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Sample records for aggressive b-cell non-hodgkin

  1. Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2017-03-15

    Aggressive Non-Hodgkin Lymphoma; CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  2. HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma.

    PubMed

    Zappasodi, Roberta; Ruggiero, Giusi; Guarnotta, Carla; Tortoreto, Monica; Tringali, Cristina; Cavanè, Alessandra; Cabras, Antonello D; Castagnoli, Lorenzo; Venerando, Bruno; Zaffaroni, Nadia; Gianni, Alessandro M; De Braud, Filippo; Tripodo, Claudio; Pupa, Serenella M; Di Nicola, Massimo

    2015-03-12

    We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock protein (HSP)H1/105 in function of their aggressiveness. Here, we now clarify its role as a functional B-NHL target by testing the hypothesis that it promotes the stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of aggressive B-NHLs was paralleled by Bcl-6 and c-Myc downregulation. In vitro and in vivo analysis of HSPH1-silenced Namalwa cells showed that this effect was associated with a significant growth delay and the loss of tumorigenicity when 10(4) cells were injected into mice. Interestingly, we found that HSPH1 physically interacts with c-Myc and Bcl-6 in both Namalwa cells and primary aggressive B-NHLs. Accordingly, expression of HSPH1 and either c-Myc or Bcl-6 positively correlated in these diseases. Our study indicates that HSPH1 concurrently favors the expression of 2 key lymphoma oncoproteins, thus confirming its candidacy as a valuable therapeutic target of aggressive B-NHLs.

  3. Post-autologous stem cell transplantation administration of rituximab improves the outcome of patients with aggressive B cell non-Hodgkin's lymphoma.

    PubMed

    Tsirigotis, Panagiotis; Dray, Liliane; Resnick, Igor B; Ackerstein, Aliza; Gesundheit, Benjamin; Elad, Sharon; Or, Reuven; Shapira, Michael-Yechiel

    2010-03-01

    The major cause of treatment failure following high-dose therapy with autologous stem cell transplantation (ASCT) for aggressive B cell non-Hodgkin's lymphoma (NHL) is persistent disease or recurrence. We describe our experience with the administration of rituximab post-ASCT, either as maintenance therapy or for the treatment of relapsed disease in patients with aggressive B cell NHL. Fifty-six patients achieved complete remission post-transplant, and 19 of them received maintenance with rituximab. Maintenance with rituximab resulted in statistically significant superior outcome in terms of progression free (PFS; p = 0.002) and overall survival (OS; p = 0.011). The median PFS and OS of patients in the maintenance arm has not been reached yet, while the median PFS and OS of patients in the control arm were 29 and 42 months, respectively. Fifty-four patients had disease progression or relapsed post-ASCT, and 15 of them received rituximab in combination with chemo- and/or radiotherapy in order to achieve disease remission. Therapeutic administration of rituximab resulted in statistically significant prolongation of OS (p = 0.021). The median OS of patients treated with rituximab was 17 months, while median OS of patients in the control group was 10 months. We consider that the results of our study are promising but need to be verified within large randomized trials.

  4. Expression of the brain transcription factor OTX1 occurs in a subset of normal germinal-center B cells and in aggressive Non-Hodgkin Lymphoma.

    PubMed

    Omodei, Daniela; Acampora, Dario; Russo, Filippo; De Filippi, Rosaria; Severino, Valeria; Di Francia, Raffaele; Frigeri, Ferdinando; Mancuso, Pietro; De Chiara, Anna; Pinto, Antonio; Casola, Stefano; Simeone, Antonio

    2009-12-01

    The roles in brain development. Previous studies have shown the association between OTX2 and OTX1 with anaplastic and desmoplastic medulloblastomas, respectively. Here, we investigated OTX1 and OTX2 expression in Non-Hodgkin Lymphoma (NHL) and multiple myeloma. A combination of semiquantitative RT-PCR, Western blot, and immunohistochemical analyses was used to measure OTX1 and OTX2 levels in normal lymphoid tissues and in 184 tumor specimens representative of various forms of NHL and multiple myeloma. OTX1 expression was activated in 94% of diffuse large B-cell lymphomas, in all Burkitt lymphomas, and in 90% of high-grade follicular lymphomas. OTX1 was undetectable in precursor-B lymphoblastic lymphoma, chronic lymphocytic leukemia, and in most marginal zone and mantle cell lymphomas and multiple myeloma. OTX2 was undetectable in all analyzed malignancies. Analysis of OTX1 expression in normal lymphoid tissues identified a subset of resting germinal center (GC) B cells lacking PAX5 and BCL6 and expressing cytoplasmic IgG and syndecan. About 50% of OTX1(+) GC B cells co-expressed CD10 and CD20. This study identifies OTX1 as a molecular marker for high-grade GC-derived NHL and suggests an involvement of this transcription factor in B-cell lymphomagenesis. Furthermore, OTX1 expression in a subset of normal GC B cells carrying plasma cell markers suggests its possible contribution to terminal B-cell differentiation.

  5. Expression of the Brain Transcription Factor OTX1 Occurs in a Subset of Normal Germinal-Center B Cells and in Aggressive Non-Hodgkin Lymphoma

    PubMed Central

    Omodei, Daniela; Acampora, Dario; Russo, Filippo; De Filippi, Rosaria; Severino, Valeria; Di Francia, Raffaele; Frigeri, Ferdinando; Mancuso, Pietro; De Chiara, Anna; Pinto, Antonio; Casola, Stefano; Simeone, Antonio

    2009-01-01

    The roles in brain development. Previous studies have shown the association between OTX2 and OTX1 with anaplastic and desmoplastic medulloblastomas, respectively. Here, we investigated OTX1 and OTX2 expression in Non-Hodgkin Lymphoma (NHL) and multiple myeloma. A combination of semiquantitative RT-PCR, Western blot, and immunohistochemical analyses was used to measure OTX1 and OTX2 levels in normal lymphoid tissues and in 184 tumor specimens representative of various forms of NHL and multiple myeloma. OTX1 expression was activated in 94% of diffuse large B-cell lymphomas, in all Burkitt lymphomas, and in 90% of high-grade follicular lymphomas. OTX1 was undetectable in precursor-B lymphoblastic lymphoma, chronic lymphocytic leukemia, and in most marginal zone and mantle cell lymphomas and multiple myeloma. OTX2 was undetectable in all analyzed malignancies. Analysis of OTX1 expression in normal lymphoid tissues identified a subset of resting germinal center (GC) B cells lacking PAX5 and BCL6 and expressing cytoplasmic IgG and syndecan. About 50% of OTX1+ GC B cells co-expressed CD10 and CD20. This study identifies OTX1 as a molecular marker for high-grade GC-derived NHL and suggests an involvement of this transcription factor in B-cell lymphomagenesis. Furthermore, OTX1 expression in a subset of normal GC B cells carrying plasma cell markers suggests its possible contribution to terminal B-cell differentiation. PMID:19893048

  6. B-cell Non-Hodgkin Lymphomas with Plasmacytic Differentiation.

    PubMed

    Harmon, Charles M; Smith, Lauren B

    2016-03-01

    B-cell non-Hodgkin lymphomas with plasmacytic differentiation are a diverse group of entities with extremely variable morphologic features. Diagnostic challenges can arise in differentiating lymphoplasmacytic lymphoma from marginal zone lymphoma and other low-grade B-cell lymphomas. In addition, plasmablastic lymphomas can be difficult to distinguish from diffuse large B-cell lymphoma or other high-grade lymphomas. Judicious use of immunohistochemical studies and molecular testing can assist in appropriate classification.

  7. Primary non-hodgkin B cell lymphoma in a man.

    PubMed

    Alhabshi, Sh M I; Ismail, Z; Arasaratnam, Sh A

    2011-03-01

    Malignant breast lymphoma is a rare condition and primary breast lymphoma is extremely rare in the male population. We present a case of a 26-year-old man (transgender) who presented with a large palpable mass in the right breast. This mass was rapidly growing in size associated with right axillary lymphadenopathy. Ultrasound and MRI findings were consistent with BIRADS IV lesion which was suspicious of malignancy. Core biopsy was performed and histopathology confirmed the diagnosis of primary non Hodgkin B cell lymphoma of the breast.

  8. L-PROBe: A Novel Non-anthracycline Combination Chemotherapy Regimen for Aggressive B Cell Non-Hodgkin Lymphoma in Elderly Patients.

    PubMed

    Law, Arjun Datt; Prakash, Gaurav; Khadwal, Alka; Das, Ashim; Varma, Subhash; Malhotra, Pankaj

    2017-03-01

    The management of aggressive B cell lymphomas in elderly patients is associated with poor tolerability of commonly used chemotherapeutic agents. The safety and tolerability of a novel combination chemotherapy regimen utilizing rituximab, lenalidomide, bendamustine, vincristine and prednisolone was assessed in a series of elderly patients with new onset or relapsed/refractory aggressive B cell lymphoma and inability to receive conventional chemotherapy due to poor performance status and/or significant comorbidities. Ten patients (7 male, 3 female) with a median age of 72 years (range 58-79 years) received therapy with lenalidomide (10 mg/day on days 1-14), rituximab (375 mg/m(2) on day 1), bendamustine (90 mg/m(2) on days 1 and 2), vincristine (1.4 mg/m(2) on day 1) and prednisolone (60 mg/m(2)/day on days 1-5) with cycles repeated every 28 days. Grade 3/4 hematological toxicities included neutropenia (30 %), anemia (30 %) and thrombocytopenia (10 %). An overall response rate of 40 % was observed with a median survival of 120 days (range 14-286 days). Three of the patients who responded achieved complete remission at the end of six cycles of therapy. This combination chemotherapy appears to be well tolerated and effective in elderly patients with poor performance status. Larger controlled studies are indicated to clearly demonstrate applicability of this novel regimen.

  9. Clinical association of baseline levels of conjugated dienes in low-density lipoprotein and nitric oxide with aggressive B-cell non-Hodgkin lymphoma and their relationship with immunoglobulins and Th1-to-Th2 ratio

    PubMed Central

    Haddouche, Mustapha; Meziane, Warda; Hadjidj, Zeyneb; Mesli, Naima; Aribi, Mourad

    2016-01-01

    Objective The aim of this study was to highlight the clinical association of baseline levels of conjugated dienes in low-density lipoprotein (LDL-BCD) and nitric oxide (NO) with immunoglobulins (Igs) and T helper (Th)1/Th2 ratio in patients with newly diagnosed B-cell non-Hodgkin lymphoma (NHL). Patients and methods Thirty-two newly diagnosed patients with aggressive B-cell NHL and 25 age-, sex-, and body-mass-index-matched healthy controls were randomly selected for a cross-sectional case–control study conducted at the Hematology Department of Tlemcen Medical Centre University (northwest of Algeria). Results Circulating levels of LDL-BCD and NO and those of IgA and IgM were significantly higher in patients than in controls. The levels of Th1/Th2 ratio and plasma total antioxidant capacity were significantly lower in patients compared with controls, while malondialdehyde and protein carbonyl levels were significantly higher in patients. B-cell NHL was significantly associated with high levels of LDL-BCD from 25th to 75th percentile (25th percentile: relative risk [RR] =2.26, 95% confidence interval [CI] 1.42–3.59, P=0.014; 50th percentile: RR =2.84, 95% CI 1.72–4.68, P<0.001; 75th percentile: RR =5.43, 95% CI 2.58–11.42, P<0.001). Similarly, the disease was significantly associated with high levels of NO production from 25th to 75th percentile (25th percentile: RR =2.07, 95% CI 1.25–3.44, P=0.024; 50th percentile: RR =2.78, 95% CI 1.63–4.72, P<0.001; 75th percentile: RR =4.68, 95% CI 2.21–9.91, P<0.001). Moreover, LDL-BCD levels were positively and significantly correlated with interferon (IFN)-γ, whereas NO levels were inversely and significantly correlated with IFN-γ and Th1/Th2 ratio. Conclusion LDL-BCD and NO production seem to be associated with aggressive B-cell NHL and alteration of Th1/Th2 ratio. Our results have to be examined using ex vivo mechanistic studies leading to further investigations of these parameters, with an interest in the

  10. A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma

    PubMed Central

    Arora, Mili; Gowda, Sonia; Tuscano, Joseph

    2016-01-01

    Lenalidomide, an immunomodulatory drug that the US Food and Drug Administration (FDA) approved for the treatment of multiple myeloma, 5q- myelodysplasia and mantle-cell lymphoma (MCL), has encouraging efficacy in other B-cell malignancies. Its unique mechanism of action is in part due to altering the tumor microenvironment and potentiating the activity of T and natural-killer (NK) cells. Impressive clinical activity and excellent tolerability allows broad applicability. Lenalidomide has been used in a wide range of B-cell malignancies for years, but in 2013, the FDA marked its approval as a single agent only in relapsed/refractory mantle-cell lymphoma. Perhaps most impressive is the efficacy of lenalidomide when combined with monoclonal antibodies. Impressive efficacy and toxicity profiles with the combination of lenalidomide and rituximab in B-cell lymphomas in both the upfront and relapsed/refractory setting may allow a shift in our current treatment paradigm in both indolent and aggressive non-Hodgkin lymphoma (NHL). This review will summarize the current data in the relapsed/refractory and front-line setting of NHL with single-agent lenalidomide as well as its use in combination with other agents. PMID:27493711

  11. A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma.

    PubMed

    Witzig, T E; Nowakowski, G S; Habermann, T M; Goy, A; Hernandez-Ilizaliturri, F J; Chiappella, A; Vitolo, U; Fowler, N; Czuczman, M S

    2015-08-01

    Lenalidomide is an oral non-chemotherapy immunomodulator with direct and indirect effects on non-Hodgkin lymphoma (NHL) cells and with single-agent activity in relapsed/refractory aggressive and indolent B-cell NHL, including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma, and follicular lymphoma. Based on the pivotal phase II MCL-001 trial of lenalidomide in heavily pretreated patients with relapsed/refractory MCL, lenalidomide was approved by the US Food and Drug Administration for the treatment of relapsed/refractory MCL after failure of two prior therapies, one of which includes bortezomib, at a recommended starting dose of 25 mg on days 1-21 of each 28-day cycle. Lenalidomide enhanced the survival benefit in combination with rituximab in preclinical models, prompting clinical evaluation of the lenalidomide-rituximab (R2) combination. In phase II trials, lenalidomide 20 mg on days 1-21 in combination with different standard-dose rituximab schedules exhibited promising activity in both first-line and relapsed/refractory disease across multiple B-cell NHL subtypes. The feasibility of combining lenalidomide with immunochemotherapy, including R-CHOP and rituximab-bendamustine, has been demonstrated in phase I/II trials. These latter regimens are currently being evaluated in ongoing phase II and III trials. The role of lenalidomide monotherapy and R2 in maintenance therapy is also being examined. Based on available evidence, a comprehensive review of lenalidomide in all treatment phases of B-cell NHL-relapsed/refractory disease, first-line, and maintenance-is presented here.

  12. Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2017-03-21

    Aggressive Non-Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Small Lymphocytic Lymphoma

  13. 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

  14. huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2017-03-31

    Adult B Acute Lymphoblastic Leukemia; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Adult Acute Lymphoblastic Leukemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  15. 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

  16. Targeting CD20+ Aggressive B-cell Non-Hodgkin Lymphoma by Anti-CD20 CAR mRNA-Modified Expanded Natural Killer Cells In Vitro and in NSG Mice.

    PubMed

    Chu, Yaya; Hochberg, Jessica; Yahr, Ashlin; Ayello, Janet; van de Ven, Carmella; Barth, Matthew; Czuczman, Myron; Cairo, Mitchell S

    2015-04-01

    The prognosis is very dismal for patients with relapsed CD20(+) B-cell non-Hodgkin lymphoma (B-NHL). Facilitating the development of alternative novel therapeutic strategies is required to improve outcomes in patients with recurrent/refractory CD20(+) B-NHL. In this study, we investigated functional activities of anti-CD20 CAR-modified, expanded peripheral blood NK cells (exPBNK) following mRNA nucleofection against CD20(+) B-NHL in vitro and in vivo. CAR(+) exPBNK had significantly enhanced in vitro cytotoxicity, compared with CAR(-) exPBNK against CD20(+) Ramos (P < 0.05), Daudi, Raji, and two rituximab-resistant cell lines, Raji-2R and Raji-4RH (P < 0.001). As expected, there was no significant difference against CD20(-) RS4;11 and Jurkat cells. CD107a degranulation and intracellular IFNγ production were also enhanced in CAR(+) exPBNK in response to CD20(+) B-NHL -: specific stimulation. In Raji-Luc and Raji-2R-Luc xenografted NOD/SCID/γ-chain(-/-) (NSG) mice, the luciferase signals measured in the CAR(+) exPBNK-treated group were significantly reduced, compared with the signals measured in the untreated mice and in mice treated with the CAR(-) exPBNK. Furthermore, the CAR exPBNK-treated mice had significantly extended survival time (P < 0.001) and reduced tumor size, compared with those of the untreated and the CAR(-) exPBNK-treated mice (P < 0.05). These preclinical data suggest that ex vivo-exPBNK modified with anti-CD20 CAR may have therapeutic potential for treating patients with poor-risk CD20(+) hematologic malignancies.

  17. 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

  18. Mechanisms of Action of Lenalidomide in B-Cell Non-Hodgkin Lymphoma

    PubMed Central

    Gribben, John G.; Fowler, Nathan; Morschhauser, Franck

    2015-01-01

    Lenalidomide is an orally active immunomodulatory drug that has direct antineoplastic activity and indirect effects mediated through multiple types of immune cells found in the tumor microenvironment, including B, T, natural killer (NK), and dendritic cells. Recently, the E3 ubiquitin ligase cereblon was identified as a molecular target that may underlie the effects of lenalidomide on tumor cells, as well as on cells in the tumor microenvironment. Decreases in cereblon attenuate these effects and also confer resistance to lenalidomide. Tumoricidal effects of lenalidomide are associated with reduced interferon regulatory factor 4, a downstream target of cereblon. Lenalidomide stimulates proliferation and activation of NK cells, thereby enhancing NK cell–mediated cytotoxicity and antibody-dependent cellular cytotoxicity. These effects appear to be secondary to cytokine production from T cells. Lenalidomide has been shown to produce synergistic effects in experimental models when evaluated in combination with rituximab, dexamethasone, bortezomib, and B-cell receptor signaling inhibitors, consistent with mechanisms complementary to these agents. These experimental findings have translated to the clinic, where single-agent use displays durable responses in relapsed/refractory non-Hodgkin lymphoma, and combination with rituximab and other agents leads to improved responses at first line and in relapsed/refractory disease. The activity of lenalidomide is evident across multiple lymphoma subtypes, including indolent and aggressive forms. The interaction among cell types in the immune microenvironment is increasingly recognized as important to tumor cell recognition and destruction, as well as to protection of normal immune cells, as reflected by lenalidomide studies across multiple types of B-cell lymphomas. PMID:26195701

  19. Mechanisms of Action of Lenalidomide in B-Cell Non-Hodgkin Lymphoma.

    PubMed

    Gribben, John G; Fowler, Nathan; Morschhauser, Franck

    2015-09-01

    Lenalidomide is an orally active immunomodulatory drug that has direct antineoplastic activity and indirect effects mediated through multiple types of immune cells found in the tumor microenvironment, including B, T, natural killer (NK), and dendritic cells. Recently, the E3 ubiquitin ligase cereblon was identified as a molecular target that may underlie the effects of lenalidomide on tumor cells, as well as on cells in the tumor microenvironment. Decreases in cereblon attenuate these effects and also confer resistance to lenalidomide. Tumoricidal effects of lenalidomide are associated with reduced interferon regulatory factor 4, a downstream target of cereblon. Lenalidomide stimulates proliferation and activation of NK cells, thereby enhancing NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. These effects appear to be secondary to cytokine production from T cells. Lenalidomide has been shown to produce synergistic effects in experimental models when evaluated in combination with rituximab, dexamethasone, bortezomib, and B-cell receptor signaling inhibitors, consistent with mechanisms complementary to these agents. These experimental findings have translated to the clinic, where single-agent use displays durable responses in relapsed/refractory non-Hodgkin lymphoma, and combination with rituximab and other agents leads to improved responses at first line and in relapsed/refractory disease. The activity of lenalidomide is evident across multiple lymphoma subtypes, including indolent and aggressive forms. The interaction among cell types in the immune microenvironment is increasingly recognized as important to tumor cell recognition and destruction, as well as to protection of normal immune cells, as reflected by lenalidomide studies across multiple types of B-cell lymphomas.

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

    ClinicalTrials.gov

    2017-02-10

    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

  1. Ileocecal Obstruction Due to B-cell Non-Hodgkin Lymphoma.

    PubMed

    Negrean, Vasile; Graur, Florin; Moiş, Emil; Al-Hajjar, Nadim

    2016-01-01

    We report a rare case of non-Hodgkin lymphoma presented as an ileocecal mass. The patient was a 77-year-old man with history of symptoms of partial bowel obstruction, intermittent right iliac fossa pain, loss of weight, vomiting and fatigue. Clinical signs included moderate abdominal tenderness with a palpable mass in the right iliac fossa at the physical examination. Colonoscopy revealed an intussusception of the right colon causing a complete stenosis. The patient developed complete bowel obstruction during hospitalization that required emergent surgical intervention. Intraoperatively an ileocecal mass was found measuring 10-12 cm in diameter, causing complete stenosis at its level and bowel dilatation proximally. Multiple nodules were found in the liver and the parietal peritoneum as well. An ileotransverso-anastomosis was performed and biopsies of the nodules were taken. Pathological evaluation revealed a diffuse large B cell non-Hodgkin'™s lymphoma of the ileocecum and the parietal peritoneum.

  2. Differential expression of enhancer of zeste homolog 2 (EZH2) protein in small cell and aggressive B-cell non-Hodgkin lymphomas and differential regulation of EZH2 expression by p-ERK1/2 and MYC in aggressive B-cell lymphomas.

    PubMed

    Tian, Xuejun; Pelton, Ashley; Shahsafaei, Ali; Dorfman, David M

    2016-09-01

    EZH2, a member of the polycomb protein group, is an important methyltransferase that is overexpressed in various neoplasms. We found that in small cell B-cell lymphomas, EZH2 is expressed in <40% of neoplastic cells, with heterogenous signal intensity. In aggressive B-cell lymphomas, 70-100% of tumor cells were positive for EZH2 expression with high signal intensity, which correlated with a high proliferation rate. We investigated the potential signaling molecules that regulate EZH2 overexpression in aggressive B-cell lymphomas and found that 80% of cases of EZH2-positive diffuse large B-cell lymphoma show high p-ERK1/2 expression (average ~57% tumor cell positivity). In contrast, only a small percentage of tumor cells (~10%) show p-ERK1/2 expression in Burkitt lymphoma and double hit lymphoma. On average, 91 and 76% of neoplastic cells were positive for MYC expression in Burkitt lymphoma and double hit lymphoma, respectively, while only 20% neoplastic cells were positive for MYC expression in diffuse large B-cell lymphoma. None of the aggressive B-cell lymphomas showed significant p-STAT3 expression in EZH2-overexpressed cases. The correlation of EZH2 expression with aggressive behavior and proliferation rate in B-cell neoplasms suggests that this molecule may function as an oncogenic protein in these neoplasms, with possible regulation by different signaling cascades in different types of aggressive B-cell lymphomas: p-ERK-related signaling in diffuse large B-cell lymphoma, and MYC-related signaling in Burkitt lymphoma and double hit lymphoma. Furthermore, EZH2 and associated signaling cascades may serve as therapeutic targets for the treatment of aggressive B-cell lymphomas.

  3. Pretransplant FDG-PET in aggressive non-Hodgkin lymphoma: systematic review and meta-analysis.

    PubMed

    Adams, Hugo J A; Kwee, Thomas C

    2017-04-01

    This study aimed to systematically review and meta-analyze the value of pretransplant FDG-PET in predicting outcome after autologous stem cell transplantation in aggressive non-Hodgkin lymphoma. MEDLINE was systematically searched; included studies were methodologically assessed and meta-analyzed, when possible. Overall methodological quality of included studies (n = 11) was poor, with moderate risk of bias in the domains of study participation (n = 7) and prognostic factor measurement (n = 7), and high risk of bias in the domains of outcome measurement (n = 10), and study confounding (n = 11). In all aggressive non-Hodgkin lymphomas, pooled sensitivity and specificity were 54.0% and 73.1% in predicting treatment failure, and 54.5% and 68.7% in predicting death. Because of interstudy heterogeneity, additional subgroup analyses were performed. In newly diagnosed aggressive non-Hodgkin lymphoma, pooled sensitivity and specificity were 20.0% and 70.0% in predicting treatment failure, and 8.3% % and 30.5% in predicting death. In refractory/relapsed aggressive non-Hodgkin lymphoma, pooled sensitivity and specificity were 68.1% and 72.1% in predicting treatment failure, and 77.3% and 69.6% in predicting death. At present, pretransplant FDG-PET cannot be recommended in aggressive non-Hodgkin lymphoma, because available studies suffer from major methodological flaws, and reported prognostic estimates are low (i.e., poor in newly diagnosed and moderate in refractory/relapsed aggressive non-Hodgkin lymphoma).

  4. Primary bone marrow B-cell non-Hodgkin's lymphoma successfully treated with R-CHOP.

    PubMed

    Qian, Liren; Zhang, Zhi; Shen, Jianliang; Liu, Yi

    2013-01-01

    Primary isolated bone marrow disease as a presenting feature of lymphoma is very rare. We describe the case of a Chinese with isolated bone marrow small B-cell lymphoma as a first manifestation. A 55-year old woman was admitted to our hospital with fever. Her peripheral blood smear and laboratory findings were suggestive of bicytopenia. Bone marrow specimen showed diffusely distributed small-sized lymphocytes. Combined with immunophenotypic and chromosomal analysis, a diagnosis of primary bone marrow B-cell non-Hodgkin's lymphoma was made. The patient was treated with R-CHOP (rituximab and cyclophosphamide, epirubicin, vindesine, and prednisone) regimen for six cycles. She had complete remission and is still alive without relapse. We concluded that primary bone marrow mature small B-cell lymphoma is a rare but distinctive subtype of lymphoma. The prognosis for this entity is poor but rituximab-based treatment is promising for improving its outcomes.

  5. Aberrant Circulating Th17 Cells in Patients with B-Cell Non-Hodgkin's Lymphoma.

    PubMed

    Lu, Ting; Yu, Shuang; Liu, Yan; Yin, Congcong; Ye, Jingjing; Liu, Zhi; Ma, Daoxin; Ji, Chunyan

    2016-01-01

    Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of neoplasm in which 90% are B-cell lymphomas and 10% T-cell lymphomas. Although T-helper 17 (Th17) cells have been implicated to be essential in the pathogenesis of autoimmune and inflammatory diseases, its role in B-cell non-Hodgkin's lymphoma (B-NHL) remains unknown. In this study, we observed a significantly decreased frequency of Th17 cells in peripheral blood from B-NHL patients compared with healthy individuals, accompanied with increased Th1 cells. IL-17AF plasma levels were remarkably decreased in B-NHL patients, accompanied with undetectable IL-17FF and unchangeable IL-17AA. Moreover, Th17 and Th1 cells became normalized after one or two cycles of chemotherapy. Interestingly, in B-NHL, circulating Th17 cells frequencies were significantly higher in relapsed patients than those in untreated patients or normal individuals. Meanwhile, there was no statistical difference regarding the frequencies of Th1 cells between relapsed and untreated patients. Taken these data together, circulating Th17 subset immune response may be associated with the response of patients to treatment and with different stages of disease.

  6. Obinutuzumab, Venetoclax, and Lenalidomide in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2017-03-01

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  7. Lack of TERT Promoter Mutations in Human B-Cell Non-Hodgkin Lymphoma

    PubMed Central

    Lam, Gary; Xian, Rena R.; Li, Yingying; Burns, Kathleen H.; Beemon, Karen L.

    2016-01-01

    Non-Hodgkin lymphomas (NHL) are a heterogeneous group of immune cell neoplasms that comprise molecularly distinct lymphoma subtypes. Recent work has identified high frequency promoter point mutations in the telomerase reverse transcriptase (TERT) gene of different cancer types, including melanoma, glioma, liver and bladder cancer. TERT promoter mutations appear to correlate with increased TERT expression and telomerase activity in these cancers. In contrast, breast, pancreatic, and prostate cancer rarely demonstrate mutations in this region of the gene. TERT promoter mutation prevalence in NHL has not been thoroughly tested thus far. We screened 105 B-cell lymphoid malignancies encompassing nine NHL subtypes and acute lymphoblastic leukemia, for TERT promoter mutations. Our results suggest that TERT promoter mutations are rare or absent in most NHL. Thus, the classical TERT promoter mutations may not play a major oncogenic role in TERT expression and telomerase activation in NHL. PMID:27792139

  8. The molecular pathogenesis of B-cell non-Hodgkin lymphoma.

    PubMed

    Blombery, Piers A; Wall, Meaghan; Seymour, John F

    2015-10-01

    The B-cell non-Hodgkin lymphomas (B-NHL) are a diverse group of haematological malignancies which arise from the mature B-lymphocyte compartment. Recently, our understanding of the molecular pathogenesis of these disorders has greatly increased due to technological advances such as high-throughput DNA sequencing techniques. A paradigm of B-NHL pathogenesis has emerged where the normal genetic processes that are central to generating B-cell receptor diversity (somatic hypermutation and class switch/VDJ recombination) also drive the genesis of large-scale, chromosomal-level genetic lesions and smaller-scale gene-level mutations to produce the malignant phenotypes observed. Whilst a significant degree of genetic heterogeneity exists within each B-NHL subtype, the genetic lesions present within each subtype show a degree of convergence on common intracellular signalling, epigenetic and cell cycle pathways. This convergence gives an insight into the key oncogenic drivers of specific B-NHL subtypes and potential targets for therapeutic intervention. This review covers the current understanding of the causative genetic processes of B-NHL, the associated driving molecular lesions and the implications of these findings for the treatment of this group of disorders.

  9. Clinical development of radioimmunotherapy for B-cell non-Hodgkin's lymphoma

    SciTech Connect

    Meredith, Ruby F. . E-mail: rmeredith@uabmc.edu; Knox, Susan J.

    2006-10-01

    Over the past several decades, several biomolecules have been investigated for their ability to deliver radiation to cancer cells, but antibodies have been the carriers of choice in systemic targeted radionuclide therapy (STaRT). Two radioimmunotherapy agents that target the CD20 antigen, {sup 131}I-tositumomab and {sup 9}Y-ibritumomab tiuxetan, have been approved by the U.S. Food and Drug Administration for the treatment of patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL), and clinical trials have shown that they are effective as monotherapies in the salvage setting, producing response rates that are often higher and durations of response that are often longer than those with chemotherapy. Escalated doses of these agents can be supported with stem cell transplantation and can produce high rates of complete response and greater survival in patients with relapsed NHL. The quality and duration of responses are greater with radioimmunotherapy when it is used earlier in the course of treatment.

  10. Cold Autoimmune Hemolytic Anemia due to High-grade non Hodgkin's B cell Lymphoma with Weak Response to Rituximab and Chemotherapy Regimens.

    PubMed

    Nazel Khosroshahi, Behzad; Jafari, Mohammad; Vazini, Hossein; Ahmadi, Alireza; Shams, Keivan; Kholoujini, Mahdi

    2015-07-01

    Autoimmune hemolytic anemia (AIHA) is characterized by shortening of red blood cell (RBC) survival and the presence of autoantibodies directed against autologous RBCs. Approximately 20% of autoimmune hemolytic anemia cases are associated with cold-reactive antibody. About half of patients with AIHA have no underlying associated disease; these cases are termed primary or idiopathic. Secondary cases are associated with underlying diseases or with certain drugs. We report herein a rare case of cold autoimmiune hemolytic anemia due to high-grade non-Hodgkin's lymphoma of B-cell type with weak response to rituximab and chemotherapy regimens. For treatment B cell lymphoma, Due to lack of treatment response, we used chemotherapy regimens including R- CHOP for the first time, and then Hyper CVAD, R- ICE and ESHAP were administered, respectively. For treatment of autoimmune hemolytic anemia, we have used the corticosteroid, rituximab, plasmapheresis and blood transfusion and splenectomy. In spite of all attempts, the patient died of anemia and aggressive lymphoma nine months after diagnosis. To our knowledge, this is a rare report from cold autoimmune hemolytic anemia in combination with high-grade non-Hodgkin's lymphoma of B-cell type that is refractory to conventional therapies.

  11. 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

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

    ClinicalTrials.gov

    2017-02-20

    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

  13. [Atypical presentation of diffuse large B-cell non-Hodgkin lymphoma].

    PubMed

    Alcocer-Gamba, Marco Antonio; León-González, Salvador; Castro-Montes, Eliodoro; Loarca-Piña, Luis Martín; Lugo-Gavidia, Leslie Marisol; García-Hernández, Enrique

    2015-01-01

    The non-Hodgkin lymphoma is a neoplastic entity that presents in extranodal form in 20 % of cases, usually occurs as solitary or generalized lymphadenopathy. There may be misdiagnosis if it manifests as primary extranodal disease because the primary infiltration may occur with different organs, despite the difficulty of diagnosis of primary extranodal location of non-Hodgkin lymphoma, histological and immunohistochemical studies are effective in preventing misdiagnosis. The presentation of this case is to describe this condition in its extranodal variety with cardiac infiltration in a 23 year-old woman with progressive dyspnea. Tumor mass was detected in right-atrial, venous catheterization biopsy was performed, this enabled the histopathological diagnosis and establish treatment. We present experiences from the attention of the case and review of the literature with special reference to diagnosis and treatment.

  14. CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi

    PubMed Central

    Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D.; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M.; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L.; Shea, Thomas C.; Liomba, N. George

    2016-01-01

    There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV. PMID:26934054

  15. 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

  16. Rarity of microsatellite genomic instability in B-cell non-Hodgkin's lymphomas in hepatitis C virus-infected patients.

    PubMed

    De Vita, S; Gasparotto, D; Pivetta, B; Vukosavljevic, T; Zagonel, V; Carbone, A; Boiocchi, M

    1997-05-01

    Several groups have emphasized the likely implication of the hepatitis C virus (HCV) in a fraction of B-cell non-Hodgkin's lymphomas. Since only a minority of patients with HCV infection and monoclonal mixed cryoglobulinaemia develop overt lymphoma, the identification of predisposing factors has relevant clinical implications. The replication error phenotype (RER+), as revealed by widespread microsatellite instability, is caused by defects in DNA mismatch repair genes, and has been frequently disclosed in subsets of B-cell lymphomas with underlying infection and chronic inflammation. We therefore investigated the occurrence of the RER+ phenotype in a series of eight consecutive B-cell NHLs in patients with chronic infection by HCV. A polymerase chain reaction-based assay was used to analyse an extended panel of 15 microsatellite loci. Microsatellite instability was not observed in six tumour samples in any locus; the two remaining cases showed instability at only one locus. Therefore genetic instability by defects in DNA mismatch repair genes should not represent the general mechanism predisposing to overt lymphoma in HCV-infected patients. Although a clearer definition of HCV-related B-cell disorders should better address future studies on genetic instability in larger series, we recommend additional oncogenetic pathways as the target of further research.

  17. Bruton's tyrosine kinase (Btk) is a useful marker for Hodgkin and B cell non-Hodgkin lymphoma.

    PubMed

    Fernández-Vega, Iván; Quirós, Luis M; Santos-Juanes, Jorge; Pane-Foix, María; Marafioti, Teresa

    2015-02-01

    Bruton's tyrosine kinase (Btk) is a member of the Tec family of protein tyrosine kinases involved in B cell development and proliferation in neoplastic human lymphoid tissues. We used immunohistochemistry to evaluate a polyclonal anti-Btk antibody on formalin-fixed paraffin-embedded tissue blocks. The tested samples included normal lymphoid tissues, tissue samples of 395 different lymphomas and 14 malignant lymphoid cell lines. Btk was expressed more often in B cell lymphomas than in T cell lymphomas. This correlated well with the results obtained on B cell lymphoma cell lines, which strongly expressed Btk, in contrast to T cell lymphoma cell lines. More than 60% of myelomas expressed Btk. Among Hodgkin lymphomas, the nodular lymphocyte predominant variant was more often positive (14/16) than the classical variant (6/27). Only one out of three Hodgkin lymphoma-derived cell lines showed a few atypical large cells expressing Btk. Btk represents a useful marker to identify B cell non-Hodgkin lymphomas. Furthermore, Btk might help to distinguish the nodular lymphocyte predominant variant of Hodgkin lymphomas from the classical form. Finally, in view of the recently discovered therapeutic potential of Btk inhibitors in lymphoma, we report the pattern of expression of Btk in a large collection of different types of lymphoma.

  18. Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity.

    PubMed

    Bende, Richard J; Aarts, Wilhelmina M; Riedl, Robert G; de Jong, Daphne; Pals, Steven T; van Noesel, Carel J M

    2005-04-18

    We analyzed the structure of antigen receptors of a comprehensive panel of mature B non-Hodgkin's lymphomas (B-NHLs) by comparing, at the amino acid level, their immunoglobulin (Ig)V(H)-CDR3s with CDR3 sequences present in GenBank. Follicular lymphomas, diffuse large B cell lymphomas, Burkitt's lymphomas, and myelomas expressed a CDR3 repertoire comparable to that of normal B cells. Mantle cell lymphomas and B cell chronic lymphocytic leukemias (B-CLLs) expressed clearly restricted albeit different CDR3 repertoires. Lymphomas of mucosa-associated lymphoid tissues (MALTs) were unique as 8 out of 45 (18%) of gastric- and 13 out of 32 (41%) of salivary gland-MALT lymphomas expressed B cell antigen receptors with strong CDR3 homology to rheumatoid factors (RFs). Of note, the RF-CDR3 homology without exception included N-region-encoded residues in the hypermutated IgV(H) genes, indicating that they were stringently selected for reactivity with auto-IgG. By in vitro binding studies with 10 MALT lymphoma-derived antibodies, we showed that seven of these cases, of which four with RF-CDR3 homology, indeed possessed strong RF reactivity. Of one MALT lymphoma, functional proof for selection of subclones with high RF affinity was obtained. Interestingly, RF-CDR3 homology and t(11;18) appeared to be mutually exclusive features and RF-CDR3 homology was not encountered in any of the 19 pulmonary MALT lymphomas studied.

  19. Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma

    PubMed Central

    Gardner, Heather L.; Izumi, Raquel; Hamdy, Ahmed; Rothbaum, Wayne; Coombes, Kevin R.; Covey, Todd; Kaptein, Allard; Gulrajani, Michael; Van Lith, Bart; Krejsa, Cecile; Coss, Christopher C.; Russell, Duncan S.; Zhang, Xiaoli; Urie, Bridget K.; London, Cheryl A.; Byrd, John C.; Johnson, Amy J.; Kisseberth, William C.

    2016-01-01

    Acalabrutinib (ACP-196) is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL). First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR) was 25% (5/20) with a median progression free survival (PFS) of 22.5 days. Clinical benefit was observed in 30% (6/20) of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL). PMID:27434128

  20. Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.

    PubMed

    Harrington, Bonnie K; Gardner, Heather L; Izumi, Raquel; Hamdy, Ahmed; Rothbaum, Wayne; Coombes, Kevin R; Covey, Todd; Kaptein, Allard; Gulrajani, Michael; Van Lith, Bart; Krejsa, Cecile; Coss, Christopher C; Russell, Duncan S; Zhang, Xiaoli; Urie, Bridget K; London, Cheryl A; Byrd, John C; Johnson, Amy J; Kisseberth, William C

    2016-01-01

    Acalabrutinib (ACP-196) is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL). First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR) was 25% (5/20) with a median progression free survival (PFS) of 22.5 days. Clinical benefit was observed in 30% (6/20) of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL).

  1. 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

  2. Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin's lymphomas

    PubMed Central

    Vacca, A; Ribatti, D; Ruco, L; Giacchetta, F; Nico, B; Quondamatteo, F; Ria, R; Iurlaro, M; Dammacco, F

    1999-01-01

    Node biopsies of 30 benign lymphadenopathies and 71 B-cell non-Hodgkin's lymphomas (B-NHLs) were investigated for microvessel and macrophage counts using immunohistochemistry and morphometric analysis. Both counts were significantly higher in B-NHL. Moreover, when these were grouped into low-grade and high-grade lymphomas, according to the Kiel classification and Working Formulation (WF), statistically significant higher counts were found in the high-grade tumours. Immunohistochemistry and electron microscopy revealed a close spatial association between microvessels and macrophages. Overall, the results suggest that, in analogy to what has already been shown in solid tumours, angiogenesis occurring in B-NHLs increases with tumour progression, and that macrophages promote the induction of angiogenesis via the release of their angiogenic factors. © 1999 Cancer Research Campaign PMID:10070898

  3. 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

  4. Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma

    PubMed Central

    Miller, Thomas P.; Friedberg, Jonathan W.; Peterson, Derick R.; Baran, Andrea M.; Herr, Megan; Spier, Catherine M.; Cui, Haiyan; Roe, Denise J.; Persky, Daniel O.; Casulo, Carla; Littleton, Jamie; Schwartz, Mark; Puvvada, Soham; Landowski, Terry H.; Rimsza, Lisa M.; Dorr, Robert T.; Fisher, Richard I.; Bernstein, Steven H.; Briehl, Margaret M.

    2014-01-01

    Lymphoma cells are subject to higher levels of oxidative stress compared with their normal counterparts and may be vulnerable to manipulations of the cellular redox balance. We therefore designed a phase 2 study of imexon (Amplimexon/NSC-714597), a prooxidant molecule, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Imexon was administered at 1000 mg/m2 IV daily for 5 days in 21-day cycles. Gene expression analysis performed on pretreatment tumor specimens included 13 transcripts used to generate a redox signature score, previously demonstrated to correlate with lymphoma prognosis. Twenty-two patients were enrolled having follicular (n = 9), diffuse large B-cell (DLBCL) (n = 5), mantle cell (n = 3), transformed follicular (n = 2), small lymphocytic (n = 2), and Burkitt (n = 1) lymphoma. The most common grade 3/4 adverse events were anemia (14%) and neutropenia (9%). The overall response rate was 30%, including responses in follicular lymphoma (4 of 9) and DLBCL (2 of 5). Gene expression analyses revealed CD68 and the redox-related genes, GPX1 and SOD2, as well as a higher redox score to correlate with clinical responses. Therefore, pretreatment markers of oxidative stress may identify patients likely to respond to this therapeutic approach. This trial was registered at www.clinicaltrials.gov as #NCT01314014. PMID:25016003

  5. Histopathological analysis of B-cell non-Hodgkin lymphomas without light chain restriction by using flow cytometry.

    PubMed

    Ohmoto, Akihiro; Maeshima, Akiko Miyagi; Taniguchi, Hirokazu; Tanioka, Kensaku; Makita, Shinichi; Kitahara, Hideaki; Fukuhara, Suguru; Munakata, Wataru; Suzuki, Tatsuya; Maruyama, Dai; Kobayashi, Yukio; Tobinai, Kensei

    2015-01-01

    Detection of immunoglobulin light chain restriction (LCR) by flow cytometry (FCM) is a useful tool for B-cell non-Hodgkin lymphoma (B-NHL) diagnosis. Here, we identified B-NHLs without LCR by FCM and investigated the pathological causes for lack of LCR. A total of 89/471 cases (19%) of B-NHL were LCR-negative. The incidence of lack of LCR was 30% both in diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL), and was 6% in follicular lymphoma (FL). In DLBCL cases, low expression of surface membrane light chain (33%), low proportion of lymphoma cells (11%), CD45 negativity (9%), and destruction or sampling error were suggested as reasons for lack of LCR. In MZL cases, the low proportion of lymphoma cells owing to admixture of many reactive germinal centres, and non-detection of plasmacytoid lymphoma cells by CD45 gating might be the reasons. Based on pathological subtypes, the frequency and reasons for lack of LCR by FCM varied.

  6. Hepatitis C virus-associated B-cell non-Hodgkin lymphomas.

    PubMed

    Vannata, Barbara; Zucca, Emanuele

    2014-12-05

    Epidemiological studies have demonstrated an increased risk of developing B-cell lymphomas in patients with chronic hepatitis C virus (HCV) infection. However, the strength of the association shows great geographic discrepancies, with higher relative risk in countries with high HCV prevalence. It remains unclear whether additional environmental and genetic factors are involved or if the international variability is simply a consequence of the variable infection prevalence. Therefore, a causal relationship remains controversial. Other confounding factors may affect the comparability of the different studies, including the method of HCV assessment, the selection of normal controls, the lymphoma classification used, and the year of publication. The most convincing proof is the observation, mainly limited to some indolent subtypes, of B-cell lymphoma regressions after HCV eradication with IFN and ribavirin. However, the molecular mechanisms of the HCV-induced lymphomagenesis are mainly hypothetical. According to the model considered to be most plausible, lymphoma growth is a consequence of the continuous antigenic stimulation of the B-cell immunologic response induced by the chronic viral infection. This review summarizes the current epidemiological and biological evidence of a role of HCV in lymphomagenesis, describing the putative mechanisms for a causative relationship. The clinical characteristics and management difficulties of the HCV-associated lymphomas are also discussed. HCV treatment with IFN cannot be given safely in concomitance with cytotoxic lymphoma treatment because of hematological and liver toxicity. However, novel and better tolerated antiviral regimens are under development and will hopefully make the treatment of both lymphoma and hepatitis easier in the future.

  7. Comprehensive characterization of programmed death ligand structural rearrangements in B-cell non-Hodgkin lymphomas.

    PubMed

    Chong, Lauren C; Twa, David D W; Mottok, Anja; Ben-Neriah, Susana; Woolcock, Bruce W; Zhao, Yongjun; Savage, Kerry J; Marra, Marco A; Scott, David W; Gascoyne, Randy D; Morin, Ryan D; Mungall, Andrew J; Steidl, Christian

    2016-09-01

    Programmed death ligands (PDLs) are immune-regulatory molecules that are frequently affected by chromosomal alterations in B-cell lymphomas. Although PDL copy-number variations are well characterized, a detailed and comprehensive analysis of structural rearrangements (SRs) and associated phenotypic consequences is largely lacking. Here, we used oligonucleotide capture sequencing of 67 formalin-fixed paraffin-embedded tissues derived from primary B-cell lymphomas and 1 cell line to detect and characterize, at base-pair resolution, SRs of the PDL locus (9p24.1; harboring PDL1/CD274 and PDL2/PDCD1LG2). We describe 36 novel PDL SRs, including 17 intrachromosomal events (inversions, duplications, deletions) and 19 translocations involving BZRAP-AS1, CD44, GET4, IL4R, KIAA0226L, MID1, RCC1, PTPN1 and segments of the immunoglobulin loci. Moreover, analysis of the precise chromosomal breakpoints reveals 2 distinct cluster breakpoint regions (CBRs) within either CD274 (CBR1) or PDCD1LG2 (CBR2). To determine the phenotypic consequences of these SRs, we performed immunohistochemistry for CD274 and PDCD1LG2 on primary pretreatment biopsies and found that PDL SRs are significantly associated with PDL protein expression. Finally, stable ectopic expression of wild-type PDCD1LG2 and the PDCD1LG2-IGHV7-81 fusion showed, in coculture, significantly reduced T-cell activation. Taken together, our data demonstrate the complementary utility of fluorescence in situ hybridization and capture sequencing approaches and provide a classification scheme for PDL SRs with implications for future studies using PDL immune-checkpoint inhibitors in B-cell lymphomas.

  8. Increased frequency of circulating Th22 cells in patients with B-cell non-Hodgkin's lymphoma

    PubMed Central

    Yu, Shuang; Yin, Congcong; Li, Peng; Ye, Jingjing; Ma, Daoxin; Ji, Chunyan

    2016-01-01

    T helper (Th) 22 cells play important roles in the pathogenesis of autoimmune and inflammatory diseases, and their function in tumors remains uncertain. In the current study, we investigated the alternations and clinical significance of circulating Th22 cells in patients with B-cell non-Hodgkin's lymphoma (B-NHL). We found that the frequency of Th22 cells was significantly elevated in peripheral blood of newly-diagnosed B-NHL patients, and returned to normal level after chemotherapy. In consistent with increased Th22 frequency, plasma IL-22 and IL-6 levels in B-NHL patients were remarkably increased. Moreover, the increased Th22 frequency was associated with the older age (> 60 yr) and a poorer response to therapy in B-NHL patients. In addition, there existed a statistically positive correlation between circulating Th22 and Th17 frequencies in B-NHL patients. Our data demonstrated that circulating Th22 frequency was associated with the clinical outcome and prognosis of B-NHL patients, indicating that Th22 immune response might play an important role in the development and progression of B-NHL. PMID:27489357

  9. Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin's lymphoma.

    PubMed

    Czuczman, Myron S; Kahanic, Stephen; Forero, Andres; Davis, Glen; Munteanu, Mihaela; Van Den Neste, Eric; Offner, Fritz; Bron, Dominique; Quick, Donald; Fowler, Nathan

    2015-04-01

    The efficacy/tolerability of bendamustine, a unique alkylator, plus ofatumumab, a human anti-CD20 monoclonal antibody, was evaluated for previously untreated indolent B cell non-Hodgkin's lymphoma (NHL). The study investigated whether the overall response rate (ORR) for bendamustine-ofatumumab was similar to historical bendamustine-rituximab ORRs (≥90 %). In this multicenter, open-label, single-arm, phase II study, patients received six planned 28-day cycles of bendamustine (90 mg/m(2) on days 1 and 2 of each cycle) and ofatumumab (300 mg on day 1, 1000 mg on day 8 of cycle 1, and on day 1 of subsequent cycles). The primary outcome was ORR. Secondary objectives included safety and tolerability. Exploratory evaluations included percentage of patients with positive baseline [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans who converted to negative postbaseline and quality of life (QOL) scores. The treated/safety analysis population received ≥1 dose of either therapy. The bendamustine-ofatumumab ORR was 90 % (95 % confidence interval, 77.8-96.6) in 49 treated patients (67 % complete response, 22 % partial response). No patients had progressive disease. Bendamustine-ofatumumab was acceptably tolerated. All 49 patients had ≥1 adverse event, the most common being nausea (61 %), fatigue (55 %), and infusion-related reactions (45 %, all but 1 occurring during cycle 1). The proportion of patients whose FDG-PET scans converted to negative postbaseline was 88 %. Changes in QOL scores were minor. In patients with treatment-naive, indolent B cell NHL, bendamustine-ofatumumab exhibited a high degree of activity (90 % ORR), comparable with historical bendamustine-rituximab ORRs (≥90 %), and was adequately tolerated ( ClinicalTrials.gov identifier: NCT01108341).

  10. Infusional etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone +/- rituximab as first-line therapy for aggressive non-Hodgkin lymphoma

    PubMed Central

    Lamar, Zanetta S.; Fino, Nora; Palmer, Jodi; Gruber, Lindsey; Morris, Bonny B.; RaetskayaSolntseva, Olga; Kennedy, LeAnne; Vaidya, Rakhee; Hurd, David; Zamkoff, Kenneth

    2015-01-01

    Introduction Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) was developed in an effort to overcome inadequate drug concentrations and to compensate for increased drug clearance. The goal of this study was to examine risk factors and outcomes in patients with aggressive non-Hodgkin lymphoma (aNHL) treated with DA-EPOCH. Patients and Methods We report 136 patients with previously untreated aNHL treated with infusional DA-EPOCH chemotherapy +/- rituximab from 2005-2013. Overall survival was estimated by Kaplan Meier methods. Univariate and multivariate logistic regression was used to determine factors associated with experiencing death, progression, or relapse at two years. Results The overall response rate was 82%. Relapse-free survival at 1, 3, and 5 years was 68%, 63%, and 52% with 95% CIs [0.59,0.85], [0.54,0.70], and [0.31,0.70], respectively. Patients with T-cell aNHL had increased risk of death, progression or relapse [OR:3.5, 95% CI: 1.4, 8.8] compared to those with B-cell aNHL. In multivariate analysis, current smoking, disease in the bone marrow and number of cycles completed were independent predictors of death or relapse. Conclusion Our data suggests EPOCH+/-R is active in both B and T-cell aNHL. Toxicity did not significantly delay treatment or negatively impact outcomes. Dose adjustment by hematopoietic nadir had no impact on outcomes. The impact of smoking during chemotherapy should be further evaluated. PMID:26725264

  11. 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

  12. Long-term risk of cardiovascular disease after treatment for aggressive non-Hodgkin lymphoma.

    PubMed

    Moser, Elizabeth C; Noordijk, Evert M; van Leeuwen, Flora E; le Cessie, Saskia; Baars, Joke W; Thomas, José; Carde, Patrice; Meerwaldt, Jacobus H; van Glabbeke, Martine; Kluin-Nelemans, Hanneke C

    2006-04-01

    Cardiovascular disease frequently occurs after lymphoma therapy, but it is common in the general population too. Therefore, risk estimation requires comparison to population-based rates. We calculated risk by standardized incidence ratios (SIRs) and absolute excess risks (AERs) per 10,000 person-years based on general population rates (Continuous Morbidity Registry Nijmegen) in 476 (Dutch and Belgian) patients with aggressive non-Hodgkin lymphoma (NHL) treated with at least 6 cycles of doxorubicin-based chemotherapy in 4 European Organization for Research on Treatment of Cancer (EORTC) trials (1980-1999). Cumulative incidence of cardiovascular disease, estimated in a competing risk model, was 12% at 5 years and 22% at 10 years (median follow-up, 8.4 years). Risk of chronic heart failure appeared markedly increased (SIR, 5.4; 95% CI, 4.1-6.9) with an AER of 208 excess cases per 10 000 person-years, whereas risk of coronary artery disease matched the general population (SIR, 1.2; 95% CI, 0.8-1.8; AER, 8 per 10 000 person-years). Risk of stroke was raised (SIR, 1.8; 95% CI, 1.1-2.4; AER, 15 per 10 000 person-years), especially after additional radiotherapy (> 40 Gy). Preexisting hypertension, NHL at young age, and salvage treatment increased risk of all cardiovascular events; the effect of radiotherapy was dose dependent. In conclusion, patients are at long-term high risk of chronic heart failure after NHL treatment and need therefore life-long monitoring. In contrast, risk of coronary artery disease appeared more age dependent than treatment related.

  13. Quality of Life is Similar between Long-term Survivors of Indolent and Aggressive Non-Hodgkin Lymphoma.

    PubMed

    Beaven, Anne W; Samsa, Greg; Zimmerman, Sheryl; Smith, Sophia K

    2016-07-02

    Differences in quality of life (QOL) of long-term survivors of aggressive or indolent subtypes of non-Hodgkin lymphoma (NHL) have not been frequently evaluated. We assessed these differences by analyzing results of a large QOL survey of long-term NHL survivors. We hypothesized that the incurable nature of indolent NHL would relate to worse QOL in long-term survivors while the potentially cured long-term survivors of aggressive lymphoma would have better QOL. We found that QOL was similar between the two groups. Results suggest that patients with indolent NHL are coping well with their disease, yet experience some overall feelings of life threat.

  14. Expression levels of TWIST1 are associated with the clinicopathological stage of B-cell non-Hodgkin lymphoma

    PubMed Central

    JIA, CUNDONG; LIANG, LIPING; YANG, LILI; ZHAO, FENG; BAI, JINGPING

    2014-01-01

    The aim of the present study was to investigate the expression level of TWIST1 in B-cell non-Hodgkin lymphoma (BNHL) and its association with the clinicopathological characteristics of BNHL. Expression levels of TWIST1 were analyzed in patients with BNHL (n=45) and lymphadenosis (n=21) using immunohistochemical staining and western blot analysis. In addition, the mRNA expression levels of TWIST1 in the peripheral blood were detected by fluorescent quantitative polymerase chain reaction. The positive rate of TWIST1 expression in the BNHL tissue was 82.2%, which was significantly higher compared with the lymphadenosis tissue (5%; P<0.05). In addition, the protein expression level of TWIST1 in the BNHL tissue was higher compared with the lymphadenosis tissue. TWIST1 expression was also higher in stage III/IV BNHL tissues than in stage I/II tissues (P<0.05). The tissues were staged following the Ann Arbor system. Furthermore, the mRNA expression level of TWIST1 in the peripheral blood of the BNHL tissue (3.03±0.03) was higher compared with the lymphadenosis tissue, and the mRNA expression level of TWIST1 was higher in stage III/IV (4.41±0.12) tissues than in stage I/II BNHL (2.03±0.08) tissues. In conclusion, TWIST1 expression was higher in the tissue and peripheral blood of patients with BNHL when compared with those with lymphadenosis. Thus, TWIST1 expression was associated with the clinicopathological stage of BNHL. PMID:25289047

  15. Diffuse large B-cell non-Hodgkin lymphoma involving the unilateral carotid space in an elderly man: A case report

    PubMed Central

    Chen, Bo; Zou, Chunying; Wu, Jianqing

    2017-01-01

    An 84-year-old man presented with a history of repeated syncope and decreased heart rate and blood pressure over the last month. On physical examination, a mass sized ~3×3 cm was palpable in the left submandibular area; the mass was hard, poorly mobile, without tenderness or local skin irritation. The computed tomography angiography examination revealed a soft tissue mass in the neck, at the level of the left carotid bifurcation and above. The left common carotid artery bifurcation and internal and external carotid artery segment were embedded in the mass, and there were multiple enlarged lymph nodes in the left neck. The diagnosis of diffuse large B-cell non-Hodgkin lymphoma was confirmed by a percutaneous biopsy of the left submandibular mass. To the best of our knowledge, this is the first reported case of non-Hodgkin lymphoma involvign the carotid space. PMID:28123742

  16. 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

    2016-12-26

    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

  17. Mantle cell lymphoma and diffuse large B-cell lymphoma of the testis: a unique case of composite non-Hodgkin lymphoma.

    PubMed

    Andhavarapu, Swati; Crozier, Jennifer A; Jiang, Liuyan; Sher, Taimur

    2014-12-01

    Primary testicular non-Hodgkin lymphoma (NHL) is a rare entity with the most common histologic subtype consisting of diffuse large B-cell lymphoma (DLBCL). Patients with primary testicular lymphoma (PTL) have a poor prognosis and a higher propensity for relapse. Also rare are composite lymphomas (CL) defined as two or more morphologically and phenotypically distinct lymphomas coexisting in a single organ or tissue. Here we present the first reported case of primary testicular composite lymphoma consisting of DLBCL and mantle cell lymphoma (MCL).

  18. Immunotherapy of B-cell non-Hodgkin lymphoma by targeting the chemokine receptor CXCR5 in a preclinical mouse model.

    PubMed

    Panjideh, Hossein; Müller, Gerd; Koch, Mathias; Wilde, Frank; Scheu, Susanne; Moldenhauer, Gerhard; Lipp, Martin

    2014-12-01

    Bispecific antibodies are promising agents for immunotherapy. Here, we describe a quadroma-based trifunctional bispecific antibody binding the chemokine receptor CXCR5 and the T-cell antigen CD3 that efficiently prevents tumor growth in a mouse B-cell lymphoma model. CXCR5 regulates the tissue homeostasis of mature B cells and is highly expressed on B-cell non-Hodgkin and lymphocyte-predominant Hodgkin lymphoma, as well as on a subset of CD4(+) T cells known as follicular T-helper cells. In vitro, the bispecific CXCR5::CD3 antibody efficiently recruited effector T cells to CXCR5 expressing B cells and induced a co-stimulation-independent activation of CD8(+) and CD4(+) T cells as demonstrated by the de novo expression of CD25 and CD69, and secretion of the cytokines IFN-γ, TNF-α, IL-6 and IL-10 by peripheral blood mononuclear cells. Notably, at low antibody concentrations, CXCR5::CD3 displayed a significantly higher cytotoxic activity against autologous B cells than its parental antibodies or rituximab. In vivo imaging revealed that CXCR5::CD3 and its parental CXCR5 antibody efficiently prevent tumor growth in a xenograft model of B-cell lymphoma in mice and prolong their survival. Taken together, our results identify CXCR5 as a promising target for antibody-based therapies in the treatment of B-cell malignancies.

  19. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    ClinicalTrials.gov

    2017-01-04

    Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  20. JCAR014 and Durvalumab in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2017-01-05

    Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  1. Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-06-10

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

  2. Phase I study of obinutuzumab (GA101) in Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma.

    PubMed

    Ogura, Michinori; Tobinai, Kensei; Hatake, Kiyohiko; Uchida, Toshiki; Suzuki, Tatsuya; Kobayashi, Yukio; Mori, Masakazu; Terui, Yasuhito; Yokoyama, Masahiro; Hotta, Tomomitsu

    2013-01-01

    As CD20 has become an established target for treating B-cell malignancies, there is interest in developing anti-CD20 antibodies with different functional activity from rituximab that might translate into improved efficacy. Obinutuzumab (GA101) is a glycoengineered, humanized type II anti-CD20 monoclonal antibody that has demonstrated superior activity to type I antibodies in preclinical studies and is currently being investigated in phase III trials. In this phase I dose-escalating study in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the primary endpoint was to characterize the safety of GA101; secondary endpoints were efficacy, pharmacokinetics and pharmacodynamics. Patients received up to nine doses of GA101 with up to 52 weeks' follow up. Most adverse events were grade 1 or 2 infusion-related reactions, and 10 grade 3/4 adverse events occurred. No dose-limiting toxicities were observed and the maximum tolerated dose was not identified. Out of 12 patients, 7 responded (end-of-treatment response rate 58%), with 2 complete responses and 5 partial responses. Responses were observed from low to high doses, and no dose-efficacy relationship was observed. B-cell depletion occurred in all patients after the first infusion and was maintained for the duration of treatment. Serum levels of GA101 increased in a dose-dependent fashion, although there was inter-patient variability. This phase I study demonstrated that GA101 has an acceptable safety profile and offers encouraging activity to Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

  3. Dual Inhibiton of Bruton's Tyrosine Kinase and Phosphoinositide-3-Kinase p110δ as a Therapeutic Approach to Treat non-Hodgkin's B cell Malignancies.

    PubMed

    Alfaro, Jennifer; Perez de Arce, Felipe; Belmar, Sebastian; Fuentealba, Glenda; Avila, Patricio; Ureta, Gonzalo; Flores, Camila; Acuna, Claudia; Delgado, Luz; Gaete, Diana; Pujala, Brahmam; Barde, Anup; Nayak, Anjan K; Upendra, Tvr; Patel, Dhananjay; Chauhan, Shailender; Sharma, Vijay K; Kanno, Stacy; Almirez, Ramona G; Hung, David T; Chakravarty, Sarvajit; Rai, Roopa; Bernales, Sebastian; Quinn, Kevin P; Pham, Son M; McCullagh, Emma

    2017-03-15

    Although new targeted therapies such as ibrutinib and idelalisib have made a large impact on non-Hodgkin's lymphoma (NHL) patients, the disease is often fatal because patients are initially resistant to these targeted therapies or because they eventually develop resistance. New drugs and treatments are necessary for these patients. One attractive approach is to inhibit multiple parallel pathways that drive the growth of these hematologic tumors and possibly prolonging the duration of the response and reducing resistance. Early clinical trials have tested this approach by dosing two drugs in combination in NHL patients. We have discovered a single molecule MDVN1003 that inhibits Bruton's tyrosine kinase (BTK) and phosphatidylinositol-3-kinase delta (PI3Kδ), two proteins regulated by the B cell receptor (BCR) that drive the growth of many NHLs. In this report, we show that this dual inhibitor prevents the activation of B cells and inhibits the phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK 1/2), two downstream mediators that are important for this process. Additionally, MDVN1003 induces cell death in a B cell lymphoma cell line but not in an irrelevant erythroblast cell line. Importantly, we found that this orally bioavailable dual inhibitor reduced tumor growth in a B cell lymphoma xenograft model more effectively than either ibrutinib or idelalisib. Taken together these results suggest that dual inhibition of these two key pathways by a single molecule could be a viable approach for treatment of NHL patients.

  4. Detection of MYD88 L265P in patients with lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia and other B-cell non-Hodgkin lymphomas

    PubMed Central

    Shin, Sang-Yong; Kim, Hyun-Young; Park, Chang-Hun; Kim, Hee-Jin; Kim, Jong-Won; Kim, Seok Jin; Kim, Won Seog

    2016-01-01

    Background Recent studies have identified a high prevalence of the MYD88 L265P mutation in lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) cases, whereas low frequencies have been observed in other B cell non-Hodgkin lymphomas (NHLs). Methods We evaluated the sensitivity of the mutant enrichment 3'-modified oligonucleotide (MEMO)-PCR technique, a new detection method. We examined the MYD88 L265P mutation in a series of Korean patients with LPL/WM and other B cell NHLs in bone marrow aspirates, using the MEMO-PCR technique. Results The sensitivity of MEMO-PCR was estimated to be approximately 10-16.7%. MYD88 L265P was detected in 21 of 28 LPL cases (75%) and only three of 69 B cell NHL cases (4.3%). Conclusion Although MEMO-PCR had relatively low sensitivity, we confirmed the high prevalence of the MYD88 L265P mutation in Korean LPL patients. Our study suggests the diagnostic value of MYD88 L265P for differentiating B-cell NHLs. PMID:27722129

  5. In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas

    PubMed Central

    Rabiega, Pascaline; Molina, Thierry J.; Charlotte, Frédéric; Lazure, Thierry; Davi, Frédéric; Settegrana, Catherine; Berger, Françoise; Alric, Laurent; Cacoub, Patrice; Terrier, Benjamin; Suarez, Felipe; Sibon, David; Dupuis, Jehan; Feray, Cyrille; Tilly, Hervé; Pol, Stanislas; Deau Fischer, Bénédicte; Roulland, Sandrine; Thieblemont, Catherine; Leblond, Véronique; Carrat, Fabrice; Hermine, Olivier; Besson, Caroline

    2016-01-01

    Hepatitis C Virus (HCV) infection is associated with the B-cell non-Hodgkin lymphomas (NHL), preferentially marginal zone lymphomas (MZL) and diffuse large B-cell lymphomas (DLBCL). While chronic antigenic stimulation is a main determinant of lymphomagenesis in marginal zone lymphomas (MZL), a putative role of HCV infection of B-cells is supported by in vitro studies. We performed a pathological study within the "ANRS HC-13 LymphoC" observational study focusing on in situ expression of the oncogenic HCV non structural 3 (NS3) protein. Lympho-C study enrolled 116 HCV-positive patients with B-NHL of which 86 histological samples were collected for centralized review. Main histological subtypes were DLBCL (36%) and MZL (34%). Almost half of DLBCL (12/26) were transformed from underlying small B-cell lymphomas. NS3 immunostaining was found positive in 17 of 37 tested samples (46%). There was a striking association between NS3 detection and presence of high grade lymphoma features: 12 out of 14 DLBCL were NS3+ compared to only 4 out of 14 MZL (p = 0.006). Moreover, 2 among the 4 NS3+ MZL were enriched in large cells. Remarkably, this study supports a new mechanism of transformation with a direct oncogenic role of HCV proteins in the occurrence of high-grade B lymphomas. PMID:27257992

  6. Obinutuzumab (GA101) for the treatment of chronic lymphocytic leukemia and other B-cell non-hodgkin's lymphomas: a glycoengineered type II CD20 antibody.

    PubMed

    Goede, Valentin; Klein, Christian; Stilgenbauer, Stephan

    2015-01-01

    Obinutuzumab (GA101) is a humanized, monoclonal type II CD20 antibody modified by glycoengineering. The glycoengineered Fc portion enhances the binding affinity to the FcγRIII receptor on immune effector cells, resulting in increased antibody-dependent cellular cytotoxicity and phagocytosis. In addition, the type II antibody binding characteristics of obinutuzumab to CD20 lead to an efficient induction of direct non-apoptotic cell death. Preclinical data demonstrated more efficient B-cell depletion in whole blood and superior antitumor activity in xenograft models of obinutuzumab as compared to the type I CD20 antibody rituximab. In previously untreated patients with chronic lymphocytic leukemia (CLL) and comorbidities, obinutuzumab plus chlorambucil increased response rates and prolonged progression-free survival compared with rituximab plus chlorambucil. Obinutuzumab had an acceptable and manageable safety profile, with infusion-related reactions during the first infusion as the most common adverse event. Further phase I/II clinical trials have also shown promising activity in other CD20-positive B-cell non-Hodgkin's lymphomas (NHL). Therefore, several clinical studies are planned or ongoing to investigate obinutuzumab with different combination partners in both untreated and relapsed/refractory patients with different B-cell NHL entities, which in addition to CLL include diffuse large B-cell lymphoma and follicular lymphoma. © 2015 S. Karger GmbH, Freiburg.

  7. Cardiac tamponade and paroxysmal third-degree atrioventricular block revealing a primary cardiac non-Hodgkin large B-cell lymphoma of the right ventricle: a case report

    PubMed Central

    2011-01-01

    Introduction Primary cardiac lymphoma is rare. Case Presentation We report the case of a 64-year-old non-immunodeficient Caucasian man, with cardiac tamponade and paroxysmal third-degree atrioventricular block. Echocardiography revealed the presence of a large pericardial effusion with signs of tamponade and a right ventricular mass was suspected. Scanner investigations clarified the sites, extension and anatomic details of myocardial and pericardial infiltration. Surgical resection was performed due to the rapid impairment of his cardiac function. Analysis of the pericardial fluid and histology confirmed the diagnosis of non-Hodgkin large B-cell lymphoma. He was treated with chemotherapy. Conclusion The prognosis remains poor for this type of tumor due to delays in diagnosis and the importance of the site of disease. PMID:21892927

  8. A 92-year-old man with primary cutaneous diffuse large B-cell non-Hodgkin's lymphoma manifesting as a giant scalp mass

    PubMed Central

    Liao, Chenlong; Yang, Min; Liu, Pengfei; Zhang, Wenchuan

    2017-01-01

    Abstract Rationale: Primary cutaneous non-Hodgkin's lymphoma (NHL) is an uncommon entity, representing 10% of all extranodal NHLs. Among all cutaneous sites, the scalp is a rare site of representation. Patient concerns: A 92-year-old Chinese man visited our hospital with a multiple-nodular huge scalp mass on the right parieto-occipital regions. The mass was of 7-month duration and progressively enlarging in size. Diagnoses: On the basis of the result of biopsy, diffuse large B-cell NHL was diagnosed. Interventions: The mass was partially resected by surgery and no further treatment was conducted due to the advanced age and poor physical status. Outcomes: The tumor relapsed in situ after 6 months and the patient died after 2 years. Lessons: This case highlighted the limited access to standard treatment options in patients with advanced age. A thorough examination is necessary to decide upon the treatment for the primary cutaneous lymphoma. PMID:28272240

  9. Unusual Presentation of Epstein-Barr Virus-Positive Diffuse Large B-Cell Non-Hodgkin Lymphoma of the Elderly.

    PubMed

    Hong, Bosun; Petrosyan, Vahe; Kruger, Anton R

    2016-06-01

    This report describes the case of a 76-year-old woman diagnosed with Epstein-Barr virus-positive diffuse large B-cell non-Hodgkin lymphoma of the elderly. She had an unusual presentation of the disease with widespread skeletal muscle, masticatory muscle, and parotid gland involvement and the development of interesting erythematous lesions in the neck during chemotherapy. One month after completion of chemotherapy, positron-emission tomography (PET) showed features of persistent lymphoma, but a repeat PET scan a month later showed no active disease. This case reiterates 2 important points: first, to consider lymphoma a differential diagnosis in masticatory muscle enlargement and second, to question false positivity when interpreting post-treatment PET scan results, especially in the absence of clinical disease.

  10. 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

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

    ClinicalTrials.gov

    2017-01-11

    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

  12. Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma

    PubMed Central

    Cartron, Guillaume; Hourcade-Potelleret, Florence; Morschhauser, Franck; Salles, Gilles; Wenger, Michael; Truppel-Hartmann, Anna; Carlile, David J.

    2016-01-01

    Obinutuzumab (GA101) is a type II, glycoengineered anti-CD20 monoclonal antibody for the treatment of hematologic malignancies. Obinutuzumab has mechanisms of action that are distinct from those of rituximab, potentially translating into improved clinical efficacy. We present the pharmacokinetic and clinical data from the phase I/II GAUGUIN and phase I GAUDI studies that were used to identify the obinutuzumab dose and regimen undergoing phase III assessment. In phase I (GAUGUIN and GAUDI), non-Hodgkin lymphoma patients received up to a maximum 9 fixed doses (obinutuzumab 50–2000 mg). In GAUGUIN phase II, patients received obinutuzumab 400/400 mg or 1600/800 mg [first dose day (D)1, D8, cycle (C) 1; second dose D1, C2–C8]. The influence of demographic factors on pharmacokinetics and drug exposure on tumor response and toxicity were analyzed using exploratory graphical analyses. Obinutuzumab serum concentrations with 1600/800 mg were compared with a 1000 mg fixed-dose regimen (D1, D8 and D15, C1; D1, C2–C8) using pharmacokinetic modeling simulations. Factors related to CD20-antigenic mass were more influential on obinutuzumab pharmacokinetics with 400/400 versus 1600/800 mg. Higher serum concentrations were observed with 1600/800 versus 400/400 mg, irrespective of CD20-antigenic mass. Tumor shrinkage was greater with 1600/800 versus 400/400 mg; there was no significant increase in adverse events. Fixed dose 1000 mg with an additional C1 infusion resulted in similar serum concentrations to 1600/800 mg in model-based analyses. The obinutuzumab 1000 mg fixed-dose regimen identified in this exploratory analysis was confirmed in a full covariate analysis of a larger dataset, and is undergoing phase III evaluation. GAUGUIN and GAUDI are registered at www.clinicaltrials.gov (clinicaltrials.gov identifier:00517530 and 00825149, respectively). PMID:26659915

  13. Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma.

    PubMed

    Cartron, Guillaume; Hourcade-Potelleret, Florence; Morschhauser, Franck; Salles, Gilles; Wenger, Michael; Truppel-Hartmann, Anna; Carlile, David J

    2016-02-01

    Obinutuzumab (GA101) is a type II, glycoengineered anti-CD20 monoclonal antibody for the treatment of hematologic malignancies. Obinutuzumab has mechanisms of action that are distinct from those of rituximab, potentially translating into improved clinical efficacy. We present the pharmacokinetic and clinical data from the phase I/II GAUGUIN and phase I GAUDI studies that were used to identify the obinutuzumab dose and regimen undergoing phase III assessment. In phase I (GAUGUIN and GAUDI), non-Hodgkin lymphoma patients received up to a maximum 9 fixed doses (obinutuzumab 50-2000 mg). In GAUGUIN phase II, patients received obinutuzumab 400/400 mg or 1600/800 mg [first dose day (D)1, D8, cycle (C) 1; second dose D1, C2-C8]. The influence of demographic factors on pharmacokinetics and drug exposure on tumor response and toxicity were analyzed using exploratory graphical analyses. Obinutuzumab serum concentrations with 1600/800 mg were compared with a 1000 mg fixed-dose regimen (D1, D8 and D15, C1; D1, C2-C8) using pharmacokinetic modeling simulations. Factors related to CD20-antigenic mass were more influential on obinutuzumab pharmacokinetics with 400/400 versus 1600/800 mg. Higher serum concentrations were observed with 1600/800 versus 400/400 mg, irrespective of CD20-antigenic mass. Tumor shrinkage was greater with 1600/800 versus 400/400 mg; there was no significant increase in adverse events. Fixed dose 1000 mg with an additional C1 infusion resulted in similar serum concentrations to 1600/800 mg in model-based analyses. The obinutuzumab 1000 mg fixed-dose regimen identified in this exploratory analysis was confirmed in a full covariate analysis of a larger dataset, and is undergoing phase III evaluation. GAUGUIN and GAUDI are registered at www.clinicaltrials.gov (clinicaltrials.gov identifier:00517530 and 00825149, respectively).

  14. Clinical Applications of the Genomic Landscape of Aggressive Non-Hodgkin Lymphoma.

    PubMed

    Moffitt, Andrea B; Dave, Sandeep S

    2017-03-20

    In this review, we examine the genomic landscapes of lymphomas that arise from B, T, and natural killer cells. Lymphomas represent a striking spectrum of clinical behaviors. Although some lymphomas are curable with standard therapy, the majority of the affected patients succumb to their disease. Here, the genetic underpinnings of these heterogeneous entities are reviewed. We consider B-cell lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary mediastinal B-cell lymphoma. We also examine T-cell lymphomas, including anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma, and other peripheral T-cell lymphomas. Together, these malignancies make up most lymphomas diagnosed around the world. Genomic technologies, including microarrays and next-generation sequencing, have enabled a better understanding of the molecular underpinnings of these cancers. We describe the broad genomics findings that characterize these lymphoma types and discuss new therapeutic opportunities that arise from these findings.

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

    ClinicalTrials.gov

    2016-08-09

    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

  16. Impact of involved field radiotherapy in partial response after doxorubicin-based chemotherapy for advanced aggressive non-Hodgkin's lymphoma

    SciTech Connect

    Moser, Elizabeth C. . E-mail: e.c.moser@lumc.nl; Kluin-Nelemans, Hanneke C.; Carde, Patrice; Meerwaldt, Jacobus H.; Tirelli, Umberto; Aleman, Berthe M.P.; Baars, Joke; Thomas, Jose; Glabbeke, Martine van; Noordijk, Evert M.

    2006-11-15

    Purpose: Whether salvage therapy in patients with advanced aggressive non-Hodgkin's lymphoma (NHL) in partial remission (PR) should consist of radiotherapy or autologous stem-cell transplantation (ASCT) is debatable. We evaluated the impact of radiotherapy on outcome in PR patients treated in four successive European Organization for Research and Treatment of Cancer trials for aggressive NHL. Patients and Methods: Records of 974 patients (1980-1999) were reviewed regarding initial response, final outcome, and type and timing of salvage treatment. After 8 cycles of doxorubicin-based chemotherapy, 227 NHL patients were in PR and treated: 114 received involved field radiotherapy, 16 ASCT, 93 second-line chemotherapy, and 4 were operated. Overall survival (OS) and progression-free survival (PFS) after radiotherapy were estimated (Kaplan-Meier method) and compared with other treatments (log-rank). Impact on survival was evaluated by multivariate analysis (Cox proportional hazards model). Results: The median PFS in PR patients was 4.2 years and 48% remained progression-free at 5 years. Half of the PR patients converted to a complete remission. After conversion, survival was comparable to patients directly in complete remission. Radiotherapy resulted in better OS and PFS compared with other treatments, especially in patients with low to intermediate International Prognostic Index score, bulky disease, or nodal disease only. Correction by multivariate analysis for prognostic factors such as stage, bulky disease, and number of extranodal locations showed that radiotherapy was clearly the most significant factor affecting both OS and PFS. Conclusion: This retrospective analysis demonstrates that radiotherapy can be effective for patients in PR after fully dosed chemotherapy; assessment in a randomized trial (radiotherapy vs. ASCT) is justified.

  17. Dexa-BEAM as salvage therapy in patients with primary refractory aggressive non-Hodgkin lymphoma.

    PubMed

    Atta, Johannes; Chow, Kai U; Weidmann, Eckhart; Mitrou, Paris S; Hoelzer, Dieter; Martin, Hans

    2007-02-01

    Although aggressive NHL in relapse after remission can still be cured by second-line treatment followed by high-dose therapy and autologous stem cell transplantation, the long-term prognosis of patients who fail to obtain remission after first-line therapy remains extremely poor. We retrospectively evaluated a series of 29 consecutive patients with primary refractory high-grade NHL who were treated with Dexa-BEAM (DB) as uniform salvage therapy at a single institution. Twenty-nine patients with aggressive NHL primary refractory to CHOP or CHOP-like induction therapy with a median age of 47 (range, 22 - 64) years received 1 - 2 cycles of DB and were candidates for subsequent autologous stem cell (PBSC) mobilization and transplantation (PBSCT). Follow-up of all patients was updated in March 2004. Eight of 29 patients (28%) responded to one cycle of DB (1 complete/7 partial remissions); 2 of whom are alive after PBSCT (1 autologous/1 matched unrelated donor), 1 patient died after autologous PBSCT. Reasons for failure to proceed to high-dose therapy in spite of response to DB were recurrent progressive disease (n = 2), septicemia (n = 1), and allogeneic transplant-related mortality after mobilization failure to DB (n = 2). Twenty-one patients failed to respond to DB and died of progressive disease. Overall survival was 7% after 41 months. We conclude that Dexa-BEAM salvage therapy is not effective in patients with truly primary refractory high-grade NHL. The efficiency of rituximab combined with Dexa-BEAM or novel chemotherapeutic strategies needs to be established.

  18. Pharmacokinetic profile and first preliminary clinical evaluation of bendamustine in Taiwanese patients with heavily pretreated indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma.

    PubMed

    Hsiao, Liang-Tsai; Tien, Hwei-Fang; Kuo, Ching-Yuan; Wu, Jin-Hou; Hou, Hsin-An; Wang, Ming-Chung; Liu, Chun-Yu; Chen, Po-Min; Chiou, Tzeon-Jye

    2015-12-01

    Prior studies found bendamustine is efficacious in patients with indolent B-cell non-Hodgkin lymphoma (NHL). To date, no studies have reported the efficacy of bendamustine in a Chinese population. This multicentre phase II trial evaluated the pharmacokinetics (PK), safety and efficacy of bendamustine monotherapy in Chinese patients in Taiwan with pretreated indolent B-cell NHL or mantle cell lymphoma (MCL). For PK assessments, patients were randomized (n = 16; 11 with indolent B-cell NHL and five with MCL) to 90 or 120 mg/m(2) of bendamustine for the first cycle. Plasma levels of bendamustine and its two metabolites were analyzed. For efficacy and safety evaluations, bendamustine 120 mg/m(2) was given to all patients every 3 weeks starting at cycle 2 for a minimum of a total of six cycles. The median age of patients was 61.7 years, and the majority were men (75%). The median number of prior treatments was 4 (range, 1-9 regimens), and all patients were previously treated with rituximab. Bendamustine plasma concentration peaked near the end of infusion and was rapidly eliminated with a mean elimination half-life (t(1/2)) of 0.67-0.8 h. Of the evaluable patients (n = 14), the overall response rate was 78.6%, including 7.2% of patients having a complete response. Mean progression-free survival was 27.5 weeks. The most common grade 3-4 adverse events were leucopenia (56.3%), neutropenia (56.3%) and thrombocytopenia (25%). In conclusion, bendamustine was efficacious and well tolerated in Taiwanese patients with indolent NHL and MCL with a similar PK profile to that of other populations.

  19. Primary bone marrow lymphoma: an uncommon extranodal presentation of aggressive non-hodgkin lymphomas.

    PubMed

    Martinez, Antonio; Ponzoni, Maurilio; Agostinelli, Claudio; Hebeda, Konnie M; Matutes, Estella; Peccatori, Jacopo; Campidelli, Cristina; Espinet, Blanca; Perea, Granada; Acevedo, Agustin; Mehrjardi, Ali Zare; Martinez-Bernal, Monica; Gelemur, Marta; Zucca, Emanuele; Pileri, Stefano; Campo, Elias; López-Guillermo, Armando; Rozman, Maria

    2012-02-01

    Bone marrow involvement by lymphoma is considered a systemic dissemination of the disease arising elsewhere, although some tumors may arise primarily in the bone marrow microenvironment. Primary bone marrow lymphoma (PBML) is a rare entity whose real boundaries and clinicobiological significance are not well defined. Criteria to diagnose PBML encompass isolated bone marrow infiltration, with no evidence of nodal or extranodal involvement, including the bone, and the exclusion of leukemia/lymphomas that are considered to primarily involve the bone marrow. Twenty-one out of 40 lymphomas retrospectively reviewed by the International Extranodal Lymphoma Study Group from 12 institutions in 7 different countries over a 25-year period fulfilled the inclusion criteria. These cases comprised 4 follicular lymphomas (FLs), 15 diffuse large B-cell lymphomas (DLBCLs), and 2 peripheral T-cell lymphomas, not otherwise specified. The FL cases showed paratrabecular infiltration, BCL2 protein and CD10 expression, and BCL2 gene rearrangement. DLBCL showed nodular infiltration in 6 cases and was diffuse in 9 cases; it also showed positivity for BCL2 protein (9/10) and IRF4 (6/8). Median age was 65 years with male predominance. All but 3 FL patients were symptomatic. Most cases presented with cytopenias and high lactate dehydrogenase. Four patients (3 FL cases and 1 DLBCL case) had leukemic involvement. Most DLBCL patients received CHOP-like or R-CHOP-like regimens. The outcome was unfavorable, with a median overall survival of 1.8 years. In conclusion, PBML is a very uncommon lymphoma with particular clinical features and heterogenous histology. Its recognition is important to establish accurate diagnosis and adequate therapy.

  20. A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma.

    PubMed

    Ogura, Michinori; Ando, Kiyoshi; Suzuki, Tatsuya; Ishizawa, Kenichi; Oh, Sung Yong; Itoh, Kuniaki; Yamamoto, Kazuhito; Au, Wing Yan; Tien, Hwei-Fang; Matsuno, Yoshihiro; Terauchi, Takashi; Yamamoto, Keiko; Mori, Masahiko; Tanaka, Yoshinobu; Shimamoto, Takashi; Tobinai, Kensei; Kim, Won Seog

    2014-06-01

    Although initial rituximab-containing chemotherapies achieve high response rates, indolent B-cell non-Hodgkin lymphoma (B-NHL), such as follicular lymphoma (FL), is still incurable. Therefore, new effective agents with novel mechanisms are anticipated. In this multicentre phase II study, patients with relapsed/refractory indolent B-NHL and mantle cell lymphoma (MCL) received vorinostat 200 mg twice daily for 14 consecutive days in a 21-d cycle until disease progression or unacceptable toxicity occurred. The primary endpoint was overall response rate (ORR) in FL patients and safety and tolerability in all patients. Secondary endpoints included progression-free survival (PFS). Fifty-six eligible patients were enrolled; 50 patients (39 with FL, seven with other B-NHL, and four with MCL) were evaluable for ORR, and 40 patients had received rituximab-containing prior chemotherapeutic regimens. For the 39 patients with FL, the ORR was 49% [95% confidence interval (CI): 32·4, 65·2] and the median PFS was 20 months (95% CI: 11·2, 29·7). Major toxicities were manageable grade 3/4 thrombocytopenia and neutropenia. Vorinostat offers sustained antitumour activity in patients with relapsed or refractory FL with an acceptable safety profile. Further investigation of vorinostat for clinical efficacy is warranted.

  1. Bezafibrate and medroxyprogesterone acetate target resting and CD40L-stimulated primary marginal zone lymphoma and show promise in indolent B-cell non-Hodgkin lymphomas.

    PubMed

    Hayden, Rachel E; Kussaibati, Racha; Cronin, Laura M; Pratt, Guy; Roberts, Claudia; Drayson, Mark T; Bunce, Christopher M

    2015-04-01

    B cell non-Hodgkin lymphomas (B-NHLs) are the most common adult hematological cancers and many remain incurable. Development of chemotherapy regimens is confounded by the prevalence of B-NHL in older, frailer patients and the chemo-protective tumor microenvironment. Although biological therapies such as rituximab have significantly improved outcomes and selective kinase inhibitors are showing promise, the rate of new drug discovery remains disappointing, the treatments expensive and long-term benefits uncertain. An alternative strategy is redeployment of available, inexpensive and non-toxic drugs. Here, we demonstrate the antiproliferative and mitochondrial superoxide (MSO) driven pro-apoptotic activities of bezafibrate (BEZ) and medroxyprogesterone acetate (MPA) against B-NHL cells, with a bias toward MZL, in the presence and absence of the microenvironmental signal CD40L. Our study is the first to confirm the presence of CD40L within the lymph node of B-NHL and its capacity to drive B-NHL proliferation. These findings implicate BEZ + MPA as a potential therapeutic strategy in B-NHL.

  2. Association of cytotoxic T-lymphocyte antigen 4 genetic polymorphism, hepatitis C viral infection and B-cell non-Hodgkin lymphoma: an Egyptian study.

    PubMed

    Khorshied, Mervat Mamdooh; Gouda, Heba Mahmoud; Khorshid, Ola M Reda

    2014-05-01

    Abstract Genetic and environmental factors are involved in the pathogenesis of non-Hodgkin lymphoma (NHL). The present study aimed to investigate the association between cytotoxic T-lymphocyte antigen 4 (CTLA-4) genetic polymorphism, hepatitis C virus (HCV) infection and B-cell NHL risk in Egypt. Genotyping of CTLA-4 single nucleotide polymorphisms (SNPs) was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for 181 adult patients with B-NHL and 200 controls. Our study revealed that CTLA-4 + 49 A/G polymorphism conferred increased risk of B-NHL (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.36-2.565). The prevalence of HCV infection in individuals harboring the mutant genotype + 49 A/G and - 318 C/T SNPs was higher in patients with B-NHL and was associated with increased risk of B-NHL (OR = 2.79, 95% CI = 1.24-6.93 for + 49 A/G and OR = 3.9, 95% CI = 1.01-15.98 for - 318 C/T). In conclusion, some SNPs of CTLA-4 are genetic risk factors for B-NHL. Moreover, this study identified an association of CTLA-4 + 49 A/G and - 318 C/T promoter polymorphisms with HCV infection.

  3. A microenvironment-mediated c-Myc/miR-548m/HDAC6 amplification loop in non-Hodgkin B cell lymphomas

    PubMed Central

    Lwin, Tint; Zhao, Xiaohong; Cheng, Fengdong; Zhang, Xinwei; Huang, Andy; Shah, Bijal; Zhang, Yizhuo; Moscinski, Lynn C.; Choi, Yong Sung; Kozikowski, Alan P.; Bradner, James E.; Dalton, William S.; Sotomayor, Eduardo; Tao, Jianguo

    2013-01-01

    A dynamic interaction occurs between the lymphoma cell and its microenvironment, with each profoundly influencing the behavior of the other. Here, using a clonogenic coculture growth system and a xenograft mouse model, we demonstrated that adhesion of mantle cell lymphoma (MCL) and other non-Hodgkin lymphoma cells to lymphoma stromal cells confers drug resistance, clonogenicity, and induction of histone deacetylase 6 (HDAC6). Furthermore, stroma triggered a c-Myc/miR-548m feed-forward loop, linking sustained c-Myc activation, miR-548m downregulation, and subsequent HDAC6 upregulation and stroma-mediated cell survival and lymphoma progression in lymphoma cell lines, primary MCL and other B cell lymphoma cell lines. Treatment with an HDAC6-selective inhibitor alone or in synergy with a c-Myc inhibitor enhanced cell death, abolished cell adhesion–mediated drug resistance, and suppressed clonogenicity and lymphoma growth ex vivo and in vivo. Together, these data suggest that the lymphoma-stroma interaction in the lymphoma microenvironment directly impacts the biology of lymphoma through genetic and epigenetic regulation, with HDAC6 and c-Myc as potential therapeutic targets. PMID:24216476

  4. Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study

    PubMed Central

    Alric, Laurent; Besson, Caroline; Lapidus, Nathanael; Jeannel, Juliette; Michot, Jean-Marie; Cacoub, Patrice; Canioni, Danielle; Pol, Stanislas; Davi, Frédéric; Rabiega, Pascaline; Ysebaert, Loic; Bonnet, Delphine; Hermine, Olivier

    2016-01-01

    Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. Methods: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL. Results: The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient. Conclusions: The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection. PMID:27749916

  5. The association between hepatitis C virus infection, genetic polymorphisms of oxidative stress genes and B-cell non-Hodgkin's lymphoma risk in Egypt.

    PubMed

    Farawela, Hala; Khorshied, Mervat; Shaheen, Iman; Gouda, Heba; Nasef, Aya; Abulata, Nelly; Mahmoud, Hebat-Allah; Zawam, Hamdy M; Mousa, Somaia M

    2012-08-01

    Hepatitis C virus (HCV) has been postulated to be an etiological agent for lymphoid malignancies. Polymorphisms in oxidative stress genes as; superoxide dismutase (SOD2), glutathione peroxidase (GPX1), catalase (CAT), myeloperoxidase (MPO) and nitric oxide synthase (NOS2) may influence non-Hodgkin's lymphoma (NHL) risk. HCV screening and polymorphisms in these five genes coding for antioxidant enzymes were studied in 100 Egyptian patients with B cell-NHL and 100 controls to clarify the association between HCV infection, oxidative stress genes polymorphisms and B cell-NHL risk. A significantly higher prevalence of HCV infection was detected among NHL patients relative to controls and this carried a 14-fold increased NHL risk (odds ratio (OR)=14.3, 95% confidence interval (CI)=5.4-38.3, p<0.0001). GPX1 and MPO genetic polymorphisms conveyed increase in B-NHL risk (OR=3.3, 95% CI=1.4-7.4, p=0.004 and OR=4.4, 95% CI=1.3-14.2, p=0.009 respectively). Further analyses stratified by HCV infection revealed that concomitant HCV infection and GPX1 gene polymorphism had a synergetic effect on NHL risk with an OR of 15 (95%CI=2.2-69.6, p<0.0001). In addition, combined HCV infection and MPO gene polymorphisms had a pronounced NHL risk (OR=9.2, 95%CI=2.5-33.9, p<0.0001). SOD2, CAT and NOS2 genetic polymorphisms were not found to confer increased NHL risk. This study revealed that HCV infection is a risk factor for NHL in Egypt. Polymorphisms in GPX1 and MPO genes may influence NHL risk in HCV infected Egyptian patients. Larger scale studies are warranted to establish this genetic susceptibility for NHL.

  6. Infundibulo-hypophysitis-like radiological image in a patient with pituitary infiltration of a diffuse large B-cell non-Hodgkin lymphoma

    PubMed Central

    León-Suárez, A; Roldán-Sarmiento, P; Gómez-Sámano, M A; Nava-De la Vega, A; Enríquez-Estrada, V M; Gómez-Pérez, F J

    2016-01-01

    Summary Non-Hodgkin lymphoma (NHL) is a hematological tumor caused by abnormal lymphoid proliferation. NHL can arise in any part of the body, including central nervous system (CNS). However, pituitary involvement is a quite rare presentation. The diffuse large B-cell lymphoma (DLBCL) is the most common subtype when pituitary is infiltrated. Here, we report a case of pituitary infiltration of NHL DLBCL type in a woman with hypopituitarism and an infundibulum-hypophysitis-like image on magnetic resonance imaging (MRI). A female aged 64 years, complained of dyspepsia, fatigue, weight loss and urine volume increment with thirst. Endoscopy and gastric biopsy confirmed diffuse large B-cell lymphoma. Treatment with chemotherapy using R-CHOP was initiated. During her hospitalization, hypotension and polyuria were confirmed. Hormonal evaluation was compatible with central diabetes insipidus and hypopituitarism. Simple T1 sequence of MRI showed thickening of the infundibular stalk with homogeneous enhancement. After lumbar puncture analysis, CNS infiltration was confirmed showing positive atypical lymphocytes. Pituitary and infundibular stalk size normalized after R-CHOP chemotherapy treatment. In conclusion, pituitary infiltration of NHL with infundibular-hypophysitis-like image on MRI is a rare finding. Clinical picture included hypopituitarism and central diabetes insipidus. Diagnosis should be suspected after biochemical analysis and MRI results. Treatment consists of chemotherapy against NHL and hormonal replacement for pituitary dysfunction. Learning points: Pituitary infiltration by lymphoma can present with signs and symptoms of panhypopituitarism and diabetes insipidus. MRI findings can resemble an autoimmune hypophysitis. Patients can recover pituitary function as well as normalization of MRI after chemotherapy treatment. PMID:28035285

  7. A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90 yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B-cell non-Hodgkin lymphoma.

    PubMed

    Witzig, Thomas E; Wiseman, Gregory A; Maurer, Matthew J; Habermann, Thomas M; Micallef, Ivana N M; Nowakowski, Grzegorz S; Ansell, Stephen M; Colgan, Joseph P; Inwards, David J; Porrata, Luis F; Link, Brian K; Zent, Clive S; Johnston, Patrick B; Shanafelt, Tait D; Allmer, Cristine; Asmann, Yan W; Gupta, Mamta; Ballas, Zuhair K; Smith, Brian J; Weiner, George J

    2013-07-01

    Radioimmunotherapy (RIT) for relapsed indolent non-Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B-cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial, we tested systemic administration of both CpG and RIT. Eligible patients had biopsy-proven previously treated CD20+ B-cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m(2) days 1,8, and 15; (111) In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of (90) Y-ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hr without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18-NR); and median duration of response (DR) of 35 months (4.6-76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1β, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation.

  8. A Phase I Trial of Immunostimulatory CpG 7909 Oligodeoxynucleotide and 90Yttrium Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed B-cell Non-Hodgkin Lymphoma

    PubMed Central

    Witzig, Thomas E.; Wiseman, Gregory A.; Maurer, Matthew J.; Habermann, Thomas M.; Micallef, Ivana N. M.; Nowakowski, Grzegorz S.; Ansell, Stephen M.; Colgan, Joseph P.; Inwards, David J.; Porrata, Luis F.; Link, Brian K.; Zent, Clive S.; Johnston, Patrick B.; Shanafelt, Tait D.; Allmer, Cristine; Asmann, Yan W.; Gupta, Mamta; Ballas, Zuhair K.; Smith, Brian J.; Weiner, George J.

    2014-01-01

    Radioimmunotherapy (RIT) for relapsed indolent non-Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B-cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial we tested systemic administration of both CpG and RIT. Eligible patients had biopsy-proven previously treated CD20+ B-cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m2 days 1,8, and 15; 111In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of 90Y-ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hours without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18-NR); and median duration of response (DR) of 35 months (4.6-76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1β, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation. PMID:23619698

  9. Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

    SciTech Connect

    Tseng, Yolanda D.; Chen, Yu-Hui; Catalano, Paul J.; Ng, Andrea

    2015-01-01

    Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treated with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a shorter

  10. A new construct of antibody-drug conjugates for treatment of B-cell non-Hodgkin's lymphomas.

    PubMed

    Zhang, Libin; Fang, Yixin; Kopeček, Jindřich; Yang, Jiyuan

    2017-02-27

    The aim of this study was to develop a new class of antibody-drug conjugates (ADCs) with the potential to not only enhance treatment efficacy but also improve tolerability for patients with B-cell lymphomas. Classic ADCs consist of monoclonal antibodies (mAbs) linked to drugs or toxins. They selectively deliver toxic moieties to tumor cells. As such, they greatly improve the therapeutic index compared to traditional chemotherapeutic agents. However, the therapeutic efficacy and safety of ADCs are dependent on linker stability and payload toxicity. Limited payload number on a single antibody (drug-to-antibody ratio, or DAR) has been driving investigators to use extremely toxic agents; however, even very low off-target binding of these ADCs may kill patients. Herein we report a new design of ADCs that consists of rituximab (RTX) and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin conjugates. The latter was selectively attached to RTX via reduced disulfide bonds. Such design allows the introduction of a large payload of drug on the antibody without adding attachment sites and without compromising the antigen-targeting ability. The binding of the new conjugate, namely RTX-P-EPI, to Ramos cells (with high CD20 expression) was confirmed. The cytotoxicity of RTX-P-EPI against Raji and Ramos cells was also determined. Interestingly, two-fold inhibition of cell proliferation was observed when using RTX-P-EPI compared with their equivalent physical mixture of RTX and P-EPI. Treatment of male SCID mice bearing subcutaneous Ramos B-cell lymphoma tumors demonstrated that RTX-P-EPI possessed superior efficacy when compared to combination of RTX with chemotherapy EPI (RTX+EPI) and P-EPI (RTX+P-EPI), whereas single RTX and a non-specific conjugate IgG-P-EPI only showed marginal effect. The conjugate RTX-EPI in which EPI was directly attached to RTX demonstrated much less antitumor activity compared with RTX-P-EPI. The results suggest that this new design possesses

  11. BCL2 mutation spectrum in B-cell non-Hodgkin lymphomas and patterns associated with evolution of follicular lymphoma.

    PubMed

    Burkhard, Regula; Bhagat, Govind; Cogliatti, Sergio B; Rossi, Davide; Gaidano, Gianluca; Pasqualucci, Laura; Novak, Urban

    2015-03-01

    BCL2 is a target of somatic hypermutation in t(14;18) positive and also in a small fraction of t(14;18) negative diffuse large B-cell lymphoma (DLBCL), suggesting an aberrant role of somatic hypermutation (ASHM). To elucidate the prevalence of BCL2 mutations in lymphomas other than DLBCL, we Sanger-sequenced the hypermutable region of the BCL2 gene in a panel of 69 mature B-cell lymphomas, including Richter's syndrome DLBCL, marginal-zone lymphomas, post-transplant lymphoproliferative disorders, HIV-associated and common-variable immunodeficiency-associated DLBCL, all known to harbour ASHM-dependent mutations in other genes, as well as 16 t(14,18) negative and 21 t(14;18) positive follicular lymphomas (FLs). We also investigated the pattern of BCL2 mutations in longitudinal samples from 10 FL patients relapsing to FL or transforming to DLBCL (tFL). By direct sequencing, we found clonally represented BCL2 mutations in 2/16 (13%) of t(14;18) negative FLs, 2/16 (13%) HIV-DLBCLs, 1/9 (11%) of Richter's syndrome DLBCL, 1/17 (6%) of post-transplant lymphoproliferative disorders and 1/2 (50%) common-variable immunodeficiency-associated DLBCL. The proportion of mutated cases was significantly lower than in FLs carrying the t(14;18) translocation (15/21, 71%). However, the absence of t(14;18) by FISH or PCR and the molecular features of the mutations strongly suggest that BCL2 represents an additional target of ASHM in these entities. Analysis of the BCL2 mutation pattern in clonally related FL/FL and FL/tFL samples revealed two distinct scenarios of genomic evolution: (i) direct evolution from the antecedent FL clone, with few novel clonal mutations acquired by the tFL major clone, and (ii) evolution from a common mutated long-lived progenitor cell, which subsequently acquired distinct mutations in the FL and in the relapsed or transformed counterpart.

  12. Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA).

    PubMed

    Gisselbrecht, C; Gaulard, P; Lepage, E; Coiffier, B; Brière, J; Haioun, C; Cazals-Hatem, D; Bosly, A; Xerri, L; Tilly, H; Berger, F; Bouhabdallah, R; Diebold, J

    1998-07-01

    Peripheral T-cell lymphomas (PTCL) have been generally reported to have a worse prognosis than B-cell lymphomas (BCL). Because of their heterogeneity and scarcity, the outcomes of the different histological subtypes have not been compared. From October 1987 to March 1993, 1,883 patients with diffuse aggressive non-Hodgkin's lymphomas (NHL) included in the LNH87 protocol could be assessed for both morphology and immunophenotyping. Among them, 288 (15%) had PTCL and 1,595 (85%) had BCL. According to the Kiel classification, most PTCL were classified as angioimmunoblastic (AIL; 23%), pleomorphic medium and large T-cell (PML; 49%), or anaplastic large cell (ALCL; 20%) lymphomas. Comparing PTCL with BCL patients, the former had more disseminated disease (78% v 58%), B symptoms (57% v 40%), bone marrow involvement (31% v 17%), skin involvement (21% v 4%), and increased beta2-microglobulin (50% v 34%), whereas BCL patients had more bulky disease (41% v 26%). According to the International Prognostic Index (IPI), PTCL and BCL scores were, respectively: 0 factors, 13% and 15%; 1 factor, 17% and 22%; 2 factors, 24% and 25%; >/=3 factors, 45% and 37% (P = .09). For BCL and PTCL, respectively, complete remission rates were 63% and 54% (P = .004); the 5-year overall survival (OS) rates were 53% and 41% (P = .0004) and event-free survival (EFS) rates were 42% and 33% (P < . 0001). Comparison of the different histological subtypes of lymphoma showed that the 5-year OS rate for T-ALCL (64%) was superior to those of other PTCL (35%) as well as diffuse large B-cell (53%) NHL. When multivariate analysis was applied using the IPI score as one factor, nonanaplastic PTCL remained an independent parameter (P = . 0004). Although the poor prognosis of non-ALCL PTCL could be due in part to the presence of adverse prognostic factors at diagnosis, this study shows that the T-cell phenotype is an independent significant factor, which should be incorporated into the definition of prognostic

  13. The feedback loop of LITAF and BCL6 is involved in regulating apoptosis in B cell non-Hodgkin's-lymphoma

    PubMed Central

    Shi, Yaoyao; Kuai, Yue; Lei, Lizhen; Weng, Yuanyuan; Berberich-Siebelt, Friederike; Zhang, Xinxia; Wang, Jinjie; Zhou, Yuan; Jiang, Xin; Ren, Guoping; Pan, Hongyang; Mao, Zhengrong; Zhou, Ren

    2016-01-01

    Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6. Therefore, we sought to explore the feedback loop between LITAF and BCL6 in B-NHL. Here, our data for the first time show that LITAF can repress expression of BCL6 by binding to Region A (−87 to +65) containing a putative LITAF-binding motif (CTCCC) within the BCL6 promoter. Furthermore, the regulation of BCL6 targets (PRDM1 or c-Myc) by LITAF may be associated with B-cell differentiation. Results also demonstrate that ectopic expression of LITAF induces cell apoptosis, activated by releasing cytochrome c, cleaving PARP and caspase 3 in B-NHL cells whereas knockdown of LITAF robustly protected cells from apoptosis. Interestingly, BCL6, in turn, could reverse cell apoptosis mediated by LITAF. Collectively, our findings provide a novel apoptotic regulatory pathway in which LITAF, as a transcription factor, inhibits the expression of BCL6, which leads to activation of the intrinsic mitochondrial pathway and tumor apoptosis. Our study is expected to provide a possible biomarker as well as a target for clinical therapies to promote tumor cell apoptosis. PMID:27764808

  14. MRD detection in B-cell non-Hodgkin lymphomas using Ig gene rearrangements and chromosomal translocations as targets for real-time quantitative PCR.

    PubMed

    Pott, Christiane; Brüggemann, Monika; Ritgen, Matthias; van der Velden, Vincent H J; van Dongen, Jacques J M; Kneba, Michael

    2013-01-01

    Minimal residual disease (MRD) diagnostics is of high clinical relevance in patients with indolent B-cell Non-Hodgkin lymphomas (B-NHL) and serves as a surrogate parameter to evaluate treatment effectiveness and long-term prognosis. MRD diagnostics performed by real-time quantitative PCR (RQ-PCR) is the gold-standard and currently the most sensitive and the most broadly applied method in follicular lymphoma (FL) and mantle cell lymphoma (MCL). RQ-PCR analysis of the junctional regions of the rearranged immunoglobulin heavy-chain gene (IgH) serves as the most broadly applicable MRD target in B-NHL (∼80%). Chromosomal translocations as t(14;18) translocation in FL and t(11;14) translocation in MCL can be used in selected lymphoma subtypes. In patients with B-cell chronic lymphocytic leukemia, both flow-cytometry as well as RQ-PCR are equally suitable for MRD assessment as long as a sensitivity of ≤10(-4) shall be achieved.MRD diagnostics targeting the IgH gene is complex and requires extensive knowledge and experience because the junctional regions of each lymphoma have to be identified before the patient-specific RQ-PCR assays can be designed for MRD monitoring. Furthermore, somatic mutations of the IgH region occurring during B-cell development of germinal center and post-germinal center lymphomas may hamper appropriate primer binding leading to false negative results. The translocations mentioned above have the advantage that consensus forward primers and probes, both placed in the breakpoint regions of chromosome 18 in FL and chromosome 11 in MCL, can be used in combination with a reverse primer placed in the IgH joining region of chromosome 14. RQ-PCR-based methods can reach a good sensitivity (≤10(-4)). This chapter provides all relevant background information and technical aspects for the complete laboratory process from detection of the clonal IgH gene rearrangement and the chromosomal translocations at diagnosis to the actual MRD measurements in

  15. Medical History, Lifestyle, Family History, and Occupational Risk Factors for Diffuse Large B-Cell Lymphoma: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

    PubMed Central

    Kricker, Anne; Paltiel, Ora; Flowers, Christopher R.; Wang, Sophia S.; Monnereau, Alain; Blair, Aaron; Maso, Luigino Dal; Kane, Eleanor V.; Nieters, Alexandra; Foran, James M.; Miligi, Lucia; Clavel, Jacqueline; Bernstein, Leslie; Rothman, Nathaniel; Slager, Susan L.; Sampson, Joshua N.; Morton, Lindsay M.; Skibola, Christine F.

    2014-01-01

    Background Although risk factors for diffuse large B-cell lymphoma (DLBCL) have been suggested, their independent effects, modification by sex, and association with anatomical sites are largely unknown. Methods In a pooled analysis of 4667 cases and 22639 controls from 19 studies, we used stepwise logistic regression to identify the most parsimonious multivariate models for DLBCL overall, by sex, and for selected anatomical sites. Results DLBCL was associated with B-cell activating autoimmune diseases (odds ratio [OR] = 2.36, 95% confidence interval [CI] = 1.80 to 3.09), hepatitis C virus seropositivity (OR = 2.02, 95% CI = 1.47 to 2.76), family history of non-Hodgkin lymphoma (OR = 1.95, 95% CI = 1.54 to 2.47), higher young adult body mass index (OR = 1.58, 95% CI = 1.12 to 2.23, for 35+ vs 18.5 to 22.4 kg/m2), higher recreational sun exposure (OR = 0.78, 95% CI = 0.69 to 0.89), any atopic disorder (OR = 0.82, 95% CI = 0.76 to 0.89), and higher socioeconomic status (OR = 0.86, 95% CI = 0.79 to 0.94). Additional risk factors for women were occupation as field crop/vegetable farm worker (OR = 1.78, 95% CI = 1.22 to 2.60), hairdresser (OR = 1.65, 95% CI = 1.12 to 2.41), and seamstress/embroider (OR = 1.49, 95% CI = 1.13 to 1.97), low adult body mass index (OR = 0.46, 95% CI = 0.29 to 0.74, for <18.5 vs 18.5 to 22.4 kg/m2), hormone replacement therapy started age at least 50 years (OR = 0.68, 95% CI = 0.52 to 0.88), and oral contraceptive use before 1970 (OR = 0.78, 95% CI = 0.62 to 1.00); and for men were occupation as material handling equipment operator (OR = 1.58, 95% CI = 1.02 to 2.44), lifetime alcohol consumption (OR = 0.57, 95% CI = 0.44 to 0.75, for >400kg vs nondrinker), and previous blood transfusion (OR = 0.69, 95% CI = 0.57 to 0.83). Autoimmune disease, atopy, and family history of non-Hodgkin lymphoma showed similar associations across selected anatomical sites, whereas smoking was associated with central nervous system, testicular and cutaneous DLBCLs

  16. Is there a benefit to adding rituximab to CHOP in the overall survival of patients with B-cell non-Hodgkin's lymphoma in a developing country?

    PubMed

    Ruiz-Delgado, Guillermo J; Gómez-Almaguer, David; Tarín-Arzaga, Luz C; Cantú-Rodriguez, Olga G; Urdaneta, Carlos Alarcón; Rodríguez-Morales, Uxmal; Calderón-Garcia, Jackeline; Fernández-Vargas, Omar; Montes-Montiel, Maryel; Sánchez-Cárdenas, Mónica; Ruiz-Argüelles, Guillermo J

    2012-07-01

    Rituximab (R) has changed the prognosis of patients with non-Hodgkin's lymphoma (NHL) in developed countries, but its role has not been analyzed in underprivileged circumstances. One hundred and two patients with NHL treated in a developing country were analyzed: 28 patients with follicular lymphoma (FL) and 74 with diffuse large B-cell lymphoma (DLCL). Patients were treated upfront with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or R-CHOP; the decision to employ R depending solely on the ability of patients to defray it. In DLCL, 42 were given CHOP and 32 R-CHOP, whereas in FL, 19 were given CHOP and 9 R-CHOP. The impact of the addition of R was found to be clearer in FL than in DLCL. In patients with DLCL, the overall survival (OS) was 87% at 80 months for those treated with R-CHOP and 84% at 145 months for those treated with CHOP (not significant). In patients with FL, the OS was 89% at 88 months for those treated with R-CHOP and 71% at 92 months for those treated with CHOP (P = 0··05). In a multivariate analysis, other variables which were identified to be associated with the OS were IPI and number of cycles in DLCL. It is concluded that R produced a mild positive impact in the OS of patients with FL, but not in those with DLCL. Since the addition of R results in a 36-fold increase in treatment costs, these observations may be important to decide therapeutic approaches in NHL patients living in underprivileged circumstances.

  17. Hepatitis C virus syndrome: A constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin's lymphoma, and cancer.

    PubMed

    Ferri, Clodoveo; Sebastiani, Marco; Giuggioli, Dilia; Colaci, Michele; Fallahi, Poupak; Piluso, Alessia; Antonelli, Alessandro; Zignego, Anna Linda

    2015-03-27

    The clinical course of chronic hepatitis C virus (HCV) infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinico-epidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells non-Hodgkin's lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCV-related thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients' populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases.

  18. The anti-lymphoma activity of antiviral therapy in HCV-associated B-cell non-Hodgkin lymphomas: a meta-analysis.

    PubMed

    Peveling-Oberhag, J; Arcaini, L; Bankov, K; Zeuzem, S; Herrmann, E

    2016-07-01

    Many epidemiological studies provide solid evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin's lymphoma (B-NHL). However, the most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). We conducted a literature search to identify studies that included patients with HCV-associated B-NHL (HCV-NHL) who received AVT, with the intention to treat lymphoma and viral disease at the same time. The primary end point was the correlation of sustained virological response (SVR) under AVT with lymphoma response. Secondary end points were overall lymphoma response rates and HCV-NHL response in correlation with lymphoma subtypes. We included 20 studies that evaluated the efficacy of AVT in HCV-NHL (n = 254 patients). Overall lymphoma response rate through AVT was 73% [95%>confidence interval, (CI) 67-78%]. Throughout studies there was a strong association between SVR and lymphoma response (83% response rate, 95%>CI, 76-88%) compared to a failure in achieving SVR (53% response rate, 95%>CI, 39-67%, P = 0.0002). There was a trend towards favourable response for AVT in HCV-associated marginal zone lymphomas (response rate 81%, 95%>CI, 74-87%) compared to nonmarginal zone origin (response rate 71%, 95%>CI, 61-79%, P = 0.07). In conclusion, in the current meta-analysis, the overall response rate of HCV-NHL under AVT justifies the recommendation for AVT as first-line treatment in patients who do not need immediate conventional treatment. The strong correlation of SVR and lymphoma regression supports the hypothesis of a causal relationship of HCV and lymphomagenesis.

  19. Hashimoto's thyroiditis in a patient with non-Hodgkin's thyroid lymphoma of B cell type and originated from mucosa-associated lymphoid tissue (MALT): A case report.

    PubMed

    Chuengsamarn, Somlak

    2005-06-01

    This is a rare case report of Hashimoto's thyroiditis in a patient with MALT thyroid lymphomas. The patient presented with an enlarged neck mass over the past 10 years and had rapidly enlarged neck mass with compressive symptoms for about 2 months. Examination by an endocrinologist found that the size of the thyroid gland was 120 gm with firm consistency and with no tenderness. She had clinical hypothyroidism and no abnormality of neither lymphadenopathy nor any masses. She was diagnosed with Hashimoto's thyroiditis because her thyroids function lest showed primary hypothyroidism [(FT4 = 0.76 ng/dl (0.93-1.71), FT3 = 1.76 pg/ml (1.8-4.6), TSH = 8.24 mIU/L (0.27-4.21)] with antimicrosomal antibody positive titers (> 1:409,600): Diagnosis of primary thyroid lymphoma was diagnosed by FNA and total thyroidectomy was performed. About 1 day after total thyroidectomy, she developed clinical hypocalcemia and the laboratory showed that calcium was = 6.2 ng/dl (8.5-10.1), phosphorus = 6.4 mg/dl (2.5-4.9). After 10% calcium gluconate replacement, her hypocalcemic symptoms didn't appear and she received oral replacement of calcium carbonate and vitamin D before discharge. During OPD follow up, her pathological report from Maha Chakri Sirinthorn Medical Center was a diagnosis of Non Hodgkin's lymphoma, low grade and the latter 1 week immunohistochemically staining of tumor markers indicated B-cell type (CD20) with MALT (AE1/AE3) lymphoma. Staging of the disease was stage IE and she received one course of CHOP (Cyclophosphamide, doxorubicin, vincristin and prednisolone). After one course of CHOP regimen, she was healthy and the hematologist ordered two courses of CHOP and external radiation.

  20. Non-Hodgkin lymphoma

    MedlinePlus

    ... January 26, 2015. cancer.gov/cancertopics/pdq/treatment/child-non-hodgkins/HealthProfessional . Accessed March 17, 2016. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-Hodgkin lymphomas. Version 2.2016. www.nccn. ...

  1. Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma.

    PubMed

    Lopes de Menezes, Daniel E; Denis-Mize, Kimberly; Tang, Yan; Ye, Helen; Kunich, John C; Garrett, Evelyn N; Peng, Jing; Cousens, Lawrence S; Gelb, Arnold B; Heise, Carla; Wilson, Susan E; Jallal, Bahija; Aukerman, Sharon L

    2007-01-01

    Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated. The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as evidenced by significant tumor regressions and increased time to tumor progression, compared with rIL-2 and rituximab single agents. In contrast, rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and showed an increased response when combined with rituximab. Using in vitro killing assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC. Antiproliferative and apoptotic tumor responses, along with an influx of immune effector cells, were observed by immunohistochemistry. Collectively, the data suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in part, through activation and trafficking of monocytes and natural killer cells to tumors. These data support the mechanistic and therapeutic rationale for combination of rIL-2 with rituximab in NHL clinical trials and for single-agent rIL-2 in rituximab-resistant NHL patients.

  2. Ethnic variation in medical and lifestyle risk factors for B cell non-Hodgkin lymphoma: A case-control study among Israelis and Palestinians

    PubMed Central

    Perlman, Riki; Khatib, Areej; Abdeen, Ziad; Elyan, Husein; Nirel, Ronit; Amir, Gail; Ramlawi, Asad; Sabatin, Fouad; Boffetta, Paolo; Dann, Eldad J.; Kedmi, Meirav; Ellis, Martin; Nagler, Arnon; Ben Yehuda, Dina; Paltiel, Ora

    2017-01-01

    Background Risk factors for B-cell non-Hodgkin lymphoma (B-NHL) have not been assessed among Palestinian Arabs (PA) and Israeli Jews (IJ). Methods In a case-control study we investigated self-reported medical and lifestyle exposures, reporting odds ratios (ORs) and 95% confidence intervals [CIs], by ethnicity, for overall B-NHL and subtypes. Results We recruited 823 cases and 808 healthy controls. Among 307 PA/516 IJ B-NHL cases (mean age at diagnosis = 51 [±17] versus 60 [±15] years, respectively) subtype distributions differed, with diffuse large B-cell lymphoma (DLBCL) being prominent among PA (71%) compared to IJ (41%); follicular lymphoma (FL), was observed in 14% versus 28%, and marginal zone lymphoma, in 2% versus 14%, respectively. Overall B-NHL in both populations was associated with recreational sun exposure OR = 1.43 [CI:1.07–1.91], black hair-dye use OR = 1.70 [CI:1.00–2.87], hospitalization for infection OR = 1.68 [CI:1.34–2.11], and first-degree relative with hematopoietic cancer, OR = 1.69 [CI:1.16–2.48]. An inverse association was noted with alcohol use, OR = 0.46 [CI:0.34–0.62]. Subtype-specific exposures included smoking (FL, OR = 1.46 [CI:1.01–2.11]) and >monthly indoor pesticide use (DLBCL, OR = 2.01 [CI:1.35–3.00]). Associations observed for overall B-NHL in PA only included: gardening OR = 1.93 [CI:1.39–2.70]; history of herpes, mononucleosis, rubella, blood transfusion (OR>2.5, P<0.01 for all); while for IJ risk factors included growing fruits and vegetables, OR = 1.87 [CI:1.11–3.15]; and self-reported autoimmune diseases, OR = 1.99 [CI:1.34–2.95]. Conclusions In these geographically proximate populations we found some unique risk factors for B-NHL. Heterogeneity in the observed associations by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by histology infer specific etiologic factors for lymphoma subtypes. PMID:28196110

  3. Increased expression of microRNA-503 and reduced expression of kangai-1 in B-cell non-Hodgkin's lymphoma

    PubMed Central

    WU, JINGJING; LI, AIMIN; ZHANG, PENGYU; SUN, ZHENCHANG; HAN, LIJUAN; NAN, FEIFEI; GENG, LI

    2016-01-01

    The aim of the present study was to determine the expression levels of microRNA-503 (miR-503) and the tumor suppressor gene, kangai-1 (KAI1), in B-cell non-Hodgkin's lymphoma (B-NHL). A total of 45 patients with B-NHL (including 29 cases with stage III/IV disease and 16 cases with stage I/II disease) were enrolled in this study. In addition, 26 patients with reactive lymphoid hyperplasia (RLH) were enrolled as the control patients. Reverse transcription-quantitative polymerase chain reaction was performed in order to measure the expression levels of miR-503 in B-NHL and RLH tissues, and to detect the expression levels of miR-503 and KAI1 in peripheral blood samples. In addition, KAI1 expression levels in B-NHL and RLH tissues were detected using western blotting and immunohistochemical analysis. The expression levels of miR-503 were found to be significantly increased in the tissues and peripheral blood of B-NHL patients when compared with those in RLH patients (P<0.05). However, KAI1 was strongly expressed in RLH tissues and weakly expressed in B-NHL tissues. Furthermore, the expression levels of KAI1 were significantly decreased in the tissues and peripheral blood of B-NHL patients when compared with those in the tissues and peripheral blood of RLH patients (P<0.05). The expression levels of miR-503 in the tissues and peripheral blood of patients with stage III/IV B-NHL were significantly higher compared with those with stage I/II B-NHL (P<0.05). By contrast, the expression levels of KAI1 in stage III/IV B-NHL tissues were significantly higher compared with those in stage I/II B-NHL tissues (P<0.05). In conclusion, miR-503 was highly expressed, whereas KAI1 was poorly expressed, in the tissues and peripheral blood of B-NHL patients. Thus, miR-503 may have an application as a novel therapeutic and diagnostic marker in B-NHL patients. PMID:26998012

  4. microRNA levels in paraffin-embedded indolent B-cell non-Hodgkin lymphoma tissues from patients chronically infected with hepatitis B or C virus

    PubMed Central

    2014-01-01

    Background Epidemiological evidence links Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) to B-cell non-Hodgkin lymphoma (B-NHL). These B-NHLs, particularly those associated with HCV, may represent a distinct sub-group with peculiar molecular features, including peculiar expression of microRNAs (miRs). The aim of the present study was to search for miRs whose level in indolent B-NHL tissues could be associated with HBV or HCV infection. Methods Fourteen formalin fixed paraffin embedded (FFPE) tissues from HBV+, HCV+ and HBV-/HCV- indolent B-NHL patients were analyzed for levels of 34 selected miRs by quantitative Real-Time PCR. Reactive lymph nodes (RLNs) from HBV-/HCV- patients were included as non-tumor control. Statistical analysis of output data included Pearson and Spearman correlation and Mann-Whitney test and were carried out by the STATA software. Results MiR-92a was decreased exclusively in HBV-/HCV- B-NHLs, while miR-30b was increased in HBV+ and HCV+ samples, though only the HCV+ achieved full statistical significance. Analysis of a small subset of B-NHLs belonging to the same histological subtype (Nodal Marginal Zone Lymphoma) highlighted three miRs associated with HCV infection (miR-223, miR-29a and miR-29b) and confirmed decreased level of miR-92a in HBV-/HCV- samples also when considering this restricted B-NHL group. Conclusions Although caution is needed due to the limited number of analyzed samples, overall the results suggest that differences at the miR expression level exist between indolent B-NHLs developed in patients with or without HBV or HCV infection. The identification of three further miRs associated with HCV by analyzing histologically homogeneous samples suggests that variations of miR levels possibly associated with HBV or HCV may be obscured by the tissue-specific variability of miR level associated with the different histological subtypes of B-NHL. Thus, the identification of further miRs will require, in addition to an increased

  5. Placental involvement by non-Hodgkin lymphoma in a Crohn disease patient on long-term thiopurine therapy.

    PubMed

    Chen, G; Crispin, P; Cherian, M; Dahlstrom, J E; Sethna, F F; Kaye, G; Pavli, P; Subramaniam, K

    2016-01-01

    We report the first published case of aggressive diffuse large B-cell (non-Hodgkin) lymphoma in a 35-year-old pregnant woman who had Crohn disease and was taking long-term thiopurine therapy: the patient developed placental insufficiency, and there was intrauterine fetal death.

  6. AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas.

    PubMed

    Qi, Wenqing; Liu, Xiaobing; Cooke, Laurence S; Persky, Daniel O; Miller, Thomas P; Squires, Matthew; Mahadevan, Daruka

    2012-06-15

    Aurora kinases are oncogenic serine/threonine kinases that play key roles in regulating the mitotic phase of the eukaryotic cell cycle. Auroras are overexpressed in numerous tumors including B-cell non-Hodgkin's lymphomas and are validated oncology targets. AT9283, a pan-aurora inhibitor inhibited growth and survival of multiple solid tumors in vitro and in vivo. In this study, we demonstrated that AT9283 had potent activity against Aurora B in a variety of aggressive B-(non-Hodgkin lymphoma) B-NHL cell lines. Cells treated with AT9283 exhibited endoreduplication confirming the mechanism of action of an Aurora B inhibitor. Also, treatment of B-NHL cell lines with AT9283 induced apoptosis in a dose and time dependent manner and inhibited cell proliferation with an IC(50) < 1 μM. It is well known that inhibition of auroras (A or B) synergistically enhances the effects of microtubule targeting agents such as taxanes and vinca alkaloids to induce antiproliferation and apoptosis. We evaluated whether AT9283 in combination with docetaxel is more efficient in inducing apoptosis than AT9283 or docetaxel alone. At very low doses (5 nM) apoptosis was doubled in the combination (23%) compared to AT9283 or docetaxel alone (10%). A mouse xenograft model of mantle cell lymphoma demonstrated that AT9283 at 15 mg/kg and docetaxel (10 mg/kg) alone had modest anti-tumor activity. However, AT9283 at 20 mg/kg and AT9283 (15 or 20 mg/kg) plus docetaxel (10 mg/kg) demonstrated a statistically significant tumor growth inhibition and enhanced survival. Together, our results suggest that AT9283 plus docetaxel may represent a novel therapeutic strategy in B-cell NHL and warrant early phase clinical trial evaluation.

  7. Factors predictive of early death in patients receiving high-dose CHOP (ACVB regimen) for aggressive non-Hodgkin's lymphoma: a GELA study.

    PubMed

    Dumontet, Charles; Mounier, Nicolas; Munck, Jean Nicolas; Bosly, André; Morschauser, Frank; Simon, Daniele; Marit, Gérald; Casasnovas, Olivier; Reman, Oumédaly; Molina, Thierry; Reyes, Felix; Coiffier, Bertrand

    2002-07-01

    Death during the induction phase of chemotherapy remains a common event in patients with aggressive non-Hodgkin's lymphoma (NHL). In a series of patients with aggressive NHL homogeneously treated with intensive induction chemotherapy [ACVB (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) regimen], we determined the clinical and biological parameters that were predictive of early death. Early death was defined as death, for whatever reason, occurring within 100 d of randomization. Predictive factors were identified by logistic regression and an index predictive for individual risk of early death was designed. Among the 2210 patients treated with ACVB, there were 162 (7.3%) early deaths. There was no significant reduction in the rate of early death between 1987 and 1998. In a multivariate analysis, age > 60 years, Eastern Cooperative Oncology Group performance status > 1, serum lactate dehydrogenase > normal, serum albumin < 30 g/l, leucocyte counts > 10 x 10(9)/l and haemoglobin levels < 8.5 g/dl were found to be independent predictive factors for early death. An early death index was designed, enabling the evaluation of the individual risk of early death in young (range 2-31% risk of early death) and elderly patients (range 5-53%). Clinical and biological parameters available at diagnosis can help physicians identify patients with aggressive lymphoma at low or high risk of early death.

  8. A selective high affinity ligand (SHAL) designed to bind to an over-expressed human antigen on non-Hodgkin's lymphoma also binds to canine B-cell lymphomas.

    PubMed

    Balhorn, Rod L; Skorupski, Katherine A; Hok, Saphon; Balhorn, Monique Cosman; Guerrero, Teri; Rebhun, Robert B

    2010-10-15

    Therapies using antibodies directed against cell surface proteins have improved survival for human patients with non-Hodgkin's lymphoma (NHL). It is possible that similar immuno-therapeutic approaches may also benefit canine NHL patients. Unfortunately, variability between human and canine epitopes often limits the usefulness of such therapies in pet dogs. The Lym-1 antibody recognizes a unique epitope on HLA-DR10 that is expressed on the majority of human B-cell malignancies. The Lym-1 antibody has now been observed to bind to dog lymphocytes and B-cell NHL. Sequence comparisons and computer modeling of a human and three canine DRB1 proteins identified several orthologs of human HLA-DR10 expressed by dog lymphocytes. Immuno-staining confirmed the presence of proteins containing the Lym-1 epitope on dog lymphocytes and B-cell NHL. In addition, a selective high affinity ligand (SHAL) SH-7139 designed to bind within the Lym-1 epitope of HLA-DR10 was also observed to bind to canine B-cell NHL tissue. This SHAL, which is selectively cytotoxic to cells expressing HLA-DR10 and has been shown to cure mice bearing human B-cell lymphoma xenografts, may prove useful in treating B-cell malignancies in pet dogs.

  9. Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo(®) ) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas.

    PubMed

    Hagemeister, Fredrick; Rodriguez, Maria Alma; Deitcher, Steven R; Younes, Anas; Fayad, Luis; Goy, Andre; Dang, Nam H; Forman, Arthur; McLaughlin, Peter; Medeiros, Leonard Jeffrey; Pro, Barbara; Romaguera, Jorge; Samaniego, Felipe; Silverman, Jeffrey A; Sarris, Andreas; Cabanillas, Fernando

    2013-09-01

    Vincristine sulfate liposome injection (VSLI; Marqibo(®) ; M) is active in relapsed and refractory lymphomas, and approved in the United States for relapsed and refractory adult acute lymphocytic leukaemia. We evaluated VSLI (2·0 mg/m(2) without dose cap) substituted for non-liposomal vincristine (VCR) in a cyclophosphamide, doxorubicin, vincristine, prednisone ± ritiximab (CHOP±R) regimen, creating CHMP±R in 72 untreated, aggressive non-Hodgkin lymphoma patients, including 60 with diffuse large B-cell lymphoma (DLBCL). The overall response rate was 96% (69/72) including complete response (CR) in 65 (90%) and unconfirmed CR in 2 (3%). Median progression-free survival (PFS) and overall survival (OS) were not reached at median follow-up of 8 and 10·2 years, respectively. The 5- and 10-year PFS and OS were 75%, 63%, 87%, and 77%, respectively. Despite VSLI exposure of up to 35 mg, the safety profile of CHMP±R was comparable to that reported for CHOP±R. Grade 3 peripheral neuropathy was reported in 2 (3%) patients; there was no reported Grade 3/4 constipation. CHMP±R was highly active, generally well tolerated, and compared favourably to historical trials with R-CHOP in DLBCL. This enhanced activity probably reflects VCR dose intensification, pharmacokinetic optimization, and enhanced delivery afforded by VSLI. A Phase 3 trial of R-CHMP versus R-CHOP in elderly patients with untreated DLBCL is ongoing.

  10. Non-Hodgkin Lymphoma

    MedlinePlus

    ... Lymphoma? A lymphoma is a cancer of the lymphatic system , which is a part of the body's immune ... non-Hodgkin lymphoma, cancer cells form in the lymphatic system and start to grow. Most of the time, ...

  11. Mechanisms of Idelalisib-Associated Diarrhea in Patients With Relapsed Chronic Lymphocytic Leukemia, Indolent Non-hodgkin Lymphoma, or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2016-10-06

    Absence of Signs or Symptoms; B-Cell Non-Hodgkin Lymphoma; Digestive System Signs and Symptoms; Indolent Adult Non-Hodgkin Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma

  12. 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

  13. 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

  14. Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients.

    PubMed

    André, Marc; Mounier, Nicolas; Leleu, Xavier; Sonet, Anne; Brice, Pauline; Henry-Amar, Michel; Tilly, Hervé; Coiffier, Bertrand; Bosly, André; Morel, Pierre; Haioun, Corinne; Gaulard, Philippe; Reyes, Felix; Gisselbrecht, Christian

    2004-02-15

    The survival of patients with aggressive non-Hodgkin lymphoma (NHL) is increasing, but the incidence of secondary cancer and late toxicity is poorly defined for those treated with cyclophosphamide-hydroxydaunomycin/doxorubicin-Oncovin-prednisone (CHOP)-like chemotherapy. From February 1984 to January 1998, 2837 patients with aggressive NHL received the control-arm chemotherapy adriamycin-cyclophosphamide-vindesine-bleomycin-prednisone (ACVBP) in 3 consecutive Groupe d'Etude des Lymphomes de l'Adulte (GELA) studies. With a median follow-up time of 74 months, the 5-year overall and event-free survival rates were 60% and 52%. Two hundred two occurrences of nonneoplastic late toxicity were reported, resulting in a 5.35% cumulative probability of incidence at 7 years. Eighty-one second tumors developed, for which the 7-year cumulative incidence rate was 2.75%; 64 were solid tumors, and 17 were hematologic malignancies. In multivariate analysis, age was the only risk factor for the second development of cancer. Epidemiologic analysis allowed a comparison of this NHL group with the general population. Considering all tumors, no excess of second cancer was observed. In the male population, however, there was an excess of lung cancer (standardized incidence ratio [SIR], 2.45; P <.001) and myelodysplastic syndrome/acute myelocytic leukemia (MDS/AML) (SIR, 5.65; P =.006), and in the female population there was an excess of MDS/AML (SIR, 19.9; P <.001). With a long follow-up, the ACVBP regimen was highly effective for the treatment of aggressive NHL. Increases occurred in secondary MDS/AML and in lung cancer among men.

  15. Serum Levels of Cytokines, and Biomarkers for Inflammation and Immune Activation, and HIV-Associated Non-Hodgkin B cell Lymphoma Risk

    PubMed Central

    Vendrame, Elena; Hussain, Shehnaz K.; Breen, Elizabeth Crabb; Magpantay, Larry; Widney, Daniel P.; Jacobson, Lisa P.; Variakojis, Daina; Knowlton, Emilee R.; Bream, Jay H.; Ambinder, Richard F.; Detels, Roger; Martínez-Maza, Otoniel

    2013-01-01

    Background: HIV infection is associated with a marked increase in risk for non-Hodgkin lymphoma (AIDS-NHL). However, the mechanisms that promote the development of AIDS-NHL are not fully understood. Methods: In this study serum levels of several cytokines and other molecules associated with immune activation were measured in specimens collected longitudinally during 1-to-5 years preceding AIDS-NHL diagnosis, in 176 AIDS-NHL cases and 176 HIV+ controls from the Multicenter AIDS Cohort Study (MACS). Results: Multivariate analyses revealed that serum levels of immunoglobulin free light chains (FLC), IL-6, IL-10, IP-10/CXCL10, neopterin, and TNFα were elevated in those HIV+ individuals who went on to develop AIDS-NHL. Additionally, the fraction of specimens with detectable IL-2 was increased, and the fraction with detectable IL-4 was decreased, in these subjects. Conclusions: These results suggest that long term, chronic immune activation, possibly driven by macrophage-produced cytokines, precedes development of NHL in HIV+ individuals. Impact: FLC, IL-6, IL-10, IP-10/CXCL10, neopterin, and TNFα may serve as biomarkers for AIDS-NHL. PMID:24220912

  16. Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA).

    PubMed

    Hermine, O; Haioun, C; Lepage, E; d'Agay, M F; Briere, J; Lavignac, C; Fillet, G; Salles, G; Marolleau, J P; Diebold, J; Reyas, F; Gaulard, P

    1996-01-01

    Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new

  17. Equitoxicity of bolus and infusional etoposide: results of a multicenter randomised trial of the German High-Grade Non-Hodgkins Lymphoma Study Group (DSHNHL) in elderly patients with refractory or relapsing aggressive non-Hodgkin lymphoma using the CEMP regimen (cisplatinum, etoposide, mitoxantrone and prednisone).

    PubMed

    Zwick, Carsten; Birkmann, Josef; Peter, Norma; Bodenstein, Heinrich; Fuchs, Roland; Hänel, Mathias; Reiser, Marcel; Hensel, Manfred; Clemens, Michael; Zeynalova, Samira; Ziepert, Marita; Pfreundschuh, Michael

    2008-09-01

    To compare toxicity of etoposide bolus with continuous infusion and to assess the efficacy of the CEMP (cisplatinum, etoposide, mitoxantrone, prednisone) regimen, 47 patients with refractory or relapsed aggressive non-Hodgkin's lymphoma older than 60 years (n=43) or not qualifying for high-dose chemotherapy (n=4) received five four-weekly CEMP cycles. Patients were randomised to start with bolus or continuous-infusion etoposide and then received bolus and infusional etoposide in an alternating fashion. The primary objective was the comparison of differences in the course of leukocytopenia and thrombocytopenia between the two application schedules. CEMP was well tolerated with little organ and moderate haematotoxicity. There was no difference in toxicity between bolus and continuous-infusion etoposide. Complete remission rate was 44% in patients relapsing >or=1 year, 27% in patients relapsing within the first year after achieving complete remission and 5% in primary refractory patients. Median event-free and overall survivals for all patients were 3 and 10 months, respectively. The observed equitoxicity and the more challenging logistics of a 60-h infusion make bolus injection the preferred application of etoposide. As the CEMP regimen is well tolerated and efficacious in elderly patients with relapsed or refractory aggressive non-Hodgkin's lymphoma for whom more aggressive therapies are not feasible, a three-weekly modification of CEMP should be tested in combination with rituximab.

  18. Reduced-intensity conditioning followed by related allografts in hematologic malignancies: long-term outcomes most successful in indolent and aggressive non-Hodgkin lymphomas.

    PubMed

    Warlick, Erica D; Tomblyn, Marcie; Cao, Qing; Defor, Todd; Blazar, Bruce R; Macmillan, Margaret; Verneris, Michael; Wagner, John; Dusenbery, Kathryn; Aurora, Mukta; Bachanova, Veronika; Brunstein, Claudio; Burns, Linda; Cooley, Sarah; Kaufman, Dan; Majhail, Navneet S; McClune, Brian; McGlave, Philip; Miller, Jeffrey; Oran, Betul; Slungaard, Arne; Vercellotti, Gregory; Weisdorf, Daniel J

    2011-07-01

    Reduced-intensity conditioning (RIC) extends the curative potential of allogeneic hematopoietic cell transplantation (HCT) to patients with hematologic malignancies unable to withstand myeloablative conditioning. We prospectively analyzed the outcomes of 123 patients (median age, 57 years; range, 23-70 years) with hematologic malignancies treated with a uniform RIC regimen of cyclophosphamide, fludarabine, and total-body irradiation (200 cGy) with or without antithymocyte globulin followed by related donor allogeneic HCT at the University of Minnesota between 2002 and 2008. The cohort included 45 patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), 27 with aggressive non-Hodgkin lymphoma (NHL), 8 with indolent NHL, 10 with Hodgkin lymphoma (HL), 10 with myeloma, and 23 with acute lymphocytic leukemia, chronic myelogenous leukemia, other leukemias, or myeloproliferative disorders. The probability of 4-year overall survival was 73% for patients with indolent NHL, 58% for those with aggressive NHL, 67% for those with HL, 30% for those with AML/MDS, and only 10% for those with myeloma. Corresponding outcomes for relapse in these patients were 0%, 32%, 50%, 33%, and 38%, and those for progression-free survival were 73%, 45%, 27%, 27%, and 10%. The incidence of treatment-related mortality was 14% at day +100 and 22% at 1 year. The incidence of grade II-IV acute graft-versus-host disease was 38% at day +100, and that of chronic graft-versus-host disease was 50% at 2 years. Multivariate analysis revealed superior overall survival and progression-free survival in patients with both indolent and aggressive NHL compared with those with AML/MDS, HL, or myeloma. Worse 1-year treatment-related mortality was observed in patients with a Hematopoietic Cell Transplantation Comorbidity Index score ≥ 3 and in cytomegalovirus-seropositive recipients. These results suggest that (1) RIC conditioning was well tolerated by an older, heavily pretreated

  19. REDUCED INTENSITY CONDITIONING FOLLOWED BY RELATED ALLOGRAFTS IN HEMATOLOGIC MALIGNANCIES: LONG TERM OUTCOMES MOST SUCCESSFUL IN INDOLENT AND AGGRESSIVE NON-HODGKINS LYMPHOMAS

    PubMed Central

    Warlick, Erica D; Tomblyn, Marcie; Cao, Qing; DeFor, Todd; Blazar, Bruce R; MacMillan, Margaret; Verneris, Michael; Wagner, John; Dusenbery, Kathryn; Aurora, Mukta; Bachanova, Veronika; Brunstein, Claudio; Burns, Linda; Cooley, Sarah; Kaufman, Dan; Majhail, Navneet S; McClune, Brian; McGlave, Philip; Miller, Jeffrey; Oran, Betul; Slungaard, Arne; Vercellotti, Gregory; Weisdorf, Daniel J

    2014-01-01

    Reduced intensity conditioning (RIC) extends the curative potential of allogeneic hematopoietic cell transplantation (HCT) to patients with hematologic malignancies unable to withstand myeloablative conditioning. We prospectively analyzed the outcomes of 123 patients, median age of 57 (range 23-70), with hematologic malignancies treated with a uniform RIC regimen of cyclophosphamide, fludarabine, and total body irradiation (200 cGy) with or without anti-thymocyte globulin (ATG) followed by related donor allogeneic HCT at the University of Minnesota from 2002-2008. Forty-five patients had acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), 27 patients had aggressive non-Hodgkin lymphoma (NHL), 8 indolent NHL, 10 Hodgkin Lymphoma (HL), 10 myeloma and the remaining 23 had acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), other leukemias, or myeloproliferative disorders. Probability of four year overall survival (OS) was 73% for patients with indolent NHL, 58% for aggressive NHL, 67% for HL, 30% for AML/MDS, and only 10% for those with myeloma. Corresponding outcomes for relapse were 0%, 32%, 50%, 33%, and 38% and for progression free survival (PFS) were 73%, 45%, 27%, 27%, and 10%, respectively. The incidence of treatment related mortality (TRM) was 14% at day +100 and 22% at 1 year. The incidence of grade II-IV acute graft-versus-host disease (aGVHD) at day +100 was 38% and chronic GVHD at 2 years was 50%. Multivariate analysis revealed superior OS and PFS in patients with both indolent and aggressive NHL compared with AML/MDS, HL, or myeloma. Worse 1 year TRM was observed with hematopoietic cell transplant comorbidity index (HCT-CI) score ≥ 3 and CMV seropositive recipients. These results suggest that: 1) RIC conditioning was well tolerated by an older, heavily pre-treated population; 2) indolent and aggressive NHLs respond well to RIC conditioning highlighting the importance of the graft versus lymphoma (GVL) effect; and 3

  20. Carmustine, etoposide, cytarabine, and melphalan (BEAM)-campath allogeneic stem cell transplantation for aggressive non-hodgkin lymphoma: an analysis of outcomes from the British Society of Blood and Marrow Transplantation.

    PubMed

    Truelove, Edward; Fox, Christopher; Robinson, Stephen; Pearce, Rachael; Perry, Julia; Kirkland, Keiren; McQuaker, Grant; Pagliuca, Antonio; Johnson, Peter; Russell, Nigel; Cook, Gordon

    2015-03-01

    The role of allogeneic stem cell transplantation (SCT) in the management of aggressive non-Hodgkin lymphoma (NHL) remains to be defined, but the number of procedures performed continues to increase. We report here the outcomes of allogeneic SCT using carmustine, etoposide, cytarabine, and melphalan (BEAM)-Campath (Genzyme Corporation, Cambridge, MA) conditioning for aggressive NHL as reported to the British Society of Blood and Marrow Transplantation (BSBMT). This retrospective study identified 46 patients who reported to the BSBMT registry as having undergone BEAM-Campath conditioned allogeneic SCT for aggressive NHL between 1999 and 2010. Disease histology was diffuse large B cell lymphoma (DLBCL, n = 25), DLBCL/Burkitt lymphoma (n = 5), and T cell lymphoma (n = 16). At diagnosis, the median age was 42.5 (range, 17 to 59), 37 had advanced stage disease (Ann Arbor III/IV), 28 had 2 or more extra-nodal sites of disease, and 23 had elevated lactate dehydrogenase. International prognostic index was high or high/intermediate in 58%. The median number of prior therapies was 3 (range, 1 to 5) and 5 patients had previously undergone transplantation (4 autologous, 1 allogeneic). The median age at transplantation was 44.8 (range, 18 to 59), with 34 patients demonstrating chemo-sensitive disease and 22 undergoing transplantation in first response. Performance score was good in 40 patients and all engrafted with a median of 14 days (range, 11 to 27) to neutrophil recovery. At latest follow-up, 20 patients were alive with 17 in complete remission. Acute graft-versus-host disease (GVHD) developed in 7 patients and chronic GVHD developed in 13 (7 limited, 6 extensive). Five patients died from nonrelapse causes, with a cumulative incidence of nonrelapse mortality of 7% at 100 days and 11% at 3 and 5 years. Twenty-one patients died after lymphoma relapse, with a cumulative incidence of relapse/progression of 51% at 1 year and 53% at 5 years. Disease status at transplantation had

  1. Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia

    ClinicalTrials.gov

    2016-10-24

    Childhood B Acute Lymphoblastic Leukemia; Childhood Burkitt Leukemia; Childhood Diffuse Large Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma

  2. TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma | Office of Cancer Genomics

    Cancer.gov

    Recently, the landscape of single base mutations in diffuse large B-cell lymphoma (DLBCL) was described. Here we report the discovery of a gene fusion between TBL1XR1 and TP63, the only recurrent somatic novel gene fusion identified in our analysis of transcriptome data from 96 DLBCL cases. Based on this cohort and a further 157 DLBCL cases analyzed by FISH, the incidence in de novo germinal center B cell-like (GCB) DLBCL is 5% (6 of 115).

  3. Rituximab in combination with CODOX-M/IVAC: a retrospective analysis of 23 cases of non-HIV related B-cell non-Hodgkin lymphoma with proliferation index >95%.

    PubMed

    Mohamedbhai, Sajir G; Sibson, Keith; Marafioti, Teresa; Kayani, Irfan; Lowry, Lisa; Goldstone, Anthony H; Linch, David C; Ardeshna, Kirit M

    2011-01-01

    The safety and efficacy of rituximab with CODOX-M/IVAC (cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine) was retrospectively analysed in 23 patients with non-human immunodeficiency virus-related B-cell non-Hodgkin lymphoma with proliferation index >95% [14 with classical Burkitt lymphoma (BL), five with B-cell lymphoma unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and BL, and four with DLBCL]. Six (26%) low-risk (LR) patients received three cycles of CODOX-M and 17 (74%) high-risk (HR) cases were assigned to four cycles of alternating CODOX-M/IVAC. Rituximab 375 mg/m² was infused on days 1 and 10 of each cycle. Toxicity was comparable to that reported with CODOX-M/IVAC, with no treatment-related death. Two patients developed grade 3 rituximab-induced delayed neutropenia, with no adverse outcome. After completing treatment, 83% LR patients and 71% HR patients achieved CR by positron emission tomography-computerized tomography (PET-CT). Three (13%) patients received salvage treatment. At a median follow-up of 34 months (range = 18-75), 19 (83%) patients (100% LR and 74% HR) were alive, including one case undergoing salvage for late relapse. Four HR patients (17%) had died, three from primary progressive disease and one from treatment-refractory relapse 2 months after achieving CR. These results with R-CODOX-M/R-IVAC compare favourably with existing data using CODOX-M/IVAC and warrant further prospective studies. The potential pitfalls of PET-CT to assess response are highlighted.

  4. Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.

    PubMed

    Pinheiro, Dammy; Chang, Yu-Mei; Bryant, Hannah; Szladovits, Balazs; Dalessandri, Tim; Davison, Lucy J; Yallop, Elizabeth; Mills, Emily; Leo, Chiara; Lara, Ana; Stell, Anneliese; Polton, Gerry; Garden, Oliver A

    2014-01-01

    The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

  5. Randomized study of granulocyte colony stimulating factor for childhood B-cell non-Hodgkin lymphoma: a report from the Japanese pediatric leukemia/lymphoma study group B-NHL03 study.

    PubMed

    Tsurusawa, Masahito; Watanabe, Tomoyuki; Gosho, Masahiko; Mori, Tetsuya; Mitsui, Tetsuo; Sunami, Shosuke; Kobayashi, Ryoji; Fukano, Reiji; Tanaka, Fumiko; Fujita, Naoto; Inada, Hiroko; Sekimizu, Masahiro; Koh, Katsuyoshi; Kosaka, Yoshiyuki; Komada, Yoshihiro; Saito, Akiko M; Nakazawa, Atsuko; Horibe, Keizo

    2016-07-01

    The objective of this study was to assess the impact of the primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) in the management of childhood B-cell non-Hodgkin lymphoma (B-NHL). Patients with advanced-stage mature B-NHL were randomized to receive prophylactic G-CSF (G-CSF+) or not receive G-CSF (G-CSF-) based on protocols of the B-NHL03 study. The G-CSF group received 5 μg/kg/d Lenograstim from day 2 after each course of six chemotherapy courses. Fifty-eight patients were assessable, 29 G-CSF + and 29 G-CSF-. G-CSF + patients showed a positive impact on the meantime to neutrophil recovery and hospital stay. On the other hand, they had no impact in the incidences of febrile neutropenia, serious infections, stomatitis and total cost. Our study showed that administration of prophylactic G-CSF through all six chemotherapy courses for childhood B-NHL showed no clinical and economic benefits for the management of childhood B-NHL treatment.

  6. The combination of milatuzumab, a humanized anti-CD74 antibody, and veltuzumab, a humanized anti-CD20 antibody, demonstrates activity in patients with relapsed and refractory B-cell non-Hodgkin lymphoma.

    PubMed

    Christian, Beth A; Poi, Ming; Jones, Jeffrey A; Porcu, Pierluigi; Maddocks, Kami; Flynn, Joseph M; Benson, Don M; Phelps, Mitch A; Wei, Lai; Byrd, John C; Wegener, William A; Goldenberg, David M; Baiocchi, Robert A; Blum, Kristie A

    2015-06-01

    As a result of the anti-tumour activity observed in vitro and in vivo with combined anti-CD20 and anti-CD74 antibodies, we initiated a phase I/II trial of veltuzumab and milatuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Patients received an induction of veltuzumab 200 mg/m(2) weekly combined with escalating doses of milatuzumab at 8, 16 and 20 mg/kg weekly for 4 weeks. Patients without disease progression could receive an extended induction with treatment on weeks 12, 20, 28 and 36. A total of 35 patients enrolled on the study. Median age was 63 years, median number of prior therapies was 3, and 63% of patients were rituximab refractory. No dose-limiting toxicities were observed in the phase I study. Related grade 3-4 toxicities included lymphopenia, leucopenia, neutropenia, anaemia, infusion reactions, hyperglycaemia, fatigue and atrial tachycardia. Median weeks of therapy was 12 and 29% of patients completed all 36 weeks of therapy. The overall response rate was 24%, median duration of response was 12 months, and responses were observed at all dose levels and in 50% of patients refractory to rituximab. Combination therapy with veltuzumab and milatuzumab demonstrated activity in a population of heavily pre-treated patients with relapsed or refractory indolent NHL.

  7. Endobronchial non-Hodgkin's lymphoma presenting as mass lesion.

    PubMed

    Mohapatra, P R; Bhuniya, S; Garg, S; Dimri, K; Janmeja, A K

    2009-01-01

    A 40-year-old male presented with clinical and radiological manifestations of right lung atelectasis and post-obstructive pneumonia. Flexible bronchoscopy revealed gross narrowing of the right upper lobe bronchus and a smooth, white endobronchial mass completely occluding the right lower lobe bronchus. Endobronchial biopsy from the mass lesion yielded low grade B-cell non-Hodgkin's lymphoma. This is one of the rarest presentation of non-Hodgkin's lymphoma.

  8. Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B-cell non-Hodgkin lymphomas, ANRS HC-13 lympho-C study.

    PubMed

    Michot, Jean-Marie; Canioni, Danielle; Driss, Henda; Alric, Laurent; Cacoub, Patrice; Suarez, Felipe; Sibon, David; Thieblemont, Catherine; Dupuis, Jehan; Terrier, Benjamin; Feray, Cyrille; Tilly, Hervé; Pol, Stanislas; Leblond, Véronique; Settegrana, Catherine; Rabiega, Pascaline; Barthe, Yoann; Hendel-Chavez, Houria; Nguyen-Khac, Florence; Merle-Béral, Hélène; Berger, Françoise; Molina, Thierry; Charlotte, Frédéric; Carrat, Fabrice; Davi, Frédéric; Hermine, Olivier; Besson, Caroline

    2015-03-01

    Hepatitis C virus (HCV) infection increases the risk of B-cell non-Hodgkin lymphomas (B-NHL). Antiviral treatment (AT) can induce hematological responses in patients with marginal zone lymphomas (MZL). The ANRS HC-13 Lympho-C study aimed at a better understanding of the impact of AT on HCV associated B-NHL. This multicentric study enrolled 116 HCV-positive patients with B-NHL between 2006 and 2012. Cytological and histological samples were collected for centralized review. At lymphoma diagnosis, median age was 61 years and gender ratio M/F was 1. Cytohistological distribution was marginal zone lymphoma (MZL) n = 45 (39%), diffuse large B-cell lymphoma (DLBCL) n = 45 (39%), and other types n = 26 (22%). MZL patients had more frequent detection of rheumatoid factor (68% vs. 35%; P = 0.001) and more frequently mixed cryoglobulinemia (74% vs. 44%; P = 0.021) than patients with DLBCL. Among patients receiving AT, a sustained virologic response was achieved in 23 of 38 (61%) patients with MZL and in 9 of 17 (53%) with DLBCL (P = 0.42). Three-year overall survival (OS) and progression-free survival were 78% 95%CI [63-88] and 64% [48-76], respectively, without difference between cytohistological groups. Outcome analysis showed a favorable association between OS and AT in all patients (P = 0.05) and in the subgroup of MZL patients only (P = 0.04). Our data support that AT improves the outcomes of HCV-associated NHLs. The impact of new AT regimen with protease inhibitor needs to be investigated in this setting. [clinicalTrials.gov Identification number NCT01545544

  9. Relevance of ID3-TCF3-CCND3 pathway mutations in pediatric aggressive B-cell lymphoma treated according to the NHL-BFM protocols.

    PubMed

    Rohde, Marius; Bonn, Bettina R; Zimmermann, Martin; Lange, Jonas; Möricke, Anja; Klapper, Wolfram; Oschlies, Ilske; Szczepanowski, Monika; Nagel, Inga; Schrappe, Martin; Loeffler, Markus; Siebert, Reiner; Reiter, Alfred; Burkhardt, Birgit

    2017-02-16

    Mature B-cell Non-Hodgkin lymphoma is the most common subtype of Non-Hodgkin lymphoma in childhood and adolescence. B-cell Non-Hodgkin lymphoma are further classified into histological subtypes, with Burkitt lymphoma and Diffuse large B-cell lymphoma being the most common subgroups in pediatric patients. Translocations involving the MYC oncogene are known as relevant but not sufficient hit for Burkitt lymphoma pathogenesis. Recently published large-scale next-generation sequencing studies unveiled sets of additional recurrently mutated genes in samples of pediatric and adult B-cell Non-Hodgkin lymphoma patients. ID3, TCF3 and CCND3 are potential drivers of Burkitt-lymphomagenesis. In the present study frequency and clinical relevance of mutations in ID3, TCF3 and CCND3 were analyzed within a well-defined cohort of 84 uniformly diagnosed and treated pediatric B-cell Non-Hodgkin lymphoma patients of the Berlin-Frankfurt-Munster group (NHL-BFM). Mutation frequency was 78% (ID3), 13% (TCF3) and 36% (CCND3) in Burkitt lymphoma (including Burkitt leukemia). ID3 and CCND3 mutations were associated with more advanced stages of the disease in MYC rearrangement positive Burkitt lymphoma. In conclusion ID3-TCF3-CCND3 pathway genes are mutated in more than 88% of MYC-rearranged pediatric B-cell Non-Hodgkin lymphoma and the pathway may represent a highly relevant second hit of Burkitt lymphoma pathogenesis especially in children and adolescents.

  10. Long-term follow-up of tandem high-dose therapy with autologous stem cell support for adults with high-risk age-adjusted international prognostic index aggressive non-Hodgkin Lymphomas: a GOELAMS pilot study.

    PubMed

    Monjanel, Hélène; Deconinck, Eric; Perrodeau, Elodie; Gastinne, Thomas; Delwail, Vincent; Moreau, Anne; François, Sylvie; Berthou, Christian; Gyan, Emmanuel; Milpied, Noël

    2011-06-01

    Single high-dose therapy (HDT) followed by autologous peripheral blood stem cell (PBSC) support improves complete response and overall survival (OS) in untreated aggressive non-Hodgkin's lymphoma (NHL). However, patients with a high age-adjusted international prognostic index (aa-IPI equal to 3) still have poor clinical outcome despite high dose intensity regimen. To improve complete response in this subgroup, the French Groupe Ouest-Est des Leucémies et Autres Maladies du Sang (GOELAMS) conducted a pilot phase II trial (073) evaluating tandem HDT with PBSC support in a series of 45 patients with aa-IPI equal to 3 untreated aggressive non-Hodgkin's lymphoma. After induction with an anthracyclin-containing regimen, responders underwent tandem HDT conditioned by high-dose mitoxantrone plus cytarabine for the first HDT and total-body irradiation (TBI), carmustine, etoposide, and cyclophosphamide for the second HDT. Thirty-one patients out of 41 evaluable patients completed the program. There were 4 toxic deaths. The complete response rate was 49%. With a median follow-up of 114 months for surviving patients, the OS was 51%, and 19 out of the 22 patients (86%) who reached a complete response are alive and relapse-free. Recent prospective evaluation of quality of life and comorbidities of surviving patients does not reveal long-term toxicities of the procedure. In the era of monoclonal antibodies and response-adapted therapy, the role of tandem HDT still need to be determined.

  11. Primary T-Cell Non-Hodgkin Lymphoma of the Vagina

    PubMed Central

    Herraiz, J. L.; Llueca, A.; Maazouzi, Y.; Piquer, D.; Palmeiro, A.; Calpe, E.

    2015-01-01

    The primary vaginal T-cell non-Hodgkin lymphoma is a rare form of lymphoma. Most of the previously published cases were about B-cell non-Hodgkin lymphomas. We present the case of a vaginal mass in an 82-year-old patient presenting vaginal bleeding. The results of the immunohistological studies of the mass revealed the presence of a cytotoxic T-cell non-Hodgkin lymphoma, which is the least common subtype. PMID:26101677

  12. Combination of rituximab and nonpegylated liposomal doxorubicin (R-NPLD) as front-line therapy for aggressive non-Hodgkin lymphoma (NHL) in patients 80 years of age or older: a single-center retrospective study.

    PubMed

    Ricciuti, Giuseppina; Finolezzi, Erica; Luciani, Stefania; Ranucci, Elena; Federico, Massimo; Di Nicola, Marta; Zecca, Isaia Antonio Luca; Angrilli, Francesco

    2017-02-03

    The incidence of non-Hodgkin lymphoma in patients 80 years of age or older is 50 times higher than in 20- to 24-year-olds. Very elderly patients are often not treated with standard immunochemotherapy because of poor performance status, comorbidities, and toxicity concerns. We retrospectively analyzed data for 29 patients diagnosed with diffuse large B-cell lymphoma or grade 3B follicular lymphoma and treated with rituximab in combination with nonpegylated liposomal doxorubicin between January 2010 and August 2015. The median age was 84 years. The overall 3-year survival, cause-specific survival, and progression-free survival rates were 46%, 55%, and 44%, respectively. Among prognostic factors, only the achievement of complete remission strongly correlated with overall survival, cause-specific survival, and progression-free survival rates. Treatment caused very mild toxicity, without treatment-related hospitalization or toxic deaths.

  13. A Phase 1-2 Multi-Center Study Evaluating KTE-C19 in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1)

    ClinicalTrials.gov

    2016-12-03

    Refractory Diffuse Large B Cell Lymphoma; Refractory Primary Mediastinal B Cell Lymphoma; Refractory Transformed Follicular Lymphoma; Relapsed/Refractory Transplant Ineligible Diffuse Large B Cell Lymphoma; Relapsed/Refractory Transplant Ineligible Primary Mediastinal B Cell Lymphoma; Relapsed/Refractory Transplant Ineligible Transformed Follicular Lymphoma

  14. Role of routine imaging in detecting recurrent lymphoma: A review of 258 patients with relapsed aggressive non-Hodgkin and Hodgkin lymphoma.

    PubMed

    El-Galaly, T C; Mylam, Karen Juul; Bøgsted, Martin; Brown, Peter; Rossing, Maria; Gang, Anne Ortved; Haglund, Anne; Arboe, Bente; Clausen, Michael Roost; Jensen, Paw; Pedersen, Michael; Bukh, Anne; Jensen, Bo Amdi; Poulsen, Christian Bjørn; d'Amore, Francesco; Hutchings, Martin

    2014-06-01

    After first-line therapy, patients with Hodgkin lymphoma (HL) and aggressive non-HL are followed up closely for early signs of relapse. The current follow-up practice with frequent use of surveillance imaging is highly controversial and warrants a critical evaluation. Therefore, a retrospective multicenter study of relapsed HL and aggressive non-HL (nodal T-cell and diffuse large B-cell lymphomas) was conducted. All included patients had been diagnosed during the period 2002-2011 and relapsed after achieving complete remission on first-line therapy. Characteristics and outcome of imaging-detected relapses were compared with other relapses. A total of 258 patients with recurrent lymphoma were included in the study. Relapse investigations were initiated outside preplanned visits in 52% of the patients. Relapse detection could be attributed to patient-reported symptoms alone or in combination with abnormal blood tests or physical examination in 64% of the patients. Routine imaging prompted relapse investigations in 27% of the patients. The estimated number of routine scans per relapse was 91-255 depending on the lymphoma subtype. Patients with imaging-detected relapse had lower disease burden (P = 0.045) and reduced risk of death following relapse (hazard ratio = 0.62, P = 0.02 in multivariate analysis). Patient-reported symptoms are still the most common factor for detecting lymphoma relapse and the high number of scans per relapse calls for improved criteria for use of surveillance imaging. However, imaging-detected relapse was associated with lower disease burden and a possible survival advantage. The future role of routine surveillance imaging should be defined in a randomized trial.

  15. Non Hodgkin's lymphoma involving the adrenal glands and the central nervous system (CNS): a particular evolution after chemotherapy.

    PubMed

    Vélayoudom, F-L; Cardot-Bauters, C; Decouvelaere, A-V; Vlaeminck, V; Bauters, F; Wémeau, J-L

    2005-12-01

    Adrenal lymphoma is extremely rare. The prognostic depends on involvement of other organs (such as the central nervous system) responsible for lower median survival. We report the case of a 51-year-old man with non Hodgkin's Diffuse Large B Cell Lymphoma (DLBCL) involving the central nervous system (CNS) and the adrenal glands simultaneously. The endocrine exploration revealed a partial adrenal insufficiency and ruled out a pheochromocytoma. Computerized tomographic (CT) scan directed needle biopsy of the adrenal gland allowed the diagnostic of non-Hodgkin lymphoma (NHL). CNS biopsies showed similar histopathologic lesions. After aggressive polychemotherapy and methotrexate intrathecal injection, a dissociated therapeutic response was observed with a decrease of the cerebral lesion and an increase of the adrenal mass. This result may be explained by the efficacy of corticosteroid therapy on cerebral edema. The prognosis was poor with tumor infiltration of the leptomeninges and death 16 months after diagnosis.

  16. Essential Role for Survivin in the Proliferative Expansion of Progenitor and Mature B Cells.

    PubMed

    Miletic, Ana V; Jellusova, Julia; Cato, Matthew H; Lee, Charlotte R; Baracho, Gisele V; Conway, Edward M; Rickert, Robert C

    2016-03-01

    Survivin is a member of the inhibitor of apoptosis family of proteins and a biomarker of poor prognosis in aggressive B cell non-Hodgkin's lymphoma. In addition to its role in inhibition of apoptosis, survivin also regulates mitosis. In this article, we show that deletion of survivin during early B cell development results in a complete block at the cycling pre-B stage. In the periphery, B cell homeostasis is not affected, but survivin-deficient B cells are unable to mount humoral responses. Correspondingly, we show that survivin is required for cell division in response to mitogenic stimulation. Thus, survivin is essential for proliferation of B cell progenitors and activated mature B cells, but is dispensable for B cell survival. Moreover, a small-molecule inhibitor of survivin strongly impaired the growth of representative B lymphoma lines in vitro, supporting the validity of survivin as an attractive therapeutic target for high-grade B cell non-Hodgkin's lymphoma.

  17. Aggressive B-cell lymphomas: how many categories do we need?

    PubMed Central

    Said, Jonathan W

    2015-01-01

    Aggressive B-cell lymphomas are diverse group of neoplasms that arise at different stages of B-cell development and by various mechanisms of neoplastic transformation. The aggressive B-cell lymphomas include many types, subtypes and variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle cell lymphoma and its blastoid variant, and B lymphoblastic lymphoma. Differences in histology, cytogenetic and molecular abnormalities, as well as the relationship with the tumor microenvironment, help define characteristic signatures for these neoplasms, and in turn dictate potential therapeutic targets. Rather than survey the entire spectrum of aggressive B-cell lymphomas, this report aims to identify and characterize important clinically aggressive subtypes of DLBCL, and explore the relationship of DLBCL to BL and the gray zone between them (B-cell lymphoma unclassifiable with features intermediate between DLBCL and BL). PMID:23154748

  18. ProMACE-C-MOPP in aggressive non-Hodgkin's lymphoma. Long-term results in 45 patients treated in a single institution.

    PubMed

    Carrión, J R; Delgado, J R; Dominguez, S; Flores, E; Garcia, P; Jaen, J; Santos, J A

    1991-01-01

    Forty-five previously untreated patients with intermediate or high-grade non-Hodgkin's lymphoma were treated with the Pro-MACE-C-MOPP regimen (flexitherapy). The median age of the patients was 51 years, 51% had constitutional symptoms, 78% were in Ann Arbor stage III-IV, 40% had two or more involved extranodal sites and 87% had serum lactate dehydrogenase (LDH) above 225 U/l. Twenty-two (49%) patients had immunoblastic lymphoma (Working Formulation). Overall, 40% of the patients attained complete response (CR) and there were no relapses. The dose-limiting toxicity was myelosuppression (69% of the patients with WBC less than 1.9 x 10(9)/l). Three deaths were attributed primarily to chemotherapy, but another two patients died of long-term complications of therapy. After a median follow-up of 50 months (18-80), 15 patients (33%) were alive without lymphoma. Only histologic subtype (intermediate vs. high) and abdominal involvement were prognostic factors for CR rate. Our results indicate that ProMACE-C-MOPP is an effective regimen for intermediate-grade lymphomas. However, in high-risk patients the regimen seems to be less effective than originally reported.

  19. Gene Therapy and Combination Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2017-02-23

    AIDS-Related Burkitt Lymphoma; AIDS-Related Diffuse Large B-cell Lymphoma; AIDS-Related Plasmablastic Lymphoma; AIDS-Related Primary Effusion Lymphoma; HIV Infection; AIDS Related Non-Hodgkin Lymphoma

  20. Non-Hodgkin lymphomas in childhood: how to move on?

    PubMed

    Dokmanović, Lidija; Rodić, Predrag; Krstovski, Nada; Lazić, Jelena; Dragana, Janić

    2014-01-01

    Non-Hodgkin lymphomas of childhood represent a diverse group of neoplasms with different clinical, pathological, immunophenotypical and genetic features. A vast majority of childhood non-Hodgkin lymphomas could be classified into one of the three major histological subgroups: mature B-cell neoplasms, lymphoblastic lymphomas or anaplastic large cell lymphomas. Modern therapeutic strategies lead to cure in more than 80% of patients. Conversely, refractory diseases, as well as disease relapse convey a dismal prognosis. This fact requires much better stratification based on prognostic markers which would ideally recognize distinct groups of patients requiring different therapeutic regimens. Defining novel diagnostic and prognostic markers should improve diagnosis and prognosis as well as patient follow-up. It should also allow introduction of individually tailored treatment regimens in selected groups of patients with non-Hodgkin lymphomas, with the main goal of improving treatment results and decreasing short- and long-term complications.

  1. New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling.

    PubMed

    Martín-Subero, José I; Kreuz, Markus; Bibikova, Marina; Bentink, Stefan; Ammerpohl, Ole; Wickham-Garcia, Eliza; Rosolowski, Maciej; Richter, Julia; Lopez-Serra, Lidia; Ballestar, Esteban; Berger, Hilmar; Agirre, Xabier; Bernd, Heinz-Wolfram; Calvanese, Vincenzo; Cogliatti, Sergio B; Drexler, Hans G; Fan, Jian-Bing; Fraga, Mario F; Hansmann, Martin L; Hummel, Michael; Klapper, Wolfram; Korn, Bernhard; Küppers, Ralf; Macleod, Roderick A F; Möller, Peter; Ott, German; Pott, Christiane; Prosper, Felipe; Rosenwald, Andreas; Schwaenen, Carsten; Schübeler, Dirk; Seifert, Marc; Stürzenhofecker, Benjamin; Weber, Michael; Wessendorf, Swen; Loeffler, Markus; Trümper, Lorenz; Stein, Harald; Spang, Rainer; Esteller, Manel; Barker, David; Hasenclever, Dirk; Siebert, Reiner

    2009-03-12

    Lymphomas are assumed to originate at different stages of lymphocyte development through chromosomal aberrations. Thus, different lymphomas resemble lymphocytes at distinct differentiation stages and show characteristic morphologic, genetic, and transcriptional features. Here, we have performed a microarray-based DNA methylation profiling of 83 mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) characterized for their morphologic, genetic, and transcriptional features, including molecular Burkitt lymphomas and diffuse large B-cell lymphomas. Hierarchic clustering indicated that methylation patterns in maB-NHLs were not strictly associated with morphologic, genetic, or transcriptional features. By supervised analyses, we identified 56 genes de novo methylated in all lymphoma subtypes studied and 22 methylated in a lymphoma subtype-specific manner. Remarkably, the group of genes de novo methylated in all lymphoma subtypes was significantly enriched for polycomb targets in embryonic stem cells. De novo methylated genes in all maB-NHLs studied were expressed at low levels in lymphomas and normal hematopoietic tissues but not in nonhematopoietic tissues. These findings, especially the enrichment for polycomb targets in stem cells, indicate that maB-NHLs with different morphologic, genetic, and transcriptional background share a similar stem cell-like epigenetic pattern. This suggests that maB-NHLs originate from cells with stem cell features or that stemness was acquired during lymphomagenesis by epigenetic remodeling.

  2. B-Cell Hematologic Malignancy Vaccination Registry

    ClinicalTrials.gov

    2016-12-28

    Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

  3. A prospective study of reduced-dose three-course CHOP followed by involved-field radiotherapy for patients 70 years old or more with localized aggressive non-Hodgkin's lymphoma

    SciTech Connect

    Shikama, Naoto . E-mail: shikama@hsp.md.shinshu-u.ac.jp; Oguchi, Masahiko; Isobe, Koichi; Nakamura, Katsumasa; Tamaki, Yoshio; Hasegawa, Masatoshi; Kodaira, Takeshi; Sasaki, Shigeru; Kagami, Yoshikazu

    2006-09-01

    Purpose: We conducted a multicenter prospective study to evaluate the efficacy and safety of reduced-dose three-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by involved-field radiotherapy for elderly patients with localized aggressive non-Hodgkin's lymphoma. The primary endpoint was compliance with the combined modality. Methods and Materials: This study included untreated patients, {>=}70 years old, with diffuse aggressive lymphoma, Stage IA or contiguous nonbulky Stage IIA. 80%-CHOP (cyclophosphamide 600 mg/m{sup 2}, doxorubicin 40 mg/m{sup 2}, vincristine 1.1 mg/m{sup 2}, and prednisolone at 80 mg/day for 5 days) was repeated every 3 weeks. After three cycles of chemotherapy, involved-field radiotherapy was performed with a radiation dose of 30-50 Gy in 15-28 fractions. Results: Twenty-four patients with a median age of 75 years (range, 70-84 years) were enrolled. The compliance rate of the protocol study was 87.5% (95% confidence interval [CI], 67.6-97.3). Three patients received only two cycles of chemotherapy because of toxicity or second neoplasm. There were no deaths caused by severe toxicity. The 3-year progression-free and overall survival rates were 83.1% (95% CI, 75.4-90.8) and 82.9% (95% CI, 75.1-90.6), respectively. Conclusion: Three-course 80%-CHOP followed by involved-field radiotherapy may be safe for administration to elderly patients over 70 years old. The next step is to evaluate three-course 80%-CHOP and rituximab followed by radiotherapy in elderly patients with localized disease.

  4. Promising long-term outcome of gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule as salvage regimen for patients with previously heavily treated Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma.

    PubMed

    Bai, Bing; Huang, Hui-Qiang; Cai, Qing-Qing; Wang, Xiao-Xiao; Cai, Qi-Chun; Lin, Ze-Xiao; Gao, Yan; Xia, Yi; Bu, Qing; Guo, Ying

    2013-03-01

    The combination of gemcitabine (G), vinorelbine (V), and pegylated liposomal doxorubicin (D) has proved to be effective in relapsed Hodgkin's lymphoma (HL). Its efficacy in non-Hodgkin's lymphoma (NHL) remains to be discussed. We retrospectively evaluated the efficacy and toxicity of the dose-adjusted gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule in 35 heavily pretreated patients with relapsed and refractory aggressive NHL or HL. Treatment consisted of G: 800 mg/m(2) intravenous (i.v.) on day 1, V: 15 mg/m(2) i.v. on day 1; D: 20 mg/m(2) i.v. on day 1, repeated for 14 days. Patients responded to GVD proceeded to subsequent autologous stem cell transplantation. The objective response rate (ORR) was 48.6 %, with 31.4 % complete remission. A higher ORR was observed in patients with HL than in patients with NHL (80.0 vs. 36.0 %, P = 0.023). With a median follow-up of 26 months, the estimated median progression-free survival and overall survival were 5 (range 1-73 months) and 36 months (range 2-73 months), respectively. The estimated 5-year survival rate was 44.6 % (95 % confidence interval 28.1-61.1 %). Toxicities were mild (grade 3/4 neutropenia 34.3 %, thrombocytopenia 5.7 %). Our results suggest that the dose-adjusted GVD in 14-day schedule is effective and well tolerated in patients with refractory and relapsed HL and aggressive NHL. The potential long-term survival in NHL is promising.

  5. Ongoing investigations and new uses of radioimmunotherapy in the treatment of non-Hodgkin's lymphoma

    SciTech Connect

    Meredith, Ruby F. . E-mail: rmeredith@uabmc.edu

    2006-10-01

    Studies in radiation oncology are focusing on the optimal use of systemic targeted radionuclide therapy (STaRT) in the treatment of patients with cancer. The two approved radioimmunotherapy agents, yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab, are being studied in a range of lymphoid malignancies, from low-grade to aggressive B-cell non-Hodgkin's lymphomas. Studies of standard- and escalated-dose radioimmunotherapy with or without stem cell support are reviewed, as are radioimmunotherapy with other therapeutic modalities in these settings. The results of these trials have important implications for clinical practice, and it is hoped that they will further clarify the optimal timing and dosing of these agents.

  6. Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-12-08

    CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  7. Response-adapted therapy for aggressive non-Hodgkin's lymphomas based on early [18F] FDG-PET scanning: ECOG-ACRIN Cancer Research Group study (E3404).

    PubMed

    Swinnen, Lode J; Li, Hailun; Quon, Andrew; Gascoyne, Randy; Hong, Fangxin; Ranheim, Erik A; Habermann, Thomas M; Kahl, Brad S; Horning, Sandra J; Advani, Ranjana H

    2015-07-01

    A persistently positive positron emission tomography (PET) scan during therapy for diffuse large B-cell lymphoma (DLBCL) is predictive of treatment failure. A response-adapted strategy consisting of an early treatment change to four cycles of R-ICE (rituximab, ifosfamide, carboplatin, etoposide) was studied in the Eastern Cooperative Oncology Group E3404 trial. Previously untreated patients with DLBCL stage III, IV, or bulky II, were eligible. PET scan was performed after three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and scored as positive or negative by central review during the fourth cycle. PET-positive patients received four cycles of R-ICE, PET-negative patients received two more cycles of R-CHOP. A ≥ 45% 2-year progression-free survival (PFS) for mid-treatment PET-positive patients was viewed as promising. Of 74 patients, 16% were PET positive, 79% negative. The PET positivity rate was much lower than the 33% expected. Two-year PFS was 70%; 42% [90% confidence interval (CI), 19-63%] for PET-positives and 76% (90% CI 65-84%) for PET-negatives. Three-year overall survival (OS) was 69% (90% CI 43-85%) and 93% (90% CI 86-97%) for PET-positive and -negative cases, respectively. The 2-year PFS for mid-treatment PET-positive patients intensified to R-ICE was 42%, with a wide confidence interval due to the low proportion of positive mid-treatment PET scans. Treatment modification based on early PET scanning should remain confined to clinical trials.

  8. Advanced Stage, Increased Lactate Dehydrogenase, and Primary Site, but Not Adolescent Age (≥ 15 Years), Are Associated With an Increased Risk of Treatment Failure in Children and Adolescents With Mature B-Cell Non-Hodgkin's Lymphoma: Results of the FAB LMB 96 Study

    PubMed Central

    Cairo, Mitchell S.; Sposto, Richard; Gerrard, Mary; Auperin, Anne; Goldman, Stanton C.; Harrison, Lauren; Pinkerton, Ross; Raphael, Martine; McCarthy, Keith; Perkins, Sherrie L.; Patte, Catherine

    2012-01-01

    Purpose Adolescents (age 15 to 21 years) compared with younger children with mature B-cell non-Hodgkin's lymphoma (NHL) have been historically considered to have an inferior prognosis. We therefore analyzed the impact of age and other diagnostic factors on the risk of treatment failure in children and adolescents treated on the French-American-British Mature B-Cell Lymphoma 96 (FAB LMB 96) trial. Patients and Methods Patients were divided by risk: group A (limited), group B (intermediate), and group C (advanced), as previously described. Prognostic factors analyzed for event-free survival (EFS) included age (< 15 v ≥ 15 years), stage (I/II v III/IV), primary site, lactate dehydrogenase (LDH), bone marrow/CNS (BM/CNS) involvement, and histology (diffuse large B-cell lymphoma v mediastinal B-cell lymphoma v Burkitt lymphoma or Burkitt-like lymphoma). Results The 3-year EFS for the whole cohort was 88% ± 1%. Age was not associated as a risk factor for increased treatment failure in either univariate analysis (P = .15) or multivariate analysis (P = .58). Increased LDH (≥ 2 × upper limit of normal [ULN] v < 2 × ULN), primary site, and BM-positive/CNS-positive disease were all independent risk factors associated with a significant increase in treatment failure rate (relative risk, 2.0; P < .001, P < .012, and P < .001, respectively). Conclusion LDH level at diagnosis, mediastinal disease, and combined BM-positive/CNS-positive involvement are independent risk factors in children with mature B-cell NHL. Future studies should be developed to identify specific therapeutic strategies (immunotherapy) to overcome these risk factors and to identify the biologic basis associated with these prognostic factors in children with mature B-cell NHL. PMID:22215753

  9. 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.

  10. The combined evaluation of interim contrast-enhanced computerized tomography (CT) and FDG-PET/CT predicts the clinical outcomes and may impact on the therapeutic plans in patients with aggressive non-Hodgkin's lymphoma.

    PubMed

    Yang, Deok-Hwan; Min, Jung-Joon; Jeong, Yong Yeon; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Cho, Sang-Hee; Chung, Ik-Joo; Bom, Hee-Seung; Kim, Hyeoung-Joon; Lee, Je-Jung

    2009-05-01

    We investigated the concomitant interim response of patients with aggressive non-Hodgkin's lymphoma (NHL) using multi-detector row computerized tomography (CT) and (18)F-fluoro-2-deoxy-D: -glucose-positron emission tomography (PET)/CT for prediction of clinical outcomes. One hundred six newly diagnosed patients with aggressive NHL were enrolled. Both the CT and PET/CT were serially performed at the time of diagnosis and after three to four cycles of chemotherapy (interim). The patients were categorized into four different responsive groups according to the interim PET/CT and CT: (1) complete metabolic response (CMR)-complete response unconfirmed (CRu), (2) CMR-partial response (PR), (3) partial metabolic response (PMR)-Cru, and (4) PMR-PR. Fifty-five patients with CMR-CRu, 20 patients with CMR-PR, seven patients with PMR-Cru, and 23 patients with PMR-PR were distributed. In addition, one patient experienced a disease progression. There was a significant difference in relapse rates between PET/CT-positive (67.3%) and PET/CT-negative patients (17.3%; P < 0.01). Also, there was a significant difference between patients with PMR-PR (32.0% and 26.1%) and CMR-CRu (89.3% and 80.0%) for 3-year overall survival (OS) and event-free survival (EFS), respectively. A multivariate analysis revealed that high international prognostic index (> or =3) at diagnosis, T-cell phenotype, and PMR-PR in interim PET/CT and CT were independent prognostic significances for OS. Moreover, bulky disease (>10 cm), T-cell phenotype, and PMR-PR showed significant associations for EFS. PMR-PR in interim response was the predictive prognostic determinant for both OS and EFS, with a hazard ratio of 3.93 (1.61-9.60) and 3.60 (1.62-7.98), respectively. The combined evaluation of interim PET/CT and CT was found to be a significant predictor of disease progression, OS, and EFS.

  11. Cell adhesion induces p27Kip1-associated cell-cycle arrest through down-regulation of the SCFSkp2 ubiquitin ligase pathway in mantle-cell and other non-Hodgkin B-cell lymphomas

    PubMed Central

    Lwin, Tint; Hazlehurst, Lori A.; Dessureault, Sophie; Lai, Raymond; Bai, Wenlong; Sotomayor, Eduardo; Moscinski, Lynn C.; Dalton, William S.

    2007-01-01

    Mounting evidence suggests that dynamic interactions between a tumor and its microenvironment play a critical role in tumor development, cell-cycle progression, and response to therapy. In this study, we used mantle cell lymphoma (MCL) as a model to characterize the mechanisms by which stroma regulate cell-cycle progression. We demonstrated that adhesion of MCL and other non-Hodgkin lymphoma (NHL) cells to bone marrow stromal cells resulted in a reversible G1 arrest associated with elevated p27Kip1 and p21 (WAF1) proteins. The adhesion-mediated p27Kip1 and p21 increases were posttranslationally regulated via the down-regulation of Skp2, a subunit of SCFSkp2 ubiquitin ligase. Overexpression of Skp2 in MCL decreased p27Kip1, whereas inhibition of Skp2 by siRNA increased p27Kip1 and p21 levels. Furthermore, we found cell adhesion up-regulated Cdh1 (an activating subunit of anaphase-promoting complex [APC] ubiquitin ligase), and reduction of Cdh1 by siRNA induced Skp2 accumulation and hence p27Kip1 degradation, thus implicating Cdh1 as an upstream effector of the Skp2/p27Kip1 signaling pathway. Overall, this report, for the first time, demonstrates that cell-cell contact controls the tumor cell cycle via ubiquitin-proteasome proteolytic pathways in MCL and other NHLs. The understanding of this novel molecular pathway may prove valuable in designing new therapeutic approaches for modifying tumor cell growth and response to therapy. PMID:17502456

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

    ClinicalTrials.gov

    2017-01-31

    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

  13. What's New in Non-Hodgkin Lymphoma Research and Treatment?

    MedlinePlus

    ... Non-Hodgkin Lymphoma About Non-Hodgkin Lymphoma What’s New in Non-Hodgkin Lymphoma Research and Treatment? Research ... done on NHL is focused on looking at new and better ways to treat this disease. Chemotherapy ...

  14. What Are the Key Statistics about Non-Hodgkin Lymphoma?

    MedlinePlus

    ... About Non-Hodgkin Lymphoma What Are the Key Statistics About Non-Hodgkin Lymphoma? Non-Hodgkin lymphoma (NHL) ... coming years. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Written by References ...

  15. The role of bone marrow biopsy and FDG-PET/CT in identifying bone marrow infiltration in the initial diagnosis of high grade non-Hodgkin B-cell lymphoma and Hodgkin lymphoma. Accuracy in a multicenter series of 372 patients.

    PubMed

    Chen-Liang, Tzu-Hua; Martin-Santos, Taida; Jerez, Andres; Senent, Leonor; Orero, Maria Teresa; Remigia, Maria Jose; Muiña, Begoña; Romera, Marta; Fernandez-Muñoz, Hermogenes; Raya, Jose M; Fernandez-Gonzalez, Marta; Lancharro, Aima; Villegas, Carolina; Carlos Herrera, Juan; Frutos, Laura; Luis Navarro, Jose; Uña, Jon; Igua, Carolina; Sanchez-Vaño, Raquel; Cozar, Maria Del Puig; Contreras, Jose; Sanchez-Blanco, Jose Javier; Perez-Ceballos, Elena; Ortuño, Francisco Jose

    2015-08-01

    Bone marrow infiltration (BMI), categorized as an extra-nodal site, affects stage and is associated with poor prognosis in newly diagnosed lymphoma patients. We have evaluated the accuracy of PET/CT and bone marrow biopsy (BMB) to assess BMI in 372 lymphoma patients [140 Hodgkin Lymphoma (HL) and 232 High Grade B-cell non-Hodgkin Lymphoma (HG B-NHL), among them 155 Diffuse Large B-Cell Lymphoma (DLCL)]. For HL cases, and taking into account PET/CT, sensitivity, negative predictive value (NPV) and accuracy were 96.7, 99.3, and 99.3% while those of BMB were 32.3, 83.8, and 85%, respectively. For HG B-NHL and considering PET/CT, sensitivity, NPV, and accuracy were 52.7, 81.7, and 84.1%, while those of BMB were 77.6, 90.2, and 90.7%, respectively. In the HG B-NHL group, 25 patients would have been under-staged without BMB. These results lead us to recommend PET/CT and the avoidance of BMB to assess BMI in HL. In the case of HG B-NHL, bone marrow status should be assessed firstly by means of PET/CT; only in either focal or diffuse PET/CT with low borderline SUV max values or in negative cases, should BMB be carried out afterwards. In the HG B-NHL setting and at the present moment, both techniques are complementary.

  16. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial

    PubMed Central

    Jaeger, Ulrich; Trneny, Marek; Melzer, Helen; Praxmarer, Michael; Nawarawong, Weerasak; Ben Yehuda, Dina; Goldstein, David; Mihaljevic, Bilijana; Ilhan, Osman; Ballova, Veronika; Hedenus, Michael; Hsiao, Liang-Tsai; Au, Wing-Yan; Burgstaller, Sonja; Weidinger, Gerhard; Keil, Felix; Dittrich, Christian; Skrabs, Cathrin; Klingler, Anton; Chott, Andreas; Fridrik, Michael A.; Greil, Richard

    2015-01-01

    We investigated rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (n=662) or follicular lymphoma grade 3b (n=21) in first complete remission. Patients were randomized to rituximab maintenance (n=338) or observation (n=345). At a median follow-up of 45 months, the event-free survival rate (the primary endpoint) at 3 years was 80.1% for rituximab maintenance versus 76.5% for observation. This difference was not statistically significant for the intent-to-treat population (likelihood ratio P=0.0670). The hazard ratio by treatment arm was 0.79 (95% confidence interval 0.57–1.08; P=0.1433). The secondary endpoint, progression-free survival was also not met for the whole statistical model (likelihood ratio P=0.3646). Of note, rituximab maintenance was superior to observation when treatment arms only were compared (hazard ratio: 0.62; 95% confidence interval 0.43–0.90; P=0.0120). Overall survival remained unchanged (92.0 versus 90.3%). In subgroup analysis male patients benefited from rituximab maintenance with regards to both event-free survival (84.1% versus 74.4%) (hazard ratio: 0.58; 95% confidence interval 0.36–0.94; P=0.0267) and progression-free survival (89.0% versus 77.6%) (hazard ratio: 0.45; 95% confidence interval 0.25–0.79; P=0.0058). Women had more grade 3/4 adverse events (P=0.0297) and infections (P=0.0341). Men with a low International Prognostic Index treated with rituximab had the best outcome. In summary, rituximab maintenance in first remission after R-CHOP-like treatment did not prolong event-free, progression-free or overall survival of patients with aggressive B-non-Hodgkin lymphoma. The significantly better outcome of men warrants further studies prior to the routine use of rituximab maintenance in men with low International Prognostic Index. This trial is registered under EUDRACT #2005-005187-90 and www.clinicaltrials.gov as #NCT00400478. PMID:25911553

  17. Chemotherapy of advanced non-Hodgkin's lymphoma.

    PubMed

    Skarin, A T; Canellos, G P

    1979-10-01

    From the therapuetic point of view, non-Hodgkin's lymphomas can be classified into two groups: favourable prognosis histology (DWDL, NWDL, NPDL, and NM) and unfavourable prognosis histology (DPDL, DM, DH, NH, DU). The latter group also includes lymphoblastic lymphoma (T cell) and Burkitt's lymphoma (B cell). Further classification by immunological markers (T, B, monocyte, null cell) and functional categories (T-cell subsets) may reveal prognostic groups which require separate consideration. Intensive chemotherapy of unfavourable histoligies can result in long-term disease-free survival as reported in several series. It would appear that the 10 year survival rates will not differ greatly between several multi-drug regimens. At the present time, the histopathological subtype permits selection of patients for a trial of intensive chemotherapy. The progress in the future will be made with improved techniques for the management of bulky abdominal disease and central nervous system invasion. Although the above may result in some statistical improvement in survival of the unfavourable group, the vast majority of patients with favourable histology lymphoma require new approaches. These may take the form of treatment with immunological manoeuvres such as idiotypic-specific antibodies and/or the use of intensive chemotherapy, especially when there is convincing evidence of a change in the biology of the disease.

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

    ClinicalTrials.gov

    2017-01-31

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; CD19 Positive; Mediastinal Lymphoma; Recurrent Adult 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

  19. Primary non-Hodgkin's lymphoma of the mediastinum

    SciTech Connect

    Levitt, L.J.; Aisenberg, A.C.; Harris, N.L.; Linggood, R.M.; Poppema, S.

    1982-12-01

    Non-Hodgkin's lymphoma localized to the mediastinum and adjacent structures occurred in 12 of 215 (6%) non-Hodgkin's lymphoma patients seen at the Massachusetts General Hospital between 1975 and 1979. Lymphangiography, radionuclide scanning and whole body computerized tomography were used to exclude patients with extrathoracic disease at presentation. Eleven of the 12 patients presented with extensive contiguous extranodal disease (Stage II/sub E/) with involvement of either the pericardium, sternum, chest wall, pulmonary parenchyma or, in four cases, with superior venacaval obstruction. Diffuse large cell lymphoma (eight cases) and diffuse poorly differentiated lymphocytic lymphoma (four cases) were the prevalent histologic subtypes; no instances of lymphoblastic lymphoma without extra-thoracic spread were encountered. None of four lymphomas studied could be characterized as either B- or T-cell tumors utilizing conventional surface marker techniques. Ten of the 12 patients achieved complete remissions, either after treatment with combination chemotherapy alone (three patients) or after both chemotherapy and mediastinal irradiation (seven patients). Two of these ten have subsequently relapsed, but median survival has not been reached after a mean period of observation of 28 months. Primary nonlymphoblastic non-Hodgkin's lymphoma of the mediastinum is more common than previously realized, displays aggressive contiguous spread within the chest and responds well to combination chemotherapy with or without adjuvant mediastinal irradiation.

  20. Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies

    ClinicalTrials.gov

    2017-02-16

    Adult Burkitt Lymphoma; Adult Diffuse Large B-Cell Lymphoma; CD20-Positive Neoplastic Cells Present; Indolent Adult Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory Mature B-Cell Non-Hodgkin Lymphoma

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

    ClinicalTrials.gov

    2016-11-25

    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

  2. Post-Ganglionic Horner's Syndrome: An Unusual Presentation of Non-Hodgkin Lymphoma

    PubMed Central

    Ruiz e Resende, Lucilene Silva; Gaiolla, Rafael Dezen; Niéro-Melo, Lígia; Custódio Domingues, Maria Aparecida; de Lima Resende, Luiz Antônio

    2012-01-01

    In this paper, we present the rare case of a patient with cervical lymphadenopathy diagnosed as a T-cell-rich B-cell non-Hodgkin lymphoma that manifested Horner's syndrome due to a post-ganglionic sympathetic neuron lesion caused by the tumor. PMID:22611367

  3. A case of composite classical and nodular lymphocyte predominant Hodgkin lymphoma with progression to diffuse large B-cell non-Hodgkin lymphoma: Diagnostic difficulty in fine-needle aspiration cytology.

    PubMed

    Das, Dilip K; Sheikh, Zafar A; Al-Shama'a, Mariam H; John, Bency; Alawi, Abdulla M S; Junaid, Thamradeen A

    2017-03-01

    A small percentage of nodular lymphocytic predominant Hodgkin lymphoma (NLPHL) progresses to diffuse large B-cell lymphoma (DLBCL). There have also been rare reports of gray zone lymphoma with features intermediate between classical Hodgkin lymphoma (CHL) and DLBCL. We report a very rare case of composite lymphoma (CHL and NLPHL) progressing to DLBCL, and highlight the diagnostic difficulty faced during its fine-needle aspiration (FNA) cytology diagnosis. A 65-year-old woman presented with a right axillary swelling which was subjected to FNA cytology. The routine FNA cytology diagnosis was anaplastic large cell lymphoma (ALCL) but immunocytochemistry did not support this diagnosis completely. The histopathological diagnosis of the excised lymph node was NLPHL with progression to DLBCL in our hospital but in a hospital abroad where the patient was treated, the reviewed diagnosis was CHL. The patient had a rapid downhill course with development of terminal pleural effusion and died approximately one year from initial diagnosis.The review of the cyto-histologic material along with additional immunocyto/histochemical studies and the clinical course of the disease support the diagnosis of a composite lymphoma (CHL and NLPHL) with progression to DLBCL. It is suggested that all the three lesions were clonally related. Diagn. Cytopathol. 2017;45:262-266. © 2016 Wiley Periodicals, Inc.

  4. Variant Guillain-Barré Syndrome in a Patient with Non-Hodgkin's Lymphoma

    PubMed Central

    Bishay, R. H.; Paton, J.; Abraham, V.

    2015-01-01

    We report a 72-year-old female patient with diffuse large B cell non-Hodgkin's lymphoma (NHL) with previous treatment with standard chemotherapy presenting as an acute, ascending, sensorimotor polyneuropathy. Nerve conduction studies and lumbar puncture supported a rare, but ominous, axonal variant of Guillain-Barré Syndrome (GBS) known as acute motor and sensory axonal neuropathy (AMSAN), which is distinguished from the more common, acute demyelinating forms of GBS. Previous reports have largely focused on toxicities secondary to chemo- or radiotherapy as a major contributor to the development of acute neuropathies in malignancy. Clinicians should also be mindful of direct neoplastic invasion or, less commonly, paraneoplastic phenomenon, as alternative mechanisms, the latter possibly reflecting immune dysregulation in particularly aggressive lymphomas. At the time of writing, this is the first report in the literature of an axonal variant of GBS in a patient with diffuse large B cell NHL. A discussion regarding common and uncommon neuropathies in haematological malignancies is made, with a brief review of the anecdotal evidence supporting a paraneoplastic association with GBS or its variant forms in the setting of lymphoma. PMID:26347834

  5. Primary Liver Sinusoidal Non-Hodgkin's Lymphoma Presenting as Acute Liver Failure

    PubMed Central

    Nagral, Aabha; Jhaveri, Ajay; Kalthoonical, Vilesh; Bhat, Ganapathi; Mahajan, Pravin; Borges, Anita

    2015-01-01

    We describe a case of a middle-aged woman, who presented to us with fever, anorexia, abdominal distension from a massive hepatomegaly, low hemoglobin, and acute liver failure. A liver biopsy revealed B cell non-Hodgkin's lymphoma predominantly in the sinusoids with CD10, CD20, and Bcl-2 positive on immunohistochemistry. She initially responded well to chemotherapy but succumbed 6 months later to the recurrence of disease. Sinusoidal non-Hodgkin's lymphoma of the liver should be considered in the differential diagnosis of a patient with large hepatomegaly presenting with acute liver failure. PMID:26900276

  6. Histologic progression in non-hodgkin's lymphoma

    SciTech Connect

    Hubbard, S.M.; Chabner, B.A.; DeVita, V.T., Jr.; Simon, R.; Berard, C.W.; Jones, R.B.; Garvin, A.J.; Canellos, G.P.; Osborne, C.K.; Young, R.C.

    1982-02-01

    The clinical course and biopsy specimens from 515 consecutive non-Hodgkin's lymphoma patients was evaluated retrospectively in an attempt to determine the clinical importance of documented changes in histology over time. Two-hundred and five of these patients has an initial diagnosis of nodular lymphoma and were reviewed for this anaysis. Sixty-three underwent a repeat biopsy greater than 6 mo after initial diagnosis. In 23 patients, these repeat biopsies revealed a change in histology to a diffuse pattern and/or a change to a larger ''histiocytic'' cell type, while repeat biopsies for the other 40 (63%) disclosd persistence of a nodular pattern and no clear change in basic cell type. Progression from nodular lymphoma to diffuse histiocytic, mixed, or undifferentiated types of lymphomas of Rappaport was found in repeate biopsies obtained from 19 patients (30%). Prognosis for survival following a biopsy that demonstrated histologic change was related to the histology demonstrated at the most recent biopsy and to the response to subsequent drug treatment. Survival following repeat biopsy for these 19 patients was significantly shorter than for the 40 patients whose histology remained nodular (p < 0.001). However, attainment of a complete remission with intensive combination chemotherapy was associated with prolonged survival in eight patients and prolonged disease-free survival in one patient. Since prior treatment may compromise the ability to achieve a complete response to chemotherapy in patients with nodular lymphoma who develop an aggressive diffuse histology, the likelihood of histologic progression must be considered in the design of future clinical trials in nodular lymphoma. Histologic progression does not preclude attainment of a complete response to intensive chemotherapy.

  7. Transformative Clinical Trials in Non-Hodgkin and Hodgkin Lymphomas.

    PubMed

    Abramson, Jeremy S

    2015-06-01

    Dramatic progress in the understanding of underlying disease biology and the development of novel therapeutics has yielded a revolution that is poised to transform the face of lymphoma treatment across a broad spectrum of histologies. Ongoing randomized clinical trials are poised to unseat long-entrenched standards of care in diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, and Hodgkin lymphoma. Emerging treatment approaches are reviewed, including optimization of existing chemoimmunotherapy platforms, development of chemotherapy-sparing immunotherapy for follicular lymphoma, biologically targeted therapy for subsets of diffuse large B-cell lymphoma, and incorporation of novel agents into the treatment of mantle cell lymphoma and peripheral T-cell lymphoma. Novel therapies in early stage trials with future promise of redefining standards of care are also reviewed for non-Hodgkin and Hodgkin lymphomas, including small molecule pathway inhibitors and advances in immunotherapy.

  8. 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

    2017-01-31

    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

  9. MYC-driven aggressive B-cell lymphomas: biology, entity, differential diagnosis and clinical management

    PubMed Central

    Cai, Qingqing; Medeiros, L. Jeffrey; Xu, Xiaolu; Young, Ken H.

    2015-01-01

    MYC, a potent oncogene located at chromosome locus 8q24.21, was identified initially by its involvement in Burkitt lymphoma with t(8;14)(q24;q32). MYC encodes a helix-loop-helix transcription factor that accentuates many cellular functions including proliferation, growth and apoptosis. MYC alterations also have been identified in other mature B-cell neoplasms and are associated with aggressive clinical behavior. There are several regulatory factors and dysregulated signaling that lead to MYC up-regulation in B-cell lymphomas. One typical example is the failure of physiological repressors such as Bcl6 or BLIMP1 to suppress MYC over-expression. In addition, MYC alterations are often developed concurrently with other genetic alterations that counteract the proapoptotic function of MYC. In this review, we discuss the physiologic function of MYC and the role that MYC likely plays in the pathogenesis of B-cell lymphomas. We also summarize the role MYC plays in the diagnosis, prognostication and various strategies to detect MYC rearrangement and expression. PMID:26416427

  10. Non-Hodgkin lymphoma in the developing world: review of 4539 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

    2016-10-01

    The distribution of non-Hodgkin lymphoma subtypes varies around the world, but a large systematic comparative study has never been done. In this study, we evaluated the clinical features and relative frequencies of non-Hodgkin lymphoma subtypes in five developing regions of the world and compared the findings to the developed world. Five expert hematopathologists classified 4848 consecutive cases of lymphoma from 26 centers in 24 countries using the World Health Organization classification, and 4539 (93.6%) were confirmed to be non-Hodgkin lymphoma, with a significantly greater number of males than females in the developing regions compared to the developed world (P<0.05). The median age at diagnosis was significantly lower for both low- and high-grade B-cell lymphoma in the developing regions. The developing regions had a significantly lower frequency of B-cell lymphoma (86.6%) and a higher frequency of T- and natural killer-cell lymphoma (13.4%) compared to the developed world (90.7% and 9.3%, respectively). Also, the developing regions had significantly more cases of high-grade B-cell lymphoma (59.6%) and fewer cases of low-grade B-cell lymphoma (22.7%) compared to the developed world (39.2% and 32.7%, respectively). Among the B-cell lymphomas, diffuse large B-cell lymphoma was the most common subtype (42.5%) in the developing regions. Burkitt lymphoma (2.2%), precursor B- and T-lymphoblastic leukemia/lymphoma (1.1% and 2.9%, respectively) and extranodal natural killer/T-cell lymphoma (2.2%) were also significantly increased in the developing regions. These findings suggest that differences in etiologic and host risk factors are likely responsible, and more detailed epidemiological studies are needed to better understand these differences.

  11. Non-Hodgkin's lymphoma associated with Gaucher's disease.

    PubMed

    Perales, M; Cervantes, F; Cobo, F; Montserrat, E

    1998-11-01

    Gaucher's disease is an uncommon disorder which has been reported to be associated with an increased risk of lymphoproliferative disorders, including Non-Hodgkin's lymphoma (NHL). A new instance of such an association is described here. This was a 58 year-old-patient with adult type I Gaucher's disease who, one and a half year after the above diagnosis, presented with supraclavicular lymphadenopathy, massive splenomegaly, prominent retroperitoneal lymphadenopathy and increased serum LDH levels. This led to the diagnosis of large-cell NHL of B-cell type, successfully treated with chemotherapy. The previously published cases of Gaucher's disease associated with NHL as well as the possible mechanisms leading to this association are reviewed here.

  12. New drugs for aggressive B-cell and T-cell lymphomas.

    PubMed

    Murawski, Niels; Pfreundschuh, Michael

    2010-11-01

    Over the past decade an unprecedented number of new drugs for lymphomas have been developed. Most of these new drugs target molecules or pathways that are important for the growth and proliferation of lymphomas. The introduction of the B-lymphoma specific monoclonal anti-CD20 antibody, rituximab, has improved the prognosis of patients with B-cell lymphomas more than any other drug in the past 50 years; today less than half of the patients with aggressive B-cell lymphomas die of their disease than in the pre-rituximab era. Many new drugs are now available for clinical testing in addition to new CD20 antibodies and antibodies directed against other surface molecules specifically or preferentially expressed on the lymphoma-cell surface. A prerequisite for the development of these drugs was the recognition of aberrant cell-signal transduction involved in lymphoma pathogenesis and progression. New therapeutic targets include receptor tyrosine and cyclin-dependent kinases, histone deacetylases, and molecules involved in the regulation of apoptosis. The definition of the role of these new drugs alone or in combination with established chemotherapy regimens in adequately designed prospective trials represents one of the major challenges in clinical lymphoma research.

  13. UCH-L1 is induced in germinal center B cells and identifies patients with aggressive germinal center diffuse large B-cell lymphoma.

    PubMed

    Bedekovics, Tibor; Hussain, Sajjad; Feldman, Andrew L; Galardy, Paul J

    2016-03-24

    Gene expression profiling has identified 2 major subclasses of diffuse large B-cell lymphoma (DLBCL). Cases resembling germinal center (GC) B cells (GCB-DLBCL) generally occur in younger patients, have a distinct molecular pathophysiology, and have improved outcomes compared with those similar to activated post-GC cells (activated B-cell DLBCL). We previously found that the ubiquitin hydrolase UCH-L1 is frequently overexpressed in mature B-cell malignancies and is a potent oncogene in mice. The cause for its overexpression in lymphoma, and whether it impacts the outcome of patients with DLBCL is unknown. Here, we show that UCH-L1 reflects GC lineage in lymphoma and is an oncogenic biomarker of aggressive GCB-DLBCL. We find that UCH-L1 is specifically induced in GC B cells in mice and humans, and that its expression correlates highly with the GCB subtype in DLBCL. We also find that UCH-L1 cooperates with BCL6 in a mouse model of GC B-cell lymphoma, but not with the development of multiple myeloma derived from post-GC cells. Despite the typically good outcomes of GCB-DLBCL, increased UCHL1 identifies a subgroup with early relapses independent of MYC expression, suggesting biological diversity in this subset of disease. Consistent with this, forced Uchl1 overexpression had a substantial impact on gene expression in GC B cells including pathways of cell cycle progression, cell death and proliferation, and DNA replication. These data demonstrate a novel role for UCH-L1 outside of the nervous system and suggest its potential use as a biomarker and therapeutic target in DLBCL.

  14. p53, c-myc p62 and proliferating cell nuclear antigen (PCNA) expression in non-Hodgkin's lymphomas.

    PubMed Central

    Korkolopoulou, P; Oates, J; Kittas, C; Crocker, J

    1994-01-01

    AIMS--To investigate the immunohistochemical expression of p53 protein in non-Hodgkin's lymphomas (NHL) and its relation to that of c-myc p62 oncoprotein and proliferating cell nuclear antigen (PCNA). METHODS--Paraffin wax embedded tissue from 90 non-Hodgkin's lymphomas (72 B cell and 18 T cell) was stained immunohistochemically for p53 protein, c-myc p62 oncoprotein, and PCNA using the monoclonal antibodies DO7, c-myc 1-9 E10, and PC-10, respectively. RESULTS--Of the non-Hodgkin's lymphomas studied, 55 (61%) stained positively for p53 protein. The proportion of positive cases increased from low grade non-Hodgkin's lymphoma and was higher in tumours of T cell origin. The percentage of positive cells (labelling index or LI) was significantly lower in low grade non-Hodgkin's lymphoma, but no difference was established between intermediate and high grade non-Hodgkin's lymphoma. In a large proportion of low grade non-Hodgkin's lymphoma the LI was below 1%. c-myc p62 immunoreactivity was identified in all cases. A significant positive correlation was established between p53 LI and c-myc p62 LI (rs = 0.453) as well as between p53 LI and PCNA LI (rs = 0.338). CONCLUSIONS--p53 immunoreactivity was present in about half the cases of non-Hodgkin's lymphoma and was related to the grade of malignancy and possibly to the B or T cell origin of the tumour. It was also associated with the proliferation state as expressed by PCNA LI and c-myc p62 expression, indicating that the expression of these three cell cycle-related genes might be interrelated. Images PMID:7907610

  15. Unusually Aggressive Primary Testicular Diffuse Large B Cell Lymphoma with Post Therapy Extensive Metastasis

    PubMed Central

    Goel, Shalini; Mohapatra, Ishani; Gajendra, Smeeta; Gupta, Sunil

    2016-01-01

    Primary Testicular Lymphoma (PTL) is a rare intermediate to high grade tumour, diffuse large cell being the most common type. Unlike nodal Diffuse Large B-Cell Lymphoma (DLBCL), testicular DLBCL has a less aggressive course and better prognosis. Metastasis is uncommon in testicular DLBCL. Commonly involved sites are contralateral testes, Waldeyer’s ring, skin, lung, Central Nervous System (CNS) and prostate, however the kidneys, liver, bone marrow, pleura and bones are more rarely involved. We report a case of testicular DLBCL which has metastasized to skin and bone marrow with an aggressive clinical course in a year, in-spite of combined modality of therapy given to the patient. Bone marrow infiltration is common and well documented with nodal DLBCL, however there is no published literature for simultaneous bone marrow and skin infiltration in testicular DLBCL till date. Other large studies done in the west have shown that distinct metastasis is usually common but the median progression-free survival is usually in years. This case stresses on shorter period of progression after standard treatment protocol in this part of the world, thus highlighting the need for other extensive studies to define specific treatment protocol for testicular DLBCL. PMID:27630854

  16. Infection-associated non-Hodgkin lymphomas.

    PubMed

    Suarez, F; Lecuit, M

    2015-11-01

    Non-Hodgkin lymphomas (NHLs) are malignant proliferations of lymphoid cells. Lymphoid cells proliferate in a physiological manner in response to antigen-dependent and antigen-independent signals. Some lymphotropic viruses, such as Epstein-Barr virus and human T-lymphotropic virus 1, as well as pathogens leading to chronic antigenic stimulation (such as Helicobacter pylori and hepatitis C virus), are associated with NHL. We review here some of the pathophysiological features of infection-associated NHL.

  17. Uncommon non-Hodgkin lymphomas of childhood: pathological diagnosis, clinical features and treatment approaches.

    PubMed

    Sandlund, John T; Perkins, Sherrie L

    2015-06-01

    We provide a review of the pathological and clinical features for uncommon B-cell and T-cell lymphomas of childhood with a specific focus on advances in treatment approaches and outcomes. There is clearly a need for prospective investigation of both the clinical and biological features of the uncommon non-Hodgkin lymphoma subtypes in childhood. These results should lead to more uniform and more effective treatment approaches.

  18. Non-Hodgkin's lymphoma involving a femur bone and bilateral adrenal glands alone with adrenal insufficiency.

    PubMed

    Iwahara, Yoshihito; Shinohara, Tsutomu; Naruse, Keishi; Komatsu, Yukihisa

    2017-01-31

    Primary bone lymphoma and primary adrenal lymphoma are rare clinicopathological entities of non-Hodgkin's lymphoma (NHL). We present the first case of diffuse large B-cell lymphoma with the involvement of a single bone and both adrenal glands alone with adrenal insufficiency. As primary extranodal NHL may have other unusual extranodal lesions, which may present unexplained clinical findings, patients with primary extranodal NHL require careful systemic examination, even when lymphadenopathy is absent.

  19. [Radiotherapy in localized stages of follicular and diffuse non-Hodgkin's lymphomas].

    PubMed

    Demoor-Goldschmidt, C; Agape, P; Barillot, I; Mahé, M A

    2016-10-01

    Treatment with monoclonal antibodies, especially rituximab, is more and more frequent and questions the interest of radiotherapy in limited stages of diffuse B-cell large cell and follicular non-Hodgkin's lymphomas. From a review of literature, it appears that radiotherapy is of interest in bulky disease, patients with incomplete metabolic response, elderly patients receiving short chemotherapy and those with recurrence after exclusive chemotherapy. Finally, this article gives recommendations on available techniques of radiotherapy and doses to be delivered.

  20. A rare spindle-cell variant of non-Hodgkin's lymphoma of the mandible

    PubMed Central

    Srikant, N; Yinti, Shanmukha Raviteja; Baliga, Mohan; Kini, Hema

    2016-01-01

    A 64-year-old male farmer presented with a rapidly progressive swelling of the left mandible since 6 months. The swelling was firm to hard, diffuse, nontender, obliterating the vestibule with paresthesia of lower lip. The cone beam computed tomography imaging revealed an ill-defined, moth-eaten radiolucency with destruction of the buccal and lingual cortical plates. The rapid growth and aggressive behavior of the lesion coupled with guidance from the patient's previous reports from the incisional biopsy and fine needle aspiration cytology warranted a mandibular resection. Microscopic examination showed an encapsulated lesion situated in the connective tissue containing a mixture of proliferating spindle-shaped cells arranged in fascicles and round cells infiltrating into the connective tissue stroma and bone. The neoplastic cells exhibited atypical features such as pleomorphism, hyperchromatism and increased mitotic figures with noncleaved nuclei. A working diagnosis of a spindle-cell sarcoma was arrived at with various differentials provided such as fibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, Langerhans cell histiocytosis and lymphoma and stating the need for immunohistochemistry to subtype the tumor. The neoplastic cells were negative for Van Gieson's stain and Masson's trichrome. Immunohistochemical analysis performed using desmin, smooth muscle actin, S-100 and CD1a in a bid to determine the phenotype of the tumor and rule out the previously stated differentials were all negative for the lesion. Lymphoid markers such as leukocyte common antigen and CD20 (cluster differentiation marker for B-cells) showed positivity in spindle-shaped cells as well as round cells indicating the tumor to be a lymphoproliferative lesion of B-cell type. A final diagnosis of “spindle-cell variant of non-Hodgkin's lymphoma” was rendered based on the immunohistochemical profile. PMID:27194875

  1. Concurrent Systemic Chemoimmunotherapy and Sofosbuvir-Based Antiviral Treatment in a Hepatitis C Virus-Infected Patient With Diffuse Large B-Cell Lymphoma

    PubMed Central

    Shah, Phalgoon A.; Carmichael, Mark G.; Ferguson, Tomas M.

    2016-01-01

    Hepatitis C virus (HCV) infection is associated with the development of non-Hodgkin lymphomas. For aggressive lymphomas, such as diffuse large B-cell lymphoma (DLBCL), treatment of HCV infection is typically deferred in treatment-naive patients until after completion of lymphoma therapy [1, 2]. We report a case of HCV-associated stage IV DLBCL successfully treated concurrently using chemoimmunotherapy and a sofosbuvir-based antiviral regimen. PMID:28018926

  2. Management of Non-Hodgkin Lymphoma: ICMR Consensus Document.

    PubMed

    Thacker, Nirav; Bakhshi, Sameer; Chinnaswamy, Girish; Vora, Tushar; Prasad, Maya; Bansal, Deepak; Agarwala, Sandeep; Kapoor, Gauri; Radhakrishnan, Venkatraman; Laskar, Siddharth; Kaur, Tanvir; Rath, G K; Dhaliwal, Rupinder Singh; Arora, Brijesh

    2017-04-05

    Hitherto poor outcomes, paucity of data and heterogeneity in International approach to Pediatric NHL (Non-Hodgkin Lymphoma) prompted the need for guidelines for Indian population with vast variability in access, affordability and infrastructure across the country. These guidelines are based on consensus among the experts and best available evidence applicable to Indian setting. Evaluation of NHL should consist of easily doable and rapid tissue diagnosis (biopsy or flow cytometry of peripheral blood/malignant effusions), St Jude/IPNHLSS (International Pediatric Non-Hodgkin Lymphoma Staging System) and risk grouping with CSF (Cerebro-spinal fluid), bone marrow, whole body imaging [CECT (Contrast enhanced computerized tomography) ± MRI (Magnetic resonance imaging)] and blood investigations for LDH (Lactate dehydrogenase), TLS (Tumor lysis syndrome) and organ functions. Life threatening complications like SVCS (Superior vena cava syndrome)/Mediastinal syndrome and TLS need to pre-empted and promptly managed. All children with poor general condition, co-morbidities, metabolic or obstructive complications should receive a steroid or chemotherapy pro-phase first. For mature B-NHL (B cell - Non-Hodgkin lymphoma), in centres with good infrastructure and methotrexate levels, FAB-LMB-96 (French-American-British/Lymphomes Malins B) or BFM (Berlin-Frankfurt-Münster)-NHL-95 protocols may be used. In centres with limited infrastructure and/or no methotrexate levels; CHOP (Cyclophosphamide-hydroxydaunomycin-oncovin-prednisolone) (early stage) or MCP (Multi-centre protocol)-842 [all stages except CNS (Central nervous system) disease] may be used. Patients with poor early response should have escalated therapy. High-Risk B-NHL will benefit with addition of Rituximab to standard chemotherapy. Radiotherapy (RT) is not warranted. For lymphoblastic lymphoma, in centres with good infrastructure and methotrexate levels, BFM-95 protocol may be used. In centres with limited

  3. 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

  4. Continuous infusion of vincristine-doxorubicin with bolus of dexamethasone(VAD) alternated with CHEP in the treatment of patients over 60 years old with aggressive non-Hodgkin's lymphoma.

    PubMed

    Cartron, G; Voillat, L; Desablens, B; Le Maignan, C; Milpied, N; Foussard, C; Dugay, J; Maakaroun, A; De Muret, A; Colombat, P

    2001-02-01

    This prospective study was undertaken to evaluate the efficacy and toxicity of combination chemotherapy with alternating cycles of vincristine, doxorubicin and dexamethasone (VAD) and cyclophophamide, doxorubicin, etoposide and prednisone (CHEP) in patients over 60 years old with previously untreated and advanced non-Hodgkin's lymphoma (NHL) of intermediate- and high-grade malignancy. Eighty one consecutive, patients with NHL referred from April 1992 to October 1997 to GOELAMS centers were enrolled in this study and their outcome updated to June 1, 1999. Of 81 enrolled patients, 77 were eligible and assessable for response. The median age was 70 years (61 to 78), 85.7% were stage III or IV, 39% were of performance status > or = 2, 27.3% > or = 2 involved extra-nodal sites and 57.3% had higher LDH levels than normal. The immunophenotype was B in 87% and T in 13%. Fifty-one (66.2%) patients received the scheduled eight cycles of therapy and treatment was withdrawn in only 6 patients (7.8%) because of toxicity. Neutropenia grade 3-4 occurred in 11.1% after VAD courses vs 40.6% after CHEP courses. The mean cumulative dose of doxorubicin was 269 mg/m2 and the relative dose intensity was 84%. The overall response and complete response rates were 66.2% and 51.9% respectively, and after a median follow-up of 52 months the 3 year overall survival (OS) and event-free survival rates (EFS) were 43.5% and 33.0% respectively. In multivariate analysis, OS and EFS were statistically influenced by IPI (p = 3 x 10(-3); p < 1 x 10(-4)) and phenotype (p = 2 x 10(-3); p < 1 x 10(-4)). Our findings support the alternation of 4 courses of VAD and CHEP as it is well tolerated in patients over 60 years old with advanced intermediate- or high-grade NHL and provides response and survival rates comparable to 6 courses of CHOP.

  5. Quantitative analysis of non-Hodgkin's lymphoma.

    PubMed Central

    Abbott, C R; Blewitt, R W; Bird, C C

    1982-01-01

    A preliminary attempt has been made to characterise a small series of non-Hodgkin's lymphomas (NHL) by morphometric means using the Quantimet 720 Kontron MOP/AMO3 image analysis systems. In most cases it was found that the distribution of nuclear area and correlation between mean nuclear area and frequency per unit field, corresponded closely with tumour classification determined by light microscopy. These results suggest that it may be possible to devise an objective and reproducible grading system for NHL using quantitative morphometric techniques. PMID:7040479

  6. Adrenal involvement in non-Hodgkin lymphoma

    SciTech Connect

    Paling, M.R.; Williamson, B.R.J.

    1983-08-01

    Adrenal masses are described in seven cases of non-Hodgkin lymphoma in a series of 173 patients. In all seven patients the lymphoma was diffuse rather than nodular. Three patients had adrenal masses at the time of presentation, whereas in four cases the adrenal gland was a site of tumor recurrence after therapy. Three patients had simultaneous bilateral adrenal involvement by tumor. No characteristic features were recognized that might have distinguished these tumors from other adrenal masses. Appropriate therapy successfully resolved the adrenal masses in all but one case. The latter patient was the only one with evidence of adrenal insufficiency.

  7. L744,832 and Everolimus Induce Cytotoxic and Cytostatic Effects in Non-Hodgkin Lymphoma Cells.

    PubMed

    Mendes, José; Gonçalves, Ana Cristina; Alves, Raquel; Jorge, Joana; Pires, Ana; Ribeiro, Ana; Sarmento-Ribeiro, Ana Bela

    2016-04-01

    Non-Hodgkin Lymphoma (NHL) constitutes a very heterogeneous group of diseases with different aggressiveness. Diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma (BL) are two clinically aggressive lymphomas from the germinal center, very heterogeneous and with different genetic signatures. Several intracellular pathways are involved in lymphomagenesis, being BCR/PI3K/AKT/mTOR and RAS/RAF pathways the most frequently ones. In this context the therapeutic potential of a mTOR inhibitor--everolimus--and a RAS/RAF pathway inhibitor--L744,832--was evaluated in two NHL cell lines. Farage and Raji cells were cultured in the absence and presence of several concentrations of everolimus and L744,832 in monotherapy and in combination with each other, as well as in association with the conventional chemotherapy drug vincristine. Our results show that everolimus and L744,832 induce antiproliferative and cytotoxic effect in a time-, dose-, and cell line-dependent manner, inducing cell death mainly by apoptosis. A potentiation effect was observed when the drugs were used in combination. In conclusion, the results suggest that everolimus and L744,832, alone or in combination, could provide therapeutic benefits in these subtypes of NHL.

  8. Non-Hodgkin lymphomas in pregnancy: tackling therapeutic quandaries.

    PubMed

    Avivi, Irit; Farbstein, Dan; Brenner, Benjamin; Horowitz, Netanel A

    2014-09-01

    Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) often present with systemic symptoms such as fatigue, shortness of breath and night sweats, mimicking pregnancy-related features which may result in delayed disease diagnosis. Furthermore, the wish to avoid investigational imaging, aiming to protect the fetus from radiation exposure, may lead to a further delay, which does not often result in significant changes in HL clinical nature and patient outcome. In contrast, a more aggressive behavior (i.e., advanced disease stage and reproductive organ involvement) of most NHL types diagnosed in pregnancy may require urgent therapeutic intervention to prevent disease progression. Current management of pregnancy-associated NHL depends on histological subtype of the disease, gestational stage at diagnosis and the urgency of treatment for a specific patient. Patients diagnosed with indolent lymphoma may often be just followed, whereas those presenting with aggressive or highly aggressive disease need to be urgently treated with chemoimmunotherapy, either after undergoing an elective pregnancy termination if diagnosed at an early gestational stage, or with pregnancy preservation, if diagnosed later. Supportive care of NHL is also important; however, granulocyte colony stimulating factor (G-CSF) which is commonly used outside of pregnancy, should be cautiously employed, considering its established teratogenicity in animals, though this is less proven in humans. In conclusion, given the paucity of studies prospectively evaluating the outcome of pregnant women with NHL, international efforts are warranted to elucidate critical issues and develop guidelines for the management of such patients.

  9. New drugs for the treatment of non-Hodgkin lymphomas.

    PubMed

    Smith, Sonali M

    2015-03-01

    Non-Hodgkin lymphomas (NHL) are diverse diseases either of mature B-cell or T-cell derivation. Despite being generally chemosensitive diseases, the last decade has focused on developing more targeted agents based on improved insights of underlying biology. The hope is that more targeted and biologically rational treatments will improve both the efficacy and toxicity profile of standard approaches, with the ultimate goal of improving clinical outcomes. Among the newest agents to be approved are inhibitors of B-cell receptor (BCR) and PI3K signaling; however, a number of other classes of agents such as selective inhibitors of nuclear export (SINE), inhibitors of immune regulation such as PD1 inhibitors, and small molecule inhibitors of apoptosis are on the horizon. In addition, growing clinical evidence supports continued and new applications for immunomodulatory agents, proteasome inhibitors and histone deacetylase inhibitors. Altogether, this is an exciting time for NHL, with a number of promising agents and early clinical data. The key path forward will be to better apply these new agents in a personalized way, which will hopefully constitute the next generation of trials.

  10. Non-Hodgkin lymphoma with relapses in the lacrimal glands

    PubMed Central

    Couceiro, Rita; Proença, Helena; Pinto, Filomena; Fonseca, Ana; Monteiro-Grillo, Manuel

    2015-01-01

    Objective: To report an unusual case of systemic non-Hodgkin lymphoma (NHL) with repeated relapse in the lacrimal glands, in spite of complete remission for several years after treatment. Methods: A 78-year-old male with small lymphocytic B cell NHL, stage IV disease (lung invasion), was submitted to surgery and chemotherapy in 2001, with complete remission of the disease. In 2003 he developed a nodular lesion in the right lacrimal fossa. Pathology results revealed a local relapse of NHL. Radiation and chemotherapy were initiated and complete remission was again achieved. In 2012 the patient developed a new nodular lesion located in the left lacrimal fossa, resulting in diplopia, ptosis and proptosis of the left eye. Orbital computerized tomography (CT), ocular ultrasound and incisional biopsy were performed. Results: Orbital CT revealed a lesion infiltrating the left lacrimal gland and encircling the globe. Biopsy results confirmed a local relapse of B cell NHL. The patient was submitted to local radiation therapy with progressive resolution of ptosis, proptosis and diplopia. Response to treatment was monitored with ocular ultrasound. Conclusions: Patients with NHL diagnosis should be immediately investigated if ophthalmic or orbital symptoms develop. NHL extension to the orbit and adnexa is infrequent (5% of NHL cases) but may occur at any stage of the disease, including as a relapse site. In such cases, radiation and chemotherapy achieve good results, inducing long periods of remission. PMID:27625948

  11. Obinutuzumab for relapsed or refractory indolent non-Hodgkin's lymphomas.

    PubMed

    Gabellier, Ludovic; Cartron, Guillaume

    2016-04-01

    The use of anti-CD20 monoclonal antibodies (mAbs), such as rituximab, in CD20-positive B-cell malignancies has dramatically improved the outcome of chronic lymphoid leukemia and non-Hodgkin's lymphomas (NHL). However, the occurrence of relapse and development of rituximab-refractory disease highlight the need to develop novel anti-CD20 mAbs, with improved mechanisms of action. Obinutuzumab is the first humanized type II glycoengineered anti-CD20 mAb. In vitro and in vivo data suggested several differences compared with rituximab, including a low level of complement-dependent cytotoxicity and an increased direct nonapoptotic cell death. Moreover, the glycoengineered Fc-linked nonfucosylated oligosaccharide enhanced the Fc-Fcγ receptor (FcγR) IIIa interaction, resulting in improved antibody-dependent cellular cytotoxicity and phagocytosis. Preclinical models suggested that these differences translate into superior survival in murine lymphoma models. Phase I/II trials in monotherapy in relapsed or refractory B-cell NHL demonstrated that obinutuzumab has an acceptable safety profile, infusion-related reactions being the most common adverse event. In rituximab-refractory indolent NHL, the recent randomized phase III GADOLIN study demonstrated an improved median progression-free survival for patients treated with obinutuzumab plus bendamustine rather than bendamustine alone. Further trials are ongoing to determine the role of obinutuzumab as a first-line agent in the treatment of follicular lymphoma.

  12. 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

  13. 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.

  14. Non-Hodgkin's lymphomas: clinical governance issues.

    PubMed

    Fields, P A; Goldstone, A H

    2002-09-01

    Every patient in every part of the world has the right to expect the best possible quality of care from health care providers. Non-Hodgkin's lymphomas (NHL) are an extremely heterogeneous group of conditions which require important decisions to be taken at many points along the treatment pathway. To get this right every time requires that high-quality standards are instituted and adhered to, so that the best possible outcome is achieved. In the past this has not always been the case because of the failure of clinicians sometimes to adhere to an optimal management plan. In 1995, the UK government commissioned an inquiry into the running of cancer services in the United Kingdom, which culminated in a series of recommendations to improve them. Subsequently, these recommendations were implemented as objectives of the NHS Cancer Plan which is the framework by which the UK government wishes to improve cancer services. Concurrently another general concept has emerged which is designed to ensure that the highest quality standards may be achieved for all patients across the whole National Health Service (NHS). This concept, termed 'clinical governance', brings together a corporate responsibility of all health care workers to deliver high quality standards, in the hope that this will translate into better long-term survival of patients with malignant disease. This chapter focuses on the issues surrounding clinical governance and how the principles of this concept relate to non-Hodgkin's lymphomas.

  15. Primary Non-Hodgkin Lymphoma of the Breast: Ultrasonography, Elastography, Digital Mammography, Contrast-Enhanced Digital Mammography, and Pathology Findings.

    PubMed

    Gkali, Christina An; Chalazonitis, Athanasios N; Feida, Eleni; Giannos, Aris; Sotiropoulou, Maria; Dimitrakakis, Constantine; Loutradis, Dimitrios

    2015-12-01

    Lymphomas constitute approximately 0.15% of malignant mammary neoplasms. Less than 0.5% of all malignant lymphomas involve the breast primarily. Primary non-Hodgkin breast lymphoma is usually right sided. The combined therapy approach, with chemotherapy and radiotherapy, is the most successful treatment. Mastectomy offers no benefit in the treatment of primary non-Hodgkin breast lymphoma. To the author's knowledge, this is the first published case of primary non-Hodgkin breast lymphoma reported with conventional ultrasonography, elastography (both freehand and acoustic radiation force impulse imaging), digital mammography, contrast-enhanced digital mammography, and pathology findings. A 45-year-old woman presented with a lump in the right breast for 2 months. There was no evidence of systemic lymphoma or leukemia when the breast lesion was detected. Imaging findings were negative for lymphoma. Ipsilateral lymph nodes were not palpable. The mass was resected, and histopathology findings were diagnostic of non-Hodgkin lymphoma. Immunohistochemistry was confirmatory of non-Hodgkin lymphoma, diffuse large cell type of B-cell lineage. Although primary and secondary lymphomas of the breast are rare entities, they should be considered in the differential diagnosis of breast malignancies.

  16. Long term outcome of localized aggressive non-Hodgkin lymphoma treated with a short weekly chemotherapy regimen (doxorubicin, cyclophosphamide, bleomycin, vincristine, and prednisone) and involved field radiotherapy: result of a Gruppo Italiano Multiregionale per lo Studio dei Linfomi e Leucenie (GIMURELL) study.

    PubMed

    Cabras, Maria Giuseppina; Mamusa, Angela Maria; Vitolo, Umberto; Freilone R, Roberto; Dessalvi, Paolo; Orsucci, Lorella; Tonso, Anna; Levis, Alessandro; Liberati, Marina; Lay, Giancarlo; Angelucci, Emanuele

    2009-09-01

    Recently, management of limited stage diffuse large cell lymphoma (DLCL) is trending toward a low intensity chemotherapy approach. Since 1993 we have used a brief weekly (6 weeks) chemotherapy scheme (Doxorubicin, Cyclophosphamide, Bleomycin, Vincristine, and Prednisone = ACOP-B) followed by involved field radiotherapy in 207 consecutive patients with well defined localized DLCL without age limit (median 57 years, range 18-85). Treatment was completed as designed in 183 of 207 patients (88%). One hundred and ninety-nine patients (96%) achieved complete remission. At a median follow-up of 66 months 170 patients are alive (82%), 168 of them free of disease. Twenty-nine patients experienced relapse after achieving a complete remission. Kaplan-Meier, risk of relapse was 24% after 13 years. Thirty (14.5%) patients have died, 14 (6.8%) due to lymphoma progression, one due to regimen toxicity and 15 (7.2%) from other causes while remaining in complete remission. The probability of overall survival and event free survival at 13 years was 78% (95% CI 70-87%) and 63% (95% CI 50-75), respectively. Crude rate of secondary malignancy was 5.26 /1000 person-years. The ACOP-B regimen plus involved field radiotherapy is well tolerated both short and long term and is an effective chemotherapy scheme for very well defined limited stage aggressive non-Hodgkin lymphomas in all age categories.

  17. Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

    PubMed Central

    Ford, Catriona A.; Petrova, Sofia; Pound, John D.; Voss, Jorine J.L.P.; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L.; Gallimore, Awen M.; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E.; Dunbar, Donald R.; Murray, Paul G.; Ruckerl, Dominik; Allen, Judith E.; Hume, David A.; van Rooijen, Nico; Goodlad, John R.; Freeman, Tom C.; Gregory, Christopher D.

    2015-01-01

    Summary Background Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Results Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. Conclusions In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. PMID:25702581

  18. Trends in incidence, treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989-2010.

    PubMed

    Issa, Djamila E; van de Schans, Saskia A M; Chamuleau, Martine E D; Karim-Kos, Henrike E; Wondergem, Marielle; Huijgens, Peter C; Coebergh, Jan Willem W; Zweegman, Sonja; Visser, Otto

    2015-04-01

    Only a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment and survival in an unselected patient population. We included all patients aged 15 years and older with newly diagnosed diffuse large B-cell lymphoma or Burkitt lymphoma in the period 1989-2010 and mantle cell lymphoma in the period 2001-2010, with follow up until February 2013. We examined incidence, first-line treatment and survival. We calculated annual percentage of change in incidence and carried out relative survival analyses. Incidence remained stable for diffuse large B-cell lymphoma (n=23,527), while for mantle cell lymphoma (n=1,634) and Burkitt lymphoma (n=724) incidence increased for men and remained stable for women. No increase in survival for patients with aggressive B-cell lymphoma was observed during the period 1989-1993 and the period 1994-1998 [5-year relative survival 42% (95%CI: 39%-45%) and 41% (38%-44%), respectively], but increased to 46% (43%-48%) in the period 1999-2004 and to 58% (56%-61%) in the period 2005-2010. The increase in survival was most prominent in patients under 65 years of age, while there was a smaller increase in patients over 75 years of age. However, when untreated patients were excluded, patients over 75 years of age had a similar increase in survival to younger patients. In the Netherlands, survival for patients with aggressive B-cell lymphoma increased over time, particularly in younger patients, but also in elderly patients when treatment had been initiated. The improvement in survival coincided with the introduction of rituximab therapy and stem cell transplantation into clinical practice.

  19. Trends in incidence, treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989–2010

    PubMed Central

    Issa, Djamila E.; van de Schans, Saskia A.M.; Chamuleau, Martine E.D.; Karim-Kos, Henrike E.; Wondergem, Marielle; Huijgens, Peter C.; Coebergh, Jan Willem W.; Zweegman, Sonja; Visser, Otto

    2015-01-01

    Only a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment and survival in an unselected patient population. We included all patients aged 15 years and older with newly diagnosed diffuse large B-cell lymphoma or Burkitt lymphoma in the period 1989–2010 and mantle cell lymphoma in the period 2001–2010, with follow up until February 2013. We examined incidence, first-line treatment and survival. We calculated annual percentage of change in incidence and carried out relative survival analyses. Incidence remained stable for diffuse large B-cell lymphoma (n=23,527), while for mantle cell lymphoma (n=1,634) and Burkitt lymphoma (n=724) incidence increased for men and remained stable for women. No increase in survival for patients with aggressive B-cell lymphoma was observed during the period 1989–1993 and the period 1994–1998 [5-year relative survival 42% (95%CI: 39%–45%) and 41% (38%–44%), respectively], but increased to 46% (43%–48%) in the period 1999–2004 and to 58% (56%–61%) in the period 2005–2010. The increase in survival was most prominent in patients under 65 years of age, while there was a smaller increase in patients over 75 years of age. However, when untreated patients were excluded, patients over 75 years of age had a similar increase in survival to younger patients. In the Netherlands, survival for patients with aggressive B-cell lymphoma increased over time, particularly in younger patients, but also in elderly patients when treatment had been initiated. The improvement in survival coincided with the introduction of rituximab therapy and stem cell transplantation into clinical practice. PMID:25512643

  20. A Case of p63 Positive Diffuse Large B Cell Lymphoma of the Bladder

    PubMed Central

    Jones, Carol

    2016-01-01

    Diffuse large B cell lymphoma (DLBCL), currently the most common type of non-Hodgkin lymphoma (NHL), is an aggressive B cell neoplasm that typically presents in older adults as a rapidly enlarging mass. The enlarging mass typically represents a lymph node, although extranodal disease can occur in a significant percentage (40%) of cases. The most common extranodal sites of involvement include the gastrointestinal tract and skin; primary bladder lymphoma represents only 0.2% of extranodal non-Hodgkin lymphomas. We report a case of diffuse large B cell lymphoma occurring in the bladder of an 83-year-old gentleman with an initial presentation of hematuria. This neoplasm displayed large, atypical cells with vesicular chromatin and prominent nucleoli that involved the bladder mucosa with invasion into muscularis propria, prostate, and urethra. Positive staining for p63 initially raised suspicion for poorly differentiated urothelial carcinoma; however, lack of staining for pancytokeratin and positive staining for LCA, CD20, CD79a, and PAX-5 confirmed the diagnosis of diffuse large B cell lymphoma. Though it does not occur in all cases, p63 can be positive in a significant percentage of cases of DLBCL; therefore, a diagnosis of lymphoma remains an important entity on the differential diagnosis of aggressive and particularly poorly differentiated neoplasms. PMID:27648316

  1. 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

  2. Diagnostic laparotomy in non-Hodgkin's lymphoma.

    PubMed Central

    Jelliffe, A. M.

    1975-01-01

    Twenty patients with non-Hodgkin's lymphoma (NHL) were investigated by diagnostic laparotomy. These patients were seen over a 3 1/2 year period during which a total of 78 patients with NHL were seen. Laparotomy was considered unsuitable in 58 patients, either because widespread disease was easily demonstrated by simpler means or because of their poor general medical condition. Laparotomy revealed more extensive disease in 14 patients. Although laparotomy is proving to be a worthwhile investigative procedure, it is less likely to be useful as a routine investigation than is the case with Hodgkin's disease. Widespread involvement of mesenteric lymph nodes is common and among the 10 patients with a poor histological grade of tumour, 2 with negative laparotomy findings developed disease in the abdomen within 3 months of operation. PMID:1182072

  3. Idelalisib for the treatment of non-Hodgkin lymphoma

    PubMed Central

    Gopal, Ajay; Graf, Solomon

    2016-01-01

    Introduction B-cell Non-Hodgkin lymphomas (B-NHLs) include a number of disease subtypes, each defined by the tempo of disease progression and the identity of the cancerous cell. Idelalisib is a potent, selective inhibitor of the delta isoform of phosphatidylinositol-3-kinase (PI3K), a lipid kinase whose over-activity in B-NHL drives disease progression. Idelalisib has demonstrated activity in indolent B-NHL (iB-NHL) and is approved for use as monotherapy in patients with follicular lymphoma and small lymphocytic lymphoma and in combination with rituximab in patients with chronic lymphocytic leukemia. Areas Covered Herein we review the development and pharmacology of idelalisib, its safety and efficacy in clinical studies of iB-NHL, and its potential for inclusion in future applications in iB-NHL and in combination with other therapies. Expert Opinion Idelalisib adds to the growing arsenal of iB-NHL pharmacotherapeutics and to the progression of the field toward precision agents with good efficacy and reduced toxicities. Nevertheless, idelalisib carries important risks that require careful patient counseling and monitoring. The appropriate sequencing of idelalisib with other proven treatment options in addition to its potential for combination with established or novel drugs will be borne out in ongoing and planned investigations. PMID:26818003

  4. Testicular non-Hodgkin's lymphoma presenting in a young adult

    PubMed Central

    Ratkal, Vishal; Chawla, Arun; Mishra, Dilip Kumar; Monappa, Vidya

    2015-01-01

    We report a case of a 27-year-old man who presented with a slowly growing left testicular swelling associated with mild pain over a period of 3 months. He was evaluated by his family physician with scrotal ultrasound and testicular tumour markers. He was diagnosed and treated as epididymo-orchitis and managed with antibiotics. When he later presented to us, he had an enlarged left testis with normal spermatic cord. Scrotal Doppler evaluation showed a globally enlarged left testis and epididymis with increased vascularity in the left testis, with the right testis being normal. Testicular tumour markers were normal. Fine-needle aspiration cytology of the left testis was suggestive of lymphoma. Exploration through an inguinal approach was carried out and a Chevassu manoeuvre with frozen section study was performed, which was reported as non-Hodgkin's lymphoma. Left radical orchidectomy was performed. Histopathology reported diffuse large B-cell lymphoma, of a germinal centre type. Contrast CT of the abdomen, chest and brain were normal. Sperm cryopreservation was carried out. The patient was started on chemotherapy with cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone (CHOP) regime. PMID:25795748

  5. Phase II Study of Yttrium-90-Ibritumomab Tiuxetan as Part of Reduced-Intensity Conditioning (with Melphalan, Fludarabine ± Thiotepa) for Allogeneic Transplantation in Relapsed or Refractory Aggressive B Cell Lymphoma: A GELTAMO Trial.

    PubMed

    Cabrero, Monica; Martin, Alejandro; Briones, Javier; Gayoso, Jorge; Jarque, Isidro; López, Javier; Grande, Carlos; Heras, Inmaculada; Arranz, Reyes; Bernal, Teresa; Perez-Lopez, Estefania; López-Godino, Oriana; Conde, Eulogio; Caballero, Dolores

    2017-01-01

    We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (.4 m Ci/kg, day -14), fludarabine 30 mg/m(2) i.v. (days -3 and -2) plus melphalan 70 mg/m(2) i.v. (days -3 and -2) or 1 dose of melphalan and thiotepa 5 mg/kg (day -8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P = .046) and OS (71% versus 27%, P = .047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT.

  6. What Is Non-Hodgkin Lymphoma?

    MedlinePlus

    ... grow and spread quickly. These are known as aggressive lymphomas, and they usually need to be treated right away. The most common type of aggressive lymphoma in the United States is diffuse large ...

  7. Second cancers following non-Hodgkin's lymphoma

    SciTech Connect

    Travis, L.B.; Curtis, R.E.; Boice, J.D. Jr.; Hankey, B.F.; Fraumeni, J.F. Jr. )

    1991-04-01

    The risk of second malignancies following non-Hodgkin's lymphoma (NHL) was estimated in 29,153 patients diagnosed with NHL between 1973 and 1987 in one of nine areas participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Compared with the general population, NHL patients were at a significantly increased risk of developing second cancers (observed/expected (O/E) = 1.18; O = 1231). The O/E ratio increased significantly with time to reach 1.77 in 10-year survivors. Significant excesses were noted for acute nonlymphocytic leukemia (O/E = 2.88), cancers of the bladder (O/E = 1.30), kidney (O/E = 1.47), and lung (O/E = 1.57), malignant melanoma (O/E = 2.44), and Hodgkin's disease (O/E = 4.16). Chemotherapy appeared related to subsequent acute nonlymphocytic leukemia (ANLL) and bladder cancer. Radiation therapy was associated with ANLL and possibly cancers of the lung, bladder, and bone. Malignant melanoma was not clearly related to initial NHL treatment.

  8. 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

  9. [Diagnosis and treatment of primary testicular non-Hodgkin lymphoma].

    PubMed

    Romics, Miklós; Demeter, Judit; Romics, Imre; Nyirády, Péter

    2014-01-12

    The primary testicular non-Hodgkin lymphoma, which has been first described in 1866, is a very uncommon type of urological neoplasia occuring mostly in the elderly ages. It only gives 5% of the testicular tumors, 2% of extranodal lymphomas, and barely 1% of all non-Hodgkin diseases. Patients with testicular non-Hodgkin lymphomas need prompt multidisciplinary aid because without treatment the outcome can be unfavorable. The authors discuss the attributes, diagnostic modalities and treatment options of the primary testicular non-Hodgkin lymphoma and present a case of a 68-year-old patient who underwent orchiectomy, chemo- and radiotherapy after having been diagnosed with the tumor. The follow-up PET-CT and cerebrospinal fluid analysis found no further sign of the disease, and complete remission has been achieved.

  10. Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2017-01-06

    B-Cell Prolymphocytic Leukemia; Hypodiploidy; Loss of Chromosome 17p; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; t(14;16); t(4;14); T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  11. CT demonstration of peripelvic and periureteral non-Hodgkin lymphoma

    SciTech Connect

    McMillin, K.I.; Gross, B.H.

    1985-05-01

    Abdominal CT is often performed for the staging of lymphoma. Retroperitoneal lymphadenopathy is the most common abnormality identified, but various extranodal sites of lymphomatous involvement have been reported, especially in non-Hodgkin lymphoma. Renal involvement is not rare, but peripelvic or periureteral involvement in the absence of renal parenchymal involvement or contiguous abdominal adenopathy is extremely unusual. Two recent patients with non-Hodgkin lymphoma who did show these findings are presented.

  12. Bilateral adrenal non-Hodgkin's lymphoma with adrenal insufficiency

    PubMed Central

    Ellis, R; Read, D

    2000-01-01

    A 74 year old women presented with lethargy and weight loss and was found to have profound adrenal insufficiency and bilateral adrenal mass lesions. Histological examination revealed non-Hodgkin's lymphoma. There was no evidence of lymphoma outside the adrenal glands. Isolated bilateral adrenal masses may rarely be due to primary adrenal non-Hodgkin's lymphoma, which is often associated with adrenal insufficiency.


Keywords: lymphoma; adrenal insufficiency PMID:10908383

  13. [Therapy in Hodgkin disease and non-Hodgkin lymphomas].

    PubMed

    Sréter, Lídia

    2009-04-05

    The therapy of malignant lymphoproliferative diseases has changed many times in recent years. Treatment strategy of Hodgkin's disease is now based on risk adaptation, including not only the results of pretreatment diagnostic and prognostic factors but also the repeated PET/CT (restaging) made in the early treatment period. Possible reduction of irradiation therapy may contribute to lower the risk of secondary tumors, which are common late complications of radiochemotherapy. Autologous stem cell transplantation is the therapy of choice in chemosensitive relapsing patients. The complete remission rate today in Hodgkin's disease is around 85%. In the heterogenic group of Non-Hodgkin Lymphomas, progression of indolent lymphomas (CLL, multiple myeloma, hairy cell leukemia, cutaneous lymphomas, etc.) is slow in case of natural course. Their therapy is mostly palliative and complete remission with the latest treatment modalities is not possible. Aggressive lymphomas are characterized with rapid progression and early death without treatment.Most of them respond to chemotherapy and irradiation.With an adequate therapy, 60-70% of patients reach complete remission (CR) and 40-50% of them remain in remission. Using immune- and radioimmune therapy in indolent and aggressive NHL groups gives possibility to influence G0 tumor cells as well. Their use in combination with classic chemotherapy leads to more complete remissions and better therapy results. The introduction of routine PET/CT made the first and repeated staging of NHL more precise and contributed to more effective treatment. Using autologous stem cell transplantation in chemosensitive patients may improve outcome in selected patients.

  14. Primary Cutaneous Diffuse Large B-Cell Lymphoma With a MYC-IGH Rearrangement and Gain of BCL2: Expanding the Spectrum of MYC/BCL2 Double-Hit Lymphomas.

    PubMed

    Testo, Natalia; Olson, Luke C; Subramaniyam, Shivakumar; Hanson, Ty; Magro, Cynthia M

    2016-10-01

    Aggressive extracutaneous B-cell lymphomas span the various stages of B-cell ontogeny and include B-cell lymphoblastic lymphoma, Burkitt lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma. Diffuse large B-cell lymphomas represent the most common histologic subtype of non-Hodgkin lymphomas, comprising 30% of adult non-Hodgkin lymphomas in the United States. A distinctive form of diffuse large B-cell lymphoma is the double-hit lymphoma, with most cases exhibiting a combined MYC and BCL2 rearrangement, leading some hematopathologists to propose the term MYC/BCL2 lymphoma. More recently, MYC rearrangement with multiple copies/gain of BCL2 or multiple copies/gain of MYC with a BCL2 rearrangement have been described and exhibit a very similar clinical course to conventional double-hit lymphomas. We report the seventh case of diffuse large B-cell lymphoma exhibiting this distinct cytogenetic abnormality and the first reported case in the skin. The patient's clinical course was aggressive, succumbing to disease 18 months after his initial presentation.

  15. B-cell lymphomas with MYC/8q24 rearrangements and IGH@BCL2/t(14;18)(q32;q21): an aggressive disease with heterogeneous histology, germinal center B-cell immunophenotype and poor outcome.

    PubMed

    Li, Shaoying; Lin, Pei; Fayad, Luis E; Lennon, Patrick A; Miranda, Roberto N; Yin, C Cameron; Lin, E; Medeiros, L Jeffrey

    2012-01-01

    B-cell lymphomas with MYC/8q24 rearrangement and IGH@BCL2/t(14;18)(q32;q21), also known as double-hit or MYC/BCL2 B-cell lymphomas, are uncommon neoplasms. We report our experience with 60 cases: 52 MYC/BCL2 B-cell lymphomas and 8 tumors with extra MYC signals plus IGH@BCL2 or MYC rearrangement plus extra BCL2 signals/copies. There were 38 men and 22 women with a median age of 55 years. In all, 10 patients had antecedent/concurrent follicular lymphoma. Using the 2008 World Health Organization classification, there were 33 B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (henceforth referred to as unclassifiable, aggressive B-cell lymphoma), 23 diffuse large B-cell lymphoma, 1 follicular lymphoma grade 3B, 1 follicular lymphoma plus diffuse large B-cell lymphoma, 1 B-lymphoblastic lymphoma, and 1 composite diffuse large B-cell lymphoma with B-lymphoblastic lymphoma. Using older classification systems, the 33 unclassifiable, aggressive B-cell lymphomas most closely resembled Burkitt-like lymphoma (n=24) or atypical Burkitt lymphoma with BCL2 expression (n=9). Of 48 cases assessed, 47 (98%) had a germinal center B-cell immunophenotype. Patients were treated with standard (n=23) or more aggressive chemotherapy regimens (n=34). Adequate follow-up was available for 57 patients: 26 died and 31 were alive. For the 52 patients with MYC/BCL2 lymphoma, the median overall survival was 18.6 months. Patients with antecedent/concurrent follicular lymphoma had median overall survival of 7.8 months. Elevated serum lactate dehydrogenase level, ≥2 extranodal sites, bone marrow or central nervous system involvement, and International Prognostic Index >2 were associated with worse overall survival (P<0.05). Morphological features did not correlate with prognosis. Patients with neoplasms characterized by extra MYC signals plus IGH@BCL2 (n=6) or MYC rearrangement with extra BCL2 signals (n=2) had overall survival

  16. Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia.

    PubMed Central

    Gauwerky, C E; Huebner, K; Isobe, M; Nowell, P C; Croce, C M

    1989-01-01

    We have analyzed the oncogene rearrangements involving BCL2 and MYC in the leukemia cells of a patient with an aggressive prolymphocytic leukemia that had an abnormal karyotype including a t(14;18) translocation and a chromosome 17q+. Molecular analysis showed that BCL2 was rearranged in the major breakpoint cluster region and had joined into the immunoglobulin heavy chain gene as in follicular lymphoma. Cloning and sequence analysis of the rearranged MYC gene revealed that MYC was truncated at the Pvu II site at the end of the first exon of MYC and had joined into the regulatory elements of a gene that we called BCL3 (B-cell leukemia/lymphoma 3). The BCL3 locus was mapped to chromosome 17 band q22. We found BCL3 transcribed as a message of 1.7 kilobases in many hematopoietic cell lines representing all hematopoietic lineages. In the patient's leukemia cells, the truncated MYC gene was highly expressed under the influence of BCL3 regulatory elements, leading to an aggressive B-cell leukemia that presumably had been derived from an indolent lymphoma carrying a rearranged BCL2 gene. Images PMID:2682663

  17. Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET

    SciTech Connect

    Halasz, Lia M.; Jacene, Heather A.; Catalano, Paul J.; Van den Abbeele, Annick D.; LaCasce, Ann; Mauch, Peter M.; Ng, Andrea K.

    2012-08-01

    Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [{sup 18}F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT.

  18. LMO2-negative Expression Predicts the Presence of MYC Translocations in Aggressive B-Cell Lymphomas.

    PubMed

    Colomo, Luis; Vazquez, Ivonne; Papaleo, Natalia; Espinet, Blanca; Ferrer, Anna; Franco, Catalina; Comerma, Laura; Hernandez, Silvia; Calvo, Xavier; Salar, Antonio; Climent, Fina; Mate, José Luis; Forcada, Pilar; Mozos, Anna; Nonell, Lara; Martinez, Antonio; Carrio, Anna; Costa, Dolors; Dlouhy, Ivan; Salaverria, Itziar; Martin-Subero, Jose Ignacio; Lopez-Guillermo, Armando; Valera, Alexandra; Campo, Elias

    2017-03-10

    MYC translocation is a defining feature of Burkitt lymphoma (BL), and the new category of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 translocations, and occurs in 6% to 15% of diffuse large B-cell lymphomas (DLBCLs). The low incidence of MYC translocations in DLBCL makes the genetic study of all these lymphomas cumbersome. Strategies based on an initial immunophenotypic screening to select cases with a high probability of carrying the translocation may be useful. LMO2 is a germinal center marker expressed in most lymphomas originated in these cells. Mining gene expression profiling studies, we observed LMO2 downregulation in BL and large B-cell lymphoma (LBCL) with MYC translocations, and postulated that LMO2 protein expression could assist to identify such cases. We analyzed LMO2 protein expression in 46 BLs and 284 LBCL. LMO2 was expressed in 1/46 (2%) BL cases, 146/268 (54.5%) DLBCL cases, and 2/16 (12.5%) high-grade B-cell lymphoma cases with MYC and BCL2 and/or BCL6 translocations. All BLs carried MYC translocation (P<0.001), whereas LMO2 was only positive in 6/42 (14%) LBCL with MYC translocation (P<0.001). The relationship between LMO2 negativity and MYC translocation was further analyzed in different subsets of tumors according to CD10 expression and cell of origin. Lack of LMO2 expression was associated with the detection of MYC translocations with high sensitivity (87%), specificity (87%), positive predictive value and negative predictive value (74% and 94%, respectively), and accuracy (87%) in CD10 LBCL. Comparing LMO2 and MYC protein expression, all statistic measures of performance of LMO2 surpassed MYC in CD10 LBCL. These findings suggest that LMO2 loss may be a good predictor for the presence of MYC translocation in CD10 LBCL.

  19. Epidemiology of Non-Hodgkin's Lymphoma in India.

    PubMed

    Nair, Reena; Arora, Neeraj; Mallath, Mohandas K

    2016-01-01

    Non-Hodgkin's lymphoma (NHL) is a common hematological malignancy. The age-adjusted incidence rates for NHL in men and women in India are 2.9/100,000 and 1.5/100,000, respectively. These are about one fourth of the incidence rates reported from Western Europe or North America. Within India, the incidence is several-fold higher in urban cancer registries compared to rural areas; the incidence being higher in metropolitan cities and Indian immigrants suggesting that urban lifestyles and economic progress may increase the cancer incidence. Compared to developed nations, the key differences in the presentation in India include: median age of 54 years (almost a decade less), higher male to female ratio, higher proportion of patients with B-symptoms (40-60 vs. 20-30%), poor ECOG performance status (≥2) at diagnosis (50 vs. 20-30%), higher frequency of diffuse large B-cell lymphomas (60-70 vs. <40%), lower frequency of follicular NHL (<20 vs. 30-40%) and T-cell type in 10-20 vs. <10%. The estimated mortality rate due to NHL is higher in India than in North America and Western Europe. Diagnostic and treatment delays, incorrect diagnosis and inappropriate or suboptimal treatment may be possible reasons for the poor outcome. Any improvement in the outcomes for NHL in India will require a nationwide approach, e.g. creation of several regional and district-level centers with expertise in lymphoma management. Collection of data on patient- and disease-related characteristics, treatment outcome, development of infrastructure, centralized review of histopathology subtype, novel treatment protocols, rigorous follow-up, training of staff, and financial support towards treatment could be possible strategies to improve the outcome.

  20. Gene Therapy Shows Promise for Aggressive Lymphoma

    MedlinePlus

    ... fullstory_163824.html Gene Therapy Shows Promise for Aggressive Lymphoma Over one-third of patients appeared disease- ... 2017 (HealthDay News) -- An experimental gene therapy for aggressive non-Hodgkin lymphoma beat back more than a ...

  1. Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

    ClinicalTrials.gov

    2017-03-13

    Activated B-Cell-Like Diffuse Large B-Cell Lymphoma; ALK-Positive Large B-Cell Lymphoma; Atypical Burkitt/Burkitt-Like Lymphoma; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma of the Elderly; Epstein-Barr Virus-Positive Mucocutaneous Ulcer; Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma; High-Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements; Human Herpesvirus-8-Positive Neoplastic Cells Present; Intravascular Large B-Cell Lymphoma; MYC-Negative B-Cell Lymphoma With 11q Aberration Resembling Burkitt Lymphoma; Plasmablastic Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Primary Effusion Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Lymphomatoid Granulomatosis; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Skin Ulcer; Small Intestinal B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

  2. BET Inhibition Induces Apoptosis in Aggressive B-Cell Lymphoma via Epigenetic Regulation of BCL-2 Family Members.

    PubMed

    Hogg, Simon J; Newbold, Andrea; Vervoort, Stephin J; Cluse, Leonie A; Martin, Benjamin P; Gregory, Gareth P; Lefebure, Marcus; Vidacs, Eva; Tothill, Richard W; Bradner, James E; Shortt, Jake; Johnstone, Ricky W

    2016-09-01

    Targeting BET bromodomain proteins using small molecules is an emerging anticancer strategy with clinical evaluation of at least six inhibitors now underway. Although MYC downregulation was initially proposed as a key mechanistic property of BET inhibitors, recent evidence suggests that additional antitumor activities are important. Using the Eμ-Myc model of B-cell lymphoma, we demonstrate that BET inhibition with JQ1 is a potent inducer of p53-independent apoptosis that occurs in the absence of effects on Myc gene expression. JQ1 skews the expression of proapoptotic (Bim) and antiapoptotic (BCL-2/BCL-xL) BCL-2 family members to directly engage the mitochondrial apoptotic pathway. Consistent with this, Bim knockout or Bcl-2 overexpression inhibited apoptosis induction by JQ1. We identified lymphomas that were either intrinsically resistant to JQ1-mediated death or acquired resistance following in vivo exposure. Strikingly, in both instances BCL-2 was strongly upregulated and was concomitant with activation of RAS pathways. Eμ-Myc lymphomas engineered to express activated Nras upregulated BCL-2 and acquired a JQ1 resistance phenotype. These studies provide important information on mechanisms of apoptosis induction and resistance to BET-inhibition, while providing further rationale for the translation of BET inhibitors in aggressive B-cell lymphomas. Mol Cancer Ther; 15(9); 2030-41. ©2016 AACR.

  3. MicroRNA-155 influences B-cell receptor signaling and associates with aggressive disease in chronic lymphocytic leukemia.

    PubMed

    Cui, Bing; Chen, Liguang; Zhang, Suping; Mraz, Marek; Fecteau, Jessie-F; Yu, Jian; Ghia, Emanuela M; Zhang, Ling; Bao, Lei; Rassenti, Laura Z; Messer, Karen; Calin, George A; Croce, Carlo M; Kipps, Thomas J

    2014-07-24

    High-level leukemia cell expression of micro-RNA 155 (miR-155) is associated with more aggressive disease in patients with chronic lymphocytic leukemia (CLL), including those cases with a low-level expression of ζ-chain-associated protein of 70 kD. CLL with high-level miR-155 expressed lower levels of Src homology-2 domain-containing inositol 5-phosphatase 1 and were more responsive to B-cell receptor (BCR) ligation than CLL with low-level miR-155. Transfection with miR-155 enhanced responsiveness to BCR ligation, whereas transfection with a miR-155 inhibitor had the opposite effect. CLL in lymphoid tissue expressed higher levels of miR155HG than CLL in the blood of the same patient. Also, isolated CD5(bright)CXCR4(dim) cells, representing CLL that had been newly released from the microenvironment, expressed higher levels of miR-155 and were more responsive to BCR ligation than isolated CD5(dim)CXCR4(bright) cells of the same patient. Treatment of CLL or normal B cells with CD40-ligand or B-cell-activating factor upregulated miR-155 and enhanced sensitivity to BCR ligation, effects that could be blocked by inhibitors to miR-155. This study demonstrates that the sensitivity to BCR ligation can be enhanced by high-level expression of miR-155, which in turn can be induced by crosstalk within the tissue microenvironment, potentially contributing to its association with adverse clinical outcome in patients with CLL.

  4. R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2017-03-03

    Diffuse Large B-Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  5. Pegfilgrastim to support CHOP-14 in elderly patients with non-Hodgkin's lymphoma.

    PubMed

    Wolf, Max; Bentley, Mark; Marlton, Paula; Horvath, Noemi; Lewis, Ian D; Spencer, Andrew; Herrmann, Richard; Arthur, Chris; Durrant, Simon; van Kerkhoven, Marilyn; MacMillan, Jamie; Mrongovius, Robert

    2006-11-01

    This study investigated whether pegfilgrastim support would enable on-schedule delivery of dose-dense cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP-14) to elderly patients with non-Hodgkin's lymphoma (NHL). Thirty patients 60 years of age and older with aggressive NHL were evaluated after receiving up to six cycles of CHOP-14 supported with pegfilgrastim. The median age was 68 years (range 61 - 74). Forty-seven per cent of patients received full dose chemotherapy on schedule for all cycles (range 65 - 93). Chemotherapy was delayed in 10 patients and dose reduced in 15 patients. Hematological toxicity was the most common reason for delays and dose reduction. Six of nine patients (67%) achieved a peripheral blood CD34+ count of at least 20 cellsx106 L-1 on day 12 of cycle one. The delivery on schedule of dose-dense CHOP-14 to elderly patients with previously untreated aggressive NHL is safe and efficacious with once per cycle pegfilgrastim support.

  6. Risk of non-Hodgkin's lymphoma following tuberculosis

    PubMed Central

    Askling, J; Ekbom, A

    2001-01-01

    To study the association between chronic infections and non-Hodgkin's lymphoma (NHL), we assessed the risk of NHL in a Swedish cohort of 5050 individuals with tuberculosis 1939–1960. The overall relative risk was moderately increased, largely accounted for by high risks following severe tuberculosis diagnosed a long time ago. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11139323

  7. Restaging laparotomy in the management of the non-Hodgkin lymphomas

    SciTech Connect

    Fuks, J.Z.; Aisner, J.; Wiernik, P.H.

    1982-01-01

    The intensity of treatment and the extent of restaging necessary to document the level of response to therapy in patients with non-Hodgkin lymphoma (NHL) remains controversial. One hundred patients with advanced non-Hodgkin lymphoma were randomized to treatment with cyclophosphamide, vincristine, plus prednisone or cyclophosphamide, doxorubicin, vincristine, plus prednisone combination chemotherapy. After induction therapy sequential noninvasive restaging including lymphagiogram and /sup 67/Ga scan yielded 33 patients in clinical complete remission and 38 patients in partial remission. Twenty of these 38 patients in partial remission had complete normalization of all clinical and chemical tests (apparent clinical partial remission); however, lymphangiogram, gallium scan, abdominal sonogram, or abdominal CAT scan remained abnormal. In these 20 patients in apparent clinical partial remission, exploratory laparotomy was performed to further assess disease status. Laparotomy revealed evidence of residual disease in only four patients (20%). When correlated with the laparotomies the accuracy of repeat lymphangiograms and gallium scans was 17% and 50% respectively. Thus, restaging lymphangiogram and gallium scan in NHL patients in apparent clinical partial remission are inaccurate, and second look operations are recommended for accurate appraisal of response to therapy. The assessment of true complete remission should help define the role of aggressive treatment.

  8. Novel Brentuximab Vedotin Combination Therapies Show Promising Activity in Highly Refractory CD30+ Non-Hodgkin Lymphoma: A Case Series and Review of the Literature

    PubMed Central

    Setlik, Robert; Hassantoufighi, Arash; Daya, Shyam; Selby, Dale; Brown, Alexander

    2016-01-01

    Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of hematologic malignancies which typically respond to standard first-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent an unmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximab vedotin- (BV-) based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL) with cranial nerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate (MTX), and cytarabine (hyperCVAD) with intrathecal- (IT-) MTX and IT-cytarabine, but responded when BV was substituted for vincristine (hyperCBAD). The second patient was a man with stage IV diffuse large B-cell lymphoma (DLBCL) with leptomeningeal involvement whose disease progressed during first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and progressed despite salvage therapy with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in whom addition of BV to topotecan resulted in a significant response. This report describes the first successful salvage treatments of highly aggressive, double refractory CD30+ NHL using two unreported BV-based chemoimmunotherapy regimens. Both regimens appear effective and have manageable toxicities. Further clinical trials assessing novel BV combinations are warranted. PMID:27807492

  9. Oral clofarabine for relapsed/refractory non-Hodgkin lymphomas: results of a phase 1 study.

    PubMed

    Abramson, Jeremy S; Takvorian, Ronald W; Fisher, David C; Feng, Yang; Jacobsen, Eric D; Brown, Jennifer R; Barnes, Jeffrey A; Neuberg, Donna S; Hochberg, Ephraim P

    2013-09-01

    We conducted a phase 1 trial evaluating the oral nucleoside analog 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 six cycles. The study was conducted with a 3 + 3 design with 10 additional patients treated at the recommended phase 2 dose. Thirty patients were enrolled including indolent B-cell lymphomas (n = 21), mantle cell lymphoma (n = 6) and diffuse large B-cell lymphoma (n = 3). The primary toxicities were hematologic including grade 3-4 neutropenia (53%) and thrombocytopenia (27%). Three milligrams 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.

  10. Switching to BCL-6 Negativity in Relapsed Diffuse Large B Cell Lymphoma Correlated with More Aggressive Disease Course.

    PubMed

    Todorović, Milena; Balint, Bela; Andjelic, Bosko; Radisavljevic, Ziv; Mihaljevic, Biljana

    2014-12-01

    Diffuse large B-cell lymphoma (DLBCL) is the most frequent, complex and heterogeneous lymphoma of adulthood. Heterogeneity is expressed at clinical, genetic, and molecular levels. It is known that BCL-6 expression is a favorable prognostic factor in DLBCL. However, the underlying mechanisms of BCL-6 expression in DLBCL relapse are not yet elucidated. Here, we present so far undescribed clinical phenomenon of switching BCL-6(+) protein expression into BCL-6(-) expression in 19 of 41 relapsed DLBCL patients. The switch in relapsed DLBCL was associated with more aggressive clinical course of the disease. Bone marrow infiltration and high IPI risk were more often present in BCL-6(-) patients. Significantly increased biochemical parameters, such as LDH, beta-2 macroglobulin, CRP, and ferritin have been found, as well as significantly decreased serum Fe, TIBC, and hemoglobin. A Ki-67 proliferation marker was considerably high in relapsed DLBCL, but without significant differences between BCL-6(+) and BCL-6(-) groups of patients. Thus, switching of the positive into negative BCL-6 expression during DLBCL relapse could be used as a prognostic factor and a valuable criterion for treatment decision.

  11. Primary non-Hodgkin's lymphoma of the lung presenting as bronchiolitis obliterans organizing pneumonia.

    PubMed

    Safadi, R; Berkman, N; Haviv, Y S; Ben-Yehuda, A; Amir, G; Naparstek, Y

    1997-12-01

    A 44-year-old man presented with fever, dyspnea, and bilateral cavitary lung lesions. Following percutaneous transthoracic CT guided needle biopsy of the lung, a diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) was made and the patient was treated with corticosteroids. Despite a good initial response he developed new lung lesions within six months, associated with a lack of response to corticosteroids. Due to further deterioration and the development of Guillian-Barre' syndrome an open lung biopsy was performed and revealed T-cell rich, B-cell non Hodgkin's lymphoma with BOOP. We suggest that BOOP may be the presenting manifestation of primary lung lymphoma. We recommend that when BOOP has an atypical course or does not respond to corticosteroids open lung biopsy should be performed in order to exclude pulmonary lymphoma.

  12. Paraneoplastic Opsoclonus-Myoclonus Syndrome: initial presentation of non-Hodgkins lymphoma.

    PubMed

    Kumar, Ashwani; Lajara-Nanson, Walter A; Neilson, Robert W

    2005-05-01

    A 69 year-old man developed sudden-onset multidirectional, constant, involuntary ocular movements associated with vertigo, truncal ataxia and involuntary movements of the lower limbs. These features were typical of opsoclonus-myoclonus-ataxia syndrome (OMS). MRI of the brain was normal. CSF studies showed a single oligoclonal IgG band. A chest x-ray showed a 2-centimeter lesion in the periphery of the left lung. Fine needle aspiration biopsy of this lesion revealed large B-cell lymphoma. OMS can be either idiopathic or a paraneoplastic manifestation of underlying malignancy. 20 of OMS cases are paraneoplastic in origin; breast and lung cancer are responsible for 70 of these. Association of this syndrome with non-Hodgkins lymphoma is rare, with only one case previously reported.

  13. Disparities in conditional net survival among non-Hodgkin lymphoma survivors: a population-based analysis.

    PubMed

    Migdady, Yazan; Salhab, Mohammed; Dang, Nam H; Markham, Merry J; Olszewski, Adam J

    2016-01-01

    We evaluated the association of baseline prognostic factors with conditional net survival among survivors of six subtypes non-Hodgkin lymphoma using the SEER program data from 2000-2012. Among 2-year survivors, further prognosis markedly improved in Burkitt's (BL) and diffuse large B-cell lymphoma (DLBCL), and became the same as for follicular lymphoma (5-year net survival ≥ 85%). Mantle cell lymphoma (MCL) demonstrated the worst prognosis of all studied histologies up to 5 years of survivorship. Age and stage lost prognostic significance in BL within 2 years from diagnosis. Racial disparities in net survival disappeared within 2 years for all subtypes, except in chronic lymphocytic leukemia, where black patients had persistently worse prognosis, and in MCL, where they had unexpectedly better prognosis than other races after 2 years. Many baseline factors may lose their initial prognostic value for lymphoma survivors, which should be considered when counseling patients about their prognosis and long-term surveillance.

  14. Advancing radioimmunotherapy and its future role in non-Hodgkin lymphoma.

    PubMed

    Reagan, Patrick M; Friedberg, Jonathan W

    2015-01-01

    Radioimmunotherapy is an effective treatment modality with an acceptable toxicity profile in both indolent B-cell non-Hodgkin lymphoma and histologic transformation. Its ease of administration from a patient's perspective sets it apart from chemoimmunotherapy regimens. It has demonstrated efficacy in a range of different treatment scenarios. Despite its promise as a treatment modality, radioimmunotherapy has been seldom used, and one of the previously available agents is now off the market. Radioimmunotherapy has shown impressive activity in both the relapsed and upfront settings in follicular lymphoma, histologic transformation, as consolidation after chemotherapy, and in conjunction with high-dose chemotherapy and autologous stem cell support. Future efforts should focus on its optimal employment in the upfront setting for follicular lymphoma as well as further investigation of the promising activity in histologic transformation.

  15. Unusual presentation of non-Hodgkin's lymphoma: Case report and review of literature

    PubMed Central

    Shaikh, Abubakar Badshaha; Waghmare, Sneha; Koshti-Khude, Supriya; Koshy, Ajit Vergese

    2016-01-01

    The non-Hodgkin's lymphoma (NHLs) is a diverse group of lymphoid neoplasms, prevalence of which increased since three decades. NHL is diverse in the manner of presentation, response to various treatment and prognosis. NHL usually involves not only lymph nodes but also extranodal sites. Usually, oral manifestation of NHL is secondary to the widespread involvement throughout the body. Oral NHL is relatively rare and difficult to diagnose in clinical setting as it presents as local swelling, pain, discomfort and mimics pyogenic granuloma, periodontal disease, osteomyelitis and other malignancies. Sometimes, oral lesion may present as the early disease (primary site). Careful evaluation of patient and proper investigations is required for correct diagnosis so that patient will receive the treatment in early stage which has a good prognosis. Here, we are presenting the case of low-grade B-cell NHL of palate of a 92-year-old man. PMID:27721619

  16. Non-Hodgkin lymphoma as a cause of obstructive jaundice with simultaneous extrahepatic portal vein obstruction: a case report.

    PubMed

    Hashimoto, Masao; Umekita, Nobutaka; Noda, Kazumasa

    2008-07-07

    Non-Hodgkin lymphoma is a rare cause of biliary obstruction. To the best of our knowledge, non-Hodgkin lymphoma in the peripancreatic region causing obstructive jaundice with simultaneous portal vein (PV) invasion has not yet been reported. We present a 50-year-old patient with obstructive jaundice whose extrahepatic portal vein was obstructed by the invasion of a peripancreatic non-Hodgkin lymphoma. The patient denied any other symptoms such as recurrent fever, night sweat and loss of body weight. Computed tomography (CT) revealed a 10 cm mass in the retroperitoneal space behind the head of the pancreas causing obstruction of the distal bile duct and the PV. A pylorus-preserving pancreaticoduodenectomy combined with a PV resection was performed. The PV was reconstructed using an autologous right internal jugular vein graft. The resected specimen showed endoluminal invasion of both the bile duct and the PV. Histological examination showed the mass consisting of diffuse sheets of large malignant lymphoid cells. These cells were positive for CD20 and CD79a, partially positive for CD10, and negative for CD3, CD4, CD5, CD8 and CD30. The pathologic diagnosis was diffuse large B-cell type non-Hodgkin lymphoma and the patient was transferred to the Department of Hematology and Oncology for chemotherapy. He received four cycles of combined chemotherapy including cyclophosphamide, doxorubicin, vincristine and prednisone plus rituximab, and three cycles of intrathecal chemoprophylaxis including methotorexate, cytosine arbinoside and prednisone. The patient is alive with no evidence of the disease for 7 mo after operation and will receive additional courses of chemotherapy.

  17. 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

    2016-12-02

    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

  18. Perinephric stranding and bulky psoas mimicking pyelonephritis in a case of non-Hodgkin lymphoma of kidney.

    PubMed

    Singh, Shrawan Kumar; Sharma, Aditya Prakash; Mittal, Ankur; Lal, Anupam

    2015-05-01

    A 68-year-old male patient presented with fever and right groin pain. He had leukocytosis with azotemia. Computed tomography revealed enlarged right kidney with thickening and enhancement of walls of pelvicalyceal system and perinephric fat stranding, suggestive of pyelonephritis. Multiple enlarged lymph nodes encased right renal vessels and were present in the retrocaval region. The right psoas muscle was bulky. Fine-needle aspiration cytology and biopsy from the lesions showed features of non-Hodgkin lymphoma. Immunohistochemistry confirmed the diagnosis of diffuse, large, B-cell lymphoma. We emphasize lymphoma in differential diagnosis of atypical renal imaging suggestive of pyelonephritis and perinephritis.

  19. Ipilimumab and Local Radiation Therapy in Treating Patients With Recurrent Melanoma, Non-Hodgkin Lymphoma, Colon, or Rectal Cancer

    ClinicalTrials.gov

    2017-01-12

    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

  20. 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

  1. Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-12-06

    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

  2. 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

  3. Multimodality therapy of favorable prognosis non-Hodgkin's lymphoma

    SciTech Connect

    Corder, M.P.; Leimert, J.T.; Tewfik, H.H.; Lovett, J.M.

    1983-07-01

    Twenty-seven previously untreated patients with favorable prognosis non-Hodgkin's lymphoma were treated with a combination of total body irradiation followed by cyclophosphamide - vincristine - prednisone (CVP). The dose of total body irradiation was planned to be 150 rad followed by 6 cycles of chemotherapy. The complete response rate was 59%; the complete plus partial response rate, 93%. The 50% disease-free survival was 8 months. The actuarial projected 5 year survival was 60% and the disease-free survival at 5 years was 27%. The program was well tolerated by the majority of patients. It is possible for some patients with favorable non-Hodgkin's lymphomas to achieve prolonged periods of disesase-free survival when treated with combinations of irradiation plus chemotherapy.

  4. Non-Hodgkin's lymphoma: case control epidemiological study in Yorkshire.

    PubMed

    Cartwright, R A; McKinney, P A; O'Brien, C; Richards, I D; Roberts, B; Lauder, I; Darwin, C M; Bernard, S M; Bird, C C

    1988-01-01

    This paper reports the results of a case control study of non-Hodgkin's lymphoma in the Yorkshire Health Region. In all, 437 cases and 724 controls were interviewed. Risk factors associated with past skin conditions, family history of cancer and infectious mononucleosis, aspects of social life and contact with wood dust and epoxy glues all emerge. A comparison of high and low grade morphological forms of disease reveal contrasting risks and suggest separate aetiologies for these conditions.

  5. Extranodal oral non-Hodgkin's lymphomas. A retrospective study of 40 cases in Argentina.

    PubMed

    Keszler, Alicia; Piloni, María J; Paparella, María L; Soler, Marcela de Dios; Ron, Patricia Cabrera; Narbaitz, Marina

    2008-01-01

    A retrospective study was conducted of extranodal oral Non-Hodgkin's Lymphomas diagnosed at the Surgical Pathology Laboratory of the School of Dentistry at Buenos Aires University, Argentina, between 1985 and 2004. The 40 cases found represent 0.2% of the oral biopsies diagnosed during that time and 4.6% of malignant neoplasias. Overall mean age of patients was 49.4 years, and frequency was greater in males. 80% affected soft tissues. Prevalent location was gingival, followed by palate. Intraosseous cases were more frequent in mandible (75%) than in upper maxilla. 100% of the cases were phenotype B, with a higher frequency of high-grade aggressiveness. The most common histological type was Diffuse Large Cell Lymphoma. 60% of the Plasmablastic Lymphomas in the series came from HIV+ patients. Evolution time prior to consultation was 1 to 3 months in 57.7% of the cases.

  6. NCCN Guidelines Insights: Non-Hodgkin's Lymphomas, Version 3.2016.

    PubMed

    Horwitz, Steven M; Zelenetz, Andrew D; Gordon, Leo I; Wierda, William G; Abramson, Jeremy S; Advani, Ranjana H; Andreadis, C Babis; Bartlett, Nancy; Byrd, John C; Fayad, Luis E; Fisher, Richard I; Glenn, Martha J; Habermann, Thomas M; Lee Harris, Nancy; Hernandez-Ilizaliturri, Francisco; Hoppe, Richard T; Kaminski, Mark S; Kelsey, Christopher R; Kim, Youn H; Krivacic, Susan; LaCasce, Ann S; Lunning, Matthew; Nademanee, Auayporn; Press, Oliver; Rabinovitch, Rachel; Reddy, Nishitha; Reid, Erin; Roberts, Kenneth; Saad, Ayman A; Sokol, Lubomir; Swinnen, Lode J; Vose, Julie M; Yahalom, Joachim; Zafar, Nadeem; Dwyer, Mary; Sundar, Hema; Porcu, Pierluigi

    2016-09-01

    Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant. In recent years, several newer agents have shown significant activity in patients with relapsed or refractory disease across all 4 subtypes of PTCL. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for NHL, specific to the management of patients with relapsed or refractory PTCL.

  7. Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients

    PubMed Central

    Marini, Olivia; Spina, Cecilia; Mimiola, Elda; Cassaro, Adriana; Malerba, Giovanni; Todeschini, Giuseppe; Perbellini, Omar; Scupoli, Maria; Carli, Giuseppe; Facchinelli, Davide; Cassatella, Marco; Scapini, Patrizia; Tecchio, Cristina

    2016-01-01

    Human granulocytic myeloid-derived suppressor cells (G-MDSCs) have been described as low-density immunosuppressive CD66b+CD33dimHLA-DR-granulocytes that co-purify with mononuclear cells after density gradient centrifugation of blood from cancer patients. The role of G-MDSCs in Hodgkin (HL) and non-Hodgkin lymphoma (NHL) remains unclear. The percentage and immunophenotype of CD66b+CD33dimHLA-DR-cells were analyzed in PBMCs from HL and B-cell NHL patients (n = 124) and healthy donors (n = 48). The immunosuppressive functions of these cells were tested in vitro. Correlations between CD66b+CD33dimHLA-DR-cells and patient clinicopathological features and outcome, were evaluated. CD66b+CD33dimHLA-DR-cells were increased in PBMCs from HL and B-cell NHL patients as compared to healthy donors: 2.18 (0.02–70.92) vs 0.42 (0.04–2.97), p < 0.0001. Their percentage remained significantly higher even considering HL (n = 31), indolent (n = 31) and aggressive (n = 62) B-cell NHL patients separately: 1.54 (0.28–26.34), 2.15 (0.02–20.08), and 2.96 (0.25–70.92), respectively, p < 0.0001. CD66b+CD33dimHLA-DR-cells in patient PBMCs were mostly composed of mature CD11b+CD16+ low-density neutrophils in an activated status, as revealed by their higher CD11b and CD66b expression as compared to conventionally isolated (normal-density) autologous or healthy donor neutrophils. The in vitro depletion of CD66b+ cells from patient PBMCs restored the proliferation of autologous T cells. Higher frequencies of CD66b+CD33dimHLA-DR− G-MDSCs correlated significantly with unfavorable prognostic index scores and a shorter freedom from disease progression. PBMCs from HL and B-cell NHL patients contain a population of CD66b+CD33dimHLA-DR− G-MDSCs, mostly composed of activated low-density neutrophils with immunosuppressive properties. These findings disclose a previously unknown G-MDSC-mediated mechanism of immune-escape in lymphomas, therefore anticipating possible targets for therapeutic

  8. Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci.

    PubMed

    Wang, Sophia S; Vajdic, Claire M; Linet, Martha S; Slager, Susan L; Voutsinas, Jenna; Nieters, Alexandra; de Sanjose, Silvia; Cozen, Wendy; Alarcón, Graciela S; Martinez-Maza, Otoniel; Brown, Elizabeth E; Bracci, Paige M; Lightfoot, Tracy; Turner, Jennifer; Hjalgrim, Henrik; Spinelli, John J; Zheng, Tongzhang; Morton, Lindsay M; Birmann, Brenda M; Flowers, Christopher R; Paltiel, Ora; Becker, Nikolaus; Holly, Elizabeth A; Kane, Eleanor; Weisenburger, Dennis; Maynadie, Marc; Cocco, Pierluigi; Foretova, Lenka; Staines, Anthony; Davis, Scott; Severson, Richard; Cerhan, James R; Breen, Elizabeth C; Lan, Qing; Brooks-Wilson, Angela; De Roos, Anneclaire J; Smith, Martyn T; Roman, Eve; Boffetta, Paolo; Kricker, Anne; Zhang, Yawei; Skibola, Christine; Chanock, Stephen J; Rothman, Nathaniel; Benavente, Yolanda; Hartge, Patricia; Smedby, Karin E

    2015-03-15

    Autoimmune conditions and immune system-related genetic variations are associated with risk of non-Hodgkin lymphoma (NHL). In a pooled analysis of 8,692 NHL cases and 9,260 controls from 14 studies (1988-2007) within the International Lymphoma Epidemiology Consortium, we evaluated the interaction between immune system genetic variants and autoimmune conditions in NHL risk. We evaluated the immunity-related single nucleotide polymorphisms rs1800629 (tumor necrosis factor gene (TNF) G308A), rs1800890 (interleukin-10 gene (IL10) T3575A), rs6457327 (human leukocyte antigen gene (HLA) class I), rs10484561 (HLA class II), and rs2647012 (HLA class II)) and categorized autoimmune conditions as primarily mediated by B-cell or T-cell responses. We constructed unconditional logistic regression models to measure associations between autoimmune conditions and NHL with stratification by genotype. Autoimmune conditions mediated by B-cell responses were associated with increased NHL risk, specifically diffuse large B-cell lymphoma (odds ratio (OR) = 3.11, 95% confidence interval (CI): 2.25, 4.30) and marginal zone lymphoma (OR = 5.80, 95% CI: 3.82, 8.80); those mediated by T-cell responses were associated with peripheral T-cell lymphoma (OR = 2.14, 95% CI: 1.35, 3.38). In the presence of the rs1800629 AG/AA genotype, B-cell-mediated autoimmune conditions increased NHL risk (OR = 3.27, 95% CI: 2.07, 5.16; P-interaction = 0.03) in comparison with the GG genotype (OR = 1.82, 95% CI: 1.31, 2.53). This interaction was consistent across major B-cell NHL subtypes, including marginal zone lymphoma (P-interaction = 0.02) and follicular lymphoma (P-interaction = 0.04).

  9. Global microRNA expression profiling uncovers molecular markers for classification and prognosis in aggressive B-cell lymphoma

    PubMed Central

    Shen, Yulei; Huang, Xin; Liu, Yanyan; Wake, Laura; Liu, Cuiling; Deffenbacher, Karen; Lachel, Cynthia M.; Wang, Chao; Rohr, Joseph; Guo, Shuangping; Smith, Lynette M.; Wright, George; Bhagavathi, Sharathkumar; Dybkaer, Karen; Fu, Kai; Greiner, Timothy C.; Vose, Julie M.; Jaffe, Elaine; Rimsza, Lisa; Rosenwald, Andreas; Ott, German; Delabie, Jan; Campo, Elias; Braziel, Rita M.; Cook, James R.; Tubbs, Raymond R.; Armitage, James O.; Weisenburger, Dennis D.; Staudt, Louis M.; Gascoyne, Randy D.; McKeithan, Timothy W.; Chan, Wing C.

    2015-01-01

    We studied the global microRNA (miRNA) expression in diffuse large B-cell lymphoma (DLBCL; n = 79), Burkitt lymphoma (BL; n = 36), primary mediastinal B-cell lymphoma (PMBL; n = 12), B-cell lines (n = 11), and normal subsets of naïve B cells, centroblasts (CBs), and peripheral blood B cells along with their corresponding gene expression profiles (GEPs). The normal B-cell subsets have well-defined miRNA signatures. The CB miRNA signature was significantly associated with germinal center B-cell (GCB)–DLBCL compared with activated B-cell (ABC)–DLBCL (P = .002). We identified a 27-miRNA signature that included v-myc avian myelomatosis viral oncogene homolog (MYC) targets and enabled the differentiation of BL from DLBCL, a distinction comparable with the “gold standard” GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, including GCB-DLBCL, activated B-cell (ABC)-DLBCL, and PMBL. Interestingly, most of the unclassifiable-DLBCL by GEP showed a strong similarity to the ABC-DLBCL by miRNA expression profiling. Consistent results for BL and DLBCL subgroup classification were observed in formalin-fixed, paraffin-embedded tissue, making such tests practical for clinical use. We also identified predictive miRNA biomarker signatures in DLBCL, including high expression of miR-155, which is significantly associated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment failure. This finding was further supported by the observation that high expression of miR-155 sensitizes cells to v-akt murine thymoma viral oncogene homolog-1 inhibitors in vitro, suggesting a novel treatment option for resistant DLBCL. PMID:25498913

  10. Aminobisphosphonates prevent the inhibitory effects exerted by lymph node stromal cells on anti-tumor Vδ 2 T lymphocytes in non-Hodgkin lymphomas.

    PubMed

    Musso, Alessandra; Catellani, Silvia; Canevali, Paolo; Tavella, Sara; Venè, Roberta; Boero, Silvia; Pierri, Ivana; Gobbi, Marco; Kunkl, Annalisa; Ravetti, Jean-Louis; Zocchi, Maria Raffaella; Poggi, Alessandro

    2014-01-01

    In this study, we analyzed the influence of mesenchymal stromal cells derived from lymph nodes of non-Hodgkin's lymphomas, on effector functions and differentiation of Vdelta (δ)2 T lymphocytes. We show that: i) lymph-node mesenchymal stromal cells of non-Hodgkin's lymphoma inhibit NKG2D-mediated lymphoid cell killing, but not rituximab-induced antibody-dependent cell-mediated cytotoxicity, exerted by Vδ2 T lymphocytes; ii) pre-treatment of mesenchymal stromal cells with the aminobisphosphonates pamidronate or zoledronate can rescue lymphoma cell killing via NKG2D; iii) this is due to inhibition of transforming growth factor-β and increase in interleukin-15 production by mesenchymal stromal cells; iv) aminobisphosphonate-treated mesenchymal stromal cells drive Vδ2 T-lymphocyte differentiation into effector memory T cells, expressing the Thelper1 cytokines tumor necrosis factor-α and interferon-γ. In non-Hodgkin's lymphoma lymph nodes, Vδ2 T cells were mostly naïve; upon co-culture with autologous lymph-node mesenchymal stromal cells exposed to zoledronate, the percentage of terminal differentiated effector memory Vδ2 T lymphocytes increased. In all non-Hodgkin's lymphomas, low or undetectable transcription of Thelper1 cytokines was found. In diffused large B-cell lymphomas and in a group of follicular lymphoma, transcription of transforming growth factor β and interleukin-10 was enhanced compared to non-neoplastic lymph nodes. Thus, in non-Hodgkin lymphomas mesenchymal stromal cells interfere with Vδ2 T-lymphocyte cytolytic function and differentiation to Thelper1 and/or effector memory cells, depending on the prominent in situ cytokine milieu. Aminobisphosphonates, acting on lymph-node mesenchymal stromal cells, can push the balance towards Thelper1/effector memory and rescue the recognition and killing of lymphoma cells through NKG2D, sparing rituximab-induced antibody-dependent cell-mediated cytotoxicity.

  11. HCV Infection and B-Cell Lymphomagenesis

    PubMed Central

    Ito, Masahiko; Kusunoki, Hideki; Mochida, Keiko; Yamaguchi, Kazunari; Mizuochi, Toshiaki

    2011-01-01

    Hepatitis C virus (HCV) has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL). Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis. PMID:21789042

  12. FPA micro spectral imaging of non-Hodgkin lymphomas

    NASA Astrophysics Data System (ADS)

    Burattini, E.; Malvezzi-Campeggi, F.; Chilosi, M.; Conti, C.; Ferraris, P.; Monti, F.; Sabbatini, S.; Tosi, G.; Zamò, A.

    2007-05-01

    A FT-IR microspectroscopy study on reactive lymph nodes and non-Hodgkin lymphomas is reported. Mid infrared absorption spectra collected at diffraction limit spatial resolution from reactive and neoplastic lymph nodes resulted sufficiently different once analysed by multivariate pattern recognition analysis to distinguish tumoral from non tumoral samples. The potential of infrared spectroscopy as a post-operative screening is gained by the use of a multielement Focal Plane Array detector. Spectral differences between normal and malignant spectra were mainly in the methyl stretching and in the low frequency region.

  13. The role of angiogenesis in human non-Hodgkin lymphomas.

    PubMed

    Ribatti, Domenico; Nico, Beatrice; Ranieri, Girolamo; Specchia, Giorgina; Vacca, Angelo

    2013-03-01

    The role of angiogenesis in the growth of lymphomas and survival of patients with leukemias and other hematological malignancies has become evident since 1994. Angiogenic factors, such as vascular endothelial growth factor and its receptors together with other tumor microenvironment components, including myelo-monocytic cell, mast cells, endothelial progenitor cells, and circulating endothelial cells, have been shown to be important in the progression and maintenance of lymphoproliferative disorders. In this review article, we present an overview of the literature focusing on the relationship between angiogenesis and disease progression and the recent advantages in the antiangiogenic treatment in human non-Hodgkin lymphomas.

  14. SNPs Array Karyotyping in Non-Hodgkin Lymphoma

    PubMed Central

    Etebari, Maryam; Navari, Mohsen; Piccaluga, Pier Paolo

    2015-01-01

    The traditional methods for detection of chromosomal aberrations, which included cytogenetic or gene candidate solutions, suffered from low sensitivity or the need for previous knowledge of the target regions of the genome. With the advent of single nucleotide polymorphism (SNP) arrays, genome screening at global level in order to find chromosomal aberrations like copy number variants, DNA amplifications, deletions, and also loss of heterozygosity became feasible. In this review, we present an update of the knowledge, gained by SNPs arrays, of the genomic complexity of the most important subtypes of non-Hodgkin lymphomas. PMID:27600240

  15. Some aspects of the etiology of non-Hodgkin's lymphoma.

    PubMed

    Hardell, L; Lindström, G; van Bavel, B; Fredrikson, M; Liljegren, G

    1998-04-01

    In epidemiologic studies, non-Hodgkin's lymphoma (NHL) has been associated with exposure to chemicals such as phenoxyacetic acids; chlorophenols; dioxins; organic solvents including benzene, polychlorinated biphenyls, chlordanes; and immunosuppressive drugs. Experimental evidence and clinical observations indicate that these chemicals may impair the immune system. The risk is increased for NHL in persons with acquired and congenital immune deficiency as well as autoimmune disorders. Also, certain viruses have been suggested to be of etiologic significance for NHL. In some cases of NHL the common mechanism for all these agents and conditions may be immunosuppression, possibly in combination with viruses.

  16. Analysis of clinical characteristics of 516 patients with non-Hodgkin's lymphoma in Shanghai area.

    PubMed

    Lin, Zhiguang; Chen, Bobin; Xu, Xiaoping; Wang, Xiaoqin; Lin, Guowei

    2014-03-01

    The aim was to determine the clinical and cytogenetic characteristics of non-Hodgkin's lymphoma (NHL) in Shanghai. A retrospective analysis was conducted in 516 patients with NHL. Patient clinical data, including age, sex, diagnosis, immunophenotypes, and karyotypes, were collected. The median age was 58 years. There was a male predominance in all NHL, except extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Patients with B cell NHL (1.5%) expressed CD3. T cell NHL patients (11.5%) expressed CD20. Epstein-Barr virus latent integral membrane protein 1, BCL6, CD10, Bcl-2, CD68, myeloperoxidase, CD99, CD30, CD15, and CD43 were present in various types of NHL. Complex karyotypes accounted for 92.3% of the 73.7% patients with abnormal karyotypes. Immunoglobin heavy chain gene translocation was present in 60.3% of B cell and 23.7% of T/NK cell neoplasms. Understanding the complex clinicopathological and molecular features of NHL may help with prognosis and serve as targets for treatments.

  17. Frequent mutation of histone modifying genes in non-Hodgkin lymphoma

    PubMed Central

    Morin, Ryan D.; Mendez-Lago, Maria; Mungall, Andrew J.; Goya, Rodrigo; Mungall, Karen L.; Corbett, Richard; Johnson, Nathalie A.; Severson, Tesa M.; Chiu, Readman; Field, Matthew; Jackman, Shaun; Krzywinski, Martin; Scott, David W.; Trinh, Diane L.; Tamura-Wells, Jessica; Li, Sa; Firme, Marlo; Rogic, Sanja; Griffith, Malachi; Chan, Susanna; Yakovenko, Oleksandr; Meyer, Irmtraud M.; Zhao, Eric Y.; Smailus, Duane; Moksa, Michelle; Chittaranjan, Suganthi; Rimsza, Lisa; Brooks-Wilson, Angela; Spinelli, John J.; Ben-Neriah, Susana; Meissner, Barbara; Woolcock, Bruce; Boyle, Merrill; McDonald, Helen; Tam, Angela; Zhao, Yongjun; Delaney, Allen; Zeng, Thomas; Tse, Kane; Butterfield, Yaron; Birol, Inanc; Holt, Rob; Schein, Jacqueline; Horsman, Douglas E.; Moore, Richard; Jones, Steven J.M.; Connors, Joseph M.; Hirst, Martin; Gascoyne, Randy D.; Marra, Marco A.

    2011-01-01

    Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). To identify genes with mutations in B-cell NHL we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase. 11.4% of DLBCL and 13.4% of FL cases had somatic mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis thus suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis. PMID:21796119

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

    ClinicalTrials.gov

    2017-01-26

    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

  19. Four Lymphomas in 1 Patient: A Unique Case of Triple Composite Non-Hodgkin Lymphoma Followed by Classical Hodgkin Lymphoma.

    PubMed

    Tennese, Alysa; Skrabek, Pamela J; Nasr, Michel R; Sekiguchi, Debora R; Morales, Carmen; Brown, Theresa C; Weisenburger, Dennis D; Perry, Anamarija M

    2016-09-29

    Composite lymphomas consist of 2 or more distinct lymphomas occurring in a single anatomical site or simultaneously in different sites and can be composed of any combination of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, or Hodgkin lymphoma (HL). Cases of composite lymphomas with more than 2 lymphomas are extremely rare, with only 4 reports in the literature. We report the case of a 49-year-old man with a triple composite lymphoma in a single lymph node, consisting of small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma in situ. The patient received multiple courses of chemotherapy and an autologous stem cell transplant, which resulted in complete remission. Then, 6 years after the stem cell transplant, he developed classical HL. This unique case is, to our knowledge, the first report of a patient with triple composite lymphoma consisting of 3 small mature B-cell NHLs, who subsequently developed a fourth lymphoma.

  20. 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.

  1. Yttrium Y 90 Basiliximab and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With Mature T-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-11-09

    Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma

  2. Role of Tyrosine Kinase Inhibitors in Indolent and Other Mature B-Cell Neoplasms

    PubMed Central

    Kutsch, Nadine; Marks, Reinhard; Ratei, Richard; Held, Thomas K; Schmidt-Hieber, Martin

    2015-01-01

    Targeting tyrosine kinases represents a highly specific treatment approach for different malignancies. This also includes non-Hodgkin lymphoma since it is well known that these enzymes are frequently involved in the lymphomagenesis. Hereby, tyrosine kinases might either be dysregulated intrinsically or be activated within signal transduction pathways leading to tumor survival and growth. Among others, Bruton’s tyrosine kinase (Btk) is of particular interest as a potential therapeutic target. Btk is stimulated by B-cell receptor signaling and activates different transcription factors such as nuclear factor κB. The Btk inhibitor ibrutinib has been approved for the treatment of chronic lymphocytic leukemia and mantle-cell lymphoma recently. Numerous clinical trials evaluating this agent in different combinations (eg, with rituximab or classical chemotherapeutic agents) as a treatment option for aggressive and indolent lymphoma are under way. Here, we summarize the role of tyrosine kinase inhibitors in the treatment of indolent and other non-Hodgkin lymphomas (eg, mantle-cell lymphoma). PMID:26327780

  3. Spontaneous Remission of an Untreated, MYC and BCL2 Coexpressing, High-Grade B-Cell Lymphoma: A Case Report and Literature Review

    PubMed Central

    Potts, D. Alan; Fromm, Jonathan R.; Gopal, Ajay K.

    2017-01-01

    Non-Hodgkin lymphomas (NHL) are a heterogeneous group of hematologic malignancies typically treated with multiagent chemotherapy. Rarely, spontaneous remissions can be observed, particularly in more indolent subtypes. The prognosis of aggressive NHL can be predicted using clinical and histopathologic factors. In aggressive B-cell NHL, the importance of MYC and BCL2 proto-oncogene coexpression (as assessed by immunohistochemistry) and high-grade histologic features are particularly noteworthy. We report a unique case of spontaneous remission in a patient with an aggressive B-cell NHL which harbored high-risk histopathologic features, including MYC protein expression at 70–80%, BCL2 protein expression, and morphologic features suggestive of high-grade B-cell lymphoma, NOS (formerly B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma [BCLU]). After undergoing a biopsy to confirm this diagnosis, he opted to forego curative-intent chemotherapy. The single, yet relatively large area of involvement noted on 18F-fluorodeoxyglucose positron emission tomography-computed tomography steadily resolved on subsequent follow-up studies. He remained without evidence of recurrence one year later, having never received treatment. This case emphasizes the potential for spontaneous remission in NHL and demonstrates that this phenomenon can be observed despite contemporary high-risk histopathologic features. PMID:28321348

  4. Alisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-02-09

    Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Hepatosplenic T-Cell Lymphoma; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma

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

    ClinicalTrials.gov

    2017-01-11

    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

  6. Immunophenotyping of non-Hodgkin's lymphoma. Lack of correlation between immunophenotype and cell morphology.

    PubMed Central

    Schuurman, H. J.; van Baarlen, J.; Huppes, W.; Lam, B. W.; Verdonck, L. F.; van Unnik, J. A.

    1987-01-01

    The establishment of Clusters of Differentiation for T- and B-lymphoid cells during International Workshops on Human Leukocyte Differentiation Antigens prompted the authors to evaluate the immunophenotypes in 160 cases of non-Hodgkin's lymphoma (NHL). In this group, 130 were of B-lymphocyte lineage (117 by monotypic immunoglobulin expression), and 30 of T-cell lineage. In the B-NHL series the expression of immunoglobulin isotypes, B-cell maturation/differentiation antigens of CD9, CD10, CD19-24, CD37, and CD38 (OKT10), HLA-DR and peanut agglutinin binding showed no significant relationship with histopathologic diagnosis as defined by the Kiel classification. Of the T-cell markers, CD5, CD6, and CD7 showed lineage promiscuity by their presence on some B-NHL. Conversely, the authors grouped the cases according to phenotypes (either CD antigens or immunoglobulin isotypes) which occur in distinct stages of (physiologic) B-cell maturation/differentiation. Eighty-six of the 130 cases could be fitted according to CD phenotype expression. This approach did not yield a significant relationship between phenotype and individual histopathologic categories either. The staging by CD phenotype and by immunoglobulin isotype yielded different results in this respect. Most B-NHL had an intermediate stage of B-cell maturation/differentiation. In the T-NHL series most cases showed a phenotype (CD1-CD8, CD38, TdT, and peanut agglutinin binding capacity) compatible with mature T-lymphocyte characteristics. The exceptions were lymphoblastic convoluted lymphomas, which exhibited an immature immunophenotype. It is concluded that NHL in distinct histopathologic categories are heterogeneous in immunologic phenotypes, and that the immunophenotype of lymphoma cells has no evident association with that of their presumed counterparts in physiologic cell maturation/differentiation. PMID:3310650

  7. Mucormycosis in a Non-Hodgkin Lymphoma Patient Caused by Syncephalastrum racemosum: Case Report and Review of Literature.

    PubMed

    Rodríguez-Gutiérrez, Georgina; Carrillo-Casas, Erika M; Arenas, Roberto; García-Méndez, Jorge O; Toussaint, Sonia; Moreno-Morales, Mónica E; Schcolnik-Cabrera, Adrián A; Xicohtencatl-Cortes, Juan; Hernández-Castro, Rigoberto

    2015-08-01

    Mucormycosis is a rare opportunistic fungal infection caused by saprophytic zygomycetes. These fungal infections are caused by members of the mucorales. The clinical importance of zygomycosis, an emerging and frequently fatal mycotic disease, has increased during recent years, due to several risk factors such as (a) the use of broad-spectrum antibiotic, (b) use of empirical antifungal treatment (mainly triazoles), and (c) aggressive chemotherapy and sustained leucopenia (i.e., peripheral stem cell transplantation). An almost fulminant pneumonia caused by Syncephalastrum racemosum in an immunocompromised patient with an aggressive non-Hodgkin lymphoma (NHL) is described. Despite treatment with amphotericin B, deoxycholate, caspofungin, and surgical resection of fungal bodies from both lungs, and survival of 10 months without relapsing from fungal infection, the patient died due to hematological complications from an unresponsive disease. Herein is the description of the first case of pulmonary infection caused by Syncephalastrum racemosum.

  8. Non-Hodgkin lymphoma response evaluation with MRI texture classification

    PubMed Central

    Harrison, Lara CV; Luukkaala, Tiina; Pertovaara, Hannu; Saarinen, Tuomas O; Heinonen, Tomi T; Järvenpää, Ritva; Soimakallio, Seppo; Kellokumpu-Lehtinen, Pirkko-Liisa I; Eskola, Hannu J; Dastidar, Prasun

    2009-01-01

    Background To show magnetic resonance imaging (MRI) texture appearance change in non-Hodgkin lymphoma (NHL) during treatment with response controlled by quantitative volume analysis. Methods A total of 19 patients having NHL with an evaluable lymphoma lesion were scanned at three imaging timepoints with 1.5T device during clinical treatment evaluation. Texture characteristics of images were analyzed and classified with MaZda application and statistical tests. Results NHL tissue MRI texture imaged before treatment and under chemotherapy was classified within several subgroups, showing best discrimination with 96% correct classification in non-linear discriminant analysis of T2-weighted images. Texture parameters of MRI data were successfully tested with statistical tests to assess the impact of the separability of the parameters in evaluating chemotherapy response in lymphoma tissue. Conclusion Texture characteristics of MRI data were classified successfully; this proved texture analysis to be potential quantitative means of representing lymphoma tissue changes during chemotherapy response monitoring. PMID:19545438

  9. Intraosseous Non-Hodgkin Lymphoma Mimicking a Periapical Lesion.

    PubMed

    Pereira, Débora Lima; Fernandes, Diego Tetzner; Santos-Silva, Alan Roger; Vargas, Pablo Agustin; de Almeida, Oslei Paes; Lopes, Márcio Ajudarte

    2015-10-01

    Non-Hodgkin lymphomas are a group of disorders involving malignant monoclonal proliferation of lymphoid cells, which appear at extranodal sites in approximately 40% of the cases, particularly in the gastrointestinal tract. Intraosseous lymphomas of the head and neck region are extremely rare and can mimic other diseases such as periodontitis or periapical pathologies. This report presents an additional case of intraosseous lymphoma that was previously misdiagnosed as periapical disease. In addition, a literature review was made based on PubMed, and all cases of periapical lymphoma were analyzed. After the diagnosis of lymphoma, the current patient was treated with 6 cycles of chemotherapy and showed satisfactory outcome. The literature review displayed 29 cases of lymphoma affecting the periapical region, and in 51.7% of them endodontic treatment was performed previously to the diagnosis of lymphoma. Although lymphoma is uncommon in the oral cavity, some symptoms can assist the dentist to suspect malignant conditions, mainly in cases presenting numb chin syndrome.

  10. Reed-Sternberg-Like Cells in Non-Hodgkin Lymphomas.

    PubMed

    Gomez-Gelvez, Juan C; Smith, Lauren B

    2015-10-01

    Large atypical cells with morphologic and immunophenotypic features resembling Reed-Sternberg cells can be seen in the background of reactive lymphadenopathies as well as non-Hodgkin lymphomas. The presence of these cells is an important diagnostic pitfall that must be recognized by pathologists who regularly interpret lymph node biopsies. A thorough evaluation of the morphologic and immunophenotypic features of these cells and the cellular milieu is crucial in achieving the correct diagnosis. In this review, examples of lymphomas presenting with Reed-Sternberg-like cells will be provided. Additionally, a detailed description of the common morphologic and immunophenotypic features of these cells, as well as strategies that can be used to distinguish them from the Reed-Sternberg cells of classical Hodgkin lymphoma, will be emphasized.

  11. Combating the epigenome: epigenetic drugs against non-Hodgkin's lymphoma.

    PubMed

    Hassler, Melanie R; Schiefer, Ana-Iris; Egger, Gerda

    2013-08-01

    Non-Hodgkin's lymphomas (NHLs) comprise a large and diverse group of neoplasms of lymphocyte origin with heterogeneous molecular features and clinical manifestations. Current therapies are based on standard chemotherapy, immunotherapy, radiation or stem cell transplantation. The discovery of recurrent mutations in epigenetic enzymes, such as chromatin modifiers and DNA methyltransferases, has provided researchers with a rationale to develop novel inhibitors targeting these enzymes. Several clinical and preclinical studies have demonstrated the efficacy of epigenetic drugs in NHL therapy and a few specific inhibitors have already been approved for clinical use. Here, we provide an overview of current NHL classification and a review of the present literature describing epigenetic alterations in NHL, including a summary of different epigenetic drugs, and their use in preclinical and clinical studies.

  12. Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas.

    PubMed

    Bi, Chengfeng; Zhang, Xuan; Lu, Ting; Zhang, Xiaoyan; Wang, Xianhuo; Meng, Bin; Zhang, Huilai; Wang, Ping; Vose, Julie M; Chan, Wing C; McKeithan, Timothy W; Fu, Kai

    2017-04-01

    Mechanistic target of rapamycin (mTOR) complex 1 is a central integrator of nutrient and growth factor inputs that controls cell growth in eukaryotes. The second generation of mTOR kinase inhibitors (TORKi), directly targeting the mTOR catalytic site, are more effective than rapamycin and its analogs in cancer treatment, particularly in inducing apoptosis. However, the mechanism underlying the cytotoxic effect of TORKi remains elusive. Herein, we demonstrate that TORKi-induced apoptosis is predominantly dependent on the loss of mTOR complex 1-mediated 4EBP activation. Knocking out RICTOR, a key component of mTOR complex 2, or inhibiting p70S6K has little effect on TORKi-induced apoptosis. Conversely, increasing the eIF4E:4EBP ratio by either overexpressing eIF4E or knocking out 4EBP1/2 protects lymphoma cells from TORKi-induced cytotoxicity. Furthermore, downregulation of MCL1 expression plays an important role in TORKi-induced apoptosis, whereas BCL-2 overexpression confers resistance to TORKi treatment. We further show that the therapeutic effect of TORKi in aggressive B-cell lymphomas can be predicted by BH3 profiling, and improved by combining it with pro-apoptotic drugs, especially BCL-2 inhibitors, both in vitro and in vivo Taken together, the study herein provides mechanistic insight into TORKi cytotoxicity and identified a potential way to optimize its efficacy in the clinical treatment of aggressive B-cell lymphoma.

  13. High-level DNA amplifications are common genetic aberrations in B-cell neoplasms.

    PubMed Central

    Werner, C. A.; Döhner, H.; Joos, S.; Trümper, L. H.; Baudis, M.; Barth, T. F.; Ott, G.; Möller, P.; Lichter, P.; Bentz, M.

    1997-01-01

    Gene amplification is one of the molecular mechanisms resulting in the up-regulation of gene expression. In non-Hodgkin's lymphomas, such gene amplifications have been identified rarely. Using comparative genomic hybridization, a technique that has proven to be very sensitive for the detection of high-level DNA amplifications, we analyzed 108 cases of B-cell neoplasms (42 chronic B-cell leukemias, 5 mantle cell lymphomas, and 61 aggressive B-cell lymphomas). Twenty-four high-level amplifications were identified in 13% of the patients and mapped to 15 different genomic regions. Regions most frequently amplified were bands Xq26-28, 2p23-24, and 2p14-16 as well as 18q21 (three times each). Amplification of several proto-oncogenes and a cell cycle control gene (N-MYC (two cases), BCL2, CCND2, and GLI) located within the amplified regions was demonstrated by Southern blot analysis or fluorescence in situ hybridization to interphase nuclei of tumor cells. These data demonstrate that gene amplifications in B-cell neoplasms are much more frequent than previously assumed. The identification of highly amplified DNA regions and genes included in the amplicons provides important information for further analyses of genetic events involved in lymphomagenesis. Images Figure 2 Figure 3 PMID:9250147

  14. The risk of CNS involvement in aggressive lymphomas in the rituximab era.

    PubMed

    Benevolo, Giulia; Chiappella, Annalisa; Vitolo, Umberto

    2013-12-01

    The risk of CNS dissemination and CNS prophylaxis strategies in aggressive non-Hodgkin lymphoma (NHL) is still debated. CNS dissemination is a rare but fatal event. A CNS prophylaxis is common for Burkitt and B-cell lymphoblastic lymphoma; however, in other NHLs, prophylactic treatments are not systematically warranted. Current risk models showed low sensitivity in predicting CNS involvement, implying overtreatment in roughly 70% of high-risk patients. Risk models in the rituximab era were modulated for the detection of occult CNS disease at diagnosis using flow cytometry. The optimal regimen for CNS prophylaxis in aggressive lymphoma patients has not been established thus far and should be modulated at different levels of 'intensity' such as standard intrathecal chemotherapy, 'active' intrathecal chemotherapy with liposomal cytarabine or more aggressive systemic treatment with high doses of drugs having good CNS bioavailability reserved for patients who are truly at high risk of CNS dissemination.

  15. Silicon Phthalocyanine 4 and Photodynamic Therapy in Stage IA-IIA Cutaneous T-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-12-03

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome

  16. Radioimmunotherapy for non-Hodgkin's lymphoma: A review for radiation oncologists

    SciTech Connect

    Macklis, Roger M. . E-mail: macklir@ccf.org; Pohlman, Brad

    2006-11-01

    Purpose: The aim of this study was to review advances in radioimmunotherapy (RIT) for non-Hodgkin's lymphoma (NHL) and to discuss the role of Radiation oncologist in administering this important new form of biologically targeted radiotherapy. Methods and Materials: A review of articles and abstracts on the clinical efficacy, safety, and radiation safety of yttrium Y 90 ({sup 9}Y) ibritumomab tiuxetan (Zevalin) and iodine I 131 tositumomab (Bexxar) was performed. Results: The clinical efficacy of RIT in NHL has been shown in numerous clinical trials of {sup 9}Y ibritumomab tiuxetan and {sup 131}I tositumomab. Both agents have produced significant responses in patients with low-grade, follicular, or transformed NHL, including patients with disease that had not responded or had responded poorly to previous chemotherapy or immunotherapy. Reversible toxicities such as neutropenia, thrombocytopenia, and anemia are the most common adverse events with both agents. Conclusions: Radioimmunotherapy is safe and effective in many patients with B-cell NHL. {sup 9}Y ibritumomab tiuxetan and {sup 131}I tositumomab can produce clinically meaningful and durable responses even in patients in whom chemotherapy has failed. Treatment with RIT requires a multispecialty approach and close communication between Radiation oncologist and other members of the treatment team. Radiation oncologist plays an important role in treating patients with RIT and monitoring them for responses and adverse events after treatment.

  17. [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.

  18. Idelalisib for the treatment of indolent non-Hodgkin lymphoma: a review of its clinical potential

    PubMed Central

    Barrientos, Jacqueline C

    2016-01-01

    Idelalisib is a first-in-class, oral, selective phosphatidylinositol 3-kinase δ inhibitor that offers a chemotherapy-free option for patients with relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). Clinical trials in iNHL have evaluated idelalisib as monotherapy and as combination therapy with rituximab, bendamustine, and rituximab + bendamustine. When administered to heavily pretreated patients with R/R iNHL, idelalisib monotherapy or combination therapy showed durable antitumor activity accompanied by sustained or improved quality-of-life outcomes. Idelalisib has an acceptable safety profile; however, serious or fatal diarrhea/colitis, hepatoxicity, pneumonitis, and intestinal perforation have occurred in treated patients. Selective inhibition of phosphatidylinositol 3-kinase δ with idelalisib is a valuable addition to available treatment options for patients with iNHL, many of whom do not respond to or cannot tolerate chemoimmunotherapy. Two Phase III, randomized, placebo-controlled trials of idelalisib as combination therapy with rituximab or bendamustine + rituximab and a Phase I trial of idelalisib in combination with the Bruton’s tyrosine kinase inhibitor ONO/GS-4059 in R/R B-cell malignancies are currently ongoing. A Phase III monotherapy trial in previously treated follicular lymphoma or small lymphocytic lymphoma is planned. The development of other kinase inhibitors for the treatment of iNHL raises the potential for new treatment combinations. Additional research is needed to determine optimal therapy (monotherapy vs combination regimens), treatment sequencing, and long-term management. PMID:27274288

  19. Recreational amphetamine use and risk of HIV-related non-Hodgkin lymphoma.

    PubMed

    Chao, Chun; Jacobson, Lisa P; Tashkin, Donald; Martínez-Maza, Otoniel; Roth, Michael D; Margolick, Joseph B; Chmiel, Joan S; Holloway, Marcy N; Zhang, Zuo-Feng; Detels, Roger

    2009-07-01

    The results of many laboratory studies suggest that amphetamine use may lead to altered immune function and cytokine expression, both of which are implicated in HIV-related lymphomagenesis. We examined the hypothesis that use of amphetamines modifies risk of non-Hodgkin lymphoma (NHL) in HIV-infected men in the Multicenter AIDS Cohort Study. Data on amphetamine use were collected every six months during the follow-up period between 1984 and 2002. A total of 171 NHL cases were diagnosed from the 19,250 person-years accrued. Multivariable Cox models were used to estimate the effects of baseline exposures, time-varying recent exposures, and three years lagged exposures on risk of NHL adjusting for potential confounders such as demographics, use of other substances, and risky sexual behaviors. We found that weekly or more frequent use of amphetamines was associated with an increased risk of NHL, with hazard ratios of 1.75 (95% CI = 0.81-3.77) for use at baseline, 4.73 (1.41-15.81) for recent use, and 3.05 (1.19-7.82) for three years prior use. Similar associations were observed when we separately examined systemic NHL and diffuse large B-cell lymphoma. Given these observations, the impact of amphetamines on lymphomagenesis among HIV-infected populations should be assessed more thoroughly.

  20. Splenic non-Hodgkin's lymphoma presenting as recurrent kidney stones -- an "incidentaloma"?

    PubMed

    Doshi, Kaushik; Stanciu, John; Cervantes, Jose; Rodrigues, Lucan; Gintautas, Jonas; Alwani, Ayaz

    2008-01-01

    Splenic lymphoma, or primary malignant lymphoma of the spleen (PMLS), is an uncommon condition whose true nature is difficult to define due to the variable ways it has been classified. Out of all non-Hodgkin's lymphomas it comprises less than 2% of cases. Some experts suggest that PMLS only involves the spleen and splenic hilum, while others consider PMLS to be an entity that develops within the spleen and later has the potential for invading adjacent organs and metastasizing. Clinical features of splenic lymphoma are characterized by nonspecific systemic symptoms such as low grade fevers, night sweats and symptoms related to considerable splenomegaly. Most of these lymphomas are of B-cell origin showing low or intermediate-grade lymphoma on histological analysis. The case we present here is of a patient presenting with left sided flank pain, and given a previous history of nephrolithiasis, a presumably simple diagnosis of kidney stones was made. However, further investigation led to the discovery of splenic lymphoma, which was asymptomatic earlier but may have manifested symptoms that mimicked renal colic.

  1. Bilateral Non-Hodgkin's Lymphoma of the Temporal Bone: A Rare and Unusual Presentation

    PubMed Central

    Jadhav, Jyoti; Chandorkar, Aparna

    2016-01-01

    Primary lymphoma of the temporal bone is an unusual finding in clinical practice and bilateral affection is even more rare. To the best of our knowledge, there are no reports of bilateral primary temporal bone lymphoma without middle ear involvement in the English medical literature so far. We report, for the first time, a case of primary lymphoma involving both temporal bones which presented with left-sided infranuclear facial palsy. A combination of contrast enhanced magnetic resonance imaging (MRI) and high resolution computed tomography (HRCT) was used to characterize and to map the extent of the lesion, as well as to identify the exact site of facial nerve affection. An excision biopsy and immunohistochemistry revealed diffuse large B-cell non-Hodgkin's lymphoma (DLBCL). Whole body fluorodeoxyglucose (FDG) positron emission tomography-computed tomography study (PET-CT) was performed to stage the disease. The patient was treated with chemotherapy and radiation therapy and is now on regular follow-up. The patient is alive and asymptomatic without disease progression for the last twenty months after initial diagnosis. PMID:28116198

  2. [Role of radiotherapy in the management of non-Hodgkin lymphomas].

    PubMed

    Gastaud, L; Rossignol, B; Peyrade, F; Ré, D; Thariat, J; Thyss, A; Doyen, J

    2016-05-01

    The purpose of this review was to summarize recent data about lastest retrospective and prospective studies dealing with radiotherapy of non-Hodgkin lymphoma, in order to precise the schedule and the role of this treatment. A systematic review was done by searching studies on the website http://www.pubmed.gov (Medline) using the following keywords: radiotherapy, radiation therapy, non-Hodgkin lymphoma. The management of non-Hodgkin lymphoma varies a lot according to the histological type and stage. The dose of radiotherapy has been studied in only one randomized trial, which concluded that there was no difference between the low dose and the high dose arms. Radiotherapy is a very good option in follicular, cutaneous, digestive or orbital non-Hodgkin lymphoma. A recent post hoc analysis of randomized trials on radiotherapy for high-grade non-Hodgkin lymphoma strongly suggested a benefit of additional radiotherapy after chemotherapy in some situations. Radiotherapy of low-grade non-Hodgkin lymphoma is a very good option, while its use on high-grade non-Hodgkin lymphoma is sometimes recommended but further randomized trials are ongoing to better understand its role.

  3. Targeted PI3Kδ inhibition by the small molecule idelalisib as a novel therapy in indolent non-Hodgkin lymphoma

    PubMed Central

    Okoli, Tracy C; Peer, Cody J; Dunleavy, Kieron; Figg, William D

    2015-01-01

    Indolent Non-Hodgkin Lymphomas (iNHL) are typically B-cell malignancies and are incurable with current standard approaches. Thus, there is a demand for novel agents specific for this group of disorders. In a phase II study published by Gopal et al. in the New England Journal of Medicine, idelalisib, a small molecule inhibitor of PI3Kδ that was FDA approved in July of 2014, was shown to be effective when combined with rituximab in patients who cannot tolerate chemotherapy and as last line therapy in patients with iNHL refractory to 2 prior systemic therapies. Idelalisib demonstrated tolerable diarrhea, fatigue, nausea, pyrexia, and cough. While this novel agent is a clinically significant addition to the iNHL arsenal, further research is needed to determine its most appropriate place in iNHL therapy. PMID:25756507

  4. Diagnosis, PET/CT imaging, and treatment of extranodal non-Hodgkin lymphoma in keratinized gingiva: a case report.

    PubMed

    Aral, Cüneyt A; Ağlarcı, Osman S; Yılmaz, Hasan H; Taşlı, Funda; Karaarslan, Serap; Hatipoğlu, Filiz; Sanal, Mustafa S

    2015-03-01

    A 58-year-old patient who smoked and had uncontrolled type 2 diabetes mellitus was referred to our clinic. The patient had a suspicious asymptomatic lesion that was diagnosed as B-cell non-Hodgkin lymphoma (NHL). Immunohistochemistry revealed intense and diffuse expression of CD20, CD10, BCL-6, and Ki-67. A positron emission tomography/computed tomography (PET/CT) scan showed focal pathological uptake of F-18-fluorodeoxyglucose only in the subcutaneous tissue anterior to the left maxillary sinus. After lesion excision and five courses of chemotherapy, PET/CT scans demonstrated complete resolution of the lesion. Smoking, uncontrolled diabetes mellitus, and periodontal disease might be predisposing factors for oral NHL.

  5. Experimental models of lymphoproliferative disease. The mouse as a model for human non-Hodgkin's lymphomas and related leukemias.

    PubMed Central

    Pattengale, P. K.; Taylor, C. R.

    1983-01-01

    The present review focuses on the mouse as an experimental immunopathologic model for human non-Hodgkin's lymphomas and related leukemias. Immunomorphologic evidence is presented that clearly demonstrates that B- and T-cell subtypes of mouse (murine) lymphoma/leukemia closely resemble and are analogous to B- and T-cell subtypes of human lymphoma/leukemia as defined by recently proposed immunomorphologic classifications. Further evidence is presented that favors the hypothesis that certain types of murine and human B-cell lymphoma develop out of prodromal, prelymphomatous states, which exhibit antecedent morphologic and immunologic abnormalities. The many experimental advantages of the murine systems are stressed, as well as the concept that the presently defined immunomorphologic approach should be effectively combined with molecular and cytogenetic parameters. Images Table 6 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 10 Table 9 Figure 11 Figure 12 Figure 13 PMID:6605691

  6. WT1 overexpression affecting clinical outcome in non-hodgkin lymphomas and adult acute lymphoblastic leukemia.

    PubMed

    Ujj, Zsófia; Buglyó, Gergely; Udvardy, Miklós; Vargha, György; Biró, Sándor; Rejtő, László

    2014-07-01

    The Wilms tumor 1 (WT1) gene has a complex role as a transcriptional regulator, acting as tumor suppressor or oncogene in different malignancies. The prognostic role of its overexpression has been well-studied in leukemias, especially acute myeloid leukemia (AML), but not in lymphomas. For the first time to our knowledge, we present a study demonstrating the correlation of WT1 expression and survival in various non-Hodgkin lymphomas. We also studied the prognostic implications of WT1 overexpression in adult acute lymphoblastic leukemia (ALL). In our sample of 53 patients--25 with diffuse large B-cell lymphoma (DLBCL), 8 with mantle cell lymphoma (MCL), 9 with peripheral T-cell lymphoma (PTCL), 2 with Burkitt's lymphoma, 2 with mucosa-associated lymphoid tissue (MALT) lymphoma, and 7 with B-cell ALL--, we measured WT1 mRNA from blood samples by quantitative RT-PCR, and divided the patients into subgroups based on the level of expression. Kaplan-Meier survival curves were drawn and compared using the logrank test. In the sample of DLBCL patients, the difference in overall and disease-free survival between WT1-positive and negative subgroups was significant (p = 0.0475 and p = 0.0004, respectively), and in a few observed cases, a sudden increase in WT1 expression signified a relapse soon followed by death. Disease-free survival curves in MCL and ALL were similarly suggestive of a potential role played by WT1. In PTCL, though WT1-positivity was detected in 4 out of 9 cases, it did not seem to affect survival. The few cases of MALT and Burkitt's lymphoma all proved to be WT1-negative.

  7. Circulating Mediators of Inflammation and Immune Activation in AIDS-Related Non-Hodgkin Lymphoma

    PubMed Central

    Nolen, Brian M.; Breen, Elizabeth Crabb; Bream, Jay H.; Jenkins, Frank J.; Kingsley, Lawrence A.; Rinaldo, Charles R.; Lokshin, Anna E.

    2014-01-01

    Background Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed bead-based immunoassays. Results A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease. PMID:24922518

  8. SEOM clinical guidelines for the treatment of follicular non-Hodgkin's lymphoma.

    PubMed

    Provencio Pulla, M; Alfaro Lizaso, J; de la Cruz Merino, L; Gumá I Padró, J; Quero Blanco, C; Gómez Codina, J; Llanos Muñoz, M; Martinez Banaclocha, N; Rodriguez Abreu, D; Rueda Domínguez, A

    2015-12-01

    Follicular non-Hodgkin's lymphoma (FL) is a nodal B lymphoid malignancy that originates from the germinal center of a lymph node. FL is the second most frequent lymphoma subtype. The course of the disease is usually characterised by a typically indolent clinical course, with a median survival rate of 8-10 years, although most patients relapse after treatment. Diagnosis should always be based on a surgical specimen like an excisional node lymph biopsy. The first-line treatment of FL will depend of extension disease, tumour burden, patient symptoms, performance status and also patient decision. The addition of rituximab to conventional chemotherapy has improved ORR, PFS and OS. As first line in patients that need treatment, a combination of chemotherapy with rituximab induction followed by 2 years of rituximab maintenance is the best option. High-dose chemotherapy with autologous stem-cell transplantation in first line has not shown improvement and is not recommended as first-line therapy. Before any treatment decision in relapsed patients, a repeat biopsy is mandatory to rule out a transformation into large cell aggressive lymphoma. Standard treatment is controversial, depends on the efficacy of prior treatment, duration of the time-to-relapse, patient's age and histological findings at relapse.

  9. Acute myelofibrosis in a patient with diffuse large cell non Hodgkin's lymphoma and renal cancer.

    PubMed

    Mohren, Martin; Essbach, Uwe; Franke, Astrid; Klink, Anne; Maas, Christian; Markmann, Ilka; Pelz, Antje F; Jentsch-Ullrich, Kathleen

    2003-09-01

    Relapse after anthracycline based combination chemotherapy is frequently seen in patients with aggressive non Hodgkin's Lymphomas (NHL), whereas complications such as secondary leukemia or solid tumor rarely occur. We report a patient with diffuse large cell (DLC) NHL and concurrent renal cancer, who developed acute myelofibrosis (AMF) later in the course of her disease. This 60-year-old female patient presented with pancytopenia and a right sided renal mass. Diagnostic work up revealed severe bone marrow infiltration by DLC NHL and renal cancer T1N0M0G2. Cytogenetic and molecular evaluation of bone marow cells showed three distinct clones, (a normal 46XX karyotype, a ringed chromosome 7 and a third clone with an enlarged chromosome 2 as well as several fragments). The patient underwent nephrectomy and eventually received 6 cycles of CHOP 14 chemotherapy. Anemia persisted followed by severe granulocytopenia and thrombocytopenia 6 weeks later. Repeated bone marrow biopsy showed absence of lymphoma and/or cancer metastasis, but massive myelofibrosis with an increased number of atypical megakaryocytes. Considering the short clinical course and the absence of hepatosplenomegaly AMF was diagnosed. The concurrence of three distinctneoplasms within a short period of time as well as the complex cytogenetic aberrations found in her bone marrow cells reflect a strong individual susceptibility to malignant disease in this patient.

  10. Primary bony non-Hodgkin lymphoma of the cervical spine: a case report

    PubMed Central

    2010-01-01

    Introduction Non-Hodgkin lymphoma primarily originating from the bone is exceedingly rare. To our knowledge, this is the first report of primary bone lymphoma presenting with progressive cord compression from an origin in the cervical spine. Herein, we discuss the unusual location in this case, the presenting symptoms, and the management of this disease. Case presentation We report on a 23-year-old Caucasian-American man who presented with two months of night sweats, fatigue, parasthesias, and progressive weakness that had progressed to near quadriplegia. Magnetic resonance (MR) imaging demonstrated significant cord compression seen primarily at C7. Surgical management, with corpectomy and dorsal segmental fusion, in combination with adjuvant chemotherapy and radiation therapy, halted the progression of the primary disease and preserved neurological function. Histological analysis demonstrated an aggressive anaplastic large cell lymphoma. Conclusion Isolated primary bony lymphoma of the spine is exceedingly rare. As in our case, the initial symptoms may be the result of progressive cervical cord compression. Anterior corpectomy with posterolateral decompression and fusion succeeded in preventing progressive neurologic decline and maintaining quality of life. The reader should be aware of the unique presentation of this disease and that surgical management is a successful treatment strategy. PMID:20205845

  11. Palliation by Low-Dose Local Radiation Therapy for Indolent Non-Hodgkin Lymphoma

    SciTech Connect

    Chan, Elisa K.; Fung, Sharon; Gospodarowicz, Mary; Hodgson, David; Wells, Woodrow; Sun, Alexander; Pintile, Melania; Tsang, Richard W.

    2011-12-01

    Purpose: The purpose of this study was to assess the efficacy of a 2 Multiplication-Sign 2 Gy (total dose, 4 Gy) palliative radiation therapy (RT) regimen for treating patients with indolent non-Hodgkin lymphoma (NHL) in terms of response rate, response duration, and symptom relief. Methods and Materials: A retrospective chart review was conducted. Between 2003 and 2007, 54 patients with NHL were treated to 85 anatomical sites with a 2 Multiplication-Sign 2 Gy palliative regimen. Local response was assessed by clinical and/or radiographic data. Symptoms before and after treatment for each site treated were obtained from clinical notes in patient medical records. Median follow-up time was 1.3 years. Results: For the 54 patients, the median age at time of treatment was 71.1 years old, and 57% of them were male. Of the 85 disease sites treated, 56% of sites had indolent histology, 28% of sites were diagnosed with chronic lymphocytic leukemia (CLL), 13% of sites had aggressive histology, and 2% of sites were shown to have other histology. Overall response rate (ORR) was 81% (49% complete response [CR], 32% partial response [PR]). The 2-year rate for freedom from local progression was 50% (95% CI, 37%-61%). The ORR for follicular lymphoma, Mucosa associated lymphoid tissue (MALT), and marginal zone lymphoma (MZL) histology was 88%, compared with a 59% rate for CLL histology (p = 0.005). While the ORR was similar for tumors of different sizes, the CR rate for patients with tumors <5 cm tended to be higher than those with tumors >10 cm (CR rate of 57% vs. 27%, respectively; p = 0.06). For the 48 sites with clearly documented symptoms at pretreatment, 92% of sites improved after low-dose RT. Conclusions: Short-course low-dose palliative radiotherapy (2 Multiplication-Sign 2 Gy) is an effective treatment that results in high response rates for indolent non-Hodgkin lymphoma. This treatment regimen provides effective symptomatic relief for tumor bulk of all sizes.

  12. CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis.

    PubMed

    Charbonneau, Bridget; Wang, Alice H; Maurer, Matthew J; Asmann, Yan W; Zent, Clive S; Link, Brian K; Ansell, Stephen M; Weiner, George J; Ozsan, Nazan; Feldman, Andrew L; Witzig, Thomas E; Cunningham, Julie M; Dogan, Ahmet; Habermann, Thomas M; Slager, Susan L; Novak, Anne J; Cerhan, James R

    2013-09-01

    CXCR5 [chemokine (C-X-C motif) receptor 5; also known as Burkitt lymphoma receptor 1 (BCR1)] is expressed on mature B-cells, subsets of CD4+ and CD8+ T-cells, and skin-derived migratory dendritic cells. Together with its ligand, CXCL13, CXCR5 is involved in guiding B-cells into the B-cell zones of secondary lymphoid organs as well as T-cell migration. This study evaluated the role of common germline genetic variation in CXCR5 in the risk and prognosis of non-Hodgkin lymphoma (NHL) using a clinic-based study of 1,521 controls and 2,694 NHL cases including 710 chronic lymphocytic leukemia/small lymphocytic lymphoma, 586 diffuse large B-cell lymphoma (DLBCL), 588 follicular lymphoma (FL), 137 mantle cell lymphoma (MCL), 230 marginal zone lymphoma (MZL), and 158 peripheral T-cell lymphoma (PTCL). Of the ten CXCR5 tag SNPs in our study, five were associated with risk of NHL, with rs1790192 having the strongest association (OR 1.19, 95% CI 1.08-1.30; p = 0.0003). This SNP was most strongly associated with the risk of FL (OR 1.44, 95 % CI 1.25-1.66; p = 3.1 × 10(-7)), with a lower degree of association with DLBCL (OR 1.16, 95% CI 1.01-1.33; p = 0.04) and PTCL (OR 1.29, 95 % CI 1.02-1.64; p = 0.04) but no association with the risk of MCL or MZL. For FL patients that were observed as initial disease management, the number of minor alleles of rs1790192 was associated with better event-free survival (HR 0.64; 95% CI 0.47-0.87; p = 0.004). These results provide additional evidence for a role of host genetic variation in CXCR5 in lymphomagenesis, particularly for FL.

  13. Aggressive Lymphoma “Sarcoma Mimicker” Originating in the Gluteus and Adductor Muscles: A Case Report and Literature Review

    PubMed Central

    Elkourashy, Sarah A.; Nashwan, Abdulqadir J.; Alam, Syed I.; Ammar, Adham A.; El Sayed, Ahmed M.; Omri, Halima El; Yassin, Mohamed A.

    2016-01-01

    Extranodal lymphoma (ENL) occurs in approximately 30%–40% of all patients with non-Hodgkin lymphoma and has been described in almost all organs and tissues. However, diffuse large B-cell lymphoma is the most common histological subtype of non-Hodgkin lymphoma, primarily arising in the retroperitoneal region. In this article, we report a rare case of an adult male diagnosed with primary diffuse large B-cell lymphoma of the gluteal and adductor muscles with aggressive bone involvement. All appropriate radiological and histopathological studies were done for diagnosis and staging. After discussion with the lymphoma multidisciplinary team, it was agreed to start on R-CHOP protocol (rituximab, cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin®), and prednisone) as the standard of care, which was later changed to R-CODOX-M/R-IVAC protocol (rituximab, cyclophosphamide, vincristine (Oncovin®), doxorubicin, and high-dose methotrexate alternating with rituximab, ifosfamide, etoposide, and high-dose cytarabine) due to inadequate response. Due to the refractory aggressive nature of the disease, subsequent decision of the multidisciplinary team was salvage chemotherapy and autologous stem cell transplant. The aim of this case report was to describe and evaluate the clinical presentation and important radiological features of extranodal lymphoma affecting the musculoskeletal system. PMID:27398038

  14. An unusual presentation of a B-cell cutaneous lymphoma mimicking as nasolabial cyst.

    PubMed

    Demir, Uygar Levent; Nazlıoğlu, Hülya Oztürk

    2013-01-01

    Lymphoma is a cancer of the lymphocytes which leads to solid tumors in the lymphoid organs involving lymph nodes, spleen, liver, bone marrow and skin. Primary cutaneous lymphoma, a rare subtype of non-Hodgkin's lymphoma, can be classified as cutaneous T-cell or cutaneous B-cell lymphoma. These tumors are mostly T-cell origin and mainly locate on trunk, extremities and scalp or forehead. In this article, we report a 22-year-old female case without any symptoms of non-Hodgkin's lymphoma except a sign mimicking nasolabial cyst in the nasolabial fold, who was pathologically diagnosed with cutaneous B-cell lymphoma following surgery.

  15. Chemosensitive epidural spinal cord disease in non-Hodgkins lymphoma.

    PubMed

    Wong, E T; Portlock, C S; O'Brien, J P; DeAngelis, L M

    1996-06-01

    Epidural spinal cord disease (ESCD), an infrequent complication of systemic non-Hodgkins lymphoma (NHL), can occur at diagnosis or at relapse, and is usually treated with radiotherapy, or infrequently surgical decompression. We retrospectively analyzed 140 patients with intermediate-grade NHL (IG-NHL) who were treated on a dose-intense protocol using doxorubicin, vincristine, and high-dose cyclophosphamide (NHL-15). There were seven episodes of ESCD in six (4.3%) patients. Five episodes were asymptomatic at presentation; one patient had back pain, leg numbness, and tingling; and one had radicular pain and mild leg weakness. None had malignant cells in the CSF. One patient received high-dose dexamethasone after laminectomy for diagnostic biopsy; otherwise, dexamethasone was used only as an anti-emetic prior to chemotherapy. Patients who developed ESCD at diagnosis received the planned course of NHL-15 chemotherapy as treatment for ESCD, and those treated with NHL-15 who developed ESCD at relapse were given a regimen containing ifosfamide, carboplatin, and etoposide (ICE). After chemotherapy alone, five of seven episodes showed radiographic resolution of ESCD and improvement of neurologic deficits. One patient received consolidation radiotherapy (2,700 cGy) to the spine after ICE for relapsed ESCD and had a complete response. One patient had progression of systemic lymphoma and ESCD despite chemotherapy. These data suggest that chemotherapy may be effective as initial treatment of ESCD in IG-NHL and may reduce the potential complications of spinal surgery and radiotherapy.

  16. Combination chemotherapy and radiotherapy in non-Hodgkin's lymphomata.

    PubMed Central

    Bonadonna, G.; De Lena, M.; Lattuada, A.; Milani, F.; Monfardini, S.; Beretta, G.

    1975-01-01

    The results obtained with intensive chemotherapy and intensive chemotherapy plus radiotherapy in non-Hodgkin's lymphomata are reported. A quintuple drug regimen (mechloretamine, adriamycin, bleomycin, vincristine and prednisone) in histiocytic lymphomata (Stage III and IV) yielded complete remissions in 53% and complete plus partial remissions in 77%. These figures were 44% and 64% respectively in lymphocytic lymphoma. In Stage III complete responders after combination chemotherapy were subsequently irradiated (involved field irradiation). The median duration of complete remission after completion of radiotherapy was 9-5 months in histiocytic and 12-0 months in lymphocytic lymphomata. At 2 years actuarial survival in Stage III and IV was better in patients with the lymphocytic type and with nodular pattern than with histiocytic and diffuse patterns. A more recent trial compares, in Stage IV patients, cyclophosphamide, vincristine and prednisone (CVP) versus adriamycin, bleomycin and prednisone (ABP). Although the number of evaluable patients is still limited, there appears to be no difference in the response rate between CVP and ABP. In Stages I and II, 6 cycles of CVP were given as adjuvant treatment after radiotherapy. At the present moment, there is no statistical difference in the relapse rate between the group of patients treated with radiotherapy alone and that with radiotherapy plus CVP. PMID:52367

  17. Non-Hodgkin's lymphomas in Saskatchewan: a clinicopathologic study

    PubMed Central

    Cherian, Thomas; Skinnider, Leo F.; Wright, Joanne L.; Komjathy, Gabriel

    1978-01-01

    In a retrospective clinical study of 208 previously untreated persons with non-Hodgkin's lymphomas the disorders were classified and staged according to the histopathologic criteria of Rappaport, Winter and Hicks and the Ann Arbor clinical staging classification. Nodular types constituted 22% and diffuse types 78% of the lymphomas. The nodular lymphomas were slightly more common in females and were clustered in the age range 30 to 90 years. The diffuse lymphomas were slightly more common in males; the age distribution was bimodal, with one peak in the age range 10 to 19 years and the other in the age range 60 to 69 years, but when the age distribution of the general population in which the lymphomas occurred was taken into account, the incidence of these lymphomas was found to be significantly higher (P < 0.001) in persons more than 69 years of age than in those 40 to 69 years of age. Survival correlated with histopathologic type: persons with nodular (follicular) lymphomas and diffuse lymphocytic well differentiated lymphomas had a significantly greater survival (P < 0.05) than those with other diffuse lymphomas. No significant difference in survival was noticed between persons with nodal and extranodal lymphomas. While Rappaport and colleagues' criteria are still very useful, it is important to recognize the nodular lymphoma as a specific entity requiring generally different management from diffuse lymphomas. Appreciation of the different biologic behaviour of the various lymphomas is important to clinicians planning therapy. PMID:356951

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

    ClinicalTrials.gov

    2017-01-27

    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

  19. Case report of non-Hodgkin's lymphoma involving the lacrimal glands demonstrated by computed tomography

    SciTech Connect

    Kniskern, J.A.; Hart, K.; Decker, D.A.; Harris, J.H.

    1981-12-15

    A case of bilateral lacrimal gland infiltration by diffuse, mixed histiocytic-lymphocytic lymphoma demonstrated by computed tomography is reported. Non-Hodgkin's lymphomatous involvement of the lacrimal gland is uncommon. Computed tomography provides precise delineation of perioccular neoplasia.

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

    ClinicalTrials.gov

    2016-12-17

    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

  1. 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.

  2. HIV-1 induction of CD40 on endothelial cells promotes the outgrowth of AIDS-associated B-cell lymphomas.

    PubMed

    Moses, A V; Williams, S E; Strussenberg, J G; Heneveld, M L; Ruhl, R A; Bakke, A C; Bagby, G C; Nelson, J A

    1997-11-01

    Human immunodeficiency virus (HIV)-1 infection is associated with the development of aggressive extranodal B-cell non-Hodgkin's lymphomas. Using microvascular endothelial cell (MVEC)-enriched bone marrow stromal cultures, HIV infection of stromal MVECs from lymphoma patients induced the outgrowth of malignant B cells. MVECs were the only HIV-infected cells in the stroma, and purified brain MVECs also induced a phenotype supportive of neoplastic B-cell attachment and proliferation. HIV infection of MVECs stimulated surface expression of CD40 and allowed preferential induction of the vascular cell adhesion molecule VCAM-1 after CD40 triggering. B-lymphoma cells expressed the CD40 ligand (CD40L), and blocking of CD40-CD40L interactions between HIV-infected MVECs and B-lymphoma cells inhibited B-cell attachment and proliferation. These observations suggest that HIV promotes B-lymphoma cell growth through facilitating attachment of lymphoma cells to HIV-infected MVECs and represent a novel mechanism through which viruses may induce malignancies.

  3. Immunophenotypic criteria for the diagnosis of non-Hodgkin's lymphoma.

    PubMed Central

    Picker, L. J.; Weiss, L. M.; Medeiros, L. J.; Wood, G. S.; Warnke, R. A.

    1987-01-01

    This study examines the immunohistologic profiles of a large series of histologically proven benign and malignant lymphoproliferative processes in order to define immunophenotypic criteria useful in the diagnosis of non-Hodgkin's lymphoma. Using a method of analysis relying solely on immunoarchitectural features of a given case, the authors were able to define immunologic criteria capable of differentiating benign from malignant lymphoid processes independent from conventional morphologic analysis. In general, these criteria involved identification of abnormal expression or loss of antigens in B- and T-lineage populations. Among B-lineage populations the following features were associated with malignant histology: 1) light-chain-restricted B lineage, 2) light chain -B lineage, 3) Leu-1+ B lineage, 4) L60+ B lineage, 5) 41H+, Ki-67+ B lineage, 6) loss of pan-B antigens, and 7) LFA-1-B lineage. Among T-cell populations outside the thymus, phenotypes associated with malignancy included 1) loss of pan-T antigens (including loss of the beta chain of the T-cell antigen receptor), 2) coexpression or loss of T-subset antigens, 3) Leu-6+ T-lineage, and 4) MB-1+ T lineage. Application of these criteria to a series of nearly 500 cases of lymphoma indicated that over 90% of B-lineage and about 80% of T-lineage neoplasms manifested immunophenotypic abnormalities that could distinguish them from benign, reactive lymphoid processes. It is concluded that immunophenotypic analysis of lymphoproliferative lesions is sufficiently sensitive and specific to confirm the histologic diagnosis of lymphoma in the vast majority of cases seen in clinical practice. Furthermore, in difficult cases or those with limited material or poor histology, immunophenotypic analysis may be the only means of making a definitive diagnosis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:3111266

  4. Proteasome Inhibition and Combination Therapy for Non-Hodgkin's Lymphoma: From Bench to Bedside

    PubMed Central

    Feldman, Tatyana; Goy, André

    2012-01-01

    Although patients with B-cell non-Hodgkin's lymphoma (NHL) usually respond to initial conventional chemotherapy, they often relapse and mortality has continued to increase over the last three decades in spite of salvage therapy or high dose therapy and stem cell transplantation. Outcomes vary by subtype, but there continues to be a need for novel options that can help overcome chemotherapy resistance, offer new options as consolidation or maintenance therapy postinduction, and offer potentially less toxic combinations, especially in the elderly population. The bulk of these emerging novel agents for cancer treatment target important biological cellular processes. Bortezomib is the first in the class of proteasome inhibitors (PIs), which target the critical process of intracellular protein degradation or recycling and editing through the proteasome. Bortezomib is approved for the treatment of relapsed or refractory mantle cell lymphoma. The mechanisms of proteasome inhibition are very complex by nature (because they affect many pathways) and not fully understood. However, mechanisms of action shared by bortezomib and investigational PIs such as carfilzomib, marizomib, ONX-0912, and MLN9708 are distinct from those of other NHL treatments, making them attractive options for combination therapy. Preclinical evidence suggests that the PIs have additive and/or synergistic activity with a large number of agents both in vitro and in vivo, from cytotoxics to new biologicals, supporting a growing number of combination studies currently underway in NHL patients, as reviewed in this article. The results of these studies will help our understanding about how to best integrate proteasome inhibition in the management of NHL and continue to improve patient outcomes. PMID:22566373

  5. Residential exposure to traffic noise and risk for non-hodgkin lymphoma among adults.

    PubMed

    Sørensen, Mette; Harbo Poulsen, Aslak; Ketzel, Matthias; Oksbjerg Dalton, Susanne; Friis, Søren; Raaschou-Nielsen, Ole

    2015-10-01

    Exposure to traffic noise may result in stress and sleep disturbances, which have been associated with impairment of the immune system. People with weakened immune systems are known to have a higher risk for non-Hodgkin lymphoma (NHL). We aimed to determine whether traffic noise was associated with risk for NHL in a nationwide case-control study. We identified 2753 cases aged 30-84 years with a primary diagnosis of NHL in Denmark between 1992 and 2010. For each case we selected two random population controls, matched on sex and year of birth. Road traffic and railway noise were calculated, and airport noise was estimated for all present and historical residential addresses of cases and controls from 1987 to 2010. Associations between traffic noise and risk for NHL were estimated using conditional logistic regression, adjusted for disposable income, education, cohabiting status and comorbidity. We found that a 5-year time-weighted mean of road traffic noise above 65 dB was associated with an 18% higher risk for NHL (95% confidence interval (CI) 1.01-1.37) when compared to road traffic noise below 55 dB, whereas for exposure between 55 and 65 dB no association was found (odds ratio: 0.98; 95% CI: 0.88-1.08). In analyzes of NHL subtypes, we found no association between road traffic noise and risk for T-cell lymphoma, whereas increased risks for B-cell lymphoma and unspecified lymphomas were observed at exposures above 65 dB. In conclusion, our nationwide study may indicate that high exposure to traffic noise is associated with higher NHL risk.

  6. Polycyclic aromatic hydrocarbons: determinants of residential carpet dust levels and risk of non-Hodgkin lymphoma

    PubMed Central

    DellaValle, Curt T.; Deziel, Nicole C.; Jones, Rena R.; Colt, Joanne S.; De Roos, Anneclaire J.; Cerhan, James R.; Cozen, Wendy; Severson, Richard K.; Flory, Abigail R.; Morton, Lindsay M.

    2017-01-01

    Purpose To investigate the risk of non-Hodgkin lymphoma (NHL) associated with residential carpet dust measurements of polycyclic aromatic hydrocarbons (PAHs). Methods We evaluated the relationship between residential carpet dust PAH concentrations (benz(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, benzo(k)fluoranthene, chrysene, dibenz(a,h)anthracene, and indeno(1,2,3-c,d)pyrene, and their sum) and risk of NHL (676 cases, 511 controls) in the National Cancer Institute Surveillance Epidemiology and End Results multicenter case–control study. As a secondary aim, we investigated determinants of dust PAH concentrations. We computed odds ratios (OR) and 95 % confidence interval (CI) for associations between NHL and concentrations of individual and summed PAHs using unconditional logistic regression, adjusting for age, gender, and study center. Determinants of natural log-transformed PAHs were investigated using multivariate least-squares regression. Results We observed some elevated risks for NHL overall and B cell lymphoma subtypes in association with quartiles or tertiles of PAH concentrations, but without a monotonic trend, and there was no association comparing the highest quartile or tertile to the lowest. In contrast, risk of T cell lymphoma was significantly increased among participants with the highest tertile of summed PAHs (OR = 3.04; 95 % CI, 1.09–8.47) and benzo(k)fluoranthene (OR = 3.20; 95 % CI, 1.13–9.11) compared with the lowest tertile. Predictors of PAH dust concentrations in homes included ambient air PAH concentrations and the proportion of developed land within 2 km of a residence. Older age, more years of education, and white race were also predictive of higher levels in homes. Conclusion Our results suggest a potential link between PAH exposure and risk of T cell lymphoma and demonstrate the importance of analyzing risk by NHL histologic type. PMID:26573845

  7. Prognosis and outcome of non-Hodgkin lymphoma in primary Sjögren syndrome.

    PubMed

    Voulgarelis, Michael; Ziakas, Panayiotis D; Papageorgiou, Aristea; Baimpa, Evangelia; Tzioufas, Athanasios G; Moutsopoulos, Haralampos M

    2012-01-01

    Sjögren syndrome (SS) has been associated with the development of non-Hodgkin lymphoma (NHL). From a cohort of 584 SS patients followed in our department from 1980 to 2010, we retrospectively analyzed 53 consecutive NHL cases. Considerations included histologic type, clinical manifestation and NHL staging, treatment, response rate and overall survival (OS), event-free survival (EFS), and standardized mortality ratio (SMR).Mucosa-associated lymphoid tissue (MALT) lymphomas constituted the majority (59%) of NHL subtypes, followed by nodal marginal zone lymphomas (NMZLs) (15%) and diffuse large B-cell lymphomas (DLBCLs) (15%). Six lymphoma patients died during the median follow-up of 40.8 months. The corresponding age/sex-adjusted SMR of SS with and without NHLs versus the general population was 3.25 (95% confidence interval [CI] 1.32-6.76) and 1.08 (95% CI, 0.79-1.45), respectively. A "watch and wait" policy was adopted for 9 patients with asymptomatic localized salivary MALT lymphomas. Eight patients with limited-stage MALT lymphomas and extraglandular manifestations were treated with rituximab. Ten MALT lymphoma patients with disseminated disease received chemotherapy with or without rituximab. The 3-year OS and EFS in patients with MALT lymphomas was 97% and 78%, respectively. Rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was the chosen therapeutic intervention for patients with DLBCLs. A successful outcome was recorded for this group, with 100% OS and EFS at 3 years. Patients with NMZLs had a less favorable outcome, with a 3-year OS of 80% and EFS of 53%. Our results describe the course and prognosis of SS-associated NHL and highlight the need for a risk-stratified treatment approach.

  8. 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.

  9. Colorectal cancer DNA methylation marker panel validated with high performance in Non-Hodgkin lymphoma

    PubMed Central

    Bethge, Nicole; Lothe, Ragnhild A; Honne, Hilde; Andresen, Kim; Trøen, Gunhild; Eknæs, Mette; Liestøl, Knut; Holte, Harald; Delabie, Jan; Smeland, Erlend B; Lind, Guro E

    2014-01-01

    Genes with altered DNA methylation can be used as biomarkers for cancer detection and assessment of prognosis. Here we analyzed the methylation status of a colorectal cancer biomarker panel (CNRIP1, FBN1, INA, MAL, SNCA, and SPG20) in 97 cancer cell lines, derived from 17 different cancer types. Interestingly, the genes were frequently methylated also in hematological cancer types and were therefore subjected to analyses in primary tumor samples from the major types of non-Hodgkin lymphomas (NHL) and in healthy controls. In total, the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 were methylated in 53%, 23%, 52%, 69%, 97%, and 92% of the tumor samples, respectively, and were unmethylated in all healthy controls. With the exception of a single tumor sample, a correct prediction of lymphoma or normal sample was made in a blinded analysis of the validation series using a combination of SNCA and SPG20. The combined ROC-curve analysis of these genes resulted in an area under the curve of 0.999 (P = 4.2 × 10−18), and a sensitivity and specificity of 98% and 100%, respectively, across the test and validation series. Interestingly, the promoter methylation of CNRIP1 was associated with decreased overall survival in diffuse large B-cell lymphoma (DLBCL) (P = 0.03).   In conclusion, our results demonstrate that SNCA and SPG20 methylation might be suitable for early detection and monitoring of NHL. Furthermore, CNRIP1 could potentially be used as a prognostic factor in DLBCL. PMID:24362313

  10. Clinical Analysis of Five Cases of AIDS-related Non-Hodgkin Lymphoma

    PubMed Central

    Zuo, Shubo; Xu, Na; Li, Zhongkun; Li, Na; Xia, Hong; Ren, Hongtao; Bao, Huizheng

    2016-01-01

    Objective: Secondary malignancy is a major life-threatening complication facing patients afflicted with acquired immunodeficiency syndrome (AIDS). This study aimed to retrospectively review clinical features and treatment course of five patients with AIDS-associated non-Hodgkin lymphoma (A-NHL) in Jilin Tumor Hospital. Methods: Five A-NHL patients were retrospectively and consecutively hospitalized at our oncological unit between January 2012 and June 2014. All patients received pre-emptive highly active antiretroviral therapy (HAART) and chemotherapy, and were subsequently followed up at the outpatient clinic. All five patients were male, aged 27–53 years, and afflicted with A-NHL involving upper jaw, right inguinal region, right-side gingiva, mediastinum, or right-side neck. Histology showed diffuse large B-cell lymphoma (n = 3) or plasmablastic lymphoma (n = 2). Results: Two patients achieved complete remission after HAART and chemotherapy, whereas other three patients required a second-line treatment, with two achieving stable disease and one dying within a follow-up period of 0.5−2 years. Conclusion: The findings of the present study showed that A-NHL is a disease often diagnosed in the middle-to-late stages, with diverse clinical manifestations and short overall survival. In the cases reviewed in this study, HAART in combination with standard dose or high-dose chemotherapy, HAART and molecular targeted chemotherapy was administered, and these treatments proved to be effective for improving the prognosis of these patients. Moreover, the CD4+ cell count was important for determining the prognosis of patients. PMID:28083067

  11. Evaluation of Pax5 expression and comparison with BLA.36 and CD79αcy in feline non-Hodgkin lymphoma.

    PubMed

    Felisberto, R; Matos, J; Alves, M; Cabeçadas, J; Henriques, J

    2016-08-22

    Paired box gene 5 (Pax5) is a widely used B-cell marker for human and canine non-Hodgkin's lymphoma (nHL); however, in the literature there is only one case report using Pax5 in a cat B-cell lymphoma. The purposes of this study were to investigate the expression and detection of B-cell specific activator protein (BSAP) using a monoclonal anti-Pax5 antibody in feline nHL (FnHL) tissue samples to evaluate its diagnostic relevance as a B-cell marker. A total of 45 FnHL samples in 45 cats were evaluated. B-cell lymphoma was the most common immunophenotype (51.1%) for all the samples and T-cell the most common immunophenotype (64.3%) for the gastrointestinal (GI) form. Pax5 stained 82.6% of all B-cell lymphomas and no expression was found in any of the T-cell lymphomas. Anti-Pax5 antibody staining in FnHL is similar to that reported in human and canine counterparts and may offer an excellent B-cell marker in cats.

  12. PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium

    PubMed Central

    Conde, Lucia; Slager, Susan L.; Brooks-Wilson, Angela; Morton, Lindsay; Skibola, Danica R.; Novak, Anne J.; Riby, Jacques; Ansell, Stephen M.; Halperin, Eran; Shanafelt, Tait D.; Agana, Luz; Wang, Alice H.; De Roos, Anneclaire J.; Severson, Richard K.; Cozen, Wendy; Spinelli, John; Butterbach, Katja; Becker, Nikolaus; de Sanjose, Silvia; Benavente, Yolanda; Cocco, Pierluigi; Staines, Anthony; Maynadié, Marc; Foretova, Lenka; Boffetta, Paolo; Brennan, Paul; Lan, Qing; Zhang, Yawei; Zheng, Tongzhang; Purdue, Mark; Armstrong, Bruce; Kricker, Anne; Vajdic, Claire M.; Grulich, Andrew; Smith, Martyn T.; Bracci, Paige M.; Chanock, Stephen J.; Hartge, Patricia; Cerhan, James R.; Wang, Sophia S.; Rothman, Nathaniel; Skibola, Christine F.

    2012-01-01

    Many common genetic variants have been associated with non-Hodgkin lymphoma (NHL), but individual study results are often conflicting. To confirm the role of putative risk alleles in B-cell NHL etiology, we performed a validation genotyping study of 67 candidate single nucleotide polymorphisms within InterLymph, a large international consortium of NHL case-control studies. A meta-analysis was performed on data from 5633 B-cell NHL cases and 7034 controls from 8 InterLymph studies. rs3789068 in the proapoptotic BCL2L11 gene was associated with an increased risk for B-cell NHL (odds ratio = 1.21, P random = 2.21 × 10−11), with similar risk estimates for common B-cell subtypes. PRRC2A rs3132453 in the HLA complex class III region conferred a reduced risk of B-cell NHL (odds ratio = 0.68, P random = 1.07 × 10−9) and was likewise evident for common B-cell subtypes. These results are consistent with the known biology of NHL and provide insights into shared pathogenic components, including apoptosis and immune regulation, for the major B-cell lymphoma subtypes. PMID:23047821

  13. 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

  14. Belinostat and vincristine demonstrate mutually synergistic cytotoxicity associated with mitotic arrest and inhibition of polyploidy in a preclinical model of aggressive diffuse large B cell lymphoma.

    PubMed

    Havas, Aaron P; Rodrigues, Kameron B; Bhakta, Anvi; Demirjian, Joseph A; Hahn, Seongmin; Tran, Jack; Scavello, Margarethakay; Tula-Sanchez, Ana A; Zeng, Yi; Schmelz, Monika; Smith, Catharine L

    2016-12-01

    Diffuse Large B-cell lymphoma (DLBCL) is an aggressive malignancy that has a 60 percent 5-year survival rate, highlighting a need for new therapeutic approaches. Histone deacetylase inhibitors (HDACi) are novel therapeutics being clinically-evaluated in combination with a variety of other drugs. However, rational selection of companion therapeutics for HDACi is difficult due to their poorly-understood, cell-type specific mechanisms of action. To address this, we developed a pre-clinical model system of sensitivity and resistance to the HDACi belinostat using DLBCL cell lines. In the current study, we demonstrate that cell lines sensitive to the cytotoxic effects of HDACi undergo early mitotic arrest prior to apoptosis. In contrast, HDACi-resistant cell lines complete mitosis after a short delay and arrest in G1. To force mitotic arrest in HDACi-resistant cell lines, we used low dose vincristine or paclitaxel in combination with belinostat and observed synergistic cytotoxicity. Belinostat curtails vincristine-induced mitotic arrest and triggers a strong apoptotic response associated with downregulated MCL-1 expression and upregulated BIM expression. Resistance to microtubule targeting agents (MTAs) has been associated with their propensity to induce polyploidy and thereby increase the probability of genomic instability that enables cancer progression. Co-treatment with belinostat effectively eliminated a vincristine-induced, actively cycling polyploid cell population. Our study demonstrates that vincristine sensitizes DLBCL cells to the cytotoxic effects of belinostat and that belinostat prevents polyploidy that could cause vincristine resistance. Our findings provide a rationale for using low dose MTAs in conjunction with HDACi as a potential therapeutic strategy for treatment of aggressive DLBCL.

  15. Value of PET restaging after chemotherapy for non-Hodgkin's lymphoma: Implications for consolidation radiotherapy

    SciTech Connect

    Kahn, Shannon T.; Flowers, Christopher; Lechowicz, Mary Jo; Hollenbach, Kathryn; Johnstone, Peter . E-mail: peter@radonc.emory.org

    2006-11-15

    Purpose/Objective: Patients treated for non-Hodgkin's Lymphoma (NHL) frequently are restaged for response using positron emission tomography (PET) scanning. This study investigates the role of subsequent consolidation radiation therapy (CRT) based on PET response to chemotherapy. Materials/Methods: An IRB-approved database was queried for patients who underwent PET scans after chemotherapy for NHL between 1995 and 2004; 77 patients were identified. To determine benefit of CRT, overall survival and local control were assessed with median follow-up of 39.8 months (range, 2-125 months). Results: Median age of patients was 53 (range, 18-82 years). Multivariate analysis adjusted for age, indolent vs. aggressive histology, and time from chemotherapy to PET revealed PET positive scans (RR = 30.5; 95%CI = 5.9, 156.4), lack of RT (RR = 5.25; 95%CI = 1.26, 21.79), and Stage III/IV presentation (RR = 4.35; 95%CI = 1.03, 20) predicted increased likelihood of recurrence. Patients with positive PET scans after chemotherapy had significantly higher risk of relapse than those with negative scans (58.1% vs. 15.2%; p < 0.0001), although not everyone with positive scans recurred. Patients with positive PET scans receiving RT were not protected from relapse (63.2% relapse with RT, 50% relapse without RT; p = 0.71); in fact, over half the relapses in patients receiving RT for persistently positive PET scans were in-field. Crude 2 year OS was significantly different between PET positive and PET negative cohorts (p < 0.01). Conclusions: While RT may control relapse in PET negative patients, NHL patients who remain PET positive after chemotherapy are not well managed by RT alone.

  16. 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.

  17. Serum BLyS levels increase after rituximab as initial therapy in patients with follicular grade 1 non-Hodgkin lymphoma

    PubMed Central

    Ansell, Stephen M.; Novak, Anne J.; Ziesmer, Steven; Price-Troska, Tammy; LaPlant, Betsy; Dillon, Stacey R.; Witzig, Thomas E.

    2009-01-01

    Serum B-lymphocyte stimulator (BLyS) levels are elevated in a subset of non-Hodgkin lymphoma (NHL) patients, particularly those with a family history of B-cell malignancies or a polymorphism in the BLyS gene. BLyS promotes growth of malignant B-cells and increased serum BLyS levels are associated with a poor clinical outcome. In this study, BLyS levels were measured before and after 4 weekly doses of rituximab in 30 patients with previously untreated follicular Grade 1 NHL. A significant increase was seen in the serum levels of BLyS (P = 0.0001) after rituximab therapy. The increase was independent of genetic variability in the BLyS gene. PMID:19051265

  18. [Treatment outcome in primary testicular non-Hodgkin lymphoma].

    PubMed

    Iványi, János László; Marton, Eva; Plander, Márk; Engert, Zoltán Vendel; Tóth, Csaba

    2013-10-20

    Bevezetés: A primer herelymphoma ritkán előforduló extranodalis non-Hodgkin-lymphoma-entitás. Legtöbbször idős férfiakban fordul elő, nagy malignitású szövettani képpel és kedvezőtlen kórlefolyással. Az érintett here eltávolítása után alkalmazott immunkemoterápia ellenére a betegek kezelési eredményei elmaradnak más extranodalis lymphomásokétól. Célkitűzés: Retrospektív felmérésben a szerzők célul tűzték ki 2000 és 2012 között kórismézett és kezelt herelymphomás betegeik klinikopatológiai és kezelési eredményeinek felmérését. Módszer: Ezen időszak alatt 334 agresszív non-Hodgkin-lymphomás betegből nyolc esetben (8/334, 2,39%) kórisméztek primer herelymphomát (diffúz nagysejtes B-sejtes hét esetben, Burkitt-típusú egy esetben). A betegek medián életkora 60 év (23 és 86 év között) volt. Korai I–IIE hét betegben, előrehaladott stádium egy betegben fordult elő. Egy beteg kivételével (csak radioterápia) minden beteg kemoterápiát kapott (rituximab+CHOP, hat–nyolc ciklus 21 vagy 28 naponként). Mindössze egy beteg részesült központi idegrendszeri kemoterápiás profilaxisban, preventív ellenoldali hereirradiációt nem alkalmaztak. Eredmények: Ötven hónapos medián követés alatt semicastratiót követő rituximab- és CHOP-kúra után hét beteg került komplett remisszióba, két beteg elhunyt (egy beteg a lymphoma progressziója következtében, a remisszióban levő másik beteg szekunder tüdőtumor miatt). Komplett remissziót a betegek 87,5%-ában értek el. A betegségmentes túlélés 13–152 hónap között (medián 38 hónap), az összesített túlélés 17–156 hónap között (medián 43 hónap), az ötéves betegségmentes és összesített túlélés pedig egyaránt 37,5% volt. Következtetések: A viszonylag kedvező kezelési eredmények hátterében a korai stádium túlsúlya, a lymphoma urológiai sebészi eltávolítása, az immunkemoterápia hat

  19. Radiological study of two disseminated maligant non-Hodgkin lymphomas affecting only the bones in children

    SciTech Connect

    Vanel, D; Rebibo, G.; Tamman, S.; Bayle, C.; Hartmann, O.

    1982-12-01

    Malignant non-Hodgkin lymphomas are a neoplastic proliferation of lymphoid cells whose clinical manifestations are extremely variable. All tissues can be affected. There may be localization in lymphoid organs (Waldeyer's ring, spleen, digestive tract), other localizations (lungs, pleura, liver, bone marrow, central nervous system) and unusual localizations. Although bone marrow is often affected, bone involvement is very rare in the early stages of the disease. This report concerns the radiological study of two disseminated malignant non-Hodgkin lymphomas affecting only the bone in children.

  20. Simultaneous presentation of relapsing Hodgkin's disease and treatment-related non-Hodgkin's lymphoma

    SciTech Connect

    Perri, R.T.; Allen, J.I.; Oken, M.M.; Limas, C.; Kay, N.E.

    1985-01-01

    A 55-year-old white man was diagnosed in 1975 with Hodgkin's disease stage IIA, mixed cellularity. He was treated with 4,500 rads to an inverted-Y field followed by six cycles of MOPP and remained in complete remission. In 1983 a right axillary lymph node biopsy showed recurrent Hodgkin's disease, mixed cellularity. While receiving his initial chemotherapy he developed persistent epigastric distress. Endoscopic gastric biopsy demonstrated a diffuse large-cell non-Hodgkin's lymphoma. Surface marker studies confirmed the separate identity of these two malignant lymphoproliferative processes. This represents the first reported simultaneous occurrence of relapsing Hodgkin's disease with treatment-related non-Hodgkin's lymphoma.

  1. Roentgenographic aspects on non-Hodgkin's lymphomas presenting with osseous lesions

    SciTech Connect

    Spagnoli, I.; Gattoni, F.; Viganotti, G.

    1982-03-01

    Radiographs of 992 patients with previously untreated non-Hodgkin's lymphoma were reviewed, and bone involvement was found in 61. Ten patients had primary lymphoma of bone and 51 patients had concomitant lymph node and/or visceral involvement or several affected bones. Roentgenographic analysis of all the bone lesions showed that osteolysis predominated, but without specific diagnostic features, and that cortical destruction and soft tissue involvement carry an adverse prognosis. Routine skeletal X-ray survey in the initial staging of non-Hodgkin's lymphomas is essential.

  2. Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice

    PubMed Central

    Gil, Veronica S.; Howell, Louise; Zhang, Jiyuan; Kim, Chae H.; Stengel, Sven; Vega, Francisco; Zelent, Arthur

    2016-01-01

    ABSTRACT Histone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (Eμ). Here, we report that the Eμ-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD) with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of Eμ-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors. PMID:27799148

  3. Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma.

    PubMed

    Chen, Yingtai; Zheng, Tongzhang; Lan, Qing; Foss, Francine; Kim, Christopher; Chen, Xuezhong; Dai, Min; Li, Yumin; Holford, Theodore; Leaderer, Brian; Boyle, Peter; Chanock, Stephen J; Rothman, Nathaniel; Zhang, Yawei

    2011-01-13

    We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m(2), women with BMI more than or equal to 25 kg/m(2) had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 P(forinteraction) = .034) and IL7R (rs1494555 P(forinteraction) = .016) for NHL overall; IL7R (rs1494555 P(forinteraction) = .016) and TNF (1799724 P(forinteraction) = .031) for B-cell lymphoma; and IL5 (rs2069812 P(forinteraction) = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 P(forinteraction) = .006), IL13 (rs20541 P(forinteraction) = .019), and IL7R (rs1494555 P(forinteraction) = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 P(forinteraction) = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 P(forinteraction) = .013) and TNF (1799724 P(forinteraction) = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.

  4. Alcohol intake and the incidence of non-hodgkin lymphoid neoplasms in the cancer prevention study II nutrition cohort.

    PubMed

    Gapstur, Susan M; Diver, W Ryan; McCullough, Marjorie L; Teras, Lauren R; Thun, Michael J; Patel, Alpa V

    2012-07-01

    Although several studies have shown a lower risk of non-Hodgkin lymphoma (NHL) in alcohol drinkers compared with nondrinkers, the dose-response relation and potential differences between former and current drinking and across beverage types and subtypes are unclear. The authors examined associations of alcohol intake with risk of NHL and NHL subtypes in the Cancer Prevention Study II Nutrition Cohort, a prospective study of US men and women aged 50-74 years. Between 1992 and 2007, there were 1,991 incident NHL cases among 143,124 participants. Multivariable-adjusted relative risks and 95% confidence intervals were computed using Cox proportional hazards regression. Compared with nondrinkers, the relative risk of NHL associated with former drinking was 0.90 (95% confidence interval (CI): 0.75, 1.10); the relative risks associated with current intakes of <1, 1-2, and >2 drinks/day were 0.93 (95% CI: 0.83, 1.03), 0.91 (95% CI: 0.78, 1.06), and 0.78 (95% CI: 0.65, 0.93), respectively. Associations did not differ by sex (P-interaction = 0.45) or beverage type (P-difference = 0.22). Alcohol intake was more strongly associated with B-cell lymphoma (P-trend = 0.005) than with T-cell lymphoma (P-trend = 0.76), and associations were similar among B-cell lymphoma subtypes. In this prospective study, current heavy alcohol intake was associated with a reduced risk of NHL. Associations did not differ by beverage type and were slightly stronger for B-cell tumors than for T-cell tumors.

  5. A Review of Obinutuzumab (GA101), a Novel Type II Anti-CD20 Monoclonal Antibody, for the Treatment of Patients with B-Cell Malignancies.

    PubMed

    Tobinai, Kensei; Klein, Christian; Oya, Naoko; Fingerle-Rowson, Günter

    2017-02-01

    Obinutuzumab (GA101) is a novel, type II, glycoengineered, humanized anti-CD20 monoclonal antibody that has been developed to address the need for new therapeutics with improved efficacy in patients with lymphocytic leukemia and lymphoma of B-cell origin. Obinutuzumab has a distinct mode of action relative to type I anti-CD20 antibodies, such as rituximab, working primarily by inducing direct cell death and antibody-dependent cell-mediated cytotoxicity. Obinutuzumab is under investigation in a wide-ranging program of clinical trials in patients with B-cell malignancies. Efficacy as monotherapy has been reported in patients with relapsed/refractory indolent and aggressive non-Hodgkin lymphoma (NHL) and in chronic lymphocytic leukemia (CLL) of B-cell origin. Improved outcomes have also been noted when obinutuzumab is added to chemotherapy in patients with B-cell NHL, and superiority over rituximab has been reported with combination therapy in patients with CLL. Ongoing research is focusing on developing options for chemotherapy-free treatment and on new combinations of obinutuzumab with novel targeted agents.

  6. Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents

    PubMed Central

    Gerrard, Mary; Sposto, Richard; Auperin, Anne; Pinkerton, C. Ross; Michon, Jean; Weston, Claire; Perkins, Sherrie L.; Raphael, Martine; McCarthy, Keith; Patte, Catherine

    2007-01-01

    The prognosis for higher risk childhood B-cell non-Hodgkin lymphoma has improved over the past 20 years but the optimal intensity of treatment has yet to be determined. Children 21 years old or younger with newly diagnosed B-cell non-Hodgkin lymphoma/B-cell acute lymphoblastic leukemia (B-NHL/B-ALL) with higher risk factors (bone marrow [BM] with or without CNS involvement) were randomized to standard intensity French-American-British/Lymphoma Malignancy B (FAB/LMB) therapy or reduced intensity (reduced cytarabine plus etoposide and deletion of 3 maintenance courses M2, M3, M4). All patients with CNS disease had additional high-dose methotrexate (8 g/m2) plus extra intrathecal therapy. Fifty-one percent had BM involvement, 20% had CNS involvement, and 29% had BM and CNS involvement. One hundred ninety patients were randomized. The probabilities of 4-year event-free survival (EFS) and survival (S) were 79% ± 2.7% and 82% ± 2.6%, respectively. In patients in remission after 3 cycles who were randomized to standard versus reduced-intensity therapy, the 4-year EFS after randomization was 90% ± 3.1% versus 80% ± 4.2% (one-sided P = .064) and S was 93% ± 2.7% versus 83% ± 4.0% (one-sided P = .032). Patients with either combined BM/CNS disease at diagnosis or poor response to cyclophosphamide, Oncovin [vincristine], prednisone (COP) reduction therapy had a significantly inferior EFS and S (P < .001). Standard-intensity FAB/LMB therapy is recommended for children with high-risk B-NHL (B-ALL with or without CNS involvement). PMID:17138821

  7. Dairy Product Consumption and Risk of Non-Hodgkin Lymphoma: A Meta-Analysis.

    PubMed

    Wang, Jia; Li, Xutong; Zhang, Dongfeng

    2016-02-27

    Many epidemiologic studies have explored the association between dairy product consumption and the risk of non-Hodgkin lymphoma (NHL), but the results remain controversial. A literature search was performed in PubMed, Web of Science and Embase for relevant articles published up to October 2015. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. The dose-response relationship was assessed by restricted cubic spline. A total of 16 articles were eligible for this meta-analysis. The pooled RRs (95% CIs) of NHL for the highest vs. lowest category of the consumption of total dairy product, milk, butter, cheese, ice cream and yogurt were 1.20 (1.02, 1.42), 1.41 (1.08, 1.84), 1.31 (1.04, 1.65), 1.14 (0.96, 1.34), 1.57 (1.11, 2.20) and 0.78 (0.54, 1.12), respectively. In subgroup analyses, the positive association between total dairy product consumption and the risk of NHL was found among case-control studies (RR = 1.41, 95% CI: 1.17-1.70) but not among cohort studies (RR = 1.02, 95% CI: 0.88-1.17). The pooled RRs (95% CIs) of NHL were 1.21 (1.01, 1.46) for milk consumption in studies conducted in North America, and 1.24 (1.09, 1.40) for cheese consumption in studies that adopted validated food frequency questionnaires. In further analysis of NHL subtypes, we found statistically significant associations between the consumption of total dairy product (RR = 1.73, 95% CI: 1.22-2.45) and milk (RR = 1.49, 95% CI: 1.08-2.06) and the risk of diffuse large B-cell lymphoma. The dose-response analysis suggested that the risk of NHL increased by 5% (1.05 (1.00-1.10)) and 6% (1.06 (0.99-1.13)) for each 200 g/day increment of total dairy product and milk consumption, respectively. This meta-analysis suggested that dairy product consumption, but not yogurt, may increase the risk of NHL. More prospective cohort studies that investigate specific types of dairy product consumption are needed to confirm this conclusion.

  8. Residential proximity to industrial facilities and risk of non-Hodgkin lymphoma.

    PubMed

    De Roos, A J; Davis, S; Colt, J S; Blair, A; Airola, M; Severson, R K; Cozen, W; Cerhan, J R; Hartge, P; Nuckols, J R; Ward, M H

    2010-01-01

    Industrial pollution has been suspected as a cause of non-Hodgkin lymphoma (NHL), based on associations with chemical exposures in occupational studies. We conducted a case-control study of NHL in four SEER regions of the United States, in which residential locations of 864 cases and 684 controls during the 10 years before recruitment were used to characterize proximity to industrial facilities reporting chemical releases to the Environmental Protection Agency's Toxics Release Inventory (TRI). For each of 15 types of industry (by 2-digit SIC code), we evaluated the risk of NHL associated with having lived within 2 miles of a facility, the distance to the nearest facility (miles categories of < or =0.5, >0.5-1.0, >1.0-2.0, >2 [referent]), and the duration of residence within 2miles (years categories of 10, 1-9, 0 [referent]), using logistic regression. Increased risk of NHL was observed in relation to lumber and wood products facilities (SIC 24) for the shortest distance of residential proximity (< or =0.5 mile: odds ratio [OR]=2.2, 95% confidence interval [CI]: 0.4-11.8) or the longest duration (10 years: OR=1.9, 95% CI: 0.8-4.8); the association with lumber facilities was more apparent for diffuse large B-cell lymphoma (lived within 2 miles: OR=1.7, 95% CI: 1.0-3.0) than for follicular lymphoma (OR=1.1, 95% CI: 0.5-2.2). We also observed elevated ORs for the chemical (SIC 28, 10 years: OR=1.5, 95% CI: 1.1-2.0), petroleum (SIC 29, 10 years: OR=1.9, 95% CI: 1.0-3.6), rubber/miscellaneous plastics products (SIC 30, < or =0.5mile: OR=2.7, 95% CI: 1.0-7.4), and primary metal (SIC 33, lived within 2miles: OR=1.3, 95% CI: 1.0-1.6) industries; however, patterns of risk were inconsistent between distance and duration metrics. This study does not provide strong evidence that living near manufacturing industries increases NHL risk. However, future studies designed to include greater numbers of persons living near specific types of industries, along with fate

  9. Obese non-Hodgkin lymphoma patients tolerate full uncapped doses of chemotherapy with no increase in toxicity, and a similar survival to that seen in nonobese patients.

    PubMed

    Chan, Henry; Jackson, Sharon; McLay, Jessica; Knox, Angela; Lee, Jae; Wang, Sarah; Issa, Samar

    2016-11-01

    The aim of this study is to compare the risk of treatment-related toxicities and long-term survival between obese and nonobese patients with non-Hodgkin lymphoma when treated with full uncapped doses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. A total of 133 patients and 733 cycles of chemotherapy were analyzed. Obese patients did not experience an increased risk of acute treatment-related toxicities (adjusted odds ratio 0.825, p = 0.197), or delayed toxicities (adjusted odds ratio 0.819, p = 0.779). In the subgroup of diffuse large B-cell lymphoma patients (n = 109), treatment response rate was similar between the two body mass index (BMI) groups, and obese patients tended to have superior overall and progression-free survivals, albeit not statistically significant. Full uncapped doses of R-CHOP chemotherapy administered to obese patients with non-Hodgkin lymphoma (NHL) are safe, well tolerated, and do not lead to inferior treatment response or long-term outcomes.

  10. Phase II Study of Yttrium-90 Ibritumomab Tiuxetan Plus High-Dose BCNU, Etoposide, Cytarabine, and Melphalan for Non-Hodgkin Lymphoma: The Role of Histology.

    PubMed

    Krishnan, Amrita Y; Palmer, Joycelynne; Nademanee, Auayporn P; Chen, Robert; Popplewell, Leslie L; Tsai, Ni-Chun; Sanchez, James F; Simpson, Jennifer; Spielberger, Ricardo; Yamauchi, Dave; Forman, Stephen J

    2017-03-04

    Standard-dose (90)yttrium-ibritumomab tiuxetan (.4 mci/kg) together with high-dose BEAM (BCNU, etoposide, cytarabine, and melphalan) (Z-BEAM) has been shown to be a well-tolerated autologous hematopoietic stem cell transplantation preparative regimen for non-Hodgkin lymphoma. We report the outcomes of a single-center, single-arm phase II trial of Z-BEAM conditioning in high-risk CD20(+) non-Hodgkin lymphoma histologic strata: diffuse large B cell (DLBCL), mantle cell, follicular, and transformed. Robust overall survival and notably low nonrelapse mortality rates (.9% at day +100 for the entire cohort), with few short- and long-term toxicities, confirm the safety and tolerability of the regimen. In addition, despite a high proportion of induction failure patients (46%), the promising response and progression-free survival (PFS) rates seen in DLBCL (3-year PFS: 71%; 95% confidence interval, 55 to 82%), support the premise that the Z-BEAM regimen is particularly effective in this histologic subtype. The role of Z-BEAM in other strata is less clear in the context of the emergence of novel agents.

  11. Non-Hodgkin Lymphoma risk and insecticide, fungicide and fumigant use in the Agricultural Health Study

    EPA Science Inventory

    Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL an...

  12. Phenoxy herbicides and chlorophenols as risk factors for soft tissue sarcoma and non-Hodgkin's lymphoma

    SciTech Connect

    Woods, J.; Polissar, L.; Severson, R.; Heuser, L.

    1986-09-01

    A population-based case-control study evaluated the relationship between soft tissue sarcoma and non-Hodgkin's lymphoma and past exposure to phenoxy herbicides and chlorophenols in western Washington state. A major purpose of the study was to determine if the risk of cancer was elevated in relation to chemicals potentially contaminated with 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD). A total of 160 men with soft tissue sarcoma and 581 men with non-Hodgkin's lymphoma were group-matched with 694 randomly selected controls and were interviewed in person. Among the general population, no increased risks for either cancer were seen in relation to intensity or duration of past exposure to phenoxy herbicides or chlorophenols. Preliminary risk estimates for specific occupations that involve phenoxy herbicide or chlorophenol exposure included: farmer, herbicide formulator, applicator, forest sprayer, farmland sprayer, work in sprayed area, and work with or manufacture chlorophenyls. In addition, the risks of both soft tissue sarcoma and non-Hodgkin's lymphoma were elevated among men with past exposure to various insecticides, organic solvents and metals, and among those with preexisting compromise of the immune system. Multivariate studies are in progress to ascertain the contribution of diverse factors to the risks of soft tissue sarcoma or non-Hodgkin's lymphoma in association with phenoxy herbicides, chlorophenols, and/or TCDD.

  13. Primary non-Hodgkin's lymphoma of the breast: a report of 11 cases.

    PubMed

    Cabras, Maria Giuseppina; Amichetti, Maurizio; Nagliati, Michele; Orrù, Paola; Mamusa, Angela Maria; Angelucci, Emanuele

    2004-12-01

    The breast is a rare localization of primary non-Hodgkin's lymphoma. We review our 15 years' experience in 11 patients with primary breast lymphoma. Based on our experience and on literature data we support a management scheme with CHOP or CHOP-like combination chemotherapy followed by involved field radiotherapy.

  14. Kluver-Bucy syndrome in a boy with non-Hodgkin lymphoma.

    PubMed

    Unal, Ekrem; Koksal, Yavuz; Baysal, Tamer; Energin, Me ltem; Aydin, Kursad; Caliskan, Umran

    2007-03-01

    Kluver-Bucy syndrome is a rare neurobehavioral condition characterized by visual agnosia, excessive oral tendency, hypermetamorphosis, placidity, altered sexual behaviors, and changes in dietary habits. The authors report a case of Kluver-Bucy syndrome in a 10-year-old boy with non-Hodgkin lymphoma after intratechal methotrexate administration. He was treated by risperidone without any sequels.

  15. A Literature Revision in Primary Cutaneous B-cell Lymphoma

    PubMed Central

    Selva, R La; Violetti, S Alberti; Delfino, C; Grandi, V; Cicchelli, S; Tomasini, C; Fierro, M T; Berti, E; Pimpinelli, N; Quaglino, P

    2017-01-01

    The term “Primary Cutaneous B-Cell Lymphoma” (PCBCL) comprehends a variety of lymphoproliferative disorders characterized by a clonal proliferation of B-cells primarily involving the skin. The absence of evident extra-cutaneous disease must be confirmed after six-month follow-up in order to exclude a nodal non-Hodgkin's lymphoma (NHL) with secondary cutaneous involvement, which may have a completely different clinical behavior and prognosis. In this article, we have summarized the clinico-pathological features of main types of PCBCL and we outline the guidelines for management based on a review of the available literature.

  16. Circulating cytokine levels, Epstein-Barr viremia and risk of acquired immunodeficiency syndrome-related non-Hodgkin lymphoma

    PubMed Central

    Rabkin, Charles S.; Engels, Eric A.; Landgren, Ola; Schuurman, Rob; Camargo, M. Constanza; Pfeiffer, Ruth; Goedert, James J.

    2012-01-01

    Cytokine dysregulation and decontrol of Epstein-Barr virus (EBV) latency by human immunodeficiency virus (HIV) infection are potential mechanisms for acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). We therefore assessed circulating blood levels in pre-diagnosis plasma or serum from 63 AIDS-related NHL cases 0.1 – 2.0 (median 1.0) years pre-NHL and 181 controls matched for CD4+ T-cell count. Cytokines were measured by Millipore 30-plex Luminex assays and cell-free EBV DNA detected by polymerase chain reaction (PCR). Correlations in multiplex cytokine levels were summarized by factor analysis. Individual cytokines and their principal factors were analyzed for associations with NHL by conditional logistic regression. Cases had higher levels for 25 of the 30 cytokines. In analyses of cytokine profiles, cases had significantly higher scores for a principal factor primarily reflecting levels of interleukin (IL)-4, IL-5, IL-13, and granulocyte-macrophage colony stimulating factor (four gene products with coordinated transcription in vitro), as well as IL-1alpha. Epstein-Barr viremia was not significantly associated based on 113 evaluable samples without PCR inhibition. We found increases of T-helper type 2 interleukins and generalized elevations of other inflammatory cytokines and growth factors up to two years before AIDS-NHL. Cytokine-mediated hyperstimulation of B-cell proliferation may play a role in AIDS-related lymphomagenesis. PMID:22022727

  17. SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression.

    PubMed

    Ten, Lik-Chin; Chin, Yoon-Ming; Tai, Mei-Chee; Chin, Edmund Fui-Min; Lim, Yat-Yuen; Suthandiram, Sujatha; Chang, Kian-Meng; Ong, Tee-Chuan; Bee, Ping-Chong; Mohamed, Zahurin; Gan, Gin-Gin; Ng, Ching-Ching

    2017-01-31

    Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37-0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35-0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.

  18. Exposure to environmental tobacco smoke and risk of non-Hodgkin lymphoma in nonsmoking men and women.

    PubMed

    Diver, W Ryan; Teras, Lauren R; Gaudet, Mia M; Gapstur, Susan M

    2014-04-15

    Little is known about the risk of non-Hodgkin lymphoma (NHL) in nonsmokers who are exposed to environmental tobacco smoke (ETS). Previous research on NHL and ETS has not included men or examined doses of ETS exposure during childhood. The Cancer Prevention Study II Nutrition Cohort collected information on smoking habits and exposure to ETS during childhood and adulthood. Among 61,326 never-smoking men and women, 884 incident cases of NHL were identified between 1992 and 2009. Multivariable-adjusted relative risks and 95% confidence intervals were calculated using Cox proportional hazards regression to identify associations between ETS and NHL risk. Compared with no exposure to ETS as a child or an adult, childhood and/or adult ETS exposure was not associated with NHL overall. There was a positive association between the number of smokers in the house as a child (P for trend = 0.05) and exposure to 6 or more hours per week of ETS as an adult (relative risk = 2.37, 95% confidence interval: 1.12, 5.04) with follicular lymphoma risk. Adult ETS exposure was associated with a lower risk of diffuse large B-cell lymphoma (relative risk = 0.68, 95% confidence interval: 0.48, 0.97). This study suggests that adult and childhood ETS exposure may affect the risk of NHL, and that the associations differ by histological subtype.

  19. Navitoclax (ABT-263) and bendamustine ± rituximab induce enhanced killing of non-Hodgkin's lymphoma tumours in vivo

    PubMed Central

    Ackler, S; Mitten, MJ; Chen, J; Clarin, J; Foster, K; Jin, S; Phillips, DC; Schlessinger, S; Wang, B; Leverson, JD; Boghaert, ER

    2012-01-01

    BACKGROUND AND PURPOSE Bendamustine with or without rituximab provides an effective and more tolerable alternative to the polytherapy cyclophosphamide–doxorubicin–vincristine–prednisolone (CHOP) in the treatment of haematological tumours and is currently approved for the treatment of many haematological malignancies. Navitoclax (ABT-263) is a potent inhibitor of Bcl-2, Bcl-xL and Bcl-w, which has demonstrated efficacy in haematological tumours alone and in combination with other agents. This paper describes the in vivo efficacy of combining either bendamustine or bendamustine plus rituximab (BR) with navitoclax in xenograft models of non-Hodgkin's lymphoma EXPERIMENTAL APPROACH Activity was tested in xenograft models of diffuse large B-cell lymphoma (DoHH-2, SuDHL-4), mantle cell lymphoma (Granta 519) and Burkitt's lymphoma (RAMOS). Activity was also monitored in a systemic model of Granta 519. KEY RESULTS Navitoclax potentiated bendamustine activity in all cell lines tested. Bendamustine activated p53 in Granta 519 tumours, concurrent with activation of caspase 3. Navitoclax also improved responses to bendamustine-rituximab (BR) in a subset of tumours. CONCLUSIONS AND IMPLICATIONS Navitoclax in combination with bendamustine and BR is a viable combination strategy for use in the clinic and demonstrated superior efficacy compared with previously reported data for navitoclax plus CHOP and rituximab-CHOP. PMID:22624727

  20. Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients

    PubMed Central

    Xue, Xiaonan; Wang, Dan; Tamari, Roni; Lee, Jeannette Y.; Mounier, Nicolas; Kaplan, Lawrence D.; Ribera, Josep-Maria; Spina, Michele; Tirelli, Umberto; Weiss, Rudolf; Galicier, Lionel; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Oriol, Albert; Navarro, José-Tomás; Dunleavy, Kieron; Little, Richard F.; Ratner, Lee; Garcia, Olga; Morgades, Mireia; Remick, Scot C.; Noy, Ariela; Sparano, Joseph A.

    2013-01-01

    Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; “intensive regimens”: HR 0.35; P < .001) and OS (“intensive regimens”: HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable. PMID:24014242

  1. SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression

    PubMed Central

    Ten, Lik-Chin; Chin, Yoon-Ming; Tai, Mei-Chee; Chin, Edmund Fui-Min; Lim, Yat-Yuen; Suthandiram, Sujatha; Chang, Kian-Meng; Ong, Tee-Chuan; Bee, Ping-Chong; Mohamed, Zahurin; Gan, Gin-Gin; Ng, Ching-Ching

    2017-01-01

    Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37–0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35–0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology. PMID:28139690

  2. Targeted Radio-Immunotherapy with Bexxar Produces Durable Remissions in Patients with Late Stage Low Grade Non-Hodgkin's Lymphomas.

    PubMed Central

    Capizzi, Robert L.

    2004-01-01

    Patients with low grade (LG) non-Hodgkin's lymphomas (NHLs) typically have a median survival of 8-10 years during which they sustain a series of responses and relapses to therapy. More than 95% of B-cell NHLs express the CD20 surface antigen, affording opportunities for CD20-directed therapy of NHL. Since 1990, 5 trials have tested the safety and efficacy of the murine CD20 MAb Tositumomab and Iodine I 131 Tositumomab (Bexxar((R)) therapeutic regimen) in 250 patients with relapsed, refractory, or transformed LG NHL. The I-131 irradiates MAb-bound cells and those within the path length of the isotope. Response rates were 56% (overall) and 30% (complete). With a median follow-up of 44.6 months, 30% of the patients achieved a long-term, durable response; median time to progressive disease or death was 5 years. Thus, a single treatment with Bexxar may produce durable responses and partially reverse the natural history of LG NHL. PMID:17060972

  3. Analysis of ploidy and proliferative activity in childhood non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD).

    PubMed

    Coad, N A; Jones, T J; Muir, K R; Parkes, S E; Smith, K; Raafat, F; Mann, J R

    1997-01-01

    We have performed DNA analysis by means of fluorescence-activated cell cytometry on paraffin-embedded tissue from the diagnostic biopsy specimens in 40 cases of non-Hodgkin's lymphoma (NHL) and 25 of Hodgkin's disease (HD) and from 50 normal tonsils as controls. For HD cases, aneuploidy was found in 7 of 25 (28%), a higher proportion than in two previous studies of mainly adult patients. Diploid tumors showed S-phase fractions (SPFs) similar to those of controls. In the NHL cases aneuploidy was found in 12 of 40 (30%) with no significant association with site, stage, histopathology, immunophenotype, or prognosis. SPFs were highest in abdominal and chest primary sites but were not related to stage. Burkitt's lymphomas had the highest SPFs relative to lymphoblastic (P < .01) and centroblastic lymphomas (P < .05). Significantly higher SPFs were found in B cell than in T cell tumors (P < .001). There was considerable heterogeneity for SPFs within each NHL subgroup. Survival was worse at 5 years for those with high SPFs compared with those with normal SPFs (P = .04). These results suggest that tumor DNA analysis may be useful in the evaluation of children with NHL. Larger studies are needed to define its role as an independent prognostic variable.

  4. Primary extranodal non-Hodgkin's lymphoma of the common bile duct manifesting as obstructive jaundice: report of a case.

    PubMed

    Dote, Hideaki; Ohta, Koji; Nishimura, Rieko; Teramoto, Norihiro; Asagi, Akinori; Nadano, Seijin; Hamada, Makoto; Yoshida, Isao; Kobatake, Takaya; Nozaki, Isao; Kubo, Yoshirou; Tanada, Minoru; Kurita, Akira; Takashima, Shigemitsu

    2009-01-01

    Primary non-Hodgkin's lymphoma (NHL) of the common bile duct (CBD) manifesting as obstructive jaundice is extremely rare: to our knowledge, only 22 cases of primary NHL arising from the CBD have been reported. The patient in this case report was a 63-year-old man who presented with obstructive jaundice. Abdominal sonography, positron emission tomography, and computed tomography showed a mass with abnormal 18-fluorodeoxyglucose uptake in pancreatic head. Magnetic resonance cholangiopancreatography demonstrated a strictured segment of the CBD with proximal bile duct dilatation. We performed pancreaticoduodenectomy for a presumptive diagnosis of pancreatic head carcinoma or cholangiocarcinoma of the CBD. However, the histological diagnosis was a primary, diffuse, large B-cell lymphoma of the CBD. He received three courses of combination chemotherapy, including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The patient remains well, without evidence of tumor recurrence, 8 months after surgery. In summary, primary NHL of the CBD, despite its rarity, should be considered in the differential diagnosis of obstructive jaundice. An accurate histopathologic diagnosis and complete surgical resection, followed by combination chemotherapy plus rituximab may be effective.

  5. Dysregulated MicroRNA Expression Profiles and Potential Cellular, Circulating and Polymorphic Biomarkers in Non-Hodgkin Lymphoma

    PubMed Central

    Bradshaw, Gabrielle; Sutherland, Heidi G.; Haupt, Larisa M.; Griffiths, Lyn R.

    2016-01-01

    A large number of studies have focused on identifying molecular biomarkers, including microRNAs (miRNAs) to aid in the diagnosis and prognosis of the most common subtypes of non-Hodgkin lymphoma (NHL), Diffuse Large B-cell Lymphoma and Follicular Lymphoma. NHL is difficult to diagnose and treat with many cases becoming resistant to chemotherapy, hence the need to identify improved biomarkers to aid in both diagnosis and treatment modalities. This review summarises more recent research on the dysregulated miRNA expression profiles found in NHL, as well as the regulatory role and biomarker potential of cellular and circulating miRNAs found in tissue and serum, respectively. In addition, the emerging field of research focusing on miRNA single nucleotide polymorphisms (miRSNPs) in genes of the miRNA biogenesis pathway, in miRNA genes themselves, and in their target sites may provide new insights on gene expression changes in these genes. These miRSNPs may impact miRNA networks and have been shown to play a role in a host of different cancer types including haematological malignancies. With respect to NHL, a number of SNPs in miRNA-binding sites in target genes have been shown to be associated with overall survival. PMID:27999330

  6. Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers

    PubMed Central

    Emadali, Anouk; Rousseaux, Sophie; Bruder-Costa, Juliana; Rome, Claire; Duley, Samuel; Hamaidia, Sieme; Betton, Patricia; Debernardi, Alexandra; Leroux, Dominique; Bernay, Benoit; Kieffer-Jaquinod, Sylvie; Combes, Florence; Ferri, Elena; McKenna, Charles E; Petosa, Carlo; Bruley, Christophe; Garin, Jérôme; Ferro, Myriam; Gressin, Rémy; Callanan, Mary B; Khochbin, Saadi

    2013-01-01

    Immuno-chemotherapy elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumours in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that autonomously drives aggressive tumour growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma. The nuclear factor CYCLON is a new MYC cooperating factor that drives tumor growth and Rituximab resistance in lymphoma. This resistance mechanism can be targeted by next-generation epigenetic therapy by BET bromodomain inhibition downstream of MYC. PMID:23828858

  7. Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma.

    PubMed

    Davids, Matthew S; Roberts, Andrew W; Seymour, John F; Pagel, John M; Kahl, Brad S; Wierda, William G; Puvvada, Soham; Kipps, Thomas J; Anderson, Mary Ann; Salem, Ahmed Hamed; Dunbar, Martin; Zhu, Ming; Peale, Franklin; Ross, Jeremy A; Gressick, Lori; Desai, Monali; Kim, Su Young; Verdugo, Maria; Humerickhouse, Rod A; Gordon, Gary B; Gerecitano, John F

    2017-03-10

    Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts. Treatment commenced with a 3-week dose ramp-up period for most patients in dose-escalation cohorts and for all patients in safety expansion. Results NHL subtypes included mantle cell lymphoma (MCL; n = 28), follicular lymphoma (FL; n = 29), diffuse large B-cell lymphoma (DLBCL; n = 34), DLBCL arising from chronic lymphocytic leukemia (Richter transformation; n = 7), Waldenström macroglobulinemia (n = 4), and marginal zone lymphoma (n = 3). Venetoclax was generally well tolerated. Clinical tumor lysis syndrome was not observed, whereas laboratory tumor lysis syndrome was documented in three patients. Treatment-emergent adverse events were reported in 103 patients (97%), a majority of which were grade 1 to 2 in severity. Grade 3 to 4 events were reported in 59 patients (56%), and the most common were hematologic, including anemia (15%), neutropenia (11%), and thrombocytopenia (9%). Overall response rate was 44% (MCL, 75%; FL, 38%; DLBCL, 18%). Estimated median progression-free survival was 6 months (MCL, 14 months; FL, 11 months; DLBCL, 1 month). Conclusion Selective targeting of BCL-2 with venetoclax was well tolerated, and single-agent activity varied among NHL subtypes. We determined 1,200 mg to be the recommended single-agent dose for future studies in FL and DLBCL, with 800 mg being sufficient to consistently achieve durable response in MCL. Additional investigations including combination therapy to augment response rates and durability

  8. 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

  9. Pathophysiology and molecular aspects of diffuse large B-cell lymphoma

    PubMed Central

    Gouveia, Gisele Rodrigues; Siqueira, Sheila Aparecida Coelho; Pereira, Juliana

    2012-01-01

    Diffuse large B-Cell lymphoma is the most common subtype of non-Hodgkin lymphoma in the West. In Brazil, it is the fifth cause of cancer, with more than 55,000 cases and 26,000 deaths per year. At Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, diffuse large B-Cell lymphoma represents 49.7% of all non-Hodgkin lymphoma cases. Initially, the classification of non-Hodgkin lymphoma was based on morphology, but advances in immunology and molecular medicine allowed the introduction of a biological classification for these diseases. As for other cancers, non-Hodgkin lymphoma involves patterns of multifactorial pathogenesis with environmental factors, as well as genetic, occupational and dietary factors, contributing to its development. Multiple lesions involving molecular pathways of B-cell proliferation and differentiation may result in the activation of oncogenes such as the BCL2, BCL6, and MYC genes and the inactivation of tumor suppressor genes such as p53 and INK4, as well as other important transcription factors such as OCT-1 and OCT-2. A dramatic improvement in survival was seen after the recent introduction of the anti-CD20 monoclonal antibody. The association of this antibody to the cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (CHOP) regimen has increased overall survival of diffuse large B-Cell lymphoma and follicular lymphoma patients by 20%. However, 50% of all diffuse large B-Cell lymphoma patients remain incurable, creating a demand for more research with new advances in treatment. Thus, it is important to know and understand the key factors and molecular pathways involved in the pathogenesis of diffuse large B-Cell lymphoma. PMID:23323070

  10. 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

  11. 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

    2016-10-24

    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

  12. Primary Bilateral Non-Hodgkin's Lymphoma of the Adrenal Gland: A Case Report

    PubMed Central

    Bouchikhi, Ahmed Amine; Tazi, Mohamed fadl; Amiroune, Driss; Mellas, Soufiane; El Ammari, Jalaledine; Khallouk, Abdelhak; El fassi, Mohammed Jamal; Farih, Moulay Hassan

    2012-01-01

    Primary bilateral non-Hodgkin's lymphoma (NHL) of the adrenal gland is a very rare entity. Indeed less than 60 cases have been reported in the literature. Hence, we report a case of high-grade lymphoma of both adrenal glands that was found in a young patient of 32 years of age. The patient was admitted in the emergency department of our hospital with a profile of hemorrhagic shock. After stabilization, the imaging investigations demonstrated large bilateral adrenal masses. The CT-scan guided biopsy of both adrenal glands allowed the diagnosis of primary bilateral adrenal NHL. The patient died after the first chemotherapy session. The presence of bilateral adrenal masses associated with a rapid increase of volume should raise the diagnosis of primary adrenal non-Hodgkin's lymphoma. PMID:23304624

  13. [National guidelines of diagnosis and treatment of the non-Hodgkin lymphoma].

    PubMed

    Candelaria, Myrna; Cervera-Ceballos, Eduardo; Meneses-García, Abelardo; Avilés-Salas, Alejandro; Lome-Maldonado, Carmen; Zárate-Osorno, Alejandra; Ortiz-Hidalgo, Carlos; Rodríguez-Moguel, Leticia; Quiñónez-Urrego, Enoe Enedina; Ramos-Salazar, Patricia; Romero-Guadarrama, Mónica Belinda; Lara-Torres, César; Ramírez-Aceves, Rocío; López-Navarro, Omar; Rivas-Vera, Silvia; Díaz-Meneses, Iván Eudaldo; Estrada-Lobato, Enrique; Cervera-Ceballos, José; Rojas-Marín, Carlos Enrique; Hernández-Rodriguez, José Mario; Pérez-López, Berenice; Gómez-Almaguer, David; Altamirano-Ley, Javier; Baz, Patricia; Valero-Saldaña, Luis Manuel; Navarrete-Herrera, José René; Torres-Salgado, Francisco Gerardo; Solano-Murillo, Pedro; Nambo-Lucio, María de Jesús; Rivas-Llamas, Ramón; Aquino-Salgado, Jorge Luis; Avila-Arreguín, Elsa Verónica; Cortês-Esteban, Patricia; Chongo-Alfaro, Martha Lilia; Pérez-Ramírez, Oscar de Jesús; Toledano-Cuevas, Diana Vanesa; Lobato-Mendizábal, Eduardo; Martínez-Ramírez, Mario Alberto; Morales-Maravilla, Adrián; Sosa-Camas, Rosa Elena; Agreda-Vásquez, Gladys P; Camacho-Hernández, Alejandro; Aguayo-González, Alvaro; Espinoza-Zamora, José Ramiro; Sánchez-Guerrero, Sergio A; Lozano-Zavaleta, Valentín; Selva-Pallares, Julio Edgar; Hernádez-Rodríguez, Juan Manuel; Cardiel-Silva, Mariela; Castillo-Rivera, Manuel Héctor; Villela, Luis; Loarca-Piña, Luis Martín; Zurita-Martínez, Hugo; Graham-Casassus, Juan; Azaola-Espinosa, Patricio; Silva-López, Salvador; Armenta-San Sebastián, Jorge Antonio; Mijangos-Huesca, Francisco; Pérez-Osorio, Jorge Eduardo; Aldaco-Sarvide, Fernando; Castellanos, Guillermo; Ramírez-Ibarguen, Ana Florencia; Zapata-Canto, Nidia; Labardini-Méndez, Juan Rafael

    2013-06-01

    Non-Hodgkin lymphoma comprises a heterogeneous group of haematological malignancies, classified according to their clinic, anatomic-pathological features and, lately, to their molecular biomarkers. Despite the therapeutic advances, nearly half of the patients will die because of this disease. The new diagnostic tools have been the cornerstone to design recent therapy targets, which must be included in the current treatment guidelines of this sort of neoplasms by means of clinical trials and evidence-based medicine. In the face of poor diagnoses devices in most of the Mexican hospitals, we recommend the present diagnose stratification, and treatment guidelines for non-Hodgkin lymphoma, based on evidence. They include the latest and most innovative therapeutic approaches, as well as specific recommendations for hospitals with limited framework and therapy resources.

  14. Treatment of non-Hodgkin's lymphoma with marrow transplantation in identical twins

    SciTech Connect

    Appelbaum, F.R.; Fefer, A.; Cheever, M.A.; Buckner, C.D.; Greenberg, P.D.; Kaplan, H.G.; Storb, R.; Thomas, E.D.

    1981-09-01

    Eight patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemotherapy, a supralethal dose of total-body irradiation, and a bone marrow transplant from a normal identical twin. Seven patients experienced complete remission. Four of the seven patients (two with diffuse poorly differentiated lymphocytic lymphoma, one with composite lymphoma, and one with diffuse moderately well differentiated lymphocytic lymphoma) remain in complete unmaintained remission 12-126 mo from transplantation. One patient relapsed after 10 mo but was retreated and is alive in unmaintained complete remission 73 mo from transplantation. One patient died of Pseudomonas pneumonia while in complete remission and one patient relapsed and died of progressive lymphoma. These results demonstrate that intensive chemoradiotherapy and twin marrow transplantation can induce frequent and enduring remissions in patients with disseminated non-Hodgkin's lymphoma who have failed conventional therapy.

  15. Novel Targeted Agents in Hodgkin and Non-Hodgkin Lymphoma Therapy

    PubMed Central

    Grover, Natalie S.; Park, Steven I.

    2015-01-01

    There has been a recent emergence of novel targeted agents for treatment of Hodgkin and non-Hodgkin lymphoma. In particular, antibodies and antibody-drug conjugates directed against surface antigens, agents that block immune checkpoint pathways, and small molecule inhibitors directed against cell signaling pathways have shown significant promise in patients with relapsed and refractory disease and in the frontline setting. With the development of these new therapies, cytotoxic chemotherapy may be avoided entirely in some clinical settings. This review will present the latest information on these novel treatments in Hodgkin and non-Hodgkin lymphoma and will discuss both recently approved agents as well as drugs currently being studied in clinical trials. PMID:26393619

  16. T-cell non-Hodgkin's lymphoma after radiotherapy and chemotherapy for Hodgkin's disease

    SciTech Connect

    Lowenthal, R.M.; Harlow, R.W.H.; Mead, A.E.; Tuck, D.; Challis, D.R.

    1981-10-01

    A rapidly fatal T-cell lymphoma developed in a 25-year-old man who, over a period of seven years, had been treated with radiotherapy and combination chemotherapy for Hodgkin's disease (HD). Non-Hodgkin's lymphoma (NHL) is increasingly being recognized as a late sequel of therapy for HD, but this is the first case in which NHL of T-cell type has been identified in such circumstances.

  17. 5'-Azacitidine for therapy-related myelodysplastic syndromes after non-Hodgkin lymphoma treatment.

    PubMed

    Breccia, Massimo; Salaroli, Adriano; Loglisci, Giuseppina; Martelli, Maurizio; D'Elia, Gianna Maria; Nanni, Mauro; Mauro, Francesca Romana; Alimena, Giuliana

    2011-10-01

    Therapy-related myelodysplastic syndromes are possible complications in patients treated for previous hematologic malignancies. Therapeutic strategies in these type of disorders are still not well defined: azacitidine has been recently approved for the treatment of higher risk myelodysplastic syndromes, but few data are published relating possible efficacy in therapy-related dysplastic disorders. We reported here 4 patients treated with azacitidine for therapy related dysplasia after chemotherapy for non-Hodgkin lymphoma.

  18. Plasma organochlorine levels and risk of non-Hodgkin lymphoma in a cohort of men

    PubMed Central

    Bertrand, Kimberly A.; Spiegelman, Donna; Aster, Jon C.; Altshul, Larisa M.; Korrick, Susan A.; Rodig, Scott J.; Zhang, Shumin M.; Kurth, Tobias; Laden, Francine

    2010-01-01

    Background Environmental exposure to polychlorinated biphenyls (PCBs) and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) has been associated with the risk of non-Hodgkin lymphoma. Methods We conducted a case-control study nested within the Physicians’ Health Study, a prospective cohort established in 1982. We measured concentrations of PCBs and p,p′-DDE in baseline blood samples from 205 men later diagnosed with non-Hodgkin lymphoma and 409 age- and race-matched controls. Lipid-adjusted organochlorine concentrations were categorized into quintiles based on the distribution among controls. We used conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for each quintile relative to the lowest quintile. We also evaluated these associations for major histologic subtypes of non-Hodgkin lymphoma. Results The risk of non-Hodgkin lymphoma was positively associated with the sum of 51 PCB congeners assayed (ΣPCB); the group of immunotoxic congeners; the individual congeners 118, 138, 153, and 180; and the sum of these four congeners. The simple OR for the highest quintile of lipid-adjusted ΣPCB versus the lowest was 1.9 (95% CI = 1.1-3.2; test for trend P = 0.001), with similar trends for individual congeners and groups defined as above. Adjustment for height, body mass index, alcohol intake, smoking, and fish intake did not substantially change the effect estimates. No association was observed for p,p′-DDE. There was no evidence of statistical heterogeneity in effects by histologic subtype of lymphoma; however, this analysis was underpowered. Conclusions These results support the hypothesis of a positive association between PCB exposure and development of NHL in men. PMID:20087190

  19. Fludarabine, mitoxantrone and dexamethasone as front-line therapy in elderly patients affected by newly-diagnosed, low-grade non-Hodgkin's lymphomas with unfavorable prognostic factors: results of a phase II study.

    PubMed

    Bordonaro, Roberto; Petralia, Giuseppina; Restuccia, Nunzio; Todaro, Anna Maria; Serraino, Diego; Giuffrida, Dario; Cordio, Stefano; Giannitto-Giorgio, Carmelo; Salice, Placida; Ursino, Maria; Novello, Giuseppe; Marletta, Francesco; Manusia, Mario

    2004-01-01

    About one-third of the cases of non-Hodgkin's lymphomas occur in patients aged 60 years or more. Nevertheless, there are very few data in the literature regarding the optimal therapeutic approach for both aggressive and indolent histologies. Fludarabine-based combination regimens are an effective choice for younger patients affected by low-grade non-Hodgkin's lymphomas, but there is a lack of information about their tolerability and efficacy in older patients. We performed a phase II study to test the efficacy and safety of the combination of Fludarabine, Mitoxantrone and Dexamethasone (FND) in newly-diagnosed, chemo-naive elderly patients affected by low-grade non-Hodgkin's lymphomas with unfavorable prognostic factors. From March 1999 to March 2002, 18 patients were enrolled into the study. All the patients were evaluated for toxicity and response. Neutropenia and thrombocytopenia have been registered as the main toxicities. Thirteen (72%) patients experienced a complete response and 4 (22%) a partial response: the overall response rate was 94%. At a median follow-up of 19 months, the median time for progression-free-survival and the median survival time were not reached yet. The 2-years projected progression-free-survival and overall-survival are 52% and 67% respectively. When administered as first-line treatment to a population of elderly patients affected by high-risk, low-grade non-Hodgkin's lymphomas, FND showed a high efficacy and a good toxicity profile. Our data compare favorably to those reported for the same schedule administered both as first- or second-line therapy in younger patients.

  20. No involvement of bovine leukemia virus in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma

    SciTech Connect

    Bender, A.P.; Robison, L.L.; Kashmiri, S.V.; McClain, K.L.; Woods, W.G.; Smithson, W.A.; Heyn, R.; Finlay, J.; Schuman, L.M.; Renier, C.

    1988-05-15

    Bovine leukemia virus (BLV) is the causative agent of enzootic bovine lymphosarcoma. Much speculation continues to be directed at the role of BLV in human leukemia. To test this hypothesis rigorously, a case-control study of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma was conducted between December 1983 and February 1986. Cases (less than or equal to 16 years at diagnosis) derived from patients diagnosed at the primary institutions and affiliated hospitals were matched (age, sex, and race) with regional population controls. DNA samples from bone marrow or peripheral blood from 157 cases (131 acute lymphoblastic leukemia, 26 non-Hodgkin's lymphoma) and peripheral blood from 136 controls were analyzed by Southern blot technique, under highly stringent conditions, using cloned BLV DNA as a probe. None of the 157 case or 136 control DNA samples hybridized with the probe. The high statistical power and specificity of this study provide the best evidence to date that genomic integration of BLV is not a factor in childhood acute lymphoblastic leukemia/non-Hodgkin's lymphoma.

  1. Potential benefits of therapeutic splenectomy for patients with Hodgkin's disease and non-Hodgkin's lymphomas

    SciTech Connect

    Schreiber, D.P.; Jacobs, C.; Rosenberg, S.A.; Cox, R.S.; Hoppe, R.T.

    1985-01-01

    Thirty-four patients with Hodgkin's disease and non-Hodgkin's lymphoma underwent therapeutic splenectomies to improve hematologic tolerance for chemotherapy. The mean age was 40 years; there were 16 males and 18 females. Fourteen had Hodgkin's disease, 19 had non-Hodgkin's lymphoma, and 1 had malignant histocytosis. Nineteen had palpable splenomegaly, 19 had marrow involvement and 20 had splenic involvement by lymphoma. The following data were analyzed before and after splenectomy: mean white blood cell count (WBC) and platelet count on planned first day of cycle, delay ratio of chemotherapy delivery and percent maximal dose rate. Thirteen patients had non-Hodgkin's lymphoma, splenomegaly and positive bone marrow and showed significant benefit in all of the aforementioned parameters. Of the patients with prior irradiation, only those who completed their radiation greater than six months prior to splenectomy showed benefit. Ten patients had Hodgkin's disease, negative bone marrow and no splenomegaly. This group showed significant improvement in mean platelet count but more limited benefit in delay ratio and percent maximal dose rate. Thus, selected patients with lymphoma who are experiencing delays in chemotherapy because of poor count tolerance may benefit from splenectomy.

  2. [Femoral osteolytic lesions with soft tissue tumors and hypercalcemia as presentation form of a B-cell lymphoma].

    PubMed

    Hernández Hernández, J L; Olmos Martínez, J M; Figols Ladrón de Guevara, J; Riancho Moral, J A; González Macías, J

    2000-05-01

    Hypercalcemia associated with haematological neoplasms account for 15 to 20% of hipercalcemia in malignancy, and occurs usually in patients with multiple myeloma. However, its incidence in patients with linfoma is low, and it is observed usually in T-cell linfomas. Bone affectation is also uncommon in patients with non-Hodgkin linfoma. It usually is seen as a late manifestation of the disease, and its occurrence as the form of presentation is exceptional. We hereby report a patient with a B-cell non-Hodgkin linfoma presenting with hypercalcemia and femoral osteolytic lesions.

  3. The potential relevance of the endocannabinoid, 2-arachidonoylglycerol, in diffuse large B-cell lymphoma

    PubMed Central

    Zhang, Jianqing; Medina-Cleghorn, Daniel; Bernal-Mizrachi, Leon; Bracci, Paige M.; Hubbard, Alan; Conde, Lucia; Riby, Jacques; Nomura, Daniel K.; Skibola, Christine F.

    2016-01-01

    Diffuse large B-cell lymphoma is an aggressive, genetically heterogenerous disease and the most common type of non-Hodgkin lymphoma among adults. To gain further insights into the etiology of DLBCL and to discover potential disease-related factors, we performed a serum lipid analysis on a subset of individuals from a population-based NHL case-control study. An untargeted mass-spectrometry-based metabolomics platform was used to analyze serum samples from 100 DLBCL patients and 100 healthy matched controls. Significantly elevated levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), were detected in the serum of DLBCL patients (121%, P < 0.05). In the male controls, elevated 2-AG levels were observed in those who were overweight (BMI ≥ 25 - < 30 kg/m2; 108%, P < 0.01) and obese (BMI ≥ 30 kg/m2; 118%, P < 0.001) compared to those with a BMI < 25 kg/m2. DLBCL cell lines treated with exogenous 2-AG across a range of concentrations, exhibited heterogenous responses: proliferation rates were markedly higher in 4 cell lines by 22%-68% (P < 0.001) and lower in 8 by 20%-75% (P < 0.001). The combined findings of elevated 2-AG levels in DLBCL patients and the proliferative effects of 2-AG on a subset of DLBCL cell lines suggests that 2-AG may play a potential role in the pathogenesis or progression of a subset of DLBCLs. PMID:26973858

  4. Periodontal disease and risk of non-Hodgkin lymphoma in the Health Professionals Follow-Up Study.

    PubMed

    Bertrand, Kimberly A; Shingala, Janki; Evens, Andrew; Birmann, Brenda M; Giovannucci, Edward; Michaud, Dominique S

    2017-03-01

    Periodontal disease is a chronic inflammatory condition that has been associated with chronic diseases, including cancer. In an earlier prospective cohort analysis within the Health Professionals Follow-Up Study (HPFS), we observed a 31% higher risk of non-Hodgkin lymphoma (NHL) among participants with severe periodontal disease at baseline. Here, we extend the study with an additional 8 years of follow-up, and conduct analyses with updated periodontal disease status and NHL subtypes. The HPFS is an ongoing prospective cohort study of 51,529 men in the USA Between baseline in 1986 and 2012, 875 cases of NHL were diagnosed, including 290 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 85 diffuse large B-cell lymphomas and 91 follicular lymphomas. We performed multivariable Cox proportional hazards regression to evaluate associations of interest. History of periodontal disease at baseline was positively associated with risk of NHL overall (hazard ratio (HR) = 1.26, 95% confidence interval (CI): 1.06-1.49) and CLL/SLL (HR = 1.41, 95% CI: 1.04-1.90). With updated periodontal status, HRs were 1.30 (95% CI: 1.11-1.51) for NHL overall and 1.41 (95% CI: 1.08-1.84) for CLL/SLL. In contrast, after adjusting for periodontal disease, tooth loss was inversely associated with NHL, suggesting that other causes or consequences of tooth loss may have different implications for NHL etiology. Our findings suggest that periodontal disease is a risk factor for NHL. Whether periodontal disease is a direct or indirect cause of NHL, or is a marker of underlying systemic inflammation and/or immune dysregulation, warrants further investigation.

  5. ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphomas

    SciTech Connect

    Zhu, Xinghua; Miao, Xiaobing; Wu, Yaxun; Li, Chunsun; Guo, Yan; Liu, Yushan; Chen, Yali; Lu, Xiaoyun; Wang, Yuchan; He, Song

    2015-07-15

    Enolases are glycolytic enzymes responsible for the ATP-generated conversion of 2-phosphoglycerate to phosphoenolpyruvate. In addition to the glycolytic function, Enolase 1 (ENO1) has been reported up-regulation in several tumor tissues. In this study, we investigated the expression and biologic function of ENO1 in Non-Hodgkin's Lymphomas (NHLs). Clinically, by western blot analysis we observed that ENO1 expression was apparently higher in diffuse large B-cell lymphoma than in the reactive lymphoid tissues. Subsequently, immunohistochemical staining of 144 NHLs suggested that the expression of ENO1 was significantly lower in the indolent lymphomas compared with the progressive lymphomas. Further, we identified ENO1 as an independent prognostic factor, and it was significantly correlated with overall survival of NHL patients. In addition, we found that ENO1 could promote cell proliferation, regulate cell cycle associated gene and PI3K/AKT signaling pathway in NHLs. Finally, we verified that ENO1 participated in the process of lymphoma cell adhesion mediated drug resistance (CAM-DR). Adhesion to FN or HS5 cells significantly protected OCI-Ly8 and Daudi cells from cytotoxicity compared with those cultured in suspension, and these effects were attenuated when transfected with ENO1-siRNA. Based on the study, we propose that inhibition of ENO1 expression may be a novel strategy for therapy for NHLs patients, and it may be a target for drug resistance. - Highlights: • ENO1 expression is reversely correlated with clinical outcomes of patients with NHLs. • ENO1 promotes the proliferation of NHL cells. • ENO1 regulates cell adhesion mediated drug resistance.

  6. 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

  7. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification.

    PubMed

    Cheson, Bruce D; Fisher, Richard I; Barrington, Sally F; Cavalli, Franco; Schwartz, Lawrence H; Zucca, Emanuele; Lister, T Andrew

    2014-09-20

    The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.

  8. Human Cytokine Genetic Variants Associated With HBsAg Reverse Seroconversion in Rituximab-Treated Non-Hodgkin Lymphoma Patients

    PubMed Central

    Hsiao, Liang-Tsai; Wang, Hao-Yuan; Yang, Ching-Fen; Chiou, Tzeon-Jye; Gau, Jyh-Pyng; Yu, Yuan-Bin; Liu, Hsiao-Ling; Chang, Wen-Chun; Chen, Po-Min; Tzeng, Cheng-Hwai; Chan, Yu-Jiun; Yang, Muh-Hwa; Liu, Jin-Hwang; Huang, Yi-Hsiang

    2016-01-01

    Abstract Hepatitis B virus (HBV) reactivation has been noted in HBV surface antigen (HBsAg)-seronegative patients with CD20+ B-cell non-Hodgkin lymphoma (NHL) undergoing rituximab treatment. Clinically, hepatitis flares are usually associated with the reappearance of HBsAg (reverse seroconversion of HBsAg, HBV-RS). It is unclear whether human genetic factors are related to rituximab-associated HBV reactivation. Unvaccinated HBsAg-seronegative adults (n = 104) with CD20+ NHL who had received rituximab-containing therapy without anti-HBV prophylaxis were enrolled. Eighty-nine candidate single nucleotide polymorphisms (SNPs) of 49 human cytokine genes were chosen and were analyzed using the iPLEX technique. Competing risk regression was used to identify the factors associated with HBV-RS. Participants had a median age of 66.1 years and 56.7% were male (n = 59). The anti-HBs and anti-HBc positivity rates were 82.4% and 94.1%, respectively, among patients for whom data were available (approximately 81%). A mean of 7.14 cycles of rituximab therapy were administered, and a total of 14 (13.4%) patients developed HBV-RS. Nine SNPs showed significant differences in frequency between patients with or without HBV-RS: CD40 rs1883832, IL4 rs2243248 and rs2243263, IL13 rs1295686, IL18 rs243908, IL20 rs1518108, and TNFSF13B rs12428930 and rs12583006. Multivariate analysis showed that ≥6 cycles of rituximab therapy, IL18 rs243908, and the IL4 haplotype rs2243248∼rs2243263 were independently associated with HBV-RS. The IL4 haplotype rs2243248∼rs2243263 was significantly associated with HBV-RS regardless of anti-HBs status. Polymorphisms in human cytokine genes impact the risk of rituximab-associated HBV-RS. PMID:26986131

  9. Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents.

    PubMed

    Attarbaschi, Andishe; Carraro, Elisa; Abla, Oussama; Barzilai-Birenboim, Shlomit; Bomken, Simon; Brugieres, Laurence; Bubanska, Eva; Burkhardt, Birgit; Chiang, Alan K S; Csoka, Monika; Fedorova, Alina; Jazbec, Janez; Kabickova, Edita; Krenova, Zdenka; Lazic, Jelena; Loeffen, Jan; Mann, Georg; Niggli, Felix; Miakova, Natalia; Osumi, Tomoo; Ronceray, Leila; Uyttebroeck, Anne; Williams, Denise; Woessmann, Wilhelm; Wrobel, Grazyna; Pillon, Marta

    2016-12-01

    Children and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, large-scale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international Berlin-Frankfurt-Münster Study Group. The study identified 213 patients with non-Hodgkin lymphoma and a pre-existing condition. Four subcategories were established: a) cancer predisposition syndromes (n=124, 58%); b) primary immunodeficiencies not further specified (n=27, 13%); c) genetic diseases with no increased cancer risk (n=40, 19%); and d) non-classifiable conditions (n=22, 10%). Seventy-nine of 124 (64%) cancer predispositions were reported in groups with more than 20 patients: ataxia telangiectasia (n=32), Nijmegen breakage syndrome (n=26), constitutional mismatch repair deficiency (n=21). For the 151 patients with a known cancer risk, 5-year event-free survival and overall survival rates were 40%±4% and 51%±4%, respectively. Five-year cumulative incidences of progression/relapse and treatment-related death as a first event were 22%±4% and 24%±4%, respectively. Ten-year incidence of second malignancy was 24%±5% and 7-year overall survival of the 21 patients with a second malignancy was 41%±11%. Patients with non-Hodgkin lymphoma and pre-existing conditions have an inferior survival rate with a large proportion of therapy-related deaths compared to patients with non-Hodgkin lymphoma and no pre-existing conditions. They may require special vigilance when receiving standard or modified/reduced-intensity chemotherapy or when undergoing allogeneic stem cell transplantation.

  10. Evaluation of Occupational Risk Factors in Non-Hodgkin Lymphoma and Hodgkin's Disease in Iranian Men

    PubMed Central

    Aminian, Omid; Abedi, Ali; Chavoshi, Farzaneh; Ghasemi, Mohammad; Rahmati-Najarkolaei, Fatemeh

    2012-01-01

    Background Lymphoma is a malignancy, arises from lymphoid tissue. Nowadays, it is the ninth most common cancer in Iran. The risk factors of malignant lymphomas have not well determined, but since 20 years ago till now, too many epidemiological researches have been concerning either Non-Hodgkin Lymphoma (NHL) or Hodgkin's Disease (HD). It is a common usual hypothesis that idiosyncratic reaction to common physical, chemical, and viral agents could lead to lymphoma without obvious immune deficiency. Some occupations has reported to cause increasing "NHL" risks, such as rubber industry, veterinaries, uranium mining, metal working, asbestos exposing, farming, textile industry, and benzene exposing. The roles of ionizing radiation, benzene and other environmental agents have not been clear, because of the lack of confirmed evidences for relation between the occupational and environmental agents with "HD". Methods A case-control study with 150 cases of malignant lymphoma and 150 controls have performed in Tehran. Data have selected through face-to-face interviews about the medical and occupational histories. Results In this study, there was a significantly increased risk for Non-Hodgkin Lymphoma in these occupations; welders, metal workers, founders, aluminium workers OR=4.6 [Confidence Interval (CI): 1.47-14.35] and increased risk for Hodgkin's Disease in drivers OR=2.34 [(CI):0.86-6.35]. We have found out decreased NHL risk in office workers OR=0.54 [(CI):0.29-1.02] and also found out a non-significant increased NHL risk in farmers OR=1.58 [(CI):0.82-3.03]. In this study, we have found no relation between smoking and HD, or NHL. Conclusion The results of this study suggest that several occupations could alter the risk of Non-Hodgkin Lymphoma and Hodgkin's Disease. PMID:25352969

  11. Combination Chemotherapy, Rituximab, and Ixazomib Citrate in Treating Patients With Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-08-19

    Adult Burkitt Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Diffuse Large B-Cell Lymphoma; MYC Gene Mutation; Plasmablastic Lymphoma

  12. Hepatic Sinusoidal Obstruction Syndrome Induced by Non-transplant Chemotherapy for Non-Hodgkin Lymphoma

    PubMed Central

    Sakumura, Miho; Tajiri, Kazuto; Miwa, Shigeharu; Nagata, Kohei; Kawai, Kengo; Miyazono, Takayoshi; Arita, Kotaro; Wada, Akinori; Murakami, Jun; Sugiyama, Toshiro

    2017-01-01

    Hepatic sinusoidal obstruction syndrome (SOS), a serious complication that mainly occurs after hematopoietic-stem cell transplantation (HSCT), is caused by damage to the sinusoidal endothelial cells after the obstruction of the sinusoid. Recently, hepatic SOS was reported to occur after non-HSCT chemotherapies. This report describes a patient who experienced hepatic SOS after non-HSCT chemotherapy for non-Hodgkin lymphoma. A liver biopsy showed the slight dilatation of the hepatic sinusoid, which may be indicative of hepatic SOS. Hepatic SOS should be included in the differential diagnosis of patients with severe liver injury following the administration of chemotherapy regimens that are toxic to the vascular endothelial cells. PMID:28202860

  13. AIDS-related non-Hodgkin's lymphoma presenting as delayed healing of an extraction wound.

    PubMed

    Nittayananta, W; Chungpanich, S; Pongpanich, S; Mitarnun, W

    1996-08-10

    Non-Hodgkin's lymphoma (NHL) of the oral cavity frequently occurs in patients infected with human immunodeficiency virus (HIV). This report describes a lesion presenting as delayed healing of an extraction wound with hyperaemic swollen gingivae and ulceration in an apparently healthy 34-year-old Thai fisherman. The lesion was the first evidence of his HIV-positivity. It is, therefore, imperative that clinicians should consider a diagnosis of HIV infection in cases of non-healing extraction wounds in patients in high risk categories.

  14. New insights into the epidemiology of non-Hodgkin lymphoma and implications for therapy

    PubMed Central

    Chihara, Dai; Nastoupil, Loretta J.; Williams, Jessica N.; Lee, Paul; Koff, Jean L.; Flowers, Christopher R.

    2015-01-01

    Non-Hodgkin lymphoma (NHL) comprises numerous biologically and clinically heterogeneous subtypes, with limited data examining risk factors for these distinct disease entities. Many limitations exist when studying lymphoma epidemiology, therefore until recently little was known regarding the etiology of NHL subtypes. This review highlights the results of recent pooled analyses examining risk factors for NHL subtypes. We outline heterogeneity and commonality among risk factors for NHL subtypes, with proposed subtype-specific as well as shared etiologic mechanisms. In addition, we describe how the study of lymphoma epidemiology may translate into prevention or therapeutic targeting as we continue to explore the complexities of lifestyle and genetic factors that impact lymphomagenesis. PMID:25864967

  15. Value of gallium scans and lymphangiography in non-Hodgkin's lymphoma of the Waldeyer's ring

    SciTech Connect

    Shigematsu, N.; Kondo, M.; Kubo, A.; Hashimoto, S.

    1986-12-15

    In 37 patients with seemingly localized non-Hodgkin's lymphoma of the Waldeyer's ring (WR-NHL), lymphangiography (LAG) and/or gallium-67 scans (Ga-67 scans) were done. Before these procedures, 20 patients were diagnosed as Stage I, and 17 as Stage II. LAG was done for 30, and Ga-67 scans for 32, 25 of whom had both. Five patients (16%) were upstaged to Stage III or IV by Ga-67 scans. Only one (3%) had abnormal LAG findings, in whom Ga-67 scans also showed abnormal accumulation in the para-aortic region. Because of this low positive rate, LAG is not recommended for staging of WR-NHL.

  16. Development of non-Hodgkin's lymphoma following therapy for Hodgkin's disease

    SciTech Connect

    Kim, H.D.; Bedetti, C.D.; Boggs, D.R.

    1980-12-15

    Three patients developed non-Hodgkin's lymphoma (NHL) 3 to 6 years after treatment for Hodgkin's disease (HD). In no instance was there evidence of recurrence of HD following the initial chemotherapy or radiotherapy. None of these patients had received both radiation therapy and chemotherapy. All patients responded well to conventional chemotherapy for NHL and are alive at 23 +, 37 +, and 65+ months after that secondary diagnosis. This report, when coupled with at least ten other such reported patients, suggests that NHL may be a relatively uncommon but significant complication of therapy for HD and must be distinguished for recurrence of HD.

  17. Cervical spontaneous epidural hematoma as a complication of non-Hodgkin's lymphoma.

    PubMed

    Mastronardi, L; Carletti, S; Frondizi, D; Spera, C; Maira, G

    1996-01-01

    Epidural hematoma is a rare cause of spinal cord compression, which usually provokes severe neurological deficits. It is presumed to originate from venous or, more probably, arterial bleeding. Thrombocytopenia and other disorders of coagulation may precipitate the onset of epidural hematoma and facilitate the evolution of the disease. We report the case of a patient suffering from a non-Hodgkin's lymphoma with severe thrombocytopenia during a MACOP-B schedule, who presented with a spontaneous cervical epidural hematoma. We discuss the etiopathological aspects, diagnosis, and treatment of this rare cause of acute cervical spinal cord compression.

  18. [Primary presentation of non-hodgkin lymphoma. Report of a case].

    PubMed

    Mirpuri-Mirpuri, P G; Alvarez-Cordovés, M M; Pérez-Monje, A

    2013-09-01

    Lymphomas are the most common non-epithelial tumors of the head and neck and its incidence has increased in recent decades. Around 10% are extranodal lymphomas, and in more than half of the cases are located in Waldeyer's lymphatic ring. The most common presenting symptoms are odynophagia and dysphagia (68%), and symptoms suggestive of oropharyngeal cancer such as cough, hoarseness, earache, feeling of occupation in the back of the mouth, throat or neck. In non-Hodgkin lymphomas in this location, B symptoms (weight loss, fever and sweating) are rare (5%). The histological subtype of each individual lymphoma affects the evaluation, therapy and prognosis.

  19. Distribution of plasma fatty acids is associated with response to chemotherapy in non-Hodgkin's lymphoma patients.

    PubMed

    Cvetković, Zorica; Vučić, Vesna; Cvetković, Bora; Karadžić, Ivana; Ranić, Marija; Glibetić, Marija

    2013-12-01

    Our recent data have linked plasma phospholipid fatty acid (FA) profile in patients with non-Hodgkin's lymphoma (NHL) with the clinical stage and aggressiveness of the disease. Thus, we proposed that plasma FA status in these patients may influence the effect of chemotherapy. The aim of this work was to assess FA status in NHL patients undergoing chemotherapy in relation to their response to therapy. We analyzed plasma FA profile in 47 newly diagnosed NHL patients before chemotherapy, after 3 cycles and after the end of the planned chemotherapy. Patients were treated according to the hospital protocol: 28 patients with cyclophosphamide, doxorubicin, vincristine and prednisone, 7 with other anthracycline-containing regimens, 4 patients with cyclophosphamide, vincristine and prednisone and 8 with fludarabine-based regimens. Rituximab was added in 22 patients. Ten patients who did not receive all planned chemotherapy due to death or toxicity (non-completers) had significantly lower (p < 0.05) baseline proportion of palmitoleic, linoleic, eicosapentaenoic and docosahexaenoic acid, as well as n-3 and n-6 FA, than the patients who completed chemotherapy (completers). Furthermore, the completers were divided according to the response to chemotherapy to complete remission (CR), stable disease and progressive disease (PD). Proportion of palmitic acid after the end of chemotherapy was the highest in the PD group, while stearic acid showed the opposite trend. Palmitoleic acid and all n-3 FA (18:3, 20:5, 22:5 and 22:6) were the highest in the patients in remission and the lowest in PD (p < 0.001). Linoleic acid decreased and arachidonic acid increased from the CR to the PD group (p < 0.001). These results suggest that aberrations in plasma FA may influence response to chemotherapy in patients with NHL.

  20. [Diagnosis, prophylaxis and treatment of central nervous system involvement by non-Hodgkin lymphoma in HIV-infected patients].

    PubMed

    Miralles, Pilar; Berenguer, Juan; Ribera, Josep-Maria

    2010-09-18

    With the widespread use of highly active antiretroviral therapy (HAART) the incidence of systemic non-Hodgkin lymphoma (NHL) in patients infected with the Human Immunodeficiency Virus (HIV) has declined. HAART has also modified the clinical manifestations of these tumors, with a lower frequency of involvement of the central nervous system (CNS). Currently, the frequency of meningeal involvement at the time of diagnosis of NHL in HIV-infected patients varies between 3% and 5%. These figures are similar to those observed among immunocompetent hosts. The diagnosis of meningeal lymphoma relies in clinical findings, imaging techniques, and cerebrospinal fluid (CSF) examination. Flow cytometry is a diagnostic technique with a higher sensitivity and specificity than conventional cytology for the diagnosis of meningeal lymphoma. However, flow cytometry is not yet considered to be the gold standard for this purpose. Until recently, most experts recommended neuromeningeal prophylaxis for all HIV-infected patients with aggressive NHL. However, at present this prophylaxis is recommended only in patients with higher risk of CNS relapse according to different sites of involvement, stage and histological subtype. There are different regimens of prophylaxis and treatment for meningeal lymphoma. The drugs most commonly used for this purpose are methotrexate and cytosine arabinoside. However, there are other alternatives such as liposomal cytosine arabinoside that requires fewer spinal taps for drug administration and whose results are very promising. In summary, in the context of an effective HAART, HIV infected patients with NHL have a frequency of CNS involvement by lymphoma similar to that found among immunocompetent hosts. Consequently, indications and regimens for CNS prophylaxis in HIV-infected patients with NHL should not be different than those employed in the general population. Universal CNS prophylaxis should be reserved for the few patients unable to receive an

  1. Non-Hodgkin lymphoma in South East Asia: An analysis of the histopathology, clinical features, and survival from Thailand.

    PubMed

    Intragumtornchai, Tanin; Bunworasate, Udomsak; Wudhikarn, Kitsada; Lekhakula, Arnuparp; Julamanee, Jakrawadi; Chansung, Kanchana; Sirijerachai, Chittima; Norasetthada, Lalita; Nawarawong, Weerasak; Khuhapinant, Archrob; Siritanaratanakul, Noppadol; Numbenjapon, Tontanai; Prayongratana, Kannadit; Chuncharunee, Suporn; Niparuck, Pimjai; Suwanban, Tawatchai; Kanitsap, Nongluk; Wongkhantee, Somchai; Pornvipavee, Rutchanid; Wong, Peerapon; Makruasi, Nisa; Wannakrairot, Pongsak; Assanasen, Thamathorn; Sukpanichnant, Sanya; Boonsakan, Paisarn; Kanoksil, Wasana; Ya-In, Charin; Kayasut, Kanita; Mitranun, Winyu; Warnnissorn, Naree

    2017-03-23

    Systemic reports on the descriptive epidemiology of non-Hodgkin lymphoma (NHL) from Southeast Asia are scarce. A nationwide multi-institutional registry was conducted to compare the histopathology, clinical features, and survival of Thai adult patients with NHL using large registries, especially those from Far East Asia (FEA). Using a web-based registry system, 13 major medical centers from the 4 geographic regions of Thailand prospectively collected, from 2007 to 2014, the diagnostic pathology, according to the World Health Organization classification, 2008, clinical features and survival of 4056 patients who were newly diagnosed with NHL. The median age of the patients was 56 years (range, 16-99 years). The male-to-female ratio was 1.3:1. From the total of 4056 patients, T/NK-cell lymphoma (TNKCL) accounted for 12.6% of cases, and 5.1% had human immunodeficiency virus-associated lymphoma. The four leading histological subtypes were diffuse large B-cell lymphoma, not otherwise specified (58.1%); follicular lymphoma (5.6%); extranodal mucosa-associated lymphoid tissue lymphoma (5.2%); and peripheral T-cell lymphoma, not otherwise specified (4.0%). With a median follow-up duration of 46.1 months, the median overall survival of B-cell NHL was significantly longer than that of patients with TNKCL (76.5 vs 28.8 months, P = .0001). Compared to FEA, the Thai registry had an approximately one-half lower relative frequency of TNKCL; the prevalence of extranodal mucosa-associated lymphoid tissue lymphoma was much lower than in Korea, and the frequency of extranodal TNKCL, nasal type, was strikingly low compared to China. It is concluded that while the median age of Thai patients with NHL was approximately a decade younger than for Caucasians, the long-term survival rates for most histological subtypes were comparable. While the histological distribution generally complied with the characteristic Asian features, some differences from FEA were observed.

  2. Non-Hodgkin Lymphoma and Occupational Exposure to Agricultural Pesticide Chemical Groups and Active Ingredients: A Systematic Review and Meta-Analysis

    PubMed Central

    Schinasi, Leah; Leon, Maria E.

    2014-01-01

    This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world’s agriculture, were missing in the literature that were reviewed. PMID:24762670

  3. Expression and Function of the Chemokine, CXCL13, and Its Receptor, CXCR5, in Aids-Associated Non-Hodgkin's Lymphoma.

    PubMed

    Widney, Daniel P; Gui, Dorina; Popoviciu, Laura M; Said, Jonathan W; Breen, Elizabeth C; Huang, Xin; Kitchen, Christina M R; Alcantar, Juan M; Smith, Jeffrey B; Detels, Roger; Martínez-Maza, Otoniel

    2010-01-01

    Background. The homeostatic chemokine, CXCL13 (BLC, BCA-1), helps direct the recirculation of mature, resting B cells, which express its receptor, CXCR5. CXCL13/CXCR5 are expressed, and may play a role, in some non-AIDS-associated B cell tumors. Objective. To determine if CXCL13/CXCR5 are associated with AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Methods. Serum CXCL13 levels were measured by ELISA in 46 subjects who developed AIDS-NHL in the Multicenter AIDS Cohort Study and in controls. The expression or function of CXCL13 and CXCR5 was examined on primary AIDS-NHL specimens or AIDS-NHL cell lines. Results. Serum CXCL13 levels were significantly elevated in the AIDS-NHL group compared to controls. All primary AIDS-NHL specimens showed CXCR5 expression and most also showed CXCL13 expression. AIDS-NHL cell lines expressed CXCR5 and showed chemotaxis towards CXCL13. Conclusions. CXCL13/CXCR5 are expressed in AIDS-NHL and could potentially be involved in its biology. CXCL13 may have potential as a biomarker for AIDS-NHL.

  4. A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling.

    PubMed

    Hildebrand, Joanne M; Luo, Zhenghua; Manske, Michelle K; Price-Troska, Tammy; Ziesmer, Steven C; Lin, Wai; Hostager, Bruce S; Slager, Susan L; Witzig, Thomas E; Ansell, Stephen M; Cerhan, James R; Bishop, Gail A; Novak, Anne J

    2010-11-22

    The cytokine B cell activating factor (BAFF) and its receptor, BAFF receptor (BAFF-R), modulate signaling cascades critical for B cell development and survival. We identified a novel mutation in TNFRSF13C, the gene encoding human BAFF-R, that is present in both tumor and germline tissue from a subset of patients with non-Hodgkin lymphoma. This mutation encodes a His159Tyr substitution in the cytoplasmic tail of BAFF-R adjacent to the TRAF3 binding motif. Signaling through this mutant BAFF-R results in increased NF-κB1 and NF-κB2 activity and increased immunoglobulin production compared with the wild-type (WT) BAFF-R. This correlates with increased TRAF2, TRAF3, and TRAF6 recruitment to His159Tyr BAFF-R. In addition, we document a requirement for TRAF6 in WT BAFF-R signaling. Together, these data identify a novel lymphoma-associated mutation in human BAFF-R that results in NF-κB activation and reveals TRAF6 as a necessary component of normal BAFF-R signaling.

  5. Occupation and Risk of Non-Hodgkin Lymphoma and Its Subtypes: A Pooled Analysis from the InterLymph Consortium

    PubMed Central

    ‘t Mannetje, Andrea; De Roos, Anneclaire J.; Boffetta, Paolo; Vermeulen, Roel; Benke, Geza; Fritschi, Lin; Brennan, Paul; Foretova, Lenka; Maynadié, Marc; Becker, Nikolaus; Nieters, Alexandra; Staines, Anthony; Campagna, Marcello; Chiu, Brian; Clavel, Jacqueline; de Sanjose, Silvia; Hartge, Patricia; Holly, Elizabeth A.; Bracci, Paige; Linet, Martha S.; Monnereau, Alain; Orsi, Laurent; Purdue, Mark P.; Rothman, Nathaniel; Lan, Qing; Kane, Eleanor; Costantini, Adele Seniori; Miligi, Lucia; Spinelli, John J.; Zheng, Tongzhang; Cocco, Pierluigi; Kricker, Anne

    2015-01-01

    Background: Various occupations have been associated with an elevated risk of non-Hodgkin lymphoma (NHL), but results have been inconsistent across studies. Objectives: We investigated occupational risk of NHL and of four common NHL subtypes with particular focus on occupations of a priori interest. Methods: We conducted a pooled analysis of 10,046 cases and 12,025 controls from 10 NHL studies participating in the InterLymph Consortium. We harmonized the occupational coding using the 1968 International Standard Classification of Occupations (ISCO-1968) and grouped occupations previously associated with NHL into 25 a priori groups. Odds ratios (ORs) adjusted for center, age, and sex were determined for NHL overall and for the following four subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and peripheral T-cell lymphoma (PTCL). Results: We confirmed previously reported positive associations between NHL and farming occupations [field crop/vegetable farm workers OR = 1.26; 95% confidence interval (CI): 1.05, 1.51; general farm workers OR = 1.19; 95% CI: 1.03, 1.37]; we also confirmed associations of NHL with specific occupations such as women’s hairdressers (OR = 1.34; 95% CI: 1.02, 1.74), charworkers/cleaners (OR = 1.17; 95% CI: 1.01, 1.36), spray-painters (OR = 2.07; 95% CI: 1.30, 3.29), electrical wiremen (OR = 1.24; 95% CI: 1.00, 1.54), and carpenters (OR = 1.42; 95% CI: 1.04, 1.93). We observed subtype-specific associations for DLBCL and CLL/SLL in women’s hairdressers and for DLBCL and PTCL in textile workers. Conclusions: Our pooled analysis of 10 international studies adds to evidence suggesting that farming, hairdressing, and textile industry–related exposures may contribute to NHL risk. Associations with women’s hairdresser and textile occupations may be specific for certain NHL subtypes. Citation: ‘t Mannetje A, De Roos AJ, Boffetta P, Vermeulen R, Benke G

  6. Protein kinase C-associated kinase is required for NF-kappaB signaling and survival in diffuse large B-cell lymphoma cells.

    PubMed

    Kim, Sang-Woo; Oleksyn, David W; Rossi, Randall M; Jordan, Craig T; Sanz, Ignacio; Chen, Luojing; Zhao, Jiyong

    2008-02-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive and the most common type of non-Hodgkin lymphoma. Despite recent advances in treatment, less than 50% of the patients are cured with current multiagent chemotherapy. Abnormal NF-kappaB activity not only contributes to tumor development but also renders cancer cells resistant to chemotherapeutic agents. Identifying and targeting signaling molecules that control NF-kappaB activation in cancer cells may thus yield more effective therapy for DLBCL. Here, we show that while overexpression of protein kinase C-associated kinase (PKK) activates NF-kappaB signaling in DLBCL cells, suppression of PKK expression inhibits NF-kappaB activity in these cells. In addition, we show that NF-kappaB activation induced by B cell-activating factor of tumor necrosis factor family (BAFF) in DLBCL cells requires PKK. Importantly, we show that knockdown of PKK impairs the survival of DLBCL cells in vitro and inhibits tumor growth of xenografted DLBCL cells in mice. Suppression of PKK expression also sensitizes DLBCL cells to treatment with chemotherapeutic agents. Together, these results indicate that PKK plays a pivotal role in the survival of human DLBCL cells and represents a potential target for DLBCL therapy.

  7. Usefulness of Flow Cytometric Analysis for Detecting Leptomeningeal Diseases in Non-Hodgkin Lymphoma

    PubMed Central

    Shin, Sang-Yong; Kim, Hee-Jin; Oh, Young Lyun; Kim, Seok Jin; Kim, Won Seog

    2016-01-01

    Background The clinical usefulness of flow cytometry (FCM) for the diagnosis of leptomeningeal diseases (LMD) in non-Hodgkin lymphomas has been suggested in previous studies but needs to be further validated. With this regards, we evaluated the use of FCM for LMD in a series of Korean patients with non-Hodgkin lymphoma. Methods FCM and cytomorphology were conducted using samples obtained from clinically suspected LMD patients, follow-up LMD patients, and those with high risk of developing tumorigenic diseases. We then compared results of FCM and cytomorphology. In total, 55 and 47 CSF samples were analyzed by FCM and cytomorphology, respectively. Results Of the samples analyzed, 25.5% (14/55) and 12.8% (6/47) were positive by FCM and cytomorphology, respectively. No samples were determined as negative by FCM but positive by cytomorphology. Seven patients were positive only by FCM and negative by cytomorphology, and six among them were clinically confirmed to have LMD either by follow-up cytomorphology or imaging study. Conclusions We observed a high detection rate of tumor cells by FCM compared with cytomorphology. FCM study can be useful in early sensitive detection of LMD. PMID:26915608

  8. Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy

    SciTech Connect

    Bajetta, E.; Valagussa, P.; Bonadonna, G.; Lattuada, A.; Buzzoni, R.; Rilke, F.; Banfi, A.

    1988-07-01

    This paper reports the 5-year results of a prospective randomized study beginning in 1976 on 177 evaluable patients with pathologic Stage I-IE and II-IIE non-Hodgkin's lymphomas with diffuse histology according to the Rappaport classification. Treatment consisted of either CVP or BACOP chemotherapy (3 cycles) followed by regional radiotherapy (40 to 50 Gy) and further cycles of either combination. In both arms, complete remission at the end of combined treatment was high (CVP 93%, BACOP 98%) regardless of age, stage or bulky disease. At 5 years, the comparative freedom from first progression was 62% for CVP vs 78% for BACOP (p = 0.02), respectively. Clinically relevant differences favoring BACOP chemotherapy were essentially documented in patients with large cell lymphomas (International Working Formulation), those with Stage II having more than three involved anatomical sites, bulky disease and age over 60 years. Recurrence within radiation fields was documented in only 5% of complete responders. Combined treatment was, in general, well tolerated particularly when BACOP was used. In only 2 patients given CVP post radiation cutaneous fibrosis was documented. Second solid tumors were detected in 4 patients. One patient started on CVP died because of brain stem necrosis after 45 Gy. We conclude that in Stage I-II patients with nodal and extranodal diffuse non-Hodgkin's lymphomas, particularly large cell lymphomas, combined modality approach with primary Adriamycin and bleomycin containing regimen, such as BACOP, followed by adjuvant radiotherapy offers high chances of cure with minimal toxicity.

  9. Guillain-Barré Syndrome as First Presentation of Non-Hodgkin's Lymphoma.

    PubMed

    Ertiaei, Abolhassan; Ghajarzadeh, Mahsa; Javdan, Azizollah; Taffakhori, Abbas; Siroos, Bahaaddin; Esfandbod, Mohsen; Saberi, Hooshang

    2016-07-01

    We present a woman referred with underlying non-Hodgkin's lymphoma (NHL) masquerading clinically with Guillain-Barré syndrome (GBS) like syndrome. At first evaluation, chest CT-Scan along with brain and whole spine MRI were normal. Electrodiagnostic studies were in favor of acute generalized polyradiculoneuropathy. Laboratory evaluation revealed hypoglycorrhachia. She treated with plasmapheresis after two weeks; she was discharged from hospital, but neurological recovery was not complete. After 6 months, she came back with acute onset of weakness in lower limbs, back pain, fever and urinary incontinence. Pinprick and light touch complete sensory loss was found beneath umbilicus. Thoracic MRI with contrast revealed a dorsal epidural mass extending smoothly from T8 to T12 (10 cm) with spinal cord compression. She underwent urgent laminectomy for spinal cord decompression. Histological examination revealed small round cell tumor suggestive of malignant T-cell type lymphoma. In cases with Guillain-Barré syndrome presentation, systemic hematologic disorders such as non-Hodgkin's lymphoma should be considered as one of the differential diagnosis of underlying disease.

  10. Regular use of aspirin or acetaminophen and risk of non-Hodgkin lymphoma.

    PubMed

    Baker, Julie A; Weiss, Joli R; Czuczman, Myron S; Menezes, Ravi J; Ambrosone, Christine B; Moysich, Kirsten B

    2005-04-01

    Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of non-Hodgkin lymphoma (NHL), although previous results have been inconsistent. The current study investigated the effects of regular aspirin or acetaminophen use on non-Hodgkin lymphoma risk among 625 individuals with primary, incident NHL and 2512 age and sex matched hospital controls with non-neoplastic conditions who completed a comprehensive epidemiologic questionnaire. Results indicate that regular aspirin use may be associated with decreased NHL risk among men [adjusted odds ratio (aOR) 0.82, 95% confidence interval (CI), 0.65--1.04], but not among women (aOR 0.93, 95% CI, 0.71--1.23). In contrast, regular acetaminophen use was associated with elevated NHL risk among women (aOR 1.71, 95% CI, 1.18--2.50) but not among men (aOR 0.75, 95% CI, 0.48--1.17). Other studies have demonstrated that acetaminophen is associated with transient decreases in DNA repair, and lymphocytes may be particularly susceptible to DNA damage, suggesting a mechanism for the elevated NHL risk observed.

  11. [The problems of immunological diagnosis of childhood acute leukemia and non-Hodgkin's lymphoma].

    PubMed

    Pituch-Noworolska, Anna

    2003-01-01

    The immunophenotyping of leukaemia and non-Hodgkin's lymphoma cells is based on staining the cells with monoclonal antibodies against surface and cytoplasmic determinants followed with flow cytometry analysis. The problems of immuno-phenotyping are associated with technical difficulties, changes in expression of determinants and the rare types of leukaemia and haematological disorders typical for newborns and infants. The lack of blast cells within cell suspension obtained for test may be the result of bone marrow disorder (aplastic anaemia, preleukaemic cytopenia) or technical pitfall. The changed expression of determinants on blastic cells observed as weak expression or overexpression or atypical combination of determinants requires a careful interpretation. In the diagnosis of rare types of acute leukaemia (e.g. erythroleukaemia, megakaryoblastic leukaemia, mixed lineage or undifferentiated leukaemia) the additional monoclonal antibodies beyond routine set are needed. A special concern is necessary in diagnosis of newborns and infants leukaemia or bone marrow disorders like myelodisplastic syndrome particularly in children with other systemic diseases e.g. congenital immunological deficiencies, Down's syndrome. The problems of immunophenotyping in non-Hodgkin's lymphoma are frequently associated with obtaining a representative material e.g. surgical tumour biopsy, lymph node. In some case the differential diagnosis including small round cell tumours and anaplastic type of lymphoma is necessary what requires an additional set of monoclonal antibodies. Despite of modern technology, morphology, immunophenotyping and histopathology remain the standard of complex diagnosis of lymphoproliferative diseases and haematopoietic disorders in children.

  12. Rituximab with dose-adjusted EPOCH as first-line treatment in patients with highly aggressive diffuse large B-cell lymphoma and autologous stem cell transplantation in selected patients

    PubMed Central

    Pejša, Vlatko; Prka, Željko; Lucijanić, Marko; Mitrović, Zdravko; Piršić, Mario; Jakšić, Ozren; Ajduković, Radmila; Kušec, Rajko

    2017-01-01

    Aim To assess the benefit of rituximab with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-DA-EPOCH) regimen as a first-line treatment for patients with diffuse large B-cell lymphoma (DLBCL) presenting with unfavorable or aggressive features, and autologous stem cell transplantation (ASCT) as a part of the first-line treatment for selected DLBCL patients with additional aggressive features. Methods We retrospectively analyzed 75 newly diagnosed DLBCL patients with Ki-67+≥80% or International Prognostic Index ≥2 who were treated with R-DA-EPOCH between 2005 and 2015. Of 24 DLBCL patients with additional aggressive features (Ki-67+≥90% or age-adjusted IPI≥2) who were planned to receive consolidation with ASCT, 17 patients underwent the procedure. We determined the overall response rate (ORR), complete remission (CR), partial remission (PR), 5-year overall survival (OS), and progression free survival (PFS) in all DLBCL patients and specifically those planned to receive ASCT. Results All 75 patients included in the analysis started one or more cycles of therapy. The ORR, CR, and PR rates were 80%, 55%, and 25%, respectively. The response was non-evaluable in 10 of 75 patients due to treatment discontinuation. The OS and PFS rates for all 75 patients were 70% and 61%, respectively, and 80% and 79%, respectively, for 24 planned-to-receive-ASCT patients. Age (≤65 vs >65 years) had no prognostic impact on OS and PFS (P = 0.994 and P = 0.827, respectively). Conclusion Our retrospective analysis of one of the largest DLBCL patient cohorts outside the US National Cancer Institute showed that R-DA-EPOCH is a very effective therapeutic option as a first-line treatment of DLBCL patients with unfavorable prognostic features irrespective of their age. ASCT provided additional benefit for DLBCL patients with additional aggressive features. PMID:28252874

  13. Classification of non-Hodgkin lymphoma in South-eastern Europe: review of 632 cases from the international non-Hodgkin lymphoma classification project.

    PubMed

    Dotlic, Snjezana; Perry, Anamarija M; Petrusevska, Gordana; Fetica, Bogdan; Diebold, Jacques; MacLennan, Kenneth A; Müller-Hermelink, Hans K; Nathwani, Bharat N; Boilesen, Eugene; Bast, Martin; Armitage, James O; Weisenburger, Dennis D

    2015-11-01

    The distribution of non-Hodgkin lymphoma (NHL) subtypes varies around the world, but a systematic study of South-eastern Europe (SEEU) has never been done. Therefore, we evaluated the relative frequencies of NHL subtypes in three SEEU countries--Croatia, Romania and Macedonia. Five expert haematopathologists reviewed 632 consecutive cases of newly diagnosed NHL from the three SEEU countries using the World Health Organization classification. The results were compared to 399 cases from North America (NA) and 580 cases from Western Europe (WEU). The proportions of B- and T-cell NHL and the sex distribution in SEEU were similar to WEU and NA. However, the median ages of patients with low- and high-grade B-NHL in SEEU (60 and 59 years, respectively) were significantly lower than in NA (64 and 68 years, respectively; P < 0·05). SEEU had a significantly lower proportion of low-grade B-NHL (46·6%) and higher proportion of high-grade B-NHL (44·5%) compared to both WEU (54·5% and 36·4%, respectively) and NA (56·1% and 34·3%, respectively). There were no significant differences in the relative frequencies of T-NHL subtypes. This study provides new insights into differences in the relative frequencies of NHL subtypes in different geographic regions. Epidemiological studies are needed to better characterize and explain these differences.

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

    PubMed Central

    Benavente, Yolanda; Turner, Jennifer J.; Paltiel, Ora; Slager, Susan L.; Vajdic, Claire M.; Norman, Aaron D.; Cerhan, James R.; Chiu, Brian C. H.; Becker, Nikolaus; Cocco, Pierluigi; Dogan, Ahmet; Nieters, Alexandra; Holly, Elizabeth A.; Kane, Eleanor V.; Smedby, Karin E.; Maynadié, Marc; Spinelli, John J.; Roman, Eve; Glimelius, Bengt; Wang, Sophia S.; Sampson, Joshua N.; Morton, Lindsay M.; de Sanjosé, Silvia

    2014-01-01

    Background Marginal zone lymphoma (MZL), comprised of nodal, extranodal, and splenic subtypes, accounts for 5%–10% of non-Hodgkin lymphoma cases. A detailed evaluation of the independent effects of risk factors for MZL and its subtypes has not been conducted. Methods Data were pooled from 1052 MZL cases (extranodal [EMZL] = 633, nodal [NMZL] = 157, splenic [SMZL] = 140) and 13766 controls from 12 case–control studies. Adjusted unconditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). Results Novel findings for MZL subtypes include increased risk for B-cell activating autoimmune conditions (EMZL OR = 6.40, 95% CI = 4.24 to 9.68; NMZL OR = 7.80, 95% CI = 3.32 to 18.33; SMZL OR = 4.25, 95% CI = 1.49 to 12.14), hepatitis C virus seropositivity (EMZL OR = 5.29, 95% CI = 2.48 to 11.28), self-reported peptic ulcers (EMZL OR = 1.83, 95% CI = 1.35 to 2.49), asthma without other atopy (SMZL OR = 2.28, 95% CI = 1.23 to 4.23), family history of hematologic cancer (EMZL OR = 1.90, 95% CI = 1.37 to 2.62) and of non-Hodgkin lymphoma (NMZL OR = 2.82, 95% CI = 1.33 to 5.98), permanent hairdye use (SMZL OR = 6.59, 95% CI = 1.54 to 28.17), and occupation as a metalworker (NMZL OR = 3.56, 95% CI = 1.67 to 7.58). Reduced risks were observed with consumption of any alcohol (EMZL fourth quartile OR = 0.48, 95% CI = 0.28 to 0.82) and lower consumption of wine (NMZL first to third quartile ORs < 0.45) compared with nondrinkers, and occupation as a teacher (EMZL OR = 0.58, 95% CI = 0.37 to 0.88). Conclusion Our results provide new data suggesting etiologic heterogeneity across MZL subtypes although a common risk of MZL associated with B-cell activating autoimmune conditions was found. PMID:25174026

  15. Renal Infiltration by Diffuse Large B-Cell Lymphoma as a Rare Cause of Fanconi's Syndrome: A Case Report.

    PubMed

    Saadat, Shoab; Mahmud, Syed Nayer; Qureshi, Asim

    2016-11-30

    We report the case of a 16-year-old female patient with a known history of coeliac disease, who presented with the complaints of diarrhea, vomiting and generalized body weakness. On examination, she was found to have dehydration, decreased power in all her limbs, cervical lymphadenopathy and hepatosplenomegaly. Investigations showed severe hypokalemia, hyponatremia, hypomagnesemia, hypoglycemia and mildly enlarged kidneys on ultrasonography. Biopsy of the duodenum confirmed the flare up of coeliac disease, while cervical lymph node biopsy was positive for atypical lymphoid infiltrate and a morphology suggestive of non-Hodgkin's lymphoma. The immune profile performed on this sample confirmed the presence of activated/non-germinal center type of diffuse large B cell lymphoma (DLBCL), which was morphologically aggressive in type. The bone marrow biopsy was hypocellular and was negative for any infiltration. The patient was suspected to have developed infiltration of one or both kidneys leading to a rare presentation of Fanconi's syndrome. She was given first dose of rituximab on the 14th day of her admission. Unfortunately, she developed cardiopulmonary arrest and expired on the next day. We recommend screening for a possible renal involvement in patients with DLBCL and in patients with unusually deranged serum electrolytes as seen in Fanconi's syndrome. Renal biopsy is considered the gold standard modality for diagnosis and if possible, an earlier sample in a patient with newly developed acute kidney injury can save future complications.

  16. Childhood B cell lymphomas arising in the mediastinum.

    PubMed Central

    Carr, T F; Lockwood, L; Stevens, R F; Morris-Jones, P H; Lewis, I; DaCosta, P E; Kelsey, A M

    1993-01-01

    AIMS--To report the clinical features and pathology of four childhood cases of primary mediastinal non-Hodgkin's lymphoma of non-lymphoblastic pathology. METHODS--Biopsy material was fixed in formol-saline and routinely processed and stained. Immunohistochemical staining was performed on paraffin wax embedded sections using the alkaline phosphatase anti-alkaline phosphatase method. RESULTS--The four patients presented with a large mediastinal mass and symptoms consistent with superior vena cava syndrome secondary to lymphoma. None of the patients had any clinically important disease outside the mediastinum. The four tumours had a histological appearance similar to diffuse large cell non-Hodgkin's lymphoma with sclerosis. Immunohistochemical staining showed that these tumours were of B cell origin. One patient died from infection during treatment and two patients died with progressive disease. The remaining patient remained well 43 months off all treatment. CONCLUSIONS--These four cases further illustrate the heterogeneity of paediatric large cell lymphomas. Clinically, they seem to be equivalent to the B cell lymphoma of the mediastinum, sclerosing type, that is seen in young (predominantly female) adults. The clinical and biological features of this type of tumour in childhood are largely unknown. Using standard treatment protocols, this tumour seems to have a poor prognosis and its optimal treatment therefore requires further clarification. Images PMID:8331171

  17. The novel kinesin spindle protein (KSP) inhibitor SB-743921 exhibits marked activity in in vivo and in vitro models of aggressive large B-cell lymphoma.

    PubMed

    Bongero, Danielle; Paoluzzi, Luca; Marchi, Enrica; Zullo, Kelly M; Neisa, Roberto; Mao, Yinghui; Escandon, Rafael; Wood, Ken; O'Connor, Owen A

    2015-01-01

    The kinesin spindle protein (KSP) is a mitotic protein essential for cell cycle control and motility. SB-743921 (hereafter SB-921) is an inhibitor that selectively targets the ATP-binding domain of the KSP. The preclinical activity of SB-921 was evaluated in models of diffuse large B-cell lymphoma (DLBCL). The cytotoxicity of SB-921 was evaluated in a series of germinal center (GC-DLBCL) and post-germinal center (ABC-DLBCL) DLBCL cell lines and a murine lymphoma xenograft model. GC-DLBCL lines generally demonstrated greater sensitivity to SB-921. IC50 values ranged between 1 nM and 900 nM for GC-DLBCL compared to 1 nM to 10 μM for ABC lines. SB-921 demonstrated marked activity in a xenograft model of Ly-1 (GC-DLBCL). While SB-921 was relatively more active in GC derived cell lines, ABC-derived lines still underwent apoptosis at higher concentrations. These results demonstrate that SB-921 inhibits proliferation and induces apoptosis in both GC-DLBCL and ABC-DLBCL.

  18. RD-CODOX-M/IVAC with rituximab and intrathecal liposomal cytarabine in adult Burkitt lymphoma and 'unclassifiable' highly aggressive B-cell lymphoma.

    PubMed

    Corazzelli, Gaetano; Frigeri, Ferdinando; Russo, Filippo; Frairia, Chiara; Arcamone, Manuela; Esposito, Gennaro; De Chiara, Annarosaria; Morelli, Emanuela; Capobianco, Gaetana; Becchimanzi, Cristina; Volzone, Francesco; Saggese, Mariangela; Marcacci, Giampaolo; De Filippi, Rosaria; Vitolo, Umberto; Pinto, Antonio

    2012-01-01

    Specific trials on adult Burkitt lymphoma (BL) and 'unclassifiable' lymphomas with features intermediate between BL and diffuse large B-cell lymphoma (BL/DLBCL) are advocated which include substantial numbers of older patients, to improve treatment feasibility, while countering risks of systemic and central nervous system (CNS) recurrences. We prospectively evaluated a modified CODOX-M/IVAC (CODOX-M: cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate; IVAC: ifosfamide, etoposide and high-dose cytarabine) regimen by the addition of rituximab (R) and liposome-encapsulated cytarabine (D) to increase antitumour activity and halve the number of intrathecal treatments. Thirty adults (40% >60years) with BL (n=15) and BL/DLBCL (n=15) were accrued. Primary endpoints were progression-free survival (PFS), CNS recurrence, and liposomal cytarabine-associated toxicity. Eighty percent of patients received the whole treatment programme, the remaining cases received at least three full courses. Application of the RD-CODOX-M/IVAC regimen resulted in remarkable 4-year PFS (78%) and complete remission (CR) rates (93%). However, PFS was significantly lower in patients older than 60years as compared to younger ones (49%vs 93%, P=0·03; median, 36months), despite high actual dose-intensity, CR rate and tolerability. Reduced-intensity intratechal prophylaxis through liposomal cytarabine was effective because the CNS failure rate was low (3·4%) and without severe neurological toxicities. The RD-CODOX-M/IVAC strategy is feasible and highly effective, but improving outcomes in elderly patients remains a priority.

  19. Identification of β-Lapachone Analogs as Novel MALT1 Inhibitors To Treat an Aggressive Subtype of Diffuse Large B-Cell Lymphoma.

    PubMed

    Lim, Sang Min; Jeong, Yujeong; Lee, Suhyun; Im, Honggu; Tae, Hyun Seop; Kim, Byung Gyu; Park, Hee Dong; Park, Jonghoon; Hong, Sungwoo

    2015-11-12

    The treatment of activated B cell-like DLBCL (ABC-DLBCL) is one of the urgent unmet medical needs because it is the most resistant DLBCL subtype to current therapies eagerly awaiting effective therapeutic strategies. Recently, the paracaspase MALT1 has emerged as a promising therapeutic target for the treatment of ABC-DLBCL. Herein, we report a new class of MALT1 inhibitors developed by high-throughput screening and structure-based drug design. The original hit, 4-amino-1,2-naphthoquinone series inhibited MALT1 activity but suffered from poor cellular activity. The extensive pharmacophore search led to the discovery of structurally similar β-lapachone that is a direct inhibitor of MALT1 and possesses favorable physicochemical properties. Molecular simulation studies suggested the possibility of the formation of a covalent bond between MALT1 and β-lapachone, which was corroborated by experimental wash-out studies. Inspired by this, we explored the structure-activity relationships by incorporating electron-withdrawing substituents at C8 position of β-lapachone. These MALT1 inhibitors exhibited potent antiproliferative activity to OCI-LY3 cell line and inhibited the cleavage of CYLD mediated MALT1.

  20. Primary B cell lymphoma of the tongue base: a case report.

    PubMed

    Bechir, Achour; Asma, Achour; Haifa, Regaieg; Nesrine, Abdessayed; Yosra, Ben Youssef; Badreddine, Sriha; Abderrahim, Khelif

    2016-01-01

    Primary non-Hodgkin's lymphoma's of the tongue is very rare and accounts for 1% of all malignant tumor of the oral cavity. Clinical features are non-specific ulcerative lesions that do not heal. In the literature, the majority of cases are diffuse large B cell type however, T cell phenotype also may occur. We describe a 77 years old man, who presented with an ulcerative mass in the left margin of the tongue the diagnosis diffuse large B cell lymphoma was confirmed. The patient is actually on treatment R-mini CEOP and has favorable evolution.

  1. Study on effectiveness of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related non-Hodgkin's lymphoma.

    PubMed

    Zhong, Dong Ta; Shi, Chun Mei; Chen, Qiang; Huang, Jing Ze; Liang, Jian Gang

    2012-11-01

    Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. Even though NHL is commonly chemosensitive to primary treatment, failure or relapse still occurs in a large number of patients. We conducted this retrospective study to evaluate the efficacy and safety of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related NHL (AIDS-NHL). Forty-eight patients with relapsed or refractory AIDS-NHL were treated with intravenous combination chemotherapy with GDP. The overall objective response rate was 54.1% (95% confidence interval, CI, 40.1-68.3%), with 10 complete responses and 16 partial responses. The 2-year overall survival rate (OS) was 70.8% (95% CI 58.0-83.7%), and the 5-year OS was 41.7% (95% CI 27.7-55.6%). The 2-year progression-free survival rate (PFS) was 37.5% (95% CI 23.8-51.2%), and the 5-year PFS was 25.0% (95% CI 12.8-37.3%). The median progression-free survival was 8.8 months (95% CI 0-20.3 months), and the median overall survival was 40.6 months (95% CI 22.6-58.6 months). Patients with B cell tumors who relapsed but had no B symptoms were clinical stage I/II, had infiltration fewer than two extranodal sites, had CD4⁺ counts >200 cells/μL, and had lactate dehydrogenase (LDH) less than the upper limit of normal benefited from GDP. The level of LDH had a significant impact on the response rate to chemotherapy with GDP (P = 0.015). Myelosuppression was the main side effect; the incidence of grade 3-4 anemia was 8.3%; leukopenia, 37.5%; and thrombocytopenia, 48.3%. Univariate and multivariate analyses were performed to determine variables for OS and PFS. This study confirms that GDP is an effective and safe salvage regimen in relapsed or refractory AIDS-NHL, was associated with modest declines in CD4⁺ lymphocyte counts, and did not promote HIV-1 viral replication.

  2. The T-cell Receptor Repertoire Influences the Tumor Microenvironment and Is Associated with Survival in Aggressive B-cell Lymphoma.

    PubMed

    Keane, Colm; Gould, Clare; Jones, Kimberley; Hamm, David; Talaulikar, Dipti; Ellis, Jonathan; Vari, Frank; Birch, Simone; Han, Erica; Wood, Peter; Le-Cao, Kim-Anh; Green, Michael R; Crooks, Pauline; Jain, Sanjiv; Tobin, Josh; Steptoe, Raymond J; Gandhi, Maher K

    2017-04-01

    Purpose: To investigate the relationship between the intra-tumoral T-cell receptor (TCR) repertoire and the tumor microenvironment (TME) in de novo diffuse large B-cell lymphoma (DLBCL) and the impact of TCR on survival.Experimental Design: We performed high-throughput unbiased TCRβ sequencing on a population-based cohort of 92 patients with DLBCL treated with conventional (i.e., non-checkpoint blockade) frontline "R-CHOP" therapy. Key immune checkpoint genes within the TME were digitally quantified by nanoString. The primary endpoints were 4-year overall survival (OS) and progression-free survival (PFS).Results: The TCR repertoire within DLBCL nodes was abnormally narrow relative to non-diseased nodal tissues (P < 0.0001). In DLBCL, a highly dominant single T-cell clone was associated with inferior 4-year OS rate of 60.0% [95% confidence interval (CI), 31.7%-79.6%], compared with 79.8% in patients with a low dominant clone (95% CI, 66.7%-88.5%; P = 0.005). A highly dominant clone also predicted inferior 4-year PFS rate of 46.6% (95% CI, 22.5%-76.6%) versus 72.6% (95% CI, 58.8%-82.4%, P = 0.008) for a low dominant clone. In keeping, clonal expansions were most pronounced in the EBV(+) DLBCL subtype that is known to express immunogenic viral antigens and is associated with particularly poor outcome. Increased T-cell diversity was associated with significantly elevated PD-1, PD-L1, and PD-L2 immune checkpoint molecules.Conclusions: Put together, these findings suggest that the TCR repertoire is a key determinant of the TME. Highly dominant T-cell clonal expansions within the TME are associated with poor outcome in DLBCL treated with conventional frontline therapy. Clin Cancer Res; 23(7); 1820-8. ©2016 AACR.

  3. Non-Hodgkin lymphoma: computed tomographic demonstration of unusual extranodal involvement

    SciTech Connect

    Glazer, H.S.; Lee, J.K.T.; Balfe, D.M.; Mauro, M.A.; Griffith, R.; Sagel, S.S.

    1983-10-01

    With the advent of computed tomography, lymphomatous involvement of sites other than lymph nodes is being seen with increasing frequency. Review of computed tomographic scans in 400 patients with newly diagnosed or recurrent non-Hodgkin lymphoma revealed 37 patients to have involvement of 56 unusual sites below the diaphragm: psoas/iliacus muscle (16 patients), kidney (13 patients), pancreas (5 patients), adrenal (4 patients), skin/subcutaneous tissue (4 patients), abdominal wall musculature (4 patients), peritoneum (4 patients), omentum (3 patients), and female reproductive tract (3 patients). These were mostly seen in patients with lymphomas of diffuse architecture, especially diffuse histiocytic lymphoma. Concomitant retroperitoneal and/or mesenteric adenopathy was very common; extraodal involvement was rarely the only site of initial or recurrent lymphoma.

  4. Clinical outcome in patients with small-intestinal non-Hodgkin lymphoma.

    PubMed

    Kako, Shinichi; Oshima, Kumi; Sato, Miki; Terasako, Kiriko; Okuda, Shinya; Nakasone, Hideki; Yamazaki, Rie; Tanaka, Yukie; Tanihara, Aki; Kawamura, Yutaka; Kiyosaki, Hirokazu; Higuchi, Takakazu; Nishida, Junji; Konishi, Fumio; Kanda, Yoshinobu

    2009-10-01

    The clinical features and outcome of small intestinal lymphoma remain unclear. We retrospectively analyzed 23 patients who had non-Hodgkin lymphoma with a small intestinal lesion. With a median follow-up of 37 months, the 5-year overall survival and failure-free survival (FFS) were 64% and 60%, respectively. In a univariate analysis, a worse performance status at the start of treatment and the occurrence of abdominal symptoms or perforation during treatment were associated with poor survival. Perforation often resulted in a dismal prognosis in patients with uncontrollable lymphoma, but not in patients with lymphoma in remission. The role of surgery in small intestinal lymphoma remains equivocal. In the current study, surgery before other therapies favorably influenced FFS, and all patients who underwent complete resection of the small intestinal lesion had extremely favorable results. Further studies are warranted to establish optimal therapeutic strategies.

  5. Post-therapeutic acute malignant myeloproliferative syndrome and acute nonlymphocytic leukemia in non-Hodgkin's lymphoma

    SciTech Connect

    Gomez, G.A.; Aggarwal, K.K.; Han, T.

    1982-12-01

    In a prospective randomized study of treatment with radiation therapy (RT) or RT + chemotherapy (CT) for patients with non-Hodgkin's lymphoma Stages I-III, one patient developed an acute malignant myeloproliferative syndrome (AMMS) and four others acute nonlymphocytic leukemia (ANLL). There was correlation between the intensity of treatment and development of this complication: Among patients treated with local radiation with or without chemotherapy no cases of AMMS or ANLL were observed. However, patients treated with total lymphoid irradiation alone (TLI) had an observed to expected ratio of 162. Among patients treated with TLI plus CT this ratio increased to over 1000. The cytogenetic, clinical, and hematologic abnormalities of these patients are discussed.

  6. Single high dose-large field irradiation in drug resistant non-Hodgkin's lymphoma

    SciTech Connect

    Scarantino, C.W.; Greven, K.M.; Buss, D.H.

    1988-05-01

    Single high dose-large field irradiation (SHD-LFI), also described as half-body irradiation (HBI), has previously been reported as an effective modality for the palliation of symptoms in a number of solid tumors. This report concerns the ability of SHD-LFI to produce palliation of symptoms and/or objective response in patients with drug resistant non-Hodgkin's lymphoma (NHL). From 1981 to 1984, 34 patients with advanced drug resistant NHL were treated with SHD-LFI either to the whole abdomen (24 patients) or to the upper half body (10 patients). Overall, 19 of 23 patients achieved symptomatic improvement, while objective response was noted in 23 of 30 patients. We noted subjective and objective response in all histologies, and duration of response was not significantly different. Our results suggest a beneficial role for the early and judicious use of SHD-LFI in NHL.

  7. Preoperative ultrasound and gallium-67 evaluation of abdominal non-Hodgkin's lymphoma

    SciTech Connect

    White, L.; Miller, J.H.; Reid, B.S.

    1984-08-01

    The diagnostic accuracy of abdominal ultrasonography followed by gallium (Ga)-67 scintigraphy in 21 patients, aged 1 to 14 years, appearing with abdominal non-Hodgkin's lymphoma (NHL) was analyzed. All cases were confirmed by biopsy; in a majority (16 patients), the tissue was obtained from an abdominal mass at the time of laparotomy subsequent to the imaging studies. Nineteen satisfactory abdominal ultrasound examinations were performed; 18 were interpreted as characteristic of NHL. Sixteen of these were of masses involving the gastrointestinal tract. All 21 patients had /sup 67/Ga scintigraphy that demonstrated abnormal radionuclide accumulation in the abdomen. In no instance was the final diagnosis different from the one predicted by the combined imaging studies. Ultrasonography is recommended as the initial test in the evaluation of clinical presentations consistent with abdominal NHL to expedite suitable management and prevent inappropriate surgery.

  8. Whole abdominal irradiation in non-Hodgkin's lymphomas. I. Tolerance and outcome

    SciTech Connect

    Yaeger TE 4; Calvo, F.A.; Brady, L.W.

    1986-10-01

    Thirty patients, over a 16-year period, treated with whole abdominal irradiation for non-Hodgkin's lymphoma were reviewed. Therapy tolerance, acute toxicity, and long-term outcome were determined. When adequate protection of vital intraabdominal organs was instituted properly, patient tolerance required only conservative medical management. Peripheral hematologic values exhibited mild depressions to nadir values near completion (3500-4000 rad) of treatment. Blood count recovery and general functional normalization occurred within the first post-treatment month. Average total weight loss was only 3.5 pounds with a similar pattern of recovery following therapy completion. Sixteen patients with average follow-up of 6 years still survive. Comparative studies involving total abdominal irradiation for human malignancies are also discussed.

  9. Morphologic changes in the thyroid after irradiation for Hodgkin's and non-Hodgkin's lymphoma

    SciTech Connect

    Carr, R.F.; LiVolsi, V.A.

    1989-08-15

    Four cases of thyroidectomy for suspected thyroid carcinoma after previous irradiation for Hodgkin's or non-Hodgkin's lymphoma are reviewed. The patients ranged in age from 18 to 33 years at the time of thyroid surgery with an average latency period of 12 years (range, 8-20 years) from radiation therapy to thyroidectomy. All patients had a clinically palpable thyroid nodule, and pathologically showed a pattern of multiple adenomatous nodules with cytologic atypia. The microscopic changes were sufficiently striking to cause the primary pathologist to request consultation to rule out thyroid carcinoma in each case. Fine-needle aspiration was performed in one case and suggested a thyroid neoplasm. The pathologic findings are reviewed and distinction of this lesion from thyroid carcinoma is discussed.

  10. [Gastro-intestinal involvement in non Hodgkin's lymphomas, 31 cases (author's transl)].

    PubMed

    Najman, A; Gorin, N C; Barranger, C; Duhamel, G

    1977-11-12

    Gastro-intestinal involvement is a distinctive feature of non-Hodgkin's lymphomas. 31 cases are reported among 200 cases on NHL observed between 1960 and 1976. Multiple involvement appeared in 61%; a diffuse histological pattern is frequent (67%). The relapse of primary isolated gastro-intestinal localization (always) affected extra-digestive tissues (nodes, cavum). Chemotherapy is the mainstay of treatment COP, COAP and MOCA. Surgery is associated in localized involvement or in case of obstruction. High energy radiation therapy is indicated only in lymphosarcomas: -- to residual tumor after chemotherapy--in localized involvement diffuse on all the abdomen at 25 grays after surgery and a brief course of chemotherapy versus surgery and long course of chemotherapy alone.

  11. Non-Hodgkin lymphoma: computed tomographic demonstration of unusual extranodal involvement.

    PubMed

    Glazer, H S; Lee, J K; Balfe, D M; Mauro, M A; Griffith, R; Sagel, S S

    1983-10-01

    With the advent of computed tomography, lymphomatous involvement of sites other than lymph nodes is being seen with increasing frequency. Review of computed tomographic scans in 400 patients with newly diagnosed or recurrent non-Hodgkin lymphoma revealed 37 patients to have involvement of 56 unusual sites below the diaphragm: psoas/iliacus muscle (16 patients), kidney (13 patients), pancreas (5 patients), adrenal (4 patients), skin/subcutaneous tissue (4 patients), abdominal wall musculature (4 patients), peritoneum (4 patients), omentum (3 patients), and female reproductive tract (3 patients). These were mostly seen in patients with lymphomas of diffuse architecture, especially diffuse histiocytic lymphoma. Concomitant retroperitoneal and/or mesenteric adenopathy was very common; extranodal involvement was rarely the only site of initial or recurrent lymphoma.

  12. Molecular genetics of childhood, adolescent and young adult non-Hodgkin lymphoma

    PubMed Central

    Miles, Rodney R.; Shah, Rikin K.; Frazer, J. Kimble

    2017-01-01

    Summary Molecular genetic abnormalities are ubiquitous in non-Hodgkin lymphoma (NHL), but genetic changes are not yet used to define specific lymphoma subtypes. Certain recurrent molecular genetic abnormalities in NHL underlie molecular pathogenesis and/or are associated with prognosis or represent potential therapeutic targets. Most molecular genetic studies of B- and T-NHL have been performed on adult patient samples, and the relevance of many of these findings for childhood, adolescent and young adult NHL remains to be demonstrated. In this review, we focus on NHL subtypes that are most common in young patients and emphasize features actually studied in younger NHL patients. This approach highlights what is known about NHL genetics in young patients but also points to gaps that remain, which will require cooperative efforts to collect and share biological specimens for genomic and genetic analyses in order to help predict outcomes and guide therapy in the future. PMID:26969846

  13. [Hipercalcemia and non-Hodgkin's lymphomas. Report of three patients (author's transl)].

    PubMed

    Saro, E; Redón, J; Herranz, C; Munarriz, B; Montalar, J; Caballero, M

    1980-05-10

    Three out of 140 patients with non-hodgkin's lymphoma treated in a Department of Internal Medicine showed hypercalcemia during their clinical course. Hypercalcemia was symptomatic in two patients causing renal failure in one of them and a metabolic encephalopathy in the other. In the third case hypercalcemia was a casual finding. Serum calcium levels varied between 14.8 and 16.6 mg/100 ml; serum phosphate and tubular reabsorption of phosphate were normal. Alkaline phosphatase were high in the three cases. Bone disease was present in two cases. Transient responses were obtained with the administration of prednisone and calcitonin associated to forced diuresis. Indomethacin was ineffective. Pathogenesis of hypercalcemia could be related to the release of an osteoclastic activator factor. The role of prostaglandins and the presence of PTH-like mechanisms were discarded in our cases by indirect methods. The poor prognosis of patients with non-hogkin's lymphoma and hypercalcemia in stressed.

  14. New insights into the epidemiology of non-Hodgkin lymphoma and implications for therapy.

    PubMed

    Chihara, Dai; Nastoupil, Loretta J; Williams, Jessica N; Lee, Paul; Koff, Jean L; Flowers, Christopher R

    2015-05-01

    Non-Hodgkin lymphoma (NHL) comprises numerous biologically and clinically heterogeneous subtypes, with limited data examining the risk factors for these distinct disease entities. Many limitations exist when studying lymphoma epidemiology; therefore, until recently, little was known regarding the etiology of NHL subtypes. This review highlights the results of recent pooled analyses examining the risk factors for NHL subtypes. We outline the heterogeneity and commonality among the risk factors for NHL subtypes, with proposed subtype-specific as well as shared etiologic mechanisms. In addition, we describe how the study of lymphoma epidemiology may translate into prevention or therapeutic targeting as we continue to explore the complexities of lifestyle and genetic factors that impact lymphomagenesis.

  15. 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

  16. High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2010-08-05

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Childhood Acute Promyelocytic Leukemia (M3); Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; De Novo Myelodysplastic Syndromes; 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; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent

  17. Diffuse large B-cell lymphoma, not otherwise specified of the palate: A case report

    PubMed Central

    Pereira, Thaís SF.; Castro, Alexandre F.; Mesquita, Ricardo A.

    2013-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin´s lymphoma found in oral and maxillofacial regions. A large number of cases may be biologically heterogeneous, which are commonly defined as DLBCL, not otherwise specified (NOS) by the World Health Organization (WHO-2008). The present case reports on an ulcer of raised and irregular edges, found on the border between the hard and soft palate, as the first and only manifestation of an extranodal non-Hodgkin lymphoma in an 85-year-old patient. Incisional biopsy was carried out, and the specimen revealed a proliferation of large lymphoid cells suggestive of diffuse large cell lymphoma. An immunohistochemical analysis was performed. EBV-RNA was assessed by in situ hybridization that also proved to be negative. Immunohistochemical and EBV analyses are important to avoid delays and inappropriate treatment strategies. Although advanced age is considered an adverse prognostic factor, early diagnosis did prove to be a key contributory factor in the cure of non-Hodgkin lymphoma. Key words:Diffuse large B-cell lymphoma, elderly, EBV. PMID:24455096

  18. Hodgkin disease and non-Hodgkin lymphomas in children: utilization of radiological modalities

    SciTech Connect

    Cohen, M.D.; Siddiqui, A.; Weetman, R.; Provisor, A.; Coates, T.

    1986-02-01

    If costs of medical care are to be reduced, the choice of which imaging modality to use must be made as carefully as possible. This study was done to show how radiological modalities were used to evaluate patients with Hodgkin disease and non-Hodgkin lymphoma. We kept a record of every radiological study performed on 66 children with both diseases seen in the past 6 1/3 years. The results of these studies were analyzed to see which areas of the body were studied, which imaging modality was used, how frequently the studies were repeated, and how frequently the studies gave abnormal results. Our findings disclosed that radiological studies have been appropriately performed in anatomic regions of the body in which disease is present. New imaging modalities have been introduced, and the use of some of the older modalities has been decreased. With some modalities, such as skeletal survey, liver/spleen scan, whole-lung tomography, contrast studies of the bowel, and excretory urography, utilization is higher than it ought to be in view of the fact that the yield of positive results is low and the information is obtainable in many cases from other more sensitive procedures. These studies should not be performed as a routine on initial evaluation or follow-up of all patients with Hodgkin or non-Hodgkin lymphomas. On initial presentation all patients should undergo chest radiography and CT scanning of both chest and abdomen. A problem area is that the timing of follow-up studies has been somewhat erratic, with some inappropriate studies particularly 3 or 4 years after diagnosis. Too many imaging procedures have probably been done in follow-up of our patients.

  19. Outcome of lower-intensity allogeneic transplantation in non-Hodgkin lymphoma after autologous transplantation failure.

    PubMed

    Freytes, César O; Zhang, Mei-Jie; Carreras, Jeanette; Burns, Linda J; Gale, Robert Peter; Isola, Luis; Perales, Miguel-Angel; Seftel, Matthew; Vose, Julie M; Miller, Alan M; Gibson, John; Gross, Thomas G; Rowlings, Philip A; Inwards, David J; Pavlovsky, Santiago; Martino, Rodrigo; Marks, David I; Hale, Gregory A; Smith, Sonali M; Schouten, Harry C; Slavin, Simon; Klumpp, Thomas R; Lazarus, Hillard M; van Besien, Koen; Hari, Parameswaran N

    2012-08-01

    We studied the outcome of allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning regimens (reduced-intensity conditioning and nonmyeloablative) in patients with non-Hodgkin lymphoma who relapsed after autologous hematopoietic stem cell transplantation. Nonrelapse mortality, lymphoma progression/relapse, progression-free survival (PFS), and overall survival were analyzed in 263 patients with non-Hodgkin lymphoma. All 263 patients had relapsed after a previous autologous hematopoietic stem cell transplantation and then had undergone allogeneic hematopoietic stem cell transplantation from a related (n = 26) or unrelated (n = 237) donor after reduced-intensity conditioning (n = 128) or nonmyeloablative (n = 135) and were reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2006. The median follow-up of survivors was 68 months (range, 3-111 months). Three-year nonrelapse mortality was 44% (95% confidence interval [CI], 37%-50%). Lymphoma progression/relapse at 3 years was 35% (95% CI, 29%-41%). Three-year probabilities of PFS and overall survival were 21% (95% CI, 16%-27%) and 32% (95% CI, 27%-38%), respectively. Superior Karnofsky Performance Score, longer interval between transplantations, total body irradiation-based conditioning regimen, and lymphoma remission at transplantation were correlated with improved PFS. Allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning is associated with significant nonrelapse mortality but can result in long-term PFS. We describe a quantitative risk model based on pretransplantation risk factors to identify those patients likely to benefit from this approach.

  20. Histamine-releasing factor/translationally controlled tumor protein plays a role in induced cell adhesion, apoptosis resistance and chemoresistance in non-Hodgkin lymphomas.

    PubMed

    He, Song; Huang, Yuejiao; Wang, Yuchan; Tang, Jie; Song, Yan; Yu, Xiafei; Ma, Jing; Wang, Shitao; Yin, Haibing; Li, Qiuyue; Ji, Lili; Xu, Xiaohong

    2015-07-01

    Mounting evidence has proved that cellular adhesion confers resistance to chemotherapy in multiple lymphomas. The molecular mechanism underlying cell adhesion-mediated drug resistance (CAM-DR) is, however, poorly understood. In this study, we investigated the expression and biologic function of histamine-releasing factor (HRF) in non-Hodgkin lymphomas (NHLs). Clinically, by immunohistochemistry analysis we observed obvious up-regulation of HRF in NHLs including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and natural killer (NK)/T-cell lymphoma. Functionally, overexpression and knockdown of HRF demonstrated the antiapoptotic effect of HRF in NHL cells, which may be associated with activation of the p-CREB/BCL-2 signaling pathway. Moreover, cell adhesion assay demonstrated that adhesion to fibronectin (FN) or HS-5 up-regulated HRF expression, while knockdown of HRF resulted in decreased cell adhesion, which led to reversed CAM-DR. Our finding supports the role of HRF in NHL cell apoptosis, adhesion and drug resistance, and may provide a clinical therapeutic target for CAM-DR in NHL.

  1. Loss in MCL-1 function sensitizes non-Hodgkin's lymphoma cell lines to the BCL-2-selective inhibitor venetoclax (ABT-199)

    PubMed Central

    Phillips, D C; Xiao, Y; Lam, L T; Litvinovich, E; Roberts-Rapp, L; Souers, A J; Leverson, J D

    2015-01-01

    As a population, non-Hodgkin's lymphoma (NHL) cell lines positive for the t(14;18) translocation and/or possessing elevated BCL2 copy number (CN; BCL2High) are exquisitely sensitive to navitoclax or the B-cell lymphoma protein-2 (BCL-2)-selective inhibitor venetoclax. Despite this, some BCL2High cell lines remain resistant to either agent. Here we show that the MCL-1-specific inhibitor A-1210477 sensitizes these cell lines to navitoclax. Chemical segregation of this synergy with the BCL-2-selective inhibitor venetoclax or BCL-XL-selective inhibitor A-1155463 indicated that MCL-1 and BCL-2 are the two key anti-apoptotic targets for sensitization. Similarly, the CDK inhibitor flavopiridol downregulated MCL-1 expression and synergized with venetoclax in BCL2High NHL cell lines to a similar extent as A-1210477. A-1210477 also synergized with navitoclax in the majority of BCL2Low NHL cell lines. However, chemical segregation with venetoclax or A-1155463 revealed that synergy was driven by BCL-XL inhibition in this population. Collectively these data emphasize that BCL2 status is predictive of venetoclax potency in NHL not only as a single agent, but also in the adjuvant setting with anti-tumorigenic agents that inhibit MCL-1 function. These studies also potentially identify a patient population (BCL2Low) that could benefit from BCL-XL (navitoclax)-driven combination therapy. PMID:26565405

  2. Lenalidomide monotherapy in heavily pretreated patients with non-Hodgkin lymphoma: an Italian observational multicenter retrospective study in daily clinical practice.

    PubMed

    Zinzani, Pier Luigi; Rigacci, Luigi; Cox, Maria Cristina; Devizzi, Liliana; Fabbri, Alberto; Zaccaria, Alfonso; Zaja, Francesco; Di Rocco, Alice; Rossi, Giuseppe; Storti, Sergio; Fattori, Pier Paolo; Argnani, Lisa; Tura, Sante; Vitolo, Umberto

    2015-06-01

    Clinical trial results indicate that lenalidomide, an immunomodulatory drug, is a promising treatment in relapsed/refractory non-Hodgkin lymphoma (NHL). This retrospective multicenter study was conducted in patients with relapsed/refractory NHL treated with lenalidomide monotherapy through a Named Patient Program in Italy. Principal endpoints were overall response rate (ORR), safety and overall survival (OS). The ORR in 64 evaluable patients was 42.2% and was similar among patients receiving 10, 15 or 25 mg/day lenalidomide. Response rates in patients with mantle cell, diffuse large B-cell and follicular lymphoma were 45.5%, 42.1% and 20%, respectively. Among patients who responded to most recent prior therapy, ORR was 50.0% versus 36.8% in patients with refractory NHL. Mean duration of response in patients receiving any lenalidomide dose was 10.5 months; 1-year progression-free survival and OS were 50.3% and 82.6%, respectively. These findings suggest that lenalidomide is effective and safe for heavily pretreated patients with NHL in the clinical setting.

  3. Preclinical evaluation of a diabody-based (177)Lu-radioimmunoconjugate for CD22-directed radioimmunotherapy in a non-Hodgkin lymphoma mouse model.

    PubMed

    Weber, Tobias; Bötticher, Benedikt; Arndt, Michaela A E; Mier, Walter; Sauter, Max; Exner, Evelyn; Keller, Armin; Krämer, Susanne; Leotta, Karin; Wischnjow, Artjom; Grosse-Hovest, Ludger; Strumberg, Dirk; Jäger, Dirk; Gröne, Hermann-Josef; Haberkorn, Uwe; Brem, Gottfried; Krauss, Jürgen

    2016-10-28

    Radioimmunotherapy is considered as treatment option in recurrent and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). To overcome the dose limiting bone marrow toxicity of IgG-based radioimmunoconjugates (RICs), we modified a humanized diabody with 5-, 10-, or 20-kDa polyethylene glycol (PEG) for CD22-targeted radioimmunotherapy using the low-energy β-emitter lutetium-177 ((177)Lu). A favorable pharmacokinetic profile was observed for the 10-kDa-PEG-diabody in nude mice being xenografted with subcutaneous human Burkitt lymphoma. Even at high doses of 16 MBq this diabody RIC was well tolerated by NOD Rag1(null) IL2rγ(null) (NRG) mice and did not reveal signs of organ long-term toxicity 80 days post injection. Combination therapy of the diabody RIC with unconjugated anti-CD20 Rituximab demonstrated therapeutic efficacy in established disseminated mantle cell lymphoma xenograft models. When compared with the combination of the IgG formatted (177)Lu anti-CD22 antibody and Rituximab, dual targeted therapy with the diabody RIC achieved an improved reduction of disease burden in the first nine days following treatment. The data indicate that the PEGylated anti-CD22 diabody may have potential for extending the repertoire of radiopharmaceuticals for the treatment of patients with B-NHL.

  4. Epstein-Barr virus and risk of non-Hodgkin lymphoma in the cancer prevention study-II and a meta-analysis of serologic studies.

    PubMed

    Teras, Lauren R; Rollison, Dana E; Pawlita, Michael; Michel, Angelika; Brozy, Johannes; de Sanjose, Silvia; Blase, Jennifer L; Gapstur, Susan M

    2015-01-01

    Epstein-Barr virus (EBV) causes rare, malignant lymphomas. The role of EBV in other non-Hodgkin lymphomas (NHLs) remains unclear, but mildly reduced immune function could lead to reactivation of EBV and subsequent NHL. We examined the association between prospectively-collected plasma EBV antibodies and NHL risk in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort and conducted a meta-analysis of our and published results. The CPS-II study included 225 NHL cases and 2:1 matched controls. No associations were observed between EBV serostatus or antibody levels and risk of NHL overall. However, when including only the three most common types of NHL (diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma), high compared to low early antigen (EA-D) diffuse and BZLF1-encoded replication activator antibodies were associated with approximately 60% higher risk of NHL. Odds ratios (ORs) for EBV nuclear antigen-1 and viral capsid antigen (VCA)-p18 were elevated but not statistically significant. In the meta-analysis, both EA (summary OR = 1.52, 95% confidence interval (CI): 1.16-2.00) and VCA (summary OR = 1.20, 95% CI: 1.00-1.44) were positively associated with NHL risk. These results suggest EBV may be associated with a wider spectrum of NHL subtypes, but further study is needed to confirm and fully understand these associations.

  5. [Acquired pure red cell aplasia associated with relapsed non-Hodgkin's lymphoma: a case report-improvement of PRCA after acute hepatitis].

    PubMed

    Kuramoto, K; Oda, K; Katsutani, S; Fujii, T; Abe, K; Imamura, N; Kimura, A

    1998-04-01

    A 47-year-old male patient was admitted because of anemia. He had been diagnosed as non-Hodgkin's lymphoma (Follicular mixed, B cell type, stage ISA) by splenectomy two years before. Bone marrow examination on admission revealed lymphoma cell infiltration and marked decrease in erythroid cells. These findings confirmed relapsed lymphoma with acquired pure red cell aplasia. After several courses of combination chemotherapy, lymphoma cells disappeared from bone marrow, but PRCA was not improved. In this case there were two times remission of PRCA. At first time, acute B type hepatitis occurred during the chemotherapy, anemia improved transiently. At the second time, mild acute hepatitis associated with herpes zoster occurred. Twenty days after hepatic injury, PRCA was improved, and continued in remission state till present day. To disclose the mechanism of PRCA in this case, erythroid colony assay of marrow cells was performed. This showed the presence of inhibitory factor in patient's serum at PRCA state, that was considered to be related to the occurrence of PRCA. These findings suggest that the improvement of PRCA was associated with the changes on immunological condition after acute hepatitis in this case.

  6. Loss in MCL-1 function sensitizes non-Hodgkin's lymphoma cell lines to the BCL-2-selective inhibitor venetoclax (ABT-199).

    PubMed

    Phillips, D C; Xiao, Y; Lam, L T; Litvinovich, E; Roberts-Rapp, L; Souers, A J; Leverson, J D

    2015-11-13

    As a population, non-Hodgkin's lymphoma (NHL) cell lines positive for the t(14;18) translocation and/or possessing elevated BCL2 copy number (CN; BCL2(High)) are exquisitely sensitive to navitoclax or the B-cell lymphoma protein-2 (BCL-2)-selective inhibitor venetoclax. Despite this, some BCL2(High) cell lines remain resistant to either agent. Here we show that the MCL-1-specific inhibitor A-1210477 sensitizes these cell lines to navitoclax. Chemical segregation of this synergy with the BCL-2-selective inhibitor venetoclax or BCL-XL-selective inhibitor A-1155463 indicated that MCL-1 and BCL-2 are the two key anti-apoptotic targets for sensitization. Similarly, the CDK inhibitor flavopiridol downregulated MCL-1 expression and synergized with venetoclax in BCL2(High) NHL cell lines to a similar extent as A-1210477. A-1210477 also synergized with navitoclax in the majority of BCL2(Low) NHL cell lines. However, chemical segregation with venetoclax or A-1155463 revealed that synergy was driven by BCL-XL inhibition in this population. Collectively these data emphasize that BCL2 status is predictive of venetoclax potency in NHL not only as a single agent, but also in the adjuvant setting with anti-tumorigenic agents that inhibit MCL-1 function. These studies also potentially identify a patient population (BCL2(Low)) that could benefit from BCL-XL (navitoclax)-driven combination therapy.

  7. Phase IA/II, multicentre, open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma.

    PubMed

    Fanale, Michelle; Assouline, Sarit; Kuruvilla, John; Solal-Céligny, Philippe; Heo, Dae S; Verhoef, Gregor; Corradini, Paolo; Abramson, Jeremy S; Offner, Fritz; Engert, Andreas; Dyer, Martin J S; Carreon, Daniel; Ewald, Brett; Baeck, Johan; Younes, Anas; Freedman, Arnold S

    2014-01-01

    Despite advancements in the treatment of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), patients continue to relapse and thus a need for new targeted therapies remains. The CD40 receptor is highly expressed on neoplastic B cells and activation leads to enhanced proliferation and survival. Lucatumumab (HCD122) is a fully human antagonistic CD40 monoclonal antibody. A phase IA/II study was designed to determine the maximum tolerated dose (MTD) and activity of lucatumumab in patients with relapsed/refractory lymphoma. Determination of the MTD was the primary objective of the phase IA dose escalation portion and clinical response was the primary objective of the phase II dose expansion portion. Patients received escalating doses of lucatumumab administered intravenously once weekly for 4 weeks of an 8-week cycle. MTD was determined at 4 mg/kg of lucatumumab. A total of 111 patients with NHL (n = 74) and HL (n = 37) were enrolled. Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (FL) and marginal zone lymphoma of mucosa-associated lymphatic tissue (MZL/MALT) was 33·3% and 42·9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of CD40 warrants further investigation.

  8. Postmenopausal unopposed estrogen and estrogen plus progestin use and risk of non-Hodgkin lymphoma in the American Cancer Society Cancer Prevention Study-II Cohort.

    PubMed

    Teras, Lauren R; Patel, Alpa V; Hildebrand, Janet S; Gapstur, Susan M

    2013-04-01

    Results of epidemiologic studies on postmenopausal hormone (PMH) use and non-Hodgkin lymphoma (NHL) are inconsistent. To help clarify this issue, PMH and NHL incidence was examined in the Cancer Prevention Study-II Nutrition Cohort. Between 1992 and 2007, 616 cases of NHL were identified among 67 980 postmenopausal women who were cancer-free at baseline. PMH use was updated during follow-up. Using extended Cox regression, we observed a statistically significant 29% higher risk of NHL for ever unopposed estrogen use compared to never use, which was restricted to follicular lymphoma (current estrogen compared to never use, hazard ratio [HR] = 2.25, 95% confidence interval [CI]: 1.17-4.33) and diffuse large B-cell lymphoma (DLBCL, HR = 1.95, 95% CI: 1.13-3.35). There was no association between current estrogen plus progestin (E + P) use and NHL incidence overall, but a suggested positive association between current E + P use and DLBCL, as well as former E + P use and follicular lymphoma. These results suggest that postmenopausal hormones might play a role in NHL etiology, particularly for follicular lymphoma and DLBCL.

  9. Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin's lymphoma

    PubMed Central

    Gui, Lin; Han, Xiaohong; He, Xiaohui; Song, Yuanyuan; Yao, Jiarui; Yang, Jianliang; Liu, Peng; Qin, Yan; Zhang, Shuxiang; Zhang, Weijing; Gai, Wenlin; Xie, Liangzhi

    2016-01-01

    Objective: This study was designed to determine the safety, pharmacokinetics and biologic effects of a human-mouse chimeric anti-CD20 monoclonal antibody (SCT400) in Chinese patients with CD20-positive B-cell non-Hodgkin's lymphoma (CD20+ B-cell NHL). SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods: Fifteen patients with CD20+ B-cell NHL received dose-escalating SCT400 infusions (250 mg/m2: n=3; 375 mg/m2: n=9; 500 mg/m2: n=3) once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacokinetics and pharmacodynamics analyses. Results: No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 neutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer (NK) cell count or immunoglobulin levels. No patient developed anti-SCT400 antibodies during the course of the study. SCT400 serum half-life (T1/2), maximum concentration (Cmax) and area under the curve (AUC) generally increased between the first and fourth infusions (P<0.05). At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0±75.0 h, respectively, and the Cmax was 200.6±20.2 g/mL vs. 339.1±71.0 g/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner (P<0.05). Patients with a high tumor burden had markedly lower serum SCT400 concentrations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions: SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20+ B-cell NHL. PMID:27199517

  10. Autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma: what 18F-fluorodeoxyglucose positron emission tomography/computed tomography can do in the management of these patients? Suggestions from a case report.

    PubMed

    Cistaro, A; Pazè, F; Durando, S; Cogoni, M; Faletti, R; Vesco, S; Vallero, S; Quartuccio, N; Treglia, G; Ramenghi, U

    2014-01-01

    A young patient with undefined autoimmune lymphoproliferative syndrome (ALPS-U) and low back pain underwent a CT and MRI study that showed enhancing vertebral lesions, some pulmonary nodules and diffuse latero-cervical lymphadenopathy. A (18)F-FDG-PET/CT scan showed many areas of intense (18)F-FDG uptake in multiple vertebrae, in some ribs, in the sacrum, in the liver, in both lungs, in multiple lymph nodes spread in the cervical, thoracic and abdominal chains. A bone marrow biopsy showed a "lymphomatoid granulomatosis", a rare variant of B-cell non-Hodgkin lymphoma (NHL). After the treatment, the (18)F-FDG-PET/CT scan showed a complete metabolic response.

  11. Soluble levels of CD27 and CD30 are associated with risk of non-Hodgkin lymphoma in three Chinese prospective cohorts

    PubMed Central

    Bassig, Bryan A.; Shu, Xiao-Ou; Koh, Woon-Puay; Gao, Yu-Tang; Purdue, Mark P.; Butler, Lesley M.; Adams-Haduch, Jennifer; Xiang, Yong-Bing; Kemp, Troy J.; Wang, Renwei; Pinto, Ligia A.; Zheng, Tongzhang; Ji, Bu-Tian; Hosgood, H. Dean; Hu, Wei; Yang, Gong; Zhang, Heping; Chow, Wong-Ho; Kim, Christopher; Seow, Wei Jie; Zheng, Wei; Yuan, Jian-Min; Lan, Qing; Rothman, Nathaniel

    2015-01-01

    Prospective studies conducted in Western populations have suggested that alterations in soluble CD27 (sCD27) and soluble CD30 (sCD30), two markers indicative of B-cell activation, are associated with risk of non-Hodgkin lymphoma (NHL). Given that the characteristics of NHL in East Asia differ from the West, and mechanistic commonalities between these populations with respect to the role of intermediate endpoint biomarkers in lymphomagenesis have not been explored, we conducted a pooled nested case-control study from three prospective studies of Chinese men and women including 218 NHL cases and 218 individually matched controls. Compared to the lowest quartile, ORs (95% CIs) for the 2nd, 3rd, and 4th quartiles of sCD27 were 1.60 (0.83-3.09), 1.94 (0.98-3.83), and 4.45 (2.25-8.81), respectively (ptrend = 0.000005). The corresponding ORs for sCD30 were 1.74 (0.85-3.58), 1.86 (0.94-3.67), and 5.15 (2.62-10.12) (ptrend = 0.0000002). These associations remained statistically significant in individuals diagnosed with NHL 10 or more years after blood draw. Notably, the magnitude of the associations with NHL risk was very similar to those in Western populations in previous studies. These findings of the similar association between sCD27 or sCD30 and NHL risk across different populations support an important underlying mechanism of B-cell activation in lymphomagenesis. PMID:26095604

  12. Immunotherapy of non-Hodgkin lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells

    PubMed Central

    Turtle, Cameron J.; Hanafi, Laïla-Aïcha; Berger, Carolina; Hudecek, Michael; Pender, Barbara; Robinson, Emily; Hawkins, Reed; Chaney, Colette; Cherian, Sindhu; Chen, Xueyan; Soma, Lorinda; Wood, Brent; Li, Daniel; Heimfeld, Shelly; Riddell, Stanley R.; Maloney, David G.

    2016-01-01

    CD19-specific chimeric antigen receptor (CAR)-modified T cells have antitumor activity in B cell malignancies, but factors that impact toxicity and efficacy have been difficult to define because of differences in lymphodepletion regimens and heterogeneity of CAR-T cells administered to individual patients. We conducted a clinical trial in which CD19 CAR-T cells were manufactured from defined T cell subsets and administered in a 1:1 CD4+:CD8+ ratio of CAR-T cells to 32 adults with relapsed and/or refractory B cell non-Hodgkin lymphoma after cyclophosphamide (Cy)-based lymphodepletion chemotherapy with or without fludarabine (Flu). Patients who received Cy/Flu lymphodepletion had markedly increased CAR-T cell expansion and persistence, and higher response rates (50% CR, 72% ORR, n=20) than patients who received Cy-based lymphodepletion without Flu (8% CR, 50% ORR, n=12). The complete response (CR) rate in patients treated with Cy/Flu at the maximally tolerated dose was 64% (82% ORR, n=11). Cy/Flu minimized the effects of an immune response to the murine scFv component of the CAR, which limited CAR-T cell expansion, persistence, and clinical efficacy in patients who received Cy-based lymphodepletion without Flu. Severe cytokine release syndrome (sCRS) and grade ≥ 3 neurotoxicity were observed in 13% and 28% of all patients, respectively. Serum biomarkers one day after CAR-T cell infusion correlated with subsequent development of sCRS and neurotoxicity. Immunotherapy with CD19 CAR-T cells in a defined CD4+:CD8+ ratio allowed identification of correlative factors for CAR-T cell expansion, persistence, and toxicity, and facilitated optimization of a lymphodepletion regimen that improved disease response and overall and progression-free survival. PMID:27605551

  13. Genetic polymorphisms in nitric oxide synthase genes modify the relationship between vegetable and fruit intake and risk of non-Hodgkin lymphoma.

    PubMed

    Han, Xuesong; Zheng, Tongzhang; Lan, Qing; Zhang, Yaqun; Kilfoy, Briseis A; Qin, Qin; Rothman, Nathaniel; Zahm, Shelia H; Holford, Theodore R; Leaderer, Brian; Zhang, Yawei

    2009-05-01

    Oxidative damage caused by reactive oxygen species and other free radicals is involved in carcinogenesis. It has been suggested that high vegetable and fruit intake may reduce the risk of non-Hodgkin lymphoma (NHL) as vegetables and fruit are rich in antioxidants. The aim of this study is to evaluate the interaction of vegetable and fruit intake with genetic polymorphisms in oxidative stress pathway genes and NHL risk. This hypothesis was investigated in a population-based case-control study of NHL and NHL histologic subtypes in women from Connecticut, including 513 histologically confirmed incident cases and 591 randomly selected controls. Gene-vegetable/fruit joint effects were estimated using unconditional logistic regression model. The false discovery rate method was applied to adjust for multiple comparisons. Significant interactions with vegetable and fruit intake were mainly found for genetic polymorphisms on nitric oxide synthase (NOS) genes among those with diffuse large B-cell lymphoma and follicular lymphoma. Two single nucleotide polymorphisms in the NOS1 gene were found to significantly modify the association between total vegetable and fruit intake and risk of NHL overall, as well as the risk of follicular lymphoma. When vegetables, bean vegetables, cruciferous vegetables, green leafy vegetables, red vegetables, yellow/orange vegetables, fruit, and citrus fruits were examined separately, strong interaction effects were narrowed to vegetable intake among patients with diffuse large B-cell lymphoma. Our results suggest that genetic polymorphisms in oxidative stress pathway genes, especially in the NOS genes, modify the association between vegetable and fruit intake and risk of NHL.

  14. Immunohistochemical and Molecular Characteristics with Prognostic Significance in Diffuse Large B-Cell Lymphoma

    PubMed Central

    Bellas, Carmen; García, Diego; Vicente, Yolanda; Kilany, Linah; Abraira, Victor; Navarro, Belen; Provencio, Mariano; Martín, Paloma

    2014-01-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the prognostic value of immunohistochemical markers derived from the gene expression profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1 protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC and FOXP1 using fluorescence in situ hybridization and assessed their prognostic significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene alteration (rearrangement and/or amplification) was associated with the non-germinal center B subtype (non-GCB). BCL2 translocation was associated with the GCB phenotype, and BCL2 protein expression was associated with the translocation and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases, and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly of the non-GCB subtype, was demonstrated in 37% of cases. Co-expression of the MYC and BCL2 proteins, with non-GCB subtype predominance, was observed in 21% of cases. We detected an association between high FOXP1 expression and a high proliferation rate as well as a significant positive correlation between MYC overexpression and FOXP1 overexpression. MYC, BCL2 and FOXP1 expression were significant predictors of overall survival. The co-expression of MYC and BCL2 confers a poorer clinical outcome than MYC or BCL2 expression alone, whereas cases negative for both markers had the best outcomes. Our study confirms that DLBCL, characterized by the co-expression of MYC and BCL2 proteins, has a poor prognosis and establishes a significant positive correlation with MYC and FOXP1 over-expression in this entity. PMID:24887414

  15. Campylobacter jejuni Fatal Sepsis in a Patient with Non-Hodgkin's Lymphoma: Case Report and Literature Review of a Difficult Diagnosis.

    PubMed

    Gallo, Maria Teresa; Di Domenico, Enea Gino; Toma, Luigi; Marchesi, Francesco; Pelagalli, Lorella; Manghisi, Nicola; Ascenzioni, Fiorentina; Prignano, Grazia; Mengarelli, Andrea; Ensoli, Fabrizio

    2016-04-12

    Campylobacter jejuni (C. jejuni) bacteremia is difficult to diagnose in individuals with hematological disorders undergoing chemotherapy. The cause can be attributed to the rarity of this infection, to the variable clinical presentation, and to the partial overlapping symptoms underlying the disease. Here, we report a case of a fatal sepsis caused by C. jejuni in a 76-year-old Caucasian man with non-Hodgkin's lymphoma. After chemotherapeutic treatment, the patient experienced fever associated with severe neutropenia and thrombocytopenia without hemodynamic instability, abdominal pain, and diarrhea. The slow growth of C. jejuni in the blood culture systems and the difficulty in identifying it with conventional biochemical phenotyping methods contributed to the delay of administering a targeted antimicrobial treatment, leading to a fatal outcome. Early recognition and timely intervention are critical for the successful management of C. jejuni infection. Symptoms may be difficult to recognize in immunocompromised patients undergoing chemotherapy. Thus, it is important to increase physician awareness regarding the clinical manifestations of C. jejuni to improve therapeutic efficacy. Moreover, the use of more aggressive empirical antimicrobial treatments with aminoglycosides and/or carbapenems should be considered in immunosuppressed patients, in comparison to those currently indicated in the guidelines for cancer-related infections supporting the use of cephalosporins as monotherapy.

  16. Philadelphia chromosome-negative non-Hodgkin's lymphoma occurring in Philadelphia chromosome-positive chronic myeloid leukemia: A case report and literature review

    PubMed Central

    SHEN, ZHENG-LEI; YIN, LIE-FEN; MAO, WEN-WEN; LIANG, JIN; YANG, LING

    2016-01-01

    The current study reports the case of a patient with Philadelphia chromosome-negative (Ph−) non-Hodgkin's lymphoma (NHL) and chronic phase (CP) Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that also possessed characteristic enlarged lymph nodes. A lymph node biopsy resulted in the diagnosis of CP-CML, in addition to T-lymphoblastic cell NHL with negative break point cluster/Abelson tyrosine kinase fusion genes in the lymph node of the patient, which was diagnosed as Ph− NHL. A review of the literature was performed in the present study to investigate the genetic differences between Ph− NHL and Ph+ NHL in patients with CML. The median age of patients with NHL and CML was 41 years. The follow-up time of patients with Ph+ NHL was significantly shorter (mean, <6 months) compared to the follow-up time of patients with Ph− NHL (mean, >15 months). Therefore the present study concludes that Ph+ NHL may be more aggressive compared with Ph+ NHL. The present study suggests that additional studies are required to assess the clinical and genetic characteristics of NHL patients with CML. PMID:27073575

  17. Non-Hodgkin's lymphoma “masquerading” as Pott's disease in a 13-year old boy

    PubMed Central

    Adegboye, Olasunkanmi Abdulrasheed

    2011-01-01

    Lymphomas are malignant neoplasms of the lymphoid lineage. They are broadly classified as either Hodgkin disease or as non-Hodgkin lymphoma (NHL). Burkitt's lymphoma, a variety of NHL, is significantly most common in sub-Saharan Africa, where it accounts for approximately one half of childhood cancers. Lymphoblastic lymphoma is less common. A case of paravertebral high grade non-Hodgkin's lymphoma (lymphoblastic lymphoma) “masquerading” as Pott's disease in a 13-year-old child is reported. The present report was informed by the unusual presentation of this case and the intent of increasing the index of diagnostic suspicion. A brief appraisal is provided of the clinical parameters, management strategies and challenges. AT was a 13-year boy that presented on account of a slowly evolving and progressively increasing hunch on the back and inability to walk over 4 and 8 months duration, respectively. There was subsequent inability to control defecation and urination. There was no history of cough. He and his twin brother lived with their paternal grandfather who had chronic cough with associated weight loss. The grandfather died shortly before the child's admission. The child had no BCG immunization. The essential findings on examination were in keeping with lower motor neurons (LMN) paralysis of the lower limbs. The upper limbs appeared normal. There was loss of cutaneous sensation from the umbilicus (T10) downward. There was a firm, (rather tense), non-tender non-pulsatile, smooth swelling over the mid-third of the back (T6-L1) the mass had no differential warmth. It measures about 20×12 cm. Chest radiograph showed no active focal lung lesion, but the thoraco-lumbar spine showed a vertebral planner at L1 and a wedged collapse of T11-T12 vertebrae. There was sclerosis of the end plates of all the vertebral bodies with associated reduction in the bone density. He had an excision biopsy on the 90th day on admission, following which his clinical state rapidly

  18. Y-90-DOTA-hLL2: An Agent for Radioimmunotherapy of Non-Hodgkin's Lymphoma

    SciTech Connect

    Griffiths, Gary L.; Govindan, Serengulam V.; Sharkey, Robert M.; Fisher, Darrell R. ); Goldenberg, David M.

    2003-01-01

    The goal of this work was to determine an optimal radioimmunotherapy agent for non-Hodgkin's lymphoma. We established the stability profile of yttrium-90-labeled humanized LL2 (hLL2) monoclonal antibody prepared with different chelating agents, and from these data estimated the improvement using the most stable yttrium-90 chelate-hLL2 complex. Methods: The complementary-determining region- (cdr)-grafted (humanized) anti-CD22 mAb, hLL2 (epratuzumab), was conjugated to derivatives of DTPA and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). The conjugates were labeled with Y-90 and tested against a 10,000-fold molar excess of free DTPA and against human serum. The conjugates were also labeled with Y-88 and compared for biodistribution in normal and lymphoma xenograft-bearing athymic mice. In vivo data were analyzed for uptake of yttrium in bone and washed bone when either the DOTA or the Mx-DTPA chelates were used, and dosimetry calculations were made for each. Results: Y-90-DOTA -mAb were stable to either DTPA or serum challenge. DTPA complexes of hLL2 lost 3-4% of Y-90 (days 1-4) and 10-15% thereafter. In vivo, stability differences showed lower Y-90 uptake in bone using DOTA. Absorbed doses per 37 MBq (1 mCi) Y-90-mAb were 3555 and 5405 cGy for bone, and 2664 and 4524 cGy for washed-bone for 90Y-DOTA-hLL2 and 90Y-MxDTPA-hLL2, respectively, amounting to 52% and 69.8% increases in absorbed radiation doses for bone and washed-bone when switching from a DOTA to a Mx-DTPA chelate. Conclusion: Y-90-hLL2 prepared with the DOTA chelate represents a preferred agent for RAIT of non-Hodgkin's lymphoma, with an in vivo model demonstrating a large reduction in bone-deposited yttrium, as compared to yttrium-90-hLL2 agents prepared with open-chain DTPA-type chelating agents. Dosimetry suggests that this will result in a substantial toxicological advantage for a DOTA-based hLL2 conjugate.

  19. PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas

    PubMed Central

    Valentino, Elena; Vitiello, Michela; Luciano, Antonio; Palma, Giuseppe; Arra, Claudio; Mantia, Elvira La; Panico, Luigi; Tenneriello, Valentina; Pinto, Antonello; Frigeri, Ferdinando; Capobianco, Gaetana; Botti, Gerardo; Cerchia, Laura; De Chiara, Annarosaria; Fedele, Monica

    2016-01-01

    Non-Hodgkin lymphomas (NHLs) include a heterogeneous group of diseases, which differ in both cellular origin and clinical behavior. Among the aggressive malignancies of this group, the diffuse large B-cell lymphomas (DLBCLs) are the most frequently observed. They are themselves clinically and molecularly heterogeneous and have been further sub-divided in three sub-types according to different cell of origin, mechanisms of oncogenesis and clinical outcome. Among them, the germinal center B-cell-like (GCB) derives from the germinal center and expresses the BCL6 oncogene. We have previously shown that Patz1-knockout mice develop B-cell neoplasias, suggesting a tumor suppressor role for PATZ1 in human NHLs. Here, by immunohistochemical analysis of a tissue-microarray including 170 NHLs, we found that PATZ1 nuclear expression is down-regulated in follicular lymphomas and DLBCLs. Moreover, consistent with our previous results showing a PATZ1-dependent regulation of BCL6 and BAX transcription, we show that low PATZ1 nuclear expression significantly correlates with high BCL6 expression, mainly in DLBCLs, and with low BAX expression, also considering separately follicular lymphomas and DLBCLs. Finally, by analyzing overall and progression-free survival in DLBCL patients that underwent rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, low levels of PATZ1 were significantly associated to a worst outcome and demonstrated an independent prognostic factor in multivariate analysis, including known prognostic factors of DLBCL, IPI score and cell of origin (GCB/non-GCB). Therefore, we propose PATZ1 as a new prognostic marker of DLBCLs, which may act as a tumor suppressor by enhancing apoptosis through inhibiting and enhancing transcription of BCL6 and BAX, respectively. PMID:27494852

  20. PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas.

    PubMed

    Franco, Renato; Scognamiglio, Giosuè; Valentino, Elena; Vitiello, Michela; Luciano, Antonio; Palma, Giuseppe; Arra, Claudio; La Mantia, Elvira; Panico, Luigi; Tenneriello, Valentina; Pinto, Antonello; Frigeri, Ferdinando; Capobianco, Gaetana; Botti, Gerardo; Cerchia, Laura; De Chiara, Annarosaria; Fedele, Monica

    2016-09-13

    Non-Hodgkin lymphomas (NHLs) include a heterogeneous group of diseases, which differ in both cellular origin and clinical behavior. Among the aggressive malignancies of this group, the diffuse large B-cell lymphomas (DLBCLs) are the most frequently observed. They are themselves clinically and molecularly heterogeneous and have been further sub-divided in three sub-types according to different cell of origin, mechanisms of oncogenesis and clinical outcome. Among them, the germinal center B-cell-like (GCB) derives from the germinal center and expresses the BCL6 oncogene. We have previously shown that Patz1-knockout mice develop B-cell neoplasias, suggesting a tumor suppressor role for PATZ1 in human NHLs. Here, by immunohistochemical analysis of a tissue-microarray including 170 NHLs, we found that PATZ1 nuclear expression is down-regulated in follicular lymphomas and DLBCLs. Moreover, consistent with our previous results showing a PATZ1-dependent regulation of BCL6 and BAX transcription, we show that low PATZ1 nuclear expression significantly correlates with high BCL6 expression, mainly in DLBCLs, and with low BAX expression, also considering separately follicular lymphomas and DLBCLs. Finally, by analyzing overall and progression-free survival in DLBCL patients that underwent rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, low levels of PATZ1 were significantly associated to a worst outcome and demonstrated an independent prognostic factor in multivariate analysis, including known prognostic factors of DLBCL, IPI score and cell of origin (GCB/non-GCB). Therefore, we propose PATZ1 as a new prognostic marker of DLBCLs, which may act as a tumor suppressor by enhancing apoptosis through inhibiting and enhancing transcription of BCL6 and BAX, respectively.

  1. Inhibition of methyltransferases accelerates degradation of cFLIP and sensitizes B-cell lymphoma cells to TRAIL-induced apoptosis.

    PubMed

    Braun, Frank K; Mathur, Rohit; Sehgal, Lalit; Wilkie-Grantham, Rachel; Chandra, Joya; Berkova, Zuzana; Samaniego, Felipe

    2015-01-01

    Non-Hodgkin lymphomas (NHLs) are characterized by specific abnormalities that alter cell cycle regulation, DNA damage response, and apoptotic signaling. It is believed that cancer cells are particularly sensitive to cell death induced by tumor necrosis factor α-related apoptosis-inducing ligand (TRAIL). However, many cancer cells show blocked TRAIL signaling due to up-regulated expression of anti-apoptotic factors, such as cFLIP. This hurdle to TRAIL's tumor cytotoxicity might be overcome by combining TRAIL-based therapy with drugs that reverse blockages of its apoptotic signaling. In this study, we investigated the impact of a pan-methyltransferase inhibitor (3-deazaneplanocin A, or DZNep) on TRAIL-induced apoptosis in aggressive B-cell NHLs: mantle cell, Burkitt, and diffuse large B-cell lymphomas. We characterized TRAIL apoptosis regulation and caspase activation in several NHL-derived cell lines pre-treated with DZNep. We found that DZNep increased cancer cell sensitivity to TRAIL signaling by promoting caspase-8 processing through accelerated cFLIP degradation. No change in cFLIP mRNA level indicated independence of promoter methylation alterations in methyltransferase activity induced by DZNep profoundly affected cFLIP mRNA stability and protein stability. This appears to be in part through increased levels of cFLIP-targeting microRNAs (miR-512-3p and miR-346). However, additional microRNAs and cFLIP-regulating mechanisms appear to be involved in DZNep-mediated enhanced response to extrinsic apoptotic stimuli. The capacity of DZNep to target cFLIP expression on multiple levels underscores DZNep's potential in TRAIL-based therapies for B-cell NHLs.

  2. Overexpression of MicroRNAs from the miR-17-92 Paralog Clusters in AIDS-Related Non-Hodgkin's Lymphomas

    PubMed Central

    Thapa, Dharma R.; Li, Xinmin; Jamieson, Beth D.; Martínez-Maza, Otoniel

    2011-01-01

    Background Individuals infected by HIV are at an increased risk for developing non-Hodgkin's lymphomas (AIDS-NHL). In the highly active antiretroviral therapy (HAART) era, there has been a significant decline in the incidence of AIDS-associated primary central nervous system lymphoma (PCNSL). However, only a modest decrease in incidence has been reported for other AIDS-NHL subtypes. Thus, AIDS-NHLs remain a significant cause of morbidity and mortality in HIV infected individuals. Recently, much attention has been directed toward the role of miRNAs in cancer, including NHL. Several miRNAs, including those encoded by the miR-17-92 polycistron, have been shown to play significant roles in B cell tumorigenesis. However, the role of miRNAs in NHL in the setting of HIV infection has not been defined. Methodology/Principal Findings We used quantitative realtime PCR to assess the expression of miRNAs from three different paralog clusters, miR-17-92, miR-106a-363, and miR-106b-25 in 24 cases of AIDS-NHLs representing four tumor types, Burkitt's lymphoma (BL, n = 6), diffuse large B-cell lymphoma (DLBCL, n = 8), primary central nervous system lymphoma (PCNSL, n = 5), and primary effusion lymphoma (PEL, n = 5). We also used microarray analysis to identify a differentiation specific miRNA signature of naïve, germinal center, and memory B cell subsets from tonsils (n = 4). miRNAs from the miR-17-92 paralog clusters were upregulated by B cells, specifically during the GC differentiation stage. We also found overexpression of these miRNA clusters in all four AIDS-NHL subtypes. Finally, we also show that select miRNAs from these clusters (miR-17, miR-106a, and miR-106b) inhibited p21 in AIDS-BL and DLBCL cases, thus providing a mechanistic role for these miRNAs in AIDS-NHL pathogenesis. Conclusion Dysregulation of miR-17-92 paralog clusters is a common feature of AIDS-associated NHLs. PMID:21698185

  3. Rituximab Faster Infusion for Patients With Non-Hodgkin's Lymphoma in the United States: Implications for Nursing Practice.

    PubMed

    Dawson, Keith

    2015-01-01

    The majority of follicular non-Hodgkin's lymphoma patients in the United States receive an initial treatment strategy that includes the infusion of rituximab. Data from a phase III multicenter clinical trial led to the 2012 US Food and Drug Administration approval of a 90-minute infusion of rituximab (Rituxan) starting at Cycle 2 for patients with non-Hodgkin's lymphoma who did not experience a Grade 3 or 4 infusion-related adverse event during Cycle 1. A review of literature was undertaken to identify existing evidence regarding both the safety of rituximab faster infusion and its impact on nursing practice. The aim of this article is to stimulate discussion and lead to implementation of evidence-based nursing practices to improve the delivery of patient care.

  4. Rituximab faster infusion for patients with non-Hodgkin's lymphoma in the United States: implications for nursing practice.

    PubMed

    Dawson, Keith

    2013-01-01

    The majority of follicular non-Hodgkin's lymphoma patients in the United States receive an initial treatment strategy that includes the infusion of rituximab. Data from a phase III multicenter clinical trial led to the 2012 US Food and Drug Administration approval of a 90-minute infusion of rituximab (Rituxan) starting at Cycle 2 for patients with non-Hodgkin's lymphoma who did not experience a Grade 3 or 4 infusion-related adverse event during Cycle 1. A review of literature was undertaken to identify existing evidence regarding both the safety of rituximab faster infusion and its impact on nursing practice. The aim of this article is to stimulate discussion and lead to implementation of evidence-based nursing practices to improve the delivery of patient care.

  5. The Role of Surgery in the Clinical Management of Primary Gastrointestinal Non-Hodgkin's Lymphoma.

    PubMed

    MacQueen, Ian T; Shannon, Evan M; Dawes, Aaron J; Ostrzega, Nora; Russell, Marcia M; Maggard-Gibbons, Melinda

    2015-10-01

    Primary gastrointestinal non-Hodgkin's lymphoma (PGINHL) is a heterogeneous family of tumors, with treatment modalities including chemotherapy, surgery, and radiotherapy. Because the role of surgery in PGINHL remains disputed, this study aims to assess the impact of operative resection on survival. We used a pathology database to identify all cases of PGINHL diagnosed at a single academic-affiliated medical center from 1988 to 2013. Demographic and clinical data were abstracted from the medical record. We summarized the clinical courses of patients with PGINHL and then performed a survival analysis to compare overall and disease-free survival, stratified by demographic and clinical variables. We identified 33 patients diagnosed with PGINHL during the study period. Of 29 who subsequently received treatment at the institution, 15 initially underwent chemotherapy, 10 underwent surgical resection, and 4 underwent surgery for other reasons such as diagnosis without resection or management of disease complications. Three patients suffered surgical complications and two of these patients died. We found no difference in overall survival between patients receiving surgical resection and patients managed initially with chemotherapy. This case series supports a continued role for surgical resection in the management of patients with PGINHL, though anticipated benefits should be weighed against the risk of complications.

  6. Imaging of non-Hodgkin lymphomas: diagnosis and response-adapted strategies.

    PubMed

    El-Galaly, Tarec Christoffer; Hutchings, Martin

    2015-01-01

    Optimal lymphoma management requires accurate pretreatment staging and reliable assessment of response, both during and after therapy. Positron emission tomography with computerized tomography (PET/CT) combines functional and anatomical imaging and provides the most sensitive and accurate methods for lymphoma imaging. New guidelines for lymphoma imaging and recently revised criteria for lymphoma staging and response assessment recommend PET/CT staging, treatment monitoring, and response evaluation in all FDG-avid lymphomas, while CT remains the method of choice for non-FDG-avid histologies. Since interim PET imaging has high prognostic value in lymphoma, a number of trials investigate PET-based, response-adapted therapy for non-Hodgkin lymphomas (NHL). PET response is the main determinant of response according to the new response criteria, but PET/CT has little or no role in routine surveillance imaging, the value which is itself questionable. This review presents from a clinical point of view the evidence for the use of imaging and primarily PET/CT in NHL before, during, and after therapy. The reader is given an overview of the current PET-based interventional NHL trials and an insight into possible future developments in the field, including new PET tracers.

  7. Primary gastrointestinal non-Hodgkin's lymphoma in a population-based registry.

    PubMed Central

    Otter, R.; Bieger, R.; Kluin, P. M.; Hermans, J.; Willemze, R.

    1989-01-01

    In a population-based registry of 580 patients with non-Hodgkin's lymphoma (NHL) 54 patients had a primary gastric lymphoma, 42 an intestinal, 113 a primary extranodal lymphoma localised elsewhere than in the gastrointestinal tract and 371 a primary nodal NHL. Histological specimens were reviewed by a panel of pathologists and classified according to the Kiel classification and the International Working Formulation. The 4-year survival rates for primary gastric, intestinal, other extranodal and nodal NHL ranged from 50 to 60%; the 4-year recurrence-free survival rates were 50%, 35%, 19% and 19%, respectively. Among patients with localised intermediate-grade disease survival for those with gastric NHL was better than for those with intestinal lymphoma. Because it is population-based, our study cohort was not subjected to exclusion due to age, performance scale, etc. and therefore provides a more realistic picture of the occurrence and presentation of as well as prognosis for lymphoma in the population. PMID:2803951

  8. Burkitt-type lymphoma in France among non-Hodgkin malignant lymphomas in Caucasian children.

    PubMed Central

    Philip, T.; Lenoir, G. M.; Bryon, P. A.; Gerard-Marchant, R.; Souillet, G.; Philippe, N.; Freycon, F.; Brunat-Mentigny, M.

    1982-01-01

    In a retrospective analysis of 87 cases of Caucasian childhood non-Hodgkin malignant lymphoma (NHML) from Lyon, France, all the case were diffuse lymphomas, but 47 were diagnosed as monomorphic small non-cleaved NHML, pathologically indistinguishable from Burkitt's lymphoma (BL). BL could then be the most frequent childhood lymphoma in France. This homogeneous series allows better definition of the characteristics of BL within NHML. Age distribution is similar to that of endemic BL, with a sex ratio of 3.7/1. Abdominal masses are initially present in 68% of the cases, whereas jaw is involved in only 4%. The disease is characterized by its overwhelming evolution in the absence of therapy. However, complete remission (CR) is usually obtained after the first chemtherapy regimen. Most relapses occur at 3-8 months. Death could be related to cerebrospinal fluid (CSF) involvement, local recurrence or secondary marrow involvement. Ninety per cent of the patients alive with no evidence of disease (NED) 8 months after CR can be considered as definitely cured. Our study on Caucasian children with NHML indicates that, from histological and clinical criteria, nearly half the cases are very similar to African BL. Even though EBV rarely associated with our cases, BL could be a worldwide lymphoma. PMID:7082553

  9. Widespread Use of Complementary and Alternative Medicine (CAM) among Non-Hodgkin Lymphoma (NHL) Survivors

    PubMed Central

    Osian, S. Rausch; Leal, A.D.; Allmer, C.; Maurer, M.J.; Nowakowski, G.; Inwards, D.J.; Macon, W.R.; Ehlers, S.L.; Weiner, G.J.; Habermann, T.M.; Cerhan, J.R.; Thompson, C.A.

    2015-01-01

    There are few studies examining complementary and alternative medicine (CAM) use and beliefs among non-Hodgkin lymphoma (NHL) survivors. 719 NHL patients from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource who completed the 3-year post-diagnosis questionnaire were included in this study. 636 (89%) reported ever using CAM, with 78% utilizing vitamins, 54% alternative therapies and 45% herbals. Female gender was associated with increased overall CAM use (P<.0001) as well as use of vitamins (P<.0001), herbals (P=.006) and alternative therapy (P=.0002) for cancer. Older age (>60) was associated with increased vitamin use (P=.005) and decreased herbal use (P=.008). Among users, 143 (20%) believe CAM assists healing, 123 (17%) believe CAM relieves symptoms, 122 (17%) believe CAM gives a feeling of control, 110 (15%) believe CAM assists other treatments, 108 (15%) believe CAM boosts immunity, 26 (4%) believe CAM cures cancer, and 36 (5%) believe CAM prevents the spread of cancer. PMID:24745936

  10. Multiple Autoimmune Propensity and B-Non-Hodgkin Lymphoma: Cause or Effect?

    PubMed Central

    Koumati, E.; Palassopoulou, M.; Matsouka, P.; Polyzos, A.; Dalekos, G. N.; Zachou, K.

    2011-01-01

    We report a case of multiple autoimmunity consisting of the presence of autoimmune haemolytic anaemia (AIHA), antimitochondrial antibodies (AMAs), and antiphospholipid antibodies (APLAbs) as the presenting manifestations of an extrahepatic B-non-Hodgkin lymphoma (B-NHL) in a 63-year-old woman. The patient presented with fatigue attributed to severe AIHA. Due to increased serum IgM and γ-GT levels, an investigation for AMA was performed, which proved positive with anti-M2 specificity. A prolongation of activated partial thromboplastin time (aPTT) led to the determination of APLAbs (lupus anticoagulant and other APLAbs) which were also positive. Bone marrow biopsy in combination with immmunohistochemical studies established the diagnosis of lymphoplasmacytic B-NHL. Ten months later, B-NHL was in remission while AMA and APLAbs were still positive. In conclusion, we documented the coexistence of multiple autoimmune reactions together with B-NHL highlighting the possible common pathogenetic pathways of the two entities. PMID:21687651

  11. FDG PET/CT of extranodal involvement in non-Hodgkin lymphoma and Hodgkin disease.

    PubMed

    Paes, Fabio M; Kalkanis, Dimitrios G; Sideras, Panagiotis A; Serafini, Aldo N

    2010-01-01

    The term extranodal disease refers to lymphomatous infiltration of anatomic sites other than the lymph nodes. Almost any organ can be affected by lymphoma, with the most common extranodal sites of involvement being the stomach, spleen, Waldeyer ring, central nervous system, lung, bone, and skin. The prevalence of extranodal involvement in non-Hodgkin lymphoma and Hodgkin disease has increased in the past decade. The imaging characteristics of extranodal involvement can be subtle or absent at conventional computed tomography (CT). Imaging of tumor metabolism with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) has facilitated the identification of affected extranodal sites, even when CT has demonstrated no lesions. More recently, hybrid PET/CT has become the standard imaging modality for initial staging, follow-up, and treatment response assessment in patients with lymphoma and has proved superior to CT in these settings. Certain PET/CT patterns are suggestive of extranodal disease and can help differentiate tumor from normal physiologic FDG activity, particularly in the mucosal tissues, bone marrow, and organs of the gastrointestinal tract. Familiarity with the different extranodal manifestations in various locations is critical for correct image interpretation. In addition, a knowledge of the differences in FDG avidity among the histologic subtypes of lymphoma, appropriate timing of scanning after therapeutic interventions, and use of techniques to prevent brown fat uptake are essential for providing the oncologist with accurate information.

  12. Non-Hodgkin's malignant lymphomas of upper digestive and respiratory tracts

    SciTech Connect

    Plantenga, K.F.; Hart, G.; Van Heerde, P.; Tierie, A.H.

    1981-10-01

    The history of 102 patients with primary Non-Hodgkin's lymphoma of the upper digestive and respiratory tract is reviewed. An analysis is presented of the histopathologic, clinical and prognostic features of these patients, who presented to the Antoni van Leeuwenhoek Hospital in Amsterdam between 1958-1976. The histological slides were reviewed in 91 patients. Ilio-lumbar lymphography and bone marrow examination were performed in 44 and 66 patients respectively: 4 lymphograms and 4 bone marrows were found to be abnormal. Of 82 patients with Stage I and II disease, there were 72 remissions with locoregional irradiation. Among these patients 36 suffered a relapse, 27 (75%) during the first year after treatment. The median survival was 14 months for all stages. The survival at 5 years was 28% for Stage I and 12% for Stage II patients. Prognosis was influenced by follicular cb/cc lymphomas, histiocytic poorly differentiated cell type, stage, size of primary tumor, and the radiation dose. We recommend adjuvant chemotherapy in Stage I and II patients after primary radiation treatment because of the high rate of primary relapse in distant sites.

  13. Pathologic fracture after radiation therapy for primary non-Hodgkin's malignant lymphoma of bone

    SciTech Connect

    Stokes, S.H.; Walz, B.J.

    1983-08-01

    Between 1963 and 1981, 32 patients with biopsy proven non-Hodgkin's lymphoma involving bone were treated at the Mallinckrodt Institute of Radiology either with radiation alone or in conjunction with chemotherapy. An unexpectedly high rate of fracture at the site of the tumor was observed. Six patients were excluded because they survived less than six months after the completion of radiotherapy or were lost to follow-up within six months. There were 15 appendicular and 17 axial sites treated. Local control was achieved in 30 of 32. There were 10 patients with appendicular lesions of which seven suffered a fracture. Of the seven patients with lesions in a weight bearing bone, six suffered fractures. Twenty-six sites of involvement received less than 5000 rad. Of the six patients receiving high dose, two presented with pathologic fractures of the femur requiring surgical stabilization and the remaining four patients suffered subsequent fractures 7 to 30 months after completion of therapy. Two of these six had local recurrence of disease. It appears that involvement of the appendicular skeleton by lymphoma frequently results in fracture. Doses of 5000 rad or greater do not increase the probability of local control but may contribute to the risk of fracture following radiotherapy.

  14. Uptake of carbon-11-methionine and fluorodeoxyglucose in non-Hodgkin's lymphoma: A PET study

    SciTech Connect

    Leskinen-Kallio, S.; Ruotsalainen, U.; Nagren, K.T.; Teraes, M.J.; Joensuu, H. )

    1991-06-01

    Uptake of L-(methyl-11C)methionine (11C-methionine) and (18F)-2-fluoro-2-deoxy-D-glucose (FDG) was studied with PET in 14 patients with non-Hodgkin's lymphomas. The low molecular weight fraction of venous plasma separated by fast gel filtration was used as the input function for 11C-methionine studies, and tracer accumulation was analyzed according to Patlak and Gjedde. The average uptake rate of 11C-methionine was 0.0775 {plus minus} 0.0245 min-1 (s.d.) and of FDG 0.0355 {plus minus} 0.0293 min-1, 11C-methionine uptake rate being significantly higher than that of FDG (p less than 0.01). Carbon-11-methionine accumulated strongly in all but one of the lymphomas. FDG accumulated clearly in lymphomas of high-grade malignancy, whereas two intermediate- and three low-grade malignant lymphomas had a poor uptake rate. The tumor/plasma ratio of both 11C-methionine and FDG increased faster in high and intermediate-grade lymphomas than in low-grade lymphomas, but there was considerable overlap between the histologic grades. Carbon-11-methionine seems to be preferable in detecting tumors, while FDG was superior to 11C-methionine in distinguishing the high-grade malignant lymphomas from the other grades.

  15. Childhood leukaemia and non-Hodgkin's lymphoma in relation to proximity to railways.

    PubMed

    Dickinson, H O; Hammal, D M; Dummer, T J B; Parker, L; Bithell, J F

    2003-03-10

    We investigated whether living close to railway lines is a risk factor for childhood leukaemia and non-Hodgkin's lymphoma in electoral wards in England and Wales, 1966-1987. The national rail network, 1966-1987, was digitised and the numbers of cases in each ward were related to two measures of environmental exposure to railways: a proximity and a density function, contributions to these functions being weighted by the frequency of use and time in use of each stretch of railway. Poisson regression was used to derive rate ratios in relation to these measures of exposure to railways, both unadjusted and adjusted for population mixing. We found no association between risk of leukaemia and railway proximity (unadjusted rate ratio for trend from the lowest to the median value=1.006, 95% CI: 0.998 - 1.013, P=0.14) and a very small association with railway density, of marginal statistical significance (rate ratio for trend=1.001, 95% CI: 1.000 - 1.003, P=0.05). This effect depended on two deprived, urban wards with high railway density and high population mixing and became nonsignificant (P=0.09) after allowing for population mixing. The very weak association between railway density and risk of childhood leukaemia is likely to be a consequence of the association between population mixing and proximity to railways in very deprived, urban wards.

  16. Treatment of non-Hodgkin's lymphoma in Mexican children. The effectiveness of chemotherapy during malnutrition.

    PubMed

    Rivera-Luna, R; Martinez-Guerra, G; Martinez-Avalos, A; Altamirano-Alvarez, E; Ayon-Cardenas, A; Cardenas-Cardoz, R; Borrego-Roman, R; Lanche-Guevara, T; Lopez-Corella, E

    1987-01-01

    The histological diagnosis of non-Hodgkin's lymphoma (Burkitt's lymphoma excluded) in 147 children was reviewed. The most common site of presentation was in the abdomen (32.6%). The most frequent site of metastatic disease at diagnosis was the bone marrow (27.2%). The most common histology was diffuse undifferentiated non-Burkitt type (37.4%). According to the Murphy staging system, 40.1% were stage III and 27.2% were stage IV. In a nonrandomized prospective study, 121 patients were submitted to a treatment regimen (protocol 8001) and compared with 26 historical controls treated with the COP regimen, consisting of cyclophosphamide, vincristine, and prednisone. Of those patients treated with protocol 8001, nine had intestinal perforation at the site of primary disease. All patients in this group were malnourished at the time of perforation. The overall rate of initial complete remission in those patients treated with protocol 8001 was 90.7%. The duration of remission was from 16 to 108 months, with a median of 39 months. The actuarial rate of disease-free survival was 69% at 2 years and 63% at 6 years, compared with 36% at 6 years of the control group (COP) (p less than 0.01). None of the patients have relapsed after 4 years.

  17. Occupational exposures and non-Hodgkin's lymphoma: Canadian case-control study

    PubMed Central

    Karunanayake, Chandima P; McDuffie, Helen H; Dosman, James A; Spinelli, John J; Pahwa, Punam

    2008-01-01

    Background The objective was to study the association between Non-Hodgkin's Lymphoma (NHL) and occupational exposures related to long held occupations among males in six provinces of Canada. Methods A population based case-control study was conducted from 1991 to 1994. Males with newly diagnosed NHL (ICD-10) were stratified by province of residence and age group. A total of 513 incident cases and 1506 population based controls were included in the analysis. Conditional logistic regression was conducted to fit statistical models. Results Based on conditional logistic regression modeling, the following factors independently increased the risk of NHL: farmer and machinist as long held occupations; constant exposure to diesel exhaust fumes; constant exposure to ionizing radiation (radium); and personal history of another cancer. Men who had worked for 20 years or more as farmer and machinist were the most likely to develop NHL. Conclusion An increased risk of developing NHL is associated with the following: long held occupations of faer and machinist; exposure to diesel fumes; and exposure to ionizing radiation (radium). The risk of NHL increased with the duration of employment as a farmer or machinist. PMID:18687133

  18. Primary non-Hodgkin's lymphoma of the infratemporal fossa: a rare case report

    PubMed Central

    Thakur, Jagdeep S; Minhas, Ravinder S; Mohindroo, Narinder K; Sharma, Dev R; Mohindroo, Shobha; Thakur, Anamika

    2009-01-01

    Background The head and neck are two of the most common sites of extranodal non-Hodgkin's lymphoma (NHL). However, primary tumors of the infratemporal fossa are infrequent, and NHL in this region is extremely rare. Case presentation We present a case of a 41-year-old female that presented with swelling in the right preauricular region that had persisted for the past two years. The patient was diagnosed as having a small lymphocytic NHL. She initially underwent chemo-radiation but reported relapse. The tumor was excised and again the patient underwent chemotherapy. The patient remained symptomatic and developed a second primary squamous cell carcinoma in the right retromolar trigone. Discussion and conclusion We discussed NHL with an emphasis on extranodal manifestations. Extranodal NHL that is limited to a single site can be managed by surgery and regular follow up. To the best of our knowledge, this is only the second case of primary NHL of the infratemporal fossa to be reported in the literature. PMID:19545392

  19. Personal use of hair dye and the risk of certain subtypes of non-Hodgkin lymphoma.

    PubMed

    Zhang, Yawei; Sanjose, Silvia De; Bracci, Paige M; Morton, Lindsay M; Wang, Rong; Brennan, Paul; Hartge, Patricia; Boffetta, Paolo; Becker, Nikolaus; Maynadie, Marc; Foretova, Lenka; Cocco, Pierluigi; Staines, Anthony; Holford, Theodore; Holly, Elizabeth A; Nieters, Alexandra; Benavente, Yolanda; Bernstein, Leslie; Zahm, Shelia Hoar; Zheng, Tongzhang

    2008-06-01

    Personal use of hair dye has been inconsistently linked to risk of non-Hodgkin lymphoma (NHL), perhaps because of small samples or a lack of detailed information on personal hair-dye use in previous studies. This study included 4,461 NHL cases and 5,799 controls from the International Lymphoma Epidemiology Consortium 1988-2003. Increased risk of NHL (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.4) associated with hair-dye use was observed among women who began using hair dye before 1980. Analyses by NHL subtype showed increased risk for follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) but not for other NHL subtypes. The increased risks of FL (OR = 1.4, 95% CI: 1.1, 1.9) and CLL/SLL (OR = 1.5, 95% CI: 1.1, 2.0) were mainly observed among women who started using hair dyes before 1980. For women who began using hair dye in 1980 or afterward, increased FL risk was limited to users of dark-colored dyes (OR = 1.5, 95% CI: 1.1, 2.0). These results indicate that personal hair-dye use may play a role in risks of FL and CLL/SLL in women who started use before 1980 and that increased risk of FL among women who started use during or after 1980 cannot be excluded.

  20. Meta-analysis and causal inference: a case study of benzene and non-Hodgkin lymphoma.

    PubMed

    Weed, Douglas L

    2010-05-01

    Meta-analysis is an important method in the practice of occupational epidemiology, with a legitimate, but limited role to play in causal inference. Meta-analysis provides an assessment of consistency-one of several classic causal criteria-through tests of heterogeneity and an assessment of differences across studies. It can also provide an increase in the precision of effect estimates, including the precision of dose response relationships. Causal inference, however, involves much more: a complete assessment of the classic causal criteria, for example. Causal claims, therefore, should not emerge from meta-analyses as such. A recent meta-analysis of epidemiological studies of benzene exposure and non-Hodgkin lymphoma (NHL), however, does exactly that. Using studies from a previous narrative review in which the authors made no causal claim, the same authors performed a meta-analysis and concluded that it represented new evidence that benzene causes NHL. Despite a lack of consistency (i.e., significant heterogeneity), weak associations, no evidence of dose-response, no effort to provide an assessment of biological plausibility, and no new epidemiological evidence, the authors, nevertheless, changed their conclusion from association to causation. By using case study as an illustrative platform, this commentary provides cautionary and critical comments about the use of meta-analysis and causal inference in occupational epidemiology.

  1. A Canadian perspective on the subcutaneous administration of rituximab in non-Hodgkin lymphoma

    PubMed Central

    MacDonald, D.; Crosbie, T.; Christofides, A.; Assaily, W.; Wiernikowski, J.

    2017-01-01

    Rituximab is widely used for the treatment of non-Hodgkin lymphoma, being a key component in most therapeutic regimens. Administration of the intravenous (IV) formulation is lengthy and places a significant burden on health care resources and patient quality of life. A subcutaneous (sc) formulation that provides a fixed dose of rituximab is being examined in a number of studies. Results indicate that the pharmacokinetics are noninferior and response rates are comparable to those obtained with the IV formulation. Moreover, the sc formulation is preferred by patients and health care providers and reduces administration and chair time. Additional advantages include a lesser potential for dosing errors, shorter preparation time, reduced drug wastage, and fewer infusion-related reactions. Despite the success of the sc formulation, correct administration is needed to reduce administration-related reactions. By using a careful procedure, the sc formulation can be given safely and effectively, potentially reducing the burden on health care resources and improving quality of life for patients. PMID:28270723

  2. Low versus high cell turnover in diffusely growing non-Hodgkin's lymphomas.

    PubMed

    Spina, D; Leoncini, L; Del Vecchio, M T; Megha, T; Minacci, C; Poggi, S A; Pileri, S; Tosi, P; Kraft, R; Laissue, J A

    1995-12-01

    Cell loss, perhaps as important as cell production in determining the size of an expanding cell population, has not usually been registered in quantitative cellular kinetic analyses of neoplastic disorders. The present retrospective study on various types and subtypes of non-Hodgkin's lymphomas (NHLs; n = 170) was designed to test the usefulness of a novel additional parameter, the 'turnover index' (TI), which is the sum per case of the mitotic index and the apoptotic index. Results document that TIs clearly distinguished between categories and subtypes of NHLs according to the Kiel classification. Cluster analysis of TIs plotted against the percentage of Ki-67-positive cells per case revealed that about one-third of the high-grade malignancy lymphomas actually belonged to the low-turnover lymphomas. Overall survival was longer in the low- than in the high-turnover group of lymphomas. Assessment of TIs can, for practical diagnostic purposes, be replaced by counting mitotic figures and apoptotic cells in several high-power fields. The TI concept may help to interpret the kinetics of NHLs in terms of accumulation vs. proliferation of cells.

  3. Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-07-09

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma

  4. 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

  5. Pax5 expression in non-Hodgkin's lymphomas and acute leukemias.

    PubMed

    Zhang, Xianglan; Lin, Zhenhua; Kim, Insun

    2003-12-01

    The Pax5 gene encodes the B-cell-specific activator protein which is a key regulator in development and differentiation of B-cell. We studied the expression of Pax5 in hematologic malignancies to evaluate the diagnostic utility as a B cell marker. Materials included 70 B cell lymphomas, 26 T cell lymphomas, 53 acute leukemias, and 6 multiple myelomas (MMs). Representative areas from the paraffin embedded tissues were selected for tissue microarray, and the expressions of Pax5 was immunohistochemically evaluated. Pax5 was strongly expressed in most of the B cell lymphomas; 44 of 47 diffuse large B cell lymphomas (93.6%), 15 of 16 marginal zone B cell lymphomas (93.8%), all 3 mantle cell lymphomas, 2 follicular lymphomas, and 2 Burkitt's lymphomas (100%). However, Pax5 was expressed in only one of 26 T cell lymphomas. Among leukemias, it was expressed in 10 of the 14 B acute lymphocytic leukemias (ALLs) (72.4%), but also in 3 of the 6 T ALLs (50%), 13 of the 26 acute myelogenous leukemias (AMLs) (50%) and in all 3 ALL arising in chronic myelogenous leukemias and 4 mixed B ALL and AML. In MMs, Pax5 was negative in all cases. We concluded that Pax5 is very useful B cell marker in classification of lymphomas, but not of acute leukemias.

  6. Pax5 expression in non-Hodgkin's lymphomas and acute leukemias.

    PubMed Central

    Zhang, Xianglan; Lin, Zhenhua; Kim, Insun

    2003-01-01

    The Pax5 gene encodes the B-cell-specific activator protein which is a key regulator in development and differentiation of B-cell. We studied the expression of Pax5 in hematologic malignancies to evaluate the diagnostic utility as a B cell marker. Materials included 70 B cell lymphomas, 26 T cell lymphomas, 53 acute leukemias, and 6 multiple myelomas (MMs). Representative areas from the paraffin embedded tissues were selected for tissue microarray, and the expressions of Pax5 was immunohistochemically evaluated. Pax5 was strongly expressed in most of the B cell lymphomas; 44 of 47 diffuse large B cell lymphomas (93.6%), 15 of 16 marginal zone B cell lymphomas (93.8%), all 3 mantle cell lymphomas, 2 follicular lymphomas, and 2 Burkitt's lymphomas (100%). However, Pax5 was expressed in only one of 26 T cell lymphomas. Among leukemias, it was expressed in 10 of the 14 B acute lymphocytic leukemias (ALLs) (72.4%), but also in 3 of the 6 T ALLs (50%), 13 of the 26 acute myelogenous leukemias (AMLs) (50%) and in all 3 ALL arising in chronic myelogenous leukemias and 4 mixed B ALL and AML. In MMs, Pax5 was negative in all cases. We concluded that Pax5 is very useful B cell marker in classification of lymphomas, but not of acute leukemias. PMID:14676435

  7. Early B-cell-specific inactivation of ATM synergizes with ectopic CyclinD1 expression to promote pre-germinal center B-cell lymphomas in mice.

    PubMed

    Yamamoto, K; Lee, B J; Li, C; Dubois, R L; Hobeika, E; Bhagat, G; Zha, S

    2015-06-01

    Ataxia telangiectasia-mutated (ATM) kinase is a master regulator of the DNA damage response. ATM is frequently inactivated in human B-cell non-Hodgkin lymphomas, including ~50% of mantle cell lymphomas (MCLs) characterized by ectopic expression of CyclinD1. Here we report that early and robust deletion of ATM in precursor/progenitor B cells causes cell autonomous, clonal mature B-cell lymphomas of both pre- and post-germinal center (GC) origins. Unexpectedly, naive B-cell-specific deletion of ATM is not sufficient to induce lymphomas in mice, highlighting the important tumor suppressor function of ATM in immature B cells. Although EμCyclinD1 is not sufficient to induce lymphomas, EμCyclinD1 accelerates the kinetics and increases the incidence of clonal lymphomas in ATM-deficient B-cells and skews the lymphomas toward pre-GC-derived small lymphocytic neoplasms, sharing morphological features of human MCL. This is in part due to CyclinD1-driven expansion of ATM-deficient naive B cells with genomic instability, which promotes the deletions of additional tumor suppressor genes (i.e. Trp53, Mll2, Rb1 and Cdkn2a). Together these findings define a synergistic function of ATM and CyclinD1 in pre-GC B-cell proliferation and lymphomagenesis and provide a prototypic animal model to study the pathogenesis of human MCL.

  8. OCCUPATION/INDUSTRY AND RISK OF NON HODGKIN LYMPHOMA IN THE UNITED STATES

    PubMed Central

    Schenk, Maryjean; Purdue, Mark P.; Colt, Joanne S.; Hartge, Patricia; Blair, Aaron; Stewart, Patricia; Cerhan, James R.; De Roos, Anneclaire J.; Cozen, Wendy; Severson, Richard K.

    2011-01-01

    Aims To identify occupations and industries associated with non-Hodgkin lymphoma in a large population-based case-control study in the United States. Methods Cases (n = 1,189) of histologically confirmed malignant NHL ages 20–74 were prospectively identified in four geographic areas covered by the National Cancer Institute SEER Program. Controls (n = 982) were selected from the general population by random digit dialing (< 65 years of age) and from residents listed in Medicare files (65–74 years of age). Odds ratios and 95% confidence intervals for occupations and industries were calculated by unconditional logistic regression analyses, adjusting for age, gender, ethnicity, and study center. Further analyses stratified for gender and histological subtype were also performed. Results Risk of NHL was increased for a few occupations and industries. Several white collar occupations, with no obvious hazardous exposures, had elevated risks, including purchasing agents and buyers, religious workers, physical therapists, and information clerks. Occupations with excesses that may have exposures of interest include launderers and ironers, service occupations, food/beverage preparation supervisors, hand packers and packagers, roofing and siding, leather and leather products, transportation by air, nursing and personal care facilities, and specialty outpatient clinics. Significantly decreased risks of NHL were found for a number of occupations and industries including post secondary teachers and chemical and allied products. Conclusions The results of this study suggest that several occupations and industries may alter the risk of NHL. Our results support previously reported increased risks among farmers, printers, medical professionals, electronic workers, and leather workers. These findings should be evaluated further in larger studies that have the power to focus on specific exposures and histologic subtypes of NHL. PMID:18805886

  9. Whole-abdomen radiotherapy for non-Hodgkin's lymphoma using twice-daily fractionation

    SciTech Connect

    Liauw, Stanley L.; Yeh, Alexander M.; Morris, Christopher G.; Olivier, Kenneth R.; Mendenhall, Nancy Price . E-mail: mendenan@shands.ufl.edu

    2006-12-01

    Purpose: To report the tolerability and efficacy of twice-daily whole-abdomen irradiation (WAI) for non-Hodgkin's lymphoma (NHL). Methods and Materials: Of 123 patients treated for NHL with WAI, 37% received previous chemotherapy, 28% received WAI as part of comprehensive lymphatic irradiation (CLI), and 32% received WAI for palliation. The median dose to the whole abdomen was 25.0 Gy, followed by a median tumor boost of 9.8 Gy in 58 patients. Fractionation was 1.0 Gy once daily (54%) or 0.8 Gy twice daily (46%). Blood counts were measured weekly. Results: At a median follow-up of 4.3 years, local control was 72% and overall survival was 55% at 5 years. Median time of WAI was 42 days for once-daily treatment and 32 days for twice-daily treatment. Patients receiving twice-daily WAI did not have a significantly higher rate of acute side effects (e.g., nausea, diarrhea, platelet or red blood cell toxicity). Overall, acute thrombocytopenia was the most frequent side effect of treatment; 24 of 96 patients (25%) with available hematologic data had Grade 3+ toxicity. There was no acute Grade 3 gastrointestinal toxicity and no late small bowel obstruction. Multiple regression indicated that patients with four or less involved sites and disease size {<=}6 cm had improved local control and overall survival. Conclusions: Twice-daily WAI using 0.8 Gy/fraction does not appear to have any greater toxicity compared with once-daily treatment using 1 Gy/fraction. Small doses per fraction (0.8-1 Gy/fx) are effective, tolerated well in the acute setting, and associated with a low rate of late toxicity.

  10. Long-term results of low dose total body irradiation for advanced non-Hodgkin lymphoma.

    PubMed

    Lybeert, M L; Meerwaldt, J H; Deneve, W

    1987-08-01

    Sixty-eight patients received fractionated low dose total body irradiation (LTBI) as treatment for non-Hodgkin lymphoma (NHL) at the Rotterdamsch Radio-Therapeutisch Instituut (RRTI) in the period 1973-1979. Ninety percent (61/68) of these patients had advanced disease (Stage III + IV). According to current malignancy grade classifications, 34 patients had low grade NHL, 10 intermediate, and 19 high grade. In 5 cases no exact grading was possible. LTBI was given 3 times a week, midline dose 0.1 Gy, using 6 or 25 MeV photons to a mean total dose of 1.78 Gy. Initial response rate for low, intermediate, and high grade NHL was resp. 84, 42, and 40%. The main prognostic factor for survival and recurrence-free survival (RFS) was malignancy grade. Probability of uncorrected survival at 10 years for low, intermediate, and high grade was resp. 34, 0 and 0%. Probability of RFS at 10 years was resp. 19, 0, and 0%. Neither stage nor sex had any influence on survival. Age was reversely correlated with survival, but was not correlated with RFS. Influence of prior therapy (18 patients) on survival and RFS was separately analyzed. Neither survival nor RFS of unfavorable histologic type NHL (high and intermediate grade) was influenced. On the other hand patients with a favorable histologic type NHL (low grade) had a significantly (p less than 0.05) better RFS if they received LTBI as initial treatment, but survival was not significantly influenced. RFS at 5 and 10 years of patients who received LTBI as first treatment was respectively 32% and 27%. No treatment related complications were noted. Subsequent chemotherapy in case of relapse was not hampered by previous LTBI. The high response rate and extended RFS, without maintenance therapy, makes LTBI a preferable first line treatment for patients with advanced stage low grade NHL.

  11. Study of non-Hodgkin's lymphoma mortality associated with industrial pollution in Spain, using Poisson models

    PubMed Central

    Ramis, Rebeca; Vidal, Enrique; García-Pérez, Javier; Lope, Virginia; Aragonés, Nuria; Pérez-Gómez, Beatriz; Pollán, Marina; López-Abente, Gonzalo

    2009-01-01

    Background Non-Hodgkin's lymphomas (NHLs) have been linked to proximity to industrial areas, but evidence regarding the health risk posed by residence near pollutant industries is very limited. The European Pollutant Emission Register (EPER) is a public register that furnishes valuable information on industries that release pollutants to air and water, along with their geographical location. This study sought to explore the relationship between NHL mortality in small areas in Spain and environmental exposure to pollutant emissions from EPER-registered industries, using three Poisson-regression-based mathematical models. Methods Observed cases were drawn from mortality registries in Spain for the period 1994–2003. Industries were grouped into the following sectors: energy; metal; mineral; organic chemicals; waste; paper; food; and use of solvents. Populations having an industry within a radius of 1, 1.5, or 2 kilometres from the municipal centroid were deemed to be exposed. Municipalities outside those radii were considered as reference populations. The relative risks (RRs) associated with proximity to pollutant industries were estimated using the following methods: Poisson Regression; mixed Poisson model with random provincial effect; and spatial autoregressive modelling (BYM model). Results Only proximity of paper industries to population centres (>2 km) could be associated with a greater risk of NHL mortality (mixed model: RR:1.24, 95% CI:1.09–1.42; BYM model: RR:1.21, 95% CI:1.01–1.45; Poisson model: RR:1.16, 95% CI:1.06–1.27). Spatial models yielded higher estimates. Conclusion The reported association between exposure to air pollution from the paper, pulp and board industry and NHL mortality is independent of the model used. Inclusion of spatial random effects terms in the risk estimate improves the study of associations between environmental exposures and mortality. The EPER could be of great utility when studying the effects of industrial pollution

  12. Adipose tissue levels of organochlorine pesticides and polychlorinated biphenyls and risk of non-Hodgkin's lymphoma.

    PubMed Central

    Quintana, Penelope J E; Delfino, Ralph J; Korrick, Susan; Ziogas, Argyrios; Kutz, Frederick W; Jones, Ellen L; Laden, Francine; Garshick, Eric

    2004-01-01

    In this nested case-control study we examined the relationship between non-Hodgkin's lymphoma (NHL) and organochlorine pesticide exposure. We used a data set originally collected between 1969 and 1983 in the U.S. Environmental Protection Agency National Human Adipose Tissue Survey. Adipose samples were randomly collected from cadavers and surgical patients, and levels of organochlorine pesticide residues were determined. From the original study population, 175 NHL cases were identified and matched to 481 controls; 173 controls were selected from accident victims, and 308 from cases with a diagnosis of myocardial infarction. Cases and controls were mainly from cadavers (> 96%) and were matched on sex, age, region of residence within the United States, and race/ethnicity. Conditional logistic regression showed the organochlorine pesticide residue heptachlor epoxide to be significantly associated with NHL [compared with the lowest quartile: third quartile odds ratio (OR) = 1.82, 95% confidence interval (CI), 1.01-3.28; fourth quartile OR = 3.41, 95% CI, 1.89-6.16]. The highest quartile level of dieldrin was also associated with elevated NHL risk (OR = 2.70; 95% CI, 1.58-4.61), as were higher levels of oxychlordane, p,p'-DDE [p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], and ss-benzene hexachloride (ORs = 1.79, 1.99, and 2.47, respectively). The p-values for trends for these associations were significant. In models containing pairs of pesticides, only heptachlor epoxide and dieldrin remained significantly associated with risk of NHL. Limitations of this study include collection of samples after diagnosis and a lack of information on variables affecting organochlorine levels such as diet, occupation, and body mass index. Given the persistence of pesticides in the environment, these findings are still relevant today. PMID:15175172

  13. Occupation and risk of non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

    PubMed

    Zheng, Tongzhang; Blair, Aaron; Zhang, Yawei; Weisenburger, Dennis D; Zahm, Shelia H

    2002-05-01

    To investigate the association between occupation and the risk of non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), and to test whether the associations may vary by histological type of NHL, we analyzed data from two population-based, case-control studies of NHL performed in Kansas and Nebraska. A total of 555 incident NHL cases, 56 CLL cases, and 2380 population-based controls were included in the analysis. Information on occupation and other confounding factors was collected through telephone interviews. Study pathologists reviewed slides of tumor tissues in all cases. In men, we found an increased risk of NHL and CLL for those working in agricultural, forestry, and logging industries (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2 to 2.1). The OR was 1.9 (95% CI, 1.4 to 2.6) for those producing crops. An increased risk was also observed for industries involving metalworking machinery and equipment (OR, 8.4; 95% CI, 1.4 to 50.6), motor vehicles and motor vehicle equipment (OR, 4.2; 95% CI, 1.3 to 13.9), and telephone communications (OR, 3.1; 95% CI, 1.2 to 8.0), and for teachers (OR, 2.5; 95% CI, 1.0 to 6.5), farmers (OR, 2.0; 95% CI, 1.5 to 2.8), and welders and solderers (OR, 2.9; 95% CI, 1.2 to 6.9). The risks for these associations increased by duration of employment and seem to vary by histological type. Work in the printing and publishing industry was also associated with an increased risk of NHL among women. These data suggest that the workers employed in these industries or occupations experienced an increased risk of NHL and CLL, and the risks associated with these industries or occupations may vary by histological type of NHL.

  14. Aspirin and other nonsteroidal anti-inflammatory drugs and risk of non-hodgkin lymphoma.

    PubMed

    Teras, Lauren R; Gapstur, Susan M; Patel, Alpa V; Thun, Michael J; Diver, W Ryan; Zhai, Yusheng; Jacobs, Eric J

    2013-03-01

    Few large prospective studies have examined associations between nonsteroidal anti-inflammatory drug (NSAID) use and non-Hodgkin lymphoma (NHL). We examined the association between NSAID use and NHL incidence among 149,570 participants in the Cancer Prevention Study-II Nutrition cohort. Aspirin and nonaspirin NSAID use were reported at enrollment in 1992 and updated on periodic follow-up questionnaires. During follow-up through 2007, 1,709 incident NHLs were identified. Time-dependent hazard ratios were calculated using extended Cox regression. Compared to no use, current use of 60+ NSAID pills/month (aspirin and nonaspirin NSAIDs combined) was associated with slightly higher NHL incidence (hazard ratio [HR] = 1.26, 95% confidence interval [CI], 1.04-1.53), but no association with frequency of use was observed when NSAID exposure was lagged by approximately 2 years (HR = 1.08, 95% CI, 0.88-1.32). Long duration regular use (current use of 30+ pills/month for ≥5 years) was not associated with NHL incidence (HR = 1.09, 95% CI, 0.91-1.33). In subtype analyses, current use of 60+ NSAID pills/month was associated with follicular lymphoma incidence (HR = 1.87, 95% CI, 1.08-3.24). This association persisted when NSAID exposure was lagged (HR = 1.76, 95% CI, 1.04-2.98) and was similar for aspirin and nonaspirin NSAIDs. The association of current, but not lagged, NSAID use with risk of all NHL could be attributable to use of NSAIDs to relieve symptoms of undiagnosed NHL. However, the association with follicular lymphoma persisted in analyses where NSAID use was lagged and should be investigated further. These findings are particularly important for aspirin as the risks and benefits of prophylactic daily use are weighed.

  15. Drinking Water Contamination and the Incidence of Leukemia and Non-Hodgkin's Lymphoma.

    PubMed Central

    Cohn, P; Klotz, J; Bove, F; Berkowitz, M; Fagliano, J

    1994-01-01

    >A study of drinking water contamination and leukemia and non-Hodgkin's lymphoma (NHL) incidence (1979-1987) was conducted in a 75-town study area. Comparing incidence in towns in the highest trichloroethylene (TCE) stratum (>5 microg/l) to towns without detectable TCE yielded an age-adjusted rate ratio (RR) for total leukemia among females of 1.43 (95% CI 1.07-1.90). For females under 20 years old, the RR for acute lymphocytic leukemia was 3.26 (95% CI 1.27-8.15). Elevated RRs were observed for chronic myelogenous leukemia among females and for chronic lymphocytic leukemia among males and females. NHL incidence among women was also associated with the highest TCE stratum (RR = 1.36; 95% CI 1.08-1.70). For diffuse large cell NHL and non-Burkitt's high-grade NHL among females, the RRs were 1.66 (95% CI 1.07-2.59) and 3.17 (95% CI 1.23-8.18), respectively, and 1.59 (95% CI 1.04-2.43) and 1.92 (95% CI 0.54-6.81), respectively, among males. Perchloroethylene (PCE) was associated with incidence of non-Burkitt's high-grade NHL among females, but collinearity with TCE made it difficult to assess relative influences. The results suggest a link between TCE/PCE and leukemia/ NHL incidence. However, the conclusions are limited by potential misclassification of exposure due to lack of individual information on long-term residence, water consumption, and inhalation of volatilized compounds. PMID:9679115

  16. Season of birth and risk of Hodgkin and non-Hodgkin lymphoma.

    PubMed

    Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A; Sundquist, Kristina

    2014-12-01

    Infectious etiologies have been hypothesized for Hodgkin and non-Hodgkin lymphoma (HL and NHL) in early life, but findings to date for specific lymphomas and periods of susceptibility are conflicting. We conducted the first national cohort study to examine whether season of birth, a proxy for infectious exposures in the first few months of life, is associated with HL or NHL in childhood through young adulthood. A total of 3,571,574 persons born in Sweden in 1973-2008 were followed up through 2009 to examine the association between season of birth and incidence of HL (943 cases) or NHL (936 cases). We found a sinusoidal pattern in NHL risk by season of birth (p = 0.04), with peak risk occurring among birthdates in April. Relative to persons born in fall (September-November), odds ratios for NHL by season of birth were 1.25 [95% confidence interval (CI), 1.04-1.50; p = 0.02] for spring (March-May), 1.22 (95% CI, 1.01-1.48; p = 0.04) for summer (June-August) and 1.11 (95% CI, 0.91-1.35; p = 0.29) for winter (December-February). These findings did not vary by sex, age at diagnosis or major subtypes. In contrast, there was no seasonal association between birthdate and risk of HL (p = 0.78). In this large cohort study, birth in spring or summer was associated with increased risk of NHL (but not HL) in childhood through young adulthood, possibly related to immunologic effects of delayed infectious exposures compared with fall or winter birth. These findings suggest that immunologic responses in early infancy may play an important role in the development of NHL.

  17. Drinking Water Contamination and the Incidence of Leukemia and Non-Hodgkin's Lymphoma.

    PubMed

    Cohn; Klotz; Bove; Berkowitz; Fagliano

    1994-06-01

    >A study of drinking water contamination and leukemia and non-Hodgkin's lymphoma (NHL) incidence (1979-1987) was conducted in a 75-town study area. Comparing incidence in towns in the highest trichloroethylene (TCE) stratum (>5 microg/l) to towns without detectable TCE yielded an age-adjusted rate ratio (RR) for total leukemia among females of 1.43 (95% CI 1.07-1.90). For females under 20 years old, the RR for acute lymphocytic leukemia was 3.26 (95% CI 1.27-8.15). Elevated RRs were observed for chronic myelogenous leukemia among females and for chronic lymphocytic leukemia among males and females. NHL incidence among women was also associated with the highest TCE stratum (RR = 1.36; 95% CI 1.08-1.70). For diffuse large cell NHL and non-Burkitt's high-grade NHL among females, the RRs were 1.66 (95% CI 1.07-2.59) and 3.17 (95% CI 1.23-8.18), respectively, and 1.59 (95% CI 1.04-2.43) and 1.92 (95% CI 0.54-6.81), respectively, among males. Perchloroethylene (PCE) was associated with incidence of non-Burkitt's high-grade NHL among females, but collinearity with TCE made it difficult to assess relative influences. The results suggest a link between TCE/PCE and leukemia/ NHL incidence. However, the conclusions are limited by potential misclassification of exposure due to lack of individual information on long-term residence, water consumption, and inhalation of volatilized compounds.

  18. Alcohol consumption and non-Hodgkin lymphoma in a cohort of older women

    PubMed Central

    Chiu, B C-H; Cerhan, J R; Gapstur, S M; Sellers, T A; Zheng, W; Lutz, C T; Wallace, R B; Potter, J D

    1999-01-01

    We investigated the relation of alcohol consumption to risk of non-Hodgkin's lymphoma (NHL) in a cohort of 35 156 lowa women aged 55–69 years who participated in the lowa Women's Health Study in 1986. Alcohol consumption at baseline was obtained using a mailed questionnaire. During the 9-year follow-up period, 143 incident cases of NHL were identified. Higher alcohol consumption was significantly associated with a decreased risk of NHL (P-trend = 0.03). Compared to non-drinkers, multivariate-adjusted relative risks (RRs) were decreased for women with intake of ≤ 3.4 g day−1 (RR = 0.78; 95% confidence interval (CI) 0.51–1.21) and > 3.4 g day−1 (RR = 0.59; 0.36–0.97). The inverse association could not be attributed to one particular type of alcoholic beverage, although red wine (RR = 0.21 for > 2 glasses per month vs non-drinker; 0.05–0.86; P-trend = 0.02) has the most distinct effect. The apparent protective effect was universal regardless of specific NHL grade or Working Formulation subtype, but was most pronounced for nodal NHL (RR = 0.48; 0.26–0.90; P-trend = 0.01) and low-grade NHL (RR = 0.52; 0.21–1.26; P-trend = 0.05). These data suggest that moderate alcohol consumption is inversely associated with the risk of NHL in older women and the amount of alcohol consumed, rather than the type of alcoholic beverages, appears to be the main effect determinant. © 1999 Cancer Research Campaign PMID:10424754

  19. Genetic Variation in Cell Death Genes and Risk of Non-Hodgkin Lymphoma

    PubMed Central

    Schuetz, Johanna M.; Daley, Denise; Graham, Jinko; Berry, Brian R.; Gallagher, Richard P.; Connors, Joseph M.; Gascoyne, Randy D.; Spinelli, John J.; Brooks-Wilson, Angela R.

    2012-01-01

    Background Non-Hodgkin lymphomas are a heterogeneous group of solid tumours that constitute the 5th highest cause of cancer mortality in the United States and Canada. Poor control of cell death in lymphocytes can lead to autoimmune disease or cancer, making genes involved in programmed cell death of lymphocytes logical candidate genes for lymphoma susceptibility. Materials and Methods We tested for genetic association with NHL and NHL subtypes, of SNPs in lymphocyte cell death genes using an established population-based study. 17 candidate genes were chosen based on biological function, with 123 SNPs tested. These included tagSNPs from HapMap and novel SNPs discovered by re-sequencing 47 cases in genes for which SNP representation was judged to be low. The main analysis, which estimated odds ratios by fitting data to an additive logistic regression model, used European ancestry samples that passed quality control measures (569 cases and 547 controls). A two-tiered approach for multiple testing correction was used: correction for number of tests within each gene by permutation-based methodology, followed by correction for the number of genes tested using the false discovery rate. Results Variant rs928883, near miR-155, showed an association (OR per A-allele: 2.80 [95% CI: 1.63–4.82]; pF = 0.027) with marginal zone lymphoma that is significant after correction for multiple testing. Conclusions This is the first reported association between a germline polymorphism at a miRNA locus and lymphoma. PMID:22347493

  20. B-cell receptor pathway modulators in NHL

    PubMed Central

    Blum, Kristie A.

    2016-01-01

    With the recent success of the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, and the phosphoinositide-3-kinase (PI3K) inhibitor, idelalisib, in the treatment of patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), a number of new agents targeting the B-cell receptor (BCR) pathway are in clinical development. In addition, multiple trials combining these agents with conventional cytotoxic chemotherapy, immunomodulatory agents, monoclonal antibodies, or other kinase inhibitors are underway. This review will summarize the current data with the use of single agent and combination therapy with BCR inhibitors in NHL. In addition, commonly encountered as well as serious toxicities and hypothesized resistance mechanisms will be discussed. Lastly, this review will examine the future of these agents and opportunities to maneuver them into the front-line setting in selected NHL subtypes. PMID:26637705