Sample records for b-cell nonhodgkins lymphoma

  1. Selinexor Plus Combination Chemotherapy in Treating Patients With Advanced B Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2018-02-12

    Diffuse Large B-Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Extranodal Marginal Zone Lymphoma; Recurrent Follicular Lymphoma; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Extranodal Marginal Zone Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Stage III Non-Hodgkin Lymphoma; Stage IV Non-Hodgkin Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  2. 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

    2018-04-10

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; 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; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt 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 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 Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; 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

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

    ClinicalTrials.gov

    2018-04-17

    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

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

    ClinicalTrials.gov

    2018-05-15

    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

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

    ClinicalTrials.gov

    2018-05-25

    Adult B Acute Lymphoblastic Leukemia; BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; MYC Gene Rearrangement; 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

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

    ClinicalTrials.gov

    2015-06-03

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

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

    ClinicalTrials.gov

    2017-10-17

    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

  8. 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

  9. Diagnosis of B-Cell Non-Hodgkin Lymphomas with Small-/Intermediate-Sized Cells in Cytopathology

    PubMed Central

    Schwock, Joerg; Geddie, William R.

    2012-01-01

    Fine needle sampling is a fast, safe, and potentially cost-effective method of obtaining tissue for cytomorphologic assessment aimed at both initial triage and, in some cases, complete diagnosis of patients that present clinically with lymphadenopathy. The cytologic diagnosis of B-cell non-Hodgkin lymphomas composed of small-/intermediate-sized cells, however, has been seen as an area of great difficulty even for experienced observers due to the morphologic overlap between lymphoma and reactive lymphadenopathies as well as between the lymphoma entities themselves. Although ancillary testing has improved diagnostic accuracy, the results from these tests must be interpreted within the morphological and clinical context to avoid misinterpretation. Importantly, the recognition of specific cytologic features is crucial in guiding the appropriate selection of ancillary tests which will either confirm or refute a tentative diagnosis. For these reasons, we here review the cytologic characteristics particular to five common B-cell non-Hodgkin lymphomas which typically cause the most diagnostic confusion based on cytological assessment alone: marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and lymphoplasmacytic lymphoma. We summarize the most pertinent cytomorphologic features for each entity as well as for reactive lymphoid hyperplasia, contrast them with each other to facilitate their recognition, and highlight common diagnostic pitfalls. PMID:22693682

  10. 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

    2017-11-15

    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

  11. Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases

    ClinicalTrials.gov

    2018-04-06

    B-Cell Non-Hodgkin Lymphoma; Waldenstrom Macroglobulinemia; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Lymphoplasmacytic Lymphoma; Follicular Lymphoma; Indolent Non-Hodgkin Lymphoma; Marginal Zone Lymphoma

  12. Evaluation of a low density DNA microarray for small B-cell non-Hodgkin lymphoma differential diagnosis.

    PubMed

    Gillet, Jean-Pierre; Molina, Thierry Jo; Jamart, Jacques; Gaulard, Philippe; Leroy, Karen; Briere, Josette; Theate, Ivan; Thieblemont, Catherine; Bosly, Andre; Herin, Michel; Hamels, Jacques; Remacle, Jose

    2009-03-01

    Lymphomas are classified according to the World Health Organisation (WHO) classification which defines subtypes on the basis of clinical, morphological, immunophenotypic, molecular and cytogenetic criteria. Differential diagnosis of the subtypes is sometimes difficult, especially for small B-cell lymphoma (SBCL). Standardisation of molecular genetic assays using multiple gene expression analysis by microarrays could be a useful complement to the current diagnosis. The aim of the present study was to develop a low density DNA microarray for the analysis of 107 genes associated with B-cell non-Hodgkin lymphoma and to evaluate its performance in the diagnosis of SBCL. A predictive tool based on Fisher discriminant analysis using a training set of 40 patients including four different subtypes (follicular lymphoma n = 15, mantle cell lymphoma n = 7, B-cell chronic lymphocytic leukemia n = 6 and splenic marginal zone lymphoma n = 12) was designed. A short additional preliminary analysis to gauge the accuracy of this signature was then performed on an external set of nine patients. Using this model, eight of nine of those samples were classified successfully. This pilot study demonstrates that such a microarray tool may be a promising diagnostic approach for small B-cell non-Hodgkin lymphoma.

  13. 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

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

    ClinicalTrials.gov

    2018-05-02

    High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; MYC Positive; 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

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

    ClinicalTrials.gov

    2017-05-25

    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

  16. A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas

    ClinicalTrials.gov

    2018-04-11

    CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Transformed Indolent Non-Hodgkin Lymphoma

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

    ClinicalTrials.gov

    2017-10-11

    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

  18. 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

  19. 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. Copyright© Ferrata Storti Foundation.

  20. 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

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

    ClinicalTrials.gov

    2018-06-25

    CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; 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

  2. Clinical utility of bone marrow flow cytometry in B-cell non-Hodgkin lymphomas (B-NHL).

    PubMed

    Perea, G; Altés, A; Bellido, M; Aventín, A; Bordes, R; Ayats, R; Remacha, A F; Espinosa, I; Briones, J; Sierra, J; Nomdedéu, J F

    2004-09-01

    To determine the efficacy of flow cytometry (FC) in the assessment of bone marrow (BM) in B-cell non-Hodgkin lymphoma (B-NHL). FC is a common practice, but is far from being validated. Morphological analysis and FC immunophenotyping were performed on 421 samples. T-cell lymphomas, Hodgkin's disease, chronic lymphocytic leukaemia and hairy cell leukaemia were not included in the study. Clonality was assessed by the standard kappa/lambda/CD19 test. Aberrant immunophenotypes present in the B-cell subpopulation were also investigated. A double-step procedure was employed in all cases to increase the sensitivity of the FC procedure. Of 380 evaluable samples, 188 corresponded to follicular lymphoma (FL), 58 to diffuse large B-cell lymphoma (DLBCL), 57 to mantle cell lymphoma (MCL), seven to Burkitt's lymphoma and the remaining 70 samples to other low-grade lymphomas. Morphological marrow infiltration was found in 148 cases, and flow immunophenotyping identified 138 cases with BM involvement. A concordance between the two methods was detected in 298 cases (79%). There was a discordance in 82 cases (21%): morphology positive/FC negative in 46 cases and morphology negative/FC positive in 36 (61% of all cases with discordance were from FL). There was no difference in outcome when patients with discordances were compared with patients without discordances. Most samples showed concordance between morphological and FC results. FC identified BM involvement in the absence of morphological infiltration. Morphology/FC discordance seems to have no influence on the outcome of FL patients. Copyright 2004 Blackwell Publishing Limited

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

    ClinicalTrials.gov

    2017-10-24

    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 Acute Lymphoblastic Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  4. TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas

    ClinicalTrials.gov

    2018-04-18

    B-Cell Non-Hodgkin Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Small Lymphocytic Lymphoma

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

    ClinicalTrials.gov

    2018-04-19

    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

  6. Study of Safety,Efficacy and Pharmacokinetics of CT-1530 in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

    ClinicalTrials.gov

    2017-07-18

    Relapsed or Refractory B Cell Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Waldenstrom's Macroglobulinemia; Mantle Zone Lymphoma Refractory/Recurrent; Follicle Centre Lymphoma Diffuse; Diffuse Large B Cell Lymphoma

  7. 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

  8. 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

    2017-12-26

    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

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

    ClinicalTrials.gov

    2018-04-10

    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

  10. Hypophosphataemia due to FGF-23 producing B cell non-Hodgkin's lymphoma

    PubMed Central

    Elderman, Jan H; Wabbijn, Marike; de Jongh, Felix

    2016-01-01

    Oncogenic osteomalacia (or tumour-induced osteomalacia) is a rare paraneoplastic syndrome caused by overproduction of fibroblastic growth factor 23 (FGF-23) by tumours. Excessive production of FGF-23 can lead to severe, symptomatic hypophosphataemia. The majority of cases have been associated with benign tumours of bone or soft tissue, such as haemangiopericytomas or other neoplasms of mesenchymal origin. We present a case of a 68-year-old woman with an FGF-23 producing B cell non-Hodgkin's lymphoma. Treatment with immunochemotherapy resulted in normalisation of serum FGF-23 and phosphate levels. PMID:27118742

  11. 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).

  12. Pevonedistat and Ibrutinib in Treating Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2018-03-20

    B-Cell Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; Richter Syndrome

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

    ClinicalTrials.gov

    2018-06-11

    CD19 Positive; Mediastinal Lymphoma; Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma

  14. Proliferation and apoptosis in malignant and normal cells in B-cell non-Hodgkin's lymphomas.

    PubMed Central

    Stokke, T.; Holte, H.; Smedshammer, L.; Smeland, E. B.; Kaalhus, O.; Steen, H. B.

    1998-01-01

    We have examined apoptosis and proliferation in lymph node cell suspensions from patients with B-cell non-Hodgkin's lymphoma using flow cytometry. A method was developed which allowed estimation of the fractions of apoptotic cells and cells in the S-phase of the cell cycle simultaneously with tumour-characteristic light chain expression. Analysis of the tumour S-phase fraction and the tumour apoptotic fraction in lymph node cell suspensions from 95 B-cell non-Hodgkin's lymphoma (NHL) patients revealed a non-normal distribution for both parameters. The median fraction of apoptotic tumour cells was 1.1% (25 percentiles 0.5%, 2.7%). In the same samples, the median fraction of apoptotic normal cells was higher than for the tumour cells (1.9%; 25 percentiles 0.7%, 4.0%; P = 0.03). The median fraction of tumour cells in S-phase was 1.4% (25 percentiles 0.8%, 4.8%), the median fraction of normal cells in S-phase was significantly lower than for the tumour cells (1.0%; 25 percentiles 0.6%, 1.9%; P = 0.004). When the number of cases was plotted against the logarithm of the S-phase fraction of the tumour cells, a distribution with two Gaussian peaks was needed to fit the data. One peak was centred around an S-phase fraction of 0.9%; the other was centred around 7%. These peaks were separated by a valley at approximately 3%, indicating that the S-phase fraction in NHL can be classified as 'low' (< 3%) or 'high' (> 3%), independent of the median S-phase fraction. The apoptotic fractions were log-normally distributed. The median apoptotic fraction was higher (1.5%) in the 'high' S-phase group than in the 'low' S-phase group (0.8%; P = 0.02). However, there was no significant correlation between the two parameters (P > 0.05). PMID:9667654

  15. Hypophosphataemia due to FGF-23 producing B cell non-Hodgkin's lymphoma.

    PubMed

    Elderman, Jan H; Wabbijn, Marike; de Jongh, Felix

    2016-04-26

    Oncogenic osteomalacia (or tumour-induced osteomalacia) is a rare paraneoplastic syndrome caused by overproduction of fibroblastic growth factor 23 (FGF-23) by tumours. Excessive production of FGF-23 can lead to severe, symptomatic hypophosphataemia. The majority of cases have been associated with benign tumours of bone or soft tissue, such as haemangiopericytomas or other neoplasms of mesenchymal origin. We present a case of a 68-year-old woman with an FGF-23 producing B cell non-Hodgkin's lymphoma. Treatment with immunochemotherapy resulted in normalisation of serum FGF-23 and phosphate levels. 2016 BMJ Publishing Group Ltd.

  16. 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

  17. Dynamic Analysis of Human Natural Killer Cell Response at Single-Cell Resolution in B-Cell Non-Hodgkin Lymphoma.

    PubMed

    Sarkar, Saheli; Sabhachandani, Pooja; Ravi, Dashnamoorthy; Potdar, Sayalee; Purvey, Sneha; Beheshti, Afshin; Evens, Andrew M; Konry, Tania

    2017-01-01

    Natural killer (NK) cells are phenotypically and functionally diverse lymphocytes that recognize and kill cancer cells. The susceptibility of target cancer cells to NK cell-mediated cytotoxicity depends on the strength and balance of regulatory (activating/inhibitory) ligands expressed on target cell surface. We performed gene expression arrays to determine patterns of NK cell ligands associated with B-cell non-Hodgkin lymphoma (b-NHL). Microarray analyses revealed significant upregulation of a multitude of NK-activating and costimulatory ligands across varied b-NHL cell lines and primary lymphoma cells, including ULBP1, CD72, CD48, and SLAMF6. To correlate genetic signatures with functional anti-lymphoma activity, we developed a dynamic and quantitative cytotoxicity assay in an integrated microfluidic droplet generation and docking array. Individual NK cells and target lymphoma cells were co-encapsulated in picoliter-volume droplets to facilitate monitoring of transient cellular interactions and NK cell effector outcomes at single-cell level. We identified significant variability in NK-lymphoma cell contact duration, frequency, and subsequent cytolysis. Death of lymphoma cells undergoing single contact with NK cells occurred faster than cells that made multiple short contacts. NK cells also killed target cells in droplets via contact-independent mechanisms that partially relied on calcium-dependent processes and perforin secretion, but not on cytokines (interferon-γ or tumor necrosis factor-α). We extended this technique to characterize functional heterogeneity in cytolysis of primary cells from b-NHL patients. Tumor cells from two diffuse large B-cell lymphoma patients showed similar contact durations with NK cells; primary Burkitt lymphoma cells made longer contacts and were lysed at later times. We also tested the cytotoxic efficacy of NK-92, a continuously growing NK cell line being investigated as an antitumor therapy, using our droplet-based bioassay. NK

  18. 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

    2017-12-04

    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

  19. 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

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

    ClinicalTrials.gov

    2018-04-03

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

  1. 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

    2017-07-24

    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; 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

  2. Hematopoietic stem cell transplantation for non-Hodgkin lymphoma.

    PubMed

    Bhatt, Vijaya Raj; Vose, Julie M

    2014-12-01

    Up-front rituximab-based chemotherapy has improved outcomes in non-Hodgkin lymphoma (NHL); refractory or relapsed NHL still accounts for approximately 18,000 deaths in the United States. Autologous hematopoietic stem cell transplantation (SCT) can improve survival in primary refractory or relapsed aggressive NHL and mantle cell lymphoma and in relapsed follicular or peripheral T-cell lymphoma. Autologous SCT as a consolidation therapy after first complete or partial remission in high-risk aggressive NHL, mantle cell lymphoma, and peripheral T-cell lymphoma may improve progression-free survival. Allogeneic SCT offers a lower relapse rate but a higher nonrelapse mortality resulting in overall survival similar to autologous SCT. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Extranodal non-Hodgkins lymphoma of larynx.

    PubMed

    Aiyer, R G; Soni, Geeta; Chougule, Sachin; Unnikrishnan; Nagpal, Tapan

    2004-10-01

    Non-Hodgkins lymphoma is found in the older age group with extranoda involvement more commonly seen than in Hodgkins lymphomna. It isusually of B-cell type which has a better prognosis than T-cell type, Extranodal Non-Hodkin's lymphomas of larynx are rare. they can present as isolated lesions in larynx or associated with multiple involvement. They are usually found in the supraglottic region of the larynx. We present a case of 70-year-old female with extranodal Hodgkins lymphoma of epiglottis with metastasis in the liver.

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

    ClinicalTrials.gov

    2018-01-26

    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

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

    ClinicalTrials.gov

    2018-05-07

    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

  6. 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

  7. [Results of the SHOP LNHB98 (LMB89) trial in pediatric patients with B-cell non-Hodgkin's lymphoma].

    PubMed

    Forns, Marga; Javier, Germán; Estella, Jesús; Fernández-Delgado, Rafael; Gallego, Soledad; García-Miguel, Purificación; Indiano, José M; Navajas, Aurora; Pardo, Nuria

    2007-05-05

    After the good results obtained by the Société Française d'Oncologie Pédiatrique (SFOP) regarding the pediatric B-type non-Hodgkin's (Burkitt and large B-cell) lymphoma and L3 leukemia, the Sociedad Española de Hematología y Oncología Pediátricas (SHOP) decided to use the same treatment protocol. Pediatric patients diagnosed with B-type non-Hodgkin's lymphoma without a previous history of malignant diseases were eligible for this study. They were classified in 3 groups of risk: group A (resected stage I and abdominal stage II), group B (not eligible for groups A or C), and group C (with central nervous system involvement and L3 leukemia). All received treatment according to the SFOP's LMB89 protocol. A total of 153 patients were considered in this multicenter, prospective and non-randomized trial (1997-2005). The global and event-free survival (EFS) were found to be of 88% (0.88; 95% confidence interval [CI], 0.83-0.93) and 85% (0.85; 95% CI, 0.79-0.90), respectively. The EFS was 100% for the group A (n = 16), 86% (0.86; 95% CI, 0.79-0.92) for the group B (n = 113), and 68% (0.68; 95% CI, 0.49-0.86) for the group C (n = 24). The results confirm the good efficiency of the LMB89 protocol for treating B-cell lymphoma and L3 leukemia, despite having diminished the treatment intensity in the less risk groups. The worst prognostic factor was found to be a central nervous system involvement, whereas being younger than 10 years was confirmed to be a favorable prognostic factor. In addition, no differences were evidenced between Burkitt and large B-cell lymphoma.

  8. 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

  9. Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Childhood non-Hodgkin lymphoma (NHL) has three main types (aggressive mature B-cell [Burkitt, diffuse large B-cell, primary mediastinal B-cell], lymphoblastic and anaplastic large cell lymphoma) and other less common types of NHL. Get detailed information about the presentation, diagnosis, staging, prognosis, and treatment of all types of newly diagnosed and recurrent childhood NHL and lymphoproliferative disease in this summary for clinicians.

  10. 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

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

    ClinicalTrials.gov

    2018-05-18

    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

  12. 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

  13. 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

    2017-07-21

    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

  14. Atezolizumab, Gemcitabine, Oxaliplatin, and Rituximab in Treating Patients With Relapsed or Refractory Transformed Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2018-06-06

    Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Transformed Indolent Non-Hodgkin Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

  15. Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas.

    PubMed

    Friedberg, Jonathan W; Mahadevan, Daruka; Cebula, Erin; Persky, Daniel; Lossos, Izidore; Agarwal, Amit B; Jung, Jungah; Burack, Richard; Zhou, Xiaofei; Leonard, E Jane; Fingert, Howard; Danaee, Hadi; Bernstein, Steven H

    2014-01-01

    Aurora A kinase (AAK) is overexpressed in aggressive lymphomas and can correlate with more histologically aggressive forms of disease. We therefore designed a phase II study of alisertib, a selective AAK inhibitor, in patients with relapsed and refractory aggressive non-Hodgkin lymphomas. Patients age ≥ 18 years were eligible if they had relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL), transformed follicular lymphoma, Burkitt's lymphoma, or noncutaneous T-cell lymphoma. Alisertib was administered orally at 50 mg twice daily for 7 days in 21-day cycles. We enrolled 48 patients. Histologies included DLBCL (n = 21), MCL (n = 13), peripheral T-cell lymphoma (n = 8), transformed follicular lymphoma (n = 5), and Burkitt's (n = 1). Most common grade 3 to 4 adverse events were neutropenia (63%), leukopenia (54%), anemia (35%), thrombocytopenia (33%), stomatitis (15%), febrile neutropenia (13%), and fatigue (6%). Four deaths during the study were attributed to progressive non-Hodgkin lymphoma (n = 2), treatment-related sepsis (n = 1), and unknown cause (n = 1). The overall response rate was 27%, including responses in three of 21 patients with DLBCL, three of 13 with MCL, one of one with Burkitt's lymphoma, two of five with transformed follicular lymphoma, and four of eight with noncutaneous T-cell lymphoma. The alisertib steady-state trough concentration (n = 25) revealed the expected pharmacokinetic variability, with a trend for higher incidence of adverse event-related dose reductions at higher trough concentrations. Analysis for AAK gene amplification and total AAK protein revealed no differences between histologies or correlation with clinical response. The novel AAK inhibitor alisertib seems clinically active in both B- and T-cell aggressive lymphomas. On the basis of these results, confirmatory single-agent and combination studies have been initiated.

  16. Phase II Study of Alisertib, a Selective Aurora A Kinase Inhibitor, in Relapsed and Refractory Aggressive B- and T-Cell Non-Hodgkin Lymphomas

    PubMed Central

    Friedberg, Jonathan W.; Mahadevan, Daruka; Cebula, Erin; Persky, Daniel; Lossos, Izidore; Agarwal, Amit B.; Jung, JungAh; Burack, Richard; Zhou, Xiaofei; Leonard, E. Jane; Fingert, Howard; Danaee, Hadi; Bernstein, Steven H.

    2014-01-01

    Purpose Aurora A kinase (AAK) is overexpressed in aggressive lymphomas and can correlate with more histologically aggressive forms of disease. We therefore designed a phase II study of alisertib, a selective AAK inhibitor, in patients with relapsed and refractory aggressive non-Hodgkin lymphomas. Patients and Methods Patients age ≥ 18 years were eligible if they had relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL), transformed follicular lymphoma, Burkitt's lymphoma, or noncutaneous T-cell lymphoma. Alisertib was administered orally at 50 mg twice daily for 7 days in 21-day cycles. Results We enrolled 48 patients. Histologies included DLBCL (n = 21), MCL (n = 13), peripheral T-cell lymphoma (n = 8), transformed follicular lymphoma (n = 5), and Burkitt's (n = 1). Most common grade 3 to 4 adverse events were neutropenia (63%), leukopenia (54%), anemia (35%), thrombocytopenia (33%), stomatitis (15%), febrile neutropenia (13%), and fatigue (6%). Four deaths during the study were attributed to progressive non-Hodgkin lymphoma (n = 2), treatment-related sepsis (n = 1), and unknown cause (n = 1). The overall response rate was 27%, including responses in three of 21 patients with DLBCL, three of 13 with MCL, one of one with Burkitt's lymphoma, two of five with transformed follicular lymphoma, and four of eight with noncutaneous T-cell lymphoma. The alisertib steady-state trough concentration (n = 25) revealed the expected pharmacokinetic variability, with a trend for higher incidence of adverse event–related dose reductions at higher trough concentrations. Analysis for AAK gene amplification and total AAK protein revealed no differences between histologies or correlation with clinical response. Conclusion The novel AAK inhibitor alisertib seems clinically active in both B- and T-cell aggressive lymphomas. On the basis of these results, confirmatory single-agent and combination studies have been initiated. PMID:24043741

  17. 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

  18. 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

  19. 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.

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

    ClinicalTrials.gov

    2017-04-14

    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

  1. CPI-613 and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma

    ClinicalTrials.gov

    2017-12-20

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia

  2. ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells

    PubMed Central

    Talekar, Mala K; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

    2015-01-01

    ONC201/TIC10 is a small molecule initially discovered by its ability to coordinately induce and activate the TRAIL pathway selectively in tumor cells and has recently entered clinical trials in adult advanced cancers. The anti-tumor activity of ONC201 has previously been demonstrated in several preclinical models of cancer, including refractory solid tumors and a transgenic lymphoma mouse model. Based on the need for new safe and effective therapies in pediatric non-Hodgkin's lymphoma (NHL) and the non-toxic preclinical profile of ONC201, we investigated the in vitro efficacy of ONC201 in non-Hodgkin's lymphoma (NHL) cell lines to evaluate its therapeutic potential for this disease. ONC201 caused a dose-dependent reduction in the cell viability of NHL cell lines that resulted from induction of apoptosis. As expected from prior observations, induction of TRAIL and its receptor DR5 was also observed in these cell lines. Furthermore, dual induction of TRAIL and DR5 appeared to drive the observed apoptosis and TRAIL expression was correlated linearly with sub-G1 DNA content, suggesting its potential role as a biomarker of tumor response to ONC201-treated lymphoma cells. We further investigated combinations of ONC201 with approved chemotherapeutic agents used to treat lymphoma. ONC201 exhibited synergy in combination with the anti-metabolic agent cytarabine in vitro, in addition to cooperating with other therapies. Together these findings indicate that ONC201 is an effective TRAIL pathway-inducer as a monoagent that can be combined with chemotherapy to enhance therapeutic responses in pediatric NHL. PMID:26030065

  3. ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells.

    PubMed

    Talekar, Mala K; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

    2015-08-03

    ONC201/TIC10 is a small molecule initially discovered by its ability to coordinately induce and activate the TRAIL pathway selectively in tumor cells and has recently entered clinical trials in adult advanced cancers. The anti-tumor activity of ONC201 has previously been demonstrated in several preclinical models of cancer, including refractory solid tumors and a transgenic lymphoma mouse model. Based on the need for new safe and effective therapies in pediatric non-Hodgkin's lymphoma (NHL) and the non-toxic preclinical profile of ONC201, we investigated the in vitro efficacy of ONC201 in non-Hodgkin's lymphoma (NHL) cell lines to evaluate its therapeutic potential for this disease. ONC201 caused a dose-dependent reduction in the cell viability of NHL cell lines that resulted from induction of apoptosis. As expected from prior observations, induction of TRAIL and its receptor DR5 was also observed in these cell lines. Furthermore, dual induction of TRAIL and DR5 appeared to drive the observed apoptosis and TRAIL expression was correlated linearly with sub-G1 DNA content, suggesting its potential role as a biomarker of tumor response to ONC201-treated lymphoma cells. We further investigated combinations of ONC201 with approved chemotherapeutic agents used to treat lymphoma. ONC201 exhibited synergy in combination with the anti-metabolic agent cytarabine in vitro, in addition to cooperating with other therapies. Together these findings indicate that ONC201 is an effective TRAIL pathway-inducer as a monoagent that can be combined with chemotherapy to enhance therapeutic responses in pediatric NHL.

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

    PubMed

    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.

  5. Treatment Options for Childhood Non-Hodgkin Lymphoma

    MedlinePlus

    ... which malignant (cancer) cells form in the lymph system. Childhood non-Hodgkin lymphoma is a type of ... treatment for cancer and having a weakened immune system affect the risk of having childhood non-Hodgkin ...

  6. Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2015-08-05

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

  7. 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

  8. MLL duplication in a pediatric patient with B-cell lymphoblastic lymphoma.

    PubMed

    Mater, David Van; Goodman, Barbara K; Wang, Endi; Gaca, Ana M; Wechsler, Daniel S

    2012-04-01

    Lymphoblastic lymphoma is the second most common type of non-Hodgkin lymphoma seen in children. Approximately, 90% of lymphoblastic lymphomas arise from T cells, with the remaining 10% being B-cell-lineage derived. Although T-cell lymphoblastic lymphoma most frequently occurs in the anterior mediastinum (thymus), B-cell lymphoblastic lymphoma (B-LBL) predominates in extranodal sites such as skin and bone. Here, we describe a pediatric B-LBL patient who presented with extensive abdominal involvement and whose lymphoma cells displayed segmental duplication of the mixed lineage leukemia (MLL) gene. MLL duplication/amplification has been described primarily in acute myeloid leukemia and myelodysplastic syndrome with no published reports of discrete MLL duplication/amplification events in B-LBL. The MLL gene duplication noted in this case may represent a novel mechanism for tumorigenesis in B-LBL.

  9. 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

    2018-06-07

    AIDS-Related Plasmablastic Lymphoma; AIDS-Related Primary Effusion Lymphoma; CD20 Positive; HIV Infection; Plasmablastic Lymphoma; Primary Effusion Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Stage I Diffuse Large B-Cell Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage II Diffuse Large B-Cell Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage III Diffuse Large B-Cell Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Diffuse Large B-Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  10. 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

    2017-10-23

    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

  11. 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. © 2012 Japanese Cancer Association.

  12. Hematopoietic Cell Transplantation for Systemic Mature T-Cell Non-Hodgkin Lymphoma

    PubMed Central

    Smith, Sonali M.; Burns, Linda J.; van Besien, Koen; LeRademacher, Jennifer; He, Wensheng; Fenske, Timothy S.; Suzuki, Ritsuro; Hsu, Jack W.; Schouten, Harry C.; Hale, Gregory A.; Holmberg, Leona A.; Sureda, Anna; Freytes, Cesar O.; Maziarz, Richard Thomas; Inwards, David J.; Gale, Robert Peter; Gross, Thomas G.; Cairo, Mitchell S.; Costa, Luciano J.; Lazarus, Hillard M.; Wiernik, Peter H.; Maharaj, Dipnarine; Laport, Ginna G.; Montoto, Silvia; Hari, Parameswaran N.

    2013-01-01

    Purpose To analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma. Patients and Methods Outcomes of 241 patients (112 anaplastic large-cell lymphoma, 102 peripheral T-cell lymphoma not otherwise specified, 27 angioimmunoblastic T-cell lymphoma) undergoing autologous HCT (autoHCT; n = 115; median age, 43 years) or allogeneic HCT (alloHCT; n = 126; median age, 38 years) were analyzed. Primary outcomes were nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Patient, disease, and HCT-related variables were analyzed in multivariate Cox proportional hazard models to determine association with outcomes. Results AutoHCT recipients were more likely in first complete remission (CR1; 35% v 14%; P = .001) and with chemotherapy-sensitive disease (86% v 60%; P < .001), anaplastic large-cell histology (53% v 40%; P = .04), and two or fewer lines of prior therapy (65% v 44%; P < .001) compared with alloHCT recipients. Three-year PFS and OS of autoHCT recipients beyond CR1 were 42% and 53%, respectively. Among alloHCT recipients who received transplantations beyond CR1, 31% remained progression-free at 3 years, despite being more heavily pretreated and with more refractory disease. NRM was 3.5-fold higher (95% CI, 1.80 to 6.99; P < .001) for alloHCT. In multivariate analysis, chemotherapy sensitivity (hazard ratio [HR], 1.8; 95% CI, 1.16 to 2.87) and two or fewer lines of pretransplantation therapy (HR, 5.02; 95% CI, 2.15 to 11.72) were prognostic of survival. Conclusion These data describe the roles of autoHCT and alloHCT in T-cell non-Hodgkin lymphoma and suggest greater effectiveness earlier in the disease course, and limited utility in multiply relapsed disease. Notably, autoHCT at relapse may be a potential option for select patients, particularly those with anaplastic large-cell lymphoma histology. PMID:23897963

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

    ClinicalTrials.gov

    2018-02-05

    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

  14. Immunological classification of high grade non-Hodgkin's lymphomas (NHL) in children.

    PubMed

    Pituch-Noworolska, A; Miezyński, W

    1994-01-01

    The immunological classification of 28 high grade non-Hodgkin's lymphomas (NHL) in children was shown. The morphological classification was based on Working Formulation, the immunological classification--on acute lymphoblastic leukemia subtypes. The phenotypes were assayed cytofluorometrically with monoclonal antibodies and compared to ontogenic stages in B and T cell development. Small non-cleaved cell lymphoma (Burkitt's type) was seen in 13 patients, lymphoblastic lymphoma in 12 patients, low differentiated in 3 patients. Immunological classification showed B-lymphocyte origin of blast cells in 15 patients including 11 small non-cleaved Burkitt's lymphoma (mature B and cALL phenotype), 3 undifferentiated cases (pro-B and mature B cell) and 1 case of lymphoblastic lymphoma (cALL type). T-cell origin of blast cells was demonstrated in 13 patients. The immunological classification used routinely was helpful in selection of patients with unfavourable prognosis. The more precise description of blast cells was valuable for better adjustment of therapy and better prognosis.

  15. Chidamide Combined With R-GDP in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

    ClinicalTrials.gov

    2017-12-12

    Chidamide; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasm by Histology; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Cyclophosphamide; Rituximab; Gemcitabine; Cisplatin; Dexamethasone; HDAC Inhibitor

  16. Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer

    ClinicalTrials.gov

    2018-03-28

    Breast Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Nodal Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Breast Cancer AJCC v6 and v7

  17. 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.

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

    ClinicalTrials.gov

    2018-03-13

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

  19. Outcomes of autologous or allogeneic stem cell transplantation for non-Hodgkin lymphoma.

    PubMed

    Reddy, Nishitha M; Oluwole, Olalekan; Greer, John P; Engelhardt, Brian G; Jagasia, Madan H; Savani, Bipin N

    2014-01-01

    Transplant outcomes of autologous or allogeneic stem cell transplantation (SCT) have not been elucidated as a single cohort in non-Hodgkin lymphoma (NHL). We analyzed the outcomes of 270 adult recipients receiving autologous (auto) SCT (n = 198) or allogeneic (allo) SCT (n = 72) for NHL between the years 2000 and 2010. Five-year overall survival rates for B and T cell NHL were 58% and 50%, respectively (allo-SCT 51% vs. 54% for B and T-cell NHL, and auto-SCT 60% vs. 47% for B and T cell lymphoma, respectively). In multivariate analysis, the number of chemotherapy regimens and disease status pre-SCT were independently associated with long-term outcome after SCT (for both auto- and allo-SCT). We conclude that the type of transplantation offered to patients, based on patient selection and disease-related factors, can achieve long-term survival, highlighting the importance of further improvement in disease control and reducing procedure-related mortality. The role of transplantation needs to be reevaluated in the era of targeted therapy. Copyright © 2014 ISEH - Society for Hematology and Stem Cells. All rights reserved.

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

    ClinicalTrials.gov

    2018-03-02

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

  1. Lymph node non-Hodgkin's lymphoma incidentally discovered during a nephrectomy for renal cell carcinoma.

    PubMed

    Fernandez-Pello, Sergio; Rodriguez Villamil, Luis; Gonzalez Rodriguez, Ivan; Venta, Victoria; Cuervo, Javier; Menéndez, Carmen Luz

    2013-06-16

    We report the case of a left laparoscopic nephroureterectomy with the incidental discovery of a non-Hodgkin's lymphoma in one of the lymph nodes of the renal hilum. A laparoscopic nephroureterectomy was decided on for a 64-year-old man. Renal cell carcinoma in the kidney and one lymph node of the renal hilum with non-Hodgkin's lymphoma was found. Chemotherapy was not started for the lymphoma discovery. There are no signs of relapse after two years of follow up. Coexistence in the same patient is an extremely rare condition. We review the literature about this issue to clarify this association.

  2. Mature aggressive B-cell lymphoma across age groups - molecular advances and therapeutic implications.

    PubMed

    Lange, Jonas; Lenz, Georg; Burkhardt, Birgit

    2017-02-01

    Mature B-cell lymphoma represents the most common type of Non-Hodgkin lymphoma, and different subtypes prevail at different patient ages. Areas covered: We review recent data on differences and commonalities in mature B-cell lymphoma occurring in adult and pediatric patients, with a special emphasis on molecular advances and therapeutic implications. To this end, we will discuss knowledge on diffuse large B-cell lymphoma and Burkitt lymphoma/leukemia, which are the most frequent subtypes in adult and pediatric patients, respectively, and on primary mediastinal B-cell lymphoma, which is a subtype of mature B-cell lymphoma occurring mainly in adolescents and young adults with a female predominance. Expert commentary: Molecular profiling has revealed molecular alterations that can be used to further classify the subtypes of mature B-cell lymphoma. These new subgroups frequently respond differentially to targeted therapeutic strategies. Future clinical trials utilizing new drugs will address this issue by combining clinical data and response assessment with a molecular workup of the corresponding lymphomas.

  3. Identification of Highly Methylated Genes across Various Types of B-Cell Non-Hodgkin Lymphoma

    PubMed Central

    Bethge, Nicole; Honne, Hilde; Hilden, Vera; Trøen, Gunhild; Eknæs, Mette; Liestøl, Knut; Holte, Harald; Delabie, Jan; Smeland, Erlend B.; Lind, Guro E.

    2013-01-01

    Epigenetic alterations of gene expression are important in the development of cancer. In this study, we identified genes which are epigenetically altered in major lymphoma types. We used DNA microarray technology to assess changes in gene expression after treatment of 11 lymphoma cell lines with epigenetic drugs. We identified 233 genes with upregulated expression in treated cell lines and with downregulated expression in B-cell lymphoma patient samples (n = 480) when compared to normal B cells (n = 5). The top 30 genes were further analyzed by methylation specific PCR (MSP) in 18 lymphoma cell lines. Seven of the genes were methylated in more than 70% of the cell lines and were further subjected to quantitative MSP in 37 B-cell lymphoma patient samples (diffuse large B-cell lymphoma (activated B-cell like and germinal center B-cell like subtypes), follicular lymphoma and Burkitt`s lymphoma) and normal B lymphocytes from 10 healthy donors. The promoters of DSP, FZD8, KCNH2, and PPP1R14A were methylated in 28%, 67%, 22%, and 78% of the 36 tumor samples, respectively, but not in control samples. Validation using a second series of healthy donor controls (n = 42; normal B cells, peripheral blood mononuclear cells, bone marrow, tonsils and follicular hyperplasia) and fresh-frozen lymphoma biopsies (n = 25), confirmed the results. The DNA methylation biomarker panel consisting of DSP, FZD8, KCNH2, and PPP1R14A was positive in 89% (54/61) of all lymphomas. Receiver operating characteristic analysis to determine the discriminative power between lymphoma and healthy control samples showed a c-statistic of 0.96, indicating a possible role for the biomarker panel in monitoring of lymphoma patients. PMID:24260260

  4. Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

    PubMed Central

    Morton, Lindsay M.; Slager, Susan L.; Cerhan, James R.; Wang, Sophia S.; Vajdic, Claire M.; Skibola, Christine F.; Bracci, Paige M.; de Sanjosé, Silvia; Smedby, Karin E.; Chiu, Brian C. H.; Zhang, Yawei; Mbulaiteye, Sam M.; Monnereau, Alain; Turner, Jennifer J.; Clavel, Jacqueline; Adami, Hans-Olov; Chang, Ellen T.; Glimelius, Bengt; Hjalgrim, Henrik; Melbye, Mads; Crosignani, Paolo; di Lollo, Simonetta; Miligi, Lucia; Nanni, Oriana; Ramazzotti, Valerio; Rodella, Stefania; Costantini, Adele Seniori; Stagnaro, Emanuele; Tumino, Rosario; Vindigni, Carla; Vineis, Paolo; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Cocco, Pierluigi; Foretova, Lenka; Maynadié, Marc; Nieters, Alexandra; Staines, Anthony; Colt, Joanne S.; Cozen, Wendy; Davis, Scott; de Roos, Anneclaire J.; Hartge, Patricia; Rothman, Nathaniel; Severson, Richard K.; Holly, Elizabeth A.; Call, Timothy G.; Feldman, Andrew L.; Habermann, Thomas M.; Liebow, Mark; Blair, Aaron; Cantor, Kenneth P.; Kane, Eleanor V.; Lightfoot, Tracy; Roman, Eve; Smith, Alex; Brooks-Wilson, Angela; Connors, Joseph M.; Gascoyne, Randy D.; Spinelli, John J.; Armstrong, Bruce K.; Kricker, Anne; Holford, Theodore R.; Lan, Qing; Zheng, Tongzhang; Orsi, Laurent; Dal Maso, Luigino; Franceschi, Silvia; La Vecchia, Carlo; Negri, Eva; Serraino, Diego; Bernstein, Leslie; Levine, Alexandra; Friedberg, Jonathan W.; Kelly, Jennifer L.; Berndt, Sonja I.; Birmann, Brenda M.; Clarke, Christina A.; Flowers, Christopher R.; Foran, James M.; Kadin, Marshall E.; Paltiel, Ora; Weisenburger, Dennis D.; Linet, Martha S.; Sampson, Joshua N.

    2014-01-01

    Background Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes. Methods We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case–control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE). Results Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10−4), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10−4). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a

  5. Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

    ClinicalTrials.gov

    2017-12-05

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

  6. B cell lymphoma with lung involvement: what is it about?

    PubMed

    Mian, Michael; Wasle, Ines; Gritsch, Stefan; Willenbacher, Wolfgang; Fiegl, Michael

    2015-01-01

    Primary lymphoma of the lung or pleural is a very rare condition. Due to the outdated literature data, the approximate occurrence of primary and secondary lung and/or pleural involvement according to the most common B cell lymphoma entities is unknown. To answer this open question in Austria, we screened the Tyrolean registry for B cell non-Hodgkin's lymphomas regarding primary and secondary lung involvement. Of 854 patients affected by B cell lymphoma, 7.5% had lung/pleural disease. This organ was the primary site in only 0.7%, while a secondary involvement was registered in 6.8%. Most of them were affected by diffuse large B cell lymphoma (DLBCL; 29/368, 8%) followed by follicular lymphoma (7/188, 4%), mantle cell lymphoma (7/57, 12%), mucosa-associated tissue lymphoma (10/37, 27%), posttransplant lymphoproliferative disease (6/24, 25%), Burkitt lymphoma (3/19, 16%), other lymphomas (1/32, 3%) and Richter transformation (1/11, 9%). Moreover, primary lung/pleural lymphoma is one of the rarest neoplasias affecting the lung, accounting for only 0.4% of cases. Lung/pleural involvement is a very rare condition among B cell lymphomas since it mainly occurs in the setting of a generalized disease. A large majority of patients with secondary organ involvement are affected by DLBCL and have similar clinical features at diagnosis to others with advanced-stage disease. © 2014 S. Karger AG, Basel.

  7. MicroRNA signatures in B-cell lymphomas

    PubMed Central

    Di Lisio, L; Sánchez-Beato, M; Gómez-López, G; Rodríguez, M E; Montes-Moreno, S; Mollejo, M; Menárguez, J; Martínez, M A; Alves, F J; Pisano, D G; Piris, M A; Martínez, N

    2012-01-01

    Accurate lymphoma diagnosis, prognosis and therapy still require additional markers. We explore the potential relevance of microRNA (miRNA) expression in a large series that included all major B-cell non-Hodgkin lymphoma (NHL) types. The data generated were also used to identify miRNAs differentially expressed in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) samples. A series of 147 NHL samples and 15 controls were hybridized on a human miRNA one-color platform containing probes for 470 human miRNAs. Each lymphoma type was compared against the entire set of NHLs. BL was also directly compared with DLBCL, and 43 preselected miRNAs were analyzed in a new series of routinely processed samples of 28 BLs and 43 DLBCLs using quantitative reverse transcription-polymerase chain reaction. A signature of 128 miRNAs enabled the characterization of lymphoma neoplasms, reflecting the lymphoma type, cell of origin and/or discrete oncogene alterations. Comparative analysis of BL and DLBCL yielded 19 differentially expressed miRNAs, which were confirmed in a second confirmation series of 71 paraffin-embedded samples. The set of differentially expressed miRNAs found here expands the range of potential diagnostic markers for lymphoma diagnosis, especially when differential diagnosis of BL and DLBCL is required. PMID:22829247

  8. Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma.

    PubMed

    Jain, Michael D; Bachmeier, Christina A; Phuoc, Vania H; Chavez, Julio C

    2018-01-01

    Adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin's lymphomas including diffuse large B-cell lymphoma and its variants. The ZUMA-1 Phase I and II clinical trials formed the basis of the US Food and Drug Administration approval of this product, and we discuss the particulars of the clinical trials and the pharmacology of axi-cel. In addition, we review the CD19 chimeric antigen receptor T-specific toxicities of cytokine release syndrome and neurotoxicity, which remain the challenges to the safe delivery of this important therapy for aggressive B-cell lymphomas with poor prognosis.

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

    ClinicalTrials.gov

    2018-04-02

    BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; High-Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; MYC Gene Rearrangement; 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

  10. 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

  11. Acute inflammatory neuropathy with monoclonal anti-GM2 IgM antibodies, IgM-κ paraprotein and additional autoimmune processes in association with a diffuse large B-cell non-Hodgkin's lymphoma.

    PubMed

    Milnik, Annette; Roggenbuck, Dirk; Conrad, Karsten; Bartels, Claudius

    2013-01-21

    Lymphoproliferative disorders are often associated with autoimmune processes preceding or following the occurrence of a lymphoma. Here, we describe a patient with a history of recurrent diffuse large B-cell non-Hodgkin's lymphoma who suffered from an acute inflammatory neuropathy with specific monoclonal anti-GM2 IgM antibodies and associated IgM-κ paraprotein. It was possible in this case to prove that both, anti-GM2 IgM antibodies and IgM-κ paraprotein, share the same binding characteristic. In addition, the patient possibly suffered from an immune thrombocytopenia and an early-stage bullous pemphigoid with anti-BP-230 IgG antibodies. Intravenous immunoglobulin and plasmapheresis alleviated the acute neuropathy and thrombocytopenia, while the bullous pemphigoid has been aggravated. In summary, the simultaneous occurrence of multiple autoimmune processes was a sign of a dysfunctional immune system preceding the relapse of a B-cell non-Hodgkin's 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. 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

  14. Adult Non-Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Non-Hodgkin lymphoma treatment options include chemotherapy, radiation, targeted therapy, plasmapheresis, surveillance, stem cell transplant, and surgery. Get comprehensive information on Non-Hodgkin classification and treatment in this clinician summary.

  15. A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study.

    PubMed

    Fenske, Timothy S; Shah, Namrata M; Kim, Kyung Mann; Saha, Sandeep; Zhang, Chong; Baim, Arielle E; Farnen, John P; Onitilo, Adedayo A; Blank, Jules H; Ahuja, Harish; Wassenaar, Tim; Qamar, Rubina; Mansky, Patrick; Traynor, Anne M; Mattison, Ryan J; Kahl, Brad S

    2015-10-01

    Proteasome inhibitors and mammalian target of rapamycin inhibitors each have activity in various B-cell malignancies and affect distinct cellular pathways. Their combination has demonstrated synergy in vitro and in mouse models. The authors conducted a single-arm, phase 2 trial of combined temsirolimus and bortezomib in patients with relapsed and refractory B-cell non-Hodgkin lymphoma (NHL) using a dosing scheme that was previously tested in multiple myeloma. The patients received bortezomib and temsirolimus weekly on days 1, 8, 15, and 22 of a 35-day cycle. Of 39 patients who received treatment, 3 achieved a complete response (7.7%; 95% confidence interval [CI], 1.6%-21%), and 9 had a partial response (PR) (23%; 95% CI, 11%-39%). Thus, the overall response rate (12 of 39 patients) was 31% (95% CI, 17%-48%), and the median progression-free survival was 4.7 months (95% CI, 2.1-7.8 months; 2 months for patients with diffuse large B-cell lymphoma [n = 18], 7.5 months for those with mantle cell lymphoma [n = 7], and 16.5 months for those with follicular lymphoma [n = 9]). Two extensively treated patients with diffuse large B-cell lymphoma achieved a complete response. There were no unexpected toxicities from the combination. The current results demonstrate that the combination of a mammalian target of rapamycin inhibitor and a proteasome inhibitor is safe and has activity in patients with heavily pretreated B-cell NHL. Further studies with this combination are warranted in specific subtypes of NHL. © 2015 American Cancer Society.

  16. General Information about Adult Non-Hodgkin Lymphoma

    MedlinePlus

    ... Non-Hodgkin Lymphoma Treatment (PDQ®)–Patient Version General Information About Adult Non-Hodgkin Lymphoma Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  17. General Information about Childhood Non-Hodgkin Lymphoma

    MedlinePlus

    ... Non-Hodgkin Lymphoma Treatment (PDQ®)–Patient Version General Information About Childhood Non-Hodgkin Lymphoma Go to Health ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  18. 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

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

    ClinicalTrials.gov

    2018-05-25

    Follicular T-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Angioimmunoblastic T-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage IB Mycosis Fungoides AJCC v7; Stage II Mycosis Fungoides AJCC v7; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides AJCC v7; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides AJCC v7

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

    ClinicalTrials.gov

    2015-12-03

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

  1. EZH2 and CD79B mutational status over time in B-cell non-Hodgkin lymphomas detected by high-throughput sequencing using minimal samples

    PubMed Central

    Saieg, Mauro Ajaj; Geddie, William R; Boerner, Scott L; Bailey, Denis; Crump, Michael; da Cunha Santos, Gilda

    2013-01-01

    BACKGROUND: Numerous genomic abnormalities in B-cell non-Hodgkin lymphomas (NHLs) have been revealed by novel high-throughput technologies, including recurrent mutations in EZH2 (enhancer of zeste homolog 2) and CD79B (B cell antigen receptor complex-associated protein beta chain) genes. This study sought to determine the evolution of the mutational status of EZH2 and CD79B over time in different samples from the same patient in a cohort of B-cell NHLs, through use of a customized multiplex mutation assay. METHODS: DNA that was extracted from cytological material stored on FTA cards as well as from additional specimens, including archived frozen and formalin-fixed histological specimens, archived stained smears, and cytospin preparations, were submitted to a multiplex mutation assay specifically designed for the detection of point mutations involving EZH2 and CD79B, using MassARRAY spectrometry followed by Sanger sequencing. RESULTS: All 121 samples from 80 B-cell NHL cases were successfully analyzed. Mutations in EZH2 (Y646) and CD79B (Y196) were detected in 13.2% and 8% of the samples, respectively, almost exclusively in follicular lymphomas and diffuse large B-cell lymphomas. In one-third of the positive cases, a wild type was detected in a different sample from the same patient during follow-up. CONCLUSIONS: Testing multiple minimal tissue samples using a high-throughput multiplex platform exponentially increases tissue availability for molecular analysis and might facilitate future studies of tumor progression and the related molecular events. Mutational status of EZH2 and CD79B may vary in B-cell NHL samples over time and support the concept that individualized therapy should be based on molecular findings at the time of treatment, rather than on results obtained from previous specimens. Cancer (Cancer Cytopathol) 2013;121:377–386. © 2013 American Cancer Society. PMID:23361872

  2. Adult Non-Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Non-Hodgkin lymphomas (NHL) include indolent types (follicular lymphoma, Waldenstrom macroglobulinemia, and MALT) and aggressive types (diffuse large cell, Burkitt, and mantle cell). Treatment and prognosis depend on the specific type. Get comprehensive information on NHL classification and treatment in this clinician summary.

  3. Creation of a pediatric mature B-cell non-Hodgkin lymphoma cohort within the Pediatric Health Information System Database.

    PubMed

    Citrin, Rebecca; Horowitz, Joseph P; Reilly, Anne F; Li, Yimei; Huang, Yuan-Shung; Getz, Kelly D; Seif, Alix E; Fisher, Brian T; Aplenc, Richard

    2017-01-01

    Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a collection of relatively rare pediatric malignancies. In order to utilize administrative data to perform large-scale epidemiologic studies within this population, a two-step process was used to assemble a 12-year cohort of B-NHL patients treated between 2004 and 2015 within the Pediatric Health Information System database. Patients were identified by ICD-9 codes, and their chemotherapy data were then manually reviewed against standard B-NHL treatment regimens. A total of 1,409 patients were eligible for cohort inclusion. This process was validated at a single center, utilizing both an institutional tumor registry and medical record review as the gold standards. The validation demonstrated appropriate sensitivity (91.5%) and positive predictive value (95.1%) to allow for the future use of this cohort for epidemiologic and comparative effectiveness research.

  4. Small bowel intussusception due to a primary non-Hodgkin's lymphoma. An unusual presentation and clinical course.

    PubMed

    Salemis, Nikolaos S; Tsiambas, Evangelos; Liatsos, Christos; Karameris, Andreas; Tsohataridis, Efstathios

    2010-12-01

    Adult intussusception is a rare clinical entity accounting for 5% of all intussusceptions. Symptoms and signs are often vague and non-specific making a preoperative diagnosis difficult. The purpose of this study is to present a rare case of a jejuno-jejunal intussusception due to primary intestinal non-Hodgkin's lymphoma in a patient with an unusual clinical course. A 78-year-old man presented with a 1-month history of abdominal pain, nausea, epigastric fullness, and weight loss. Computed tomography scan and ultrasonography findings were suggestive of small bowel intussusception. Laparotomy revealed a jejuno-jejunal intussusception caused by a primary B cell non-Hodgkin's lymphoma 20 cm distal to the ligament of Treitz. Resection without prior reduction was performed. The patient refused postoperative adjuvant chemotherapy. Seven months later, he presented with upper gastrointestinal bleeding, and the diagnostic evaluation revealed gastric infiltration of large B cell non-Hodgkin's lymphoma. Despite chemotherapy, he died of disseminated progressive disease 7 months later. Adult jejuno-jejunal intussusception due to primary non-Hodgkin's lymphoma is a rare clinical entity. A high index of suspicion is needed as symptoms and signs are not pathognomonic. Appropriate investigations can lead to a prompt preoperative diagnosis. Resection without prior reduction is the treatment of choice. Our patient's refusal of postoperative adjuvant chemotherapy likely resulted in relapse of the disease in another part of the gastrointestinal tract.

  5. 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

  6. Dysregulation of fatty acid synthesis and glycolysis in non-Hodgkin lymphoma

    PubMed Central

    Bhatt, Aadra P.; Jacobs, Sarah R.; Freemerman, Alex J.; Makowski, Liza; Rathmell, Jeffrey C.; Dittmer, Dirk P.; Damania, Blossom

    2012-01-01

    The metabolic differences between B-NHL and primary human B cells are poorly understood. Among human B-cell non-Hodgkin lymphomas (B-NHL), primary effusion lymphoma (PEL) is a unique subset that is linked to infection with Kaposi's sarcoma-associated herpesvirus (KSHV). We report that the metabolic profiles of primary B cells are significantly different from that of PEL. Compared with primary B cells, both aerobic glycolysis and fatty acid synthesis (FAS) are up-regulated in PEL and other types of nonviral B-NHL. We found that aerobic glycolysis and FAS occur in a PI3K-dependent manner and appear to be interdependent. PEL overexpress the fatty acid synthesizing enzyme, FASN, and both PEL and other B-NHL were much more sensitive to the FAS inhibitor, C75, than primary B cells. Our findings suggest that FASN may be a unique candidate for molecular targeted therapy against PEL and other B-NHL. PMID:22752304

  7. Radioimmunotherapy for treatment of B-cell lymphomas and other hematologic malignancies.

    PubMed

    Park, Steven I; Press, Oliver W

    2007-11-01

    Radioimmunotherapy has emerged as one of the most promising treatment options for hematologic malignancies. This review will present the latest information on radioimmunotherapy for treatment of hematologic malignancies in various clinical settings and assess its long-term safety profile. Recent data suggest that radioimmunotherapy with 131I-tositumomab or 90Y-ibritumomab tiuxetan not only induces high response rates but also results in durable remissions in patients with relapsed or refractory indolent non-Hodgkin's lymphomas. Even more notable response rates have been observed when radioimmunotherapy is used as front-line treatment in patients with indolent non-Hodgkin's lymphomas. The use of radioimmunotherapy has been evaluated in the treatment of aggressive lymphomas with promising results, but it remains investigational. Standard doses of radioimmunotherapy given as a conditioning regimen for hematopoietic stem-cell transplant or myeloablative doses of radioimmunotherapy given in conjunction with stem-cell support have yielded encouraging outcomes with durable remissions and a low incidence of treatment-related mortality. The safety and efficacy of radioimmunotherapy has been demonstrated for patients with B-cell lymphomas and other hematologic malignancies in various clinical settings. A number of randomized phase III clinical trials are currently underway to further define radioimmunotherapy's role in the treatment of lymphomas.

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

    ClinicalTrials.gov

    2014-05-07

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

  9. Non-Hodgkin lymphoma in Romania: a single-centre experience.

    PubMed

    Fetica, Bogdan; Achimas-Cadariu, Patriciu; Pop, Bogdan; Dima, Delia; Petrov, Ljubomir; Perry, Anamarija M; Nathwani, Bharat N; Müller-Hermelink, Hans K; Diebold, Jacques; MacLennan, Kenneth A; Fulop, Annamaria; Blaga, Mihaiela L; Coza, Daniela; Nicula, Florian Al; Irimie, Alexandru; Weisenburger, Dennis D

    2017-06-01

    Epidemiologic studies of non-Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the "Ion Chiricuta" Institute of Oncology in Cluj-Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004-2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B-cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T-cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male-to-female ratio of 0.94. Patients with indolent B-cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age-standardized incidence rate/100 000 (ASR)-5.9; 95% CI 5.1-6.6] than in women (ASR-4.1; 95% CI 3.5-4.7) with age-standardized male-to-female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B-cell lymphoma (36%). The 5-year, age-standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006-2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Bovine lactoferricin induces caspase-independent apoptosis in human B-lymphoma cells and extends the survival of immune-deficient mice bearing B-lymphoma xenografts.

    PubMed

    Furlong, Suzanne J; Mader, Jamie S; Hoskin, David W

    2010-06-01

    Although current treatments based on the use of B-cell-specific anti-CD20 monoclonal antibodies and aggressive combinatorial chemotherapy have improved the survival of patients suffering from B-cell non-Hodgkin's lymphoma (NHL), some individuals fail to respond to treatment and relapses remain common. New and more effective treatments for B-cell NHL are therefore required. Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that is cytotoxic for several human tumor cell lines but does not harm healthy cells. Here we show that in vitro treatment with LfcinB caused Raji and Ramos human B-lymphoma cells to die by apoptosis, as indicated by DNA fragmentation, chromatin condensation, and nuclear disintegration. LfcinB killed B-lymphoma cells more efficiently at low serum concentrations and was inhibited in the presence of exogenous bovine serum albumin, suggesting partial neutralization of cationic LfcinB by anionic serum components. LfcinB-induced apoptosis in B-lymphoma cells was caspase-independent since caspase-3 activation was not detected by Western blotting and the general caspase inhibitor z-VAD-fmk did not prevent LfcinB-induced DNA fragmentation. Importantly, immune-deficient SCID/beige mice that were inoculated intravenously with Ramos B-lymphoma cells in order to model B-cell NHL exhibited extended survival following systemic administration of LfcinB, indicating that LfcinB warrants further investigation as a novel therapeutic agent for the possible treatment of B-cell NHL. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)—Patient Version

    Cancer.gov

    Childhood non-Hodgkin lymphoma treatment can include chemotherapy, radiation therapy, targeted therapy, and high-dose chemotherapy with stem cell transplant. Learn more in this expert-reviewed summary.

  12. A case of non-Hodgkin lymphoma in a patient with chronic myeloid leukemia.

    PubMed

    Găman, Amelia Maria; Dobrea, Camelia; Rotaru, Ionela

    2013-01-01

    Chronic myeloid leukemia is a clonal expansion of hematopoietic progenitor cells characterized by exaggerated proliferation of granulocytic lineage, with chronic phase, accelerated phase and blast crisis. Accelerated phase and blast crisis may be associated with extramedulary disease. Extramedullary transformation of CML can be determined both in nodal and extranodal sites. Non-Hodgkin lymphoma is rare in chronic myeloid leukemia and may be misdiagnosed as an extramedullary lymphoid blast transformation; the majorities are T-cell lymphomas with an immature thymic phenotype, while peripheral B-cell lymphomas are rarer. We report the case of a 79-year-old woman carrier Ph+ chronic myeloid leukemia who developed at eight months of diagnosis an accelerated phase of CML associated simultaneous with a tumor of soft palate, which was initial considering an extramedullary disease. The patient was treated with specific chemotherapy for accelerated phase of CML (Cytosinarabinoside) + Anagrelide, and reversed to secondary chronic phase of CML, but soft palate tumor persists. The immunohistochemical findings of bone marrow trephine biopsy examination showed chronic phase of CML (negativity for immature cells such as CD34, Tdt) and the biopsy of soft palate tumor and immunohistochemical findings revealed a primitive non-Hodgkin lymphoma (NHL) with medium B-cells (CD20, CD79a positive) and excluding an extramedullary blast crisis (CD34 negative, Tdt negative). Cytogenetic analysis in tumor revealed absence of Philadelphia chromosome. The patient was treated with local radiotherapy for NHL, with a favorable evolution and Hydroxyurea 1 g/day for CML with hematological remission. A localized lymphoid neoplasm may be an extramedullary localized blast crisis of CML or a distinct malignancy, with distinguished therapy and prognosis. A correct diagnosis based on a complex investigation: immunohistochemistry, conventional cytogenetic analysis and fluorescence in situ hybridization (FISH

  13. Classification of non-Hodgkin lymphoma in Algeria according to the World Health Organization classification.

    PubMed

    Boudjerra, Nadia; Perry, Anamarija M; Audouin, Josée; Diebold, Jacques; Nathwani, Bharat N; MacLennan, Kenneth A; Müller-Hermelink, Hans K; Bast, Martin; Boilesen, Eugene; Armitage, James O; Weisenburger, Dennis D

    2015-04-01

    The relative distribution of non-Hodgkin lymphoma (NHL) subtypes differs markedly around the world. The aim of this study was to report this distribution in Algeria. A panel of four hematopathologists classified 197 consecutive cases according to the World Health Organization classification, including 87.3% B-cell and 12.7% T- or natural killer (NK)-cell NHLs. This series was compared with similar cohorts from Western Europe (WEU) and North America (NA). Algeria had a significantly higher frequency of diffuse large B-cell lymphoma (DLBCL: 52.8%) and a lower frequency of follicular lymphoma (FL: 13.2%) compared with WEU (DLBCL: 32.2%; FL: 20.0%) and NA (DLBCL: 29.3%; FL: 33.6%). The frequency of mantle cell lymphoma was lower in Algeria (2.5%) compared with WEU (8.3%). Smaller differences were also found among the NK/T-cell lymphomas. In conclusion, we found important differences between Algeria and Western countries, and further epidemiologic studies are needed to explain these differences.

  14. Adult Non-Hodgkin Lymphoma Treatment (PDQ®)—Patient Version

    Cancer.gov

    Non-Hodgkin lymphoma (NHL) options include chemotherapy, radiation, targeted therapy, plasmapheresis, surveillance, stem cell transplant, and surgery. Learn more about types of NHL and treatments in this expert-reviewed summary.

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

    ClinicalTrials.gov

    2017-05-23

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

  16. Oral diffuse B-cell non-Hodgkin's lymphoma associated to Gorlin-Goltz syndrome: a case report with one year follow-up.

    PubMed

    Pereira, Cláudio M; Lopes, Ana Paula M; Meneghini, Alexandre J; Silva, Alberto F; Botelho, Tessa de L

    2011-01-01

    Nevoid cell carcinoma syndrome or Gorlin-Goltz syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinoma, multiple keratocyst tumors, and skeletal anomalies. The Gorlin-Goltz syndrome has been associated with numerous benign and malignant neoplasms. The authors describe a case of Gorlin-Goltz syndrome in association with non-Hodgkin's lymphoma. To the best of our knowledge, this is the second case described in the English literature.

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

    ClinicalTrials.gov

    2018-04-20

    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

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

    PubMed Central

    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.

    2013-01-01

    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 1521 controls and 2694 NHL cases including 710 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL), 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 (EFS) (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. PMID:23812490

  19. Brentuximab Vedotin and Lenalidomide in Treating Patients With Stage IB-IVB Relapsed or Refractory T-Cell Lymphoma

    ClinicalTrials.gov

    2018-03-19

    Lymphomatoid Papulosis; Primary Cutaneous Anaplastic Large Cell Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage I Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage II Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma

  20. CD19 chimeric antigen receptor (CD19 CAR)-redirected adoptive T-cell immunotherapy for the treatment of relapsed or refractory B-cell Non-Hodgkin's Lymphomas.

    PubMed

    Onea, Alexandra S; Jazirehi, Ali R

    2016-01-01

    Recovery rates for B-cell Non-Hodgkin's Lymphoma (NHL) are up to 70% with current standard-of-care treatments including rituximab (chimeric anti-CD20 monoclonal antibody) in combination with chemotherapy (R-CHOP). However, patients who do not respond to first-line treatment or develop resistance have a very poor prognosis. This signifies the need for the development of an optimal treatment approach for relapsed/refractory B-NHL. Novel CD19- chimeric antigen receptor (CAR) T-cell redirected immunotherapy is an attractive option for this subset of patients. Anti-CD19 CAR T-cell therapy has already had remarkable efficacy in various leukemias as well as encouraging outcomes in phase I clinical trials of relapsed/refractory NHL. In going forward with additional clinical trials, complementary treatments that may circumvent potential resistance mechanisms should be used alongside anti-CD19 T-cells in order to prevent relapse with resistant strains of disease. Some such supplementary tactics include conditioning with lymphodepletion agents, sensitizing with kinase inhibitors and Bcl-2 inhibitors, enhancing function with multispecific CAR T-cells and CD40 ligand-expressing CAR T-cells, and safeguarding with lymphoma stem cell-targeted treatments. A therapy regimen involving anti-CD19 CAR T-cells and one or more auxiliary treatments could dramatically improve prognoses for patients with relapsed/refractory B-cell NHL. This approach has the potential to revolutionize B-NHL salvage therapy in much the same way rituximab did for first-line treatments.

  1. B cell-stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B cell lymphoma

    PubMed Central

    Breen, Elizabeth Crabb; Hussain, Shehnaz K.; Magpantay, Larry; Jacobson, Lisa P.; Detels, Roger; Rabkin, Charles S.; Kaslow, Richard A.; Variakojis, Daina; Bream, Jay H.; Rinaldo, Charles R.; Ambinder, Richard F.; Martínez-Maza, Otoniel

    2011-01-01

    Background The risk of developing non-Hodgkin lymphoma (NHL) is greatly increased in HIV infection. The aim of this study was to determine if elevated serum levels of molecules associated with B cell activation precede the diagnosis of AIDS-associated NHL. Methods Serum levels of B cell activation-associated molecules, interleukin-6 (IL6), interleukin-10 (IL10), soluble CD23 (sCD23), soluble CD27 (sCD27), soluble CD30 (sCD30), C-reactive protein (CRP), and IgE were determined in 179 NHL cases and HIV+ controls in the Multicenter AIDS Cohort Study, collected at up to three time points per subject, 0–5 years prior to AIDS-NHL diagnosis. Results Serum IL6, IL10, CRP, sCD23, sCD27, and sCD30 levels were all significantly elevated in the AIDS-NHL group, when compared to HIV+ controls or to AIDS controls, after adjusting for CD4 T cell number. Elevated serum levels of B cell activation-associated molecules were seen to be associated with the development of systemic (non-CNS) NHL, but not with the development of primary CNS lymphoma. Conclusions Levels of certain B cell stimulatory cytokines and molecules associated with immune activation are elevated for several years preceding the diagnosis of systemic AIDS-NHL. This observation is consistent with the hypothesis that chronic B cell activation contributes to the development of these hematologic malignancies. Impact Marked differences in serum levels of several molecules are seen for several years pre-diagnosis in those who eventually develop AIDS-NHL. Some of these molecules may serve as candidate biomarkers and provide valuable information to better define the etiology of NHL. PMID:21527584

  2. Venetoclax Synergizes with Radiotherapy for Treatment of B-cell Lymphomas.

    PubMed

    O'Steen, Shyril; Green, Damian J; Gopal, Ajay K; Orozco, Johnnie J; Kenoyer, Aimee L; Lin, Yukang; Wilbur, D Scott; Hamlin, Donald K; Fisher, Darrell R; Hylarides, Mark D; Gooley, Theodore A; Waltman, Amelia; Till, Brian G; Press, Oliver W

    2017-07-15

    Constitutive B-cell receptor signaling leads to overexpression of the antiapoptotic BCL-2 protein and is implicated in the pathogenesis of many types of B-cell non-Hodgkin lymphoma (B-NHL). The BCL-2 small-molecule inhibitor venetoclax shows promising clinical response rates in several lymphomas, but is not curative as monotherapy. Radiotherapy is a rational candidate for combining with BCL-2 inhibition, as DNA damage caused by radiotherapy increases the activity of pro-apoptotic BCL-2 pathway proteins, and lymphomas are exquisitely sensitive to radiation. We tested B-NHL responses to venetoclax combined with either external beam radiotherapy or radioimmunotherapy (RIT), which joins the selectivity of antibody targeting with the effectiveness of irradiation. We first tested cytotoxicity of cesium-137 irradiation plus venetoclax in 14 B-NHL cell lines representing five lymphoma subtypes. Combination treatment synergistically increased cell death in 10 of 14 lines. Lack of synergy was predicted by resistance to single-agent venetoclax and high BCL-XL expression. We then assessed the efficacy of external beam radiotherapy plus venetoclax in murine xenograft models of mantle cell (MCL), germinal-center diffuse large B-cell (GCB-DLBCL), and activated B-cell (ABC-DLBCL) lymphomas. In each model, external beam radiotherapy plus venetoclax synergistically increased mouse survival time, curing up to 10%. We finally combined venetoclax treatment of MCL and ABC-DLBCL xenografts with a pretargeted RIT (PRIT) system directed against the CD20 antigen. Optimal dosing of PRIT plus venetoclax cured 100% of mice with no detectable toxicity. Venetoclax combined with radiotherapy may be a promising treatment for a wide range of lymphomas Cancer Res; 77(14); 3885-93. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma

    ClinicalTrials.gov

    2018-01-05

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; 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; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

  4. A case of primary osseous malignant immunoblastic B-cell lymphoma with intracytoplasmic mu lambda immunoglobulin inclusions.

    PubMed

    Fiche, M; Le Tourneau, A; Audouin, J; Touzard, R C; Diebold, J

    1990-02-01

    Primary malignant lymphoma of bone, so-called Parker-Jackson reticulosarcoma, is a rare form of extranodal lymphoma with a relatively good prognosis. It often corresponds to B-cell lymphoma of high-grade malignancy. We report a case of mu lambda immunoblastic lymphoma showing two distinctive features: an abundant reactive T-lymphocytic population and unusual intra-cytoplasmic inclusions. These inclusions were PAS positive and consisted of monotypic mu lambda immunoglobulin localized in peculiar aggregates of rough endoplasmic reticulum. Their morphological appearances resembled the well-documented inclusions described in some varieties of non-Hodgkin's lymphoma.

  5. Interleukin 21 - its potential role in the therapy of B-cell lymphomas.

    PubMed

    Bhatt, Shruti; Sarosiek, Kristopher A; Lossos, Izidore S

    2017-01-01

    Interleukin-21 (IL-21), a member of IL-2 cytokine family, has pleotropic biological effects on lymphoid and myeloid cells. During the past 15 years, since the discovery of IL-21, great advances have been made regarding its biological activity and the mechanisms controlling IL-21-mediated cellular responses, especially in hematological malignancies. Preclinical studies have shown that IL-21R is expressed on healthy and neoplastic B-cells and exogenous IL-21 can induce direct apoptosis of IL-21R expressing B-cell non-Hodgkin lymphomas (NHL), making it a potentially attractive anti-lymphoma therapy. However, in some hematological malignancies such as multiple myeloma, Hodgkin lymphoma and Burkitt lymphoma, IL-21 can induce proliferation of neoplastic B-cells. In NHL, the underlying mechanism of cell death was found to be different between the various subtypes, including activation of different JAK/STAT signal transduction pathways or other factors. Immunomodulatory effects of IL-21 have also been reported to contribute to its anti-tumor effects as described by earlier studies in solid tumors and B-cell associated malignancies. These effects are predominantly mediated by IL-21's ability to activate cytolytic activities by NK-cells and CD4 + /CD8 + T-cells. In this review, we provide an overview of IL-21's effects in NHL, results from clinical trials utilizing IL-21, and propose how IL-21 can be therapeutically exploited for treating these lymphomas.

  6. Medical history, lifestyle, family history, and occupational risk factors for diffuse large B-cell lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

    PubMed

    Cerhan, James R; Kricker, Anne; Paltiel, Ora; Flowers, Christopher R; Wang, Sophia S; Monnereau, Alain; Blair, Aaron; Dal Maso, Luigino; 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

    2014-08-01

    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. 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. 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/m(2)), 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/m(2)), 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 >400 kg 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; inflammatory bowel

  7. 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

  8. Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy.

    PubMed

    Porpaczy, Edit; Tripolt, Sabrina; Hoelbl-Kovacic, Andrea; Gisslinger, Bettina; Bago-Horvath, Zsuzsanna; Casanova-Hevia, Emilio; Clappier, Emmanuelle; Decker, Thomas; Fajmann, Sabine; Fux, Daniela A; Greiner, Georg; Gueltekin, Sinan; Heller, Gerwin; Herkner, Harald; Hoermann, Gregor; Kiladjian, Jean-Jacques; Kolbe, Thomas; Kornauth, Christoph; Krauth, Maria-Theresa; Kralovics, Robert; Muellauer, Leonhard; Mueller, Mathias; Prchal-Murphy, Michaela; Putz, Eva Maria; Raffoux, Emmanuel; Schiefer, Ana-Iris; Schmetterer, Klaus; Schneckenleithner, Christine; Simonitsch-Klupp, Ingrid; Skrabs, Cathrin; Sperr, Wolfgang R; Staber, Philipp Bernhard; Strobl, Birgit; Valent, Peter; Jaeger, Ulrich; Gisslinger, Heinz; Sexl, Veronika

    2018-06-14

    Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 MPN patients including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4/69 patients (5.8%) upon JAK1/2 inhibition compared to 2/557 (0.36%) with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 MPN patients. Considering primary myelofibrosis only (N=216), 3 lymphomas were observed in 31 inhibitor-treated patients (9.7%) versus 1/185 controls (0.54%). Lymphomas were of aggressive B-cell type, extra-nodal or leukemic with high MYC expression in the absence of JAK2 V617F or other MPN-associated mutations. Median time from initiation of inhibitor therapy to lymphoma diagnosis was 25 months. Clonal immunoglobulin gene rearrangements were already detected in the bone marrow during myelofibrosis in 16.3% of patients. Lymphomas occurring during JAK1/2 inhibitor treatment were preceded by a pre-existing B-cell clone in all 3 patients tested. Sequencing verified clonal identity in 2 patients. The effects of JAK1/2 inhibition were mirrored in Stat1 -/- mice: 16/24 mice developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells. Transplantations of bone marrow from diseased mice unmasked the outgrowth of a malignant B-cell clone evolving into aggressive B-cell leukemia-lymphoma. We conclude that JAK/STAT1 pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. Detection of a pre-existing B-cell clone may identify individuals at risk. Copyright © 2018 American Society of Hematology.

  9. Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

    ClinicalTrials.gov

    2018-02-12

    Prolymphocytic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  10. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study.

    PubMed

    Advani, Anjali; Coiffier, Bertrand; Czuczman, Myron S; Dreyling, Martin; Foran, James; Gine, Eva; Gisselbrecht, Christian; Ketterer, Nicolas; Nasta, Sunita; Rohatiner, Ama; Schmidt-Wolf, Ingo G H; Schuler, Martin; Sierra, Jorge; Smith, Mitchell R; Verhoef, Gregor; Winter, Jane N; Boni, Joseph; Vandendries, Erik; Shapiro, Mark; Fayad, Luis

    2010-04-20

    PURPOSE Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. This was a phase I study to determine the maximum-tolerated dose (MTD), safety, and preliminary efficacy of inotuzumab ozogamicin in an expanded MTD cohort of patients with relapsed or refractory CD22(+) B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Inotuzumab ozogamicin was administered intravenously as a single agent once every 3 or 4 weeks at doses ranging from 0.4 to 2.4 mg/m(2). Outcomes included MTD, safety, pharmacokinetics, response, progression-free survival (PFS), and overall survival. Results Seventy-nine patients were enrolled. The MTD was determined to be 1.8 mg/m(2). Common adverse events at the MTD were thrombocytopenia (90%), asthenia (67%), and nausea and neutropenia (51% each). The objective response rate at the end of treatment was 39% for the 79 enrolled patients, 68% for all patients with follicular NHL treated at the MTD, and 15% for all patients with diffuse large B-cell lymphoma treated at the MTD. Median PFS was 317 days (approximately 10.4 months) and 49 days for patients with follicular NHL and diffuse large B-cell lymphoma, respectively. CONCLUSION Inotuzumab ozogamicin has demonstrated efficacy against CD22(+) B-cell NHL, with reversible thrombocytopenia as the main toxicity.

  11. Development of DOTA-Rituximab to be Labeled with 90Y for Radioimmunotherapy of B-cell Non-Hodgkin Lymphoma

    PubMed Central

    Johari doha, Fariba; Rahmani, Siyavash; Rikhtechi, Pedram; Rasaneh, Samira; Sheikholislam, Zahra; Shahhosseini, Soraya

    2017-01-01

    NHL is the most common hematologic cancer in adults. Rituximab is the FDA approved treatment of relapsed or refractory low grade B-cell Non-Hodgkin Lymphoma (NHL). But patients eventually become resistant to rituximab. Since lymphocytes and lymphoma cells are highly radiosensitive, low grade NHL that has relapsed or refractory to standard therapy is treated by RIT in which a beta-emitting radionuclide coupled to anti-CD20 antibody. The association of beta emitter radionuclide to rituximab enhances its therapeutic efficacy. The cells which lack antigen or cells which cannot be reached due to poor vascularization and intratumoral pressure in a bulky tumor would be irradiated and killed by cross fire effect of beta emitter. 90Y, a pure high energy β-emitter with a half-life of 64 h, a maximum energy of 2.28 MeV, and maximum board of 11.3 mm in tissue is radionuclide of choice for radioimmunotherapy of outpatient administration. In this study, rituximab was conjugated to DOTA and radiolabeled with 90YCl3. The stability, affinity, and immunoreactivity of radiolabeled antibody was determined in vitro and the conditions were optimized. Biodistribution studies were done in normal mice. The optimum conditions of conjugation and radiolabeling was 1-2 h at 37 °C and 1 h at 45 °C, respectively. Results showed approximately 4 DOTA molecules conjugated per antibody molecule. The purified antibody was stable and intact over 6 months stored at -20 °C. The result of immunoreactivity (≈70%), affinity (≈3 nM) and biodistribution in normal mice are acceptable. PMID:28979315

  12. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.

    PubMed

    Xu-Monette, Zijun Y; Zhou, Jianfeng; Young, Ken H

    2018-01-04

    Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1 + tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials. The median duration of response was 16 months in a phase 2 trial. PD-1 blockade has also shown promise in a phase 1 trial of nivolumab in relapsed/refractory B-cell non-Hodgkin lymphomas, including follicular lymphoma, which often displays abundant PD-1 expression on intratumoral T cells, and diffuse large B-cell lymphoma, which variably expresses PD-1 and PD-L1. In primary mediastinal large B-cell lymphoma, which frequently has 9p24.1 alterations, the ORR was 35% in a phase 2 trial of pembrolizumab. In contrast, the ORR with pembrolizumab was 0% in relapsed chronic lymphocytic leukemia (CLL) and 44% in CLL with Richter transformation in a phase 2 trial. T cells from CLL patients have elevated PD-1 expression; CLL PD-1 + T cells can exhibit a pseudo-exhaustion or a replicative senescence phenotype. PD-1 expression was also found in marginal zone lymphoma but not in mantle cell lymphoma, although currently anti-PD-1 clinical trial data are not available. Mechanisms and predictive biomarkers for PD-1 blockade immunotherapy, treatment-related adverse events, hyperprogression, and combination therapies are discussed in the context of B-cell lymphomas. © 2018 by The American Society of Hematology.

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

    ClinicalTrials.gov

    2017-04-14

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

  14. 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

  15. 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. © 2015 Royal Australasian College of Physicians.

  16. Protein kinase C-beta inhibition induces apoptosis and inhibits cell cycle progression in AIDS-related Non-Hodgkin lymphoma cells

    PubMed Central

    Saba, Nakhle S.; Levy, Laura S.

    2011-01-01

    AIDS-related Non-Hodgkin Lymphoma (AIDS-NHL) constitutes an aggressive variety of lymphomas characterized by increased extranodal involvement, relapse rate and resistance to chemotherapy. PKCβ targeting showed promising results in preclinical and clinical studies involving a wide variety of cancers, but studies describing the role of PKCβ in AIDS-NHL are primitive if not lacking. In the present study, three AIDS-NHL cell lines were examined: 2F7 (AIDS-Burkitt Lymphoma), BCBL-1 (AIDS-Primary Effusion Lymphoma) and UMCL01-101 (AIDS-Diffuse Large B Cell Lymphoma). Immunoblot analysis demonstrated expression of PKCβ1 and PKCβ2 in 2F7 and UMCL01-101 cells, and PKCβ1 alone in BCBL-1 cells. The viability of 2F7 and BCBL-1 cells decreased significantly in the presence of PKCβ-selective inhibitor at IC50 of 14 μM and 15 μM, respectively, as measured by MTS assay. In contrast, UMCL01-101 cells were relatively resistant. As determined using flow cytometric TUNEL assay with propidium iodide staining, the responsiveness of sensitive cells was associated with apoptotic induction and cell cycle inhibition. PKCβ-selective inhibition was observed not to affect AKT phosphorylation, but to induce a rapid and sustained reduction in the phosphorylation of GSK3β, ribosomal protein S6, and mTOR in sensitive cell lines. The results indicate that PKCβ plays an important role in AIDS-related NHL survival, and suggest that PKCβ targeting should be considered in a broader spectrum of NHL. The observations in BCBL-1 were unexpected in the absence of PKCβ2 expression and implicate PKCβ1 as a regulator in those cells. PMID:21997316

  17. The Role of Angiogenesis in Human Non-Hodgkin Lymphomas1

    PubMed Central

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

    2013-01-01

    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. PMID:23479502

  18. PI3Kδ-selective and PI3Kα/δ-combinatorial inhibitors in clinical development for B-cell non-Hodgkin lymphoma.

    PubMed

    Lampson, Benjamin L; Brown, Jennifer R

    2017-11-01

    The efficacy of the prototypical phosphatidylinositol-3-kinase (PI3K) inhibitor idelalisib for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL) has led to development of multiple compounds targeting this pathway. Areas Covered: We review the hypothesized therapeutic mechanisms of PI3K inhibitors, including abrogation of B cell receptor signaling, blockade of microenvironmental pro-survival signals, and enhancement of anti-tumor immunity. We examine toxicities of idelalisib, including bacterial infections (possibly secondary to drug-induced neutropenia), opportunistic infections (possibly attributable to on-target inhibition of T cell function), and organ toxicities such as transaminitis and enterocolitis (possibly autoimmune, secondary to on-target inhibition of p110δ in regulatory T cells). We evaluate PI3K inhibitors that have entered trials for the treatment of lymphoma, focusing on agents with selectivity for PI3Kα and PI3Kδ. Expert Opinion: PI3K inhibitors, particularly those that target p110δ, have robust efficacy in the treatment of CLL and iNHL. However, idelalisib has infectious and autoimmune toxicities that limit its use. Outside of trials, idelalisib should be restricted to CLL patients with progression on ibrutinib or iNHL patients with progression on two prior therapies. Whether newer PI3K inhibitors will demonstrate differentiated toxicity profiles in comparable patient populations while retaining efficacy remains to be seen.

  19. Diffuse large B cell lymphoma of the mesentery: an unusual presentation and review of the literature.

    PubMed

    Salemis, Nikolaos S; Gourgiotis, Stavros; Tsiambas, Evangelos; Karagkiouzis, Grigorios; Nakos, Georgios; Karathanasis, Vasilios

    2009-01-01

    Diffuse large B cell lymphoma is the most commonly diagnosed non-Hodgkin's lymphoma, whereas lymphoma is the most common cause of mesenteric masses. We herein present a very rare case of a young male patient with a giant diffuse large B cell lymphoma of the mesentery that was incidentally diagnosed during his admission for a road traffic accident. At laparotomy, a huge tumor measuring 18 x 14 x 10 cm was found originating from the jejunal mesentery. Despite the giant size of the tumor, the patient was completely asymptomatic. After complete surgical recection with clear margins, he recieved six cycles of CHOP chemotherapy in the pre-rituximab era. He remained disease-free 2 years after surgery, but unfortunately, he relapsed with disseminated disease and died 6 months later. Mesenteric lymphomas may remain asymptomatic until they reach a large size. The presence of a bulky mesenteric mass is a poor prognostic indicator. Although chemotherapy is the treatment of choice for diffuse large B cell lymphoma, in some cases radical surgery has a role in establishing a definitive diagnosis.

  20. Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma.

    PubMed

    Battistello, Elena; Katanayeva, Natalya; Dheilly, Elie; Tavernari, Daniele; Donaldson, Maria C; Bonsignore, Luca; Thome, Margot; Christie, Amanda L; Murakami, Mark A; Michielin, Olivier; Ciriello, Giovanni; Zoete, Vincent; Oricchio, Elisa

    2018-05-24

    In diffuse large B-cell lymphoma (DLBCL), activation of the B-cell receptor (BCR) promotes multiple oncogenic signals, which are essential for tumor proliferation. Inhibition of the Bruton's tyrosine kinase (BTK), a BCR downstream target, is therapeutically effective only in a subgroup of patients with DLBCL. Here, we used lymphoma cells isolated from patients with DLBCL to measure the effects of targeted therapies on BCR signaling and to anticipate response. In lymphomas resistant to BTK inhibition, we show that blocking BTK activity enhanced tumor dependencies from alternative oncogenic signals downstream of the BCR, converging on MYC upregulation. To completely ablate the activity of the BCR, we genetically and pharmacologically repressed the activity of the SRC kinases LYN, FYN, and BLK, which are responsible for the propagation of the BCR signal. Inhibition of these kinases strongly reduced tumor growth in xenografts and cell lines derived from patients with DLBCL independent of their molecular subtype, advancing the possibility to be relevant therapeutic targets in broad and diverse groups of DLBCL patients. © 2018 by The American Society of Hematology.

  1. Capable Infection of Hepatitis B Virus in Diffuse Large B-cell Lymphoma

    PubMed Central

    Wang, Yanchun; Wang, Huijie; Pan, Shaokun; Hu, Tao; Shen, Jiabin; Zheng, Hui; Xie, Suhong; Xie, Youhua; Lu, Renquan; Guo, Lin

    2018-01-01

    Background: Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type of non-Hodgkin lymphoma (NHL). It is strongly correlated to the host immunity and infection status. Aim: This study tested the hypothesis that hepatitis B virus (HBV) infection is also associated with DLBCL. Methods: Clinical analysis of the correlation between DLBCL and HBV infection, detection of HBV in situ of DLBCL tissue, and biological experiments that determined whether HBV infects B lymphocytes were conducted. Results: Our long-term clinical data showed that the positive rate of serum HBV was significantly increased in DLBCL patients (23.6%) compared to that in the general Chinese population (7.2%, P<0.001), especially in advanced stage lymphoma patients (P=0.003). In addition, HBV could infect B lymphocytes in vitro and the HBV antigen and nucleic acid could be detected intracellularly. Hepatitis B x protein (HBx) was also strongly expressed in tissues from DLBCL patients that were serum HBV surface antigen (HBsAg) positive. These patients responded less well to therapy with an odds ratio (OR) of 3.04. Conclusions: HBV can infect B lymphocytes. It might be related to the development of DLBCL and may also impact the efficacy of treatment. PMID:29760795

  2. cdc25 cell cycle-activating phosphatases and c-myc expression in human non-Hodgkin's lymphomas.

    PubMed

    Hernández, S; Hernández, L; Beà, S; Cazorla, M; Fernández, P L; Nadal, A; Muntané, J; Mallofré, C; Montserrat, E; Cardesa, A; Campo, E

    1998-04-15

    cdc25A, cdc25B, and cdc25C are a family of human phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and cdc25B have been shown to have oncogenic potential, and they have been identified as transcriptional targets of c-myc. To determine the role of cdc25 genes in the pathogenesis of human lymphomas and their possible correlation with c-myc deregulation, we have analyzed the expression of cdc25A, cdc25B, and cdc25C and c-myc genes in a series of 63 non-Hodgkin's lymphomas and 8 nonneoplastic lymphoid tissues. The mRNA levels of the three phosphatases in the nonneoplastic tissues were negative or negligible. cdc25B overexpression was detected in 35 tumors (56%). This overexpression was more frequently found in aggressive (81%) than in indolent lymphomas (36%; P < 0.01). cdc25B overexpression was also significantly associated with a higher proliferative activity of the tumors. No cdc25B gene amplification or rearrangements were detected by Southern blot analysis. A biallelic EcoRI polymorphism of cdc25B gene was identified with a similar distribution in patients with lymphoma and in a normal population. cdc25A was overexpressed in three aggressive lymphomas. No detectable cdc25C mRNA levels were seen in any of the tumors. c-myc was overexpressed in 43% of tumors, and it correlated significantly with the presence of cdc25B up-regulation. Twenty-six of 35 (74%) lymphomas with high levels of cdc25B mRNA also showed c-myc overexpression, whereas 27 of 28 (96%) tumors without detectable or with very low cdc25B expression also had undetectable c-myc levels (P < 0.0001). In addition, a significant linear correlation was found between the cdc25B and c-myc mRNA levels (r = 0.575, P < 0.001). These findings suggest that cdc25B overexpression in non-Hodkin's lymphoma may participate in the pathogenesis of aggressive variants, and it may cooperate with c-myc oncogene in the development of these tumors.

  3. Strategic Therapeutic Targeting to Overcome Venetoclax Resistance in Aggressive B-cell Lymphomas.

    PubMed

    Pham, Lan V; Huang, Shengjian; Zhang, Hui; Zhang, Jun; Bell, Taylor; Zhou, Shouhao; Pogue, Elizabeth; Ding, Zhiyong; Lam, Laura; Westin, Jason; Davis, R Eric; Young, Ken H; Medeiros, L Jeffrey; Ford, Richard J; Nomie, Krystle; Zhang, Leo; Wang, Michael

    2018-04-17

    Purpose: B-cell lymphoma-2 (BCL-2), an antiapoptotic protein often dysregulated in B-cell lymphomas, promotes cell survival and provides protection from stress. A recent phase I first-in-human study of the BCL-2 inhibitor venetoclax in non-Hodgkin lymphoma showed an overall response rate of 44%. These promising clinical results prompted our examination of the biological effects and mechanism of action underlying venetoclax activity in aggressive B-cell lymphoma, including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). Experimental Design: MCL and DLBCL cell lines, primary patient samples, and in vivo patient-derived xenograft (PDX) models were utilized to examine venetoclax efficacy. Furthermore, the mechanisms underlying venetoclax response and the development of venetoclax resistance were evaluated using proteomics analysis and Western blotting. Results: Potential biomarkers linked to venetoclax activity and targeted combination therapies that can augment venetoclax response were identified. We demonstrate that DLBCL and MCL cell lines, primary patient samples, and PDX mouse models expressing high BCL-2 levels are extremely sensitive to venetoclax treatment. Proteomics studies showed that venetoclax substantially alters the expression levels and phosphorylation status of key proteins involved in cellular processes, including the DNA damage response, cell metabolism, cell growth/survival, and apoptosis. Short- and long-term exposure to venetoclax inhibited PTEN expression, leading to enhanced AKT pathway activation and concomitant susceptibility to PI3K/AKT inhibition. Intrinsic venetoclax-resistant cells possess high AKT activation and are highly sensitive to PI3K/AKT inhibition. Conclusions: These findings demonstrate the on-target effect of venetoclax and offer potential mechanisms to overcome acquired and intrinsic venetoclax resistance through PI3K/AKT inhibition. Clin Cancer Res; 1-14. ©2018 AACR. ©2018 American Association for

  4. Epstein-Barr virus viral load and serology in childhood non-Hodgkin's lymphoma and chronic inflammatory conditions in Uganda: implications for disease risk and characteristics.

    PubMed

    Orem, Jackson; Sandin, Sven; Mbidde, Edward; Mangen, Fred Wabwire; Middeldorp, Jaap; Weiderpass, Elisabete

    2014-10-01

    Epstein-Barr virus (EBV) has been linked to malignancies and chronic inflammatory conditions. In this study, EBV detection was compared in children with non-Hodgkin's lymphoma and children with chronic inflammatory conditions, using samples and data from a case-control study carried out at the Mulago National Referral Hospital between 2004 and 2008. EBV viral load was measured in saliva, whole blood and white blood cells by real-time PCR. Serological values for IgG-VCA, EBNA1, and EAd-IgG were compared in non-Hodgkin's lymphoma and chronic inflammatory conditions; and in Burkitt's lymphoma and other subtypes of non-Hodgkin's lymphoma. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Of the 127 children included (87 males and 40 females; median age 7 years, range 2-17), 96 had non-Hodgkin's lymphoma (46 Burkitt's lymphoma and 50 other non-Hodgkin's lymphoma), 31 had chronic inflammatory conditions, and only 10% were HIV-positive. The most common clinical presentations for all disease categories considered were fever, night sweats, and weight loss. EBV viral load in whole blood was elevated in Burkitt's lymphoma compared to other non-Hodgkin's lymphoma (OR 6.67, 95% CI 1.32, 33.69; P-value = 0.04), but EBV viral loads in saliva and white blood cells were not different in any of the disease categories considered. A significant difference in EAd-IgG was observed when non-Hodgkin's lymphoma was compared with chronic inflammatory conditions (OR 0.19, 95% CI 0.07, 0.51; P-value = 0.001). When compared to chronic inflammatory conditions, EBV viral load was elevated in Burkitt's lymphoma, and EA IgG was higher in non-Hodgkin's lymphoma. This study supports an association between virological and serological markers of EBV and childhood non-Hodgkin's lymphoma, irrespective of subtype, in Uganda. © 2014 Wiley Periodicals, Inc.

  5. Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review

    PubMed Central

    Berger, Garrett K.; McBride, Ali; Lawson, Stephanie; Royball, Kelsey; Yun, Seongseok; Gee, Kevin; Riaz, Irbaz Bin; Saleh, Ahlam A.; Puvvada, Soham; Anwer, Faiz

    2016-01-01

    Background Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL. Objective Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30+ malignancies in humans. Data sources We searched various databases including PubMed (1946–2015), EMBASE (1947–2015), and Cochrane Central Register of Controlled Trials (1898–2015). Eligibility criteria Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered. Included studies A total of 28 articles met these criteria and are summarized in this manuscript. Conclusion Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30+ malignancies. PMID:28010897

  6. Persistent Organic Pollutant and Hormone Levels in Harbor Porpoise with B Cell Lymphoma.

    PubMed

    Norman, Stephanie A; Winfield, Zach C; Rickman, Barry H; Usenko, Sascha; Klope, Matthew; Berta, Susan; Dubpernell, Sandra; Garrett, Howard; Adams, Mary Jo; Lambourn, Dyanna; Huggins, Jessica L; Lysiak, Nadine; Clark, Adelaide E; Sanders, Rebel; Trumble, Stephen J

    2017-05-01

    B-cell lymphoma, a common morphologic variant of non-Hodgkin lymphoma, has been associated with persistent pollutants in humans, but this association is not well-characterized in top-level predators sharing marine resources with humans. We characterized and compared blubber contaminants and hormones of a pregnant harbor porpoise (Phocoena phocoena) with B-cell lymphoma, with those in two presumed healthy fishery by-caught porpoises with no lymphoma: a pregnant adult and female juvenile. Common historic use compounds, including polychlorinated biphenyls, polybrominated diphenyl ethers, and pesticides, were evaluated in blubber samples from three porpoises. In addition, blubber cortisol and progesterone levels (ng/g) were determined in all three animals. Total pollutant concentrations were highest in the juvenile porpoise, followed by the lymphoma porpoise and the nonlymphoma adult. Blubber cortisol concentrations were 191% greater in the pregnant with lymphoma porpoise compared with the pregnant no lymphoma porpoise, and 89% greater in the juvenile female compared with the pregnant no lymphoma porpoise. Although both adults were pregnant, progesterone levels were substantially greater (90%) in the healthy compared with the lymphoma adult. Health monitoring of top-level marine predators, such as porpoise, provides a sentinel measure of contaminants that serve as indicators of potential environmental exposure to humans.

  7. [Unusual cases of non-Hodgkin's lymphomas--case reports].

    PubMed

    Wach, M; Dmoszyńska, A; Wasik-Szczepanek, E; Skomra, D

    2000-01-01

    We describe 4 cases of non-Hodkin's lymphomas that were interesting because of their curiosal clinical courses and spontaneous complete remissions during the course of high malignancy lymphoma. We present three of them for the first time in Poland. Case 1: a 61-year old woman was admitted to the hospital because of the headache, lasting for 4 months before hospitalization and right hemiparesis. CT scans revealed the presence of tumor in the temporo-occipital region. The diagnosis of B-cell lymphoma was established at histopathological examination of the postoperative material. Co60--therapy of these region was applied after the operation with good response. Case 2: a 38-year woman was admitted to the hospital because of L5-S1 spondylolisthesis to operate it. During the hospitalization haemolytic anaemia of unknown origin, thrombocytopoenia, splenomegaly, fever and rising acute insufficiency of kidneys, heart, liver and CNS were occurred. The patient died, despite applying corticosteroidotherapy. The diagnosis of intravascular lymphoma was established at postmortem examination. Case 3: a 51-year old woman was admitted to the hospital with diagnosis: anaplastic non-Hodgkin lymphoma B-cell type high malignancy established after the double histopathological examination of lymph nodes and biopsy of the lung. At the admission to the Department of Haematology we stated absolute regression of these changes. The patient had been only observed in the Outpatient Department over 1 year. She died after 6 months since the beginning of the relapse despite intensive chemotherapy. Case 4: a 43-year old man was admitted to the hospital because of great hyperleukocytosis, hepatosplenomegaly and neurological symptoms. The diagnosis: chronic prolymphocytic leukaemia was established. The cerebrospinal fluid examination showed presence of mononuclears which infiltrated CNS. CT scans of the brain revealed leucaemic infiltrations of the hemispheres and cerebellum. The patient died despite

  8. 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.

  9. Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)

    ClinicalTrials.gov

    2018-06-25

    Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; BRAF NP_004324.2:p.V600X; Ependymoma; Ewing Sarcoma; Hepatoblastoma; Histiocytosis; Langerhans Cell Histiocytosis; Malignant Germ Cell Tumor; Malignant Glioma; Osteosarcoma; Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Rhabdomyosarcoma; Soft Tissue Sarcoma; Wilms Tumor

  10. [Application of digital pathology tools. An unusual case of non-Hodgkin lymphoma].

    PubMed

    Meyer, A-S K; Dallenbach, F E; Lienert, G; Möller, P; Lennerz, J K

    2012-11-01

    Currently, lymphoma diagnosis is based on a combination of morphology, immunophenotyping, and molecular testing. Using the example of an unusual case of malignant non-Hodgkin lymphoma, we show that improved visualization using digital pathology contributes to the convergence of these complementary diagnostic modalities. A 45-year-old woman presented with skin rash and cervical lymphadenopathy. Histological workup of an excised lymph node showed loss of normal architecture with diffuse infiltration and increased mitotic activity. Immunohistochemistry for CD3/CD5 showed atypical arrangement and infiltration of a T-cell population that dominated over regionally dense, MUM1-positive plasmacellular infiltrates. Expanded CD21/CD23-positive meshworks of follicular dendritic cells were present within and between regressed follicles and the T-cell infiltrate; staining for CD56 and cyclin-D1 was negative. Quantification of Ki-67 staining within the T-, B- and plasmacellular compartments was achieved by digital image conversion, overlay and subsequent quantification algorithms that revealed proliferation within more than 60% of T-cells, over 50% of plasma cells and only 20% of B-cells. Clonality analysis by PCR revealed monoclonal rearrangement for both T-cell receptor gamma chains and immunoglobulin heavy chains. Taken together, we present an unusual combination of an angioimmunoblastic T-cell lymphoma (AITL) and simultaneous plasmacellular lymphoma. This report demonstrates how application of modern tools of digital pathology can visually integrate unusual morphological and molecular findings.

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

    ClinicalTrials.gov

    2018-01-02

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

  12. Primary non-Hodgkin lymphoma of the right femur and subsequent metastasis to the left femur: A case report and literature review.

    PubMed

    Hu, Jing-Yu; Yu, Dan; Wu, Yao-Hui

    2018-04-01

    Non-Hodgkin lymphoma of the bone is rare and typically causes an extensive bone lesion. The present study describes a case of diffuse large B-cell primary non-Hodgkin lymphoma of the bone, which occurred in the right femur, and was initially treated with surgery and chemotherapy. Following a 7-year period of complete remission, a new, similar lesion was identified in the left femur. With both lesions, there was no accompanying destruction of any other bones or organ involvement. Metastasis of PLB to the contralateral side is extremely rare and, to the best of our knowledge, this is the first report of this particular presentation in China or worldwide. We hypothesized that the present situation arose due to mechanisms involving the tumor microenvironment, circulating tumor cells, lymphocyte homing and self-seeding. The present report describes the case in detail, and discusses the possible underlying mechanisms and their potential contribution to the treatment of non-Hodgkin lymphoma, as well as the prevention of metastasis and recurrence, which may be of considerable clinical significance.

  13. Exposure-response evaluations of venetoclax efficacy and safety in patients with non-Hodgkin lymphoma.

    PubMed

    Parikh, Apurvasena; Gopalakrishnan, Sathej; Freise, Kevin J; Verdugo, Maria E; Menon, Rajeev M; Mensing, Sven; Salem, Ahmed Hamed

    2018-04-01

    Exposure-response analyses were performed for a venetoclax monotherapy study in 106 patients with varying subtypes of non-Hodgkin lymphoma (NHL) (NCT01328626). Logistic regression, time-to-event, and progression-free survival (PFS) analyses were used to evaluate the relationship between venetoclax exposure, NHL subtype and response, PFS, or occurrence of serious adverse events. Trends for small increases in the probability of response with increasing venetoclax exposures were identified, and became more evident when assessed by NHL subtype. Trends in exposure-PFS were shown for the mantle cell lymphoma (MCL) subtype, but not other subtypes. There was no increase in the probability of experiencing a serious adverse event with increasing exposure. Overall, the results indicate that venetoclax doses of 800-1200 mg as a single agent may be appropriate to maximize efficacy in MCL, follicular lymphoma, and diffuse large B-cell lymphoma subtypes with no expected negative impact on safety.

  14. Impact of salvage treatment modalities in patients with positive FDG-PET/CT after R-CHOP chemotherapy for aggressive B-cell non-Hodgkin lymphoma.

    PubMed

    Chin, Vicky; Fulham, Michael; Hertzberg, Mark; Jackson, Michael; Lindeman, Robert; Brighton, Timothy; Kidson-Gerber, Giselle; Wegner, Eva A; Cheung, Carol; MacCallum, Susan; Williams, Janet; Thompson, Stephen R

    2018-06-01

    To compare outcomes of different salvage treatment modalities in patients with aggressive B-cell non-Hodgkin lymphoma (NHL) who remain FDG-PET positive after R-CHOP chemotherapy. Existing data on these patients with FDG-PET primary refractory disease are limited. Patients with diffuse large B-cell lymphoma or grade 3 follicular lymphoma were retrospectively reviewed from the Prince of Wales Hospital databases. Eligibility criteria were: age≥18 years, treated with R-CHOP, with positive post-chemotherapy FDG-PET. Salvage treatment modalities were: radical radiotherapy (RT, dose≥30 Gy), high dose chemotherapy and autologous stem cell transplant (ASCT), or non-radical management. Survival was calculated from date of post-chemotherapy FDG-PET to last follow-up. Twenty-six patients from 2003-2015 met the inclusion criteria. Median age was 60 (range 19-84). Most had adverse baseline features: 21 (81%) stage III-IV, 24 (92%) bulky disease and nine (35%) skeletal involvement. Characteristics of PET-positivity post-chemotherapy were single site in 16 (62%), sites of prior bulk in 24 of 24, skeletal sites in five of nine, and able to be encompassed by RT in 21 (81%). Salvage treatment was: radical RT in 17 (65%), ASCT in four (15%) and non-radical in five (20%). Median follow-up of surviving patients was 31 months. Kaplan-Meier estimates of 3-year PFS and OS were 41% and 52%, respectively. By salvage modality, 3-year PFS was 51% for RT, 25% for ASCT and 20% for non-radical treatment, (P = 0.453); 3-year OS was respectively 65%, 25% and 40% (P = 0.173). Patients with FDG-PET positive disease after R-CHOP for aggressive B-cell NHL are salvageable with radiotherapy. © 2018 The Royal Australian and New Zealand College of Radiologists.

  15. Phase I Study of Inotuzumab Ozogamicin Combined with R-CVP for Relapsed/Refractory CD22+ B-cell Non-Hodgkin Lymphoma.

    PubMed

    Ogura, Michinori; Tobinai, Kensei; Hatake, Kiyohiko; Davies, Andrew; Crump, Michael; Ananthakrishnan, Revathi; Ishibashi, Taro; Paccagnella, M Luisa; Boni, Joseph; Vandendries, Erik; MacDonald, David

    2016-10-01

    To evaluate the safety, preliminary efficacy, and pharmacokinetics of inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, in combination with the immunochemotherapeutic regimen, rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), in patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma (NHL). In part 1 (n = 16), patients received inotuzumab ozogamicin plus R-CVP on a 21-day cycle with escalating doses of cyclophosphamide first then inotuzumab ozogamicin. Part 2 (n = 10) confirmed the safety and tolerability of the maximum tolerated dose (MTD), which required a dose-limiting toxicity rate of <33% in cycle 1 and <33% of patients discontinuing before cycle 3 due to treatment-related adverse events (AEs). Part 3 (n = 22) evaluated the preliminary efficacy of inotuzumab ozogamicin plus R-CVP. The MTD was determined to be standard-dose R-CVP plus inotuzumab ozogamicin 0.8 mg/m 2 The most common treatment-related grade ≥3 AEs in the MTD cohort (n = 38) were hematologic: neutropenia (74%), thrombocytopenia (50%), lymphopenia (42%), and leukopenia (47%). Among the 48 patients treated in the study, 13 discontinued due to AEs, most commonly thrombocytopenia (n = 10). Overall, 13 patients died, including one death due to treatment-related pneumonia secondary to neutropenia. Among patients receiving the MTD (n = 38), the overall response rate (ORR) was 84% (n = 32), including 24% (n = 9) with complete response; the ORR was 100% for patients with indolent lymphoma (n = 27) and 57% for those with aggressive histology lymphoma (n = 21). Inotuzumab ozogamicin at 0.8 mg/m 2 plus full dose R-CVP was associated with manageable toxicities and demonstrated a high rate of response in patients with relapsed/refractory CD22+ B-cell NHL. The study is registered at ClinicalTrials.gov (NCT01055496). Clin Cancer Res; 22(19); 4807-16. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma

    ClinicalTrials.gov

    2018-03-12

    Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Plasma Cell Myeloma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Refractory Plasma Cell Myeloma; Refractory T-Cell Non-Hodgkin Lymphoma

  17. Downbeat nystagmus caused by thiamine deficiency: an unusual presentation of CNS localization of large cell anaplastic CD 30-positive non-Hodgkin's lymphoma.

    PubMed

    Mulder, A H; Raemaekers, J M; Boerman, R H; Mattijssen, V

    1999-02-01

    A 24-year-old woman with a large cell anaplastic CD 30-positive T-cell non-Hodgkin's lymphoma (NHL) developed downbeat nystagmus, anisocoria, and oscillopsia. Prior to overt cerebral invasion by NHL, she had a thiamine deficiency with very low thiamine concentrations in the CSF, probably caused by protracted vomiting and increased vitamin B1 consumption by intrathecal tumor cells. We believe that her neurologic symptoms were caused -- at least partly -- by thiamine deficiency, as she reacted well to thiamine supplementation at the beginning of treatment.

  18. Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma

    ClinicalTrials.gov

    2015-10-09

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; 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; 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 Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  19. Allogeneic hematopoietic cell transplantation as curative therapy for patients with non-Hodgkin lymphoma: increasingly successful application to older patients

    PubMed Central

    Fenske, Timothy S.; Hamadani, Mehdi; Cohen, Jonathon B.; Costa, Luciano J.; Kahl, Brad; Evens, Andrew M.; Hamlin, Paul A.; Lazarus, Hillard M.; Petersdorf, Effie; Bredeson, Christopher

    2016-01-01

    Non-Hodgkin lymphoma (NHL) constitutes a collection of lymphoproliferative disorders with widely varying biologic, histologic and clinical features. For the B-cell NHLs, great progress has been made due to the addition of monoclonal antibodies and, more recently, other novel agents such as B-cell receptor signaling inhibitors, immunomodulatory agents, and proteasome inhibitors. Autologous hematopoietic cell transplantation (auto-HCT) offers the promise of cure or prolonged remission in some NHL patients. For some patients, however, auto-HCT may never be a viable option, while in others their disease may progress despite auto-HCT. In those settings, allogeneic HCT (allo-HCT) offers the potential for cure. Over the past 10–15 years, considerable progress has been made in the implementation of allo-HCT, such that this approach now is a highly effective therapy for patients up to (and even beyond) age 75. Recent advances in conventional lymphoma therapy, peri-transplant supportive care, patient selection, and donor selection (including the use of alternative hematopoietic cell donors), has allowed broader application of allo-HCT to NHL patients. As a result, an ever-increasing number of NHL patients over age 60–65 years stand to benefit from allo-HCT. In this review, we present data in support of the use of allo-HCT for patients with diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. These histologies account for a large majority of allo-HCT performed for patients over 60 in the U.S. Where possible, we highlight available data in older patients. This body of literature strongly supports the concept that allo-HCT should be offered to fit patients well beyond age 65 and, accordingly, that this treatment should therefore be covered by their insurance carriers. PMID:27131863

  20. Genetic variation in cell death genes and risk of non-Hodgkin lymphoma.

    PubMed

    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

    Non-Hodgkin lymphomas are a heterogeneous group of solid tumours that constitute the 5(th) 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. 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. Variant rs928883, near miR-155, showed an association (OR per A-allele: 2.80 [95% CI: 1.63-4.82]; p(F) = 0.027) with marginal zone lymphoma that is significant after correction for multiple testing. This is the first reported association between a germline polymorphism at a miRNA locus and lymphoma.

  1. miR-28 regulates the germinal center reaction and blocks tumor growth in preclinical models of non-Hodgkin lymphoma

    PubMed Central

    Bartolomé-Izquierdo, Nahikari; Mur, Sonia M.

    2017-01-01

    Non-Hodgkin lymphoma comprises a variety of neoplasms, many of which arise from germinal center (GC)-experienced B cells. microRNA-28 (miR-28) is a GC-specific miRNA whose expression is lost in numerous mature B-cell neoplasms. Here we show that miR-28 regulates the GC reaction in primary B cells by impairing class switch recombination and memory B and plasma cell differentiation. Deep quantitative proteomics combined with transcriptome analysis identified miR-28 targets involved in cell-cycle and B-cell receptor signaling. Accordingly, we found that miR-28 expression diminished proliferation in primary and lymphoma cells in vitro. Importantly, miR-28 reexpression in human Burkitt (BL) and diffuse large B-cell lymphoma (DLBCL) xenografts blocked tumor growth, both when delivered in viral vectors or as synthetic, clinically amenable, molecules. Further, the antitumoral effect of miR-28 is conserved in a primary murine in vivo model of BL. Thus, miR-28 replacement is uncovered as a novel therapeutic strategy for DLBCL and BL treatment. PMID:28188132

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

    ClinicalTrials.gov

    2017-09-28

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

  3. 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.

  4. Difficult Diagnosis between B Cell Lymphoma and Classical Hodgkin's Lymphoma.

    PubMed

    Rentas Torres, Yaixa; Rodríguez-López, Joshua L; Valentin, Maria; Silva, Hector

    2015-01-01

    Although primary mediastinal large B-cell lymphoma and classic Hodgkin lymphoma of nodular sclerosis type are distinct disease, they share several clinical characteristics and biologic features. However, there are mediastinal lymphomas that not fit in either category. These types of lymphomas are recognized as mediastinal gray zone lymphomas. Gray zone lymphomas are lymphatic tumors that cannot be assigned to a defined lymphoma entity due to morphological, clinical, or genetic reasons. In this report, we present a case of a 22 year-old-Hispanic-female diagnosed with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Hodgkin lymphoma.

  5. Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)

    ClinicalTrials.gov

    2018-06-25

    Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; FGFR1 Gene Mutation; FGFR2 Gene Mutation; FGFR3 Gene Mutation; FGFR4 Gene Mutation; Histiocytosis; Low Grade Glioma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

  6. Durvalumab With or Without Lenalidomide in Treating Patients With Relapsed or Refractory Cutaneous or Peripheral T Cell Lymphoma

    ClinicalTrials.gov

    2018-04-06

    Folliculotropic Mycosis Fungoides; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Sezary Syndrome; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma

  7. Onalespib in Treating Patients With Relapsed or Refractory Anaplastic Large Cell Lymphoma, Mantle Cell Lymphoma, or Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2018-05-23

    ALK Positive; BCL6 Positive; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma

  8. Non-Hodgkin's lymphoma in McKusick syndrome. A case report.

    PubMed

    Torkzad, M R; Hjalmar, V; Blomqvist, L

    2002-07-01

    The McKusick syndrome in a female who developed highly malignant lymphoma at the age of 23, with multiple parenchymal lesions involving both kidneys, the lungs and the pancreas and also splenomegaly but without lymphadenopathy, is described together with diagnostic imaging findings. McKusick syndrome is associated with impaired cell-mediated immunity and might, like several other similar syndromes, harbor an increased risk of certain types of lymphoma. To our knowledge, there are no previous reports of non-Hodgkin's lymphoma in a patient with McKusick syndrome. The increased incidence of lymphoma in certain cases of congenital immunodeficiency raises the issue of a possible relationship between McKusick syndrome and lymphoma and could perhaps serve as one of the primary steps for a further characterization of this syndrome.

  9. [Long-term remission of non-Hodgkin lymphoma secondary to the treatment for essential thrombocythemia].

    PubMed

    Kubota, Yoshitsugu; Waki, Masato

    2009-03-01

    A 45-year-old woman was diagnosed with essential thrombocythemia (ET) in August 1987 and received treatment with alkylating agents (total administration dose, busulfan 378 mg, MCNU 700 mg) because of a history of myocardial infarction. In June 2000, anemia gradually progressed. A few blast cells were detected in the peripheral blood at that time. Since bone marrow biopsy revealed myelofibrosis, she received anabolic hormone therapy. She was admitted to our hospital for an evaluation of abdominal distension in February 2003. Swelling of a large paraaortic lymph node of 6 cm in diameter was detected by CT scan. Lymph node biopsy revealed diffuse large B-cell lymphoma. Lymphoma cells were positive for CD10, CD19, CD20 and kappa-chain. The clinical stage was I. Complete remission has been achieved for 57 months after treatment with combination chemotherapy combined with rituximab followed by local radiation therapy. Non-Hodgkin lymphoma secondary to ET is a rare event. Such cases should therefore be accumulated to evaluate the mechanism of onset and clinical characteristics of lymphoma secondary to ET.

  10. Atrazine and Nitrate in Public Drinking Water Supplies and Non-Hodgkin Lymphoma in Nebraska, USA

    PubMed Central

    Rhoades, Martha G.; Meza, Jane L.; Beseler, Cheryl L.; Shea, Patrick J.; Kahle, Andy; Vose, Julie M.; Eskridge, Kent M.; Spalding, Roy F.

    2013-01-01

    A secondary analysis of 1999–2002 Nebraska case-control data was conducted to assess the risk of non-Hodgkin lymphoma (NHL) associated with exposure to nitrate- and atrazine-contaminated drinking water. Water chemistry data were collected and weighted by well contribution and proximity of residence to water supply, followed by logistic regression to determine odds ratios (OR) and 95% confidence intervals (CI). We found no association between NHL risk and exposure to drinking water containing atrazine or nitrate alone. Risk associated with the interaction of nitrate and atrazine in drinking water was elevated (OR, 2.5; CI, 1.0–6.2). Risk of indolent B-cell lymphoma was higher than risk of aggressive B-cell lymphoma (indolent: OR, 3.5; CI, 1.0–11.6 vs. aggressive: OR, 1.9; CI, 0.6–5.58). This increased risk may be due to in vivo formation and subsequent metabolism of N-nitrosoatrazine. A larger study is warranted to confirm our findings. PMID:23515852

  11. Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

    ClinicalTrials.gov

    2018-05-22

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

  12. Inhibition of COP9-signalosome (CSN) deneddylating activity and tumor growth of diffuse large B-cell lymphomas by doxycycline

    PubMed Central

    Pulvino, Mary; Chen, Luojing; Oleksyn, David; Li, Jing; Compitello, George; Rossi, Randy; Spence, Stephen; Balakrishnan, Vijaya; Jordan, Craig; Poligone, Brian; Casulo, Carla; Burack, Richard; Shapiro, Joel L.; Bernstein, Steven; Friedberg, Jonathan W.; Deshaies, Raymond J.; Land, Hartmut; Zhao, Jiyong

    2015-01-01

    In searching for small-molecule compounds that inhibit proliferation and survival of diffuse large B-cell lymphoma (DLBCL) cells and may, therefore, be exploited as potential therapeutic agents for this disease, we identified the commonly used and well-tolerated antibiotic doxycycline as a strong candidate. Here, we demonstrate that doxycycline inhibits the growth of DLBCL cells both in vitro and in mouse xenograft models. In addition, we show that doxycycline accumulates in DLBCL cells to high concentrations and affects multiple signaling pathways that are crucial for lymphomagenesis. Our data reveal the deneddylating activity of COP-9 signalosome (CSN) as a novel target of doxycycline and suggest that doxycycline may exert its effects in DLBCL cells in part through a CSN5-HSP90 pathway. Consistently, knockdown of CSN5 exhibited similar effects as doxycycline treatment on DLBCL cell survival and HSP90 chaperone function. In addition to DLBCL cells, doxycycline inhibited growth of several other types of non-Hodgkin lymphoma cells in vitro. Together, our results suggest that doxycycline may represent a promising therapeutic agent for DLBCL and other non-Hodgkin lymphomas subtypes. PMID:26142707

  13. [Hematopoietic cells raising with plerixafor in non-Hodgkin lymphoma].

    PubMed

    Pérez-Lozano, Uendy; Tripp-Villanueva, Francisco; Ramírez-Alvarado, Aline; Vela-Ojeda, Jorge; Limón-Flores, Alejandro; Kramis-Cerezo, José Luis

    2012-01-01

    bone marrow autologous transplantation (BMAT) has proven benefits in patients treated for non-Hodgkin's lymphoma (NHL). Plerixafor is an inhibitor of CXCR4 receptor. The aim was to report the raise of hematopoietic cells with plerixafor in patients with NHL. patient 1 with follicular NHL, GI, intermediate FLIPI, CD20+, CD45+, BCL-2+, who reached complete response after three chemotherapy regimes. Mobilization failed after use of filgrastim (G-CSF) alone and G-CSF + cyclophosphamide. A new attempt was made with G-CSF + plerixafor (G-CSF, 10 μg/kg for 7 days + plerixafor, 240 μg/kg in days 4 to 7). Patient 2 with follicular NHL and CD20+ reached complete remission with MINE after therapeutic failure with other regimes, but develops severe marrow toxicity. Mobilization was supported with G-CSF 10 μg/kg/d + plerixafor in days 4 and 5. In case one, proper cell counts where obtained after three aphaeresis. In the second case, two harvests add of 2.7 × 106/kg were obtained. plerixafor raised the hematopoietic stem cells in peripheral blood and improves mobilization of proper cell population.

  14. Time-to-treatment of diffuse large B-cell lymphoma in São Paulo

    PubMed Central

    Xavier, Flávia Dias; Levy, Debora; Pereira, Juliana

    2014-01-01

    OBJECTIVE: Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma, accounting for nearly 50% of the cases in the Hematology Department of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo. The treatment outcome is influenced by age, abnormal lactate dehydrogenase levels, extranodal infiltration, the disease stage and the patient's performance status. In this study, we sought to report the time-to-treatment of diffuse large B-cell lymphoma in São Paulo's public health system network and its impact on patient outcomes. METHODS: We prospectively followed a cohort of 42 consecutive patients with de novo diffuse large B-cell lymphoma between 2008 and 2012. RESULTS: Our patients had more advanced disease than that reported in the literature (61.9% vs. 46%). In São Paulo's public health system network, it took an average of 7.4 months for a diagnosis to be made and an additional 1.4 months to obtain an appointment with a specialist. Once at our Hematology Department, it took less than 20 days for staging, confirmation of the diagnosis and treatment initiation. An interval from signs or symptoms to treatment of more than 6 months was associated with inferior progression-free survival in 3 years (p = 0.049). CONCLUSION: A delay in the diagnosis of diffuse large B-cell lymphoma is a public health problem and may be associated with worse progression-free survival. PMID:24838904

  15. Human leukocyte antigen class I and II alleles in non-Hodgkin lymphoma etiology

    PubMed Central

    Abdou, Amr M.; Morton, Lindsay M.; Thomas, Rasmi; Cerhan, James R.; Gao, Xiaojiang; Cozen, Wendy; Rothman, Nathaniel; Davis, Scott; Severson, Richard K.; Bernstein, Leslie; Hartge, Patricia; Carrington, Mary

    2010-01-01

    Genome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes. PMID:20385791

  16. Protein kinase C-beta inhibition induces apoptosis and inhibits cell cycle progression in acquired immunodeficiency syndrome-related non-hodgkin lymphoma cells.

    PubMed

    Saba, Nakhle S; Levy, Laura S

    2012-01-01

    Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL) constitutes an aggressive variety of lymphomas characterized by increased extranodal involvement, relapse rate, and resistance to chemotherapy. Protein kinase C-beta (PKCβ) targeting showed promising results in preclinical and clinical studies involving a wide variety of cancers, but studies describing the role of PKCβ in AIDS-NHL are primitive if not lacking. In the present study, 3 AIDS-NHL cell lines were examined: 2F7 (AIDS-Burkitt lymphoma), BCBL-1 (AIDS-primary effusion lymphoma), and UMCL01-101 (AIDS-diffuse large B-cell lymphoma). Immunoblot analysis demonstrated expression of PKCβ1 and PKCβ2 in 2F7 and UMCL01-101 cells, and PKCβ1 alone in BCBL-1 cells. The viability of 2F7 and BCBL-1 cells decreased significantly in the presence of PKCβ-selective inhibitor at half-maximal inhibitory concentration of 14 and 15 μmol/L, respectively, as measured by tetrazolium dye reduction assay. In contrast, UMCL01-101 cells were relatively resistant. As determined using flow cytometric deoxynucleotidyl transferase dUTP nick-end labeling assay with propidium iodide staining, the responsiveness of sensitive cells was associated with apoptotic induction and cell cycle inhibition. Protein kinase C-beta-selective inhibition was observed not to affect AKT phosphorylation but to induce a rapid and sustained reduction in the phosphorylation of glycogen synthase kinase-3 beta, ribosomal protein S6, and mammalian target of rapamycin in sensitive cell lines. The results indicate that PKCβ plays an important role in AIDS-related NHL survival and suggest that PKCβ targeting should be considered in a broader spectrum of NHL. The observations in BCBL-1 were unexpected in the absence of PKCβ2 expression and implicate PKCβ1 as a regulator in those cells.

  17. Long-term survival in patients with peripheral T-cell non-Hodgkin lymphomas after allogeneic hematopoietic stem cell transplant.

    PubMed

    Goldberg, Jenna D; Chou, Joanne F; Horwitz, Steven; Teruya-Feldstein, Julie; Barker, Juliet N; Boulad, Farid; Castro-Malaspina, Hugo; Giralt, Sergio; Jakubowski, Ann A; Koehne, Guenther; van den Brink, Marcel R M; Young, James W; Zhang, Zhigang; Papadopoulos, Esperanza B; Perales, Miguel-Angel

    2012-06-01

    Peripheral T-cell non-Hodgkin lymphomas (T-NHL) are rare diseases, with a worse prognosis compared to their B-cell counterparts. Allogeneic hematopoietic stem cell transplant may have a role in the treatment of relapsed/refractory disease or high-risk histologies in the upfront setting. However, there is limited information on the efficacy of allogeneic transplant for these diseases, as well as what factors may predict outcomes. We therefore performed a retrospective study of 34 patients who received an allogeneic transplant for the treatment of T-NHL at a single center between 1 January 1992 and 31 December 2009. The median follow-up for survivors was 45 months (range 9-160 months). The 2-year overall survival (OS) was 0.61 (95% confidence interval [CI]: 0.43-0.75) with a plateau at 28 months. Ki-67 expression ≤ 25% was predictive of improved OS (p < 0.01), and transplant in complete remission was predictive of a decreased cumulative incidence of events (p = 0.04). Three patients received a donor leukocyte infusion, and two patients demonstrated a response, supporting a graft-versus-lymphoma effect. These data demonstrate that allogeneic transplant is a viable option for the treatment of T-NHL and merits prospective evaluation.

  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. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  19. A case of primary diffuse large B-cell non-Hodgkin's lymphoma misdiagnosed as chronic periapical periodontitis.

    PubMed

    Jessri, M; AbdulMajeed, A A; Matias, M A; Farah, C S

    2013-06-01

    Lymphoma is a malignant neoplasm of component cells of the lymphoid system which is very rare in the jaws. Here we report a case of primary diffuse large B-cell lymphoma located in the periapical region of a mandibular molar which was misdiagnosed as chronic periapical periodontitis. The present case was diagnosed at an early stage and effectively managed by chemotherapy. Although lymphoma of the mandible is rare, it must be considered in the differential diagnosis of radiolucent lesions in this region. Lack of knowledge of this rare presentation may lead to delays in diagnosis and poor prognosis. © 2013 Australian Dental Association.

  20. Residential and occupational exposure to sunlight and mortality from non-Hodgkin's lymphoma: composite (threefold) case-control study.

    PubMed Central

    Freedman, D. M.; Zahm, S. H.; Dosemeci, M.

    1997-01-01

    OBJECTIVE: To determine whether non-Hodgkin's lymphoma mortality is associated with sunlight exposure. DESIGN: Three case-control studies based on death certificates of non-Hodgkin's lymphoma, melanoma, and skin cancer mortality examining associations with potential sunlight exposure from residence and occupation. SETTING: 24 states in the United States. SUBJECTS: All cases were deaths from non-Hodgkin's lymphoma, melanoma, and non-melanotic skin cancer between 1984 and 1991. Two age, sex, and race frequency matched controls per case were selected from non-cancer deaths. MAIN OUTCOME MEASURES: Odds ratios for non-Hodgkin's lymphoma, melanoma, and skin cancer from residential and occupational sunlight exposure adjusted for age, sex, race, socioeconomic status, and farming occupation. RESULTS: Non-Hodgkin's lymphoma mortality was not positively associated with sunlight exposure based on residence. Both melanoma and skin cancer were positively associated with residential sunlight exposure. Adjusted odds ratios for residing in states with the highest sunlight exposure were 0.83 (95% confidence interval 0.81 to 0.86) for non-Hodgkin's lymphoma, 1.12 (1.06 to 1.19) for melanoma, and 1.30 (1.18 to 1.43) for skin cancer. In addition, non-Hodgkin's lymphoma mortality was not positively associated with occupational sunlight exposure (odds ratio 0.88; 0.81 to 0.96). Skin cancer was slightly positively associated with occupational sunlight exposure (1.14; 0.96 to 1.36). CONCLUSIONS: Unlike skin cancer and to some extent melanoma, non-Hodgkin's lymphoma mortality was not positively associated with exposure to sunlight. The findings do not therefore support the hypothesis that sunlight exposure contributes to the rising rates of non-Hodgkin's lymphoma. PMID:9167561

  1. B-Cell Hematologic Malignancy Vaccination Registry

    ClinicalTrials.gov

    2017-12-29

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

  2. Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)

    ClinicalTrials.gov

    2018-06-25

    Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Malignant Glioma; NTRK1 Fusion Positive; NTRK2 Fusion Positive; NTRK3 Fusion Positive; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Refractory Central Nervous System Neoplasm; Refractory Childhood Malignant Germ Cell Tumor; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor

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

    ClinicalTrials.gov

    2014-02-21

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

  4. Intravascular large B-cell lymphoma diagnosed by FDG-PET/CT and endometrial biopsy.

    PubMed

    Takeoka, Yasunobu; Inaba, Akiko; Fujitani, Yotaro; Kosaka, Saori; Yamamura, Ryosuke; Senzaki, Hideto; Okamura, Terue; Ohta, Kensuke

    2011-11-01

    Intravascular large B-cell lymphoma (IVLBCL) is a rare form of non-Hodgkin's lymphoma characterized by a proliferation of tumor cells within the lumina of small to medium-sized vessels. Because there are few or no concomitant solid lesions, a diagnosis of IVLBCL usually cannot be established by CT or MR imaging. Herein, we describe a case of IVLBCL involving the uterus, in which (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was useful for diagnosis. A 47-year-old woman was referred to our hospital because of fever and anemia. Laboratory examination demonstrated anemia and thrombocytopenia. Bone marrow aspiration and biopsy showed hemophagocytosis without involvement of lymphoma cells. Random skin biopsy did not demonstrate lymphoma involvement. FDG-PET/CT imaging showed FDG accumulation in the uterus. MR imaging demonstrated uterine leiomyoma only. Based on these findings, uterine endometrial biopsy was performed and histological diagnosis of IVLBCL involving the uterus was established. She received 6 courses of R-CHOP therapy and high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. At present, she remains in complete remission after 33 months.

  5. Copanlisib and Nivolumab in Treating Participants With Recurrent or Refractory Diffuse Large B-cell Lymphoma or Primary Mediastinal Large B-cell Lymphoma

    ClinicalTrials.gov

    2018-06-11

    Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  6. Second Malignancy Risks After Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia: Differences by Lymphoma Subtype

    PubMed Central

    Morton, Lindsay M.; Curtis, Rochelle E.; Linet, Martha S.; Bluhm, Elizabeth C.; Tucker, Margaret A.; Caporaso, Neil; Ries, Lynn A.G.; Fraumeni, Joseph F.

    2010-01-01

    Purpose Previous studies have shown increased risks of second malignancies after non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL); however, no earlier investigation has quantified differences in risk of new malignancy by lymphoma subtype. Patients and Methods We evaluated second cancer and leukemia risks among 43,145 1-year survivors of CLL/small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL) from 11 Surveillance, Epidemiology, and End Results (SEER) population-based registries during 1992 to 2006. Results Among patients without HIV/AIDS–related lymphoma, lung cancer risks were significantly elevated after CLL/SLL and FL but not after DLBCL (standardized incidence ratio [SIR], CLL/SLL = 1.42, FL = 1.28, DLBCL = 1.00; Poisson regression P for difference among subtypes, PDiff = .001). A similar pattern was observed for risk of cutaneous melanoma (SIR: CLL/SLL = 1.92, FL = 1.60, DLBCL = 1.06; PDiff = .004). Acute nonlymphocytic leukemia risks were significantly elevated after FL and DLBCL, particularly among patients receiving initial chemotherapy, but not after CLL/SLL (SIR: CLL/SLL = 1.13, FL = 5.96, DLBCL = 4.96; PDiff < .001). Patients with HIV/AIDS–related lymphoma (n = 932) were predominantly diagnosed with DLBCL and had significantly and substantially elevated risks for second anal cancer (SIR = 120.50) and Kaposi's sarcoma (SIR = 138.90). Conclusion Our findings suggest that differing immunologic alterations, treatments (eg, alkylating agent chemotherapy), genetic susceptibilities, and other risk factors (eg, viral infections, tobacco use) among lymphoma subtypes contribute to the patterns of second malignancy risk. Elucidating these patterns may provide etiologic clues to lymphoma as well as to the second malignancies. PMID:20940199

  7. Brentuximab Vedotin and Lenalidomide in Treating Patients With Relapsed or Refractory T-Cell Lymphomas

    ClinicalTrials.gov

    2018-06-15

    CD30-Positive Neoplastic Cells Present; Folliculotropic Mycosis Fungoides; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome

  8. Ten-year follow-up of pediatric patients with non-Hodgkin lymphoma treated with allogeneic or autologous stem cell transplantation.

    PubMed

    Giulino-Roth, Lisa; Ricafort, Rosanna; Kernan, Nancy A; Small, Trudy N; Trippett, Tanya M; Steinherz, Peter G; Prockop, Susan E; Scaradavou, Andromachi; Chiu, Michelle; O'Reilly, Richard J; Boulad, Farid

    2013-12-01

    Autologous or allogeneic hematopoietic stem cell transplant (SCT) is often considered in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) but there are limited data on the use of SCT for the treatment of NHL in the pediatric setting. To evaluate the role of SCT for children with NHL, we reviewed 36 consecutive pediatric patients with NHL who underwent an allogeneic (n = 21) or autologous (n = 15) SCT at our institution between 1982 and 2004. Pathologic classification included: lymphoblastic lymphoma (n = 12), Burkitt lymphoma (BL) (n = 5), diffuse large B-cell lymphoma (n = 4), anaplastic large cell lymphoma (ALCL) (n = 13), peripheral T cell lymphoma (n = 1), and undifferentiated NHL (n = 1). Donor source for allogeneic-SCT recipients was an HLA-matched related donor (n = 15), a matched unrelated donor (n = 4), or a mismatched donor (related n = 1; unrelated n = 1). Twenty-eight patients (78%) had chemotherapy responsive disease at the time of transplant (either CR or PR). Overall survival (OS) and disease-free survival (DFS) were 55% and 53% with a median follow-up of 9.75 years. Outcomes were similar in patients receiving autologous and allogeneic-SCT (DFS 53% in both groups). Patients with ALCL had a DFS of 76.9%. In contrast, of five patients transplanted for BL, none survived. DFS among patients with chemotherapy sensitive disease was 61%, compared with 25% among patients with relapsed/refractory disease (P = 0.019). Allogeneic and autologous SCT offer the prospect of durable, disease-free survival for a significant proportion of pediatric patients with relapsed or refractory NHL. Survival is superior among patients with chemotherapy sensitive disease. © 2013 Wiley Periodicals, Inc.

  9. Dulanermin with rituximab in patients with relapsed indolent B-cell lymphoma: an open-label phase 1b/2 randomised study.

    PubMed

    Cheah, Chan Yoon; Belada, David; Fanale, Michelle A; Janikova, Andrea; Czucman, Myron S; Flinn, Ian W; Kapp, Amy V; Ashkenazi, Avi; Kelley, Sean; Bray, Gordon L; Holden, Scott; Seymour, John F

    2015-04-01

    Dulanermin-a non-polyhistidine-tagged soluble recombinant human apoptosis ligand 2 (Apo2L) or tumour-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-has pro-apoptotic activity in a range of cancers and synergistic preclinical activity with rituximab against lymphoma in vivo. We aimed to assess the safety, pharmacokinetics, and efficacy of dulanermin and rituximab in patients with relapsed indolent B-cell non-Hodgkin lymphoma. We did an open-label phase 1b/2 randomised study. Four study centres in the USA enrolled patients into phase 1b, and 27 study centres in the USA, Italy, Australia, France, Czech Republic, New Zealand, and Poland enrolled patients into phase 2. In phase 1b, patients (age ≥18 years) with indolent B-cell non-Hodgkin lymphoma with stable disease or better lasting at least 6 months after the most recent rituximab-containing regimen were included. In phase 2, patients (age ≥18 years) with follicular lymphoma grades 1-3a were included. In phase 1b, patients received 4 mg/kg or 8 mg/kg intravenous dulanermin on days 1-5 of up to four 21-day cycles and intravenous rituximab 375 mg/m(2) weekly for up to eight doses. In phase 2, patients were randomly assigned (1:1:1) centrally by an interactive voice response system to dulanermin (8 mg/kg for a maximum of four 21-day cycles), rituximab (375 mg/m(2) weekly for up to eight doses), or both in combination, stratified by baseline follicular lymphoma International Prognostic Index (0-3 vs 4-5) and geographic site (USA vs non-USA). The primary endpoints of the phase 1b study were the safety, tolerability, and pharmacokinetics of dulanermin with rituximab. The primary endpoint of phase 2 was the proportion of patients who achieved an objective response. All patients who received any dose of study drug were included in safety analyses. Efficacy analyses were per protocol. Treatment was open label; all patients and investigators were unmasked to treatment allocation. This study is registered with

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

    ClinicalTrials.gov

    2013-01-23

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

  11. Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)

    ClinicalTrials.gov

    2018-06-25

    Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Deleterious ATM Gene Mutation; Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Deleterious RAD51C Gene Mutation; Deleterious RAD51D Gene Mutation; Histiocytosis; Low Grade Glioma; Malignant Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Wilms Tumor

  12. 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. Copyright © 2016 by the National Comprehensive Cancer Network.

  13. A Phase 1/2 Study To Evaluate ASN002 In Relapsed/Refractory Lymphoma And Advanced Solid Tumors

    ClinicalTrials.gov

    2018-04-30

    Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Cancer; Neoplasm; Tumor; Lymphoma, Malignant; Lymphoma, B-cell; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; B-Cell Leukemia, Chronic; B-Lymphocytic Leukemia, Chronic; Chronic Lymphocytic Leukemia; Leukemia, Lymphocytic, Chronic; Leukemia, Lymphocytic, Chronic, B Cell; Myelofibrosis; Chronic Idiopathic Myelofibrosis; Idiopathic Myelofibrosis; Lymphoma, T Cell, Peripheral; Peripheral T-Cell Lymphoma; T-Cell Lymphoma, Peripheral

  14. Epstein-Barr virus-positive diffuse large B-cell lymphoma in children: a disease reminiscent of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

    PubMed

    Uccini, Stefania; Al-Jadiry, Mazin F; Scarpino, Stefania; Ferraro, Daniela; Alsaadawi, Adel R; Al-Darraji, Amir F; Moleti, Maria Luisa; Testi, Anna Maria; Al-Hadad, Salma A; Ruco, Luigi

    2015-05-01

    Pediatric Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare disease in nonimmunocompromised hosts. In a review of 231 cases of malignant lymphoma (87 Hodgkin lymphoma and 144 non-Hodgkin lymphoma) occurring in Iraqi children, 7 cases (5% of NHLs) were classified as EBV+ DLBCL. Six children presented with nodal disease, and 1 presented with extranodal localization (bone). In all cases, the disease was at an advanced clinical stage (III/IV). Evidence of immunodeficiency (Evans syndrome and selective IgA deficiency) was observed in a single case. Two cases were "monomorphic" with immunoblastic histology, and 5 cases were "polymorphic" with histologic aspects reminiscent of nodular lymphocyte-predominant Hodgkin lymphoma (2 cases) and of CD30+ classical Hodgkin lymphoma (3 cases). In all cases, tumor cells were EBV infected (EBER+/LMP-1+), were medium-large B-cells (CD20+/CD79a+/PAX-5+/BOB-1+/OCT-2+) of non-germinal center (non-GC) origin (CD10-/MUM-1+), and had high proliferative activity (50%-70%). Chromosomal translocations involving BCL2, MYC, and IGH genes were not observed. IGH monoclonality could be demonstrated in 3 of 3 investigated cases. Six cases of EBV-negative DLBCL (4% of NHL) were present in the same series. All had monomorphic histology with centroblastic/immunoblastic morphology; 3 cases were of GC type and 3 of non-GC type. Our findings indicate that in Iraq, DLBCLs are 9% of NHLs. Moreover, 2 different types of the disease do exist; the EBV-positive cases, with strong histologic and immunohistochemical resemblance with EBV+ DLBCL of the elderly, and the EBV-negative cases, which are similar to the pediatric DLBCL usually observed in Western populations. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Toxoplasmosis masking non-Hodgkin's lymphoma: a case report.

    PubMed

    Mighell, A; Carton, A; Carey, P; High, A

    1995-12-01

    A 39-year-old female with persistent cervical lymphadenopathy is reported. Initial investigations resulted in a diagnosis of toxoplasmosis, but subsequently the patient proved to have high grade immunoblastic non-Hodgkin's lymphoma. This paper highlights the difficulties in accurately diagnosing some cases of either toxoplasmosis or lymphoma, and briefly mentions some of the ongoing technical advances which will increase diagnostic specificity and sensitivity by early detection of genetic mutations.

  16. Irradiated Donor Cells Following Stem Cell Transplant in Controlling Cancer in Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2018-05-16

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia in Remission; Hematopoietic Cell Transplantation Recipient; JAK2 Gene Mutation; Loss of Chromosome 17p; Mantle Cell Lymphoma; Minimal Residual Disease; Myelodysplastic Syndrome; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; RAS Family Gene Mutation; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hematologic Malignancy; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Therapy-Related Acute Myeloid Leukemia; Therapy-Related Myelodysplastic Syndrome; TP53 Gene Mutation

  17. Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

    ClinicalTrials.gov

    2018-04-23

    Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  18. Computer tomographic evaluation of digestive tract non-Hodgkin lymphomas.

    PubMed

    Lupescu, Ioana G; Grasu, Mugur; Goldis, Gheorghe; Popa, Gelu; Gheorghe, Cristian; Vasilescu, Catalin; Moicean, Andreea; Herlea, Vlad; Georgescu, Serban A

    2007-09-01

    Computer Tomographic (CT) study is crucial for defining distribution, characteristics and staging of primary gastrointestinal lymphomas. The presence of multifocal sites, the wall thickening with diffuse infiltration of the affected gastrointestinal (GI) segment in association with regional adenopathies, permit the orientation of the CT diagnosis for primary GI lymphomas. The gold standard for diagnosis remains, in all cases of digestive tract non-Hodgkin lymphomas (NHL), the histological examination, which allows a tissue diagnosis, performed preferably by transmural biopsy.

  19. Modified BEAM with triple autologous stem cell transplantation for patients with relapsed aggressive non-Hodgkin lymphoma.

    PubMed

    Hohloch, Karin; Zeynalova, Samira; Chapuy, Björn; Pfreundschuh, Michael; Loeffler, Markus; Ziepert, Marita; Feller, Alfred C; Trümper, Lorenz; Hasenclever, Dirk; Wulf, Gerald; Schmitz, Norbert

    2016-06-01

    Treatment of relapse and primary progression in aggressive lymphoma remains unsatisfactory; outcome is still poor. Better treatment strategies are much needed for this patient population. The R1 study is a prospective multi-center phase I/II study evaluating a dose finding approach with a triple transplant regimen in four BEAM dose levels in patients with relapsed aggressive non-Hodgkin lymphoma. The aim of the study was to determine feasibility, toxicity, and remission rate. In a total of 39 patients (pts.) enrolled in the study, 24 pts. were evaluated in the following analysis. Twenty pts. had aggressive B cell lymphoma, and two pts. had T cell lymphoma. All evaluated patients responded to DexaBEAM with a sufficient stem cell harvest. The phase I/II study was started with BEAM dose level II. Four patients were treated at dose level II, and 20 pts. were treated at dose level III. Due to the early termination of the study, dose levels I and IV were never administered. Sixteen pts. completed therapy according to protocol, and eight pts. (33.3 %) stopped treatment early. Infections (27 %) and stomatitis (13 %) were the most frequent grade III/IV non-hematologic toxicities. Thirteen percent of patients presented with severe grade III/IV lung toxicity during modified BEAM (m-BEAM). Fourteen pts. achieved a complete response (CR), one pt. achieved no change (NC), six pts. had progressive disease (PD), and two pts. died; for one pt., outcome is not known. One-year and 3-year event-free survival (EFS) was 38 and 33 %, respectively. Overall survival (OS) after 1 and 3 years was 50 and 38 %. In conclusion, dose escalation of standard BEAM is not feasible due to toxicity.

  20. Phase 1 study of inotuzumab ozogamicin combined with R-GDP for the treatment of patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma.

    PubMed

    Sangha, Randeep; Davies, Andrew; Dang, Nam H; Ogura, Michinori; MacDonald, David A; Ananthakrishnan, Revathi; Paccagnella, M Luisa; Vandendries, Erik; Boni, Joseph; Goh, Yeow Tee

    2017-01-01

    Objective : To evaluate safety, tolerability, and preliminary activity of inotuzumab ozogamicin (InO) plus rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) in patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma (NHL). Methods : Patients received InO plus R-GDP (21-day cycle; six-cycle maximum) using up-and-down dose-escalation schema for gemcitabine and cisplatin to define the highest dosage regimen(s) with acceptable toxicity (Part 1; n  = 27). Part 2 ( n  = 10) confirmed safety and tolerability; Part 3 ( n  = 18) evaluated preliminary efficacy. Results: Among 55 patients enrolled, 42% were refractory at baseline (median 2 [range, 1-6] prior therapies); 38% had diffuse large B-cell lymphoma (DLBCL). The highest dosage regimen with acceptable toxicity was InO 0.8 mg/m 2 , rituximab 375 mg/m 2 , cisplatin 50 mg/m 2 , gemcitabine 500 mg/m 2 (day 1 only) and dexamethasone 40 mg (days 1-4); this was confirmed in Part 2, in which three patients had dose-limiting toxicities (grade 4 thrombocytopenia [ n  = 2], febrile neutropenia [ n  = 2]). Most frequent treatment-related adverse events were thrombocytopenia (any grade, 85%; grade ≥3, 75%) and neutropenia (69%; 62%). Overall (objective) response rate (ORR) was 53% (11 complete, 18 partial responses); ORR was 71%, 33%, and 62% in patients with follicular lymphoma ( n  = 14), DLBCL ( n  = 21), and mantle cell lymphoma ( n  = 13), respectively. Conclusions: InO 0.8 mg/m 2 plus R-GDP was associated with manageable toxicity, although gemcitabine and cisplatin doses were lower than in the standard R-GDP regimen due to hematologic toxicity. Evidence of antitumor activity was observed; however, these exploratory data should be interpreted with caution due to the small sample size and short follow-up duration (Clinicaltrials.gov number: NCT01055496).

  1. Case report of precursor B-cell lymphoblastic lymphoma presenting as syncope and cardiac mass in a nonimmunocompromised child.

    PubMed

    Hahn, Barry; Rao, Sudha; Shah, Binita

    2007-08-01

    We report the case of a previously healthy, 10-year-old boy who presented to the emergency department with a syncopal episode. In the emergency department, the patient was diagnosed with a right atrial mass, later identified as a precursor B-cell lymphoblastic lymphoma (LL). Most causes of syncope in children are not life threatening. In most cases, it indicates a predisposition to vasovagal episodes. Lymphomas account for approximately 7% of malignancies among children younger than 20 years, are more common in white males and immunocompromised patients, and are predominantly tumors of T-cell origin. Children with non-Hodgkin lymphoma usually present with extranodal disease, most frequently involving the abdomen (31%), mediastinum (26%), or head and neck (29%). Our patient was unique in that he was a nonimmunocompromised, black boy, presenting with syncope in the setting of a large atrial mass identified as a precursor B-cell LL. To our knowledge, there are no reported cases of precursor B-cell LL presenting as syncope and a cardiac mass.

  2. Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC, BCL-2, and BCL-6.

    PubMed

    Li, Xiaomei; Huang, Ying; Bi, Chengfeng; Yuan, Ji; He, Hong; Zhang, Hong; Yu, QiuBo; Fu, Kai; Li, Dan

    2017-06-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well. Nineteen cases of primary central nervous system DLBCL were stratified according to immunostaining algorithms of Hans, Choi and Meyer (Tally) and we investigated the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53. The Epstein-Barr virus and Borna disease virus infection were also detected. Among nineteen cases, most (15-17 cases) were assigned to the activated B-cell-like subtype, highly expression of C-MYC (15 cases, 78.9%), BCL-2 (10 cases, 52.6%), BCL-6 (15 cases, 78.9%). Unfortunately, two cases were positive for PD-L1 while PD-L2 was not expressed in any case. Two cases infected with BDV but no one infected with EBV. In conclusion, most primary central nervous system DLBCLs show an activated B-cell-like subtype characteristic and have multiple expressions of C-MYC, BCL-2, BCL-6 protein, these features might be significant factor to predict the outcome and guide treatment of PCNS-DLBCLs. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma

    ClinicalTrials.gov

    2017-10-24

    Composite Lymphoma; Grade 3b Follicular Lymphoma; Stage I Diffuse Large B-Cell Lymphoma; Stage I Follicular Lymphoma; Stage II Diffuse Large B-Cell Lymphoma; Stage II Follicular Lymphoma; Stage III Diffuse Large B-Cell Lymphoma; Stage III Follicular Lymphoma; Stage IV Diffuse Large B-Cell Lymphoma; Stage IV Follicular Lymphoma

  4. Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

    ClinicalTrials.gov

    2018-06-13

    Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

  5. Molecular subtyping of diffuse large B-cell lymphoma: update on biology, diagnosis and emerging platforms for practising pathologists.

    PubMed

    Gifford, Grace K; Gill, Anthony J; Stevenson, William S

    2016-01-01

    Molecular classification of diffuse large B-cell lymphoma (DLBCL) is critical. Numerous methodologies have demonstrated that DLBCL is biologically heterogeneous despite morphological similarities. This underlies the disparate outcomes of treatment response or failure in this common non-Hodgkin lymphoma. This review will summarise historical approaches to lymphoma classifications, current diagnosis of DLBCL, molecular techniques that have primarily been used in the research setting to distinguish and subclassify DLBCL, evaluate contemporary diagnostic methodologies that seek to translate lymphoma biology into clinical practice, and introduce novel diagnostic platforms that may overcome current issues. The review concludes with an overview of key molecular lesions currently identified in DLBCL, all of which are potential targets for drug treatments that may improve survival and cure. Copyright © 2015 The Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  6. Exposure to Coxiella burnetii and risk of non-Hodgkin lymphoma: a retrospective population-based analysis in the Netherlands.

    PubMed

    van Roeden, Sonja E; van Houwelingen, Fedor; Donkers, Chiel M J; Hogewoning, Sander J; de Lange, Marit M A; van der Hoek, Wim; Kampschreur, Linda M; Bonten, Marc J M; Hoepelman, Andy I M; Bleeker-Rovers, Chantal P; Wever, Peter C; Oosterheert, Jan Jelrik

    2018-05-01

    An association between Coxiella burnetii and non-Hodgkin lymphoma has been suggested. After a large Q fever epidemic in the Netherlands (2007-10), we postulated that the incidence of non-Hodgkin lymphoma would be increased during and after the epidemic in areas with a high endemicity of Q fever compared with those with low endemicity. We did a retrospective population-based analysis and calculated relative risks (RRs) of non-Hodgkin lymphoma during 1-year periods before, during, and after the Q fever epidemic, for areas with intermediate and high endemicity of Q fever compared with low endemic areas. We also calculated the RR of non-Hodgkin lymphoma in people with chronic Q fever compared with the general population. Between Jan 1, 2002, and Dec 31, 2013, 48 760 cases of non-Hodgkin lymphoma were diagnosed. The incidence of non-Hodgkin lymphoma ranged from 21·4 per 100 000 per year in 2002 to 26·7 per 100 000 per year in 2010. A significant association with non-Hodgkin lymphoma was noted in 2009 for areas with a high endemicity of Q fever compared with low endemic areas (RR 1·16, 95% CI 1·02-1·33; p=0·029); no further associations were noted in any other year or for areas with intermediate Q fever endemicity. Among 439 individuals with chronic Q fever, five developed non-Hodgkin lymphoma, yielding a crude absolute risk of 301·0 cases per 100 000 per year (RR 4·99, 95% CI 2·07-11·98; p=0·0003) compared with the general population in the Netherlands. These findings do not support the hypothesis that Q fever has a relevant causal role in the development of non-Hodgkin lymphoma. Several limitations, inherent to the design of this study, might lead to both underestimation and overestimation of the studied association. Foundation Q-support and Institut Mérieux. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    ClinicalTrials.gov

    2014-05-22

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

  8. A Review of Autologous Stem Cell Transplantation in Lymphoma.

    PubMed

    Zahid, Umar; Akbar, Faisal; Amaraneni, Akshay; Husnain, Muhammad; Chan, Onyee; Riaz, Irbaz Bin; McBride, Ali; Iftikhar, Ahmad; Anwer, Faiz

    2017-06-01

    Chemotherapy remains the first-line therapy for aggressive lymphomas. However, 20-30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin lymphoma (HL) recur after initial therapy. We want to explore the role of high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients. There is some utility of upfront consolidation for-high risk/high-grade B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma, but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL. Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high-dose consolidation or in the maintenance setting.

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

    ClinicalTrials.gov

    2013-01-24

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

  10. Management of mantle cell lymphoma in the elderly: current and potential strategies.

    PubMed

    Vignon, Marguerite; Venon, Marie-Dominique; Hermine, Olivier; Delarue, Richard

    2013-12-01

    Mantle cell lymphoma is a distinct subtype of B-cell non-Hodgkin lymphoma, accounting for 3-10 % of all non-Hodgkin lymphoma cases. The median age at diagnosis is nearly 70 years. The prognosis of patients is based on the Mantle Cell Lymphoma International Prognostic Index, which is calculated on the basis of four independent prognostic factors (age, performance status, serum lactate dehydrogenase and leukocyte count). Treatment of elderly patients with de novo untreated mantle cell lymphoma is based on rituximab combined with chemotherapy. The most commonly used regimen is the classical CHOP21 (cyclophosphamide, doxorubicin, vincristine and prednisone) regimen. Bendamustine is also an option, especially for patients with cardiac comorbidities. In elderly patients who are relatively young and fit, an approach based on treatment usually used for younger patients, with cytarabine-based induction followed by autologous stem cell transplantation, should be discussed. Treatment of relapsing patients is based on the use of newer effective drugs, including bortezomib, lenalidomide and thalidomide, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus. These drugs are often combined with rituximab and can be prescribed in combination with chemotherapy. Promising new drugs are Bruton tyrosine kinase inhibitors and other inhibitors of the phosphoinositide 3-kinase (PI3K)-mTOR-protein kinase B (AKT) pathway. Despite these new advances, mantle cell lymphoma remains an incurable disease, and further basic and clinical research is warranted.

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

    ClinicalTrials.gov

    2013-01-23

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

  12. Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination.

    PubMed

    Magro, Cynthia M; Wang, Xuan; Subramaniyam, Shivakumar; Darras, Natasha; Mathew, Susan

    2014-04-01

    Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.

  13. CCR investigators use liquid biopsies to uncover cancer in the blood of lymphoma patients | Center for Cancer Research

    Cancer.gov

    CCR investigators are using circulating tumor DNA (ctDNA) as a type of noninvasive liquid biopsy for patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma. are using circulating tumor DNA (ctDNA) as a type of noninvasive liquid biopsy for patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma.

  14. Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)

    ClinicalTrials.gov

    2018-06-20

    Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Hodgkin Lymphoma; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; EZH2 Gain of Function; EZH2 Gene Mutation; Histiocytosis; Loss of BRG1 Protein Expression; Loss of INI 1 Protein Expression; Low Grade Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Hodgkin Lymphoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Hodgkin Lymphoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Soft Tissue Sarcoma; Rhabdoid Tumor; SMARCA4 Gene Inactivation; SMARCB1 Gene Inactivation; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

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

    ClinicalTrials.gov

    2017-02-21

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

  16. T-cell receptor signaling activates an ITK/NF-κB/GATA-3 axis in T-cell lymphomas facilitating resistance to chemotherapy

    PubMed Central

    Wang, Tianjiao; Lu, Ye; Polk, Avery; Chowdhury, Pinki; Zamalloa, Carlos Murga; Fujiwara, Hiroshi; Suemori, Koichiro; Beyersdorf, Niklas; Hristov, Alexandra C.; Lim, Megan S.; Bailey, Nathanael G.; Wilcox, Ryan A.

    2016-01-01

    Purpose T-cell lymphomas are a molecularly heterogeneous group of non-Hodgkin lymphomas (NHL) that account for a disproportionate number of NHL disease-related deaths due to their inherent and acquired resistance to standard multiagent chemotherapy regimens. Despite their molecular heterogeneity and frequent loss of various T-cell specific receptors, the T-cell antigen receptor is retained in the majority of these lymphomas. As T-cell receptor (TCR) engagement activates a number of signaling pathways and transcription factors that regulate T-cell growth and survival, we examined the TCR’s role in mediating resistance to chemotherapy. Experimental Design Genetic and pharmacologic strategies were utilized to determine the contribution of tyrosine kinases and transcription factors activated in conventional T cells following T-cell receptor (TCR) engagement in acquired chemotherapy resistance in primary T-cell lymphoma cells and patient-derived cell lines. Results Here we report that TCR signaling activates a signaling axis that includes ITK, NF-κB, and GATA-3, and promotes chemotherapy resistance. Conclusions These observations have significant therapeutic implications, as pharmacologic inhibition of ITK prevented activation of this signaling axis and overcame chemotherapy resistance. PMID:27780854

  17. miR expression in MYC-negative DLBCL/BL with partial trisomy 11 is similar to classical Burkitt lymphoma and different from diffuse large B-cell lymphoma.

    PubMed

    Zajdel, Michalina; Rymkiewicz, Grzegorz; Chechlinska, Magdalena; Blachnio, Katarzyna; Pienkowska-Grela, Barbara; Grygalewicz, Beata; Goryca, Krzysztof; Cieslikowska, Maria; Bystydzienski, Zbigniew; Swoboda, Pawel; Walewski, Jan; Siwicki, Jan Konrad

    2015-07-01

    Fast and reliable differential diagnosis of Burkitt lymphoma (BL) vs. diffuse large B cell lymphoma (DLBCL) is of major importance for therapeutic decisions and patient outcome. Aggressive B cell non-Hodgkin lymphomas (B-NHLs) that do not belong to the abovementioned entities were categorized by the current WHO lymphoma classification as "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (DLBCL/BL). We have recently described a DLBCL/BL subgroup with recurrent chromosome 11q aberrations, resembling BL (B-NHLs[11q]). Here, we analyzed 102 prospectively collected fine needle aspirates from patients with aggressive B-NHLs in order to investigate the potential of microRNA (miR)-155, its precursor BIC, as well as miR-21 and miR-26a to differentiate BL from DLBCL, and from DLBCL/BL that include B-NHLs[11q]. Both BL and DLBCL/BL cases, including B-NHLs[11q], demonstrated significantly lower expression levels of miR-155/BIC, miR-21, and miR-26a compared to primary DLBCL. In conclusion, the miRs expression in B-NHLs[11q] provides a new suggestion, in addition to pathomorphological and clinical similarities between classical, i.e., MYC translocation-positive BL, and B-NHLs[11q], to recognize the B-NHLs[11q] subgroup of DLBCL/BL category as a MYC translocation-negative variant of BL in most cases, and points to the potential utility of miR-155/BIC/miR-21/miR-26a for the differential diagnosis of a heterogeneous category of DLBCL/BL.

  18. Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment

    PubMed Central

    2014-01-01

    Background Although rituximab in the combination of CHOP chemotherapy has been widely used as the standard treatment for several kinds of B-cell non-Hodgkin lymphoma (B-NHL), a great number of B-NHL patients treated with this immunotherapy still develop primary and secondary resistance. Recently Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib showed promising therapeutic effect in relapsed/refractory CLL and B-cell NHL, which provided essential alternatives for these patients. Methods The proliferation and apoptosis induction of tumor cells were measured by cell viability assay and Annexin-V staining. Western Blotting analysis and real-time PCR were used to detect the expression level of target proteins and chemokines production. Results We demonstrated that ibrutinib inhibited the proliferation and induced apoptosis of GCB-DLBCL cell lines through suppression of BCR signaling pathway and activation of caspase-3. Furthermore, the chemokines CCL3 and CCL4 production from tumor cells were also found to be attenuated by ibrutinib treatment. But different cell lines exhibited distinct sensitivity after ibrutinib treatment. Interestingly, the decreasing level of p-ERK after ibrutinib treatment, but not the basal expression level of Btk, correlated with different drug sensitivity. Conclusions Ibrutinib could be a potentially useful therapy for GCB-DLBCL and the decreasing level of p-ERK could become a useful biomarker to predict related therapeutic response. PMID:24693884

  19. [Outcome of haploidentical hematopoietic stem cell transplantation for non-Hodgkin lymphoma].

    PubMed

    Xu, T; Chen, J; Jin, Z M; Miao, M; Fu, C C; Qiu, H Y; Tang, X W; Han, Y; Sun, A N; Wu, D P

    2016-08-14

    To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation (Haplo- HSCT) for refractory, relapsed or highly aggressive non- Hodgkin lymphoma (NHL) patients. A total of 26 patients with refractory, relapsed or highly aggressive NHL who received Haplo- HSCT from Jan. 2004 to Mar. 2015 were analyzed retrospectively. Of them, 4 patients had diffuse large B-cell lymphoma (DLBCL), 1 had follicular lymphoma, 5 had B-lymphoblastic lymphoma/leukemia, 9 had T- lymphoblastic lymphoma/leukemia, 1 patient anaplastic large cell lymphoma (ALK-negative), 5 had peripheral T-cell lymphoma (NOS), and 1 had NK/T-cell lymphoma. At the time of initial diagnosis, 6 patients had Ann Arbor stage Ⅲ disease, 20 patients showed stage Ⅳ. At the time of Haplo- HSCT, 7 patients were in the first complete remission (CR1), 4 in the second complete remission (CR2), 7 in partial remission, 1 in stable disease, 7 in progressive disease, and 19 of 26 patients were refractory or relapsed. The neutrophil and platelet counts recovered at 12 (11-17) d and 14 (11-31) d after Haplo- HSCT, respectively. All patients achieved full donor chimerism at 30d after Haplo- HSCT. With a median follow- up of 14 (4- 136) months, 20 cases (76.92%) survived, 15 (57.69%) survived without lymphoma, and 7 (26.92%) relapsed. Conditioning regimen related adverse reactions were all disappeared after treatment. The estimated 2-year recurrence rate after Haplo-HSCT was 42.20%. The estimated 2-year overall survival (OS) and disease-free survival (DFS) rate was 71.60% and 48.90%, respectively. Patients in CR before Haplo- HSCT experienced better 2- year OS (100.0% vs 52.4%, P=0.023) and 2- year DFS (88.9% vs 27.0%, P=0.013). Haplo- HSCT may effective and safe for those relapsed, refractory or highly aggressive NHL patients who did not have matched donor nor suitable for autologous HSCT.

  20. RS3PE revealing recurrent non-Hodgkin's lymphoma.

    PubMed

    Gisserot, Olivier; Crémades, Serge; Landais, Cécile; Leyral, Guénaelle; Bernard, Philippe; de Jauréguiberry, Jean-Pierre

    2004-09-01

    A patient meeting published criteria for remitting seronegative symmetrical synovitis with pitting edema (RS3PE) was found to have a synchronous recurrence of non-Hodgkin's malignant lymphoma. Reported cases of RS3PE associated with hematological malignancies and other forms of cancer are reviewed.

  1. A clinical analysis of two indolent lymphoma entities: mantle cell lymphoma and marginal zone lymphoma (including the mucosa-associated lymphoid tissue and monocytoid B-cell subcategories): a Southwest Oncology Group study.

    PubMed

    Fisher, R I; Dahlberg, S; Nathwani, B N; Banks, P M; Miller, T P; Grogan, T M

    1995-02-15

    The objectives of this study were (1) to determine the clinical presentation and natural history associated with two newly recognized pathologic entities termed mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), including the mucosa-associated lymphoid tissue (MALT) and monocytoid B-cell subcategories, and (2) to determine whether these entities differ clinically from the other relatively indolent non-Hodgkin's lymphomas with which they have been previously classified. We reviewed the conventional pathology and clinical course of 376 patients who had no prior therapy; had stage III/IV disease; were classified as Working Formulation categories A, B, C, D, or E; and received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) on Southwest Oncology Group (SWOG) studies no. 7204, 7426, or 7713. All slides were reviewed by the three pathologists who reached a consensus diagnosis. Age, sex, performance status, bone marrow and/or gastrointestinal involvement, failure-free survival, and overall survival were compared among all the categories. We found that (1) MCL and MZL each represent approximately 10% of stage III or IV patients previously classified as Working Formulation categories A through E and treated with CHOP on SWOG clinical trials; (2) the failure-free survival and overall survival of patients with MZL is the same as that of patients with Working Formulation categories A through E, but the failure-free survival and overall survival of the monocytoid B-cell patients were higher than that of the MALT lymphoma patients (P = .009 and .007, respectively); and (3) the failure-free survival and overall survival of patients with MCL is significantly worse than that of patients with Working Formulation categories A through E (P = .0002 and .0001, respectively). In conclusion, patients with advanced stage MALT lymphomas may have a more aggressive course than previously recognized. Patients with MCL do not have an indolent lymphoma and are candidates

  2. Treatment of initial parenchymal central nervous system involvement in systemic aggressive B-cell lymphoma.

    PubMed

    Nijland, Marcel; Jansen, Anne; Doorduijn, Jeanette K; Enting, Roelien H; Bromberg, Jacoline E C; Kluin-Nelemans, Hanneke C

    2017-09-01

    Central nervous system (CNS) involvement in systemic B-cell non-Hodgkin lymphoma (B-NHL) at diagnosis (sysCNS) is rare. We investigated the outcome of 21 patients with sysCNS, most commonly diffuse large B-cell lymphoma, treated with high dose methotrexate (HD-MTX) and R-CHOP. The median number of cycles of HD-MTX and R-CHOP was 4 (range 1-8) and 6 (range 0-8), respectively. Consolidative whole brain radiotherapy (WBRT) was given to 33% (7/21) patients. With a median follow-up of 44 months the 3-year progression free survival (PFS) and overall survival (OS) were 45% (95%CI 34-56%) and 49% (95%CI 38-60%), respectively. Over 90% of patients had an unfavorable international prognostic index score, reflected by treatment-related mortality of 19% (4/21) and relapse-related mortality of 28% (6/21). The outcome of these patients was, however, unexpectedly good when compared to secondary CNS relapses. Prospective studies are needed to define the optimal treatment for patients with sysCNS, but its rarity might be challenging.

  3. Biodynamic imaging of therapeutic efficacy for canine B-cell lymphoma: preclinical trial results

    NASA Astrophysics Data System (ADS)

    Choi, H.; Turek, J.; Li, Z.; Childress, M.; Nolte, D.

    2018-02-01

    Biodynamic imaging uses coherence-gated dynamic light scattering to create three dimensional maps of intracellular dynamics in living tissue biopsies. The technique is sensitive to changes in intracellular dynamics dependent on the mechanism of action (MoA) of therapeutics applied in vitro to the living samples. A preclinical trial in the assessment of chemotherapeutic response of dogs with B-cell lymphoma to the doxorubicin-based therapy CHOP has been completed using biodynamic imaging. The trial enrolled 19 canine patients presenting with non-Hodgkin's B-cell lymphoma. Biopsies were acquired through surgery or through needle cores. The time-varying power spectrum of scattered light after drugs are applied ex vivo to the biopsies represent biodynamic biomarkers that are used in machine learning algorithms to predict the patient clinical outcome. Two distinct phenotypes emerged from the analysis that correlate with patient drug resistance or sensitivity. Cross validation of the algorithms perform with an accuracy of 90% in the prediction of dogs that will respond to treatment. Biodynamic imaging has the potential to help select chemotherapy for personalized cancer care.

  4. Influence of morphology on survival for non-Hodgkin lymphoma in Europe and the United States.

    PubMed

    Sant, Milena; Allemani, Claudia; De Angelis, Roberta; Carbone, Antonino; de Sanjosè, Silvia; Gianni, Alessandro M; Giraldo, Pilar; Marchesi, Francesca; Marcos-Gragera, Rafael; Martos-Jiménez, Carmen; Maynadié, Marc; Raphael, Martine; Berrino, Franco

    2008-03-01

    We explored the influence of morphology on geographic differences in 5-year survival for non-Hodgkin lymphoma (NHL) diagnosed in 1990-1994 and followed for 5years: 16,955 cases from 27 EUROCARE-3 cancer registries, and 22,713 cases from 9 US SEER registries. Overall 5-year relative survival was 56.1% in EUROCARE west, 47.1% in EUROCARE east and 56.3% in SEER. Relative excess risk (RER) of death was 1.05 (95% confidence interval (CI) 1.01-1.10) in EUROCARE west, 1.52 (95% CI 1.44-1.60) in EUROCARE east (SEER reference). Excess risk of death was significantly above reference (diffuse B lymphoma) for Burkitt's and NOS lymphoma; not different for lymphoblastic and other T-cell; significantly below reference (in the order of decreasing relative excess risk) for NHL NOS, mantle cell/centrocytic, lymphoplasmacytic, follicular, small lymphocytic/chronic lymphocytic leukaemia, other specified NHL and cutaneous morphologies. Interpretation of marked variation in survival with morphology is complicated by classification inconsistencies. The completeness and standardisation of cancer registry morphology data needs to be improved.

  5. CCR investigators use liquid biopsies to uncover cancer in the blood of lymphoma patients | Center for Cancer Research

    Cancer.gov

    CCR investigators are using circulating tumor DNA (ctDNA) as a type of noninvasive liquid biopsy for patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma. are using circulating tumor DNA (ctDNA) as a type of noninvasive liquid biopsy for patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin

  6. Peripheral T-cell lymphoma: autologous hematopoietic cell transplantation as first-line therapy.

    PubMed

    Laport, Ginna G

    2010-09-01

    The peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin's lymphomas associated with an unfavorable prognosis compared with the B-cell non-Hodgkin's lymphomas. The PTCLs are characterized by high remission rates after frontline therapy, but relapse inevitably occurs. The impact of high-dose chemotherapy with autologous hematopoietic cell transplantation (AHCT) as early consolidation therapy will be the focus of this review. In several prospective trials, only PTCL patients with responsive disease after induction chemotherapy proceeded to AHCT. The progression-free survivals ranged from 30% to 40% with low toxicity. The outcomes in retrospective trials appear more favorable but such trials were affected by a selection bias because only chemosensitive patients actually proceeded to AHCT, whereas the prospective studies were intention-to-treat analyses. Most of the published trials demonstrated that prognostic models such as the International Prognostic Index and the Prognostic Index for T-cell lymphoma help predict outcome after AHCT. Current data support the use of AHCT as early consolidation therapy for PTCL patients who are chemosensitive after induction chemotherapy. However, approximately one-third of patients are early induction failures and thus are not able to proceed to AHCT. Additionally, disease relapse remains the leading cause of treatment failure after AHCT, and thus more intensive treatment strategies or better noncross-resistant therapies are greatly needed early in the course of the disease.

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

    ClinicalTrials.gov

    2013-01-08

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

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

    ClinicalTrials.gov

    2014-02-21

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

  9. Advances and issues in mantle cell lymphoma research: report of the 2014 Mantle Cell Lymphoma Consortium Workshop.

    PubMed

    Kahl, Brad S; Gordon, Leo I; Dreyling, Martin; Gascoyne, Randy D; Sotomayor, Eduardo M

    2015-01-01

    Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma characterized by the t(11;14) chromosomal translocation and cyclin D1 over-expression. A biologically and clinically heterogeneous lymphoma, MCL, remains clinically challenging, with no proven curative therapy and no established standard of care. However, there have been considerable advances in the last several years in the treatment and understanding of MCL with the FDA approval of lenalidomide and ibrutinib, the development of other potentially active novel agents and the identification of recurrent mutations through new genomic sequencing approaches that may contribute to the biology of MCL and to therapeutic resistance. At the Lymphoma Research Foundation's 11th MCL Workshop, researchers gathered to discuss recent studies and current issues related to the biology of MCL, novel therapeutic targets and new treatment strategies. The presentations are summarized in this manuscript, which is intended to highlight areas of active investigation and identify topics for future research.

  10. 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

  11. T-cell/histiocyte-rich large B-cell lymphoma of stomach.

    PubMed

    Barut, Figen; Kandemir, Nilufer Onak; Gun, Banu Dogan; Ozdamar, Sukru Oguz

    2016-07-01

    T-cell/histiocyte-rich large B-cell lymphoma is an unusually encountered lymphoid neoplasm of stomach with aggressive course, and is an uncommon morphologic variant of diffuse large B-cell lymphoma. An ulcerated mass, 7x5x1 cm in size was observed within the gastrectomy specimen of a 76-year-old female patient. In cross sections, besides mature lymphoid cells displaying T-cell phenotype, a neoplastic formation composed of large, pleomorphic atypical lymphoid cells with, prominent nucleoli, vesicular nuclei and abundant eosinophilic cytoplasm displaying B-cell phenotype were observed. Meanwhile, histiocyte-like mononuclear cells and Reed-Sternberg-like multinuclear cells expressing CD68 and Mac387 were also observed. The diagnosis of the case was T cell/histiocyte-rich large B-cell lymphoma. This rarely encountered neoplasm should be kept in mind in the differential diagnosis of primary gastric lymphomas.

  12. T-cell Receptor Signaling Activates an ITK/NF-κB/GATA-3 axis in T-cell Lymphomas Facilitating Resistance to Chemotherapy.

    PubMed

    Wang, Tianjiao; Lu, Ye; Polk, Avery; Chowdhury, Pinki; Zamalloa, Carlos Murga; Fujiwara, Hiroshi; Suemori, Koichiro; Beyersdorf, Niklas; Hristov, Alexandra C; Lim, Megan S; Bailey, Nathanael G; Wilcox, Ryan A

    2017-05-15

    Purpose: T-cell lymphomas are a molecularly heterogeneous group of non-Hodgkin lymphomas (NHL) that account for a disproportionate number of NHL disease-related deaths due to their inherent and acquired resistance to standard multiagent chemotherapy regimens. Despite their molecular heterogeneity and frequent loss of various T cell-specific receptors, the T-cell antigen receptor is retained in the majority of these lymphomas. As T-cell receptor (TCR) engagement activates a number of signaling pathways and transcription factors that regulate T-cell growth and survival, we examined the TCR's role in mediating resistance to chemotherapy. Experimental Design: Genetic and pharmacologic strategies were utilized to determine the contribution of tyrosine kinases and transcription factors activated in conventional T cells following TCR engagement in acquired chemotherapy resistance in primary T-cell lymphoma cells and patient-derived cell lines. Results: Here, we report that TCR signaling activates a signaling axis that includes ITK, NF-κB, and GATA-3 and promotes chemotherapy resistance. Conclusions: These observations have significant therapeutic implications, as pharmacologic inhibition of ITK prevented the activation of this signaling axis and overcame chemotherapy resistance. Clin Cancer Res; 23(10); 2506-15. ©2016 AACR . ©2016 American Association for Cancer Research.

  13. Dioxin emissions from a solid waste incinerator and risk of non-Hodgkin lymphoma.

    PubMed

    Floret, Nathalie; Mauny, Frédéric; Challier, Bruno; Arveux, Patrick; Cahn, Jean-Yves; Viel, Jean-François

    2003-07-01

    It is not clear whether low environmental doses of dioxin affect the general population. We previously detected a cluster of patients with non-Hodgkin lymphoma around a French municipal solid waste incinerator with high dioxin emissions. To explore the environmental route suggested by these findings, we carried out a population-based case-control study in the same area. We compared 222 incident cases of non-Hodgkin lymphoma diagnosed between 1980 and 1995 and controls randomly selected from the 1990 population census, using a 10-to-1 match. Dioxin ground-level concentrations were modeled with a second-generation Gaussian-type dispersion model, yielding four dioxin exposure categories. The latter were linked to individual places of residence, using Geographic Information System technology. The risk of developing non-Hodgkin lymphoma was 2.3 times higher (95% confidence interval = 1.4-3.8) among individuals living in the area with the highest dioxin concentration than among those living in the area with the lowest dioxin concentration. No increased risk was found for the intermediate dioxin exposure categories. Adjustment for a wide range of socioeconomic characteristics at the block group level did not alter the results. Although emissions from incinerators are usually not regarded as an important source of exposure to dioxins compared with other background sources, our findings support the hypothesis that environmental dioxins increase the risk of non-Hodgkin lymphoma among the population living in the vicinity of a municipal solid waste incinerator.

  14. 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

    ClinicalTrials.gov

    2013-02-06

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

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

    ClinicalTrials.gov

    2016-01-07

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

  16. [Primary diffuse large B-cell lymphoma of the uterine cervix--a case report].

    PubMed

    Okudaira, Taeko; Nagasaki, Akitoshi; Miyagi, Takashi; Nakazato, Tetsuro; Taira, Naoya; Kudaka, Wataru; Maehama, Toshiyuki; Takasu, Nobuyuki

    2008-08-01

    Primary malignant lymphoma of the female genital tract is an extremely rare clinical entity. We report a case of primary non-Hodgkin lymphoma of the uterine cervix. A 68-year-old woman presented with abnormal genital bleeding in May 2002. A coloposcopic examination revealed a mass in the uterine cervix. Magnetic resonance imaging showed a bulky cervical tumor(7.5 x 8 cm)invading the right parametrium and adjacent levator ani muscle. Involvement of pelvic lymph nodes was also observed. The uterine lesion exhibited homogenous hypointensity on T1 weight image and isointense to hyperintense on T2-weight image. No other lesions were detected by the whole-body computed tomography, gallium scintigraphy, and bone marrow examination. Although cytology of the smear from the uterine cervix was nondiagnostic, the histologic examination of the punch biopsy material showed a diffuse proliferation of atypical lymphoid cells. Immunophenotypic studies revealed tumor cells were positive for CD19, CD20, CD30, and k-chain. A diagnosis of diffuse large B-cell lymphoma of the uterine cervix, clinical stage IIE was made. The patient was treated with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone(CHOP)chemotherapy followed by the involved field irradiation. She remains alive and free of disease more than 5 years after the diagnosis.

  17. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma

    PubMed Central

    Vose, Julie M.; Kelly, Jennifer L.; Young, Faith; Bernstein, Steven H.; Peterson, Derick; Rich, Lynn; Blumel, Susan; Proia, Nicole K.; Liesveld, Jane; Fisher, Richard I.; Armitage, James O.; Grant, Steven; Leonard, John P.

    2011-01-01

    Given the significant activity and tolerability of bendamustine, rituximab, and bortezomib in patients with relapsed indolent and mantle cell non-Hodgkin lymphoma, and laboratory studies suggesting synergistic activity, we conducted a multicenter phase 2 study of the bendamustine/bortezomib/rituximab combination. Patients with relapsed or refractory indolent and mantle cell lymphoma with adequate organ function were treated with bendamustine 90 mg/m2 days 1 and 4; rituximab 375 mg/m2 day 1, and bortezomib 1.3 mg/m2 days 1, 4, 8, 11. Six 28-day cycles were planned. Thirty patients (7 with mantle cell lymphoma) were enrolled and treated. Eight patients experienced serious adverse events, including one event of grade 5 sepsis. Common nonhematologic adverse events were generally grade 1 or grade 2 and included nausea (50%), neuropathy (47%), fatigue (47%), constipation (40%), and fever (40%). Of 29 patients evaluable for efficacy, 24 (83%) achieved an objective response (including 15 with complete response). With median follow-up of 24 months, 2-year progression-free survival is 47% (95% confidence interval, 25%-69%). On the basis of these promising results, the US cooperative groups have initiated randomized trials to evaluate this regimen in follicular and mantle cell lymphoma. This trial was registered at www.clinicaltrials.gov as #NCT00547534. PMID:21239695

  18. Autologous hematopoietic stem cell transplantation in peripheral T-cell lymphoma using a uniform high-dose regimen.

    PubMed

    Smith, S D; Bolwell, B J; Rybicki, L A; Brown, S; Dean, R; Kalaycio, M; Sobecks, R; Andresen, S; Hsi, E D; Pohlman, B; Sweetenham, J W

    2007-08-01

    The role of high-dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell non-Hodgkin's lymphoma (NHL) have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Some retrospective studies have found comparable survival rates for patients with T- and B-cell NHL. In this study, we report our single-center experience of ASCT over one decade using a uniform chemotherapy-only high-dose regimen. Thirty-two patients with PTCL-unspecified (PTCL-u; 11 patients) and anaplastic large-cell lymphoma (21 patients) underwent autologous stem cell transplant, mostly for relapsed or refractory disease. The preparative regimen consisted of busulfan, etoposide and cyclophosphamide. Kaplan-Meier 5-year overall survival (OS) and relapse-free survival (RFS) are 34 and 18%, respectively. These results suggest a poor outcome for patients with PTCL after ASCT, and new therapies for T-cell lymphoma are needed.

  19. 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

  20. Medical history, lifestyle, family history, and occupational risk factors for marginal zone lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

    PubMed

    Bracci, Paige M; 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

    2014-08-01

    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. 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). 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). 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. Published by Oxford University Press 2014.

  1. Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS

    ClinicalTrials.gov

    2016-09-21

    Graft vs Host Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphocytic; Lymphoma; Lymphoma, Mantle-cell; Lymphoma, Non-Hodgkin; Hodgkin Disease

  2. Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)

    ClinicalTrials.gov

    2018-06-25

    Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Childhood Langerhans Cell Histiocytosis; Histiocytic Sarcoma; Juvenile Xanthogranuloma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Refractory Central Nervous System Neoplasm; Refractory Childhood Malignant Germ Cell Tumor; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor

  3. Medical history, lifestyle, family history, and occupational risk factors for mantle cell lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

    PubMed

    Smedby, Karin E; Sampson, Joshua N; Turner, Jennifer J; Slager, Susan L; Maynadié, Marc; Roman, Eve; Habermann, Thomas M; Flowers, Christopher R; Berndt, Sonja I; Bracci, Paige M; Hjalgrim, Henrik; Weisenburger, Dennis D; Morton, Lindsay M

    2014-08-01

    The etiology of mantle cell lymphoma (MCL), a distinctive subtype accounting for 2%-10% of all non-Hodgkin lymphoma, is not known. We investigated associations with self-reported medical history, lifestyle, family history, and occupational risk factors in a pooled analysis of 557 patients with MCL and 13766 controls from 13 case-control studies in Europe, North America, and Australia. Odds ratios (ORs) and 95% confidence intervals (CIs) associated with each exposure were examined using multivariate logistic regression models. The median age of the MCL patients was 62 years and 76% were men. Risk of MCL was inversely associated with history of hay fever (OR = 0.63, 95% CI = 0.48 to 0.82), and the association was independent of other atopic diseases and allergies. A hematological malignancy among first-degree relatives was associated with a twofold increased risk of MCL (OR = 1.99, 95% CI = 1.39 to 2.84), which was stronger in men (OR = 2.21, 95% CI = 1.44 to 3.38) than women (OR = 1.61, 95% CI = 0.82 to 3.19). A modestly increased risk of MCL was also observed in association with ever having lived on a farm (OR = 1.40, 95% CI = 1.03 to 1.90). Unlike some other non-Hodgkin lymphoma subtypes, MCL risk was not statistically significantly associated with autoimmune disorders, tobacco smoking, alcohol intake, body mass index, or ultraviolet radiation. The novel observations of a possible role for atopy and allergy and farm life in risk of MCL, together with confirmatory evidence of a familial link, suggest a multifactorial etiology of immune-related environmental exposures and genetic susceptibility. These findings provide guidance for future research in MCL etiology. Published by Oxford University Press 2014.

  4. Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice

    PubMed Central

    Bascuas, Thais; Moreno, María; Grille, Sofía; Chabalgoity, José A.

    2018-01-01

    We have previously shown that Salmonella immunotherapy is effective to treat B-cell non-Hodgkin lymphoma (B-NHL) in mice. However, this model involves animals with high tumor burden, whereas in the clinics B-NHL patients are usually treated with chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line therapy prior to immunotherapy. Recently, we have described a NHL-B preclinical model using CHOP chemotherapy to achieve MRD in immunocompetent animals that closely resemble patients’ conditions. In this work, we assessed the efficacy of Salmonella immunotherapy in B-NHL-bearing mice undergoing chemotherapy. Salmonella administration significantly delayed tumor growth and prolonged survival of chemotherapy-treated NHL-bearing animals. Mice receiving the CHOP–Salmonella combined therapy showed increased numbers of tumor-infiltrating leukocytes and a different profile of cytokines and chemokines expressed in the tumor microenvironment. Further, Salmonella immunotherapy in CHOP-treated animals also enhanced NK cells cytotoxic activity as well as induced systemic lymphoma-specific humoral and cellular responses. Chemotherapy treatment profoundly impacted on the general health status of recipient animals, but those receiving Salmonella showed significantly better overall body condition. Altogether, the results clearly demonstrated that Salmonella immunotherapy could be safely used in individuals under CHOP treatment, resulting in a better prognosis. These results give strong support to consider Salmonella as a neoadjuvant therapy in a clinical setting. PMID:29410666

  5. Fine needle aspiration cytology of ALK1(-), CD30+ anaplastic large cell lymphoma post renal transplantation: a case report and literature review.

    PubMed

    Balachandran, Indra; Walker, Joe W; Broman, Jerry

    2010-03-01

    Post transplant lymphoproliferative disorders (PTLD) complicates the course of 0.3 to 3% of renal transplant patients receiving immunosuppression. Epstein-Barr virus (EBV) related non-Hodgkin's lymphomas of B-cell type is more common than those of T-cell origin. CD30 positive Anaplastic Large Cell Lymphoma (ALCL) is a Non-Hodgkin's lymphoma (B or T cell type) that accounts for a small percentage of PTLD's. ALCL of T-cell type are a spectrum of disease ranging from primary cutaneous to systemic nodal ALCL. The systemic nodal ALCL is further subdivided into anaplastic lymphoma kinase-1 (ALK-1) positive or negative. ALK-1 protein is a gene fusion product of translocation (2;5) and carries prognostic implications. We present an unusual manifestation of ALK-1 negative CD30 positive ALCL in a post renal transplant patient in FNA cytology with all supportive adjuvant studies and differential diagnoses and review the cytology literature on this topic.

  6. Combination Chemotherapy, Rituximab, and Ixazomib Citrate in Treating Patients With Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2018-04-30

    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

  7. Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Treatment for children with non-Hodgkin lymphoma (NHL) generally involves combination chemotherapy for most patients. The use of radiation therapy is limited in children with NHL. Get detailed treatment information for childhood NHL in this summary for clinicians.

  8. 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.

  9. Intestinal perforation that developed after chemotherapy in a patient diagnosed with non-Hodgkin lymphoma: A case report and review of literature.

    PubMed

    Tatar, Cihad; Yavas, Mazlum; Akkus, Onder; Tapkan, Bahaeddin; Batikan, Oguz Kagan; Bayrak, Savas; Arikan, Soykan

    2017-01-01

    Non-Hodgkin Lymphomas (NHL) appear with the malign transformation of mature lymphocytes. Intestinal perforations are one of the most well-known complications of NHLs. In this review, a 29-year-old male patient who was diagnosed with NHL with gastrointestinal involvement that developed intestinal perforation after chemotherapy is presented. A 29-year-old male patient who received systemic chemotherapy in another healthcare center due to Major B-Cell Lymphoma was examined because he had stomachache after the treatment. The patient was urgently taken to operation. In the exploration, there were partly mass lesions in all small intestine segments. It was determined that one of the lesion was perforated. Small intestine resection was applied. The pathology report on resection material was reported as High Grade Major B-Cell Lymphoma. In the treatment of Lymphoma with intestinal B-Cells, there is no consensus because this disease is rarely observed. Perforation may appear as a complication of the chemotherapy. Depending on the steroids given to the patient, perforation may develop, and the clinical symptoms may be masked. It must be born in mind that there may be intestinal involvement in patients diagnosed with NHL, and intestinal perforation may develop due to chemotherapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. [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.

  11. Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma

    ClinicalTrials.gov

    2018-05-23

    Adult T-Cell Leukemia/Lymphoma; Anaplastic Large Cell Lymphoma, ALK-Negative; Anaplastic Large Cell Lymphoma, ALK-Positive; Angioimmunoblastic T-Cell Lymphoma; CD30-Positive Neoplastic Cells Present; Enteropathy-Associated T-Cell Lymphoma; Hepatosplenic T-Cell Lymphoma; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Stage III Anaplastic Large Cell Lymphoma; Stage IV Anaplastic Large Cell Lymphoma

  12. Primary Uterine Peripheral T-cell Lymphoma

    PubMed Central

    Gong, Jing; Dong, Aisheng; Wang, Yang; Zhang, Xuefeng; Yang, Panpan; Wang, Li; Jing, Wei

    2016-01-01

    Abstract Primary uterine non-Hodgkin's lymphoma is extremely rare accounting for <1% of all extranodal non-Hodgkin's lymphomas. Imaging findings of primary uterine lymphoma have rarely been reported before. We present magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT findings in a patient with primary uterine peripheral T-cell lymphoma. A 27-year-old female presented with intermittent fever with neutropenia for 7 months. MRI showed an ill-defined mass involved both the uterine corpus and cervix, resulting in diffuse enlargement of the uterus. This mass showed inhomogeneous hypointensity on unenhanced T1-weighted images, hyperintensity on diffusion-weighted imaging, relative hypointensity compared to the surrounding myometrium on T2-weighted images and lower enhancement than the surrounding myometrium on enhanced T1-weighted images. FDG PET/CT showed intense FDG uptake in the thickened wall of the uterine corpus and cervix with SUVmax of 26.9. There were multiple hypermetabolic lymph nodes in the pelvis and retroperitoneum. Uterine curettage and CT-guided biopsy of the uterine mass revealed peripheral T-cell lymphoma. Bone marrow biopsy revealed no evidence of lymphomatous involvement. The imaging and pathologic findings were consistent with primary uterine lymphoma. After 3 circles of chemotherapy, follow-up enhanced MRI showed decreased thickness of the uterine wall. Despite its rarity, primary uterine non-Hodgkin's lymphoma should be taken into consideration when a uterine tumor shows large size, relative hypointesity on both T2-weighted images and enhanced T1-weighted images compared to the surrounding myometrium, and intense FDG uptake on PET/CT. MRI may be helpful for describing the relationship between the tumor and adjacent structures. FDG PET/CT may be useful for tumor detection and staging. PMID:27124063

  13. Non-Hodgkin's Lymphoma Reversal with Dichloroacetate.

    PubMed

    Flavin, Dana F

    2010-01-01

    In June 2007, a 48-year-old male patient, diagnosed with Stage 4 Non-Hodgkin's Follicular Lymphoma (NHL), was treated for 3 months with conventional chemotherapy resulting in a complete remission. Almost one year later tumors returned in the nasopharynx and neck lymph glands. Refusing all suggested chemotherapies, the patient began self-administering dichloroacetate (DCA) 900 mg daily with a PET scan showing complete remission four months later. Since his last PET scan, May, 2009, he remains tumor-free from continuous DCA usage.

  14. Non-Hodgkin's Lymphoma Reversal with Dichloroacetate

    PubMed Central

    Flavin, Dana F.

    2010-01-01

    In June 2007, a 48-year-old male patient, diagnosed with Stage 4 Non-Hodgkin's Follicular Lymphoma (NHL), was treated for 3 months with conventional chemotherapy resulting in a complete remission. Almost one year later tumors returned in the nasopharynx and neck lymph glands. Refusing all suggested chemotherapies, the patient began self-administering dichloroacetate (DCA) 900 mg daily with a PET scan showing complete remission four months later. Since his last PET scan, May, 2009, he remains tumor-free from continuous DCA usage. PMID:20886020

  15. Molecular evidence of Zn chelation of the procaspase activating compound B-PAC-1 in B cell lymphoma.

    PubMed

    Sarkar, Aloke; Balakrishnan, Kumudha; Chen, Jefferson; Patel, Viralkumar; Neelapu, Sattva S; McMurray, John S; Gandhi, Varsha

    2016-01-19

    The resistance of apoptosis in cancer cells is pivotal for their survival and is typically ruled by mutations or dysregulation of core apoptotic cascade. Mantle cell lymphoma (MCL) is a non-Hodgkin's B-cell malignancy expressing higher anti-apoptotic proteins providing survival advantage. B-PAC-1, a procaspase activating compound, induces apoptosis by sequestering Zn bound to procaspase-3, but the amino acids holding Zn in Caspase-3 is not known. Here we show that reintroduction of WT caspase-3 or 7 in Caspase3-7 double knock-out (DKO) mouse embryonic fibroblasts (MEF) promoted B-PAC-1 to induce apoptosis (27-43%), but not in DKO MEFs or MEFs expressing respective Casp3-7 catalytic mutants (12-13%). Using caspase-6 and -9 exosite analysis, we identified and mutated predicted Zn-ligands in caspase-3 (H108A, C148S and E272A) and overexpressed into DKO MEFs. Mutants carrying E272A abrogated Zn-reversal of apoptosis induced by B-PAC-1 via higher XIAP and smac expressions but not in H108A or C148S mutants. Co-immunoprecipitation analysis revealed stronger XIAP-caspase-3 interaction suggesting a novel mechanism of impulsive apoptosis resistance by disrupting predicted Zn-ligands in caspase-3. B-PAC-1 sponsored apoptosis in MCL cell lines (30-73%) via caspase-3 and PARP cleavages accompanied by loss of Mcl-1 and IAPs including XIAP while Zn substantially abrogated B-PAC-1-driven apoptosis (18-36%). In contrary, Zn is dispensable to inhibit staurosporin, bendamustine, ABT199 or MK206-induced apoptosis. Consistent to cell lines, B-PAC-1 stimulated cell death in primary B-lymphoma cells via caspase-3 cleavage with decline in both Mcl-1 and XIAP. This study underscores the first genetic evidence that B-PAC-1 driven apoptosis is mediated via Zn chelation.

  16. Atypical cytomegalovirus retinitis in non-Hodgkin's lymphoma.

    PubMed

    Tyagi, Mudit; Ambiya, Vikas; Mathai, Annie; Narayanan, Raja

    2015-08-03

    A 54-year-old woman, a known case of non-Hodgkin's lymphoma (NHL) in complete remission, presented with floaters and diminution of vision in her left eye. The eye had vitritis with non-haemorrhagic retinitis mimicking intraocular lymphoma and acute retinal necrosis. A vitreous sample was positive for cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1) DNA by PCR. The possibility of intraocular lymphoma was not confirmed by the immunohistochemistry of the vitreous sample. The patient had a relapse of NHL along with rapid deterioration of vision in her left eye to no perception of light, due to optic nerve involvement. The right eye developed a new patch of focal haemorrhagic retinitis threatening the fovea. Based on the laboratory results and the clinical findings, she was successfully managed as a case of bilateral CMV retinitis and the vision in her right eye was salvaged. 2015 BMJ Publishing Group Ltd.

  17. Several immune escape patterns in non-Hodgkin's lymphomas

    PubMed Central

    Laurent, Camille; Charmpi, Konstantina; Gravelle, Pauline; Tosolini, Marie; Franchet, Camille; Ysebaert, Loïc; Brousset, Pierre; Bidaut, Alexandre; Ycart, Bernard; Fournié, Jean-Jacques

    2015-01-01

    Follicular Lymphomas (FL) and diffuse large B cell lymphomas (DLBCL) must evolve some immune escape strategy to develop from lymphoid organs, but their immune evasion pathways remain poorly characterized. We investigated this issue by transcriptome data mining and immunohistochemistry (IHC) of FL and DLBCL lymphoma biopsies. A set of genes involved in cancer immune-evasion pathways (Immune Escape Gene Set, IEGS) was defined and the distribution of the expression levels of these genes was compared in FL, DLBCL and normal B cell transcriptomes downloaded from the GEO database. The whole IEGS was significantly upregulated in all the lymphoma samples but not in B cells or other control tissues, as shown by the overexpression of the PD-1, PD-L1, PD-L2 and LAG3 genes. Tissue microarray immunostainings for PD-1, PD-L1, PD-L2 and LAG3 proteins on additional biopsies from 27 FL and 27 DLBCL patients confirmed the expression of these proteins. The immune infiltrates were more abundant in FL than DLBCL samples, and the microenvironment of FL comprised higher rates of PD-1+ lymphocytes. Further, DLBCL tumor cells comprised a higher proportion of PD-1+, PD-L1+, PD-L2+ and LAG3+ lymphoma cells than the FL tumor cells, confirming that DLBCL mount immune escape strategies distinct from FL. In addition, some cases of DLBCL had tumor cells co-expressing both PD-1, PD-L1 and PD-L2. Among the DLBCLs, the activated B cell (ABC) subtype comprised more PD-L1+ and PD-L2+ lymphoma cells than the GC subtype. Thus, we infer that FL and DLBCL evolved several pathways of immune escape. PMID:26405585

  18. Cost comparative study of autologous peripheral blood progenitor cells (PBPC) and bone marrow (ABM) transplantations for non-Hodgkin's lymphoma patients.

    PubMed

    Woronoff-Lemsi, M C; Arveux, P; Limat, S; Deconinck, E; Morel, P; Cahn, J Y

    1997-12-01

    Intensive high-dose chemotherapy with autologous stem-cell support has become a common treatment strategy for non-Hodgkin's lymphomas. A cost-identification analysis was conducted comparing 10 patients autografted with PBSC to 10 others autografted with BM. The analysis included harvest and graft until graft day +100 and was carried out from the point of view of the hospital setting. Resources used, logistic and direct medical costs per patient were identified, and sensitivity analyses performed. The cost distribution was different. Stem cell harvest was more expensive for PBPC ($9030) and BM ($4745); on the other hand, hospitalization from graft to discharge from hospital cost savings with PBSC were about $10666. After discharge from hospital, costs were similar and cheaper in both groups. For the overall study the PBPC procedure was less expensive than ABMT, $35381 and $41759 respectively, with cost savings of $6378. The number of days spent in hospital and blood bank costs were the major cost factors. This study was based on a single pathology, non-Hodgkin's lymphoma, and the actual hospital records for each patient situation as opposed to a clinical trial, and our results were consistent with different previous studies carried out in different health care systems.

  19. Clinical images. Primary non-Hodgkin's lymphoma of the sigmoid colon in a child.

    PubMed

    Zhang, Ke Ren; Jia, Hui Min

    2009-01-01

    Primary non-Hodgkin's lymphomas of the gastrointestinal tract are rare in children, and few of these lymphomas are located in the sigmoid colon. The preoperative diagnosis rate is low. Complete resection is indicated if it can be done safely. Combination chemotherapy after resection is indicated.

  20. Avelumab, Utomilumab, Rituximab, Ibrutinib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma

    ClinicalTrials.gov

    2018-06-13

    CCND1 Positive; CD20 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

  1. 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.

  2. Association of Interleukin-2-330T/G and Interleukin-10-1082A/G Genetic Polymorphisms with B-Cell Non-Hodgkin Lymphoma in a Cohort of Egyptians.

    PubMed

    Abdel Rahman, Hala Aly; Khorshied, Mervat Mamdooh; Reda Khorshid, Ola Mohamed; Mourad, Heba Mahmoud

    2018-05-25

    Polymorphisms in the interleukin (IL)-2 and IL-10 genes are known to be associated with susceptibility to different immune-dysregulated disorders and cancers such as non-Hodgkin lymphoma (NHL). To explore the possible association between IL-2-330T/G and IL-10-1082A/G single-nucleotide polymorphisms and the susceptibility to B-cell NHL (B-NHL) in Egyptians, we conducted a case-control study. Genotyping of the studied genetic variations was done for 100 B-NHL patients as well as 100 age- and sex-matched healthy controls. The IL-2 variant allele occurred at a significantly higher rate in patients than controls and was associated with susceptibility to B-NHL [odds ratio (OR): 1.91, 95% confidence interval (CI): 1.28-2.85]. It was also associated with advanced performance status score. IL-2 polymorphism conferred an almost threefold increased risk of diffuse large B-cell lymphoma (OR: 2.64, 95% CI: 1.35-5.15) and a fourfold increased risk of indolent subtypes (OR: 4.34, 95% CI: 1.20-15.7). The distribution of IL-10-1082A/G genotypes in our patients was close to that of the controls. Co-inheritance of the variant genotypes of IL-2 and the common genotype of IL-10 conferred an almost sixfold increased risk (OR: 5.75, 95% CI: 1.39-23.72), while co-inheritance of the variant genotypes of IL-2 and IL-10 conferred fivefold increased risk of B-NHL (OR: 5.43, 95% CI: 1.44-20.45). The variant genotypes of IL-2-330T/G and IL-10-1082A/G had no effect on the disease-free survival of B-NHL patients. The present study highlights the possible involvement of the IL-2-330T/G genetic polymorphism in the susceptibility to B-NHL in Egypt, especially indolent subtypes. Moreover, IL-10-1082A/G is not a molecular susceptibility marker for B-NHL in Egyptians.

  3. Mesenchymal stem cells display hepato-protective activity in lymphoma bearing xenografts.

    PubMed

    Secchiero, Paola; Corallini, Federica; Zavan, Barbara; Tripodo, Claudio; Vindigni, Vincenzo; Zauli, Giorgio

    2012-04-01

    A disseminated model of non-Hodgkin's lymphoma with prevalent liver metastasis was generated by intraperitoneal (i.p.) injection of EBV(+) B lymphoblastoid SKW6.4 in nude-SCID mice. The survival of SKW6.4 xenografts (median survival = 27 days) was significantly improved when hyaluronan scaffolds embedded with mesenchimal stem cells (MSC) were implanted in the abdominal area 4 days after SKW6.4 injection (median survival = 39.5 days). Mice implanted with MSC showed a significant improvement of hepatic functionality in lymphoma xenografts, as demonstrated by measurement of serum ALT/AST levels. Co-culture of MSC with lymphoma cells enhanced the release of hepatocyte growth factor (HGF) by MSC. These data suggest that hyaluronan-embedded MSC exert anti-lymphoma activity by ameliorating hepatic functionality.

  4. PI3K/mTOR Inhibitor LY3023414 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)

    ClinicalTrials.gov

    2018-06-18

    Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Non-Hodgkin Lymphoma; Ann Arbor Stage IV Non-Hodgkin Lymphoma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; TSC1 Gene Mutation; TSC2 Gene Mutation; Wilms Tumor

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

    ClinicalTrials.gov

    2013-01-09

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

  6. Authentication of primordial characteristics of the CLBL-1 cell line prove the integrity of a canine B-cell lymphoma in a murine in vivo model.

    PubMed

    Rütgen, Barbara C; Willenbrock, Saskia; Reimann-Berg, Nicola; Walter, Ingrid; Fuchs-Baumgartinger, Andrea; Wagner, Siegfried; Kovacic, Boris; Essler, Sabine E; Schwendenwein, Ilse; Nolte, Ingo; Saalmüller, Armin; Murua Escobar, Hugo

    2012-01-01

    Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL). Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stability of the induced tumours and the ability to resemble the original material. CLBL-1 was injected into Rag2(-/-)γ(c) (-/-) mice. The generated tumor material was analysed by immunophenotyping and histopathology and used to establish the cell line CLBL-1M. Both cell lines were karyotyped for detection of chromosomal aberrations. Additionally, CLBL-1 was stimulated with IL-2 and DSP30 as described for primary canine B-cell lymphomas and NHL to examine the stimulatory effect on cell proliferation. CLBL-1 in vivo application resulted in lymphoma-like disease and tumor formation. Immunophenotypic analysis of tumorous material showed expression of CD45(+), MHCII(+), CD11a(+) and CD79αcy(+). PARR analysis showed positivity for IgH indicating a monoclonal character. These cytogenetic, molecular, immunophenotypical and histological characterisations of the in vivo model reveal that the induced tumours and thereof generated cell line resemble closely the original material. After DSP30 and IL-2 stimulation, CLBL-1 showed to respond in the same way as primary material. The herein described CLBL-1 in vivo model provides a highly stable tool for B-cell lymphoma research in veterinary and human medicine allowing various further in vivo studies.

  7. Genetic Susceptibility to Lymphoma

    PubMed Central

    Skibola, Christine F.; Curry, John D.; Nieters, Alexandra

    2010-01-01

    BACKGROUND Genetic susceptibility studies of lymphoma may serve to identify at risk populations and to elucidate important disease mechanisms. METHODS This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. RESULTS Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G>A and IL10 -3575T>A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol assessments are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro- and endocrine-immune cross-talk with lymphomagenesis, but will need replication in larger populations. CONCLUSIONS Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations. PMID:17606447

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

    ClinicalTrials.gov

    2017-11-07

    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

  9. Collision of Lymphoepithelioma-like Carcinoma with Diffuse Large B-cell Lymphoma of the Stomach: A Case Report.

    PubMed

    Liu, Liyan; Zhao, Huishan; Sheng, Lin; Yang, Ping; Zhou, Huihui; Wang, Ruizheng

    2017-08-01

    Collision of Epstein-Barr virus (EBV)-associated lymphoepithelioma-like carcinoma (LELC) with non-Hodgkin's lymphoma of the stomach is extremely rare. Herein we report a case of LELC with primary diffuse large B-cell lymphoma (DLBCL) of the stomach in a 65-year-old patient. Gastric endoscopy showed a poorly differentiated adenocarcinoma of the stomach. The patient underwent radical gastrectomy, and histopathological examinations revealed the collision of LELC and DLBCL of the stomach. In situ hybridization showed that most carcinoma cells of LELC were positive for EBV-encoded small RNA (EBER) suggesting that the virus infection happened in the early stage of tumorigenesis, while DLBCL was negative. This is the first report of collision of EBV-associated LELC with primary DLBCL of the stomach. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Progression of an orbital T-cell rich B-cell lymphoma to a B-cell lymphoma in a dog.

    PubMed

    Aquino, S M; Hamor, R E; Valli, V E; Kitchell, B E; Tunev, S S; Bailey, K L; Ehrhart, E J

    2000-09-01

    An 11-year-old Shetland Sheepdog was presented for exophthalmos caused by a locally extensive, poorly defined mass located behind the right eye. The primary orbital mass was identified by light microscopy and immunohistochemistry as a T-cell rich B-cell lymphoma (TCRBCL) composed predominantly of BLA.36-positive large neoplastic lymphoid cells admixed with fewer CD3- and CD79a-positive small lymphocytes. The dog was treated for lymphoma, but 6 months after presentation it was euthanatized for suspected hepatic and gastrointestinal metastasis. Gross findings revealed an enlarged liver with multiple well-demarcated, randomly distributed 0.1-1.5-cm white nodules, five firm white submucosal jejunal nodules, and ileocecal, mediastinal, and hilar lymphadenopathy. Metastatic liver lesions consisted of sheets of monomorphic large neoplastic lymphoid cells that effaced and expanded portal and centrilobular zones. These cells were morphologically similar to the large neoplastic cells of the original orbital tumor and were CD3-negative and variably BLA.36-positive, consistent with B-cell lineage. Similar cells comprised the jejunal nodules and effaced the lymph nodes. The progression of TCRBCL to a diffuse B-cell lymphoma in this case is consistent with reported human cases and has not been previously reported in the dog.

  11. Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2015-06-30

    Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult Hepatocellular Carcinoma; Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult Solid Neoplasm; Adult T Acute Lymphoblastic Leukemia; Advanced Adult Hepatocellular Carcinoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Localized Non-Resectable Adult Liver Carcinoma; Localized Resectable Adult Liver Carcinoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Progressive Hairy Cell Leukemia Initial Treatment; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Liver Carcinoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Small Lymphocytic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult

  12. Sirolimus, Cyclosporine, and Mycophenolate Mofetil in Preventing Graft-versus-Host Disease in Treating Patients With Blood Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant

    ClinicalTrials.gov

    2017-10-30

    Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloid Leukemia; Adult Diffuse Large B-Cell Lymphoma; Adult Myelodysplastic Syndrome; Adult Non-Hodgkin Lymphoma; Aggressive Non-Hodgkin Lymphoma; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia; Childhood Diffuse Large B-Cell Lymphoma; Childhood Myelodysplastic Syndrome; Childhood Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Chronic Lymphocytic Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphoid Cell Neoplasm; Mantle Cell Lymphoma; Plasma Cell Myeloma; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma

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

    ClinicalTrials.gov

    2015-04-28

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

  14. Does Radiation Have a Role in Advanced Stage Hodgkin's or Non-Hodgkin Lymphoma?

    PubMed

    Specht, Lena

    2016-01-01

    Radiation therapy (RT) is one of the most effective agents available in the treatment of lymphomas. However, it is a local treatment, and today, with systemic treatments assuming a primary role for induction of response, RT is primarily used for consolidation. For advanced stage lymphomas, the indications for the use of RT have been questioned and debated, and proper randomized evidence is sparse. RT has significant long-term side effects, and the very extended RT fields of the past yielded unacceptable toxicity in many patients. Modern advanced imaging and conformal RT techniques now enable treatment of larger and anatomically more challenging target volumes with much less radiation to normal tissues and consequently much lower risks of long-term complications. The modern concept of involved site radiation therapy (ISRT) has now been accepted as standard in lymphomas. In advanced Hodgkin lymphoma (HL), RT to residual disease and/or initial bulk benefits some patients, depending on the chemotherapy regimen used. The more intensive the chemotherapy regimen, the fewer patients benefit from RT. In advanced aggressive non-Hodgkin lymphoma (NHL), most of the evidence comes from the most common type, the diffuse large B cell lymphoma (DLBCL). In patients treated with modern immunochemotherapy, RT to initial bulky disease or extralymphatic involvement is beneficial. For both HL and aggressive NHL, RT to residual masses after systemic treatment is of benefit. The role of PET in the evaluation and indication for RT to residual masses has not been tested in randomized trials. In advanced indolent NHL, very low dose RT offers excellent palliation with very few side effects. Modern RT in advanced lymphomas warrants further evaluation in randomized trials.

  15. Autologous hematopoietic stem cell transplantation in elderly patients (≥ 70 years) with non-Hodgkin's lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study.

    PubMed

    Hermet, E; Cabrespine, A; Guièze, R; Garnier, A; Tempescul, A; Lenain, P; Bouabdallah, R; Vilque, J P; Frayfer, J; Bordessoule, D; Sibon, D; Janvier, M; Caillot, D; Biron, P; Legros, L; Choufi, B; Drenou, B; Gorin, N C; Bilger, K; Tamburini, J; Soussain, C; Brechignac, S; Bay, J O

    2015-09-01

    Limited data is available on the feasibility of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) in elderly patients over 70 years of age with non-Hodgkin's lymphoma (NHL). In the setting of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) group, we retrospectively analyzed 81 consecutive patients with NHL over 70 years of age who received AHSCT. The median age at AHSCT was 72.3 years [70-80]. Patients' were diagnosed with diffuse large B-cell lymphoma (n=40), follicular lymphoma (n=16), mantle cell lymphoma (n=15), T-cell lymphoma (n=5), and other (n=5). Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was 0 in 73% of patients. Main conditionings were BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=61) and melphalan alone (n=14). Median delays to reach 0.5×10⁹/L neutrophils and 20 × 10(9)/L platelets were of 12 [9-76] days and 12 [0-143] days, respectively. One hundred day and one year cumulative incidence of NRM was 5.4% and 8.5%, respectively. The main cause of death remains relapse. In conclusion, this study revealed that AHSCT seemed to be acceptable in patients over 70 years of age with NHL. Patient age is not a limiting factor if clinical condition is adequate. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Possible Mitochondria-Associated Enzymatic Role in Non-Hodgkin Lymphoma Residual Disease

    PubMed Central

    Kusao, Ian; Troelstrup, David; Shiramizu, Bruce

    2009-01-01

    Background The mechanisms responsible for resistant or recurrent disease in childhood non-Hodgkin lymphoma (NHL) are not yet fully understood. A unique mechanism suggesting the role of the mitochondria as the key energy source responsible for residual cells has been assessed in the clinical setting on specimens from patients on therapy were found to have increased copies of mitochondrial DNA (mtDNA) associated with positive minimal residual disease and/or persistent disease (MRD/PD) status. The potential role of mtDNA in MRD/PD emphasizes queries into the contributions of relevant enzymatic pathways responsible for MRD/PD. This study hypothesized that in an in-vitro model, recovering or residual cells from chemotoxicity will exhibit an increase in both citrate synthase and isocitrate dehydrogenase expression and decrease in succinate dehydrogenase expression. Procedure Ramos cells (Burkitt lymphoma cell line) were exposed to varying concentrations of doxorubicin and vincristine for 1 hr; and allowing for recovery in culture over a 7-day period. cDNA was extracted on days 1 and 7 of the cell culture period to assess the relative expression of the aforementioned genes. Results Increase citrate synthase, increase isocitrate dehydrogenase and decrease succinate dehydrogenase expressions were found in recovering Ramos cells. Conclusion Recovering lymphoma cells appear to compensate by regulating enzymatic levels of appropriate genes in the Krebs Cycle suggesting an important role of the mitochondria in the presence of residual cells. PMID:19936279

  17. 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

  18. Disseminated toxoplasmosis in a patient with non-Hodgkin lymphoma.

    PubMed

    Herold, M A; Kühne, R; Vosberg, M; Ostheeren-Michaelis, S; Vogt, P; Karrer, U

    2009-12-01

    Toxoplasmosis is a well-recognized opportunistic disease in HIV-infected individuals that is caused by the reactivation of a previous infection, primarily in the central nervous system, during profound immunodeficiency. Toxoplasmosis has been described more rarely in patients with cancer and chemotherapy. We report a case of a patient with a history of chemotherapy for non-Hodgkin lymphoma who developed pain and progressive paresthesia of the right arm 6 weeks after remission. Relapsing lymphoma was suspected, and steroid and radiation treatment were initiated, but the patient died 5 days later due to multiple organ failure. Autopsy revealed disseminated toxoplasmosis. This case illustrates that toxoplasmosis should be suspected in patients with neoplastic disease, especially lymphomas, who present with unexplained neurologic, pulmonary, or febrile symptoms during or after chemotherapy.

  19. [Primary non-Hodgkin's lymphoma of the breast. A case report].

    PubMed

    Villalón-López, José Sebastián; Souto-Del Bosque, Rosalía; Méndez-Sashida, Pedro Gonzalo

    Primary breast lymphomas, a rare subtype of non-Hodgkin's lymphoma, represent 0.04 to 0.5% of all breast cancers, 0.38 to 0.7% of all lymphomas, and 1.7 to 2.2% of extranodal lymphomas. The treatment choice is based on chemotherapy containing anthracycline and rituximab. Surgery is limited to being less invasive and only for diagnostic purposes. Radiotherapy has an important role as consolidation therapy, particularly in patients with negative nodes. A 70 year old woman with a breast nodule in the left upper outer quadrant, with slow growth, expansive, painless, and accompanied by skin changes, malaise, weight loss, fatigue, chill, and sweating. There was tissue replacement by the mammary gland tumour, skin changes due to invasion, and a 5cm axillary lymphadenopathy. The mammography showed skin thickening and a dense pattern of 80% of breast tissue replacement, and the lymphadenopathy with loss of radiolucent centre and soft tissue invasion. The biopsy confirmed a diffuse high grade large cell lymphoma. She received an Rituximab (R-CHOP) chemotherapy scheme and radiotherapy with tangential and supraclavicular and axillary fields. After completing the chemotherapy, the patient is on follow-up, and at 15 months she is alive without disease activity. Primary lymphoma of the breast is a rare entity. Multimodal treatment with combined chemo-radiotherapy is the cornerstone. Surgery is reserved only for diagnostic purposes. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  20. Ibrutinib-associated tumor lysis syndrome in a patient with mantle cell lymphoma: A case report.

    PubMed

    Kaur, Varinder; Swami, Arjun

    2017-04-01

    Mantle cell lymphoma accounts for 5-7% of all non-Hodgkin's lymphomas. Under the current WHO classification, it is categorized as an indolent B cell lymphoma, but has an aggressive clinical course. New insights into leukemogenic molecular pathways of mantle cell lymphoma have uncovered unique therapeutic targets. Ibrutinib, a Bruton's tyrosine kinase inhibitor, is the newest drug in the arsenal that has shown promising efficacy in relapsed mantle cell lymphoma. Long-term studies have shown that grade 3 or 4 adverse events are infrequent. Asymptomatic lymphocytosis is frequently seen with ibrutinib use in mantle cell lymphoma; however, tumor lysis syndrome is an extremely rare complication. To date, only two patients with ibrutinib-associated tumor lysis syndrome in mantle cell lymphoma have been described in a long-term follow-up study. Both patients met laboratory criteria for tumor lysis syndrome, however, but did not develop clinical tumor lysis syndrome. We, here describe a patient with relapsed mantle cell lymphoma who developed clinical tumor lysis syndrome with ibrutinib monotherapy.

  1. non-Hodgkin's lymphoma and occupation in Sweden: a registry based analysis.

    PubMed Central

    Linet, M S; Malker, H S; McLaughlin, J K; Weiner, J A; Blot, W J; Ericsson, J L; Fraumeni, J F

    1993-01-01

    Incidence of non-Hodgkin's lymphoma in different employment categories was evaluated from the Swedish Cancer-Environment Registry, which links cancer incidence during 1961 to 1979 with occupational information from the 1960 census. New associations were found for men employed in shoemaking and shoe repair, porcelain and earthenware industries, education, and other white collar occupations. Several findings supported associations found in other countries, including excesses among woodworkers, furniture makers, electric power plant workers, farmers, dairy workers, lorry drivers, and other land transport workers. Risks were not increased among chemists, chemical or rubber manufacturing workers, or petrochemical refinery workers. Caution must be used in drawing causal inferences from these linked registry data because information on exposure and duration of employment is not available. Nevertheless, this study has suggested new clues to possible occupational determinants of non-Hodgkin's lymphoma. PMID:8431395

  2. 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

  3. Birth order and risk of non-hodgkin lymphoma--true association or bias?

    PubMed

    Grulich, Andrew E; Vajdic, Claire M; Falster, Michael O; Kane, Eleanor; Smedby, Karin Ekstrom; Bracci, Paige M; de Sanjose, Silvia; Becker, Nikolaus; Turner, Jenny; Martinez-Maza, Otoniel; Melbye, Mads; Engels, Eric A; Vineis, Paolo; Costantini, Adele Seniori; Holly, Elizabeth A; Spinelli, John J; La Vecchia, Carlo; Zheng, Tongzhang; Chiu, Brian C H; Franceschi, Silvia; Cocco, Pierluigi; Maynadié, Marc; Foretova, Lenka; Staines, Anthony; Brennan, Paul; Davis, Scott; Severson, Richard K; Cerhan, James R; Breen, Elizabeth C; Birmann, Brenda; Cozen, Wendy

    2010-09-15

    There is inconsistent evidence that increasing birth order may be associated with risk of non-Hodgkin lymphoma (NHL). The authors examined the association between birth order and related variables and NHL risk in a pooled analysis (1983-2005) of 13,535 cases and 16,427 controls from 18 case-control studies within the International Lymphoma Epidemiology Consortium (InterLymph). Overall, the authors found no significant association between increasing birth order and risk of NHL (P-trend = 0.082) and significant heterogeneity. However, a significant association was present for a number of B- and T-cell NHL subtypes. There was considerable variation in the study-specific risks which was partly explained by study design and participant characteristics. In particular, a significant positive association was present in population-based studies, which had lower response rates in cases and controls, but not in hospital-based studies. A significant positive association was present in higher-socioeconomic-status (SES) participants only. Results were very similar for the related variable of sibship size. The known correlation of high birth order with low SES suggests that selection bias related to SES may be responsible for the association between birth order and NHL.

  4. Adult T-cell leukemia/lymphoma with EBV-positive Hodgkin-like cells

    PubMed Central

    Venkataraman, Girish; Berkowitz, Jonathan; Morris, John C.; Janik, John E.; Raffeld, Mark A.; Pittaluga, Stefania

    2011-01-01

    SUMMARY Hodgkin-like cells (HLC) have been described in a variety of non-Hodgkin lymphomas (NHL) including chronic lymphocytic leukemia (CLL) and peripheral T-cell lymphoma (PTCL). There have been rare reports in the Japanese population of human T-cell lymphotrophic virus-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) harboring HLC; however, no similar cases have been described in western patients. We report a 53-year-old African-American man that presented with progressive weakness and lethargy, and was found to have generalized lymphadenopathy and hypercalcemia. A lymph node biopsy showed involvement by ATLL with scattered Epstein-Barr virus (EBV)-positive cells, some of which resembled Hodgkin cells that had a B-cell phenotype, consistent with an Epstein-Barr virus-lymphoproliferative disorder (LPD). The patient had stage 4 disease with bone marrow involvement. In light of the associated B-cell lymphoproliferative process, the patient was treated with six cycles of intensive chemotherapy that targeted both the ATLL and the EBV-LPD that resulted in a complete response. An awareness of the association of EBV-LPD with Hodgkin-like cells in the context of ATLL is necessary to avoid potential misdiagnosis and to aid in therapeutic decisions. PMID:21315416

  5. [Flowcytometry DNA analysis of oral and maxillofacial non-Hodgkin's lymphoma].

    PubMed

    Ma, Li; He, Zhixiu; Wu, Lanyan; Cai, Yixin; Huang, Hechang; Lei, Song

    2002-06-01

    The purpose of this study was to investigate the relationship between the results of flowcytometry analyses of different clinical stage, location, pathologic grade and cell origin of oral and maxillofacial non-Hodgkin's lymphoma (NHL), and the diagnostic value of flowcytometry analysis in lymphoma. This study analyzed 50 oral and maxillofacial NHL cases and 10 reactive lymph nodes (formalin fixed and paraffin embedded) by flowcytometry (FCM). Reactive lymph nodes were all diploid. The diploid rate of NHL was 54%, and aneuploidy rate was 46%. There was statistically significant difference between reactive lymph nodes and NHL in the DNA ploidy status and cell cycle data (SPF, CV, S + G2/M, DI). The S phase fraction (SPF) and S + G2/M had close relationship with the grade of NHL. SPF value and DNA ploidy status had no obvious relationship with the prognosis. The results suggested that the FCM had diagnostic value in NHL, especially when the morphological diagnosis was difficult. Although the cell cycle data had no prognostic value, SPF and SPF + G2/M can show the proliferative status of NHL, which can help clinical doctor select therapeutic method.

  6. Authentication of Primordial Characteristics of the CLBL-1 Cell Line Prove the Integrity of a Canine B-Cell Lymphoma in a Murine In Vivo Model

    PubMed Central

    Reimann-Berg, Nicola; Walter, Ingrid; Fuchs-Baumgartinger, Andrea; Wagner, Siegfried; Kovacic, Boris; Essler, Sabine E.; Schwendenwein, Ilse; Nolte, Ingo; Saalmüller, Armin; Escobar, Hugo Murua

    2012-01-01

    Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL). Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stability of the induced tumours and the ability to resemble the original material. CLBL-1 was injected into Rag2−/−γc −/− mice. The generated tumor material was analysed by immunophenotyping and histopathology and used to establish the cell line CLBL-1M. Both cell lines were karyotyped for detection of chromosomal aberrations. Additionally, CLBL-1 was stimulated with IL-2 and DSP30 as described for primary canine B-cell lymphomas and NHL to examine the stimulatory effect on cell proliferation. CLBL-1 in vivo application resulted in lymphoma-like disease and tumor formation. Immunophenotypic analysis of tumorous material showed expression of CD45+, MHCII+, CD11a+ and CD79αcy+. PARR analysis showed positivity for IgH indicating a monoclonal character. These cytogenetic, molecular, immunophenotypical and histological characterisations of the in vivo model reveal that the induced tumours and thereof generated cell line resemble closely the original material. After DSP30 and IL-2 stimulation, CLBL-1 showed to respond in the same way as primary material. The herein described CLBL-1 in vivo model provides a highly stable tool for B-cell lymphoma research in veterinary and human medicine allowing various further in vivo studies. PMID:22761949

  7. 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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Halasz, Lia M.; Jacene, Heather A.; Catalano, Paul J.

    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.more » 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.« less

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

    ClinicalTrials.gov

    2018-06-11

    ALK-Positive Large B-Cell Lymphoma; Atypical Burkitt/Burkitt-Like Lymphoma; Burkitt-Like Lymphoma With 11q Aberration; Diffuse Large B-Cell Lymphoma Activated B-Cell Type; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; EBV-Positive Mucocutaneous Ulcer; High-Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; Human Herpesvirus 8-Positive Neoplastic Cells Present; Intravascular Large B-Cell Lymphoma; Large B-Cell Lymphoma With IRF4 Rearrangement; 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 B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Lymphomatoid Granulomatosis; Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Small Intestinal High Grade B-Cell Lymphoma, Not Otherwise Specified; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

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

    ClinicalTrials.gov

    2018-02-09

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

  10. Obatoclax Mesylate, Vincristine Sulfate, Doxorubicin Hydrochloride, and Dexrazoxane Hydrochloride in Treating Young Patients With Relapsed or Refractory Solid Tumors, Lymphoma, or Leukemia

    ClinicalTrials.gov

    2014-04-30

    Acute Leukemias of Ambiguous Lineage; Acute Undifferentiated Leukemia; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Small Intestine Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  11. HIV-Resistant Gene Modified Stem Cells and Chemotherapy in Treating Patients With Lymphoma With HIV Infection

    ClinicalTrials.gov

    2017-11-08

    Human Immunodeficiency Virus 1 Positive; Stage I Adult Hodgkin Lymphoma; Stage I Adult Non-Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult Non-Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Non-Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Non-Hodgkin Lymphoma

  12. Selumetinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)

    ClinicalTrials.gov

    2018-06-25

    Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; BRAF Gene Mutation; GNA11 Gene Mutation; GNAQ Gene Mutation; Histiocytosis; HRAS Gene Mutation; KRAS Gene Mutation; NF1 Gene Mutation; NRAS Gene Mutation; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma

  13. Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies

    ClinicalTrials.gov

    2018-02-08

    Aggressive Non-Hodgkin Lymphoma; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Chronic Lymphocytic Leukemia; Loss of Chromosome 17p; Myelodysplastic/Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Aggressive Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

  14. Recent advances and future directions in mantle cell lymphoma research: report of the 2016 mantle cell lymphoma consortium workshop.

    PubMed

    Kahl, Brad S; Dreyling, Martin; Gordon, Leo I; Quintanilla-Martinez, Leticia; Sotomayor, Eduardo M

    2017-07-01

    Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma typically associated with the t(11;14) chromosomal translocation, resulting in overexpression of cyclin D1. Although MCL is associated with clinical heterogeneity, outcomes are generally poor and no standard treatment has been established. However, the recent approval of ibrutinib provides a new therapeutic option. Moreover, recent clinical trials have provided new perspectives on the relative efficacy and safety of various approaches for both transplant-eligible and transplant-ineligible patients. Multiple novel strategies are being evaluated in the treatment of MCL, including both targeted agents and cellular immunotherapies. At the Lymphoma Research Foundation's 12th MCL Workshop, researchers gathered to discuss research findings, clinical trial results, and future directions related to MCL, its biology, and its treatment. This manuscript, which includes a summary of each presentation, aims to review recent findings in MCL research and highlight potential areas for future study.

  15. A prospective study of serum soluble CD30 concentration and risk of non-Hodgkin lymphoma

    PubMed Central

    Lan, Qing; Martinez-Maza, Otoniel; Oken, Martin M.; Hocking, William; Huang, Wen-Yi; Baris, Dalsu; Conde, Betty; Rothman, Nathaniel

    2009-01-01

    Prediagnostic serum concentration of soluble CD30 (sCD30), a marker for chronic B-cell stimulation, has been associated with increased risk of developing AIDS-related non-Hodgkin lymphoma (NHL) in a recent study of HIV+ patients. To investigate among healthy persons whether serum sCD30 is associated with NHL risk, we carried out a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. There was a strong dose-response relationship between prediagnostic sCD30 concentration and NHL risk among 234 cases and 234 individually matched controls (odds ratio [95% confidence interval] for second, third, and fourth quartiles vs first quartile: 1.4 [0.8-2.6], 2.2 [1.2-4.1], 4.1 [2.2-7.8]; Ptrend < .001), which persisted among cases diagnosed 6 to 10 years after providing a blood sample. Given that a similar relationship has been observed among HIV+ patients, our findings suggest that chronic B-cell stimulation may be an important mechanism involved in B-cell lymphomagenesis among severely immunocompromised and healthy populations alike. PMID:19638620

  16. Translocation (8;22) in cold agglutinin disease associated with B-cell lymphoma.

    PubMed

    Chng, Wee Joo; Chen, Jean; Lim, Susan; Chong, Siew Meng; Kueh, Yan Koon; Lee, Szu-Hee

    2004-07-01

    Cold agglutinin disease (CAD) is a hemolytic anemia due to anti-red cell autoantibodies that are reactive at cold temperatures. In the elderly, it may be associated with underlying B-cell lymphoma, usually a lympho-plasmacytic lymphoma variant. We report a case of CAD in an elderly Indonesian female, which was associated with a B-cell lymphoma that showed a histologic appearance consistent with large-cell lymphoma. Cytogenetic analysis revealed the presence of trisomies 3 and 12, which have been reported previously in B-cell lymphoma associated with CAD. In addition, a t(8;22) was found in 24 out of 28 metaphases. Translocation (8;22) is associated with Burkitt lymphoma or acute lymphoblastic lymphoma, French-American-British subtype L3. It has not been previously reported in B-cell lymphoma asssociated with CAD, and could represent a blastic transformation of the underlying B-cell lymphoma.

  17. Impact of autologous and allogeneic stem cell transplantation in peripheral T-cell lymphomas.

    PubMed

    Reimer, Peter

    2010-01-01

    Peripheral T/NK-cell lymphomas (PTCLs) are rare malignancies characterized by poor prognosis. So far, no standard therapy has been established, due to the lack of randomised studies. High-dose therapy and autologous stem cell transplantation (HDT-autoSCT) have shown good feasibility with low toxicity in retrospective studies. In relapsing and refractory PTCL several comparison analyses suggest similar efficacy for PTCL when compared with aggressive B-cell lymphoma. In the upfront setting, prospective data show promising results with a long-lasting overall survival in a relevant subset of patients. Achieving a complete remission at transplantation seems to be the most important prognostic factor. Allogeneic stem cell transplantation (alloSCT) has been investigated only as salvage treatment. Especially when using reduced intensity conditioning regimen, eligible patients seem to benefit from this approach. To define the role for upfront stem cell transplantation a randomised trial by the German High-Grade Non-Hodgkin Lymphoma Study Group comparing HDT-autoSCT and alloSCT will be initiated this year.

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

    ClinicalTrials.gov

    2013-05-15

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

  19. Bone Marrow Transplantation for Peripheral T-Cell Non-Hodgkins' Lymphoma in First Remission.

    PubMed

    Sharma, Manish; Pro, Barbara

    2015-07-01

    Opinion statement: Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous diseases that carry, with the exception of anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma, a poor prognosis when treated with conventional chemotherapy. Historically, PTCL was treated like aggressive B-cell lymphomas, and to date cyclophosphamide, prednisone, vincristine, and doxorubicin (CHOP) remains the most commonly used regimen, despite disappointing results. Given the poor outcomes of PTCL patients, a number of studies have investigated the role of high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in the upfront setting, with different results. However, there are no prospective randomized trials, and the clinical benefit appears to be restricted to patients who achieve an objective response after induction chemotherapy. Nevertheless, with the exception of low-risk ALK+ anaplastic large cell lymphoma, in light of the available data, HDT/ASCT for consolidation should be recommended for patients deemed eligible. The results of phase II trials showed that allogeneic stem cell transplantation can cure some relapsed/refractory patients, and few studies have evaluated this strategy in the frontline setting. With the availability of recently approved new drugs as well as new targeted agents under investigation, a number of ongoing studies are testing novel combinations aiming to improve rate and durability of responses to induction chemotherapy.

  20. CD5-expressing B-cell lymphomas/leukemias: relatively high frequency of CD5+ B-cell lymphomas with an overall poor prognosis in Nagasaki Japan.

    PubMed

    Kamihira, S; Hirakata, Y; Atogami, S; Sohda, H; Tsuruda, K; Yamada, Y; Tomonaga, M

    1996-06-01

    To characterize CD5+ B-cell neoplasms in Japan, where chronic lymphocytic leukemia (CLL) is rare and of different subtypes in comparison with Western countries, we collected 58 cases of CD5+ B-cell lymphomas/leukemias and analyzed their clinicopathologic features. According to the French-American-British (FAB) and standard histologic classification, the cases corresponded to small lymphocytic lymphoma (SLL, group I; n = 22, consisting of CLL, n = 10, CLL/PL, n = 3, and CLLmixed, n = 7); intermediate differentiated lymphoma/mantle cell lymphoma (IDL/MCL, group II, n = 18); and others with CD5-positive lymphomas (group III, n = 18). The CD5+ B-cell lymphomas showed morphologic and prognostic variability among the three groups. The clinical and immunophenotypic features were remarkably consistent in leukemic disease being seen in 73% of all cases, splenomegaly in 63%, and intense CD19, CD20, surface membrane immunogobulin M (SmIgM) or SmIgM and SmIgD, light-chain expression, and no CD10 expression. The median survival time of groups I, II, and III was 7.8, 3.3, and 0.8 years, respectively. These findings suggest that CD5 antigens may serve as valid markers for the prognosis and clinical features of B-cell lymphomas and that CD5+ B-cell lymphomas with an overall poor prognosis occurs at a relatively high frequency in Japan. This also suggests that a combination of immunophenotypic and morphologic features is of value for characterizing CD5+ B-cell neoplasms.

  1. 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

  2. Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis.

    PubMed

    Schinasi, Leah; Leon, Maria E

    2014-04-23

    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.

  3. Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

    ClinicalTrials.gov

    2016-06-27

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult 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 T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Waldenström Macroglobulinemia

  4. Involved Field Radiation After Autologous Stem Cell Transplant for Diffuse Large B-Cell Lymphoma in the Rituximab Era

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Biswas, Tithi; Dhakal, Sughosh; Chen Rui

    2010-05-01

    Purpose: For patients with recurrent or refractory large B-cell non-Hodgkin's lymphoma, high-dose chemotherapy and autologous stem cell transplant (ASCT) is the treatment of choice. We evaluated the role of involved field radiation therapy (IFRT) post-ASCT for patients initially induced with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) or, more recently, rituximab-CHOP (R-CHOP). Materials and Methods: Between May 1992 and April 2005, 176 patients underwent ASCT for recurrent or refractory large B-cell non-Hodgkin's lymphoma; 164 patients were evaluable for endpoint analysis. Fifty percent of the CHOP group (n = 131), and 39% of the R-CHOP group (n = 33), received IFRT. Follow-upmore » from the time of transplant was a median/mean of 1.7/3 years (range, 0.03-13 years). Results: The 5-year overall survival (OS) and disease-specific survival (DSS) improved with IFRT in both the R-CHOP (p = 0.006 and 0.02, respectively) and CHOP (p = 0.02 and p = 0.04, respectively) groups. IFRT was associated with a 10% (p = 0.17) reduction in local failure, alone or with a distant site. On univariate analysis, IFRT was associated with superior OS (hazard ratio [HR] = 0.50 [95% CI 0.32, 0.78]; p = 0.002) and DSS (HR = 0.53 [95% CI 0.33, 0.86]; p = 0.009). Presence of B symptoms was adverse (p = 0.03). On multivariate analysis, only IFRT was associated with significant improvement in OS (HR = 0.35 [0.18, 0.68]; p = 0.002) and DSS (HR = 0.39 [95% CI 0.18, 0.84]; p = 0.01). Conclusions: Recognizing that positive and negative patient selection bias exists for the use of IFRT post-ASCT, patients initially treated with CHOP or R-CHOP and who undergo ASCT for recurrent or refractory disease may benefit from subsequent IFRT presumably due to enhanced local control that can translate into a survival advantage.« less

  5. Allogeneic Hematopoietic Cell Transplantation as Curative Therapy for Patients with Non-Hodgkin Lymphoma: Increasingly Successful Application to Older Patients.

    PubMed

    Fenske, Timothy S; Hamadani, Mehdi; Cohen, Jonathon B; Costa, Luciano J; Kahl, Brad S; Evens, Andrew M; Hamlin, Paul A; Lazarus, Hillard M; Petersdorf, Effie; Bredeson, Christopher

    2016-09-01

    Non-Hodgkin lymphoma (NHL) constitutes a collection of lymphoproliferative disorders with widely varying biological, histological, and clinical features. For the B cell NHLs, great progress has been made due to the addition of monoclonal antibodies and, more recently, other novel agents including B cell receptor signaling inhibitors, immunomodulatory agents, and proteasome inhibitors. Autologous hematopoietic cell transplantation (auto-HCT) offers the promise of cure or prolonged remission in some NHL patients. For some patients, however, auto-HCT may never be a viable option, whereas in others, the disease may progress despite auto-HCT. In those settings, allogeneic HCT (allo-HCT) offers the potential for cure. Over the past 10 to 15 years, considerable progress has been made in the implementation of allo-HCT, such that this approach now is a highly effective therapy for patients up to (and even beyond) age 75 years. Recent advances in conventional lymphoma therapy, peritransplantation supportive care, patient selection, and donor selection (including the use of alternative hematopoietic cell donors), has allowed broader application of allo-HCT to patients with NHL. As a result, an ever-increasing number of NHL patients over age 60 to 65 years stand to benefit from allo-HCT. In this review, we present data in support of the use of allo-HCT for patients with diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. These histologies account for a large majority of allo-HCTs performed for patients over age 60 in the United States. Where possible, we highlight available data in older patients. This body of literature strongly supports the concept that allo-HCT should be offered to fit patients well beyond age 65 and, accordingly, that this treatment should be covered by their insurance carriers. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2009-01-01

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

  7. Changes in the influence of lymphoma- and HIV-specific factors on outcomes in AIDS-related non-Hodgkin lymphoma

    PubMed Central

    Barta, S. K.; Samuel, M. S.; Xue, X.; Wang, D.; Lee, J. Y.; Mounier, N.; Ribera, J.-M.; Spina, M.; Tirelli, U.; Weiss, R.; Galicier, L.; Boue, F.; Little, R. F.; Dunleavy, K.; Wilson, W. H.; Wyen, C.; Remick, S. C.; Kaplan, L. D.; Ratner, L.; Noy, A.; Sparano, J. A.

    2015-01-01

    Background We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. Patients and methods We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989–1995), early cART (1996–2000), recent cART (2001–2004), and contemporary cART era (2005–2010). Results Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm3) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. Conclusions Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma

  8. Level of PAX5 in differential diagnosis of non-Hodgkin's lymphoma

    PubMed Central

    Bharti, Brij; Shukla, Sachin; Tripathi, Ratnakar; Mishra, Suman; Kumar, Mohan; Pandey, Manoj; Mishra, Rajnikant

    2016-01-01

    Background & objectives: The PAX5, a paired box transcription factor and B-cell activator protein (BSAP), activates B-cell commitment genes and represses non-B-cell lineage genes. About 14 transcript variants of PAX5 have been observed in human. Any alteration in its expression pattern leads to lymphogenesis or associated diseases and carcinogenesis in non-lymphoid tissues. Its mechanisms of function in pathophysiology of non-Hodgkin's lymphoma (NHL) are unclear. This study was intended to explore influence of PAX5 in cascade of NHL pathogenesis and diagnosis. Methods: Samples of 65 patients were evaluated by immunohistochemical staining for cellular localization of PAX5, CD19, CD3, cABL, p53, Ras and Raf and by TUNEL assay, RNA-isolation and reverse transcriptase (RT)-PCR, Western blot analysis, and lactate dehydrogenase (LDH) specific staining. Results: B-cell type NHL patients were positive for PAX5, p53, Ras, CD19, Raf and CD3. All of them showed TUNEL-positive cells. The differential expression pattern of PAX5, CD19, p53, CD3, ZAP70, HIF1α, Ras, Raf and MAPK (mitogen-activated protein kinase) at the levels of transcripts and proteins was observed. The LDH assay showed modulation of LDH4 and LDH5 isoforms in the lymph nodes of NHL patients. Interpretation & conclusions: The histological observations suggested that the patients represent diverse cases of NHL like mature B-cell type, mature T-cell type and high grade diffuse B-cell type NHL. The findings indicate that patients with NHL may also be analyzed for status of PAX5, CD19 and ZAP70, and their transcriptional and post-translational variants for the differential diagnosis of NHL and therapy. PMID:27748274

  9. Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2018-03-05

    Anemia; B-Cell Prolymphocytic Leukemia; Fatigue; Fever; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Hairy Cell Leukemia; Lymphadenopathy; Lymphocytosis; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Night Sweats; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Richter Syndrome; Splenomegaly; Thrombocytopenia; Weight Loss

  10. Non-Hodgkin's lymphoma of the breast presenting as breast abscess during pregnancy.

    PubMed

    Sultan, Naheed; Khalid, Mahvesh; Khan, Sarah Rafi; Khan, Fahadullah

    2012-10-01

    Primary non-Hodgkin's lymphoma of the breast is an uncommon disease. In all patients with breast lump, primary lymphoma of breast should be considered as it is one of the most easily missed pathology. We report a case of a 22 years old lactating mother who presented with the complaint of a painful swelling in the right breast, noticed during the last trimester of her pregnancy, mimicking breast abscess.

  11. Genomic profiling using array comparative genomic hybridization define distinct subtypes of diffuse large b-cell lymphoma: a review of the literature

    PubMed Central

    2012-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH), as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS). The advent of microarray-based studies (chromosome, RNA, gene expression, etc) has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1) array based CGH; 2) classical CGH; and 3) gene expression profiling studies. The aims of this review were three-fold: (1) to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2) to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3) to list re-classified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes. Although conventional cytogenetic methods such as Karyotypes and

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

    ClinicalTrials.gov

    2018-02-07

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

  13. Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation.

    PubMed

    Bachanova, Veronika; Weisdorf, Daniel J; Wang, Tao; Marsh, Steven G E; Trachtenberg, Elizabeth; Haagenson, Michael D; Spellman, Stephen R; Ladner, Martha; Guethlein, Lisbeth A; Parham, Peter; Miller, Jeffrey S; Cooley, Sarah A

    2016-09-01

    Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell-replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. Extranodal Marginal Zone B-cell Lymphoma of the Ocular Adnexa.

    PubMed

    Guffey Johnson, Jean; Terpak, Lauren A; Margo, Curtis E; Setoodeh, Reza

    2016-04-01

    Low-grade B-cell lymphomas located around the eye present unique challenges in diagnosis and treatment. Extranodal marginal zone B-cell lymphoma is the most common lymphoma of the ocular adnexa (conjunctiva, orbit, lacrimal gland, and eyelid). A systematic search of the relevant literature was performed. Material pertinent to the diagnosis, prognosis, pathogenesis, and treatment of extranodal marginal zone B-cell lymphoma of the ocular adnexa was identified, reviewed, and analyzed, focusing on management strategies for primary localized disease. The primary cause of extranodal marginal zone B-cell lymphoma of the ocular adnexa remains elusive, although an infectious agent is suspected. Radiotherapy is the most common initial treatment for localized disease. Initial treatment with chemotherapy, immunotherapy, and antibiotics has shown promising results, but the number of series is limited and controlled trials do not exist. Although the long-term outcome of localized extranodal marginal zone B-cell lymphoma of the ocular adnexa is good, optimal treatment remains a goal. The variation in rates of local and systemic relapse among treated stage 1E tumors suggests that critical factors affecting outcomes are not fully understood. Radiotherapy is the standard of care; at this time, the evidence is insufficient to recommend chemotherapy, immunotherapy, or antibiotics for initial treatment of extranodal marginal zone B-cell lymphoma localized to the ocular adnexa. Well-controlled comparative studies are needed.

  15. Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

    ClinicalTrials.gov

    2018-06-25

    Diffuse Large B-Cell Lymphoma Activated B-Cell Type; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; High Grade B-Cell Lymphoma, Not Otherwise Specified; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  16. Nivolumab and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

    ClinicalTrials.gov

    2018-01-25

    Grade 3a Follicular Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

  17. Multiplex Droplet Digital PCR Quantification of Recurrent Somatic Mutations in Diffuse Large B-Cell and Follicular Lymphoma.

    PubMed

    Alcaide, Miguel; Yu, Stephen; Bushell, Kevin; Fornika, Daniel; Nielsen, Julie S; Nelson, Brad H; Mann, Koren K; Assouline, Sarit; Johnson, Nathalie A; Morin, Ryan D

    2016-09-01

    A plethora of options to detect mutations in tumor-derived DNA currently exist but each suffers limitations in analytical sensitivity, cost, or scalability. Droplet digital PCR (ddPCR) is an appealing technology for detecting the presence of specific mutations based on a priori knowledge and can be applied to tumor biopsies, including formalin-fixed paraffin embedded (FFPE) tissues. More recently, ddPCR has gained popularity in its utility in quantifying circulating tumor DNA. We have developed a suite of novel ddPCR assays for detecting recurrent mutations that are prevalent in common B-cell non-Hodgkin lymphomas (NHLs), including diffuse large B-cell lymphoma, follicular lymphoma, and lymphoplasmacytic lymphoma. These assays allowed the differentiation and counting of mutant and wild-type molecules using one single hydrolysis probe. We also implemented multiplexing that allowed the simultaneous detection of distinct mutations and an "inverted" ddPCR assay design, based on employing probes matching wild-type alleles, capable of detecting the presence of multiple single nucleotide polymorphisms. The assays successfully detected and quantified somatic mutations commonly affecting enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) (Y641) and signal transducer and activator of transcription 6 (STAT6) (D419) hotspots in fresh tumor, FFPE, and liquid biopsies. The "inverted" ddPCR approach effectively reported any single nucleotide variant affecting either of these 2 hotspots as well. Finally, we could effectively multiplex hydrolysis probes targeting 2 additional lymphoma-related hotspots: myeloid differentiation primary response 88 (MYD88; L265P) and cyclin D3 (CCND3; I290R). Our suite of ddPCR assays provides sufficient analytical sensitivity and specificity for either the invasive or noninvasive detection of multiple recurrent somatic mutations in B-cell NHLs. © 2016 American Association for Clinical Chemistry.

  18. Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)

    ClinicalTrials.gov

    2018-06-25

    Advanced Malignant Solid Neoplasm; ALK Fusion Protein Expression; ALK Gene Mutation; ALK Gene Translocation; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Histiocytosis; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; ROS1 Fusion Positive; ROS1 Gene Mutation; ROS1 Gene Translocation

  19. Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin's lymphoma.

    PubMed

    Green, Michael R; Aya-Bonilla, Carlos; Gandhi, Maher K; Lea, Rod A; Wellwood, Jeremy; Wood, Peter; Marlton, Paula; Griffiths, Lyn R

    2011-05-01

    Recent developments in genomic technologies have resulted in increased understanding of pathogenic mechanisms and emphasized the importance of central survival pathways. Here, we use a novel bioinformatic based integrative genomic profiling approach to elucidate conserved mechanisms of lymphomagenesis in the three commonest non-Hodgkin's lymphoma (NHL) entities: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia. By integrating genome-wide DNA copy number analysis and transcriptome profiling of tumor cohorts, we identified genetic lesions present in each entity and highlighted their likely target genes. This revealed a significant enrichment of components of both the apoptosis pathway and the mitogen activated protein kinase pathway, including amplification of the MAP3K12 locus in all three entities, within the set of genes targeted by genetic alterations in these diseases. Furthermore, amplification of 12p13.33 was identified in all three entities and found to target the FOXM1 oncogene. Amplification of FOXM1 was subsequently found to be associated with an increased MYC oncogenic signaling signature, and siRNA-mediated knock-down of FOXM1 resulted in decreased MYC expression and induced G2 arrest. Together, these findings underscore genetic alteration of the MAPK and apoptosis pathways, and genetic amplification of FOXM1 as conserved mechanisms of lymphomagenesis in common NHL entities. Integrative genomic profiling identifies common central survival mechanisms and highlights them as attractive targets for directed therapy. 2011 Wiley-Liss, Inc.

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

    ClinicalTrials.gov

    2017-04-17

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

  1. Primary cutaneous marginal zone B-cell lymphoma: clinical and histological aspects.

    PubMed

    Khaled, A; Sassi, S; Fazaa, B; Ben Hassouna, J; Ben Romdhane, K; Kamoun, M R

    2009-02-01

    According to the WHO-EORTC classification of cutaneous lymphomas, primary cutaneous marginal zone B-cell lymphoma are now well characterized. We report here a case of primary cutaneous marginal zone B-cell lymphoma in a 51 year-old man in which the diagnosis was made using both histology and immunopathology. The patient had no remarkable medical history, no history of either acute inflammation or insect bite, and presented with a 5 cm solitary asymptomatic erythematous firm, multinodular and infiltrated plaque on the back for 12 months. Histological examination and immunohistochemical study of a cutaneous biopsy provided a differential diagnosis between B cell lymphoma and lymphocytoma cutis. Full body work up revealed no signs of extracutaneous dissemination. The patient underwent surgical excision of the nodule. Histological examination showed a histological and immunophenotyping profile typical of primary cutaneous marginal zone B-cell lymphoma. The lesion was completely excised with clear margins and no recurrence occurred after a 12 month-follow-up period. Primary cutaneous marginal zone B-cell lymphoma are low-grade lymphomas that have an indolent course and a high tendency to recur. They should be differentiated from lymphocytoma cutis and from the other types of cutaneous B cell lymphomas that have a different course and prognosis.

  2. J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

    PubMed

    Moore, Erika M; Swerdlow, Steven H; Gibson, Sarah E

    2017-10-01

    Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. We investigated the utility of J chain and myocyte enhancer factor 2B (MEF2B) in the diagnosis of CHL; NLPHL; PMBL; T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL); and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, compared with OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHLs and were negative in 43/43 (100%) CHLs. Fourteen of 15 (93%) PMBLs and 4/4 (100%) TCRLBLs were MEF2B positive, whereas 67% of PMBLs and 50% of TCRLBLs were J chain positive. Three of 3 B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL; are particularly useful in highlighting LP cells; and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.

    PubMed

    Yadav, Madhav P; Singla, Suhas; Thakral, Parul; Ballal, Sanjana; Bal, Chandrasekhar

    2016-07-01

    Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab. Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software. The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively. There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.

  4. Sporadic Burkitt’s lymphoma/acute B-cell leukaemia presenting with progressive proptosis and orbital mass in a child

    PubMed Central

    Borreggine, Carmela; Ladogana, Saverio; De Santis, Raffaela; Delle Noci, Nicola; Grilli, Gianpaolo; Macarini, Luca

    2016-01-01

    Burkitt’s lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma that is found predominantly in children, with the highest incidence occurring in Africa. The sporadic form occurs in non-endemic areas and typically involves the ileo-caecum and the bowel, whereas orbital and paranasal sinus involvement is rare. Here, we present an unusual case of sporadic BL in a Caucasian male child with rapidly progressive painful proptosis of the right eye. Magnetic resonance imaging showed an oval-shaped, extraconal mass in the supero-lateral part of the right orbit that deformed and dislocated the eyeball antero-inferiorly. The patient underwent anterior orbitotomy, and a biopsy of the excised tissue revealed a starry-sky appearance characteristic of BL. Postoperative aggressive chemotherapy was initiated with a good response after one week. PMID:27006106

  5. Consolidative autologous hematopoietic stem-cell transplantation in first remission for non-Hodgkin lymphoma: current indications and future perspective.

    PubMed

    Iams, Wade; Reddy, Nishitha M

    2014-10-01

    The non-Hodgkin lymphomas (NHLs) are a heterogeneous group of diseases with variable clinical outcomes. Autologous hematopoietic stem-cell transplantation (ASCT) as frontline, consolidative therapy has been evaluated based upon histological subtype of NHL. In this review, we summarize the major clinical trials guiding the use of frontline ASCT in NHL. With the constantly changing landscape of upfront therapy and multiple promising novel agents, the ability to conduct randomized trials to evaluate the benefit of consolidative ASCT is not only challenging but may be considered by some an inept utilization of resources. Our recommendation for consolidative ASCT is based on analyzing the current available data.

  6. Identification of LMO2 transcriptome and interactome in diffuse large B-cell lymphoma

    PubMed Central

    Cubedo, Elena; Gentles, Andrew J.; Huang, Chuanxin; Natkunam, Yasodha; Bhatt, Shruti; Lu, Xiaoqing; Jiang, Xiaoyu; Romero-Camarero, Isabel; Freud, Aharon; Zhao, Shuchun; Bacchi, Carlos E.; Martínez-Climent, Jose A.; Sánchez-García, Isidro; Melnick, Ari

    2012-01-01

    LMO2 regulates gene expression by facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the germinal center (GC) and is expressed in GC-derived non-Hodgkin lymphomas. LMO2 is one of the most powerful prognostic indicators in diffuse large B-cell (DLBCL) patients. However, its function in GC B cells and DLBCL is currently unknown. In this study, we characterized the LMO2 transcriptome and transcriptional complex in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly, and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners, such as LDB1, E2A, HEB, Lyl1, ETO2, and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, nuclear factor of activated T-cells (NFATc1), and lymphoid enhancer-binding factor1 (LEF1) proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provides a platform for future elucidation of LMO2 function in GC B cells and DLBCL pathogenesis. PMID:22517897

  7. Molecular genetics of childhood, adolescent and young adult non-Hodgkin lymphoma.

    PubMed

    Miles, Rodney R; Shah, Rikin K; Frazer, J Kimble

    2016-05-01

    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. © 2016 John Wiley & Sons Ltd.

  8. Emergency pancreatoduodenectomy (whipple procedure) for massive upper gastrointestinal bleeding caused by a diffuse B-cell lymphoma of the duodenum: report of a case.

    PubMed

    Stratigos, Panagiotis; Kouskos, Efstratios; Kouroglou, Maria; Chrisafis, Ioannis; Fois, Lucia; Mavrogiorgis, Anastasios; Axiotis, Efthimios; Zamtrakis, Sotirios

    2007-01-01

    We herein report a rare case of a massive upper gastrointestinal (GI) bleeding, caused by high-grade diffuse B-cell lymphoma of the duodenum, secondary to immunoproliferative small intestinal disease (IPSID) and treated with an emergency partial pancreatoduodenectomy. A 42-year-old man was admitted to our hospital because of hematemesis. Upper GI endoscopy was unrevealing because of the copious bleeding. Initially, the patient underwent conservative treatment, thus resulting in the temporary cessation of the bleeding. Later, the hemorrhage massively relapsed. An urgent abdominal ultrasound raised the suspicion of a large, possibly bleeding, neoplasm of the duodenum, which was finally confirmed by abdominal computed tomography. The patient underwent an emergency laparotomy, during which a partial pancreatoduodenectomy was performed (Whipple procedure). Histologically, the tumor was a high-grade B-cell lymphoma of the duodenum. The nearby small intestinal mucosa was suggestive of IPSID. A massive upper GI hemorrhage from a high-grade B-cell non-Hodgkin lymphoma of the duodenum, which develops secondary to IPSID, is a very rare clinical demonstration of this disease. Our case is one of the few reports in the English literature, for which the Whipple procedure has been performed as a curative treatment.

  9. Use of non-steroidal anti-inflammatory drugs and risk of non-Hodgkin lymphoma: a systematic review and meta-analysis.

    PubMed

    Ye, Xibiao; Casaclang, Natalie; Mahmud, Salaheddin M

    2015-12-01

    Epidemiological study findings regarding the association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and risk of non-Hodgkin lymphoma (NHL) have been inconsistent. We aimed to systematically review epidemiological studies of the association and calculate pooled relative risks using meta-analytic methods. We searched eight electronic literature databases and three clinical trial registers to identify all studies (including observational studies and randomized clinical trials) of the association published prior to October 2013. Identified studies were independently reviewed by two researchers. We used a random effects model to calculate pooled odds ratio (PORs). Heterogeneity amongst studies was examined using Cochran's Q and I-squared (I(2)) tests; and sources of heterogeneity were explored using subgroup and meta-regression analyses. A total of 17 studies (12 case-control studies and five cohort studies), all adult studies, were included. Use of NSAIDs was not associated with overall risk of NHL [POR = 1.05, and 95% confidence interval (95% CI) 0.90-1.22] or NHL subtypes including B-cell lymphoma, T-cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Aspirin use was associated with reduced risk of CLL/SLL (POR = 0.70, 95% CI 0.54-0.91) but not with the risk of all NHLs (POR = 1.02, 95% CI 0.89-1.17). Use of non-aspirin NSAIDs was associated with increased risk of NHL (POR = 1.41, 95% CI 1.01-1.97) amongst females only. The epidemiologic evidence remains inconclusive. Effects of NSAIDs may differ by drug type, NHL subtype, and sex and more studies taking into consideration these differences are needed. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma

    PubMed Central

    Devitt, Katherine; Cerny, Jan; Switzer, Bradley; Ramanathan, Muthalagu; Nath, Rajneesh; Yu, Hongbo; Woda, Bruce A.; Chen, Benjamin J.

    2014-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management. PMID:24955327

  11. Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma.

    PubMed

    Devitt, Katherine; Cerny, Jan; Switzer, Bradley; Ramanathan, Muthalagu; Nath, Rajneesh; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

    2014-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management.

  12. Atypical lymphocytosis resembling non-Hodgkin's lymphoma in peritoneal effusion of infectious mononucleosis: a case report.

    PubMed

    Tsuruta, Seiji; Ohyama, Satoko; Arai, Hanako; Kojima, Masaru; Johshita, Takashi; Suzuki, Yutaka

    2004-01-01

    Peritoneal effusion appears to be an unusual complication of infectious mononucleosis (IM). The cytological features of peritoneal effusion from a patient affected by IM are presented. The patient was a 21-year-old Japanese woman, with typical and physical findings of IM. Ascites disappeared with resolution of acute IM. The cytospin smears of the ascitic fluid were highly cellular, consisting exclusively of lymphoid cells. Lymphoid cells were composed of large cells with broad basophilic cytoplasm, as well as of small to medium-sized cells having scant cytoplasm and irregularly shaped nuclei. The overall cytomorphological pictures posed serious difficulties in differentiating this condition from those of peripheral T-cell lymphomas manifesting ascites. The majority of atypical lymphocytes, including large cells, expressed CD3 and CD8. The present case indicates that IM should be added to the list of lesions considered for the differential diagnosis of non-Hodgkin's lymphoma of the peritoneal fluid, particularly regarding young adults.

  13. Chemotoxicity Recovery of Mitochondria in Non-Hodgkin Lymphoma Resulting in Minimal Residual Disease

    PubMed Central

    Kusao, Ian; Agsalda, Melissa; Troelstrup, David; Villanueva, Nicolas; Shiramizu, Bruce

    2009-01-01

    Background The mechanisms responsible for resistant disease or recurrence of non-Hodgkin lymphoma (NHL) in children cover a wide spectrum from drug resistance to genetic mutations. A unique mechanism suggesting the role of mitochondria as the key energy source is studied following a clinical observation where pediatric Burkitt lymphoma (BL) specimens from patients on therapy were found to have increased copies of mitochondria DNA (mtDNA) in specimens which were shown to be positive for minimal residual disease and/or persistent disease (MRD/PD). This study hypothesized that the mitochondria play an important role in a cell’s recovery from toxicity via a compensatory increase in mtDNA. Procedure BL specimens with MRD/PD were assayed for mtDNA. An in vitro model was then designed using Ramos cell lines by exposing the lymphoma cells to varying concentrations of doxorubicin and vincristine for 1 hr; and allowing for recovery in culture over 7 days. DNA was extracted from aliquots over several days to determine mtDNA copy numbers by real-time polymerase chain reaction (PCR). Results Increased mtDNA copy numbers were found in clinical specimens with MRD/PD as well as in recovering Ramos cells from chemotoxicity. Conclusions The recovering lymphoma cells from the chemotoxic effects appeared to compensate by increasing mtDNA content, which may contribute to the clinical residual or resistant disease in some cases of childhood BL. PMID:18322926

  14. Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

    PubMed Central

    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.

    2017-01-01

    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

  15. [Plasmablastic lymphoma].

    PubMed

    Fernández-Álvarez, Rubén; Sancho, Juan-Manuel; Ribera, Josep-María

    2016-11-04

    Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin lymphoma that commonly occurs in human immunodeficiency virus (HIV)-positive individuals, and affects oral sites. Occasionally, it has been described in HIV-negative patients and involving non-oral sites. Pathologically, PBL is a high-grade B-cell lymphoma that displays the immunophenotype of a terminally differentiated B-lymphocyte with loss of B-cell markers (CD20) and expression of plasma-cell antigens. Epstein-Barr virus infection and MYC rearrangements are frequently observed. Treatment of PBL is challenging because of the lack of established treatment and poor outcomes, with median survival times shorter than one year. In this review, we discuss the clinical and epidemiologic spectrum of PBL as well as its distinct pathological features. Finally, we summarize the currently available approaches for the treatment of patients with PBL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  16. EBV latent membrane protein 1 activates Akt, NFkappaB, and Stat3 in B cell lymphomas.

    PubMed

    Shair, Kathy H Y; Bendt, Katherine M; Edwards, Rachel H; Bedford, Elisabeth C; Nielsen, Judith N; Raab-Traub, Nancy

    2007-11-01

    Latent membrane protein 1 (LMP1) is the major oncoprotein of Epstein-Barr virus (EBV). In transgenic mice, LMP1 promotes increased lymphoma development by 12 mo of age. This study reveals that lymphoma develops in B-1a lymphocytes, a population that is associated with transformation in older mice. The lymphoma cells have deregulated cell cycle markers, and inhibitors of Akt, NFkappaB, and Stat3 block the enhanced viability of LMP1 transgenic lymphocytes and lymphoma cells in vitro. Lymphoma cells are independent of IL4/Stat6 signaling for survival and proliferation, but have constitutively activated Stat3 signaling. These same targets are also deregulated in wild-type B-1a lymphomas that arise spontaneously through age predisposition. These results suggest that Akt, NFkappaB, and Stat3 pathways may serve as effective targets in the treatment of EBV-associated B cell lymphomas.

  17. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification

    PubMed Central

    Cheson, Bruce D.; Fisher, Richard I.; Barrington, Sally F.; Cavalli, Franco; Schwartz, Lawrence H.; Zucca, Emanuele; Lister, T. Andrew

    2014-01-01

    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. PMID:25113753

  18. Nanoparticle-based strategy for personalized B-cell lymphoma therapy

    PubMed Central

    Martucci, Nicola M; Migliaccio, Nunzia; Ruggiero, Immacolata; Albano, Francesco; Calì, Gaetano; Romano, Simona; Terracciano, Monica; Rea, Ilaria; Arcari, Paolo; Lamberti, Annalisa

    2016-01-01

    B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite) were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2) with small interfering RNA (siRNA). An idiotype-specific peptide (Id-peptide) specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells. Specific nanoparticle uptake, driven by the Id-peptide, was evaluated by flow cytometry and confocal microscopy and was increased by approximately threefold in target cells compared with nonspecific myeloma cells and when a random control peptide was used instead of Id-peptide. The specific internalization efficiency was increased by fourfold when siRNA was also added to the modified nanoparticles. The modified diatomite particles were not cytotoxic and their effectiveness in downregulation of gene expression was explored using siRNA targeting Bcl2 and evaluated by quantitative real-time polymerase chain reaction and Western blot analyses. The resulting gene silencing observed is of significant biological importance and opens new possibilities for the personalized treatment of lymphomas. PMID:27895482

  19. Biodynamic digital holography of chemoresistance in a pre-clinical trial of canine B-cell lymphoma.

    PubMed

    Choi, Honggu; Li, Zhe; Sun, Hao; Merrill, Dan; Turek, John; Childress, Michael; Nolte, David

    2018-05-01

    Biodynamic digital holography was used to obtain phenotypic profiles of canine non-Hodgkin B-cell lymphoma biopsies treated with standard-of-care chemotherapy. Biodynamic signatures from the living 3D tissues were extracted using fluctuation spectroscopy from intracellular Doppler light scattering in response to the molecular mechanisms of action of therapeutic drugs that modify a range of internal cellular motions. The standard-of-care to treat B-cell lymphoma in both humans and dogs is a combination CHOP therapy that consists of doxorubicin, prednisolone, cyclophosphamide and vincristine. The proportion of dogs experiencing durable cancer remission following CHOP chemotherapy was 68%, with 13 out of 19 dogs responding favorably to therapy and 6 dogs failing to have progression-free survival times greater than 100 days. Biodynamic signatures were found that correlate with inferior survival times, and biomarker selection was optimized to identify specific Doppler signatures related to chemoresistance. A machine learning classifier was constructed based on feature vector correlations and linear separability in high-dimensional feature space. Hold-out validation predicted patient response to therapy with 84% accuracy. These results point to the potential for biodynamic profiling to contribute to personalized medicine by aiding the selection of chemotherapy for cancer patients.

  20. Primary Intra-aortic Epstein-Barr Virus-Positive Large B-Cell Lymphoma Presenting as Aortic Mural Thrombosis: An Entity Distinct From Intravascular Large B-Cell Lymphoma.

    PubMed

    Nakao, Ryuta; Sakashita, Aki; Omoto, Atsushi; Sato, Osamu; Hino, Yoko; Yanagisawa, Akio; Urata, Yoji

    2017-12-01

    Intravascular selective growth of neoplastic B lymphocytes is a characteristic finding of intravascular large B-cell lymphoma (IVLBCL). However, because neoplastic B cells of IVLBCL grow merely in the lumina of capillaries or small vessels, primary IVLBCL of the great vessels is considered exceptional. To our knowledge, only 2 primary B-cell lymphomas in the lumina of the vena cava have been reported. However, there has been no report of primary B-cell lymphoma with intra-aortic growth. We describe a novel manifestation of primary Epstein-Barr virus-positive large B-cell lymphoma mainly affecting the lumina of the aorta and its major branches in a 76-year-old man. He had a long-term fever that was refractory to antibiotics and aortic mural thrombosis with visceral embolization. Because he had no detectable mass suggesting a malignancy, it was difficult to diagnose while he was alive. He died without anticancer treatment, and the confirmed diagnosis was made at autopsy.

  1. Enzooty of non-Hodgkin's malignant lymphoma of Papio hamadryas in Sukhumi monkey colony. Clinical and morphological signs of pre-lymphoma.

    PubMed

    Yakovleva, Lelita A; Lapin, Boris A; Agumava, Aslan A

    2018-04-01

    Inoculation of hamadryas baboons with blood of leukemia ill people-induced malignant non-Hodgkin's lymphoma in experimental animals for a very considerable latency period. At close contact of inoculated baboons with healthy non-inoculated animals, the lymphoma spread between them. The epidemiological analysis, postmortem examination, histological analysis, tissue culturing, and PCR were used for the diagnostics of lymphoma and pre-lymphoma, purification, identification of STLV-1, and HVP viruses. Characteristic clinical and morphological signs designated by us as pre-lymphoma often precede the lymphoma development. In some cases, pre-lymphoma does not develop in lymphoma because animals die from various diseases and do not reach the point of the lymphoma development. The horizontal transmission of lymphoma arising with the participation of T-lymphotropic retrovirus STLV-1 is shown. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. CXCR5+CD8+ T cells present elevated capacity in mediating cytotoxicity toward autologous tumor cells through interleukin 10 in diffuse large B-cell lymphoma.

    PubMed

    Tang, Jiahong; Zha, Jie; Guo, Xutao; Shi, Pengcheng; Xu, Bing

    2017-09-01

    Diffuse large B-cell lymphoma (DLBCL) is a common and aggressive subtype of non-Hodgkin's lymphomas, with limited treatment options in refractory and relapsed patients. Growing evidence supports the notion that CD8 + T cell immunity could be utilized to eliminate B cell lymphomas. CXCR5 + CD8 + T cell is a novel cell subtype and share CXCR5 expression with CD19 + tumor cells. In this study, we investigated the frequency and function of existing CXCR5 + CD8 + T cells in DLBCL patients. We found that DLBCL patients as a group demonstrated significantly higher level of CXCR5 + CD8 + T cells than healthy individuals, with huge variability in each patient. Using anti-CD3/CD28-stimulated CD8 + T cells as effector (E) cells and autologous CD19 + tumor cells as target (T) cells, at high E:T ratio, no difference between the intensities of CXCR5 + CD8 + T cell- and CXCR5 - CD8 + T cell-mediated cytotoxicity were observed. However, at intermediate and low E:T ratios, the CXCR5 + CD8 + T cells presented stronger cytotoxicity than CXCR5 - CD8 + T cells. The expressions of granzyme A, granzyme B, and perforin were significantly higher in CXCR5 + CD8 + T cells than in CXCR5 - CD8 + T cells, with no significant difference in the level of degranulation. Tumor cells in DLBCL were known to secrete high level of interleukin 10 (IL-10). We therefore blocked the IL-10/IL-10R pathway, and found that the expressions of granzyme A, granzyme B, and perforin by CXCR5 + CD8 + T cells were significantly elevated. Together, these results suggest that CXCR5 + CD8 + T cells are potential candidates of CD8 + T cell-based immunotherapies, could mediate elimination of autologous tumor cells in DLBCL patients, but are also susceptible to IL-10-mediated suppression. Copyright © 2017. Published by Elsevier B.V.

  3. Non-Hodgkin lymphoma subtype distribution, geodemographic patterns, and survival in the US: A longitudinal analysis of the National Cancer Data Base from 1998 to 2011.

    PubMed

    Al-Hamadani, Mohammed; Habermann, Thomas M; Cerhan, James R; Macon, William R; Maurer, Matthew J; Go, Ronald S

    2015-09-01

    The World Health Organization classification of non-Hodgkin lymphoma (NHL) was introduced in 2001. However, its incorporation into clinical practice is not well-described. We studied the distribution of NHL subtypes in adults diagnosed from 1998 to 2011, evaluated time trends, geo-demographic correlates, and changes in 5-year overall survival (OS). We obtained data prospectively collected by the National Cancer Data Base, which covers 70% of US cancer cases. There were 596,476 patients diagnosed with NHL. The major subtypes were diffuse large B-cell (32.5%), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; 18.6%), follicular (17.1%), marginal zone (8.3%), mantle cell (4.1%), peripheral T-cell not-otherwise-specified (1.7%), Burkitt (1.6%), hairy cell (1.1%), lymphoplasmacytic (1.1%), and NHL not-otherwise-specified (10.8%). Over the study period, the proportion of NHL not-otherwise-specified declined by half, while marginal zone lymphoma doubled. The distribution of major and rare NHL subtypes varied according to demographics but less so geographically or by type of treatment facility. We noted several novel findings among Hispanics (lower proportion of CLL/SLL, but higher Burkitt lymphoma and nasal NK/T-cell lymphoma), Asians (higher enteropathy-associated T-cell and angioimmunoblastic T-cell lymphomas), Blacks (higher hepatosplenic T-cell lymphoma), and Native Americans (similar proportions of CLL/SLL and nasal NK/T-cell lymphoma as Asians). With the exception of peripheral T-cell not-otherwise-specified and hairy cell leukemia, 5-year OS has improved for all the major NHL subtypes. © 2015 Wiley Periodicals, Inc.

  4. Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature.

    PubMed

    Lim, W Y; Care, R; Lau, M; Chiruka, S; Dawes, P J D

    2015-01-01

    Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL) representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia) with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

  5. Pathophysiological significance and therapeutic targeting of germinal center kinase in diffuse large B-cell lymphoma.

    PubMed

    Matthews, Julie Marie; Bhatt, Shruti; Patricelli, Matthew P; Nomanbhoy, Tyzoon K; Jiang, Xiaoyu; Natkunam, Yasodha; Gentles, Andrew J; Martinez, Ezequiel; Zhu, Daxing; Chapman, Jennifer Rose; Cortizas, Elena; Shyam, Ragini; Chinichian, Shideh; Advani, Ranjana; Tan, Li; Zhang, Jianming; Choi, Hwan Geun; Tibshirani, Robert; Buhrlage, Sara J; Gratzinger, Dita; Verdun, Ramiro; Gray, Nathanael S; Lossos, Izidore S

    2016-07-14

    Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, yet 40% to 50% of patients will eventually succumb to their disease, demonstrating a pressing need for novel therapeutic options. Gene expression profiling has identified messenger RNAs that lead to transformation, but critical events transforming cells are normally executed by kinases. Therefore, we hypothesized that previously unrecognized kinases may contribute to DLBCL pathogenesis. We performed the first comprehensive analysis of global kinase activity in DLBCL, to identify novel therapeutic targets, and discovered that germinal center kinase (GCK) was extensively activated. GCK RNA interference and small molecule inhibition induced cell-cycle arrest and apoptosis in DLBCL cell lines and primary tumors in vitro and decreased the tumor growth rate in vivo, resulting in a significantly extended lifespan of mice bearing DLBCL xenografts. GCK expression was also linked to adverse clinical outcome in a cohort of 151 primary DLBCL patients. These studies demonstrate, for the first time, that GCK is a molecular therapeutic target in DLBCL tumors and that inhibiting GCK may significantly extend DLBCL patient survival. Because the majority of DLBCL tumors (∼80%) exhibit activation of GCK, this therapy may be applicable to most patients. © 2016 by The American Society of Hematology.

  6. Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

    ClinicalTrials.gov

    2017-10-10

    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 Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  7. Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

    ClinicalTrials.gov

    2017-04-07

    Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Aggressive Non-Hodgkin Lymphoma; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Waldenstrom Macroglobulinemia

  8. Effect of citral on the cytotoxicity of doxorubicin in human B-lymphoma cells.

    PubMed

    Dangkong, Darinee; Limpanasithikul, Wacharee

    2015-02-01

    Doxorubicin is a chemotherapy agent used in non-Hodgkin's lymphoma but side effects limit its use. Citral is a mixture of neral and geranial found in essential oils of lemon grass. We evaluated the activity of citral, doxorubicin, and combination on cytotoxicity, apoptosis, and anti-proliferative effects using human lymphoma Ramos cells. Cells were treated with doxorubicin alone or in combination with citral (10, 20, and 40 μM). Cytotoxic and apoptosis studies were done after 24 and 18 h incubations, respectively. Cytotoxic effects of citral on normal human peripheral blood mononuclear cells (PBMCs) were also investigated for its safety. Changes in the expression of BCL-2 family genes were analyzed by quantitative RT-PCR. Citral had cytotoxicity on cells with an IC50 value of 77.19 ± 4.95 µM. Citral at concentrations of 10, 20, and 40 µM additively increased the cytotoxic and apoptotic effects of doxorubicin, leading to decreased IC50 (µM) of the drug from 2.50 ± 0.01 to 2.16 ± 0.03, 1.90 ± 0.04, and 1.23 ± 0.04, respectively. Enhanced cytotoxicity was not observed in normal human PBMCs. Citral (40 µM) in combination with doxorubicin (1.5 µM) increased the expression of pro-apoptotic protein BAK but significantly decreased the expression of anti-apoptotic protein BCL-XL to 5.26-fold compared with doxorubicin-treated cells. It did not change the anti-proliferative activity of drug. Citral potentiated cytotoxicity of doxorubicin by increasing apoptotic effects. We conclude that citral may have beneficial effects in patients with B cell lymphoma treated with chemotherapy.

  9. Minimal disease assessment in the treatment of children and adolescents with intermediate-risk (Stage III/IV) B-cell non-Hodgkin lymphoma: a children's oncology group report.

    PubMed

    Shiramizu, Bruce; Goldman, Stanton; Kusao, Ian; Agsalda, Melissa; Lynch, James; Smith, Lynette; Harrison, Lauren; Morris, Erin; Gross, Thomas G; Sanger, Warren; Perkins, Sherrie; Cairo, Mitchell S

    2011-06-01

    Children/adolescents with mature B-cell non-Hodgkin lymphoma (B-NHL) have an excellent prognosis but relapses still occur. While chromosomal aberrations and/or clonal immunoglobulin (Ig) gene rearrangements may indicate risk of failure, a more universal approach was developed to detect minimal disease (MD). Children/adolescents with intermediate-risk B-NHL were treated with French-British-American/Lymphome Malins de Burkitt 96 (FAB/LMB96) B4 modified chemotherapy and rituximab. Specimens from diagnosis, end of induction (EOI), and end of therapy (EOT) were assayed for MD. Initial specimens were screened for IGHV family usage with primer pools followed by individual primers to identify MD. Thirty-two diagnostic/staging specimens screened positive with primer pools and unique IGHV family primers were identified. Two patients relapsed; first relapse (4 months from diagnosis) was MD-positive at EOI, the second (36 months from diagnosis) was MD-positive at EOT. At EOI, recurrent rates were similar between the MRD-positive and MRD-negative patients (P = 0·40). At EOT, only 13/32 patients had MRD data available with one relapse in the MRD-positive group and no recurrences in the MRD-negative group (P = 0·077). The study demonstrated molecular-disseminated disease in which IgIGHV primer pools could be used to assess MD. This feasibility study supports future investigations to assess the validity and significance of MD screening in a larger cohort of patients with intermediate-risk mature B-NHL. © 2011 Blackwell Publishing Ltd.

  10. Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study.

    PubMed

    Ellin, Fredrik; Landström, Jenny; Jerkeman, Mats; Relander, Thomas

    2015-07-02

    Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas, but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, as well as the outcome of these patients, in a large population-based cohort of patients with PTCL. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis, disease characteristics at diagnosis independently associated with an increased risk for later CNS involvement were involvement of more than 1 extranodal site (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.07-6.29; P = .035) and skin (HR, 3.51; 95% CI, 1.26-9.74; P = .016) and gastrointestinal involvement (HR, 3.06; 95% CI, 1.30-7.18; P = .010). The outcome of relapsed/refractory patients was very poor, and CNS involvement was not associated with a significantly worse outcome compared with relapsed/refractory patients without CNS involvement in multivariable analysis (HR, 1.6; 95% CI, 0.96-2.6; P = .074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease. © 2015 by The American Society of Hematology.

  11. 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

  12. Ascites as the initial characteristic manifestation in a patient with primary gastric CD8-positive diffuse large B-cell lymphoma.

    PubMed

    Zhao, K-X; Dai, G-Z; Zhu, J-F

    2016-05-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and the most common type of non-Hodgkin's lymphomas, the stomach is the most common extranodal site. Gastric DLBCL is often characterized by epigastric pain and vomiting. We report a case of a 78-year-old female patient with gastric diffuse large B-cell lymphoma (DLBCL) with high CD8 level which was initially manifested with ascites of unknown origin. The patient was admitted with a chief complaint of abdominal distension and scanty urine over the last twenty days, while without anorexia and fatigue until 15 March. She had no history of viral hepatitis, tuberculosis, schistosomiasis. Laboratory data revealed normal aminotransferases and bilirubin levels, but serum lactate dehydrogenase, CA125, ascitic fluid lactate dehydrogenase, ascitic fluid lymphocytes increased. The ascitic fluid was yellow-colored with 98.5% lymphocytes. Stool occult blood test was positive. Upper gastrointestinal endoscopy performed a few days later revealed multiple gastric crateriform ulcers, and Helicobacter pylori was detected in the biopsy specimen. Peripheral blood CD8+ was increased by 51%. Pathology test showed lymphocytes with atypical hyperplasia, and immunohistochemistry test resulted CD20+, CD10-, CD79α+, κ+, bcl-6+, Ki-67+ (approximately 95%), λ-, bcl-2-, CD3-, CD43-. Immunoglobulin gene (Ig) clonal rearrangement showed IgH: FR1 (+), FR2 (+), FR3(-), Igk: VJ(+), Vkde (+) in lymphoma tissue. The features of histopathology and immunohistochemistry of the tissue confirmed diffuse large B-cell lymphoma (DLBL). The patient received an uncompleted CHOP program combined with H. pylori eradication. However, the patient deceased due to disease development sixteen days later after the diagnosis.

  13. [Nasal type natural killer/T cell lymphoma: case series and literature review].

    PubMed

    Düzlü, Mehmet; Ant, Ayça; Tutar, Hakan; Karamert, Recep; Şahin, Melih; Sayar, Erolcan; Cesur, Nesibe

    2016-01-01

    Nasal type natural killer/T-cell lymphoma is a rare type of extranodal non-Hodgkin lymphoma which originates from nasal cavity and paranasal sinuses. Exact diagnosis of nasal natural killer/T-cell lymphoma, which is a rapidly progressive clinical condition, may be established by immunohistochemical analysis on biopsy material after clinical suspicion. In this article, we report four cases of nasal natural killer/T-cell lymphoma who were followed-up in our clinic and discuss the diagnosis and treatment of the disease in light of the literature data.

  14. Targeting of CD22-positive B-cell lymphoma cells by synthetic divalent sialic acid analogues.

    PubMed

    Schweizer, Astrid; Wöhner, Miriam; Prescher, Horst; Brossmer, Reinhard; Nitschke, Lars

    2012-10-01

    CD22 is an inhibitory co-receptor of the B-cell receptor (BCR) on B cells. Since CD22 is ubiquitously expressed in the B-cell lineage and CD22 endocytosis can be triggered efficiently, antibodies and antibody-based immunotoxins against CD22 are used to target B cells both in B-cell lymphomas and leukemias, as well as in autoimmune diseases. CD22 recognizes α2,6-linked sialic acids as endogenous ligands. We have developed new synthetic sialosides as ligands for human CD22. These sialosides bind CD22 on human B cells with high affinity and can efficiently enhance IgM-triggered Ca(2+) signaling. We coupled these sialosides to Pseudomonas exotoxin A to generate a novel CD22 ligand-based immunotoxin. This sialoside-exotoxin-A construct can specifically kill CD22-positive B-cell lymphoma cells. It binds specifically to CD22-positive B-cell lymphoma cells and is dominant over endogenous cis-ligands on the B-cell surface. The sialoside-exotoxin-A construct is efficiently internalized by endocytosis into B-cell lymphoma cell lines. Thus we show the development of a new therapeutic compound for targeting CD22 on human B cells, both for B-cell lymphoma, as well as for B-cell-mediated autoimmune diseases. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Toll-like receptor expression and function differ between splenic marginal zone B cell lymphoma and splenic diffuse red pulp B cell lymphoma

    PubMed Central

    Verney, Aurélie; Traverse-Glehen, Alexandra; Callet-Bauchu, Evelyne; Jallades, Laurent; Magaud, Jean-Pierre; Salles, Gilles; Genestier, Laurent; Baseggio, Lucile

    2018-01-01

    In splenic marginal zone lymphoma (SMZL), specific and functional Toll-like Receptor (TLR) patterns have been recently described, suggesting their involvement in tumoral proliferation. Splenic diffuse red pulp lymphoma with villous lymphocytes (SDRPL) is close to but distinct from SMZL, justifying here the comparison of TLR patterns and functionality in both entities. Distinct TLR profiles were observed in both lymphoma subtypes. SDRPL B cells showed higher expression of TLR7 and to a lesser degree TLR9, in comparison to SMZL B cells. In both entities, TLR7 and TLR9 pathways appeared functional, as shown by IL-6 production upon TLR7 and TLR9 agonists stimulations. Interestingly, circulating SDRPL, but not SMZL B cells, constitutively expressed CD86. In addition, stimulation with both TLR7 and TLR9 agonists significantly increased CD80 expression in circulating SDRPL but not SMZL B cells. Finally, TLR7 and TLR9 stimulations had no impact on proliferation and apoptosis of SMZL or SDRPL B cells. In conclusion, SMZL and SDRPL may derive from different splenic memory B cells with specific immunological features that can be used as diagnosis markers in the peripheral blood.

  16. Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma.

    PubMed

    Fanale, Michelle A; Younes, Anas

    2007-01-01

    Antibody-based therapeutic approaches have had a significant impact in the treatment of non-Hodgkin's lymphoma (NHL). Rituximab's development as an anti-CD20 antibody heralded a new era in treatment approaches for NHL. While rituximab was first shown to be effective in the treatment of relapsed follicular lymphoma, it is now standard monotherapy for front-line treatment of follicular lymphoma, and is also used in conjunction with chemotherapy for other indolent, intermediate and aggressive B-cell lymphomas. The development of rituximab has led to intense interest in this type of therapeutic approach and to development and approval of the radioimmunoconjugates of rituximab, (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, which have added to the repertoire of treatments for relapsed follicular lymphoma and increased interest in developing other conjugated antibodies. Since rituximab is a chimeric antibody, there is a need to develop fully humanised antibodies, such as IMMU-106 (hA20), in order to minimise infusion reactions and eliminate the development of human antibodies against the drug. Further clinical evaluation of antibodies has been based largely on our knowledge of antigen expression on the surface of lymphoma cells and has led to the development of antibodies against CD22 (unconjugated epratuzumab and calicheamicin conjugated CMC-544 [inotuzumab ozogamicin]), CD80 (galiximab), CD52 (alemtuzumab), CD2 (MEDI-507 [siplizumab]), CD30 (SGN-30 and MDX-060 [iratumumab]), and CD40 (SGN-40). Furthermore, the VEGF (vascular endothelial growth factor) inhibitor bevacizumab, which was first approved for the treatment of colon cancer is currently under investigation in NHL, and agonists rather than antibodies to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) [rApo2L/TRAIL, HGS-ETR1{mapatumumab}, HGS-ETR2] are currently being investigated as treatments for both advanced solid tumours and NHL. Knowledge of the ability of cancer cells to become

  17. Antibodies against CD20 or B-Cell Receptor Induce Similar Transcription Patterns in Human Lymphoma Cell Lines

    PubMed Central

    Franke, Andreas; Niederfellner, Gerhard J.; Klein, Christian; Burtscher, Helmut

    2011-01-01

    Background CD20 is a cell surface protein exclusively expressed on B cells. It is a clinically validated target for Non-Hodgkin's lymphomas (NHL) and autoimmune diseases. The B cell receptor (BCR) plays an important role for development and proliferation of pre-B and B cells. Physical interaction of CD20 with BCR and components of the BCR signaling cascade has been reported but the consequences are not fully understood. Methodology In this study we employed antibodies against CD20 and against the BCR to trigger the respective signaling. These antibodies induced very similar expression patterns of up- and down-regulated genes in NHL cell lines indicating that CD20 may play a role in BCR signaling and vice versa. Two of the genes that were rapidly and transiently induced by both stimuli are CCL3 and CCL4. 4 hours after stimulation the concentration of these chemokines in culture medium reaches a maximum. Spleen tyrosine kinase Syk is a cytoplasmic tyrosine kinase and a key component of BCR signaling. Both siRNA mediated silencing of Syk and inhibition by selective small molecule inhibitors impaired CCL3/CCL4 protein induction after treatment with either anti-CD20 or anti-BCR antibodies. Conclusion Our results suggest that treatment with anti-CD20 antibodies triggers at least partially a BCR activation-like response in NHL cell lines. PMID:21364752

  18. DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Lei; Nishihara, Hiroshi, E-mail: nisihara@patho2.med.hokudai.ac.jp; Kimura, Taichi

    2010-04-23

    DOCK2; a member of the CDM protein family, regulates cell motility and cytokine production through the activation of Rac in mammalian hematopoietic cells and plays a pivotal role in the modulation of the immune system. Here we demonstrated the alternative function of DOCK2 in hematopoietic tumor cells, especially in terms of its association with the tumor progression. Immunostaining for DOCK2 in 20 cases of human B cell lymphoma tissue specimens including diffuse large B cell lymphoma and follicular lymphoma revealed the prominent expression of DOCK2 in all of the lymphoma cells. DOCK2-knockdown (KD) of the B cell lymphoma cell lines,more » Ramos and Raji, using the lentiviral shRNA system presented decreased cell proliferation compared to the control cells. Furthermore, the tumor formation of DOCK2-KD Ramos cell in nude mice was significantly abrogated. Western blotting analysis and pull-down assay using GST-PAK-RBD kimeric protein suggested the presence of DOCK2-Rac-ERK pathway regulating the cell proliferation of these lymphoma cells. This is the first report to clarify the prominent role of DOCK2 in hematopoietic malignancy.« less

  19. Unilateral uveitis masquerade syndrome caused by diffuse large B-cell lymphoma diagnosed using multiparametric flow cytometry of the aqueous humor.

    PubMed

    Monsalvo, Silvia; Serrano, Cristina; Prieto, Elena; Fernández-Sanz, Guillermo; Puente, Maria-Camino; Rodriguez-Pinilla, Maria; Garcia Raso, Aranzazu; Llamas, Pilar; Cordoba, Raul

    2017-07-01

    The uveitis masquerade syndromes (UMS) are a group of ocular diseases that may mimic chronic intraocular inflammation. Many malignant entities such as non-Hodgkin's lymphomas may masquerade as uveitis. We report a case of an HIV-positive patient with masquerade syndrome presenting unilateral uveitis. 45-year-old Caucasian man with a diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was diagnosed by a biopsy of an abdominal mass which showed fragments of gastric mucosa with diffuse growth of neoplastic cells. At diagnosis, the patient suffered from unilateral blurring of vision and a sudden decrease of left-eye visual acuity. A slit-lamp examination of the left eye revealed a diagnosis of anterior uveitis. The patient exhibited no signs of posterior uveitis. An anterior-chamber paracentesis was performed and analyzed by multiparameter flow cytometry (MFC), showing cells CD45, CD19, CD20, CD22, and CD38 positives, and moderate expression of CD10 with kappa light chain restriction, showing a monoclonal B-cell population. The patient received CHOP-R with intrathecal methotrexate followed by consolidation high dose methotrexate obtaining a complete response which is ongoing. Differential diagnosis between chronic uveitis and ocular lymphoma may be challenging. We advocate anterior-chamber paracentesis in cases of refractory uveitis in patients with hematologic malignancies. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

  20. Primary Ovarian Large B-Cell Lymphoma

    PubMed Central

    Islimye Taskın, Mine; Gokgozoglu, Levent; Kandemır, Bedrı

    2013-01-01

    The involvement of the ovary by malignant lymphoma is a well-known late manifestation of disseminated nodal disease. Primary ovarian lymphoma is rare. We herein describe a case of primary ovarian diffuse large B-cell lymphoma involving unilateral ovary in a 38-year-old woman which was detected incidentally. Preoperative ultrasonic imaging showed a 46∗42 mm heterogeneous cystic mass. Laparotomy revealed that left adnexal mass and left salpingo-oophorectomy was performed. The current diagnosis was determined after immunostaining. The patient was treated with R-CHOP regimen after the operation. She remains cancer-free 24 months after chemotherapy. PMID:24222873

  1. Multiple primary tumors: Colorectal carcinoma and non-Hodgkin's lymphoma.

    PubMed

    Pantoja Pachajoa, Diana A; Bruno, Marco Antonio; Alvarez, Fernando A; Viscido, Germán; Mandojana, Facundo; Doniquian, Alejandro

    2018-05-30

    Colorectal cancer (CRC) is the third most commonly diagnosed cancer, whereas lymphoma is the sixth leading cause of cancer death, 90% of which corresponds to non-Hodgkin's lymphoma (NHL). The association of these two primary tumors, a solid tumor with an hematological malignancy, is very uncommon. We report the case of a 47-year-old man who presented with abdominal pain, a right upper quadrant mass and 12 kg of weight loss in 9 months. The computed tomography (CT) showed a large intra-abdominal mass and a wall thickening at the rectosigmoid junction. A colonoscopic biopsy confirmed a colorectal adenocarcinoma and a laparoscopic biopsy of the intraabdominal mass confirmed a diffuse large B-cell NHL. After multidisciplinary discussion it was decided to treat first the NHL with 3 cycles of R-CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone). The patient experienced a good response with a 70% decrease in the intraabdominal mass and a negative PET/CT. Four months after diagnosis an anterior rectal resection was performed. The patient recovered uneventfully and was discharged 5 days after surgery. The patient finally died 20 months after surgery due to disease progression. The association of CRC and NHL is an extremely rare scenario that represents a great multidisciplinary challenge with respect to treatment due to the scarce literature found on this topic. When CRC and NHL are present, all the different disease patterns must be considered in a multidisciplinary and patient-oriented fashion, in order to decide the best therapeutic strategy for each individual. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. A case of oculo-cerebral B-cell lymphoma in a cat.

    PubMed

    Giordano, Cristina; Giudice, Chiara; Bellino, Claudio; Borrelli, Antonio; D'Angelo, Antonio; Gianella, Paola

    2013-01-01

    To describe a case of a cat with primary B-cell lymphoma affecting the eye and brain and which shared features similar to oculo-cerebral lymphoma in humans. A 13-year-old castrated male Persian cat presented with clinical signs of anterior uveitis and increased intraocular pressure (IOP) in the left eye (OS). A complete diagnostic work-up was declined, and left-eye enucleation was performed. The globe was submitted for histopathology. One week after surgery, the cat became inappetent, hypothermic, and aggressive. Euthanasia was requested by the owner, and a necropsy was permitted.   Histopathology of the enucleated globe revealed an extensive neoplastic infiltration consistent with large-cell lymphoma, affecting the anterior uvea, neuroretina and optic nerve. At necropsy, all organs were unremarkable except for the brain, where there was a neoplastic cell population consistent with that described in the left eye, infiltrated and expanded meninges, and perivascular spaces. Immunohistochemically, the neoplastic cells were positive for B-cell marker (CD20) and negative for T-cell marker (CD3). Histology and immunophenotyping suggested a diagnosis of primary central nervous system and ocular large B-cell lymphoma. The lymphoma in this cat resembled oculo-cerebral lymphoma in humans, sharing similar clinical features and histopathological findings, including the perivascular pattern of neoplastic cell infiltration. To the best of the authors' knowledge, this is the first description of a primary oculo-cerebral B-cell lymphoma in a cat. © 2012 American College of Veterinary Ophthalmologists.

  4. Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant

    ClinicalTrials.gov

    2018-02-13

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Hodgkin Lymphoma; Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; Waldenstrom Macroglobulinemia

  5. Benzene exposure and risk of non-Hodgkin lymphoma.

    PubMed

    Smith, Martyn T; Jones, Rachael M; Smith, Allan H

    2007-03-01

    Exposure to benzene, an important industrial chemical and component of gasoline, is a widely recognized cause of leukemia, but its association with non-Hodgkin lymphoma (NHL) is less clear. To clarify this issue, we undertook a systematic review of all case-control and cohort studies that identified probable occupational exposures to benzene and NHL morbidity or mortality. We identified 43 case-control studies of NHL outcomes that recognized persons with probable occupational exposure to benzene. Forty of these 43 (93%) studies show some elevation of NHL risk, with 23 of 43 (53%) studies finding statistically significant associations between NHL risk and probable benzene exposure. We also identified 26 studies of petroleum refinery workers reporting morbidity or mortality for lymphomas and all neoplasms and found that in 23 (88%), the rate of lymphoma morbidity or mortality was higher than that for all neoplasms. A substantial healthy-worker effect was evident in many of the studies and a comprehensive reevaluation of these studies with appropriate adjustments should be undertaken. Numerous studies have also reported associations between benzene exposure and the induction of lymphomas in mice. Further, because benzene is similar to alkylating drugs and radiation in producing leukemia, it is plausible that it might also produce lymphoma as they do and by similar mechanisms. Potential mechanisms include immunotoxicity and the induction of double-strand breaks with subsequent chromosome damage resulting in translocations and deletions. We conclude that, overall, the evidence supports an association between occupational benzene exposure and NHL.

  6. Impact of CD40 expression by flowcytometry on outcome of patients with non-Hodgkin's lymphoma.

    PubMed

    Soliman, Mohamed A; Fathy, Amr Ahmed; Alkilani, Amira; Abd El-Bary, Naser; El-Bassal, Fathai

    2009-01-01

    Lymphoid malignancies represent a wide variety of disease entities characterized by malignant proliferation of lymphoid cells which have distinct clinical features, cellular morphology, immunophenotype, cytogenetic changes and histologic features. CD40 is a member of the tumor necrosis factor receptor super-family. It was first identified and characterized in B cell, signaling through the CD40 receptor was found to play an important role in multiple events in T-cell dependent antibody response including B-cell survival and proliferation, memory B-cell formation and immunoglobulin isotype switching. The aim of this study is to detect the expression of CD40 on B lymphocytes in patients suffering from Non-Hodgkin's Lymphoma and correlate the results with the patients' response to treatment protocols. This study was carried out on 114 patients, of them only 100 patients completed 4 cycles of chemotherapy and were valuable. Their age was ranged from 17 to 63 years old. Fifteen age and gender matched individuals were, also, selected as a control group. CD40 expression was measured on peripheral blood samples by flowcytometry at patient's presentation as well as after 4 cycles of chemotherapy. This study showed that there's significant decrease in the mean values of % of CD40 on B-cell in patients with NHL in all stages when compared with normal control group. Also the study showed that there's statistical significant correlation between percent of CD40 on B-lymphocytes and stage of lymphoma, i.e., the more advanced stage, the lower the % of CD40 on B-cell. After receiving a corresponding treatment, the CD40 expression is increased in significant correlation with the response to treatment. (This is a preliminary result after 4 cycles of CHOP treatment). We concluded that CD40 Lymphocyte development occurs in discrete functional steps that are defined by the onset of expression is highly expressed in healthy subjects and its expression on B-lymphocyte is decreased with

  7. 2B4-SAP signaling is required for the priming of naive CD8+ T cells by antigen-expressing B cells and B lymphoma cells

    PubMed Central

    2017-01-01

    ABSTRACT Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein–Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8+ T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling. Sh2d1a−/− CD8+ T cells exhibited greatly diminished proliferation relative to wild type when Ag-presenting-B cells or -B lymphoma cells served as the primary Ag-presenting cell (APC). By contrast, Sh2d1a−/− CD8+ T cells responded equivalently to wild-type CD8+ T cells when B cell-depleted splenocytes, melanoma cells or breast carcinoma cells performed Ag presentation. Through application of signaling lymphocyte activation molecule (SLAM) family receptor blocking antibodies or SLAM family receptor-deficient CD8+ T cells and APCs, we found that CD48 engagement on the B cell surface by 2B4 is crucial for initiating SAP-dependent signaling required for the Ag-driven CD8+ T cell proliferation and differentiation. Altogether, a pivotal role for SAP in promoting the expansion and differentiation of B cell-primed viral-specific naive CD8+ T cells may explain the selective immune deficiency of XLP patients to EBV and B cell lymphomas. PMID:28344876

  8. 2B4-SAP signaling is required for the priming of naive CD8+ T cells by antigen-expressing B cells and B lymphoma cells.

    PubMed

    Huang, Yu-Hsuan; Tsai, Kevin; Tan, Sara Y; Kang, Sohyeong; Ford, Mandy L; Harder, Kenneth W; Priatel, John J

    2017-01-01

    Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8 + T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling. Sh2d1a - / - CD8 + T cells exhibited greatly diminished proliferation relative to wild type when Ag-presenting-B cells or -B lymphoma cells served as the primary Ag-presenting cell (APC). By contrast, Sh2d1a - / - CD8 + T cells responded equivalently to wild-type CD8 + T cells when B cell-depleted splenocytes, melanoma cells or breast carcinoma cells performed Ag presentation. Through application of signaling lymphocyte activation molecule (SLAM) family receptor blocking antibodies or SLAM family receptor-deficient CD8 + T cells and APCs, we found that CD48 engagement on the B cell surface by 2B4 is crucial for initiating SAP-dependent signaling required for the Ag-driven CD8 + T cell proliferation and differentiation. Altogether, a pivotal role for SAP in promoting the expansion and differentiation of B cell-primed viral-specific naive CD8 + T cells may explain the selective immune deficiency of XLP patients to EBV and B cell lymphomas.

  9. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study.

    PubMed

    Palanca-Wessels, Maria Corinna A; Czuczman, Myron; Salles, Gilles; Assouline, Sarit; Sehn, Laurie H; Flinn, Ian; Patel, Manish R; Sangha, Randeep; Hagenbeek, Anton; Advani, Ranjana; Tilly, Herve; Casasnovas, Olivier; Press, Oliver W; Yalamanchili, Sreeni; Kahn, Robert; Dere, Randall C; Lu, Dan; Jones, Surai; Jones, Cheryl; Chu, Yu-Waye; Morschhauser, Franck

    2015-06-01

    Patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) have an unfavourable prognosis with few treatment options. Polatuzumab vedotin is an antibody-drug conjugate containing an anti-CD79B monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the safety and clinical activity of polatuzumab vedotin in relapsed or refractory B-cell NHL and chronic lymphocytic leukaemia (CLL). In this phase 1, multicentre, open-label study, we enrolled patients with documented NHL or CLL expected to express CD79B (confirmation of CD79B expression was not required) and for whom no suitable therapy of curative intent or higher priority existed from 13 centres. The primary endpoints of the study were to assess safety and tolerability, determine the maximum tolerated dose, and identify the recommended phase 2 dose of polatuzumab vedotin as a single agent and in combination with rituximab. A 3 + 3 dose-escalation design was used in which we treated patients with polatuzumab vedotin (0·1-2·4 mg/kg every 21 days) in separate dose-escalation cohorts for NHL and CLL. After determination of the recommended phase 2 dose, we enrolled patients with relapsed or refractory diffuse large B-cell lymphoma and relapsed or refractory indolent NHL into indication-specific cohorts. We also enrolled patients with relapsed or refractory NHL into an additional cohort to assess the feasibility of the combination of polatuzumab vedotin and rituximab 375 mg/m(2). Patients who received any dose of polatuzumab vedotin were available for safety analyses. This study is registered with ClinicalTrials.gov, number NCT01290549. Between March 21, 2011, and Nov 30, 2012, we enrolled 95 patients (34 to the NHL dose-escalation cohort, 18 to the CLL dose-escalation cohort, 34 with NHL to the expansion cohort at the recommended phase 2 dose, and nine with NHL to the rituximab combination cohort; no expansion cohort of CLL was started due to lack of

  10. A phosphodiesterase 4B-dependent interplay between tumor cells and the microenvironment regulates angiogenesis in B-cell lymphoma

    PubMed Central

    Suhasini, Avvaru N.; Lin, An-Ping; Bhatnagar, Harshita; Kim, Sang-Woo; Moritz, August W.; Aguiar, Ricardo C. T.

    2015-01-01

    Angiogenesis associates with poor outcome in diffuse large B-cell lymphoma (DLBCL), but the contribution of the lymphoma cells to this process remains unclear. Addressing this knowledge gap may uncover unsuspecting proangiogenic signaling nodes and highlight alternative antiangiogenic therapies. Here we identify the second messenger cyclic-AMP (cAMP) and the enzyme that terminates its activity, phosphodiesterase 4B (PDE4B), as regulators of B-cell lymphoma angiogenesis. We first show that cAMP, in a PDE4B-dependent manner, suppresses PI3K/AKT signals to down-modulate VEGF secretion and vessel formation in vitro. Next, we create a novel mouse model that combines the lymphomagenic Myc transgene with germline deletion of Pde4b. We show that lymphomas developing in a Pde4b-null background display significantly lower microvessel density in association with lower VEGF levels and PI3K/AKT activity. We recapitulate these observations by treating lymphoma-bearing mice with the FDA-approved PDE4 inhibitor Roflumilast. Lastly, we show that primary human DLBCLs with high PDE4B expression display significantly higher microvessel density. Here, we defined an unsuspected signaling circuitry in which the cAMP generated in lymphoma cells downmodulates PI3K/AKT and VEGF secretion to negatively influence vessel development in the microenvironment. These data identify PDE4 as an actionable antiangiogenic target in DLBCL. PMID:26503641

  11. Management of aggressive B cell NHLs in the AYA population: an adult versus pediatric perspective.

    PubMed

    Dunleavy, Kieron; Gross, Thomas G

    2018-06-12

    The adolescents and young adult (AYA) population represent a group where mature B-cell lymphomas constitute a significant proportion of the overall malignancies that occur. Among these are aggressive B-cell non-Hodgkin lymphomas (NHLs) which are predominantly diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and Burkitt lymphoma (BL). For the most part, there is remarkable divide in how pediatric/adolescent patients (under the age of 18 years) with lymphoma are treated versus their young adult counterparts and molecular data are lacking, especially in pediatric and AYA series. The outcome for AYA patients with cancers has historically been inferior to that of children or older adults, highlighting the necessity to focus on this population. This review discusses the pediatric versus adult perspective in terms of how these diseases are understood and approached and emphasizes the importance of collaborative efforts in both developing consensus for treatment of this population and planning future research endeavors. Copyright © 2018 American Society of Hematology.

  12. Role of Rituximab and Rituximab Biosimilars in Diffuse Large B-Cell Lymphoma.

    PubMed

    Coleman, Morton; Lammers, Philip E; Ciceri, Fabio; Jacobs, Ira A

    2016-04-01

    Diffuse large B-cell lymphoma (DLBCL), an aggressive non-Hodgkin lymphoma (NHL), is the most-common subtype of NHL. DLBCL can be classified into at least 3 major immunologically distinct types, which contributes to considerable variation in disease prognosis and response to treatment. DLBCL potentially is curable, even when diagnosed at advanced stages. The current standard of care for most patients with untreated or relapsed/refractory DLBCL is chemoimmunotherapy containing rituximab, an anti-CD20 monoclonal antibody. With advanced understanding of the molecular mechanisms involved in the pathogenesis of DLBCL and specific signaling pathways that are activated in different subtypes, potential new therapeutic targets have been identified, some of which are at the late stages of clinical development. This review summarizes the critical role of rituximab in the current standard of care treatment for DLBCL and discusses why rituximab is likely to remain an important component of treatment options for DLBCL in the foreseeable future. In addition, current and emerging therapeutic agents, including potential benefits of rituximab biosimilars, for patients with DLBCL are discussed. The advent of rituximab biosimilars may facilitate accessibility of rituximab-based chemotherapies to patients with DLBCL and has potential cost-saving benefits for healthcare systems globally. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    ClinicalTrials.gov

    2018-03-02

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

  14. Superior Therapeutic Index in Lymphoma Therapy: CD30+ CD34+ Hematopoietic Stem Cells Resist a Chimeric Antigen Receptor T-cell Attack

    PubMed Central

    Hombach, Andreas A; Görgens, André; Chmielewski, Markus; Murke, Florian; Kimpel, Janine; Giebel, Bernd; Abken, Hinrich

    2016-01-01

    Recent clinical trials with chimeric antigen receptor (CAR) redirected T cells targeting CD19 revealed particular efficacy in the treatment of leukemia/lymphoma, however, were accompanied by a lasting depletion of healthy B cells. We here explored CD30 as an alternative target, which is validated in lymphoma therapy and expressed by a broad variety of Hodgkin's and non-Hodgkin's lymphomas. As a safty concern, however, CD30 is also expressed by lymphocytes and hematopoietic stem and progenitor cells (HSPCs) during activation. We revealed that HRS3scFv-derived CAR T cells are superior since they were not blocked by soluble CD30 and did not attack CD30+ HSPCs while eliminating CD30+ lymphoma cells. Consequently, normal hemato- and lymphopoiesis was not affected in the long-term in the humanized mouse; the number of blood B and T cells remained unchanged. We provide evidence that the CD30+ HSPCs are protected against a CAR T-cell attack by substantially lower CD30 levels than lymphoma cells and higher levels of the granzyme B inactivating SP6/PI9 serine protease, which furthermore increased upon activation. Taken together, adoptive cell therapy with anti-CD30 CAR T cells displays a superior therapeutic index in the treatment of CD30+ malignancies leaving healthy activated lymphocytes and HSPCs unaffected. PMID:27112062

  15. Minimal Disease Assessment in the Treatment of Children and Adolescents with Intermediate-Risk (Stage III/IV) B-Cell Non-Hodgkin Lymphoma: A Children’s Oncology Group Report

    PubMed Central

    Shiramizu, Bruce; Goldman, Stanton; Kusao, Ian; Agsalda, Melissa; Lynch, James; Smith, Lynette; Harrison, Lauren; Morris, Erin; Gross, Thomas G.; Sanger, Warren; Perkins, Sherrie; Cairo, Mitchell S.

    2011-01-01

    Summary Children/adolescents with mature B-cell non-Hodgkin lymphoma (B-NHL) have an excellent prognosis but relapses still occur. While chromosomal aberrations and/or clonal immunoglobulin (Ig) gene rearrangements may indicate risk of failure, a more universal approach was developed to detect minimal disease (MD). Children/adolescents with intermediate-risk B-NHL were treated with French-British-American/Lymphome Malins de Burkitt 96 (FAB/LMB96) B4 modified chemotherapy and rituximab. Specimens from diagnosis, end of induction (EOI), and end of therapy (EOT) were assayed for MD. Initial specimens were screened for IGHV family usage with primer pools followed by individual primers to identify MD. Thirty-two diagnostic/staging specimens screened positive with primer pools and unique IGHV family primers were identified. Two patients relapsed; first relapse (4 months from diagnosis) was MD-positive at EOI, the second (36 months from diagnosis) was MD-positive at EOT. At EOI, recurrent rates were similar between the MRD-positive and MRD-negative patients (p=0.40). At EOT, only 13/32 patients had MRD data available with 1 relapse in the MRD-positive group and no recurrences in the MRD-negative group (p=0.077). The study demonstrated molecular-disseminated disease in which IgIGHV primer pools could be used to assess MD. This feasibility study supports future investigations to assess the validity and significance of MD screening in a larger cohort of patients with intermediate-risk mature B-NHL. PMID:21496005

  16. Synchronous Adenocarcinoma and Mantle Cell Lymphoma of the Stomach

    PubMed Central

    Koo, Min Young

    2007-01-01

    Synchronous occurrence of mantle cell lymphoma (MCL) and gastric cancer in the same patient has not yet been reported in the English literature. MCL comprises 2.5 - 7% of non-Hodgkin's lymphomas and is characterized by a poor prognosis with a median survival probability of 3 - 4 years in most series. A 62-year-old man was referred to our hospital for evaluation of an abnormal gastric lesion. The endoscopic finding was compatible with type IIc early gastric cancer (EGC) in the middle third of the stomach, and a biopsy of the lesion proved to be carcinoma. Radical total gastrectomy with splenectomy and Roux-en-Y esophagojejunostomy were performed. The resected specimen revealed two grossly separated lesions. Postoperative histological examination reported both adenocarcinoma and MCL. Immunohistochemical staining showed positivity for CD5, CD20, and cyclin D1 in the infiltrated lymphoid cells. MCL is an aggressive non-Hodgkin's lymphoma, and the current treatment approach is still unsatisfactory. Further advancements in the understanding of the synchronous occurrence of both diseases, and more efforts on investigations of treatment are needed. PMID:18159604

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

    ClinicalTrials.gov

    2017-09-12

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

  18. Anti-cancer activity of withaferin A in B-cell lymphoma

    PubMed Central

    McKenna, MK; Gachuki, BW; Alhakeem, SS; Oben, KN; Rangnekar, VM; Gupta, RC; Bondada, S

    2015-01-01

    Withaferin A (WA), a withanolide from the plant, Ashwagandha (Withania somnifera) used in Ayurvedic medicine, has been found to be valuable in the treatment of several medical ailments. WA has been found to have anticancer activity against various solid tumors, but its effects on hematological malignancies have not been studied in detail. WA strongly inhibited the survival of several human and murine B cell lymphoma cell lines. Additionally, in vivo studies with syngeneic-graft lymphoma cells suggest that WA inhibits the growth of tumor but does not affect other proliferative tissues. We demonstrate that WA inhibits the efficiency of NF-κB nuclear translocation in diffuse large B cell lymphomas and found that WA treatment resulted in a significant decrease in protein levels involved in B cell receptor signaling and cell cycle regulation. WA inhibited the activity of heat shock protein (Hsp) 90 as reflected by a sharp increase in Hsp70 expression levels. Hence, we propose that the anti-cancer effects of WA in lymphomas are likely due to its ability to inhibit Hsp90 function and subsequent reduction of critical kinases and cell cycle regulators that are clients of Hsp90. PMID:26020511

  19. Anti-cancer activity of withaferin A in B-cell lymphoma.

    PubMed

    McKenna, M K; Gachuki, B W; Alhakeem, S S; Oben, K N; Rangnekar, V M; Gupta, R C; Bondada, S

    2015-01-01

    Withaferin A (WA), a withanolide from the plant, Ashwagandha (Withania somnifera) used in Ayurvedic medicine, has been found to be valuable in the treatment of several medical ailments. WA has been found to have anticancer activity against various solid tumors, but its effects on hematological malignancies have not been studied in detail. WA strongly inhibited the survival of several human and murine B cell lymphoma cell lines. Additionally, in vivo studies with syngeneic-graft lymphoma cells suggest that WA inhibits the growth of tumor but does not affect other proliferative tissues. We demonstrate that WA inhibits the efficiency of NF-κB nuclear translocation in diffuse large B cell lymphomas and found that WA treatment resulted in a significant decrease in protein levels involved in B cell receptor signaling and cell cycle regulation. WA inhibited the activity of heat shock protein (Hsp) 90 as reflected by a sharp increase in Hsp70 expression levels. Hence, we propose that the anti-cancer effects of WA in lymphomas are likely due to its ability to inhibit Hsp90 function and subsequent reduction of critical kinases and cell cycle regulators that are clients of Hsp90.

  20. Langerhans cell sarcoma following marginal zone lymphoma: expanding the knowledge on mature B cell plasticity.

    PubMed

    Ambrosio, Maria Raffaella; De Falco, Giulia; Rocca, Bruno Jim; Barone, Aurora; Amato, Teresa; Bellan, Cristiana; Lazzi, Stefano; Leoncini, Lorenzo

    2015-10-01

    The concept of unidirectional differentiation of the haematopoietic stem cell has been challenged after recent findings that human B cell progenitors and even mature B cells can be reprogrammed into histiocytic/dendritic cells by altering expression of lineage-associated transcription factors. The conversion of mature B cell lymphomas to Langerhans cell neoplasms is not well documented. Three previous reports have described clonally related follicular lymphoma and Langerhans cell tumours, whereas no case has been published of clonally related marginal zone lymphoma and Langerhans cell sarcoma. We describe the case of a 77-year-old patient who developed a Langerhans cell sarcoma and 6 years later a nodal marginal zone lymphoma. Mutation status examination showed 100 % gene identity to the germline sequence, suggesting direct trans-differentiation or dedifferentiation of the nodal marginal zone lymphoma to the Langerhans cell sarcoma rather than a common progenitor. We found inactivation of paired box 5 (PAX-5) in the lymphoma cells by methylation, along with duplication of part of the long arm of chromosomes 16 and 17 in the sarcoma cells. The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells. On the other hand, chromosomal imbalances might have activated genes involved in myeloid lineage maturation, transcription activation and oncogenesis. We hypothesize that this occurred because of previous therapies for nodal marginal zone lymphoma. Better understanding of this phenomenon may help in unravelling the molecular interplay between transcription factors during haematopoietic lineage commitment and may expand the spectrum of clonally related mature B cell neoplasms and Langerhans cell tumours.

  1. Immunohistochemical analysis of the novel marginal zone B-cell marker IRTA1 in malignant lymphoma.

    PubMed

    Ikeda, Jun-Ichiro; Kohara, Masaharu; Tsuruta, Yoko; Nojima, Satoshi; Tahara, Shinichiro; Ohshima, Kenji; Kurashige, Masako; Wada, Naoki; Morii, Eiichi

    2017-01-01

    Marginal zone lymphoma (MZL) is a low-grade B-cell lymphoma derived from marginal zone B cells. Because of a lack of specific immunohistochemical markers, MZL is mainly diagnosed based on the cytological appearance and growth pattern of the tumor. Marginal zone B cells were recently shown to selectively express immunoglobulin superfamily receptor translocation-associated 1 (IRTA1), but the antibody used in that study is not commercially available. We therefore investigated the IRTA1 expression in nonneoplastic lymphoid tissues and 261 malignant lymphomas, examining the ability of a commercially available antibody to accurately diagnose MZL. Among 37 MZLs, 23 of 25 extranodal MZLs of mucosa-associated lymphoid tissue (MALT lymphomas), 3 of 6 splenic MZLs and 3 of 6 nodal MZLs were positive for IRTA1. Among the 98 diffuse large B-cell lymphomas, 33 were positive for IRTA1, including 1 of 38 follicular lymphomas, and all precursor B-lymphoblastic (2/2) and T-lymphoblastic (7/7) leukemia/lymphomas. Other mature B-cell and T-cell lymphomas, and Hodgkin lymphoma were negative for IRTA1. In MALT lymphoma, positive cells were detected mainly in intraepithelial and subepithelial marginal zone B cells. In 1 case of grade 3 follicular lymphoma, IRTA1 was also expressed in the area of large cell transformation. When tumors were classified as germinal center B cell-like (GCB) or non-GCB using the algorithm of Hans, positive expression of IRTA1 was correlated significantly with non-GCB diffuse large B-cell lymphomas (P < .05). These results demonstrated the ability of the commercially available IRTA1 antibody to distinguish MALT lymphoma from other low-grade B-cell lymphomas. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma

    PubMed Central

    Skibola, Christine F.; Darabi, Hatef; Conde, Lucia; Hjalgrim, Henrik; Kumar, Vikrant; Chang, Ellen T.; Rothman, Nathaniel; Cerhan, James R.; Brooks-Wilson, Angela R.; Rehnberg, Emil; Irwan, Ishak D.; Ryder, Lars P.; Brown, Peter N.; Bracci, Paige M.; Agana, Luz; Riby, Jacques; Cozen, Wendy; Davis, Scott; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Wang, Sophia S.; Slager, Susan L.; Fredericksen, Zachary S.; Novak, Anne J.; Kay, Neil E.; Habermann, Thomas M.; Armstrong, Bruce; Kricker, Anne; Milliken, Sam; Purdue, Mark P.; Vajdic, Claire M.; Boyle, Peter; Lan, Qing; Zahm, Shelia H.; Zhang, Yawei; Zheng, Tongzhang; Leach, Stephen; Spinelli, John J.; Smith, Martyn T.; Chanock, Stephen J.; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Glimelius, Bengt; Melbye, Mads; Liu, Edison T.; Adami, Hans-Olov; Humphreys, Keith; Liu, Jianjun

    2011-01-01

    Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL–associated locus on 6p21.32, rs2647012 (ORcombined = 0.64, Pcombined = 2×10−21) located 962 bp away from rs10484561 (r2<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:ORadjusted = 0.70, Padjusted = 4×10−12; rs10484561:ORadjusted = 1.64, Padjusted = 5×10−15). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL–associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (ORcombined = 1.36, Pcombined = 1.4×10−7). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL. PMID:21533074

  3. Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

    ClinicalTrials.gov

    2016-11-17

    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 Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  4. Adenovirus infection and cytotoxicity of primary mantle cell lymphoma cells.

    PubMed

    Medina, Daniel J; Sheay, Wendy; Osman, Mona; Goodell, Lauri; Martin, John; Rabson, Arnold B; Strair, Roger K

    2005-11-01

    Mantle cell lymphoma (MCL) is a distinct form of non-Hodgkin's lymphoma (NHL) derived from CD5+ B cells. MCL cells overexpress cyclin D1 as a consequence of translocation of the gene into the immunoglobulin heavy-chain gene locus. MCL is an aggressive form of NHL with frequent relapses after standard-dose chemotherapy. In this context, a variety of novel therapies for patients with MCL have been investigated. In this study, we use an expanded panel of attenuated adenoviruses to study adenovirus-mediated cytotoxicity of MCL cells. Our results demonstrate: 1) adenovirus infection of MCL cells despite the absence of receptor/coreceptor molecules known to be important for adenovirus infection of other cells types; 2) cytotoxicity of MCL cells after infection with specific adenovirus mutants; 3) a high degree of cytotoxicity after infection of some patient samples with viruses lacking the E1B 19k "antiapoptotic" gene; and 4) cytotoxicity after infection with viruses containing mutations in E1A pRb or p300 binding. The extent of cytotoxicity with the panel of viruses demonstrated interpatient variability, but 100% cytotoxicity, as determined by molecular analysis, was detected in some samples. These studies provide the foundation for: 1) the development of adenoviruses as cytotoxic agents for MCL and 2) analyses of key regulatory pathways operative in MCL cells.

  5. Lymphoma immunotherapy: vaccines, adoptive cell transfer and immunotransplant

    PubMed Central

    Brody, Joshua; Levy, Ronald

    2017-01-01

    Therapy for non-Hodgkin lymphoma has benefited greatly from basic science and clinical research such that chemotherapy and monoclonal antibody therapy have changed some lymphoma subtypes from uniformly lethal to curable, but the majority of lymphoma patients remain incurable. Novel therapies with less toxicity and more specific targeting of tumor cells are needed and immunotherapy is among the most promising of these. Recently completed randomized trials of idiotype vaccines and earlier-phase trials of other vaccine types have shown the ability to induce antitumor T cells and some clinical responses. More recently, trials of adoptive transfer of antitumor T cells have demonstrated techniques to increase the persistence and antitumor effect of these cells. Herein, we discuss lymphoma immunotherapy clinical trial results and what lessons can be taken to improve their effect, including the combination of vaccination and adoptive transfer in an approach we have dubbed ‘immunotransplant’. PMID:20636025

  6. Genetic heterogeneity of diffuse large B-cell lymphoma.

    PubMed

    Zhang, Jenny; Grubor, Vladimir; Love, Cassandra L; Banerjee, Anjishnu; Richards, Kristy L; Mieczkowski, Piotr A; Dunphy, Cherie; Choi, William; Au, Wing Yan; Srivastava, Gopesh; Lugar, Patricia L; Rizzieri, David A; Lagoo, Anand S; Bernal-Mizrachi, Leon; Mann, Karen P; Flowers, Christopher; Naresh, Kikkeri; Evens, Andrew; Gordon, Leo I; Czader, Magdalena; Gill, Javed I; Hsi, Eric D; Liu, Qingquan; Fan, Alice; Walsh, Katherine; Jima, Dereje; Smith, Lisa L; Johnson, Amy J; Byrd, John C; Luftig, Micah A; Ni, Ting; Zhu, Jun; Chadburn, Amy; Levy, Shawn; Dunson, David; Dave, Sandeep S

    2013-01-22

    Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma in adults. The disease exhibits a striking heterogeneity in gene expression profiles and clinical outcomes, but its genetic causes remain to be fully defined. Through whole genome and exome sequencing, we characterized the genetic diversity of DLBCL. In all, we sequenced 73 DLBCL primary tumors (34 with matched normal DNA). Separately, we sequenced the exomes of 21 DLBCL cell lines. We identified 322 DLBCL cancer genes that were recurrently mutated in primary DLBCLs. We identified recurrent mutations implicating a number of known and not previously identified genes and pathways in DLBCL including those related to chromatin modification (ARID1A and MEF2B), NF-κB (CARD11 and TNFAIP3), PI3 kinase (PIK3CD, PIK3R1, and MTOR), B-cell lineage (IRF8, POU2F2, and GNA13), and WNT signaling (WIF1). We also experimentally validated a mutation in PIK3CD, a gene not previously implicated in lymphomas. The patterns of mutation demonstrated a classic long tail distribution with substantial variation of mutated genes from patient to patient and also between published studies. Thus, our study reveals the tremendous genetic heterogeneity that underlies lymphomas and highlights the need for personalized medicine approaches to treating these patients.

  7. Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells.

    PubMed

    Lin, Zhiguang; Chen, Bobin; Wu, Ting; Xu, Xiaoping

    2018-05-23

    Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot. Lymphoma cells in the coculture system differentiated into a suspended cell group and an adherent cell group. They acquired a stronger proliferative capacity and drug resistance than lymphoma cells cultured alone, and differences existed between the adherent cell and suspended cell groups. The suspended cell group acquired the most powerful clonogenic and tumorigenic potential. However, Notch3 was exclusively expressed in the adherent lymphoma cell group and the use of N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, an inhibitor of Notch pathway, could abolish the emergence of highly aggressive lymphoma cells. Highly tumorigenic lymphoma cells could be generated by coculture with stromal cells, and it was dependent on Notch3 expression in the adjacent lymphoma cells through interaction with stromal cells. © 2018 S. Karger AG, Basel.

  8. Over-expression of Thioredoxin-1 mediates growth, survival, and chemoresistance and is a druggable target in diffuse large B-cell lymphoma

    PubMed Central

    Li, Changping; Thompson, Michael A.; Tamayo, Archito T.; Zuo, Zhuang; Lee, John; Vega, Francisco; Ford, Richard J.; Pham, Lan V.

    2012-01-01

    Diffuse Large B cell lymphomas (DLBCL) are the most prevalent of the non-Hodgkin lymphomas and are currently initially treated fairly successfully, but frequently relapse as refractory disease, resulting in poor salvage therapy options and short survival. The greatest challenge in improving survival of DLBCL patients is overcoming chemo-resistance, whose basis is poorly understood. Among the potential mediators of DLBCL chemo-resistance is the thioredxoin (Trx) family, primarily because Trx family members play critical roles in the regulation of cellular redox homeostasis, and recent studies have indicated that dysregulated redox homeostasis also plays a key role in chemoresistance. In this study, we showed that most of the DLBCL-derived cell lines and primary DLBCL cells express higher basal levels of Trx-1 than normal B cells and that Trx-1 expression level is associated with decreased patients survival. Our functional studies showed that inhibition of Trx-1 by small interfering RNA or a Trx-1 inhibitor (PX-12) inhibited DLBCL cell growth, clonogenicity, and also sensitized DLBCL cells to doxorubicin-induced cell growth inhibition in vitro. These results indicate that Trx-1 plays a key role in cell growth and survival, as well as chemoresistance, and is a potential target to overcome drug resistance in relapsed/refractory DLBCL. PMID:22447839

  9. Outcome differences between children and adolescents and young adults with non-Hodgkin lymphoma following stem cell transplantation.

    PubMed

    Kobayashi, Ryoji; Mitsui, Tetsuo; Fujita, Naoto; Osumi, Tomoo; Aoki, Tomohiro; Aoki, Kazunari; Suzuki, Ritsuro; Fukuda, Takahiro; Miyamoto, Toshihiro; Kato, Koji; Nakamae, Hirohisa; Goto, Hiroaki; Eto, Tetsuya; Inoue, Masami; Mori, Takehiko; Terui, Kiminori; Onizuka, Masahito; Koh, Katsuyoshi; Koga, Yuhki; Ichinohe, Tatsuo; Sawada, Akihisa; Atsuta, Yoshiko; Suzumiya, Junji

    2017-03-01

    Several studies of patients with acute lymphoblastic leukemia and acute myeloid leukemia who received stem cell transplantation (SCT) have reported that adolescents and young adults (AYAs) experience higher transplant-related mortality than that in younger children. However, to the best of our knowledge, there have been no reports of a similar comparison of non-Hodgkin lymphoma (NHL) patients who received SCT. We analyzed 918 patients aged 30 years and younger who received their first stem cell transplantation for NHL. Of the allogeneic transplant patients, children and AYAs did not significantly differ in survival rate, event-free survival rate, relapse rate, or transplant-related mortality. However, 5-year transplant-related mortality after autologous transplantation was significantly higher in children than in AYAs (5.1% in children vs. 0.8% in AYAs, P = 0.0043). The cause of transplant-related death in three of four children was interstitial pneumonitis. In NHL patients, transplantation results in AYAs were not inferior than those in children.

  10. The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition.

    PubMed

    Varano, Gabriele; Raffel, Simon; Sormani, Martina; Zanardi, Federica; Lonardi, Silvia; Zasada, Christin; Perucho, Laura; Petrocelli, Valentina; Haake, Andrea; Lee, Albert K; Bugatti, Mattia; Paul, Ulrike; Van Anken, Eelco; Pasqualucci, Laura; Rabadan, Raul; Siebert, Reiner; Kempa, Stefan; Ponzoni, Maurilio; Facchetti, Fabio; Rajewsky, Klaus; Casola, Stefano

    2017-06-08

    Similar to resting mature B cells, where the B-cell antigen receptor (BCR) controls cellular survival, surface BCR expression is conserved in most mature B-cell lymphomas. The identification of activating BCR mutations and the growth disadvantage upon BCR knockdown of cells of certain lymphoma entities has led to the view that BCR signalling is required for tumour cell survival. Consequently, the BCR signalling machinery has become an established target in the therapy of B-cell malignancies. Here we study the effects of BCR ablation on MYC-driven mouse B-cell lymphomas and compare them with observations in human Burkitt lymphoma. Whereas BCR ablation does not, per se, significantly affect lymphoma growth, BCR-negative (BCR - ) tumour cells rapidly disappear in the presence of their BCR-expressing (BCR + ) counterparts in vitro and in vivo. This requires neither cellular contact nor factors released by BCR + tumour cells. Instead, BCR loss induces the rewiring of central carbon metabolism, increasing the sensitivity of receptor-less lymphoma cells to nutrient restriction. The BCR attenuates glycogen synthase kinase 3 beta (GSK3β) activity to support MYC-controlled gene expression. BCR - tumour cells exhibit increased GSK3β activity and are rescued from their competitive growth disadvantage by GSK3β inhibition. BCR - lymphoma variants that restore competitive fitness normalize GSK3β activity after constitutive activation of the MAPK pathway, commonly through Ras mutations. Similarly, in Burkitt lymphoma, activating RAS mutations may propagate immunoglobulin-crippled tumour cells, which usually represent a minority of the tumour bulk. Thus, while BCR expression enhances lymphoma cell fitness, BCR-targeted therapies may profit from combinations with drugs targeting BCR - tumour cells.

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

    ClinicalTrials.gov

    2016-04-25

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

  12. NonHodgkin's Lymphoma with Peritoneal Localization

    PubMed Central

    Curakova, E.; Genadieva-Dimitrova, M.; Misevski, J.; Caloska-Ivanova, V.; Andreevski, V.; Todorovska, B.; Isahi, U.; Trajkovska, M.; Misevska, P.; Joksimovic, N.; Genadieva-Stavric, S.; Antovic, S.; Jankulovski, N.

    2014-01-01

    The gastrointestinal tract is the most common extranodal site involved with lymphoma accounting for 5–20% of all cases. Lymphoma can occur at any site of the body, but diffuse and extensive involvement of the peritoneal cavity is unusual and rare. We report a case of diffuse large B-cell lymphoma in a 57-year-old female infiltrating the peritoneum and omentum and presenting with ascites and pleural effusion. The performed examinations did not discover any pathological findings affecting the digestive tract or parenchymal organs, except for diffuse thickening of the peritoneum and omentum. Peripheral, mediastinal, or retroperitoneal lymphadenopathy was not registered. The blood count revealed only elevated leukocytes and on examination there were no immature blood cells in the peripheral blood. The cytology from the ascites and pleural effusion did not detect any malignant cells. Due to the rapid disease progression the patient died after twenty-two days of admission. The diagnosis was discovered postmortem with the histological examination and immunohistochemical study of the material taken during the surgical laparoscopy performed four days before the lethal outcome. Although cytology is diagnostic in most cases, laparoscopy with peritoneal biopsy is the only procedure which can establish the definitive diagnosis of peritoneal lymphomatosis. PMID:24711934

  13. Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer

    ClinicalTrials.gov

    2017-11-08

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma; Previously Treated Myelodysplastic Syndrome; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

  14. Signet-ring cell lymphoma: clinicopathologic, immunohistochemical, and fluorescence in situ hybridization studies of 7 cases.

    PubMed

    Zhang, Shanxiang; Sun, Jihong; Fang, Yanan; Nassiri, Mehdi; Liu, Lanting; Zhou, Jiehao; Stohler, Ryan; Choi, Haki; Vance, Gail H

    2017-02-01

    Signet-ring cell lymphoma (SRCL) is a rare morphologic variant of non-Hodgkin lymphoma. Although it was initially reported as a rare morphologic variant of follicular lymphoma (FL), SRCL has to date been described in most types of non-Hodgkin lymphoma, mostly as single-case reports. To study SRCL systematically by immunohistochemical stains and fluorescent in situ hybridization analyses. Seven SRCL cases were stained for CD3, CD5, CD20, PAX-5, CD10, CD21, CD23, cyclin D1, BCL2, BCL6, Ki-67, and MUM-1, and were analyzed by fluorescent in situ hybridization for BCL2, BCL6, MYC, and MALT1 rearrangements. Clinical information and patient outcome were reviewed in all patients. The patients were 3 women and 3 men, ranging in age from 31 to 75 years (average 60.3 years). The lesions involved lymph nodes, tonsil, parotid gland, soft tissue, and breast. There were 4 FLs, 1 diffuse large B-cell lymphoma (DLBCL), 1 DLBCL with FL, and 1 DLBCL with marginal zone lymphoma. All cases had typical signet-ring cell morphology. They were positive for CD20 and BCL-2, and had low-to-intermediate Ki-67 proliferation index (10%-40%) except in the parotid DLBCL with FL (70%). BCL-6 was detected in all but 1 FL (6/7). Fluorescent in situ hybridization detected IGH/BCL2 translocation in 1 FL, increased BCL6 copy number in another FL, BCL6 rearrangement, and increased copy number of MYC and MALT1 in the DLBCL with marginal zone lymphoma. The FL with signet-ring cell morphology (1/5) tends to lack IGH/BCL2 translocation, and an extended immunohistochemical study is recommended for correct diagnosis and classification of SRCL. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Metastatic B-cell lymphoma masquerading as infectious retinitis and vasculitis.

    PubMed

    Say, Emil Anthony T; Knupp, Charles L; Gertsch, Kevin R; Chavala, Sai H

    2012-06-01

    Intraocular lymphoma is a rare ocular malignancy that may occur in the retina or the uvea. Retina or vitreoretinal lymphoma accounts for the majority of cases and is often secondary to diffuse large B-cell lymphoma. In the present study, a 66-year-old Caucasian male with a history of Waldenstrom's macroglobulinemia with diffuse large B-cell lymphoma, presented with blurred vision in the left eye one month following cycle 4 of an R-CHOP regimen. At the time of onset, the patient was being treated for bacterial pneumonia. Visual acuity was 20/25 in his right eye (OD) and 20/30 in the left (OS). Ophthalmologic examination showed intraretinal white infiltrates associated with hemorrhage in the superotemporal midperiphery of the retina and vitritis OS. Initial diagnostic considerations included infectious (cytomegalovirus retinitis, syphilis, toxoplasmosis, tuberculosis), inflammatory (retinal vasculitis associated with autoimmune disease or hypercoagulable states) or malignant (intraocular lymphoma) diseases. The patient did not respond to intravitreal injection of foscarnet and oral valgancyclovir. Systemic work-up and aqueous fluid biopsy were inconclusive. Diagnostic vitrectomy yielded inconclusive results and the patient continued to have progressive loss of vision. A repeat diagnostic vitrectomy with retinal and subretinal biopsy confirmed large B cells consistent with metastatic B-cell lymphoma. A concomitant PET/CT scan was performed that revealed bilateral new pulmonary nodules resulting in additional chemotherapy. Our case shows the diagnostic dilemmas in patients with systemic lymphoma and the possible role of concurrent systemic restaging in patients with ocular complaints, even when in systemic remission.

  16. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy

    PubMed Central

    Honigberg, Lee A.; Smith, Ashley M.; Sirisawad, Mint; Verner, Erik; Loury, David; Chang, Betty; Li, Shyr; Pan, Zhengying; Thamm, Douglas H.; Miller, Richard A.; Buggy, Joseph J.

    2010-01-01

    Activation of the B-cell antigen receptor (BCR) signaling pathway contributes to the initiation and maintenance of B-cell malignancies and autoimmune diseases. The Bruton tyrosine kinase (Btk) is specifically required for BCR signaling as demonstrated by human and mouse mutations that disrupt Btk function and prevent B-cell maturation at steps that require a functional BCR pathway. Herein we describe a selective and irreversible Btk inhibitor, PCI-32765, that is currently under clinical development in patients with B-cell non-Hodgkin lymphoma. We have used this inhibitor to investigate the biologic effects of Btk inhibition on mature B-cell function and the progression of B cell-associated diseases in vivo. PCI-32765 blocked BCR signaling in human peripheral B cells at concentrations that did not affect T cell receptor signaling. In mice with collagen-induced arthritis, orally administered PCI-32765 reduced the level of circulating autoantibodies and completely suppressed disease. PCI-32765 also inhibited autoantibody production and the development of kidney disease in the MRL-Fas(lpr) lupus model. Occupancy of the Btk active site by PCI-32765 was monitored in vitro and in vivo using a fluorescent affinity probe for Btk. Active site occupancy of Btk was tightly correlated with the blockade of BCR signaling and in vivo efficacy. Finally, PCI-32765 induced objective clinical responses in dogs with spontaneous B-cell non-Hodgkin lymphoma. These findings support Btk inhibition as a therapeutic approach for the treatment of human diseases associated with activation of the BCR pathway. PMID:20615965

  17. Primary Gastric Lymphoma Presenting as Acute Pancreatitis: A Case Report.

    PubMed

    Raj, Mithun; Ghoshal, Uday C; Choudhuri, Gourdas; Mohindra, Samir

    2013-07-10

    Diffuse large B-cell lymphoma is the commonest form of non-Hodgkin lymphoma. Gastro-intestinal tract and bone marrow are common extra-nodal sites of lymphomatous involvement. A 54-year-old woman presented with acute onset epigastric pain. On evaluation, raised serum amylase and radiological features of acute pancreatitis were detected. Gastroscopy revealed thickened folds in distal stomach, which on histopathology revealed large B-cell lymphoma. Subsequently, the patient developed extra-hepatic biliary obstruction due to peripancreatic lymph nodal mass that was relieved with plastic biliary stenting. Subsequent chemotherapy regime directed against lymphoma led to resolution of lymphoma. In this patient , pancreatitis was the initial presentation of primary gastric lymphoma, which has not been commonly reported and therefore should be considered in the etiological workup.

  18. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Ping; Fu, Shilong; Cao, Zhifei

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressivemore » ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice

  19. 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).

  20. Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

    ClinicalTrials.gov

    2018-06-25

    Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

  1. Characterization of anti-erythrocyte autoantibodies in non-Hodgkin's lymphoma patients in Brazil.

    PubMed

    Barjas de Castro, M L; Locatelli, M F; de Castilho, L M; de Souza, C A

    1998-01-01

    The existence of an association between autoimmune phenomena and lymphoproliferative neoplasms is well known. In Campinas at the University Hospital, seventy-seven adult patients with non-Hodgkin's lymphoma (NHL) were studied at diagnosis. The histological subgroup of NHL was performed using Kiel criteria and all patients were characterized by clinical and laboratory examinations according to the Ann Arbor staging. The results of the immunohaematological evaluation of our patients with NHL showed that: 28% presented erythrocyte autoantibodies (auto anti-I or auto-IgG without specificity) but only one developed haemolytic anaemia. There was a weak correlation between low-grade lymphoma and erythrocyte autoantibodies.

  2. Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.

    PubMed

    Aukema, Sietse M; Kreuz, Markus; Kohler, Christian W; Rosolowski, Maciej; Hasenclever, Dirk; Hummel, Michael; Küppers, Ralf; Lenze, Dido; Ott, German; Pott, Christiane; Richter, Julia; Rosenwald, Andreas; Szczepanowski, Monika; Schwaenen, Carsten; Stein, Harald; Trautmann, Heiko; Wessendorf, Swen; Trümper, Lorenz; Loeffler, Markus; Spang, Rainer; Kluin, Philip M; Klapper, Wolfram; Siebert, Reiner

    2014-04-01

    Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics.

  3. Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab.

    PubMed

    de Souza, Kleber Jordão; Ferro, Rodrigo Sala; Prestes-Carneiro, Luiz Euribel; Carrilho, Paula Andreia Martins; Vasconcelos, Dewton de Moraes

    2018-02-01

    The use of rituximab (RTX) is increasing, even in developing countries. It has become the first-line therapy or adjuvant to chemotherapy (CHOP; cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) for various diseases, including B cell lymphoma and autoimmune diseases. We describe the infectious diseases and immunological markers associated with RTX treatment of patients with non-Hodgkin lymphoma (NHL). Serum immunoglobulins were determined before and after intravenous immunoglobulin (IVIg) administration. Pneumo-23IgG-specific anti-pneumococcal antibodies were evaluated before and after vaccination. Immunophenotyping and lymphocyte proliferation were determined in the course of the treatment. Seven patients were followed and median age was 56.0 ± 5.0 years (range, 41.9-71.6 years). At baseline, the mean level of IgG was 333.7 ± 40.8 and IgM 40.9 ± 11.3 mg/dL, respectively; immunoglobulin A and E (IgA and IgE) were under the limit of detection. Two patients had reduced or absent B cells and T cell subsets were at normal levels in five patients. All patients failed to mount an efficient post-vaccination immune response against hepatitis B virus, tetanus, diphtheria and against the 23-valent pneumococcal polysaccharide vaccine. During RTX/CHOP treatment, human-IgG-immunoglobulin (IVIg) therapy was introduced in six patients after recurrent infections, including community-acquired pneumonia (85.7%), chronic sinusitis (85.7%) and gastroenteritis (42.9%). Poor response against pneumococcal vaccines increases the susceptibility of respiratory diseases in these patients. In patients with NHL treated with RTX, the benefits achieved with IVIg replacement for the control of recurrent infectious diseases is of paramount importance. Clinicians dealing with monoclonal antibodies against cancer therapy, especially RTX, should be aware of the increasing risks for symptomatic induced hypogammaglobulinemia and respiratory infections.

  4. TET2 mutations in B cells of patients affected by angioimmunoblastic T-cell lymphoma.

    PubMed

    Schwartz, Friederike H; Cai, Qian; Fellmann, Eva; Hartmann, Sylvia; Mäyränpää, Mikko I; Karjalainen-Lindsberg, Marja-Liisa; Sundström, Christer; Scholtysik, René; Hansmann, Martin-Leo; Küppers, Ralf

    2017-06-01

    Angioimmunoblastic T-cell lymphomas (AITLs) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they had already been detected in haematopoietic precursor cells of AITL patients. We show by analysis of whole-tissue sections and microdissected PD1 + cells that the frequency of TET2-mutated AITL is presumably even higher than reported (12/13 cases in our collection; 92%). In two-thirds of informative AITLs (6/9), a fraction of B cells was also TET2-mutated. Investigation of four AITLs by TET2 and IGHV gene sequencing of single microdissected B cells showed that between 10% and 60% of polyclonal B cells in AITL lymph nodes harboured the identical TET2 mutations of the respective T-cell lymphoma clone. Thus, TET2-mutated haematopoietic precursor cells in AITL patients not only give rise to the T-cell lymphoma but also generate a large population of mutated mature B cells. Future studies will show whether this is a reason why AITL patients frequently also develop B-cell lymphomas. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. Plasma Epstein-Barr virus and Hepatitis B virus in non-Hodgkin lymphomas: Two lymphotropic, potentially oncogenic, latently occurring DNA viruses.

    PubMed

    Sinha, Mahua; Rao, Clementina Rama; Premalata, C S; Shafiulla, Mohammed; Lakshmaiah, K C; Jacob, Linu Abraham; Babu, Govind K; Viveka, B K; Appaji, L; Subramanyam, Jayshree R

    2016-01-01

    There is a need to study potential infective etiologies in lymphomas. Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal cell functions, and promote cell division. Epstein-Barr virus (EBV) is known to be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been emphasized. The aim of this study was to elucidate the association of two potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non-HL (NHL). In this prospective study, we estimated plasma EBV and HBV DNA in NHL patients. Peripheral blood was obtained from newly diagnosed, treatment na ïve, histologically confirmed NHL patients. Plasma EBV DNA was quantified by real-time polymerase chain reaction (PCR) targeting Epstein-Barr Nucleic acid 1 while the plasma HBV DNA was detected using nested PCR targeting HBX gene. In a small subset of patients, follow-up plasma samples post-anticancer chemotherapy were available and retested for viral DNA. Of the 110 NHL patients, ~79% were B-cell NHL and ~21% were T-cell NHL. Plasma EBV-DNA was detected in 10% NHLs with a higher EBV association in Burkitt lymphoma (33.3%) than other subtypes. Pretherapy HBV DNA was detected in 21% NHLs; most of them being diffuse large B-cell lymphoma (DLBCL). Moreover, 42% of DLBCL patients had HBV DNA in plasma. Since all patients were HBV surface antigen seronegative at diagnosis, baseline plasma HBV-DNAemia before chemotherapy was indicative of occult hepatitis B infection. Our findings indicate a significant association of HBV with newly diagnosed DLBCL.

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

    PubMed

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

    2016-07-01

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

  7. Disease patterns of pediatric non-Hodgkin lymphoma: A study from a developing area in Egypt

    PubMed Central

    SHERIEF, LAILA M.; ELSAFY, USAMA R.; ABDELKHALEK, ELHAMY R.; KAMAL, NAGLAA M.; YOUSSEF, DOAA M.; ELBEHEDY, RABAB

    2015-01-01

    Non-Hodgkin lymphoma (NHL) accounts for 8–10% of all childhood cancers. NHL collectively represents various lymphoid malignancies with diverse clinicopathological and biological characteristics. In this study, we aimed to describe the epidemiological and clinicopathological characteristics and treatment outcomes of pediatric NHL patients treated at the Pediatric Oncology Unit of Zagazig University Hospital and the Benha Specialized Pediatric Hospital. We conducted a cross-sectional retrospective study by reviewing the medical records of 142 patients admitted with a diagnosis of NHL over a period of 8 years (February, 2004 to February, 2012) in these two Oncology Units. The age at presentation ranged between 2 and 15 years, with a mean ± standard deviation (SD) of 6.1±2.8 years and a male:female ratio of 1.7:1. Abdominal involvement was the most common presentation (73.2%). Burkitt's lymphoma (BL) was the most common NHL subtype (69%), followed by lymphoblastic lymphoma, diffuse large B-cell lymphoma and anaplastic large-cell lymphoma, accounting for 18.3, 10.6 and 2.1% of the cases, respectively. The majority of the patients (88.7%) had been diagnosed with advanced disease (Murphy stage III/IV). Complete remission was achieved in 120 cases (84.5%). A total of 16 patients (11.3%) succumbed to the disease during the first few months and 6 patients (4.2%) remained alive following relapse. The mean follow-up duration ± SD was 34.6±25.1 months (range, 3–84 months). The 5-year overall survival (OS) and event-free survival (EFS) rates were 88.7 and 85.1%, respectively. None of the clinical, epidemiological or pathological variables exhibited a statistically significant association with the OS or EFS. In conclusion, NHL occurs at a younger age, with a higher incidence of BL and advanced-stage disease. The outcome of NHL in our two centers was satisfactory, approaching the international rates. PMID:25469284

  8. Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning.

    PubMed

    Rezvani, A R; Kanate, A S; Efron, B; Chhabra, S; Kohrt, H E; Shizuru, J A; Laport, G G; Miklos, D B; Benjamin, J E; Johnston, L J; Arai, S; Weng, W-K; Negrin, R S; Strober, S; Lowsky, R

    2015-10-01

    We describe 47 patients with lymphoma and failed prior autologous hematopoietic cell transplantation (HCT) who received TLI-ATG (anti-thymocyte globulin) conditioning followed by allogeneic HCT. Thirty-two patients had non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma (n=19), T-cell NHL (n=6), mantle cell lymphoma (n=4) or other B-cell subtypes (n=3)), and 15 had Hodgkin lymphoma. The median follow-up was 4.9 (range, 2.1-11.9) years. The cumulative incidence of grade II-IV acute GvHD at day +100 was 12%, and the cumulative incidence of extensive chronic GvHD at 1 year was 36%. The 3-year cumulative incidences of overall survival (OS), PFS and non-relapse mortality (NRM) were 81%, 44% and 7%, respectively. Fifteen patients died (relapse, n=10; NRM, n=5). Among the 25 patients with relapse after allogeneic HCT, 11 (44%) achieved durable (>1 year) CRs following donor lymphocyte infusion or chemoradiotherapy. The majority of surviving patients (75%; n=24) were able to discontinue all immunosuppression. For patients with relapsed lymphoma after autologous HCT, allogeneic HCT using TLI-ATG conditioning is a well-tolerated, predominantly outpatient therapy with low NRM (7% at 3 years), a low incidence of GvHD, durable disease control and excellent OS (81% at 3 years).

  9. CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Patients With Recurrent or Refractory CD19 Positive Diffuse Large B-Cell Lymphoma or B Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2018-01-25

    B Acute Lymphoblastic Leukemia; CD19 Positive; 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; Minimal Residual Disease; Philadelphia Chromosome Positive; 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; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

  10. B Cell Lymphoma, Unclassifiable, Transformed from Follicular Lymphoma: A Rare Presentation with Review of the Literature

    PubMed Central

    Kanna, Anila; Agrawal, Swati; Jayant, Kumar; Kumar Pala, Varun; Altujjar, Mohammad; Hadid, Tarik; Khurram, Muhammad

    2015-01-01

    B cell lymphoma, unclassifiable, with features of diffuse large B cell lymphoma and classical Hodgkin's lymphoma (BCLu-DLBCL/CHL) is more commonly known as gray zone lymphoma. These cases more often present with mediastinal disease. In this report, we present a very rare case of BCLu-DLBCL/CHL without mediastinal involvement, transformed from follicular lymphoma (FL) to BCLu-DLBCL/CHL. This patient initially presented with a mass in the right neck; biopsy of the lymph node showed predominantly nodular, follicular pattern. Immunohistochemical (IHC) staining of tumor cells expressed positivity for mature B cell markers CD20, CD19, CD10, CD23, CD45, and CD38 but negative for CD5,11c. Hence, diagnosed with FL, he was given rituximab, cyclophosphamide, vincristine, and prednisone (RCVP) regimen, followed by maintenance rituximab. He showed good response. After 2 years, he presented again with a mass in the right side of the neck. Although the needle core biopsy of this mass was suggestive of B cell lymphoma, excisional biopsy showed morphological features of DLBCL as well as foci of histological pattern of CHL. IHC staining expressed positivity for CD20, CD79a, PAX5, and CD15 and CD30 consistent with DLBCL and CHL. He was diagnosed with BCLu-DLBCL/CHL. The patient received “ACVBP” (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) followed by radiation. BCLu-DLBCL/CHL is clinically an aggressive tumor with poorer outcomes, but our case showed complete response to ACVBP regimen with tumor regression. PMID:26380128

  11. B Cell Lymphoma, Unclassifiable, Transformed from Follicular Lymphoma: A Rare Presentation with Review of the Literature.

    PubMed

    Kanna, Anila; Agrawal, Swati; Jayant, Kumar; Kumar Pala, Varun; Altujjar, Mohammad; Hadid, Tarik; Khurram, Muhammad

    2015-01-01

    B cell lymphoma, unclassifiable, with features of diffuse large B cell lymphoma and classical Hodgkin's lymphoma (BCLu-DLBCL/CHL) is more commonly known as gray zone lymphoma. These cases more often present with mediastinal disease. In this report, we present a very rare case of BCLu-DLBCL/CHL without mediastinal involvement, transformed from follicular lymphoma (FL) to BCLu-DLBCL/CHL. This patient initially presented with a mass in the right neck; biopsy of the lymph node showed predominantly nodular, follicular pattern. Immunohistochemical (IHC) staining of tumor cells expressed positivity for mature B cell markers CD20, CD19, CD10, CD23, CD45, and CD38 but negative for CD5,11c. Hence, diagnosed with FL, he was given rituximab, cyclophosphamide, vincristine, and prednisone (RCVP) regimen, followed by maintenance rituximab. He showed good response. After 2 years, he presented again with a mass in the right side of the neck. Although the needle core biopsy of this mass was suggestive of B cell lymphoma, excisional biopsy showed morphological features of DLBCL as well as foci of histological pattern of CHL. IHC staining expressed positivity for CD20, CD79a, PAX5, and CD15 and CD30 consistent with DLBCL and CHL. He was diagnosed with BCLu-DLBCL/CHL. The patient received "ACVBP" (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) followed by radiation. BCLu-DLBCL/CHL is clinically an aggressive tumor with poorer outcomes, but our case showed complete response to ACVBP regimen with tumor regression.

  12. CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy

    ClinicalTrials.gov

    2017-11-07

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

  13. Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.

    PubMed

    Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

    2018-02-01

    We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

  14. Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma

    PubMed Central

    Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

    2018-01-01

    We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma. PMID:29380792

  15. 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...

  16. 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.

  17. PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma

    PubMed Central

    Gopal, Ajay K.; Kahl, Brad S.; de Vos, Sven; Wagner-Johnston, Nina D.; Schuster, Stephen J.; Jurczak, Wojciech J.; Flinn, Ian W.; Flowers, Christopher R.; Martin, Peter; Viardot, Andreas; Blum, Kristie A.; Goy, Andre H.; Davies, Andrew J.; Zinzani, Pier Luigi; Dreyling, Martin; Johnson, Dave; Miller, Langdon L.; Holes, Leanne; Li, Daniel; Dansey, Roger D.; Godfrey, Wayne R.; Salles, Gilles A.

    2014-01-01

    Background Phosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin's lymphomas. Methods In this single-group, open-label, phase 2 study, 125 patients with indolent non-Hodgkin's lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within 6 months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. The primary end point was the overall rate of response; secondary end points included the duration of response, progression-free survival, and safety. Results The median age of the patients was 64 years (range, 33 to 87); patients had received a median of four prior therapies (range, 2 to 12). Subtypes of indolent non-Hodgkin's lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6% meeting the criteria for a complete response. The median time to a response was 1.9 months, the median duration of response was 12.5 months, and the median progression-free survival was 11 months. Similar response rates were observed across all subtypes of indolent non-Hodgkin's lymphoma, though the numbers were small for some categories. The most common adverse events of grade 3 or higher were neutropenia (in 27% of the patients), elevations in aminotransferase levels (in 13%), diarrhea (in 13%), and pneumonia (in 7%). Conclusions In this single-group study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non-Hodgkin

  18. Early Generated B-1-Derived B Cells Have the Capacity To Progress To Become Mantle Cell Lymphoma-like Neoplasia in Aged Mice.

    PubMed

    Hayakawa, Kyoko; Formica, Anthony M; Nakao, Yuka; Ichikawa, Daiju; Shinton, Susan A; Brill-Dashoff, Joni; Smith, Mitchell R; Morse, Herbert C; Hardy, Richard R

    2018-06-13

    In mice, fetal/neonatal B-1 cell development generates murine CD5 + B cells (B1a) with autoreactivity. We analyzed B1a cells at the neonatal stage in a V H 11/D/J H knock-in mouse line (V H 11t) that generates an autoreactive antiphosphatidylcholine BCR. Our study revealed that antiphosphatidylcholine B1a cells develop in liver, mature in spleen, and distribute in intestine/colon, mesenteric lymph node (mLN), and body cavity as the outcome of B-1 cell development before B-2 cell development. Throughout life, self-renewing B-1 B1a cells circulate through intestine, mesenteric vessel, and blood. The body cavity-deposited B1a cells also remigrate. In old age, some B1a cells proceed to monoclonal B cell lymphocytosis. When neonatal B-1 B1a cells express an antithymocyte/Thy-1 autoreactivity (ATA) BCR transgene in the C.B17 mouse background, ATA B cells increase in PBL and strongly develop lymphomas in aging mice that feature splenomegaly and mLN hyperplasia with heightened expression of CD11b, IL-10, and activated Stat3. At the adult stage, ATA B cells were normally present in the mantle zone area, including in intestine. Furthermore, frequent association with mLN hyperplasia suggests the influence by intestinal microenvironment on lymphoma development. When cyclin D1 was overexpressed by the Eμ-cyclin D1 transgene, ATA B cells progressed to further diffused lymphoma in aged mice, including in various lymph nodes with accumulation of IgM hi IgD lo CD5 + CD23 - CD43 + cells, resembling aggressive human mantle cell lymphoma. Thus, our findings reveal that early generated B cells, as an outcome of B-1 cell development, can progress to become lymphocytosis, lymphoma, and mantle cell lymphoma-like neoplasia in aged mice. Copyright © 2018 by The American Association of Immunologists, Inc.

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

    ClinicalTrials.gov

    2014-08-04

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

  20. Quality of life domains among non-Hodgkin lymphoma survivors: an integrative literature review

    PubMed Central

    LEAK, ASHLEY; MAYER, DEBORAH K.; SMITH, SOPHIA

    2011-01-01

    Survival rates of individuals with non-Hodgkin lymphoma (NHL) have increased in the past several years, as has the prevalence of older adults who are managing late and long-term effects of the disease and its treatment. In this integrative review, the state of the science for determining the quality of life (QOL) among NHL survivors is outlined. An online search of Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and the Cochrane Library databases was conducted using the following Keywords: non-Hodgkin lymphoma, health-related quality of life, quality of life, and impact of cancer. Eighteen studies published between 2000 and 2010 are reviewed. Of these, 17 were descriptive, cross-sectional designs, and one was a systematic review. The studies included participants of varying ages and years post-diagnosis as reported in several countries. Importantly, many used one or more QOL measures as outcome variables. Future research is needed on older and minority cancer populations and should include longitudinal and interventional studies. PMID:21534866

  1. Association of Systemic Anaplastic Large Cell Lymphoma and Active Toxoplasmosis in a Child.

    PubMed

    Sayyahfar, Shirin; Karimi, Abdollah; Gharib, Atoosa; Fahimzad, Alireza

    2015-08-01

    Anaplastic large cell lymphoma is a subset of non-Hodgkin lymphoma and an unusual disease in children. Herein we have reported a 7- year- old girl with a large necrotic skin ulcer on the chest caused by systemic form of anaplastic large-cell lymphoma and simultaneous active toxoplasmosis diagnosed by PCR on lymph node specimen. There were few reports showing a role for toxoplasma infection to cause some malignancies such as lymphoma in adults. Based to our knowledge, this has been the first report of simultaneous systemic anaplastic large cell lymphoma and active toxoplasmosis, documented by positive PCR on tissue biopsy in a child. This case report has suggested more attention to the accompanying Toxoplasma gondii infection as a probable cause of some types of lymphomas.

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

    ClinicalTrials.gov

    2018-06-18

    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; Relapsed/Refractory Large B Cell Lymphoma Including DLBCL, PMBCL, TFL and HGBCL After Two Systemic Lines of Therapy" in Phase 2 Expanded Cohorts

  3. B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma.

    PubMed

    Snuderl, Matija; Kolman, Olga K; Chen, Yi-Bin; Hsu, Jessie J; Ackerman, Adam M; Dal Cin, Paola; Ferry, Judith A; Harris, Nancy Lee; Hasserjian, Robert P; Zukerberg, Lawrence R; Abramson, Jeremy S; Hochberg, Ephraim P; Lee, Hang; Lee, Alfred I; Toomey, Christiana E; Sohani, Aliyah R

    2010-03-01

    B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as "double-hit" lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathologic features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathologic spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. In addition, we carried out case-control comparisons of DHL with BL and International Prognostic Index (IPI)-matched DLBCL. The 11 men and 9 women had a median age of 63.5 years (range 32 to 91). Six patients had a history of grade 1 to 2 follicular lymphoma; review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology. Eighteen patients had Ann Arbor stage 3 or 4 disease and all had elevated serum lactate dehydrogenase (LDH) levels at presentation. Extranodal disease was present in 17/20 (85%), bone marrow involvement in 10/17 (59%) and central nervous system (CNS) disease in 5/11 (45%). Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy. Fourteen patients (70%) died within 8 months of diagnosis. Median overall survival in the DHL group (4.5 mo) was inferior to both BL (P=0.002) and IPI-matched DLBCL (P=0.04) control patients. Twelve DHL cases (60%) were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, 7 cases (35%) as DLBCL, not otherwise specified, and 1 case as B-LBL. Distinguishing features from BL included expression of Bcl2 (P<0.0001), Mum1/IRF4 (P=0.006), Ki-67 <95% (P<0.0001), and absence of EBV-EBER (P=0.006). DHL commonly contained the t(8;22) rather than the t(8;14) seen

  4. Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

    PubMed

    Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

    2012-11-01

    The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

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

    PubMed Central

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

    1998-01-01

    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. PMID:9599716

  6. S0349 Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Oblimersen in Treating Patients With Advanced Diffuse Large B-Cell Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-04

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  7. 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. © 2016 UICC.

  8. [Association of XRCC1 genetic polymorphism with susceptibility to non-Hodgkin's lymphoma].

    PubMed

    Li, Su-Xia; Zhu, Hong-Li; Guo, Bo; Yang, Yang; Wang, Hong-Yan; Sun, Jing-Fen; Cao, Yong-Bin

    2014-08-01

    The purpose of this study was to explore the association between X-ray repair cross-complementing group 1 (XRCC1)gene polymorphism and non-Hodgkin's lymphoma risk. A total of 282 non-Hodgkin's lymphoma (NHL) patients and 231 normal controls were used to investigate the effect of three XRCC1 gene polymorphisms (rs25487, rs25489, rs1799782) on susceptibility to non-Hodgkin's lymphoma. Genotyping was performed by using SNaPshot method. All statistical analyses were done with R software. Genotype and allele frequencies of XRCC1 were compared between the patients and controls by using the chi-square test. Crude and adjusted odd ratios and 95% confidence intervals were calculated by using logistic regression on the basis of genetic different models. For four kinds of NHL, subgroup analyses were also conducted. Combined genotype analyses of the three XRCC1 polymorphisms were also done by using logistic regression. The results showed that the variant genotype frequency was not significantly different between the controls and NHL or NHL subtype cases. Combined genotype analyses of XRCC1 399-280-194 results showed that the combined genotype was not associated with risk of NHL overall, but the VT-WT-WT combined genotype was associated with the decreased risk of T-NHL (OR: 0.21; 95%CI (0.06-0.8); P = 0.022), and the WT-VT-WT combined genotype was associated with the increased risk of FL(OR:15.23; 95%CI (1.69-137.39); P = 0.015). It is concluded that any studied polymorphism (rs25487, rs25489, rs1799782) alone was not shown to be rela-ted with the risk of NHL or each histologic subtype of NHL. The combined genotype with mutation of three SNP of XRCC1 was not related to the risk of NHL. However, further large-scale studies would be needed to confirm the association of decreased or increased risk for T-NHL and FL with the risk 3 combined SNP mutants of XRCC1 polymorphism.

  9. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes.

    PubMed

    Vose, Julie; Armitage, James; Weisenburger, Dennis

    2008-09-01

    Peripheral T-cell lymphoma (PTCL) and natural killer/T-cell lymphoma (NKTCL) are rare and heterogeneous forms of non-Hodgkin's lymphoma (NHL) that, in general, are associated with a poor clinical outcome. A cohort of 1,314 cases of PTCL and NKTCL was organized from 22 centers worldwide, consisting of patients with previously untreated PTCL or NKTCL who were diagnosed between 1990 and 2002. Tissue biopsies, immunophenotypic markers, molecular genetic studies, and clinical information from consecutive patients at each site were reviewed by panels of four expert hematopathologists and classified according to the WHO classification. A diagnosis of PTCL or NKTCL was confirmed in 1,153 (87.8%) of the cases. The most common subtypes were PTCL not otherwise specified (NOS; 25.9%), angioimmunoblastic type (18.5%), NKTCL (10.4%), and adult T-cell leukemia/lymphoma (ATLL; 9.6%). Misclassification occurred in 10.4% of the cases including Hodgkin's lymphoma (3%), B-cell lymphoma (1.4%), unclassifiable lymphoma (2.8%), or a diagnosis other than lymphoma (2.3%). We found marked variation in the frequency of the various subtypes by geographic region. The use of an anthracycline-containing regimen was not associated with an improved outcome in PTCL-NOS or angioimmunoblastic type, but was associated with an improved outcome in anaplastic large-cell lymphoma, ALK positive. The WHO classification is useful for defining subtypes of PTCL and NKTCL. However, expert hematopathology review is important for accurate diagnosis. The clinical outcome for patients with most of these lymphoma subtypes is poor with standard therapies, and novel agents and new modalities are needed to improve survival.

  10. Primary Hepatic Marginal Zone Lymphoma in a Patient with Chronic Hepatitis C.

    PubMed

    Gherlan, George S; Stoia, Razvan; Enyedi, Mihaly; Dobrea, Camelia; Calistru, Petre I

    2016-09-01

    Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is a low-grade malignant lymphoma that appears frequently in the stomach, but other sites can also be involved: the intestinal tract, lungs, head, neck, skin, thyroid, breasts and liver. Recently, epidemiological evidences support the idea that there is an association between hepatitis C and B-cell non-Hodgkin lymphomas (that include MALT as a subtype). Primary non-Hodgkin lymphomas confi ned only to the liver are very rare (only 0.016% of all cases of all non-Hodgkin's lymphomas) and MALT is not the most frequent type. We present the case of a male patient, age 62, known with chronic hepatitis C, previously relapser a" er a 72 week treatment with peg-interferon alfa and ribavirin that was diagnosed at three years a" er the relapse with multiple focal liver lesions. One of the tumors was surgically removed and the histological exam performed demonstrated an extranodal marginal zone lymphoma with small B-cell with plasmacytoid diff erentiation confi ned only to the liver. Direct acting antiviral (DAA) therapy was started, but the virologic clearance was not obtained by week 10, leading to a change of DAA regimen at week 12. The antiviral therapy was continued until week 24. Imaging showed an increase in number and size of the focal lesions until week 12. At week 12 chemo- and immune-therapy was started with bendamustine and rituximab. A" erwards the evolution was favorable, the patient being now in complete remission and with undetectable viral load.

  11. Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas.

    PubMed

    Kokovic, Ira; Jezersek Novakovic, Barbara; Novakovic, Srdjan

    2015-03-01

    Analysis of the immunoglobulin κ light chain (IGK) gene is an alternative method for B-cell clonality assessment in the diagnosis of mature B-cell proliferations in which the detection of clonal immunoglobulin heavy chain (IGH) gene rearrangements fails. The aim of the present study was to evaluate the added value of standardized BIOMED-2 assay for the detection of clonal IGK gene rearrangements in the diagnostic setting of suspected B-cell lymphomas. With this purpose, 92 specimens from 80 patients with the final diagnosis of mature B-cell lymphoma (37 specimens), mature T-cell lymphoma (26 specimens) and reactive lymphoid proliferation (29 specimens) were analyzed for B-cell clonality. B-cell clonality analysis was performed using the BIOMED-2 IGH and IGK gene clonality assays. The determined sensitivity of the IGK assay was 67.6%, while the determined sensitivity of the IGH assay was 75.7%. The sensitivity of combined IGH+IGK assay was 81.1%. The determined specificity of the IGK assay was 96.2% in the group of T-cell lymphomas and 96.6% in the group of reactive lesions. The determined specificity of the IGH assay was 84.6% in the group of lymphomas and 86.2% in the group of reactive lesions. The comparison of GeneScan (GS) and heteroduplex pretreatment-polyacrylamide gel electrophoresis (HD-PAGE) methods for the analysis of IGK gene rearrangements showed a higher efficacy of GS analysis in a series of 27 B-cell lymphomas analyzed by both methods. In the present study, we demonstrated that by applying the combined IGH+IGK clonality assay the overall detection rate of B-cell clonality was increased by 5.4%. Thus, we confirmed the added value of the standardized BIOMED-2 IGK assay for assessment of B-cell clonality in suspected B-cell lymphomas with inconclusive clinical and cyto/histological diagnosis.

  12. Treatment of Peripheral T-Cell Lymphoma: Many Shades of Gray.

    PubMed

    Lunning, Matthew A

    2015-08-01

    Previously obscured within other designations of aggressive lymphomas, peripheral T-cell lymphoma (PTCL) now represents 23 different subtypes of non-Hodgkin lymphoma (NHL). Despite the many subtypes now recognized, PTCL represents only approximately 10% of all NHL cases diagnosed. Positron emission tomography/computed tomography has become essential to accurate staging and response-evaluation for PTCL. In comparison to aggressive B-cell NHL, patients with PTCL will more often be refractory to initial therapy, and chemosensitive patients will have shorter disease-free periods. Anthracycline-based regimens, often with the inclusion of etoposide, are commonly used during induction therapy. Consolidation with high-dose therapy and autologous stem cell transplantation (ASCT) in first chemosensitive remission appears to provide the best outcome in common nodal PTCL subtypes. The commonly defined nodal subtypes are PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic lymphoma kinase (ALK)-positive or ALK-negative anaplastic large-cell lymphoma (ALCL). Four agents have been approved by the US Food and Drug Administration for use in the relapsed/refractory (rel/ref) setting, including belinostat (2014), romidepsin (2011), brentuximab vedotin (2011), and pralatrexate (2009). Brentuximab vedotin was approved only for the ALCL subtype. These agents continue to be studied as combinations in the rel/ref setting and as additions or substitutions for other agents in upfront multiagent chemotherapy regimens. Patients who have responded to treatment in the rel/ref setting and are considered transplant-eligible should be considered for allogeneic stem cell transplantation, especially those with previous ASCT. Upfront allogeneic stem cell transplantation remains a research question in the majority of PTCL subtypes, but data are emerging.

  13. Establishment of a novel feline leukemia virus (FeLV)-negative B-cell cell line from a cat with B-cell lymphoma.

    PubMed

    Mochizuki, Hiroyuki; Takahashi, Masashi; Nishigaki, Kazuo; Ide, Tetsuya; Goto-Koshino, Yuko; Watanabe, Shinya; Sato, Hirofumi; Sato, Masahiko; Kotera, Yukiko; Fujino, Yasuhito; Ohno, Koichi; Uchida, Kazuyuki; Tsujimoto, Hajime

    2011-04-15

    We established a novel feline B-cell line, MS4, from the neoplastic pleural effusion of a cat with cutaneous B-cell lymphoma. Immunophenotype staining of the MS4 cells was positive for CD20, CD79α, and IgA and negative for CD3, CD4, CD5, CD8α, CD18, CD21, CD22, IgM, IgG, Ig light chain, and MHC class II. PCR analysis for immunoglobulin heavy chain gene rearrangements revealed a monoclonal rearrangement, whereas no clonal rearrangement of the T-cell receptor γ gene was detected. Southern blotting with an exogenous feline leukemia virus (FeLV) U3 probe revealed no integration of exogenous FeLV provirus. The MS4 cell line is the first FeLV-negative feline B-cell lymphoma cell line, and may be used to investigate the pathogenesis of spontaneously occurring feline lymphoma and the development of new therapies. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer

    ClinicalTrials.gov

    2018-06-13

    Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Leukemia in Remission; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; Aplastic Anemia; B-Cell Non-Hodgkin Lymphoma; CD40 Ligand Deficiency; Chronic Granulomatous Disease; Chronic Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Congenital Amegakaryocytic Thrombocytopenia; Congenital Neutropenia; Congenital Pure Red Cell Aplasia; Glanzmann Thrombasthenia; Immunodeficiency Syndrome; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Plasma Cell Myeloma; Polycythemia Vera; Recurrent Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Severe Aplastic Anemia; Shwachman-Diamond Syndrome; Sickle Cell Disease; T-Cell Non-Hodgkin Lymphoma; Thalassemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

  15. Malignant histiocytic lymphoma with large lacunar cells.

    PubMed

    Leahu, S; Dobrea, M

    1997-01-01

    A case of lymph node biopsy with a peculiar histological aspect is described. The clinical data suggest a malignant lymphoid disease. The histological picture is that of a malignant histiocytosis but, among the majority of small histiocytes, there are some large cells like the large lacunar cells from Hodgkin's disease. These large cells (and some small cells) contain the CD 30 antigen of Reed-Sternberg cells. It is discussed whether the appropriate diagnosis is Hodgkin's disease, malignant histiocytosis, or non-Hodgkin's malignant lymphoma. Our diagnosis is Hodgkin's disease, the nodular sclerosing form.

  16. Human Lyb-2 homolog CD72 is a marker for progenitor B-cell leukemias.

    PubMed

    Schwarting, R; Castello, R; Moldenhauer, G; Pezzutto, A; von Hoegen, I; Ludwig, W D; Parnes, J R; Dörken, B

    1992-11-01

    S-HCL 2 is the prototype antibody of the recently defined CD72 cluster (human Lyb-2). Under nonreducing conditions, S-HCL 2 monoclonal antibody (mAb) precipitates a glycoprotein of 80-86 kDa. Under reducing conditions, a dimer of 43 and 39 kDa, with core proteins of 40 and 36 kDa, is precipitated. CD72 expression in normal and malignant tissues is different from expression of all other previously described human B-cell antigens. In peripheral blood and bone marrow, the antigen appears to be present on all B lymphocytes, with the exception of plasma cells. In tissue, immunohistochemical staining revealed positivity for all known B-cell compartments; however, pulpa macrophages of the spleen and von Kupffer cells exhibited distinct positivity for CD72 also. Among 83 malignant non-Hodgkin's lymphomas examined by immunohistochemistry (alkaline phosphatase anti-alkaline phosphatase technique), all 54 B-cell lymphomas, including precursor B-cell lymphomas, Burkitt's lymphomas, germinal center lymphomas, chronic lymphocytic leukemias, and hairy cell leukemias, were CD72 positive, but no T-cell lymphomas were. Flow cytometry study of more than 80 mainly acute leukemias (52 B-cell leukemias) showed reactivity with S-HCL 2 mAb over the full range of B-cell differentiation. In particular, very early B cells in cytoplasmic Ig (cIg)-negative, CD19-positive pre-pre-B-cell leukemias and hybrid leukemias (mixed myeloid and B-cell type) were consistently positive for CD72 on the cell surface. Therefore, CD72 may become an important marker for progenitor B-cell leukemias.

  17. Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma.

    PubMed

    Sato, Yusuke; Shimizu, Kanako; Shinga, Jun; Hidaka, Michihiro; Kawano, Fumio; Kakimi, Kazuhiro; Yamasaki, Satoru; Asakura, Miki; Fujii, Shin-Ichiro

    2015-03-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population with the ability to suppress immune responses and are currently classified into three distinct MDSC subsets: monocytic, granulocytic and non-monocytic, and non-granulocytic MDSCs. Although NK cells provide an important first-line defense against newly transformed cancer cells, it is unknown whether NK cells can regulate MDSC populations in the context of cancer. In this study, we initially found that the frequency of MDSCs in non-Hodgkin lymphoma (NHL) patients was increased and inversely correlated with that of NK cells, but not that of T cells. To investigate the regulation of MDSC subsets by NK cells, we used an EL4 murine lymphoma model and found the non-monocytic and non-granulocytic MDSC subset, i.e., Gr1 + CD11b + Ly6G med Ly6C med MDSC, is increased after NK cell depletion. The MDSC population that expresses MHC class II, CD80, CD124, and CCR2 is regulated mainly by CD27 + CD11b + NK cells. In addition, this MDSC subset produces some immunosuppressive cytokines, including IL-10 but not nitric oxide (NO) or arginase. We also examined two subsets of MDSCs (CD14 + HLA-DR - and CD14 - HLA-DR - MDSC) in NHL patients and found that higher IL-10-producing CD14 + HLA-DR - MDSC subset can be seen in lymphoma patients with reduced NK cell frequency in peripheral blood. Our analyses of MDSCs in this study may enable a better understanding of how MDSCs manipulate the tumor microenvironment and are regulated by NK cells in patients with lymphoma.

  18. Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma

    PubMed Central

    Sato, Yusuke; Shimizu, Kanako; Shinga, Jun; Hidaka, Michihiro; Kawano, Fumio; Kakimi, Kazuhiro; Yamasaki, Satoru; Asakura, Miki; Fujii, Shin-ichiro

    2015-01-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population with the ability to suppress immune responses and are currently classified into three distinct MDSC subsets: monocytic, granulocytic and non-monocytic, and non-granulocytic MDSCs. Although NK cells provide an important first-line defense against newly transformed cancer cells, it is unknown whether NK cells can regulate MDSC populations in the context of cancer. In this study, we initially found that the frequency of MDSCs in non-Hodgkin lymphoma (NHL) patients was increased and inversely correlated with that of NK cells, but not that of T cells. To investigate the regulation of MDSC subsets by NK cells, we used an EL4 murine lymphoma model and found the non-monocytic and non-granulocytic MDSC subset, i.e., Gr1+CD11b+Ly6GmedLy6Cmed MDSC, is increased after NK cell depletion. The MDSC population that expresses MHC class II, CD80, CD124, and CCR2 is regulated mainly by CD27+CD11b+NK cells. In addition, this MDSC subset produces some immunosuppressive cytokines, including IL-10 but not nitric oxide (NO) or arginase. We also examined two subsets of MDSCs (CD14+HLA-DR− and CD14− HLA-DR− MDSC) in NHL patients and found that higher IL-10-producing CD14+HLA-DR−MDSC subset can be seen in lymphoma patients with reduced NK cell frequency in peripheral blood. Our analyses of MDSCs in this study may enable a better understanding of how MDSCs manipulate the tumor microenvironment and are regulated by NK cells in patients with lymphoma. PMID:25949922

  19. An unusual presentation of primary malignant B-cell-type dural lymphoma

    PubMed Central

    Low, Yin Yee Sharon; Lai, Siang Hui; Ng, Wai Hoe

    2014-01-01

    Primary malignant B-cell-type dural lymphoma is a rare subtype of primary central nervous system lymphoma (PCNSL). We herein report an unusual case of diffuse B-cell lymphoma that presents as a chronic subdural haematoma without extracranial involvement. The notable aspects of this case include the patient’s immunocompetence, a short clinical history of symptom onset, rapid neurological deterioration and a final diagnosis of high-grade PCNSL. This case highlights the challenges neurosurgeons face, especially in the emergency setting, when the disease manifests in varied presentations. PMID:25631982

  20. Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States

    PubMed Central

    Hopp, Lydia; Löffler-Wirth, Henry; Binder, Hans

    2015-01-01

    Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt’s lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12. PMID:26371046

  1. Clinical Significance of "Double-hit" and "Double-protein" expression in Primary Gastric B-cell Lymphomas.

    PubMed

    He, Miaoxia; Chen, Keting; Li, Suhong; Zhang, Shimin; Zheng, Jianming; Hu, Xiaoxia; Gao, Lei; Chen, Jie; Song, Xianmin; Zhang, Weiping; Wang, Jianmin; Yang, Jianmin

    2016-01-01

    Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas. This study aims to obtain a molecular pathology prognostic model of gastric B-cell lymphoma for clinical stratified management by evaluating how the "double-hit" and "double-protein" in tumor cells as well as microenvironmental reaction of tumor stromal tissue affect clinical outcome in primary gastric B-cell lymphomas. Data and tissues of 188 cases diagnosed with gastric B-cell lymphomas were used in this study. Tumor tissue microarray (TMA) of formalin fixed and paraffin embedded (FFPE) tissues was constructed for fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analysis with a serial of biomarkers containing MYC, BCL2, BCL6, CD31, SPARC, CD10, MUM1 and Ki-67. Modeled period analysis was used to estimate 3-year and 5-year overall survival (OS) and disease-free survival (DFS) distributions. There was no definite "double-hit" case though the gene rearrangement of c-Myc (5.9%), bcl2 (0.1%) and bcl6 (7.4%) was found in gastric B-cell lymphomas. The gene amplification or copy gains of c-Myc (10.1%), bcl-2 (17.0%) and bcl-6 (0.9%) were present in these lymphomas. There were 12 cases of the lymphomas with the "double-protein" expression of MYC and BCL2/BCL6. All patients with "double-protein" gastric B-cell lymphomas had poor outcome compared with those without. More importantly, "MYC-BCL2-BCL6" negative group of gastric B-cell lymphoma patients had favorable clinical outcome regardless clinical stage, pathological types and therapeutic modalities. And the similar better

  2. Combination of Pim kinase inhibitor, SGI-1776, with bendamustine in B-cell lymphoma

    PubMed Central

    Yang, Qingshan; Chen, Lisa S; Neelapu, Sattva S.; Gandhi, Varsha

    2013-01-01

    SGI-1776 is a small molecule Pim kinase inhibitor that primarily targets c-Myc-driven transcription and cap-dependent translation in mantle cell lymphoma (MCL) cells. Bendamustine is an alkylating chemotherapeutic agent approved for use in B-cell lymphoma that is known to induce DNA damage and to initiate response to repair. We hypothesized that while each drug leads to the effects as stated above, combination of these drugs will enhance SGI-1776-induced inhibition of global transcription and translation processes, while promoting bendamustine-triggered decrease of DNA synthesis and DNA damage response in B-cell lymphoma. Both SGI-1776 and bendamustine as single agents effectively induced apoptosis and when used in combination, additive effect in cell killing was observed in MCL cell lines, JeKo-1 and Mino, as well as MCL and splenic marginal zone lymphoma (a type of B-cell lymphoma) primary cells. As expected, SGI-1776 was effective in inducing decrease of global RNA and protein synthesis, while bendamustine significantly inhibited DNA synthesis and generated DNA damage response. When used in combination, effects were intensified in DNA, RNA and protein syntheses compared to single agent treatments. Together, these data provided foundation and suggested feasibility of using Pim kinase inhibitor in combination with chemotherapeutic agents such as bendamustine in B-cell lymphoma. PMID:24290221

  3. A novel antibody-drug conjugate anti-CD19(Fab)-LDM in the treatment of B-cell non-Hodgkin lymphoma xenografts with enhanced anticancer activity.

    PubMed

    Jiang, Linlin; Yang, Ming; Zhang, Xiaoyun; Bao, Shiqi; Ma, Li; Fan, Dongmei; Zhou, Yuan; Xiong, Dongsheng; Zhen, Yongsu

    2016-01-01

    Rituximab is widely used in clinical setting for the treatment of B malignant lymphoma and has achieved remarkable success. However, in most patients, the disease ultimately relapses and become resistant to rituximab. To overcome the limitation, there is still a need to find novel strategy for improving therapeutic efficacy. To construct genetically engineered antibody anti-CD19(Fab)-LDM, and verify the anticancer activity targeted toward B-lymphoma. The anticancer activity of anti-CD19(Fab)-LDM in vitro and in vivo was examined. In vitro, the binding activity and internalization of anti-CD19(Fab)-LDP were measured. Using comet assay and apoptosis, the cytotoxicity of energized fusion proteins was observed. From in vivo experiments, targeting of therapeutic effect and anticancer efficacy bythe fusion protein was verified. Data showed that anti-CD19(Fab)-LDM does not only binding the cell surface but is also internalized into the cell. The energized fusion proteins anti-CD19(Fab)-LDM can induce DNA damage. Furthermore, significant in vivo therapeutic efficacy was observed. The present study demonstrated that the genetically engineered antibody anti-CD19(Fab)-LDM exhibited enhanced cytotoxicity compared to LDM alone. One of the most powerful advantages of anti-CD19(Fab)-LDM, however, is that it can be internalized within the cells and carry out cytotoxic effects. Therefore, anti-CD19(Fab)-LDM may be as a useful targeted therapy for B-cell lymphoma.

  4. HORIZONS: Understanding the Impact of Cancer Diagnosis and Treatment on Everyday Life

    ClinicalTrials.gov

    2018-04-09

    Breast Cancer Female; Breast Neoplasm; Non-Hodgkin's B-cell Lymphoma; Non-Hodgkin's Lymphoma, Adult High Grade; NonHodgkin Lymphoma; Diffuse Large B Cell Lymphoma; Diffuse Large Cell Lymphoma, Adult; Ovarian Cancer; Ovarian Neoplasm; Endometrial Cancer; Endometrial Neoplasms; Cervical Cancer; Cervical Neoplasm; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; Fallopian Tube Neoplasms; Vulvar Cancer; Vulvar Neoplasms

  5. Validation of 64Cu-DOTA-rituximab injection preparation under good manufacturing practices: a PET tracer for imaging of B-cell non-Hodgkin lymphoma.

    PubMed

    Natarajan, Arutselvan; Arksey, Natasha; Iagaru, Andrei; Chin, Frederick T; Gambhir, Sanjiv Sam

    2015-01-01

    Manufacturing of 64Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-rituximab injection under good manufacturing practices (GMP) was validated for imaging of patients with CD20+ B-cell non-Hodgkin lymphoma. Rituximab was purified by size exclusion high performance liquid chromatography (HPLC) and conjugated to DOTA-mono-(N-hydroxysuccinimidyl) ester. 64CuCl2, buffers, reagents, and other raw materials were obtained as high-grade quality. Following a semi-automated synthesis of 64Cu-DOTA-rituximab, a series of quality control tests was performed. The product was further tested in vivo using micro-positron emission tomography/computed tomography (PET/CT) to assess targeting ability towards human CD20 in transgenic mice. Three batches of 64Cu-DOTA-rituximab final product were prepared as per GMP specifications. The radiolabeling yield from these batches was 93.1 ± 5.8%; these provided final product with radiopharmaceutical yield, purity, and specific activity of 59.2 ± 5.1% (0.9 ± 0.1 GBq of 64Cu), > 95% (by HPLC and radio-thin layer chromatography), and 229.4 ± 43.3 GBq/µmol (or 1.5 ± 0.3 MBq/µg), respectively. The doses passed apyrogenicity and human serum stability specifications, were sterile up to 14 days, and retained > 60% immunoreactivity. In vivo micro-PET/CT mouse images at 24 hours postinjection showed that the tracer targeted the intended sites of human CD20 expression. Thus, we have validated the manufacturing of GMP grade 64Cu-DOTA-rituximab for injection in the clinical setting.

  6. A B-cell lymphoma vaccine using a depot formulation of interleukin-2 induces potent antitumor immunity despite increased numbers of intratumoral regulatory T cells.

    PubMed

    Grille, Sofía; Brugnini, Andreína; Nese, Martha; Corley, Esteban; Falkenberg, Frank W; Lens, Daniela; Chabalgoity, José A

    2010-04-01

    Therapeutic vaccination holds great potential as complementary treatment for non-Hodgkin's lymphoma. Here, we report that a therapeutic whole cell vaccine formulated with IL-2 adsorbed onto aluminum hydroxide as cytokine-depot formulation elicits potent antitumor immunity and induces delayed tumor growth, control of tumor dissemination and longer survival in mice challenged with A20-lymphoma. Therapeutic vaccination induced higher numbers of tumor's infiltrating lymphocytes (CD4(+) and CD8(+) T cells and NK cells), and the production of IFN-gamma and IL-4 by intratumoral CD4(+) T cells. Further, strong tumor antigen-specific cellular responses were detected at systemic level. Both the A20-derived antigenic material and the IL-2 depot formulation were required for induction of an effective immune response that impacted on cancer progression. All mice receiving any form of IL-2, either as part of the vaccine or alone as control, showed higher numbers of CD4(+)CD25(+/high)Foxp3(+) regulatory T cells (Treg) in the tumor, which might have a role in tumor progression in these animals. Nevertheless, for those animals that received the cytokine as part of the vaccine formulation, the overall effect was improved immune response and less disseminated disease, suggesting that therapeutic vaccination overcomes the potential detrimental effect of intratumoral Treg cells. Overall, the results presented here show that a simple vaccine formulation, that can be easily prepared under GMP conditions, is a promising strategy to be used in B-cell lymphoma and may have enough merit to be tested in clinical trials.

  7. Long non-coding RNAs in B-cell malignancies: a comprehensive overview

    PubMed Central

    Taiana, Elisa; Neri, Antonino

    2017-01-01

    B-cell malignancies constitute a large part of hematological neoplasias. They represent a heterogeneous group of diseases, including Hodgkin's lymphoma, most non-Hodgkin's lymphomas (NHL), some leukemias and myelomas. B-cell malignancies reflect defined stages of normal B-cell differentiation and this represents the major basis for their classification. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides, for which many recent studies have demonstrated a function in regulating gene expression, cell biology and carcinogenesis. Deregulated expression levels of lncRNAs have been observed in various types of cancers including hematological malignancies. The involvement of lncRNAs in cancer initiation and progression and their attractive features both as biomarker and for therapeutic research are becoming increasingly evident. In this review, we summarize the recent literature to highlight the status of the knowledge of lncRNAs role in normal B-cell development and in the pathogenesis of B-cell tumors. PMID:28947998

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Macklis, Roger M.; Pohlman, Brad

    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 inmore » 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.« less

  9. Lymphoma in pregnancy initially diagnosed as vaginal intraepithelial neoplasia and lichen planus.

    PubMed

    Nguyen, Thuong-Thuong; Gubens, Matthew; Arber, Daniel A; Advani, Ranjana; Juretzka, Margrit; Aziz, Natali

    2011-08-01

    Non-Hodgkin's lymphoma presenting as a vaginal mass in pregnancy is uncommon. A 38-year-old primigravid woman presented at 27 weeks of gestation with vaginal lesions, bleeding, and discharge. Previous vaginal biopsies had been consistent with vaginal intraepithelial neoplasia 1 and lichen planus. After admission for this enlarging vaginal mass and bleeding, she was noted to have a newly palpable breast mass. Biopsy of the breast mass and subsequent re-evaluation of original vaginal biopsies were consistent with diffuse large B-cell lymphoma. She was treated with chemoimmunotherapy during pregnancy and delivered a viable neonate at term. Although benign vaginal conditions are common, non-Hodgkin's lymphoma should be considered in the differential diagnosis of persistent or enlarging vaginal lesions in pregnancy.

  10. B-cell receptor signaling as a driver of lymphoma development and evolution.

    PubMed

    Niemann, Carsten U; Wiestner, Adrian

    2013-12-01

    The B-cell receptor (BCR) is essential for normal B-cell development and maturation. In an increasing number of B-cell malignancies, BCR signaling is implicated as a pivotal pathway in tumorigenesis. Mechanisms of BCR activation are quite diverse and range from chronic antigenic drive by microbial or viral antigens to autostimulation of B-cells by self-antigens to activating mutations in intracellular components of the BCR pathway. Hepatitis C virus infection can lead to the development of splenic marginal zone lymphoma, while Helicobacter pylori infection is associated with the development of mucosa-associated lymphoid tissue lymphomas. In some of these cases, successful treatment of the infection removes the inciting antigen and results in resolution of the lymphoma. Chronic lymphocytic leukemia has been recognized for decades as a malignancy of auto-reactive B-cells and its clinical course is in part determined by the differential response of the malignant cells to BCR activation. In a number of B-cell malignancies, activating mutations in signal transduction components of the BCR pathway have been identified; prominent examples are activated B-cell-like (ABC) diffuse large B-cell lymphomas (DLBCL) that carry mutations in CD79B and CARD11 and display chronic active BCR signaling resulting in constitutive activation of the NF-κB pathway. Despite considerable heterogeneity in biology and clinical course, many mature B-cell malignancies are highly sensitive to kinase inhibitors that disrupt BCR signaling. Thus, targeted therapy through inhibition of BCR signaling is emerging as a new treatment paradigm for many B-cell malignancies. Here, we review the role of the BCR in the pathogenesis of B-cell malignancies and summarize clinical results of the emerging class of kinase inhibitors that target this pathway. Copyright © 2013. Published by Elsevier Ltd.

  11. Double-hit or dual expression of MYC and BCL2 in primary cutaneous large B-cell lymphomas.

    PubMed

    Menguy, Sarah; Frison, Eric; Prochazkova-Carlotti, Martina; Dalle, Stephane; Dereure, Olivier; Boulinguez, Serge; Dalac, Sophie; Machet, Laurent; Ram-Wolff, Caroline; Verneuil, Laurence; Gros, Audrey; Vergier, Béatrice; Beylot-Barry, Marie; Merlio, Jean-Philippe; Pham-Ledard, Anne

    2018-03-26

    In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with

  12. Carfilzomib, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Stage I-IV Diffuse Large B-cell Lymphoma

    ClinicalTrials.gov

    2018-03-28

    CD20 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Stage I Diffuse Large B-Cell Lymphoma; Stage II Diffuse Large B-Cell Lymphoma; Stage III Diffuse Large B-Cell Lymphoma; Stage IV Diffuse Large B-Cell Lymphoma

  13. Gastric diffuse large B-cell lymphoma cured with Helicobacter pylori eradication regardless of whether it contains features of MALT lymphoma.

    PubMed

    Mitsuhashi, Kei; Yamashita, Kentaro; Goto, Akira; Adachi, Takeya; Kondo, Yoshihiro; Kasai, Kiyoshi; Suzuki, Ryo; Saito, Mayuko; Arimura, Yoshiaki; Shinomura, Yasuhisa

    2014-01-01

    A 66-year-old patient was diagnosed with primary gastric B-cell lymphoma. The pathological findings were consistent with diffuse large B-cell lymphoma (DLBCL); however, a small area showed features of mucosa-associated lymphoid tissue (MALT) lymphoma. Biopsy specimens were referred to two other pathologists, both of whom diagnosed the case as pure DLBCL, denying the area of MALT lymphoma. As the lymphoma was limited to the submucosal layer and the patient's general condition was excellent, eradication of Helicobacter pylori was selected as the initial treatment. The lymphoma completely disappeared three months after the eradication treatment, and complete remission has been maintained for nearly two years.

  14. Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin.

    PubMed

    Roggero, E; Zucca, E; Mainetti, C; Bertoni, F; Valsangiacomo, C; Pedrinis, E; Borisch, B; Piffaretti, J C; Cavalli, F; Isaacson, P G

    2000-02-01

    Primary cutaneous B-cell lymphomas have been associated with Borrelia burgdorferi, the spirochete responsible for Lyme disease. Recently, cutaneous marginal zone B-cell lymphoma has been proposed as a distinct clinical-pathological entity. We report a case of primary cutaneous marginal zone lymphoma, associated with B burgdorferi infection. Polymerase chain reaction (PCR) amplification of the third complementarity determining region (CDR3) of the immunoglobulin heavy chain gene showed the presence of a monoclonal lymphoproliferation, therefore strengthening the histological diagnosis of a malignant process. B burgdorfer-specific hbb gene sequences were detected by PCR in the lymphoma tissue at diagnosis but not after antibiotic treatment. A nearly complete clinical and histological regression was observed after B burgdorferi eradication, with immunohistochemistry studies showing disappearance of plasma cell differentiation and a marked decline in the number of CD3+ T cells and Ki-67+ cells. Our case confirms the link between B burgdorferi and some cutaneous lymphomas. The disappearance of the microorganism accompanied by the unequivocal decrease of most indicators of active T- and B-cell immune response strongly supported a pathogenetic role for B burgdorferi in sustaining an antigen-driven development and growth of this cutaneous marginal zone lymphoma. Antibiotic therapy (analogous to Helicobacter pylori infection in gastric MALT lymphoma) might be helpful with the aim of averting or at least deferring the indication for more aggressive treatment.

  15. [Hodgkin and non-Hodgkin lymphoma of adolescents and young adults].

    PubMed

    Garciaz, Sylvain; Coso, Diane; Brice, Pauline; Bouabdallah, Réda

    2016-12-01

    Lymphoma is one of the most frequent cancers in adolescent and young adults. Hodgkin Lymphoma is curable in more than 90% of cases. Recent pediatric and adults protocols aimed to decrease long term toxicities (mostly gonadic and cardiovascular) and secondary malignancies, reducing the use of alkylating agents and limiting radiation fields. Risk-adapted strategies, using positron emission tomography staging, are about to become a standard, both in adult and pediatric protocols. These approaches allow obtaining excellent results in adolescents with Hodgkin lymphoma. On the other hand, treatment of adolescents with diffuse large B-cell lymphoma raises some questions. Even through children have good outcomes when treated with risk-adapted strategies, adolescents who are between 15 and 18 years old seem to experience poorer survivals, whereas patients older than 18 years old have globally the same outcome than older adults. This category of patient needs a particular care, based on a tight coordination between adults and pediatric oncologists. Primary mediastinal lymphomas, a subtype of BLDCL frequent in young adult population, exhibits poorer outcomes in children or young adolescent population than in older ones. Taking together, B-cell lymphoma benefited from recent advances in immunotherapy (in particular with the extended utilization of rituximab) and metabolic response-adapted strategies. In conclusion, adolescent and young adult's lymphomas are very curable diseases but require a personalized management in onco-hematological units. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  16. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study

    PubMed Central

    Hu, Shimin; Xu-Monette, Zijun Y.; Balasubramanyam, Aarthi; Manyam, Ganiraju C.; Visco, Carlo; Tzankov, Alexander; Liu, Wei-min; Miranda, Roberto N.; Zhang, Li; Montes-Moreno, Santiago; Dybkær, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W. L.; Han van Krieken, J.; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés J. M.; Zhao, Xiaoying; Winter, Jane N.; Zhang, Mingzhi; Li, Ling; Møller, Michael B.; Piris, Miguel A.; Li, Yong; Go, Ronald S.; Wu, Lin; Medeiros, L. Jeffrey; Young, Ken H.

    2013-01-01

    CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD30 expression in DLBCL is unknown. Here we report that CD30 expression is a favorable prognostic factor in a cohort of 903 de novo DLBCL patients. CD30 was expressed in ∼14% of DLBCL patients. Patients with CD30+ DLBCL had superior 5-year overall survival (CD30+, 79% vs CD30–, 59%; P = .001) and progression-free survival (P = .003). The favorable outcome of CD30 expression was maintained in both the germinal center B-cell and activated B-cell subtypes. Gene expression profiling revealed the upregulation of genes encoding negative regulators of nuclear factor κB activation and lymphocyte survival, and downregulation of genes encoding B-cell receptor signaling and proliferation, as well as prominent cytokine and stromal signatures in CD30+ DLBCL patients, suggesting a distinct molecular basis for its favorable outcome. Given the superior prognostic value, unique gene expression signature, and significant value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30+ DLBCL as a distinct subgroup of DLBCL. PMID:23343832

  17. Mechanisms regulating enhanced HLA class II-mediated CD4+ T cell recognition of human B-cell lymphoma by resveratrol

    PubMed Central

    RADWAN, FAISAL F. Y.; ZHANG, LIXIA; HOSSAIN, AZIM; DOONAN, BENTLY P.; GOD, JASON; HAQUE, AZIZUL

    2015-01-01

    Malignant B-cells express measurable levels of HLA class II proteins, but often escape immune recognition by CD4+ T cells. Resveratrol (Resv) has been the focus of numerous investigations due to its potential chemopreventive and anti-cancer effects, but it has never been tested in the regulation of immune components in B-cell tumors. Here, we show for the first time that Resv treatment enhances HLA class II-mediated immune detection of B-cell lymphomas by altering immune components and class II presentation in tumor cells. Resv treatment induced an upregulation of both classical and non-classical HLA class II proteins (DR and DM) in B-lymphoma cells. Resv also altered endolysosomal cathepsins (Cat S, B and D) and a thiol reductase (GILT), increasing HLA class II-mediated antigen (Ag) processing in B-cell lymphomas and their subsequent recognition by CD4+ T cells. Mechanistic study demonstrated that Resv treatment activated the recycling class II pathway of Ag presentation through upregulation of Rab 4B protein expression in B-lymphoma cells. These findings suggest that HLA class II-mediated immune recognition of malignant B-cells can be improved by Resv treatment, thus encouraging its potential use in chemoimmunotherapy of B-cell lymphoma. PMID:21854084

  18. Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma.

    PubMed

    Kuo, Hsu-Ping; Ezell, Scott A; Schweighofer, Karl J; Cheung, Leo W K; Hsieh, Sidney; Apatira, Mutiah; Sirisawad, Mint; Eckert, Karl; Hsu, Ssucheng J; Chen, Chun-Te; Beaupre, Darrin M; Versele, Matthias; Chang, Betty Y

    2017-07-01

    Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton tyrosine kinase (BTK)-mediated B-cell receptor signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and follicular lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy. Mol Cancer Ther; 16(7); 1246-56. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Adult high-grade B-cell lymphoma with Burkitt lymphoma signature: genomic features and potential therapeutic targets.

    PubMed

    Bouska, Alyssa; Bi, Chengfeng; Lone, Waseem; Zhang, Weiwei; Kedwaii, Ambreen; Heavican, Tayla; Lachel, Cynthia M; Yu, Jiayu; Ferro, Roberto; Eldorghamy, Nanees; Greiner, Timothy C; Vose, Julie; Weisenburger, Dennis D; Gascoyne, Randy D; Rosenwald, Andreas; Ott, German; Campo, Elias; Rimsza, Lisa M; Jaffe, Elaine S; Braziel, Rita M; Siebert, Reiner; Miles, Rodney R; Dave, Sandeep; Reddy, Anupama; Delabie, Jan; Staudt, Louis M; Song, Joo Y; McKeithan, Timothy W; Fu, Kai; Green, Michael; Chan, Wing C; Iqbal, Javeed

    2017-10-19

    The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24, and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes. Mutations in genes promoting the tonic B-cell receptor (BCR)→PI3K pathway ( TCF3 and ID3 ) did not differ by age, whereas effectors of chronic BCR→NF-κB signaling were associated with adult-mBL. A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation profile similar to mBL. These double-hit lymphomas may have arisen from a tumor precursor that acquired both BCL2 and MYC translocations and/or KMT2D ( MLL2 ) mutation. Gain/amplification of MIR17HG and its paralogue loci was observed in 50% of adult-mBL. In vitro studies suggested miR-17∼92 's role in constitutive activation of BCR signaling and sensitivity to ibrutinib. Overall integrative analysis identified an interrelated gene network affected by copy number and mutation, leading to disruption of the p53 pathway and the BCR→PI3K or NF-κB activation, which can be further exploited in vivo by small-molecule inhibitors for effective therapy in adult-mBL.

  20. Homing of human B cells to lymphoid organs and B-cell lymphoma engraftment are controlled by cell adhesion molecule JAM-C.

    PubMed

    Doñate, Carmen; Ody, Christiane; McKee, Thomas; Ruault-Jungblut, Sylvie; Fischer, Nicolas; Ropraz, Patricia; Imhof, Beat A; Matthes, Thomas

    2013-01-15

    Junctional adhesion molecule C (JAM-C) is expressed by vascular endothelium and human but not mouse B lymphocytes. The level of JAM-C expression defines B-cell differentiation stages and allows the classification of marginal zone-derived (JAM-C-positive) and germinal center-derived (JAM-C-negative) B-cell lymphomas. In the present study, we investigated the role of JAM-C in homing of human B cells, using a xenogeneic nonobese diabetic/severe combined immunodeficient mouse model. Treatment with anti-JAM-C antibodies in short-term experiments reduced migration of normal and malignant JAM-C-expressing B cells to bone marrow, lymph nodes, and spleen. Blocking homing to the spleen is remarkable, as most other antiadhesion antibodies reduce homing of B cells only to bone marrow and lymph nodes. Long-term administration of anti-JAM-C antibodies prevented engraftment of JAM-Cpos lymphoma cells in bone marrow, spleen, and lymph nodes of mice. Plasmon resonance studies identified JAM-B as the major ligand for JAM-C, whereas homotypic JAM-C interactions remained at background levels. Accordingly, anti-JAM-C antibodies blocked adhesion of JAM-C-expressing B cells to their ligand JAM-B, and immunofluorescence analysis showed the expression of JAM-B on murine and human lymphatic endothelial cells. Targeting JAM-C could thus constitute a new therapeutic strategy to prevent lymphoma cells from reaching supportive microenvironments not only in the bone marrow and lymph nodes but also in the spleen.

  1. Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma.

    PubMed

    Inaba, Koji; Kushima, Ryoji; Murakami, Naoya; Kuroda, Yuuki; Harada, Ken; Kitaguchi, Mayuka; Yoshio, Kotaro; Sekii, Shuhei; Takahashi, Kana; Morota, Madoka; Mayahara, Hiroshi; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun

    2013-10-26

    There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

  2. Epidermotropic presentation by splenic B-cell lymphoma: The importance of clinical-pathologic correlation.

    PubMed

    Hedayat, Amin A; Carter, Joi B; Lansigan, Frederick; LeBlanc, Robert E

    2018-04-01

    There are exceedingly rare reports of patients with epidermotropic B-cell lymphomas. A subset presented with intermittent, variably pruritic papular eruptions and involvement of their spleens, peripheral blood and bone marrow at the time of diagnosis. Furthermore, some experienced an indolent course despite dissemination of their lymphomas. We report a 66-year-old woman with a 12-year history of intermittent eruptions of non-pruritic, salmon-colored papules on her torso and proximal extremities that occurred in winter and resolved with outdoor activity in spring. Skin biopsy revealed an epidermotropic B-cell lymphoma with a non-specific B-cell phenotype and heavy chain class switching with IgG expression. On workup, our patient exhibited mild splenomegaly and low-level involvement of her peripheral blood and bone marrow by a kappa-restricted B-cell population. A splenic B-cell lymphoma was diagnosed. Considering her longstanding history and absences of cytopenias, our patient has been followed without splenectomy or systemic therapy. Furthermore, the papules have responded dramatically to narrowband UVB. Our case and a review of similar rare reports aim to raise awareness among dermatopathologists and dermatologists of a clinically distinct and indolent subset of epidermotropic splenic lymphomas with characteristic clinical and histologic findings. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. The association of selected cancers with service in the US military in Vietnam. I. Non-Hodgkin's lymphoma. The Selected Cancers Cooperative Study Group (see comments)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1990-12-01

    As part of a series of investigations into the health of Vietnam veterans, we conducted a population-based, case-control study of non-Hodgkin's lymphoma between 1984 and 1988. All men born between 1929 and 1953 and diagnosed as having non-Hodgkin's lymphoma in an area covered by eight cancer registries were considered eligible. Control subjects were identified by random-digit dialing from these same regions and were frequency-matched to men with lymphoma by age. Analyses of 1157 men with pathologically confirmed lymphomas and 1776 control subjects showed that the risk of non-Hodgkin's lymphoma was approximately 50% higher among Vietnam veterans (odds ratio, 1.47; 95%more » confidence interval, 1.1 to 2.0) compared with men who did not serve in Vietnam. Vietnam veterans were also at higher risk relative to (1) men who had not served in the military, (2) other veterans, and (3) other veterans who served between 1964 and 1972. An analysis of the military histories of the 232 Vietnam veterans suggested that the relative risk (1) increased with length of service in Vietnam (P = .10), and (2) was higher among men in the sea-based Navy than among other veterans (P = .11). Little difference in risk, however, was noted according to dates of service, type of unit, military region, or any other characteristics that may have been associated with the use of Agent Orange. Although the cause remains uncertain, results of this study indicate that the risk of non-Hodgkin's lymphoma is higher among Vietnam veterans than among other men.« less

  4. Rare gastrointestinal lymphomas: The endoscopic investigation

    PubMed Central

    Vetro, Calogero; Bonanno, Giacomo; Giulietti, Giorgio; Romano, Alessandra; Conticello, Concetta; Chiarenza, Annalisa; Spina, Paolo; Coppolino, Francesco; Cunsolo, Rosario; Raimondo, Francesco Di

    2015-01-01

    Gastrointestinal lymphomas represent up to 10% of gastrointestinal malignancies and about one third of non-Hodgkin lymphomas. The most prominent histologies are mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma. However, the gastrointestinal tract can be the site of rarer lymphoma subtypes as a primary or secondary localization. Due to their rarity and the multifaceted histology, an endoscopic classification has not been validated yet. This review aims to analyze the endoscopic presentation of rare gastrointestinal lymphomas from disease diagnosis to follow-up, according to the involved site and lymphoma subtype. Existing, new and emerging endoscopic technologies have been examined. In particular, we investigated the diagnostic, prognostic and follow-up endoscopic features of T-cell and natural killer lymphomas, lymphomatous polyposis and mantle cell lymphoma, follicular lymphoma, plasma cell related disease, gastrointestinal lymphomas in immunodeficiency and Hodgkin’s lymphoma of the gastrointestinal tract. Contrarily to more frequent gastrointestinal lymphomas, data about rare lymphomas are mostly extracted from case series and case reports. Due to the data paucity, a synergism between gastroenterologists and hematologists is required in order to better manage the disease. Indeed, clinical and prognostic features are different from nodal and extranodal or the bone marrow (in case of plasma cell disease) counterpart. Therefore, the approach should be based on the knowledge of the peculiar behavior and natural history of disease. PMID:26265987

  5. Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

    PubMed

    Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

    2015-10-01

    Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without

  6. Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Neelis, Karen J.; Schimmel, Erik C.; Vermeer, Maarten H.

    Purpose: To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). Methods and Materials: A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. Results: The complete response rate for CBCL lesions was 72%. Of themore » 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Conclusion: Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.« less

  7. High-dose ifosfamide in combination with etoposide and epirubicin (IVE) in the treatment of relapsed/refractory Hodgkin's disease and non-Hodgkin's lymphoma: a report on toxicity and efficacy.

    PubMed

    Proctor, S J; Taylor, P R; Angus, B; Wood, K; Lennard, A L; Lucraft, H; Carey, P J; Stark, A; Iqbal, A; Haynes, A; Russel, N; Leonard, R C; Culligan, D; Conn, J; Jackson, G H

    2001-07-01

    One hundred and seven patients (61 with diffuse large B-cell non-Hodgkin's lymphomas and 46 with Hodgkin's disease) in relapse or following of primary therapy received ifosfamide 3 g/m2 i.v. daily for 3 days in combination with epirubicin 50 mg/m2 i.v. day 1 and etoposide 200 mg/m2 i.v. days 1-3. Of the 46 patients with Hodgkin's disease (28 male, 18 female, and a median age of 28 years) 85% of patients had a response to treatment, with 17 achieving complete remission and 11 good partial remission. Twenty-eight proceeded to autologous bone marrow or peripheral blood stem cell transplantation. Twenty-three patients remain alive in continuous remission with a follow-up of 12-61 months. The median overall survival time for all patients in this group is 36 months. Haematological toxicity, particularly WHO Grade IV neutropenia, occurred in all patients but improved over the three courses of treatment. There was no major non-haematological toxicity. Further trials of this regimen in this clinical situation are indicated. The patients with non-Hodgkin's lymphomas in this study had diffuse large B-cell lymphomas and had only received first-line treatment. Twenty had primarily refractory disease, 15 had only achieved partial remissions (PR), and 26 had developed relapse following primary treatment. The overall response rate was 43%; it was 60% for those who had achieved initial PR, 58% for those in relapse after an initial CR or very good PR following initial therapy, but only 10% for those with primarily refractory disease. Tolerance to the regimen was similar to that observed in treatment of the patients with Hodgkin's disease and many were able to undergo stem cell collection, following mobilization with this regimen. The 2-year overall survival result was 22% for patients with some response to first-line treatment but 0% for primary refractory patients.

  8. Magnetic resonance imaging with pathological correlation in a case of mantle cell lymphoma of the parotid gland: a case report

    PubMed Central

    2010-01-01

    Introduction Mantle cell lymphoma is a rare non-Hodgkin's lymphoma. It is a subtype of B-cell lymphoma with frequent involvement of the bone marrow and the gastrointestinal tract. Isolated parotid gland involvement seldom occurs. Here we report an unusual case of isolated infiltration of the parotid gland by mantle cell lymphoma. The aim of our study is to correlate magnetic resonance imaging findings with the histological features of the disease. To the best of our knowledge, no similar radiological findings of mantle cell lymphoma have been published before. Case presentation A 72-year-old Caucasian woman presented with a painful left parotid enlargement. She was diagnosed with mantle cell lymphoma involving the left submandibular gland seven years prior to presentation. Her whole body CT scan showed the absence of pathologically enlarged lymph nodes. However, a magnetic resonance imaging showed enlargement of her left parotid gland and an abnormal parenchyma with mixed-type solid and cystic lesions. A biopsy of her left parotid gland and subsequent histological examination confirmed a mantle cell lymphoma (common variant) relapse. Conclusion Although rare, the involvement of parotid gland with mantle cell lymphoma must be considered in the differential diagnosis of parotid tumors. PMID:20350332

  9. Comparison of clinical outcome after autologous stem cell transplantation between patients with peripheral T-cell lymphomas and diffuse large B-cell lymphoma.

    PubMed

    Sohn, B S; Park, I; Kim, E K; Yoon, D H; Lee, S S; Kang, B W; Jang, G; Choi, Y H; Kim, C; Lee, D H; Kim, S; Huh, J; Suh, C

    2009-09-01

    Although patients with T-cell phenotype lymphomas are generally accepted to have worse prognosis than B-cell phenotype lymphomas, the studies comparing outcomes after autologous stem cell transplantation (ASCT) between peripheral T-cell lymphomas (PTCLs) and with diffuse large B-cell lymphoma (DLBCL) are few. In this study, we compared outcomes after ASCT between 23 patients with PTCLs and 54 patients with DLBCL. Univariate analysis showed that the timing of ASCT, complete response (CR) at ASCT, favorable lactate dehydrogenase/performance/stage, low/low-intermediate (L-LI) International Prognostic Index (IPI) and L-LI age-adjusted IPI (aaIPI) at ASCT were significant predictors of both OS and EFS. Multivariate analysis showed that CR and L-LI aaIPI at ASCT were favorable for both OS (hazard ratio (HR), 0.34; 95% CI, 0.14-0.81; P=0.016 and HR, 0.27; 95% CI, 0.12-0.57; P=0.001) and EFS (HR, 0.38; 95% CI, 0.17-0.85; P=0.020 and HR, 0.36; 95% CI, 0.17-0.77; P=0.008). B-cell or T-cell phenotype, however, had no impact on OS (HR, 0.56; 95% CI, 0.27-1.18; P=0.126) or EFS (HR, 0.62; 95% CI, 0.30-1.30; P=0.206). In conclusion, when compared to patients with DLBCL, patients with PTCLs did not have inferior outcomes after ASCT. T-cell phenotype itself may not have an effect on outcomes of PTCL patients who underwent ASCT.

  10. Cytokine signaling pathway polymorphisms and AIDS-related non-Hodgkin lymphoma risk in the Multicenter AIDS Cohort Study

    PubMed Central

    Wong, Hui-Lee; Breen, Elizabeth C.; Pfeiffer, Ruth M.; Aissani, Brahim; Martinson, Jeremy J.; Margolick, Joseph B.; Kaslow, Richard A.; Jacobson, Lisa P.; Ambinder, Richard F.; Chanock, Stephen; Martínez-Maza, Otoniel; Rabkin, Charles S.

    2014-01-01

    Cytokine stimulation of B-cell proliferation may be an important etiologic mechanism for acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). The Epstein-Barr virus may be a co-factor, particularly for primary central nervous system (CNS) tumors, which are uniformly EBV-positive in the setting of AIDS. Thus, we examined associations of genetic variation in IL10 and related cytokine signaling molecules (IL10RA, CXCL12, IL13, IL4, IL4R, CCL5 and BCL6) with AIDS-related NHL risk and evaluated differences between primary CNS and systemic tumors. We compared 160 Multicenter AIDS Cohort Study (MACS) participants with incident lymphomas, of which 90 followed another AIDS diagnosis, to HIV-1-seropositive controls matched on duration of lymphoma-free survival post-HIV-1 infection (N=160) or post-AIDS diagnosis (N=90). We fit conditional logistic regression models to estimate odds ratios (ORs) and 95 percent confidence intervals (95%CIs). Carriage of at least one copy of the T allele for the IL10 rs1800871 (as compared to no copies) was associated with decreased AIDS-NHL risk specific to lymphomas arising from the CNS (CC vs. CT/TT: OR=0.3; 95%CI: 0.1, 0.7) but not systemically (CC vs. CT/TT: OR=1.0; 95%CI: 0.5, 1.9) (Pheterogeneity=0.03). Carriage of two copies of the “low IL10” haplotype rs1800896_A/rs1800871_T/rs1800872_A was associated with decreased lymphoma risk that varied by number of copies (Ptrend=0.02). None of the ORs for the other studied polymorphisms was significantly different from 1.0. Excessive IL10 response to HIV-1 infection may be associated with increased risk of NHL, particularly in the CNS. IL10 dysregulation may be an important etiologic pathway for EBV-related lymphomagenesis. PMID:20299965

  11. Non-Hodgkin's lymphomas of the tonsil: a retrospective analysis of twenty-eight patients with primary tonsillary lymphoma.

    PubMed

    Barişta, I; Tekuzman, G; Güllü, I; Baltali, E; Kars, A; Ozişik, Y; Güler, N; Celik, I; Atahan, I L; Firat, D

    1995-01-01

    To analyze the clinical and therapeutic aspects of patients with primary tonsillary non-Hodgkin's lymphoma. Twenty-eight patients with primary tonsillary non-Hodgkin's lymphoma who had been followed in the Hacettepe Oncology Institute between 1974 and 1992 were retrospectively analyzed. Fifteen patients were male, 13 were female. Median age was 55 years. Constitutional symptoms were present in 10 patients (35.7%). Stages according to the Ann Arbor classification were I and II in 12 and 16 patients, respectively. According to the Rappaport classification, poorly differentiated lymphocytic was the most common pathologic subgroup (42.9%). Grades according to the Working Formulation were low, intermediate and high in 3, 22 and 3 patients, respectively. Twenty-two patients had received chemotherapy. Cyclophosphamide, vincristine and prednisone (CVP), and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were the regimens most commonly employed. Eighteen patients received radiotherapy to Waldeyer's ring and neck. Eight patients achieved remission with chemotherapy plus radio-therapy, 7 patients with chemotherapy alone, and 5 patients with radiotherapy alone. In addition to the 20 patients who achieved complete remission, 3 patients achieved partial remission; the overall response rate was 82.1%. The response rates and survival attained with the combined modality, chemotherapy, or radiotherapy alone were not statistically different (P > 0.05). The median follow-up was 14 months. Overall and disease-free survival at 5 years were 62.6% and 77.6%, respectively. Pathologic grade was the most important prognostic factor influencing overall survival in the Cox multivariate model. Poorly differentiated lymphocytic lymphomas were the most common pathologic subtype, and pathologic grade was the most important prognostic factor to influence survival in the present study. Although combined modality treatment did not appear to be superior to chemotherapy or

  12. Cholecalciferol in Improving Survival in Patients With Newly Diagnosed Cancer With Vitamin D Insufficiency

    ClinicalTrials.gov

    2017-07-06

    Aggressive Non-Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Hepatosplenic T-Cell Lymphoma; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Nasal Type Extranodal NK/T-Cell Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Primary Cutaneous Anaplastic Large Cell Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Small Lymphocytic Lymphoma; Subcutaneous Panniculitis-Like T-Cell Lymphoma

  13. Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)

    ClinicalTrials.gov

    2018-06-27

    B-Cell Chronic Lymphocytic Leukemia; Monoclonal B-Cell Lymphocytosis; Lymhoma, Small Lymphocytic; Chronic Lymphocytic Leukemia; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Splenic Marginal Zone Lymphoma

  14. Early diagnosis of an isolated primary peripheral T-cell lymphoma masquerading as massive gingival enlargement in a pediatric patient

    PubMed Central

    Ghattamaneni, Sravani; Guttikonda, Venkateswara Rao; Yeluri, Sivaranjani; Kolipara, Rajani

    2017-01-01

    Lymphomas are malignant neoplasm of the lymphocyte cell lines, classified as either Hodgkin's or non-Hodgkin's lymphoma (NHL). NHL comprises a heterogeneous group of lymphoid neoplasm arising from B-cell, T-cell or natural killer cell with a spectrum of behavior ranging from relatively indolent to highly aggressive and potentially fatal. Peripheral T-cell lymphoma, a variant of NHL, is a disease characterized by the presence of diffuse lymphadenopathy, extranodal involvement, classical B symptoms such as fever (>100.4°F) for 3 consecutive days, weight loss exceeding 10% of body weight in 6 months and drenching night sweats with a tendency for recurrence. Among NHLs, extranodal presentations are relatively common. Extranodal presentation particularly in the oral cavity is very rare and may misinterpret the diagnosis. Lesions of this type should be cautiously dealt especially in pediatric patients and young adolescents. The present case report is about an atypical presentation of disease process in a 15-year-old male patient, which was diagnosed early with the help of a combination of histopathology and immunohistochemistry techniques. PMID:29391718

  15. [Bilateral ovarian Burkitt's lymphoma. A case presentation].

    PubMed

    Briseño-Hernández, Andrés Alejandro; Quezada-López, Deissy Roxana; Castañeda-Chávez, Agar; Dassaejv Macías-Amezcua, Michel; Pintor-Belmontes, Julio Cesar

    2014-01-01

    Burkitt lymphoma, is described as an aggressive form of non-Hodgkin lymphoma of B cells which occurs most often in children and young adults, ovarian lymphoma can appear as a primary lesion or more commonly referred to as a metastasis. Primary ovarian lesions are rare manifestations corresponding to 0.5% of non-Hodgkin lymphoma and 1.5% of ovarian tumors. Clinic case: 31 years old female with general weakness, march incapacity, dyspnea, hyporexia, fever, diaphoresis, weight loss of 20 kg, flat abs with abdominal pain; Ca125 610 U/ml. Abdominal computed tomography shows a solid aspect tumor which affects the right pelvic cavity. Bilateral ovarian tumors were removed. Microscopically, both lesions show a "starry sky" pattern composed by a monotonous infiltration of lymphocytes mixed with large and clear macrophages, several atypical mitoses, and necrosis and hemorrhage areas. Immunohistochemistry was positive for CD10, CD20, and negative for CD3 and high Ki67 proliferation index. Bilateral ovarian Burkitt's lymphoma was diagnosed. Bilateral ovarian Burkitt's lymphoma is a rare entity, with a variability of presentations, the abdominal pain and abdominal tumors are the most frequent. The patient's prognosis at short term is poor, therefore it's necessary to know this entity and make an early diagnosis.

  16. Birth order and sibship size: evaluation of the role of selection bias in a case-control study of non-Hodgkin's lymphoma.

    PubMed

    Mensah, F K; Willett, E V; Simpson, J; Smith, A G; Roman, E

    2007-09-15

    Substantial heterogeneity has been observed among case-control studies investigating associations between non-Hodgkin's lymphoma and familial characteristics, such as birth order and sibship size. The potential role of selection bias in explaining such heterogeneity is considered within this study. Selection bias according to familial characteristics and socioeconomic status is investigated within a United Kingdom-based case-control study of non-Hodgkin's lymphoma diagnosed during 1998-2001. Reported distributions of birth order and maternal age are each compared with expected reference distributions derived using national birth statistics from the United Kingdom. A method is detailed in which yearly data are used to derive expected distributions, taking account of variability in birth statistics over time. Census data are used to reweight both the case and control study populations such that they are comparable with the general population with regard to socioeconomic status. The authors found little support for an association between non-Hodgkin's lymphoma and birth order or family size and little evidence for an influence of selection bias. However, the findings suggest that between-study heterogeneity could be explained by selection biases that influence the demographic characteristics of participants.

  17. Characterization of B cell lymphoma in patients with Sjögren's syndrome and hepatitis C virus infection.

    PubMed

    Ramos-Casals, Manuel; la Civita, Luca; de Vita, Salvatore; Solans, Roser; Luppi, Mario; Medina, Francisco; Caramaschi, Paola; Fadda, Patrizia; de Marchi, Ginevra; Lopez-Guillermo, Armando; Font, Josep

    2007-02-15

    To characterize the clinical and immunologic patterns of expression, response to therapy, and outcome of patients with Sjögren's syndrome (SS) and associated hepatitis C virus (HCV) infection who developed B cell lymphoma. Various international reference centers constituted a multicenter study group with the purpose of creating a registry of patients with SS-HCV who developed B cell lymphoma. A protocol form was used to record the main characteristics of SS, chronic HCV infection, and B cell lymphoma. Twenty-five patients with SS-HCV with B cell lymphoma were included in the registry. There were 22 (88%) women and 3 (12%) men (mean age 55, 58, and 61 years at SS, HCV infection, and lymphoma diagnosis, respectively). The main extraglandular SS manifestations were cutaneous vasculitis in 15 (60%) patients and peripheral neuropathy in 12 (48%); the main immunologic features were positive rheumatoid factor (RF) in 24 (96%) and type II cryoglobulins in 20 (80%). The main histologic subtypes were mucosa-associated lymphoid tissue (MALT) lymphoma in 11 (44%) patients, diffuse large B cell lymphoma in 6 (24%), and follicular center cell lymphoma in 6 (24%). Fifteen (60%) patients had an extranodal primary location, most frequently in the parotid gland (5 patients), liver (4 patients), and stomach (4 patients). Twelve (52%) of 23 patients died after a median followup from the time of lymphoma diagnosis of 4 years, with lymphoma progression being the most frequent cause of death. Survival differed significantly between the main types of B cell lymphoma. Patients with SS-HCV and B cell lymphoma are clinically characterized by a high frequency of parotid enlargement and vasculitis, an immunologic pattern overwhelmingly dominated by the presence of RF and mixed type II cryoglobulins, a predominance of MALT lymphomas, and an elevated frequency of primary extranodal involvement in organs in which HCV replicates (exocrine glands, liver, and stomach).

  18. Non-Hodgkin's lymphoma is a pathological lead point causing large gut (colo-colic varity) intussusception.

    PubMed

    Saha, N; Ferdous, K N; Rahman, M A; Islam, M K

    2012-04-01

    Intussusception secondary to Primary Non-Hodgkin lymphoma presenting colo-colic variety is a very rare clinical entity and sometimes causing diagnostic dilemma due to non-specific, varied & wide spectrum presentation. In this study, a 9 years female child presented with recurrent, intermittent, colicky abdominal pain with occasional bilious vomiting, along with a left illiac fossa swelling & occasional per rectal bleeding and constipation for 3 months was clinically diagnosed as a case of recurrent obstructing intussusception. At laparotomy, a colo-colic intussusception with prolapsed intussusception was marked & finally on histopathology, she was diagnosed as a case of colo-colic variety of intussusception due to primary Non-Hodgkin lymphoma- a pathological lead point in mid transverse colon. After uneventful recovery of post operative period she was treated with combination chemotherapy accordingly & follow up was given up to 5 years. She had been found alright without any recurrence or organ involvement. The study focused on the avoidance of unusual delay in diagnosis as well as in proper management of rare variants of intussusception.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chan, Elisa K.; Fung, Sharon; Gospodarowicz, Mary

    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 patientmore » 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.« less

  20. Tanovea® for the treatment of lymphoma in dogs.

    PubMed

    De Clercq, Erik

    2018-05-17

    Tanovea® (first named GS-9219, then VDC-1101, generic name: rabacfosadine) is a pro-prodrug or "double" prodrug of PMEG [9-(2-phosphonylmethoxyethyl)guanine], which has been conditionally approved by the US FDA (Food and Drug Administration) for the treatment of lymphoma in dogs. Tanovea has been demonstrated to be effective against non-Hodgkin's lymphoma (NHL) in dogs, as well as canine cutaneous T-cell lymphoma, spontaneous canine multiple myeloma, naïve canine multicentric lymphoma and relapsed canine B-cell lymphoma. As a double prodrug of PMEG, GS-9219 is first converted intracellularly by hydrolysis to cPr-PMEDAP, then deaminated to PMEG, which is then phosphorylated twice to its active metabolite PMEGpp, acting at the level of the cellular DNA polymerases. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Combination Chemotherapy and Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2017-07-07

    Anaplastic Large Cell Lymphoma, ALK-Negative; Anaplastic Large Cell Lymphoma, ALK-Positive; Hepatosplenic T-Cell Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Stage II Angioimmunoblastic T-cell Lymphoma; Stage II Enteropathy-Associated T-Cell Lymphoma; Stage III Angioimmunoblastic T-cell Lymphoma; Stage III Enteropathy-Associated T-Cell Lymphoma; Stage IV Angioimmunoblastic T-cell Lymphoma; Stage IV Enteropathy-Associated T-Cell Lymphoma

  2. A phase 1/2 trial of ublituximab, a novel anti-CD20 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma or chronic lymphocytic leukaemia previously exposed to rituximab.

    PubMed

    Sawas, Ahmed; Farber, Charles M; Schreeder, Marshall T; Khalil, Mazen Y; Mahadevan, Daruka; Deng, Changchun; Amengual, Jennifer E; Nikolinakos, Petros G; Kolesar, Jill M; Kuhn, John G; Sportelli, Peter; Miskin, Hari P; O'Connor, Owen A

    2017-04-01

    This phase 1/2 study evaluated the safety, pharmacokinetic behavior and anti-tumour activity of ublituximab, a unique type I, chimeric, glycoengineered anti-CD20 monoclonal antibody, in rituximab-relapsed or -refractory patients with B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukaemia (CLL). Induction therapy (doses of 450-1200 mg) consisted of 4 weekly infusions in cycle 1 for NHL and 3 weekly infusions in cycles 1 and 2 for CLL. Patients received ublituximab maintenance monthly during cycles 3-5, then once every 3 months for up to 2 years. Enrolled patients with B-NHL (n = 27) and CLL (n = 8) had a median of 3 prior therapies. No dose-limiting toxicities or unexpected adverse events (AEs) occurred. The most common AEs were infusion-related reactions (40%; grade 3/4, 0%); fatigue (37%; grade 3/4, 3%); pyrexia (29%; grade 3/4, 0%); and diarrhoea (26%; grade 3/4, 0%). Common haematological AEs were neutropenia (14%; grade 3/4, 14%) and anaemia (11%; grade 3/4, 6%). The overall response rate for evaluable patients (n = 31) was 45% (13% complete responses, 32% partial responses). Median duration of response and progression-free survival were 9·2 months and 7·7 months, respectively. Ublituximab was well-tolerated and efficacious in a heterogeneous and highly rituximab-pre-treated patient population. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  3. Combination of Pim kinase inhibitor SGI-1776 and bendamustine in B-cell lymphoma.

    PubMed

    Yang, Qingshan; Chen, Lisa S; Neelapu, Sattva S; Gandhi, Varsha

    2013-09-01

    SGI-1776 is a small-molecule Pim kinase inhibitor that primarily targets c-MYC-driven transcription and cap-dependent translation in mantle cell lymphoma (MCL) cells. Bendamustine is an alkylating chemotherapeutic agent approved for use in B-cell lymphoma that is known to induce DNA damage and initiate response to repair. Our studies were conducted in MCL cell lines JeKo-1 and Mino, as well as primary B-cell lymphoma samples of MCL and splenic marginal zone lymphoma (SMZL), where we treated cells with SGI-1776 and bendamustine. We measured levels of cellular apoptosis, macromolecule synthesis inhibition, and DNA damage induced by drug treatments. Both SGI-1776 and bendamustine effectively induced apoptosis as single agents, and when used in combination, an additive effect in cell killing was observed in MCL cell lines JeKo-1 and Mino, as well as in MCL and SMZL primary cells. As expected, SGI-1776 was effective in inducing a decrease of global RNA and protein synthesis, and bendamustine significantly inhibited DNA synthesis and generated a DNA damage response. When used in combination, the effects were intensified in DNA, RNA, and protein synthesis inhibition compared with single-agent treatments. These data provide a foundation and suggest the feasibility of using Pim kinase inhibitors in combination with chemotherapeutic agents such as bendamustine in B-cell lymphoma. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Molecular Pathogenesis of MALT Lymphoma

    PubMed Central

    Troppan, Katharina; Wenzl, Kerstin; Neumeister, Peter; Deutsch, Alexander

    2015-01-01

    Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT), also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis. PMID:25922601

  5. International Lymphoma Epidemiology Consortium

    Cancer.gov

    The InterLymph Consortium, or formally the International Consortium of Investigators Working on Non-Hodgkin's Lymphoma Epidemiologic Studies, is an open scientific forum for epidemiologic research in non-Hodgkin's lymphoma.

  6. Primary B-Cell Lymphoma of Submandibular Lymph Node in a Water Deer ( Hydropotes inermis ).

    PubMed

    Park, Surim; Roh, Yoon Seok; Kim, Eun Ju; Lee, Hae Beom; Choi, Ul Soo; Kang, Seog Jin; Lim, Chae Woong; Kim, Bumseok

    2016-04-28

    We describe a B-cell lymphoma of a submandibular lymph node with metastasis to the lung and facial subcutaneous tissues in a water deer ( Hydropotes inermis ). Neoplastic cells contained pleomorphic lymphocytes that were positive for CD79a, consistent with B-cell lymphoma. PCR for bovine leukemia virus was negative.

  7. Small cell lymphocytic variant of marginal zone lymphoma: A distinct form of marginal zone lymphoma derived from naïve B cells as a cutaneous counterpart to the naïve marginal zone lymphoma of splenic origin.

    PubMed

    Magro, Cynthia M; Olson, Luke C

    2018-02-21

    Primary cutaneous marginal zone lymphoma most commonly represents an indolent form of cutaneous B cell lymphoma. However, epidermotropic marginal zone lymphoma, blastic marginal zone lymphoma and B cell dominant variants without isotype switching can be associated with extracutaneous dissemination. The presumptive cell of origin is a post germinal center B cell with plasmacytic features. In the extracutaneous setting, however, a naïve B cell origin has been proposed for a subset of marginal zone lymphomas, notably splenic marginal zone lymphoma. The author encountered 11 cases of atypical lymphocytic infiltration of the skin primarily occurring in older individuals with an upper arm and head and neck localization; there was a reproducible pattern of diffuse and nodular infiltration by small monomorphic-appearing B cells. Phenotypically, the infiltrate was one predominated by B cells exhibiting CD23 and IgD positivity without immunoreactivity for CD38 and there were either no plasma cells or only a few without light chain restriction. In cases presenting with a solitary lesion complete excision and/or radiation led to successful disease remission in all cases without recurrence or metastatic disease. Of three cases with multiple initial lesions, evidence of extracutaneous disease was seen in two cases and recurrence occurred in one case. No patients have died of lymphoma. Longer term follows up and additional cases are needed to determine if this subset of marginal zone lymphoma is associated with a worse prognosis. Copyright © 2018. Published by Elsevier Inc.

  8. Fundamentals of the management of non-Hodgkin lymphoma.

    PubMed

    Fadilah, S A W

    2009-12-01

    The incidence of Non-Hodgkin's lymphomas (NHL) is rising worldwide and if not adequately treated carries a high mortality rate. The pattern and frequency of NHL vary in different populations and geographical regions. It has considerable biologic and clinical heterogeneity and a definitive diagnosis can be made only after histopathogical examination. The histology and the extent of the lymphoma are the major determinants of optimal therapeutic regimen and treatment outcome. Additionally, the overall treatment strategies should be tailored according to medical status and preference of the patient. A holistic approach provided by a multi-disciplinary team of health care professionals is the cornerstone of ensuring successful treatment outcome. Importantly, therapy should be expedited and where possible performed in experienced centers. Patients achieving remission would require long-term monitoring for disease recurrence and late effects of cytotoxic chemotherapy and radiotherapy. Hence, clinicians should have a fundamental understanding in the biology and the principles of treatment of NHL. This review provides an evidence-based and systematic approach in designing therapeutic strategies for individual patients with newly diagnosed and relapsed NHL focusing on the common types of NHL with particular reference to the current practice within the local settings. The role of standard and novel therapeutic modalities in treatment will be summarized.

  9. Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in diffuse large B-cell lymphoma.

    PubMed

    Kinowaki, Yuko; Kurata, Morito; Ishibashi, Sachiko; Ikeda, Masumi; Tatsuzawa, Anna; Yamamoto, Masahide; Miura, Osamu; Kitagawa, Masanobu; Yamamoto, Kouhei

    2018-02-20

    Regulation of oxidative stress and redox systems has important roles in carcinogenesis and cancer progression, and for this reason has attracted much attention as a new area of cancer therapeutic targets. Glutathione peroxidase 4 (GPX4), an antioxidant enzyme, has biological important functions such as signaling cell death by suppressing peroxidation of membrane phospholipids. However, few studies exist on the expression and clinical relevance of GPX4 in malignant lymphomas such as diffuse large B-cell lymphoma. In this study, we assessed the expression of GPX4 immunohistochemically. GPX4 was expressed in 35.5% (33/93) cases of diffuse large B-cell lymphoma. The GPX4-positive group had poor overall survival (P = 0.0032) and progression-free survival (P = 0.0004) compared with those of the GPX4-negative group. In a combined analysis of GPX4 and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, there was a negative correlation between GPX4 and 8-hydroxydeoxyguanosine (P = 0.0009). The GPX4-positive and 8-hydroxydeoxyguanosine-negative groups had a significantly worse prognosis than the other groups in both overall survival (P = 0.0170) and progression-free survival (P = 0.0005). These results suggest that the overexpression of GPX4 is an independent prognostic predictor in diffuse large B-cell lymphoma. Furthermore, in vitro analysis demonstrated that GPX4-overexpressing cells were resistant to reactive oxygen species-induced cell death (P = 0.0360). Conversely, GPX4-knockdown cells were sensitive to reactive oxygen species-induced cell death (P = 0.0111). From these data, we conclude that GPX4 regulates reactive oxygen species-induced cell death. Our results suggest a novel therapeutic strategy using the mechanism of ferroptosis, as well as a novel prognostic predictor of diffuse large B-cell lymphoma.

  10. Anaplastic large cell lymphoma and breast implants: five Australian cases.

    PubMed

    Taylor, Kim O; Webster, Howard R; Prince, H Miles

    2012-04-01

    There has never been a convincing association between breast implants and breast malignancy. A total of 42 cases of non-Hodgkin's lymphoma of the breast associated with implant capsules have been reported. The majority of the patients have anaplastic large cell lymphoma of T-cell origin. These lymphoma types have less frequently been observed in women without implants. The senior author (H.R.W.) diagnosed and treated two women with anaplastic large cell lymphoma in a short period of time. After this, the authors were contacted by other surgeons in Australia who had treated similar cases. The authors report five new cases of anaplastic large cell lymphoma associated with breast implants. There is an apparent spectrum of disease, with some cases pursuing an aggressive clinical course, although most have experienced a good prognosis. Both saline and silicone implants are implicated. All implant shells were textured. Textured surface implants only became widely used in the 1990s and therefore were not significantly represented in the large cohort studies of breast implant safety undertaken in the early 1990s. The diagnosis of anaplastic large cell lymphoma in the breast needs to be considered in patients, particularly those presenting with a periprosthetic seroma 6 months or more after breast implant insertion. Risk, V.

  11. 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

  12. Primary gastrointestinal lymphoma

    PubMed Central

    Ghimire, Prasanna; Wu, Guang-Yao; Zhu, Ling

    2011-01-01

    Gastrointestinal tract is the most common extranodal site involved by lymphoma with the majority being non-Hodgkin type. Although lymphoma can involve any part of the gastrointestinal tract, the most frequent sites in order of its occurrence are the stomach followed by small intestine and ileocecal region. Gastrointestinal tract lymphoma is usually secondary to the widespread nodal diseases and primary gastrointestinal tract lymphoma is relatively rare. Gastrointestinal lymphomas are usually not clinically specific and indistinguishable from other benign and malignant conditions. Diffuse large B-cell lymphoma is the most common pathological type of gastrointestinal lymphoma in essentially all sites of the gastrointestinal tract, although recently the frequency of other forms has also increased in certain regions of the world. Although some radiological features such as bulky lymph nodes and maintenance of fat plane are more suggestive of lymphoma, they are not specific, thus mandating histopathological analysis for its definitive diagnosis. There has been a tremendous leap in the diagnosis, staging and management of gastrointestinal lymphoma in the last two decades attributed to a better insight into its etiology and molecular aspect as well as the knowledge about its critical signaling pathways. PMID:21390139

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

    ClinicalTrials.gov

    2017-03-14

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

  14. [Acute toxoplasmosis in coexistent non-Hodgkin lymphoma].

    PubMed

    Welge-Lüssen, A; Hauser, R

    1999-06-01

    There are many reasons for cervical lymph node enlargement. In particular, the large group of infectious diseases must be considered along with malignant diseases. The coexistence of an uncommon infectious disease with malignant disease is a rare event. We report the case of an otherwise healthy 69-year-old man with marked enlargement of his cervical lymph nodes. A diagnosis of a recent toxoplasmosis infection was made based on positive IgG and IgM toxoplasma titers and the results of fine-needle aspiration from a lymph node. Since the enlarged lymph nodes persisted for more than weeks, the lymph node was excised. Histological examination revealed a non-Hodgkin's lymphoma. IgM titers in toxoplasmosis can persist up to 1 year. In cases with rare infectious diseases like toxoplasmosis in immunocompromised patients, swollen lymph nodes that persist or grow should lead to the suspicion of additional disease. A diagnosis can be confirmed by removing a lymph node for histology.

  15. Piperlongumine inhibits LMP1/MYC-dependent mouse B-lymphoma cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Han, Seong-Su; Tompkins, Van S.; Son, Dong-Ju

    2013-07-12

    Highlights: •Mouse model of human Burkitt lymphoma revealed cancer inhibition by PL. •Treatment with PL led to apoptosis of malignant but not normal B cells. •PL inhibited LMP1–NF-κB–Myc-dependent target genes including p21-encoding Cdkn1a. •PL holds promise for new interventions approaches to hematologic malignancies. -- Abstract: Piperlongumine (PL), isolated from the fruit of Long pepper, Piper longum, is a cancer-inhibiting compound that selectively kills tumor cells while sparing their normal counterparts. Here we evaluated the efficacy with which PL suppresses malignant B cells derived from a newly developed, double-transgenic mouse model of human endemic Burkitt lymphoma (BL), designated mCD40-LMP1/iMyc{sup Eμ}. PLmore » inhibited tumor cell proliferation in a concentration-dependent manner and induced apoptosis of neoplastic but not normal B cells. Treatment with PL resulted in downregulation of EBV-encoded LMP1, cellular Myc, constitutive NF-κB activity, and a host of LMP1-Myc-NF-κB-regulated target genes including Aurka, Bcat1, Bub1b, Ccnb1, Chek1, Fancd2, Tfrc and Xrcc6. Of note, p21{sup Cip1}-encoding Cdkn1a was suppressed independent of changes in Trp53 mRNA levels and p53 DNA-binding activity. Considering the central role of the LMP1–NF-κB–Myc axis in B-lineage neoplasia, these findings further our understanding of the mechanisms by which PL inhibits B-lymphoma and provide a preclinical rationale for the inclusion of PL in new interventions in blood cancers.« less

  16. Efficacy and feasibility of IDEA therapy for refractory or relapsed non-Hodgkin's lymphoma.

    PubMed

    Nishimori, Hisakazu; Fujii, Nobuharu; Maeda, Yoshinobu; Matsuoka, Ken-Ichi; Takenaka, Katsuto; Shinagawa, Katsuji; Ikeda, Kazuma; Matsuo, Keitaro; Harada, Mine; Tanimoto, Mitsune

    2009-05-01

    The effects of a novel salvage regimen, IDEA (ifosfamide, cytosine arabinoside, etoposide and dexamethasone), which does not include anthracycline or platinum, in patients with non-Hodgkin's lymphoma (NHL) were examined. Thirty-four patients with refractory or relapsed NHL were treated with IDEA. The overall remission and complete remission rates were 67.6% and 35.3%, respectively. The toxicity of IDEA was tolerable. With a median follow-up of 14 months, one-year overall survival (OS) and progression-free survival rates were 75.1% and 43.7%, respectively. Adequate numbers of CD34(+) cells were obtained in 77.8% of the patients assigned to receive autologous peripheral blood stem cell (PBSC) transplantation. High-dose chemotherapy with autologous PBSC transplantation was carried out in 14 patients; their 3-year OS was 75.0%, with a median follow-up of 38 months. IDEA is an effective second-line chemotherapy regimen for NHL patients and has an excellent PBSC-mobilizing effect.

  17. Residential Proximity to Industrial Facilities and Risk of Non-Hodgkin Lymphoma

    PubMed Central

    De Roos, AJ; Davis, S; Colt, JS; Blair, A; Airola, M; Severson, RK; Cozen, W; Cerhan, JR; Hartge, P; Nuckols, JR; Ward, MH

    2009-01-01

    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 (categories of ≤0.5-mile, >0.5-1.0, >1.0-2.0, >2 [referent]), and the duration of residence within 2 miles (10 years, 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 (≤0.5-mile: odds ratio [OR]=2.2, 95% confidence interval [CI]: 0.4-11.8) or 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, ≤0.5-mile: OR=2.7, 95% CI: 1.0-7.4), and primary metal (SIC 33, lived within 2 miles: 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-transport modeling of chemical releases

  18. Detailed Functional and Proteomic Characterization of Fludarabine Resistance in Mantle Cell Lymphoma Cells

    PubMed Central

    Lorkova, Lucie; Scigelova, Michaela; Arrey, Tabiwang Ndipanquang; Vit, Ondrej; Pospisilova, Jana; Doktorova, Eliska; Klanova, Magdalena; Alam, Mahmudul; Vockova, Petra; Maswabi, Bokang

    2015-01-01

    Mantle cell lymphoma (MCL) is a chronically relapsing aggressive type of B-cell non-Hodgkin lymphoma considered incurable by currently used treatment approaches. Fludarabine is a purine analog clinically still widely used in the therapy of relapsed MCL. Molecular mechanisms of fludarabine resistance have not, however, been studied in the setting of MCL so far. We therefore derived fludarabine-resistant MCL cells (Mino/FR) and performed their detailed functional and proteomic characterization compared to the original fludarabine sensitive cells (Mino). We demonstrated that Mino/FR were highly cross-resistant to other antinucleosides (cytarabine, cladribine, gemcitabine) and to an inhibitor of Bruton tyrosine kinase (BTK) ibrutinib. Sensitivity to other types of anti-lymphoma agents was altered only mildly (methotrexate, doxorubicin, bortezomib) or remained unaffacted (cisplatin, bendamustine). The detailed proteomic analysis of Mino/FR compared to Mino cells unveiled over 300 differentially expressed proteins. Mino/FR were characterized by the marked downregulation of deoxycytidine kinase (dCK) and BTK (thus explaining the observed crossresistance to antinucleosides and ibrutinib), but also by the upregulation of several enzymes of de novo nucleotide synthesis, as well as the up-regulation of the numerous proteins of DNA repair and replication. The significant upregulation of the key antiapoptotic protein Bcl-2 in Mino/FR cells was associated with the markedly increased sensitivity of the fludarabine-resistant MCL cells to Bcl-2-specific inhibitor ABT199 compared to fludarabine-sensitive cells. Our data thus demonstrate that a detailed molecular analysis of drug-resistant tumor cells can indeed open a way to personalized therapy of resistant malignancies. PMID:26285204

  19. Human CD30+ B cells represent a unique subset related to Hodgkin lymphoma cells.

    PubMed

    Weniger, Marc A; Tiacci, Enrico; Schneider, Stefanie; Arnolds, Judith; Rüschenbaum, Sabrina; Duppach, Janine; Seifert, Marc; Döring, Claudia; Hansmann, Martin-Leo; Küppers, Ralf

    2018-06-11

    Very few B cells in germinal centers (GCs) and extrafollicular (EF) regions of lymph nodes express CD30. Their specific features and relationship to CD30-expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma are unclear but highly relevant, because numerous patients with lymphoma are currently treated with an anti-CD30 immunotoxin. We performed a comprehensive analysis of human CD30+ B cells. Phenotypic and IgV gene analyses indicated that CD30+ GC B lymphocytes represent typical GC B cells, and that CD30+ EF B cells are mostly post-GC B cells. The transcriptomes of CD30+ GC and EF B cells largely overlapped, sharing a strong MYC signature, but were strikingly different from conventional GC B cells and memory B and plasma cells, respectively. CD30+ GC B cells represent MYC+ centrocytes redifferentiating into centroblasts; CD30+ EF B cells represent active, proliferating memory B cells. HRS cells shared typical transcriptome patterns with CD30+ B cells, suggesting that they originate from these lymphocytes or acquire their characteristic features during lymphomagenesis. By comparing HRS to normal CD30+ B cells we redefined aberrant and disease-specific features of HRS cells. A remarkable downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and multinuclearity.

  20. MYC Immunohistochemistry to Identify MYC-Driven B-Cell Lymphomas in Clinical Practice.

    PubMed

    Kluk, Michael J; Ho, Caleb; Yu, Hongbo; Chen, Benjamin J; Neuberg, Donna S; Dal Cin, Paola; Woda, Bruce A; Pinkus, Geraldine S; Rodig, Scott J

    2016-02-01

    Immunohistochemistry with anti-MYC antibody (MYC IHC) detects MYC protein in fixed samples of aggressive B-cell lymphomas and, according to the number of positive staining tumor nuclei, facilitates tumor subclassification, predicts underlying MYC rearrangements, and stratifies patient outcome. We aimed to determine the performance of MYC IHC in clinical practice. We reviewed MYC IHC performed on control specimens and 256 aggressive B-cell lymphomas and compared clinically reported IHC scores with experts' review. Control tissues showed less than 5% variation in daily IHC staining. Reported and expert IHC scores were well correlated (r = 0.86) with an SD of 14.2%. Reported IHC scores 30% or less and 70% or more were accurate (94.5%) compared with experts in categorizing tumors as "MYC IHC-Low" and "MYC IHC-High," respectively, but scores 40% to 60% were not (60.3%). The mean IHC score among lymphomas with MYC rearrangements was 80%, but with a large range of scores (20%-100%). There was no statistically significant association between IHC score and MYC copy number. Under optimal conditions, clinically reported MYC IHC scores are concordant with expert scores within 15%. MYC IHC does not capture all B-cell lymphomas with MYC rearrangements, however. MYC IHC and MYC fluorescence in situ hybridization are both recommended to identify MYC-driven B-cell lymphomas. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.