of an Aroclor-induced rat liver activation system (S-9). Ester 610P gave equivocal results in the mouse lymphoma assay in the presence and absence of rat liver S-9. There was no indication of mutagenic potential for any of the other test materials in the mouse lymphoma assay, and none of the test materials increased transformation frequency in the Balb/3T3 cell transformation assay. Aldehyde metabolites of the de-esterified alcohols are postulated to play a role in the positive results for DMP and DBP. PMID:10641018

  18. [Results of radiation therapy in extranodal non-Hodgkin's lymphoma of the head and neck--a study of the Japan Lymphoma Radiation Therapy Study Group].

    PubMed

    Horiuchi, J; Shibuya, H; Niibe, H; Kaneta, K; Watanabe, S; Morita, K; Masaki, N; Hayabuchi, N

    1988-04-01

    Extranodal non-Hodgkin's lymphoma (NHL) in the head and neck except Waldeyer's ring treated with radiation were analyzed. No definite difference was observed both in actuarial and relapse-free five-year survival rate between stage I and II. There was a high survival rate with orbital NHL in which most of the patients occupied with favorable histology. Prognosis of the disease was highly influenced by the histologic subtype; five-year survival was 91.4% in DWDL, 77.2% in the DM, 52.0% in DPDL and 51.7% in DH. Application of histologic classification with the Working Formulation was also recommended. There was a high incidence of extranodal relapses to bone and/or soft tissue from the lesions with nasal cavity, paranasal sinus and oral cavity. PMID:3385929

  19. Follicular dynamics in Mangalarga mares.

    PubMed

    Buratini, J; Rosa e Silva, A A; Barros, C M; Papa, F O; Caldas, M C; Meira, C

    1997-12-01

    Ovarian follicular activity was studied by ultrasonography during 17 oestrous cycles in 9 Mangalarga mares during the second half of the ovulatory season. Sixteen oestrous cycles were considered normal and one 3-wave cycle showing a prolonged luteal phase was considered atypical. Daily ultrasonographic examinations were performed and the compiled data on follicular dynamics were studied retrospectively. One major wave of follicular growth was observed in 13 of the 16 normal cycles (81.25%), whereas 2 major waves occurred in 3 cycles (18.75%). The mean (+/- s.d.) days of emergence of the primary wave of follicular development in cycles containing one or 2 waves were Day 6.0 +/- 2.3 and Day 11.0 +/- 1.0, respectively. The secondary wave of follicular development in 2-wave cycles emerged on Day 0.0 +/- 3.6. The day of wave divergence for primary waves of follicular development in cycles which exhibited one or 2 major waves were Day 12.2 +/- 3.5 and Day 17.3 +/- 3.0, respectively. Divergence of secondary waves occurred in only one of the 3 cycles which exhibited 2 major follicular waves (Day 7). The mean (+/- s.d.) maximum diameters of the dominant follicle in the primary wave of oestrous cycles exhibiting one and 2 major waves were 39.0 +/- 3.9 mm and 34.7 +/- 2.5 mm, respectively. The mean (+/- s.d.) maximum diameter of the dominant follicle present in the secondary wave was 34.3 +/- 11.0 mm. The mean (+/- s.d.) lengths of the interovulatory intervals for cycles containing one and 2 major waves were 19.4 +/- 2.2 and 23.3 +/- 2.5 days, respectively. These data indicate that most Mangalarga mares show one major follicular wave during the oestrous cycle but a small percentage of mares show 2 major waves. PMID:9593519

  20. Utility of LRF/Pokemon and NOTCH1 protein expression in the distinction between nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma.

    PubMed

    Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

    2014-02-01

    Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a proto-oncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch de-repression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target. PMID:24326827

  1. Utility of LRF/Pokemon and NOTCH1 Protein Expression in the Distinction of Nodular Lymphocyte-Predominant Hodgkin Lymphoma and Classical Hodgkin Lymphoma

    PubMed Central

    Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

    2014-01-01

    Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a protooncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch derepression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target. PMID:24326827

  2. [Lymphoma of Ocular and Periocular Tissues - Clinicopathological Correlations].

    PubMed

    Schmack, I; Grossniklaus, H E; Hartmann, S

    2016-07-01

    Lymphomas of the ocular adnexa and intraocular tissue include a wide range of lymphoproliferative neoplastic disorders. They are predominantly extranodal non-Hodgkin lymphomas (NHL). The World Health Organization (WHO) classification of lymphoid neoplasm and individual morphological, immunophenotypical, and molecular genetic features, indicate that they may be divided into B-cell (approximately 80 % of all NHL) and T-cell lymphomas (approximately 10-20 % of all NHL). The most common forms of ocular NHL are extranodal marginal zone lymphoma (EMZL) of the mucosa-associated lymphoid tissue (MALT-type), follicular lymphoma (FL), diffuse large B-cell lymphoma, and mantel cell lymphoma. The clinical signs and symptoms are usually very unspecific and depend on the location, size, and extent of the underlying lymphoma subtype. Typical low grade lymphomas have an indolent clinical course and often remain unrecognized for many years. On the other hand, high grade NHLs, such as DLBCL or MCL, are frequently aggressive, with rapid tumour growth and poor prognosis, despite early detection. Histopathology is still the gold standard in the diagnosis of ocular lymphomas. Basic understanding of the principal pathophysiological and clinical aspects of the development and progression of orbital and ocular lymphomas seems to be mandatory for optimal diagnosis and treatment and for improving survival and prognosis. Both residents in training and board certified ophthalmologists should be aware of these problems. PMID:27468099

  3. Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

    SciTech Connect

    Hoppe, Bradford S.; Flampouri, Stella; Zaiden, Robert; Slayton, William; Sandler, Eric; Dang, Nam H.; Lynch, James W.; Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P.

    2014-08-01

    Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on {sup 18}F-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes

  4. Angiocentric and intravascular lymphomas.

    PubMed

    Tomasini, D; Berti, E

    2015-02-01

    Under the generic diagnosis of angiocentric and intravascular lymphomas are included several subtypes of lymphomas histopathologically characterized either by the predominantly endovascular-endoluminal presence of neoplastic lymphocytes of B-T or NK/T cell origin, or by a pathologic process centered around a blood vessels secondarily infiltrated and invaded by the spreading infiltrate. This group of lymphoproliferative disorders is heterogeneous regarding phenotype, but they share common features that are multiorgan involvement, worse prognosis, and, frequently Ebstein-Barr virus (EBV) genomic integration. At onset, some of these rare lymphomas, e.g. intravascular large cell lymphoma or lymphomatoid granulomatosis (Liebow dieases), are misdiagnosed as inflammatory diseases. The actual treatments of these disorders are based upon chemotherapy and/or chemotherapy plus bone marrow transplantation with variable results. Therapeutic approaches for EBV related angiocentric and intravascular lymphomas, similarly to those employed for other viral induced lymphoproliferative disease would comprise the employment of chemotherapy together with drugs able to interfere with viral infection. Such an approach has been used in rare cases of EBV-positive diffuse large B-cell lymphoma of the elderly, a lymphoproliferative disorders which development is linked to immunosuppression due to senescence. The present review will focus on intravascular and angiocentric lymphomas providing histopathologic, immunophenotypical and molecular data useful to overcome to a specific diagnosis and to differentiate them from other lymphoproliferative disorders showing a secondary vascular engulfment and infiltration and some vasculitides showing overlapping histopathologic features. PMID:25531150

  5. Genetic Susceptibility to Lymphoma

    PubMed Central

    Skibola, Christine F.; Curry, John D.; Nieters, Alexandra

    2010-01-01

    BACKGROUND Genetic susceptibility studies of lymphoma may serve to identify at risk populations and to elucidate important disease mechanisms. METHODS This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. RESULTS Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G>A and IL10 -3575T>A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol assessments are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro- and endocrine-immune cross-talk with lymphomagenesis, but will need replication in larger populations. CONCLUSIONS Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations. PMID:17606447

  6. Romidepsin in relapsed/refractory T-cell lymphomas: Italian experience and results of a named patient program.

    PubMed

    Zinzani, Pier Luigi; Pellegrini, Cinzia; Cerciello, Giuseppe; Monaco, Federico; Volpetti, Stefano; Peli, Annalisa; Angelucci, Emanuele; Corradini, Paolo; Cox, Maria Christina; Guarini, Attilio; Musso, Maurizio; Bresciani, Paola; Amato, Gabriella; Billio, Atto; Caparrotti, Giuseppe; Figuera, Amalia; Nassi, Luca; Gaudio, Francesco; Grossi, Alberto; Onida, Francesco; Merli, Michele; Rigacci, Luigi; Argnani, Lisa

    2016-10-01

    Clinical trial results indicate that romidepsin, a histone deacetylase inhibitor, is a promising treatment in relapsed/refractory T-cell lymphomas (TCLs). This retrospective multicenter study was conducted in patients with relapsed/refractory TCL treated with romidepsin monotherapy through a Named Patient Program (NPP) in Italy. Principal endpoints were overall response rate (ORR), safety, and overall survival (OS). The ORR in 33 evaluable patients was 24.2% with an ORR in the cutaneous TCL of 35.7%. Global OS was 39.3% at 30 months. There were not any specific differences on hematological and extrahematological adverse events. Data from patients treated with romidepsin outside a controlled clinical trial give additional information about the clinical use, efficacy, and toxicity of the drug given to relapsed or refractory TCL patients in a real life context as TCLs are rare diseases and more information is needed. These findings suggest that romidepsin is effective and safe for heavily pretreated TCL patients. PMID:26732313

  7. Discordant expression of immunoglobulin and its associated molecule mb-1/CD79a is frequently found in mediastinal large B cell lymphomas.

    PubMed Central

    Kanavaros, P.; Gaulard, P.; Charlotte, F.; Martin, N.; Ducos, C.; Lebezu, M.; Mason, D. Y.

    1995-01-01

    Mediastinal large B cell lymphomas are uncommon neoplasms that are thought to originate from thymic B cells. An unusual feature of these neoplasms is that they often lack surface immunoglobulin (Ig), a molecule ubiquitously expressed by most mature B cells. In the present study we have analyzed 12 cases of mediastinal large B cell lymphoma for the expression of the mb-1/CD79a polypeptide. This is a component, together with B29/CD79b, of a heterodimer that is associated with surface Ig on normal B cells. Our aim was to see whether loss of Ig in this type of lymphoma is associated with loss of the accompanying CD79a molecule. We have also evaluated 128 B cell lymphomas of other categories to see whether any of them show discordance between mb-1 and Ig expression and analyzed 30 T cell lymphomas as Ig-negative controls. We found that 5 of the 7 mediastinal large B cell lymphomas with interpretable staining results for both mb-1 and Ig, lack Ig but expressed CD79a (mb-1). This phenotype was very rare in other categories of B cell lymphoma, being found among 110 cases in only 5 cases that were all follicular lymphoma. The remaining 105 B cell lymphomas displayed mb-1+/Ig+ phenotype. All 30 T cell lymphomas were mb-1 negative. We conclude that discordant mb-1/Ig expression occurs commonly in mediastinal large B cell lymphomas. In addition, the finding that 11 of 12 of these neoplasms express a phenotype (CD10-, CD19+, CD20+, CD21-, CD22+, CD23-/+) that is very similar to that described for thymic medullary B cells reinforces the idea that most mediastinal large B cell lymphomas are of thymic B cell origin. The correlation between mb-1 and Ig staining patterns in B cell lymphomas of other categories reveals that in the majority (90%), expression of the antigen receptor complex parallels that of mature B cells. These data therefore confirm that the expression of the mb-1 protein provides independent strong evidence for the B lineage of lymphomas and may be used for their

  8. The mammalian oocyte orchestrates the rate of ovarian follicular development

    PubMed Central

    Eppig, John J.; Wigglesworth, Karen; Pendola, Frank L.

    2002-01-01

    The development of both the mammalian oocyte and the somatic cell compartments of the ovarian follicle is highly coordinated; this coordination ensures that the ovulated oocyte is ready to undergo fertilization and subsequent embryogenesis. Disruption of this synchrony results in oocyte developmental failure. Communication between the oocyte and companion somatic cells is essential for successful development of both follicular compartments. However, it was not previously known whether one cell type, either the somatic or the germ cell compartment, determines the overall rate of follicular development. To test the hypothesis that the oocyte orchestrates the rate of follicle development, mid-sized oocytes isolated from secondary follicles were transferred back to primordial follicles, the earliest stage of follicular development. This transfer doubled the rate of follicular development and the differentiation of follicular somatic cells. Oocyte development in these accelerated follicles appeared normal; recovered oocytes were competent to undergo fertilization and embryonic development. These results demonstrate that oocytes orchestrate and coordinate the development of mammalian ovarian follicles and that the rate of follicular development is based on a developmental program intrinsic to the oocyte. PMID:11867735

  9. Follicular Dendritic Cell Sarcoma

    PubMed Central

    Udayakumar, Achandira M.; Al-Bahri, Maiya; Burney, Ikram A.; Al-Haddabi, Ibrahim

    2015-01-01

    Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a non-specific and insidious presentation further complicated by the difficult diagnostic and therapeutic assessment. It has a low to intermediate risk of recurrence and metastasis. Unlike other soft tissue sarcomas or histiocytic and dendritic cell neoplasms, cytogenetic studies are very limited in FDCS cases. Although no specific chromosomal marker has yet been established, complex aberrations and different ploidy types have been documented. We report the case of a 39-year-old woman with FDCS who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in February 2013. Ultrastructural, immunophenotypical and histological findings are reported. In addition, karyotypic findings showed deletions of the chromosomes 1p, 3q, 6q, 7q, 8q and 11q. To the best of the authors’ knowledge, these have not been reported previously in this tumour. Techniques such as spectral karyotyping may help to better characterise chromosomal abnormalities in this type of tumour. PMID:26355964

  10. Cardiac Lymphoma.

    PubMed

    Jeudy, Jean; Burke, Allen P; Frazier, Aletta Ann

    2016-07-01

    Lymphoma of the heart and pericardium may develop in up to 25% of patients with disseminated nodal disease, but primary cardiac lymphoma is rare. The majority are diffuse large B-cell lymphomas, which arise in immunocompetent older individuals, men twice as often as women. Subsets are found in immunocompromised patients, including those with HIV-AIDS or allograft recipients. Cardiac lymphomas tend to arise in the wall of the right heart, especially right atrium, with contiguous infiltration of epicardium and pericardium. Pericardial implants and effusions are common. The disease is often multifocal in the heart, but cardiac valves are usually spared. PMID:27265603

  11. Subtype distribution of lymphomas in South of Iran, analysis of 1085 cases based on World Health Organization classification.

    PubMed

    Monabati, Ahmad; Safaei, Akbar; Noori, Sadat; Mokhtari, Maral; Vahedi, Amir

    2016-03-01

    Lymphoma is one of the most common malignancies worldwide. Subtype distribution is different throughout the world. Some reports from the Middle East are in record. This article is trying to report the subtype distribution of lymphoma in Iran and compare it to that of Western, Far East Asian and Middle Eastern countries. A retrospective study was done on all lymphomas diagnosed in a large referral center in the South of Iran during a time period between 2009 and 2014. All diagnoses have been made according to 2008 WHO classification. A total number of 1085 cases with diagnoses of lymphoma retrieved. Twenty-nine cases (2.6 % of all) were precursor lymphoid neoplasm, 608 cases (56 % of all) were mature B cell neoplasm, 115 cases (10.5 % of all) were mature T and NK cell neoplasm, and 333 cases (30.6 % of all) were Hodgkin lymphoma. The six most frequent subtypes of mature B cell neoplasm were diffuse large B cell lymphoma, NOS (57 %), Burkitt lymphoma (7 %), small lymphocytic lymphoma (6.9 %), mantle cell lymphoma (5.7 %), extranodal marginal zone B cell lymphoma (5.2 %) and follicular lymphoma (3.6 %). Among mature T and NK cell neoplasm, mycosis fungoides was the most common type (43.4 %) followed by peripheral T cell lymphoma, NOS (20 %) and angioimmunoblastic T cell lymphoma (9.9 %). Of Hodgkin lymphoma cases, 90.6 % were classical type and 9.3 % were nodular lymphocyte predominant Hodgkin lymphoma. Extranodal involvement was seen in 42.2 % and GI tract was the most common site. Lymphoma frequencies were similar to that of Middle Eastern countries except for lower rate of follicular lymphoma and higher incidence of diffuse large B cell lymphoma, NOS and small lymphocytic lymphoma. PMID:26754635

  12. Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status: Results from two independent cohorts

    PubMed Central

    Ghesquières, Hervé; Maurer, Matthew J.; Casasnovas, Olivier; Ansell, Stephen M.; Larrabee, Beth R.; Lech-Maranda, Eva; Novak, Anne J.; Borrel, Anne-Laure; Slager, Susan L.; Brice, Pauline; Allmer, Cristine; Brion, Annie; Ziesmer, Steven C.; Morschhauser, Franck; Habermann, Thomas M.; Gaillard, Isabelle; Link, Brian K.; Stamatoullas, Aspasia; Fermé, Christophe; Dogan, Ahmet; Macon, William R.; Audouin, Josée; Cerhan, James R.; Salles, Gilles

    2014-01-01

    Background Cytokines are important immune mediators of classical Hodgkin lymphoma (CHL) pathogenesis, and circulating levels at diagnosis may help predict prognosis. Germline single nucleotide polymorphisms (SNPs) in immune genes have been correlated with cytokine production and function. Methods We investigated whether selected germline SNPs in IL10 (rs1800890, rs1800896, rs1800871, rs1800872), TNFA (rs1800629), IL6 (rs1800795), ILRN (rs419598), INFG (rs2430561) and CCL17 (rs223828) were associated with circulating levels of related cytokines at diagnosis and progression-free survival (PFS) in CHL. Patients were from France (GELA, N = 464; median age = 32 years) and the United States (Iowa/Mayo Specialized Program Of Research Excellence [SPORE], N = 239; median age = 38 years); 22% of 346 CHL cases with EBV tumor status were positive. Results There was no association with any of the SNPs with cytokine levels. Overall, there was no association of any of the SNPs with PFS. In exploratory analyses by EBV status, TNFA rs1800629 (HRAA/AG = 2.41; 95%CI, 1.17–4.94) was associated with PFS in EBV-negative GELA patients, with similar trends in the SPORE patients (HRAA/AG = 1.63; 95%CI, 0.61–4.40). In a meta-analysis of the two studies, TNFA (HRAA/AG = 2.11; 95%CI, 1.18–3.77; P = 0.01) was statistically significant, and further adjustment for the international prognostic system did not alter this result. Conclusions This study showed that germline variation in TNFA was associated with CHL prognosis for EBV-negative patients, which will require confirmation. These results support broader studies on the differential impact of genetic variation in immune genes on EBV-positive vs. EBV-negative CHL pathogenesis. PMID:24008079

  13. Proteomics Based Identification of Proteins with Deregulated Expression in B Cell Lymphomas.

    PubMed

    Wu, Rui; Nijland, Marcel; Rutgers, Bea; Veenstra, Rianne; Langendonk, Myra; van der Meeren, Lotte E; Kluin, Philip M; Li, Guanwu; Diepstra, Arjan; Chiu, Jen-Fu; van den Berg, Anke; Visser, Lydia

    2016-01-01

    Follicular lymphoma and diffuse large B cell lymphomas comprise the main entities of adult B cell malignancies. Although multiple disease driving gene aberrations have been identified by gene expression and genomic studies, only a few studies focused at the protein level. We applied 2 dimensional gel electrophoresis to compare seven GC B cell non Hodgkin lymphoma (NHL) cell lines with a lymphoblastoid cell line (LCL). An average of 130 spots were at least two folds different in intensity between NHL cell lines and the LCL. We selected approximately 38 protein spots per NHL cell line and linked them to 145 unique spots based on the location in the gel. 34 spots that were found altered in at least three NHL cell lines when compared to LCL, were submitted for LC-MS/MS. This resulted in 28 unique proteins, a substantial proportion of these proteins were involved in cell motility and cell metabolism. Loss of expression of B2M, and gain of expression of PRDX1 and PPIA was confirmed in the cell lines and primary lymphoma tissue. Moreover, inhibition of PPIA with cyclosporine A blocked cell growth of the cell lines, the effect size was associated with the PPIA expression levels. In conclusion, we identified multiple differentially expressed proteins by 2-D proteomics, and showed that some of these proteins might play a role in the pathogenesis of NHL. PMID:26752561

  14. Chlorambucil versus observation after anti-Helicobacter therapy in gastric MALT lymphomas: results of the international randomised LY03 trial

    PubMed Central

    Hancock, Barry W; Qian, Wendi; Linch, David; Delchier, Jean-Charles; Smith, Paul; Jakupovic, Ira; Burton, Cathy; Souhami, Robert; Wotherspoon, Andrew; Copie-Bergman, Christiane; Capella, Carlo; Traulle, Catherine; Levy, Michael; Cortelazzo, Sergio; Ferreri, Andres J M; Ambrosetti, Achille; Pinotti, Graziella; Martinelli, Giovanni; Vitolo, Umberto; Cavalli, Franco; Gisselbrecht, Christian; Zucca, Emanuele

    2009-01-01

    Gastric mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon tumours characterised by a tendency to remain localised for long periods. The aetiological association between MALT lymphomas and Helicobacter pylori is well established. The role of additional chemotherapy after H. pylori eradication in localised MALT lymphomas is unclear. The LY03 trial was designed to establish whether chlorambucil after treatment for H. pylori would help prevent recurrence. Patients were treated with antibiotics for H. pylori infection. Those with successful eradication of H. pylori and no evidence of progression of lymphoma were eligible for randomisation to chlorambucil or observation. Two hundred and thirty-one patients were registered. Ninety-seven percent patients had H. pylori eradicated after antibiotics and 59% achieved macroscopically normal gastric mucosa. One hundred and ten patients were randomised. With a median follow-up of 58 months, six patients were dead and 17 had recurrent/progressive disease. The recurrence/progression rates at 5 years were 11% for chlorambucil, and 21% for observation with a difference of 10%, 95% confidence interval (CI) = −9% to 29%, P = 0·15. No difference was detected in recurrence/progression-free survival [Hazard Ratio (HR) = 0·96, 95% CI = 0·41–2·2, P = 0·91] or overall survival (HR = 1·93, 95% CI = 0·39–9·58, P = 0·42). This is the first randomised trial to show there is no good evidence to support that additional single agent chemotherapy to anti-H. pylori treatment contributes to prevent recurrence in localised gastric MALT lymphomas. PMID:19036078

  15. Primary gastrointestinal lymphoma

    PubMed Central

    Aledavood, Amir; Nasiri, Mohammad Reza Ghavam; Memar, Bahram; Shahidsales, Soodabeh; Raziee, Hamid Reza; Ghafarzadegan, Kamran; Mohtashami, Samira

    2012-01-01

    Background: Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological features and treatment results of patients with primary GI lymphoma. Materials and Methods: A total number of 30 cases with primary GI lymphoma were included in this study. Patients referred to the Radiation Oncology Department of Omid Hospital (Mashhad, Iran) during a 5-year period (2006-11). Clinical, paraclinical, and radiological data was collected from medical records of the patients. Results: Out of the 30 patients with primary GI lymphoma in the study, 12 were female (40%) and 18 were male (60%) (male to female ratio: 3/2). B symptoms were present in 27 patients (90%). Antidiuretic hormone (LDH) levels were elevated in 9 patients (32.1%). The most common primary site was stomach in 14 cases (46.7%). Other common sites included small intestine and colon each in 8 patients (26.7%). All patients had histopathologically proven non-Hodgkin's lymphoma. The most common histologic subtype was diffuse large B-cell lymphoma (DLBL) in 16 patients (53.3%). In addition, 28 patients (93.3%) received chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisolone (CHOP regimen). The median course of chemotherapy was 6 cources. Moreover, 8 patients (26.7%) received radiotherapy with cobalt 60. The median follow-up time was 26 months. The overall 5-year survival rate was 53% and the median survival time was 60 months. Conclusion: Primary GI lymphoma is commonly seen in stomach and small intestine and mostly is DLBCL or mucosa-associated lymphoid tissue (MALT) lymphoma. PMID:23626617

  16. Follicular Unit Extraction Hair Transplant

    PubMed Central

    Dua, Aman; Dua, Kapil

    2010-01-01

    Hair transplantation has come a long way from the days of Punch Hair Transplant by Dr. Orentreich in 1950s to Follicular Unit Hair Transplant (FUT) of 1990s and the very recent Follicular Unit Extraction (FUE) technique. With the advent of FUE, the dream of ‘no visible scarring’ in the donor area is now looking like a possibility. In FUE, the grafts are extracted as individual follicular units in a two-step or three-step technique whereas the method of implantation remains the same as in the traditional FUT. The addition of latest automated FUE technique seeks to overcome some of the limitations in this relatively new technique and it is now possible to achieve more than a thousand grafts in one day in trained hands. This article reviews the methodology, limitations and advantages of FUE hair transplant. PMID:21031064

  17. Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma

    PubMed Central

    Kirschbaum, Mark; Frankel, Paul; Popplewell, Leslie; Zain, Jasmine; Delioukina, Maria; Pullarkat, Vinod; Matsuoka, Deron; Pulone, Bernadette; Rotter, Arnold J.; Espinoza-Delgado, Igor; Nademanee, Auayporn; Forman, Stephen J.; Gandara, David; Newman, Edward

    2011-01-01

    Purpose We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma. Patients and Methods In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability. Results All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue. Conclusion Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted. PMID:21300924

  18. Inverted follicular keratosis successfully treated with imiquimod.

    PubMed

    Karadag, Ayse Serap; Ozlu, Emin; Uzuncakmak, Tugba Kevser; Akdeniz, Necmettin; Cobanoglu, Bengu; Oman, Berkant

    2016-01-01

    Inverted follicular keratosis is a rare benign tumor of the follicular infundibulum characterized by exo-endophytic growing. It is thought to be a rare variant of the seborrheic keratosis. The diagnosis of inverted follicular keratosis is generally established histopathologically because clinical differentiation from other lesions is difficult. Herein, we present one such rare case, successfully treated with topical 5% imiquimod cream. PMID:27294052

  19. Inverted follicular keratosis successfully treated with imiquimod

    PubMed Central

    Karadag, Ayse Serap; Ozlu, Emin; Uzuncakmak, Tugba Kevser; Akdeniz, Necmettin; Cobanoglu, Bengu; Oman, Berkant

    2016-01-01

    Inverted follicular keratosis is a rare benign tumor of the follicular infundibulum characterized by exo-endophytic growing. It is thought to be a rare variant of the seborrheic keratosis. The diagnosis of inverted follicular keratosis is generally established histopathologically because clinical differentiation from other lesions is difficult. Herein, we present one such rare case, successfully treated with topical 5% imiquimod cream. PMID:27294052

  20. Primary Lymphoma of Bone

    PubMed Central

    Choi, Jun Yong; Hahn, Jee Sook; Suh, Chang Ok; Yang, Woo Ick

    2002-01-01

    Background: Primary lymphoma of bone is a rare disease. There is yet no systematical evaluation of primary lymphoma of bone in Korea. Here we report our experience of sixteen cases with primary lymphoma of bone focusing on the survival. Methods: Sixteen cases, collected for 13 years, were evaluated on the clinical presentation, histologic subtype, stage and treatment outcomes of the primary bone lymphoma. Results: The most common presenting complaint was bone pain. Malignant lymphoma of bone involved a wide variety of sites, the most prevalent site of which in this study was the spine. Most of the cases were in the diffuse large B-cell category. The clinical stage of lymphoma was IEA in two cases, IIEA in three cases, IVEA in five cases and IVEB in three cases. All treated cases received systemic chemotherapy and ten cases among them were treated with combined modality therapy. Median overall survival was not reached after median follow-up period of 28 months and five-year overall survival rate was 54%. Conclusion: More promising therapeutic strategies are needed for survival improvement on more accumulated cases. PMID:12298430

  1. HIV infection and lymphoma

    PubMed Central

    Grogg, K L; Miller, R F; Dogan, A

    2007-01-01

    The incidence of lymphoma in patients with HIV infection greatly exceeds that of the general population. The increased risk for lymphoma appears related to multiple factors, including the transforming properties of the retrovirus itself, the immunosuppression and cytokine dysregulation that results from the disease, and, most importantly, opportunistic infections with other lymphotrophic herpes viruses such as Epstein–Barr virus and human herpesvirus 8. Histologically lymphomas fall into three groups: (1) those also occurring in immunocompetent patients; (2) those occurring more specifically in HIV‐positive patients; and (3) those also occurring in patients with other forms of immunosuppression. Aggressive lymphomas account for the vast majority cases. They frequently present with advanced stage, bulky disease with high tumour burden and, typically, involve extranodal sites. Clinical outcome appears to be worse than in similar aggressive lymphomas in the general population. However, following the introduction of highly active antiretroviral therapy, the risk for developing lymphoma in the context of HIV infection has decreased and the clinical outcome has improved. PMID:18042692

  2. [Results of the treatment of myelodysplastic syndrome (MDS)obtained by the Polish Paediatric Leukaemia /Lymphoma Study Group].

    PubMed

    Chybicka, A; Wójcik, D; Pietras, W; Bogusławska-Jaworska, J; Kolecki, P; Balcerska, A; Balwierz, W; Bubała, H; Eliasinska, A; Kowalczyk, J; Jackowska, T; Klus, K; Krenke, K; Kurylak, A; Malinowska, I; Matysiak, M; Stefańska, K; Stefaniak, M J; Rokicka-Milewska, R; Wiśniewska-Slusarz, H; Sońta-Jakimczyk, D; Wysocki, M

    2000-01-01

    Sixty children with MDS treated in six centres of the Polish Paediatric Leukaemia/Lymphoma Study Group in the period 1975-1999 were included in the study. In 20 children RAEB-T, in 13 RA, in 21 RAEB and in 6 CMML were diagnosed. Our own and literature data showed that BMT is the best therapy for children with MDS. We need a new comprehensive protocol for the diagnosis and treatment of children with MDS in Poland. PMID:12021466

  3. [How to improve the results of treatment of myelodysplastic syndromes in the studies of Polish pediatric leukemia/lymphoma group].

    PubMed

    Chybicka, A; Kołecki, P; Pietras, W; Wójcik, D; Turkiewicz, D; Armata, J; Eliasińska, A; Kowalczyk, J; Jackowska, T; Klus, K; Matysiak, M; Krauze, A; Stefańska, K; Rokicka-Milewska, R; Wiśniewska-Slusarz, H

    1998-01-01

    Fourty two children with myelodysplastic syndrome (MDS) treated in seven centres of The Polish Paediatric Leukaemia/Lymphoma Study Group in period 1975-1998 were included in the study. In 16 children RAEB-T, in 3 CMML, in 10 RA and in 13 RAEB were diagnosed. BMT is the best therapy for children with MDS. For children, who have not a donor for BMT, Roacutan therapy seems to be the most effective. PMID:10731943

  4. PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma

    PubMed Central

    Gopal, Ajay K.; Kahl, Brad S.; de Vos, Sven; Wagner-Johnston, Nina D.; Schuster, Stephen J.; Jurczak, Wojciech J.; Flinn, Ian W.; Flowers, Christopher R.; Martin, Peter; Viardot, Andreas; Blum, Kristie A.; Goy, Andre H.; Davies, Andrew J.; Zinzani, Pier Luigi; Dreyling, Martin; Johnson, Dave; Miller, Langdon L.; Holes, Leanne; Li, Daniel; Dansey, Roger D.; Godfrey, Wayne R.; Salles, Gilles A.

    2014-01-01

    Background Phosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin's lymphomas. Methods In this single-group, open-label, phase 2 study, 125 patients with indolent non-Hodgkin's lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within 6 months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. The primary end point was the overall rate of response; secondary end points included the duration of response, progression-free survival, and safety. Results The median age of the patients was 64 years (range, 33 to 87); patients had received a median of four prior therapies (range, 2 to 12). Subtypes of indolent non-Hodgkin's lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6% meeting the criteria for a complete response. The median time to a response was 1.9 months, the median duration of response was 12.5 months, and the median progression-free survival was 11 months. Similar response rates were observed across all subtypes of indolent non-Hodgkin's lymphoma, though the numbers were small for some categories. The most common adverse events of grade 3 or higher were neutropenia (in 27% of the patients), elevations in aminotransferase levels (in 13%), diarrhea (in 13%), and pneumonia (in 7%). Conclusions In this single-group study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non

  5. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma | Office of Cancer Genomics

    Cancer.gov

    In a recent Nature article, Morin et al. uncovered a novel role for chromatin modification in driving the progression of two non-Hodgkin lymphomas (NHLs), follicular lymphoma and diffuse large B-cell lymphoma. Through DNA and RNA sequencing of 117 tumor samples and 10 assorted cell lines, the authors identified and validated 109 genes with multiple mutations in these B-cell NHLs. Of the 109 genes, several genes not previously linked to lymphoma demonstrated positive selection for mutation including two genes involved in histone modification, MLL2 and MEF2B.

  6. General features and epidemiology of lymphoma in Colombia. A multicentric study.

    PubMed

    Combariza, Juan F; Lombana, Milton; Torres, Ana M; Castellanos, Ana M; Arango, Marcos

    2015-06-01

    The relative frequency of the non-Hodgkin lymphoma (NHL) subtypes varies around the world. The objective of this study was to describe the general features of patients with lymphoma in Colombia. A total of 819 patients with a new diagnosis of lymphoma were included. Nighty-nine (12 %) of them had Hodgkin lymphoma (HL) and 720 (88 %) had NHL. Most cases had advanced stage disease at presentation (63.6 %). Diffuse large B cell lymphoma (DLBCL) was the most frequent diagnosis; it was seen in 40 % of patients with NHL and in 35 % of patients in the whole series. Overall survival rates at 3 years were 77 % for HL and follicular lymphoma, 54 % for DLBCL, and 45 % for T cell lymphomas. In conclusion, the distribution of specific NHL subtypes is similar to what has been reported previously in other tropical countries. PMID:25645655

  7. Hepatitis C virus - associated B cell non-Hodgkin's lymphoma.

    PubMed

    Mihăilă, Romeo-Gabriel

    2016-07-21

    The hepatitis C virus (HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin's lymphoma (BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin's lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences. Various microenvironmental signals, such as cytokines, viral antigenic external stimulation of lymphocyte receptors by HCV antigens, and intercellular interactions contribute to B cell proliferation. HCV lymphotropism and chronic antigenic stimulation are involved in B-lymphocyte expansion, as mixted cryoglobulinemia or monoclonal gammopathy of undetermined significance, which can progress to BCNHL. HCV replication in B lymphocytes has oncogenic effect mediated by intracellular HCV proteins. It is also involved in an important induction of reactive oxygen species that can lead to permanent B lymphocyte damage, as DNA mutations, after binding to surface B-cell receptors. Post-transplant lymphoproliferative disorder could appear and it has a multiclonal potentiality that may develop into different types of lymphomas. The hematopoietic stem cell transplant made for lymphoma in HCV-infected patients can increase the risk of earlier progression to liver fibrosis and cirrhosis. HCV infected patients with indolent BCNHL who receive antiviral therapy can be potentially cured. Viral clearance was related to lymphoma response, fact that highlights the probable involvement of HCV in lymphomagenesis. Direct acting antiviral drugs could be a solution for the patients who did not tolerate or respond to interferon, as they seem to

  8. Hepatitis C virus - associated B cell non-Hodgkin's lymphoma

    PubMed Central

    Mihăilă, Romeo-Gabriel

    2016-01-01

    The hepatitis C virus (HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin’s lymphoma (BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin’s lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences. Various microenvironmental signals, such as cytokines, viral antigenic external stimulation of lymphocyte receptors by HCV antigens, and intercellular interactions contribute to B cell proliferation. HCV lymphotropism and chronic antigenic stimulation are involved in B-lymphocyte expansion, as mixted cryoglobulinemia or monoclonal gammopathy of undetermined significance, which can progress to BCNHL. HCV replication in B lymphocytes has oncogenic effect mediated by intracellular HCV proteins. It is also involved in an important induction of reactive oxygen species that can lead to permanent B lymphocyte damage, as DNA mutations, after binding to surface B-cell receptors. Post-transplant lymphoproliferative disorder could appear and it has a multiclonal potentiality that may develop into different types of lymphomas. The hematopoietic stem cell transplant made for lymphoma in HCV-infected patients can increase the risk of earlier progression to liver fibrosis and cirrhosis. HCV infected patients with indolent BCNHL who receive antiviral therapy can be potentially cured. Viral clearance was related to lymphoma response, fact that highlights the probable involvement of HCV in lymphomagenesis. Direct acting antiviral drugs could be a solution for the patients who did not tolerate or respond to interferon, as they

  9. Primary lymphoma of the brain

    MedlinePlus

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. Patients who have a weakened immune system are at high risk of primary lymphoma of the ...

  10. Primary lymphoma of the brain

    MedlinePlus

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  11. Non-Hodgkin lymphoma in the Far East: review of 730 cases from the international non-Hodgkin lymphoma classification project.

    PubMed

    Perry, Anamarija M; Diebold, Jacques; Nathwani, Bharat N; MacLennan, Kenneth A; Müller-Hermelink, Hans K; Bast, Martin; Boilesen, Eugene; Armitage, James O; Weisenburger, Dennis D

    2016-01-01

    Large and systematic studies of non-Hodgkin lymphoma (NHL) in the Far East (FE) with good comparative data are scarce in the literature. In this study, five expert hematopathologists classified 730 consecutive cases of newly-diagnosed NHL from four sites in the FE (excluding Japan) using the World Health Organization classification. The results were compared to 399 cases from North America (NA). We found a significantly higher male to female ratio in the FE compared to NA (1.7 versus 1.1; p < 0.05). The median ages of patients with low-grade (LG) and high-grade (HG) B-NHL in the FE (58 and 51 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). The FE had a significantly lower relative frequency of B-NHL and a higher frequency of T-NHL (82 vs. 18 %) compared to NA (90.5 vs. 9.5 %). Among mature B cell lymphomas, the FE had a significantly higher relative frequency of HG B-NHL (54.8 %) and a lower frequency of LG B-NHL (27.2 %) than NA (34.3 and 56.1 %, respectively). Diffuse large B cell lymphoma was more common in the FE (49.4 %) compared to NA (29.3 %), whereas the relative frequency of follicular lymphoma was lower in the FE (9.4 %) compared to NA (33.6 %). Among T-NHL, nasal NK/T cell NHL was more frequent in the FE (5.2 %) compared to NA (0 %). Peripheral T cell lymphoma was also more common in the FE (9.1 %) than in NA (5.3 %). Further epidemiologic studies are needed to better understand the pathobiology of these differences. PMID:26537613

  12. Burkitt lymphoma

    MedlinePlus

    ... is closely associated with the Epstein-Barr virus ( EBV ), the main cause of infectious mononucleosis . The North ... form of Burkitt lymphoma is not linked to EBV. People with HIV have an increased risk for ...

  13. Follicular mucinosis presenting as an acneiform eruption: a follow-up study.

    PubMed

    Brau-Javier, Cristina N; Santos-Arroyo, Aileen E; De Sanctis-González, Ivette M; Sánchez, Jorge L

    2013-12-01

    It has been proposed by many authors that follicular mucinosis is directly associated with mycosis fungoides (MF). Follicular mucinosis may be classified into 3 main clinical variants: a benign idiopathic form in children and young adults, which includes an acneiform presentation; an idiopathic form in older patients with a benign course; and a third variant that occurs in adults and is associated with MF. Our goal was to study the relationship between the acneiform variant of follicular mucinosis and MF. Eight patients previously diagnosed with the acneiform variant of follicular mucinosis were identified. Biopsy specimens were reviewed to evaluate the histopathologic attributes that characterize the disease and the infiltrate's immunohistochemistry. Also, patient follow-up was assessed to evaluate the clinical course of the disease. Median age of onset of disease was 29.5 years; 95% of lesions were located in the head and neck region. Biopsy specimens showed a moderate to dense perivascular, perifollicular, and interstitial infiltrate of lymphocytes with mucinous deposits within the follicular epithelium. On immunohistochemistry, the infiltrate showed prominent leukocyte common antigen (LCA) positivity and a CD3-positive and CD4-positive infiltrate with rare CD20-positive cells. None of the study patients showed evidence of MF after a mean follow-up of 3 years. The benign course of disease demonstrated in the study patients suggests that the acneiform variant of follicular mucinosis probably represents a subpopulation of the benign idiopathic form of the disease. However, given that histopathologically this variant cannot be distinguished from the lymphoma-associated variant of follicular mucinosis, longitudinal evaluation is still warranted in these patients. PMID:24257190

  14. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP.

    PubMed

    Pavlovsky, S; Santarelli, M T; Erazo, A; Diaz Maqueo, J C; Somoza, N; Lluesma Goñalons, M; Cervantes, G; Garcia Vela, E L; Corrado, C; Magnasco, H

    1992-03-01

    A randomized multicenter phase III study was conducted to compare the efficacy and toxicity of CHOP and CNOP in intermediate and high-grade non-Hodgkin's lymphoma. CHOP consisted of cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, doxorubicin 50 mg/m2 on day 1 and prednisone 50 mg/m2 on days 1 to 5. The CNOP regimen was identical to CHOP except for replacement of doxorubicin by 10 mg/m2 mitoxantrone. Patient characteristics were evenly distributed in the two arms, except for age and stage, which slightly favoured the CHOP arm. The rate of complete remission was 70% (31/44) in patients treated with CHOP and 51% (23/45) in those receiving CNOP (P = 0.09). At 48 months and with a median follow-up of 41 months, 44% of the complete responders treated with CHOP and 64% of those treated with CNOP were estimated to still be in their first complete remission (P = 0.14), while 31% and 34% remained alive and free of progression. The Kaplan-Meier estimate of overall survival at 48 months is 53% and 50%, respectively. The higher response rate obtained with CHOP probably reflected a less aggressive lymphoma population. The mean WBC nadir was 2.0 x 10(9)/l for CHOP and 1.8 x 10(9)/l for CNOP. One and three patients, respectively, died during induction. Nausea, vomiting and cardiac toxicity were similar. More alopecia and mucositis were observed with CHOP. We conclude that CHOP and CNOP have similar toxicities and are equivalent in previously untreated non-Hodgkin's lymphoma in terms of complete response rate, event-free survival and overall survival. PMID:1586618

  15. Enhancer mutations of Akv murine leukemia virus inhibit the induction of mature B-cell lymphomas and shift disease specificity towards the more differentiated plasma cell stage

    SciTech Connect

    Sorensen, Karina Dalsgaard; Kunder, Sandra; Quintanilla-Martinez, Leticia; Sorensen, Jonna; Schmidt, Joerg; Pedersen, Finn Skou . E-mail: fsp@mb.au.dk

    2007-05-25

    This study investigates the role of the proviral transcriptional enhancer for B-lymphoma induction by exogenous Akv murine leukemia virus. Infection of newborn inbred NMRI mice with Akv induced 35% plasma cell pr