WorldWideScience

Sample records for lymphocytic lymphoma refractory

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

    Science.gov (United States)

    2017-07-06

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

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

    Science.gov (United States)

    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

  3. Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

    Science.gov (United States)

    2013-08-20

    Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  4. 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

    Science.gov (United States)

    2016-12-01

    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

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

    Science.gov (United States)

    2016-06-02

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

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

    Science.gov (United States)

    2016-02-23

    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

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

    Science.gov (United States)

    2017-07-24

    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

  8. Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2015-11-10

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  9. Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2013-09-27

    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); Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  11. Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2017-03-27

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; T-Cell Large Granular Lymphocyte Leukemia

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

    Science.gov (United States)

    2013-01-31

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

  13. 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

    Science.gov (United States)

    2016-06-17

    B-Cell Prolymphocytic Leukemia; 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-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  14. Bendamustine + rituximab chemoimmunotherapy and maintenance lenalidomide in relapsed, refractory chronic lymphocytic leukaemia and small lymphocytic lymphoma: A Wisconsin Oncology Network Study.

    Science.gov (United States)

    Chang, Julie E; Havighurst, Thomas; Kim, KyungMann; Eickhoff, Jens; Traynor, Anne M; Kirby-Slimp, Rachel; Volk, Lynn M; Werndli, Jae; Go, Ronald S; Weiss, Matthias; Blank, Jules; Kahl, Brad S

    2016-04-01

    Bendamustine + rituximab (BR) has demonstrated high response rates in relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL). However, progression-free survival (PFS) after BR is lenalidomide after BR induction could improve PFS in R/R CLL/SLL. Thirty-four patients with R/R CLL/SLL who had received 1-5 prior chemotherapy regimens were treated with 6 cycles of BR induction. Patients achieving at least a minor response received twelve 28-d cycles of lenalidomide 5-10 mg/d. The primary endpoint was PFS. The median age was 67 years, with a median of 2 prior therapies. Eleven patients had confirmed presence of 17p and/or 11q deletions. Twenty-five (74%) completed 6 cycles of induction BR (response rate 56%). Nineteen (56%) patients received maintenance lenalidomide; only 6 patients completed the intended 12 cycles, highlighting the limited feasibility of lenalidomide in this setting, primarily due to haematological and infectious toxicities. The observed median PFS of 18·3 months is not significantly different from that of BR induction in R/R CLL/SLL without maintenance therapy (15·2 months). It is possible that lenalidomide maintenance may be more feasible and effective in the front-line setting, which is being tested in an ongoing trial (NCT01754857).

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

    Science.gov (United States)

    2014-08-26

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

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

    Science.gov (United States)

    2016-04-13

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

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

    Science.gov (United States)

    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

  18. Population Pharmacokinetics of Ofatumumab in Patients With Chronic Lymphocytic Leukemia, Follicular Lymphoma, and Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Struemper, Herbert; Sale, Mark; Patel, Bela R;

    2014-01-01

    Ofatumumab is a human monoclonal antibody directed at CD20 approved for treatment of chronic lymphocytic leukemia. The population pharmacokinetics of intravenous ofatumumab were characterized in patients with relapsed/refractory chronic lymphocytic leukemia, relapsed/refractory follicular lymphoma...

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

    Science.gov (United States)

    2016-07-29

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

  20. Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2014-10-30

    Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

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

    Science.gov (United States)

    2015-11-23

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

  2. Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2013-07-01

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  3. 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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    2017-10-09

    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

  5. Phase II MOR00208 in Combination With Lenalidomide for Patients With Relapsed or Refractory CLL, SLL or PLL or Older Patients With Untreated CLL, SLL or PLL

    Science.gov (United States)

    2017-10-04

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  6. A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma

    Science.gov (United States)

    2017-01-24

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  7. Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

    Science.gov (United States)

    2017-07-10

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  8. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-10-04

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

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

    Science.gov (United States)

    2016-06-10

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

  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

    Science.gov (United States)

    2015-10-30

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

  11. Nodular lymphocyte-predominant Hodgkin lymphoma.

    Science.gov (United States)

    Savage, Kerry J; Mottok, Anja; Fanale, Michelle

    2016-07-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma with distinct clinicopathologic features. It is typified by the presence of lymphocyte predominant (LP) cells, which are CD20(+) but CD15(-) and CD30(-) and are found scattered amongst small B lymphocytes arranged in a nodular pattern. Despite frequent and often late or multiple relapses, the prognosis of NLPHL is very favorable. There is an inherent risk of secondary aggressive non-Hodgkin lymphoma (NHL) and studies support that risk is highest in those with splenic involvement at presentation. Given disease rarity, the optimal management is unclear and opinions differ as to whether treatment paradigms should be similar to or differ from those for classical Hodgkin lymphoma (CHL). This review provides an overview of the existing literature describing pathological subtypes, outcome and treatment approaches for NLPHL.

  12. Idelalisib for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma.

    Science.gov (United States)

    Barrientos, Jacqueline C

    2016-09-01

    Idelalisib is a first-in-class selective oral PI3Kδ inhibitor for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma, a predominantly elderly population with high comorbidity. The drug promotes apoptosis in primary CLL cells ex vivo, independent of common prognostic markers and inhibits CLL cell homing, migration and adhesion to cells in the microenvironment. Idelalisib has shown efficacy with acceptable safety as monotherapy and combination therapy in relapsed/refractory CLL. Idelalisib has clinical activity in patients with CLL with del(17p). The development of other novel B-cell-targeted agents provides the opportunity to evaluate additional idelalisib treatment combinations for their potential to further improve outcomes in CLL/small lymphocytic lymphoma.

  13. Phase I study of MLN8237--investigational Aurora A kinase inhibitor--in relapsed/refractory multiple myeloma, non-Hodgkin lymphoma and chronic lymphocytic leukemia.

    Science.gov (United States)

    Kelly, Kevin R; Shea, Thomas C; Goy, André; Berdeja, Jesus G; Reeder, Craig B; McDonagh, Kevin T; Zhou, Xiaofei; Danaee, Hadi; Liu, Hua; Ecsedy, Jeffrey A; Niu, Huifeng; Benaim, Ely; Iyer, Swaminathan Padmanabhan

    2014-06-01

    Amplification or over-expression of the mitotic Aurora A kinase (AAK) has been reported in several heme-lymphatic malignancies. MLN8237 (alisertib) is a novel inhibitor of AAK that is being developed for the treatment of advanced malignancies. The objectives of this phase I study were to establish the safety, tolerability, and pharmacokinetic profiles of escalating doses of MLN8237 in patients with relapsed or refractory heme-lymphatic malignancies. Sequential cohorts of patients received MLN8237 orally as either a powder-in-capsule (PIC) or enteric-coated tablet (ECT) formulation. Patients received MLN8237 PIC 25-90 mg for 14 or 21 consecutive days plus 14 or 7 days' rest, respectively, or MLN8237 ECT, at a starting dose of 40 mg/day once-daily (QD) for 14 days plus 14 days' rest, all in 28-day cycles. Subsequent cohorts received MLN8237 ECT 30-50 mg twice-daily (BID) for 7 days plus 14 days' rest in 21-day cycles. Fifty-eight patients were enrolled (PIC n = 28, ECT n = 30). The most frequent grade ≥3 drug-related toxicities were neutropenia (45 %), thrombocytopenia (28 %), anemia (19 %), and leukopenia (19 %). The maximum tolerated dose on the ECT 7-day schedule was 50 mg BID. The terminal half-life of MLN8237 was approximately 19 h. Six (13 %) patients achieved partial responses and 13 (28 %) stable disease. The recommended phase II dose of MLN8237 ECT is 50 mg BID for 7 days in 21-day cycles, which is currently being evaluated as a single agent in phase II/III trials in patients with peripheral T-cell lymphoma.

  14. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    Science.gov (United States)

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

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

    Science.gov (United States)

    2017-03-01

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

  16. 506U78 in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or T-cell Lymphoma

    Science.gov (United States)

    2013-01-22

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

  17. 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)

    Science.gov (United States)

    2017-10-05

    B-Cell Chronic Lymphocytic Leukemia; Monoclonal B-Cell Lymphocytosis; Lymhoma, Small Lymphocytic; Chronic Lymphocytic Leukemia; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Splenic Marginal Zone Lymphoma

  18. Large-cell lymphocytic lymphoma

    African Journals Online (AJOL)

    1983-04-09

    Apr 9, 1983 ... marrow transplantation and immunological manipulation of the ... The clinical course in the patient with a biopsy-proven diagnosis of lymphoma ... in years, and in the majority of cases the tumour cell will be a small round or.

  19. Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior rituximab exposure

    Directory of Open Access Journals (Sweden)

    Man-Hsin Hung

    2013-04-01

    Conclusion: Our study results show that for patients with relapsed/refractory B-cell NHL, rituximab-containing salvage treatment is feasible and generally tolerable. A high ALC-R value was significantly associated with a better response to this treatment.

  20. Treatment Options for Primary Refractory/Recurrent Hodgkin Lymphoma in Children and Adolescents

    Science.gov (United States)

    ... Primary Refractory/Recurrent Hodgkin Lymphoma in Children and Adolescents Primary refractory Hodgkin lymphoma is lymphoma that continues ... treated with an adult treatment regimen . Children and adolescents may have treatment-related side effects that appear ...

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

    Science.gov (United States)

    2016-07-08

    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

  2. Morphometric Characterization of Small Cell Lymphocytic Lymphoma

    Directory of Open Access Journals (Sweden)

    Chisoi Anca

    2014-11-01

    Full Text Available The morphometry in histopathology is used to characterize cell populations belonging to different tissues and to identify differences in their parameters with prognostic implications. To achieve morphometric examination were selected 6 of 24 cases identified as small cell lymphocytic lymphoma. For each case analysis was done on five fields, for each field measuring the parameters of 20 cells. The studied parameters were for cytoplasm: cytoplasmic area, maximum and minimum cytoplasmic diameter, cytoplasmic perimeter; for nucleus were measured: nuclear area, minimum and maximum nuclear diameter, nuclear perimeter, nuclear contour index, nuclear ellipticity index, nuclear irregularity index. Also the nucleocytoplasmic ratio was calculated in all studied cases. Small cell lymphocytic lymphoma is characterized in morphometric terms having a small cytoplasmic area (average 29.206 and also a small nuclear area (mean 28.939 having a nucleo-cytoplasmic ratio appearance suggestive for adult lymphocyte. A nuclear contour index small value (3.946, ellipticity index value also small (3.521 and small nuclear irregularity index (3.965. Standard deviations, in any of the studied morphometric categories, is around or below 1 suggesting monomorphic cell appearance. These morphometric and microscopic features characterized mainly by a small population of adult lymphocytes, monomorphic, with rounded hipercromic nuclei, dense chromatin, support the framing into indolent lymphoma group in terms of clinical outcome.

  3. Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia and lymphoma.

    Science.gov (United States)

    Varma, Gaurav; Johnson, Tyler P; Advani, Ranjana H

    2016-07-01

    The development of Bruton's tyrosine kinase (BTK) inhibitors and their introduction into clinical practice represent a major advance in the treatment of chronic lymphocytic leukemia (CLL) and other B-cell lymphomas. Although ibrutinib is the only BTK inhibitor that has been approved by the US Food and Drug Administration, several others are under investigation. Ibrutinib is currently approved for use in relapsed/refractory CLL, CLL with 17p deletion (del[17p]), relapsed or refractory mantle cell lymphoma, and Waldenström macroglobulinemia. Although it is clear that ibrutinib has altered treatment paradigms and outcomes in these diseases, several questions remain regarding (1) its role in frontline vs salvage therapy; (2) its use as a single agent vs in combination with biologic agents, other small molecules, or traditional chemoimmunotherapy; (3) the optimal duration of treatment; and (4) the treatment of patients who cannot tolerate or have disease resistant to ibrutinib. Because sparse clinical data are available on other BTK inhibitors, it is unclear at present whether their clinical efficacy and toxicity will differ from those of ibrutinib.

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

    Science.gov (United States)

    2016-01-04

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

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

    Science.gov (United States)

    2017-09-28

    Follicular Variant Peripheral 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; Stage II Mycosis Fungoides; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides

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

    Science.gov (United States)

    2016-10-06

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

  7. Salvage abdominal irradiation for refractory non-Hodgkin′s lymphoma

    Directory of Open Access Journals (Sweden)

    Akoum Riad

    2007-01-01

    Full Text Available Background: Abdominal irradiation, as a part of treatment, is often ignored in the management of refractory non-Hodgkin′s lymphoma (NHL. Objective: To evaluate the efficacy and the toxicity of this approach after failure of chemotherapy. Materials and Methods: 27 patients with intraabdominal lymphoma underwent salvage irradiation between 1982 and 2001. All patients were treated with a Cobalt-60 machine. The total dose administered to the abdomen was 18-20 Gy at the rate of 1.5-1.8 Gy per daily fraction, followed by a boost to gross disease up to 20 Gy. All patients had previously been heavily pretreated with chemotherapy. Fourteen patients, nine with follicular and five with diffuse lymphomas, had primary refractory tumors that had never achieved remission. Thirteen patients, six with follicular and seven with aggressive tumors, had refractory relapsed tumors after achieving one or more complete remissions. Results: The response rate was 77%. The median follow-up was 53 months. The 5-year and 10-year survival rates were 25 and 17%, respectively. The in-field and out-of-field recurrence rates were 22 and 33%, respectively. Survival rates were significantly better for patients with refractory relapse compared to those with primary refractory lymphoma (P < 0.01. There was no significant difference in terms of response, recurrence, or survival rates between follicular and aggressive types. Out-of-field recurrence occurred more frequently in initial stage III and IV disease. Toxic deaths occurred in three patients (11%. Conclusion: Salvage radiotherapy for refractory abdominal NHL is a feasible alternative for both follicular and diffuse subtypes and may provide significant palliation and prolongation of survival. It is less effective in patients with primary refractory NHL than in those with refractory relapsed NHL.

  8. Chronic lymphocytic leukemia/small lymphocytic lymphoma presenting as septic arthritis of the shoulder

    Energy Technology Data Exchange (ETDEWEB)

    Donovan, Andrea; Schweitzer, Mark E.; Nomikos, George [NYU Hospital for Joint Diseases, New York, NY (United States); Garcia, Roberto A. [Bellevue Hospital Center, New York, NY (United States)

    2008-11-15

    We report a case of a 53-year-old man presenting with shoulder pain mimicking septic arthritis. Laboratory findings were atypical. Biopsy performed to assess for possible osteomyelitis demonstrated chronic lymphocytic leukemia/small lymphocytic lymphoma. Intra-articular lymphoma is a rare but important consideration in patients with atypical clinical presentation. Imaging alone may be insufficient to render diagnosis as lymphoma can mimic infection, synovial hypertrophic processes, and depositional arthropathy. (orig.)

  9. Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

    Science.gov (United States)

    2017-06-30

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

  10. Idelalisib therapy of indolent B-cell malignancies: chronic lymphocytic leukemia and small lymphocytic or follicular lymphomas

    Directory of Open Access Journals (Sweden)

    Madanat YF

    2016-03-01

    Full Text Available Yazan F Madanat,1 Mitchell R Smith,2 Alexandru Almasan,3 Brian T Hill2 1Department of Internal Medicine, 2Department of Hematology and Medical Oncology, Taussig Cancer Institute, 3Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA Abstract: Chronic lymphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma are indolent B-cell lymphoproliferative disorders that mainly affect an older population. Although the majority of patients in need of treatment derive significant benefit from conventional chemotherapeutic agents as well as monoclonal antibodies, less toxic and more effective treatments are needed. Novel agents that inhibit the B-cell receptor signaling pathway have shown promising outcomes in these disorders. Idelalisib is a potent selective oral inhibitor of phosphatidylinositol 3-kinase delta and has shown significant clinical activity in B-cell malignancies. In this review, we summarize the clinical trial data using idelalisib as monotherapy or in combination with rituximab for the treatment of relapsed/refractory disease. The adverse effect profile includes autoimmune disorders such as transaminitis, colitis, and pneumonitis. Given the efficacy and manageable toxicity profile of idelalisib, it is being increasingly incorporated into the management of indolent B-cell malignancies. Keywords: idelalisib, PI3Kδ inhibitors, chronic lymphocytic leukemia, follicular lymphoma

  11. Composite ALK-negative anaplastic large cell lymphoma and small lymphocytic lymphoma involving the right inguinal lymph node.

    Science.gov (United States)

    Persad, Paul; Pang, Changlee S

    2014-02-01

    Anaplastic large cell lymphoma and small lymphocytic lymphoma are two lymphoid malignancies with completely distinct morphologies and natural histories. We present a rare case of composite anaplastic large cell lymphoma and small lymphocytic lymphoma in an inguinal lymph node of an otherwise healthy 47-year-old male patient. Immunohistochemical and molecular studies identified the two populations clearly. Their separation is imperative as anaplastic large cell lymphoma can be an aggressive neoplasm and easily overlooked in cases of small lymphocytic lymphoma with a small population of anaplastic large cell lymphoma cells.

  12. Brentuximab vedotin desensitization in a patient with refractory Hodgkin's lymphoma.

    Science.gov (United States)

    Arora, Anubha; Bhatt, Vijaya Raj; Liewer, Susanne; Armitage, James O; Bociek, R Gregory

    2015-10-01

    Brentuximab vedotin has emerged as a useful treatment option for relapsed or refractory Hodgkin's lymphoma; however, uncommon cases of anaphylactic reactions may require its permanent discontinuation. We report a 29-yr-old woman with refractory Hodgkin's lymphoma, who developed an anaphylactic reaction during the second dose of brentuximab vedotin. A 12-step desensitization protocol was followed; after premedicating with antihistaminic agents, methylprednisolone and montelukast, a total dose of 156 mg of brentuximab vedotin (1.8 mg/kg) was given as three infusions with increasing rate and concentration. Such desensitization protocol can allow safe administration of brentuximab vedotin and may have a broader applicability in managing hypersensitivity reactions with other monoclonal antibodies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Gabellier, Ludovic; Cartron, Guillaume

    2016-04-01

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

  14. Chronic lymphocytic leukemia: treatment options for patients with refractory disease.

    Science.gov (United States)

    Motta, Marina; Wierda, William G; Ferrajoli, Alessandra

    2009-09-01

    Patients with purine analogue-refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for this population is challenging, because limited data are available from clinical trials, and because studies have enrolled mixed populations (patients with recurrent and refractory disease or patients with refractory disease and Richter transformation). Moreover, patients with refractory CLL have a high incidence of unfavorable molecular and clinical features, such as high-risk genomic profiles, unmutated immunoglobulin heavy-chain genes, expression of zeta-chain-associated protein kinase 70, and bulky lymphadenopathies. These patients are also severely immunosuppressed because of the underlying disease and the treatments received, and experience a high rate of infectious complications that pose an additional difficulty in selecting treatment. Despite these challenges, in parallel with better characterizations of the biologic features of refractory CLL, the number of available treatment modalities for this population has increased. Several chemoimmunotherapy combinations have been developed, and novel agents with a different mechanism of action are being investigated in clinical trials. Furthermore, allogeneic stem cell transplantation with nonmyeloablative conditioning regimens is a therapeutic strategy that is increasingly offered to patients with refractory CLL.

  15. Interpretation of NCCN Guideline: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 1, 2017

    Directory of Open Access Journals (Sweden)

    Lei XIA

    2016-12-01

    Full Text Available Chronic lymphocytic leukemia (CLL is a kind of chronic lymphocyte proliferative disease with corresponding clinical symptoms caused by the accumulation of mature B lymphocytes in peripheral blood, bone marrow and lymphatic tissues. In recent years, great achievements have been reached on the basic research, new prognostic markers, diagnostic criteria and therapeutic methods in CLL. This study mainly interpreted the corresponding diagnosis and treatment of CLL in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 1, 2017.

  16. Small B cell lymphocytic lymphoma presenting as obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Chang Weng-Cheng

    2004-07-01

    Full Text Available Abstract Background Most lymphomas that involve the tonsil are large B cell lymphomas. Large B-cell lymphoma is a high grade malignancy which progresses rapidly. Tonsillar lymphoma usually presents as either a unilaterally enlarged palatine tonsil or as an ulcerative and fungating lesion over the tonsillar area. Small lymphocytic lymphomas (SLL of the Waldeyer's ring are uncommon. Case presentation We report a 41-year-old male who presented with a ten-year history of snoring. Physical examination revealed smooth bilateral symmetrically enlarged tonsils without abnormal surface change or cervical lymphadenopathy. Palatal redundancy and a narrowed oropharyngeal airway were also noted. The respiratory disturbance index (RDI was 66 per hour, and severe obstruction sleep apnea (OSA was suspected. No B symptoms, sore throat, odynophagia or dysphagia was found. We performed uvulopalatopharyngoplasty (UPPP and pathological examination revealed incidental small B-cell lymphocytic lymphoma (SLL. Conclusion It is uncommon for lymphoma to initially present as OSA. SLL is an indolent malignancy and is not easy to detect in the early stage. We conclude that SLL may be a contributing factor of OSA in the present case.

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

    Science.gov (United States)

    2016-10-20

    Activated B-Cell-Like Diffuse Large B-Cell Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

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

    Science.gov (United States)

    2017-03-13

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

  19. Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study

    Science.gov (United States)

    Lazarovici, Julien; Dartigues, Peggy; Brice, Pauline; Obéric, Lucie; Gaillard, Isabelle; Hunault-Berger, Mathilde; Broussais-Guillaumot, Florence; Gyan, Emmanuel; Bologna, Serge; Nicolas-Virelizier, Emmanuelle; Touati, Mohamed; Casasnovas, Olivier; Delarue, Richard; Orsini-Piocelle, Frédérique; Stamatoullas, Aspasia; Gabarre, Jean; Fornecker, Luc-Matthieu; Gastinne, Thomas; Peyrade, Fréderic; Roland, Virginie; Bachy, Emmanuel; André, Marc; Mounier, Nicolas; Fermé, Christophe

    2015-01-01

    Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320–1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234–0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent. PMID:26430172

  20. Primary Gallbladder Small Lymphocytic Lymphoma as a Rare Postcholecystectomy Finding

    Directory of Open Access Journals (Sweden)

    Kyriakos Psarras

    2014-01-01

    Full Text Available Introduction. Primary lymphoma of the gallbladder is an extremely rare entity with approximately 50 cases reported so far. In many of these cases the presenting symptoms were mimicking symptomatic gallstone disease and the diagnosis was made postoperatively, especially when the preoperative imaging results were far from suspicious for malignant disease. Patients and Methods. We report a case of primary lymphoma of the gallbladder in an 85-year-old man with gallstone disease, who was admitted for elective cholecystectomy 2 months after an episode of acute cholecystitis and pancreatitis. Histological evaluation of the specimen revealed a small lymphocytic lymphoma of the gallbladder. This type of primary gallbladder lymphoma has not been previously reported. Discussion. The most common primary lymphomas of the gallbladder are MALT lymphomas and diffuse large B-cell lymphomas, although a variety of other histological types have been reported. The association of these lesions with chronic inflammation is the most convincing theory for their pathogenesis. For lesions confined to the gallbladder, cholecystectomy is considered to be sufficient, while supplementary chemotherapy significantly improves prognosis in more advanced disease.

  1. Nodular lymphocyte predominant hodgkin lymphoma: biology, diagnosis and treatment.

    Science.gov (United States)

    Goel, Anupama; Fan, Wen; Patel, Amit A; Devabhaktuni, Madhuri; Grossbard, Michael L

    2014-08-01

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon variant of classical Hodgkin lymphoma. It is characterized histologically by presence of lymphohistiocytic cells which have B-cell phenotype, are positive for CD19, CD20, CD45, CD79a, BOB.1, Oct.2, and negative for CD15 and CD30. Patients often present with early stage of disease and do not have classical B symptoms. The clinical behavior appears to mimic that of an indolent non-Hodgkin lymphoma more than that of classical Hodgkin disease. The purpose of the present report is to define the biology of NLPHL, review its clinical presentation, and summarize the available clinical data regarding treatment.

  2. Nodular Lymphocyte Predominant Hodgkin Lymphoma of the Thyroid

    Science.gov (United States)

    Cassis, João; Simões, Helder; Sequeira Duarte, João

    2016-01-01

    Thyroid lymphomas are rare clinical entities that may result from either the primary intrathyroid de novo or secondary thyroid gland involvement of a lymphoma. Among these, the Hodgkin's subtype is quite uncommon, accounting for 0.6–5% of all thyroid malignancies. The authors report on a 76-year-old female presenting with a thyroid nodule that, upon surgical excision, was found to be a nodular lymphocyte predominant Hodgkin lymphoma of the thyroid. So far, thyroid involvement by this variant has never been reported. Upon reporting on this clinical case, the authors emphasize the difficulties usually found in establishing the diagnosis and in defining the best management strategy. A thorough review of the available literature is done. PMID:28044111

  3. Histologic transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma.

    Science.gov (United States)

    Agbay, Rose Lou Marie C; Jain, Nitin; Loghavi, Sanam; Medeiros, L Jeffrey; Khoury, Joseph D

    2016-10-01

    Although generally considered a clinically indolent neoplasm, CLL/SLL may undergo transformation to a clinically aggressive lymphoma. The most common form of transformation, to DLBCL, is also known as Richter syndrome. Transformation determines the course of the disease and is associated with unfavorable patient outcome. Precise detection of transformation and identification of predictive biomarkers and specific molecular pathways implicated in the pathobiology of transformation in CLL/SLL will enable personalized therapeutic approach and provide potential avenues for improving the clinical outcome of patients. In this review, we present an overview of the pathologic features, risk factors, and pathogenic mechanisms of CLL/SLL transformation. Am. J. Hematol. 91:1036-1043, 2016. © 2016 Wiley Periodicals, Inc.

  4. Primary skeletal muscle lymphoma presenting as refractory cellulitis.

    Science.gov (United States)

    Baddour, L M; Haden, K H; Allen, J W

    2001-09-01

    The right torso of a 55-year-old woman showed diffuse skin and soft-tissue changes suggestive of cellulitis. However, several clinical and radiologic features, including the subacute and non-toxic nature of the illness and the patient's lack of response to antibiotic therapy, indicated a noninfectious etiology. Malignancy was suggested by striking changes seen on computed tomographic scanning--including extensive infiltration and enlargement of the musculature of the right shoulder girdle, the intercostal musculature, the latissimus dorsi, and the rhomboids; focal enlargement of the right paraspinal muscles; and enlargement of the psoas and the iliacus muscles and of the musculature around the hip joint. The mediastinal, hilar, and paraaortic regions showed no adenopathy. A large hypodense lesion of approximately 4.5 cm, which was seen in the caudate lobe of the liver, raised the concern of a metastatic focus of malignancy. Because of these findings, an immediate muscle biopsy was performed. Results showed a non-Hodgkin's lymphoma with a B-cell phenotype. Although primary skeletal muscle lymphoma is very uncommon in patients without human immunodeficiency virus infection, clinical presentation of refractory cellulitis, as seen in the current case, is extremely rare.

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

    Science.gov (United States)

    2016-07-12

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

  6. Hodgkin's Lymphoma

    Science.gov (United States)

    ... behavior. Your type determines your treatment options. Classical Hodgkin's lymphoma Classical Hodgkin's lymphoma is the more common ... Hodgkin's lymphoma Lymphocyte-rich Hodgkin's lymphoma Lymphocyte-predominant Hodgkin's lymphoma This much rarer type of Hodgkin's lymphoma ...

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

    Science.gov (United States)

    2016-03-21

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

  8. Nuclear overexpression of lymphoid-enhancer-binding factor 1 identifies chronic lymphocytic leukemia/small lymphocytic lymphoma in small B-cell lymphomas.

    Science.gov (United States)

    Tandon, Bevan; Peterson, Loann; Gao, Juehua; Nelson, Beverly; Ma, Shuo; Rosen, Steven; Chen, Yi-Hua

    2011-11-01

    Lymphoid-enhancer-binding factor 1 (LEF1), coupling with β-catenin, functions as a key nuclear mediator of WNT/β-catenin signaling, which regulates cell proliferation and survival. LEF1 has an important role in lymphopoiesis, and is normally expressed in T and pro-B cells but not mature B cells. However, gene expression profiling demonstrates overexpression of LEF1 in chronic lymphocytic leukemia, and knockdown of LEF1 decreases the survival of the leukemic cells. So far, the data on LEF1 expression in B-cell lymphomas are limited. This study represents the first attempt to assess LEF1 by immunohistochemistry in a large series (290 cases) of B-cell lymphomas. Strong nuclear staining of LEF1 was observed in virtually all neoplastic cells in 92 of 92 (100%) chronic lymphocytic leukemia/small lymphocytic lymphomas including two CD5- cases, with strongest staining in cells with Richter's transformation. LEF1 also highlighted the morphologically inconspicuous small lymphocytic lymphoma component in three composite lymphomas. All 53 mantle cell lymphomas, 31 low-grade follicular lymphomas and 31 marginal zone lymphomas, including 3 CD5+ cases, were negative. In 12 grade 3 follicular lymphomas, LEF1 was positive in a small subset (5-15%) of cells. Diffuse large B-cell lymphoma, however, demonstrated significant variability in LEF1 expression with overall positivity in 27 of 71 (38%) cases. Our results demonstrate that nuclear overexpression of LEF1 is highly associated with chronic lymphocytic leukemia/small lymphocytic lymphoma, and may serve as a convenient marker for differential diagnosis of small B-cell lymphomas. The expression of β-catenin, the coactivator of LEF1 in WNT signaling, was examined in 50 chronic lymphocytic leukemia/small lymphocytic lymphomas, of which 44 (88%) showed negative nuclear staining. The findings of universal nuclear overexpression of LEF1 but lack of nuclear β-catenin in the majority of chronic lymphocytic leukemia/small lymphocytic

  9. Therapy refractory angioimmunoblastic T-cell lymphoma in complete remission with lenalidomide.

    NARCIS (Netherlands)

    Beckers, M.M.; Huls, G.A.

    2013-01-01

    The prognosis of therapy refractory angioimmunoblastic lymphoma (AITL) is very poor. In this report we describe a patient with AITL refractory to 2 lines of chemotherapy. He was treated with lenalidomide 15 mg continuously and prednisone. After 2 yr follow-up, the patient has no detectable disease.

  10. Therapy refractory angioimmunoblastic T-cell lymphoma in complete remission with lenalidomide

    NARCIS (Netherlands)

    Beckers, Marielle M.; Huls, Gerwin

    2013-01-01

    The prognosis of therapy refractory angioimmunoblastic lymphoma (AITL) is very poor. In this report we describe a patient with AITL refractory to 2 lines of chemotherapy. He was treated with lenalidomide 15 mg continuously and prednisone. After 2 yr follow-up, the patient has no detectable disease.

  11. Small lymphocytic lymphoma with Reed Sternberg cells: a diagnostic dilemma.

    Science.gov (United States)

    Pervez, S; Abro, B; Shahbaz, H

    2017-02-14

    Reed Sternberg (RS) cells in the setting of small lymphocytic lymphoma (SLL) can complicate the histopathological diagnosis. We report a case of a man aged 54 years who presented with cervical lymphadenopathy. Resection of the lymph node was performed and sent for histopathological evaluation to a local laboratory. A diagnosis of SLL with Classic Hodgkin's lymphoma (CHL) was made. The medical oncologist who encountered this diagnosis for the first time sent the biopsy blocks to our laboratory for a second opinion. On review of the biopsy and immunohistochemical stains, it showed typical SLL morphology and immunophenotype. Focally, it showed large mononuclear RS type cells; however, no typical background of CHL was seen. The diagnosis was revised to 'SLL with RS like cells with no convincing evidence of CHL'. The patient was subsequently treated as a case of SLL and no progression was observed on a follow-up of 5 years. 2017 BMJ Publishing Group Ltd.

  12. Oxaliplatin and Irinotecan in Treating Young Patients With Refractory Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-06-04

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Melanoma; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  13. Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by CART19

    Science.gov (United States)

    2016-01-26

    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

  14. Presentation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in a Warthin Tumor: Case Report and Literature Review.

    Science.gov (United States)

    Jawad, Hadeel; McCarthy, Peter; O'Leary, Gerard; Heffron, Cynthia C

    2017-10-01

    Warthin tumor is the second most common salivary gland neoplasm. It occurs more commonly in males than in females. Malignant transformation in Warthin tumor is a rare but well-recognized phenomenon; however, the development or presentation of lymphoma in a Warthin tumor is rare. An 80-year-old man presented with painless mass of the right parotid gland of 2 years duration with recent ulceration of the overlying skin and right cervical lymphadenopathy underwent a surgical resection of parotid mass and biopsy of the periglandular lymph nodes. The histological diagnosis was malignant lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, present within the stroma of a Warthin tumor, and also present within the adjacent lymph node. This case is the third reported case describing a collision of Warthin tumor and chronic lymphocytic leukemia/small lymphocytic lymphoma. It also emphasizes the importance of careful examination of the lymphoid stroma of these tumors.

  15. Composite mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a clinicopathologic and molecular study.

    Science.gov (United States)

    Hoeller, Sylvia; Zhou, Yi; Kanagal-Shamanna, Rashmi; Xu-Monette, Zijun Y; Hoehn, Daniela; Bihl, Michel; Swerdlow, Steven H; Rosenwald, Andreas; Ott, German; Said, Jonathan; Dunphy, Cherie H; Bueso-Ramos, Carlos E; Lin, Pei; Wang, Michael; Miranda, Roberto N; Tzankov, Alexander; Medeiros, L Jeffrey; Young, Ken H

    2013-01-01

    Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) share many features and both arise from CD5+ B-cells; their distinction is critical as MCL is a more aggressive neoplasm. Rarely, cases of composite MCL and CLL/SLL have been reported. Little is known about the nature of these cases and, in particular, the clonal relationship of the 2 lymphomas. Eleven composite MCL and CLL/SLL cases were identified. The clinical, morphologic and immunophenotypic features of the MCL and CLL/SLL were characterized. IGH (immunoglobulin heavy chain) gene analysis was performed on microdissected MCL and CLL/SLL components to assess their clonal relationship. Ten patients had lymphadenopathy, and 7 patients had bone marrow involvement. The MCL component had the following growth patterns: in situ (n = 1), mantle zone (n = 3), nodular and diffuse (n = 3), diffuse (n = 3), and interstitial in the bone marrow (the only patient without lymphadenopathy) (n = 1); 6 MCLs had blastoid or pleomorphic and 5 small lymphocytic features. The CLL/SLL component was nodular (n = 9) or diffuse (n = 2). All MCL were CD5(+) and cyclin D1(+) with t(11;14) translocation. All CLL/SLL were CD5(+), CD23(+) and negative for cyclin D1 or t(11;14). IGH gene analysis showed that the MCL and CLL/SLL components displayed different sized fragments, indicating that the MCL and CLL/SLL are likely derived from different neoplastic B-cell clones. The lack of a clonal relationship between the MCL and CLL/SLL components suggests that MCL and CLL/SLL components represent distinct disease processes and do not share a common progenitor B-cell.

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

    Science.gov (United States)

    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. Flavopiridol in Treating Children With Relapsed or Refractory Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-07-01

    Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Retinoblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  18. Treatment of patients with refractory chronic lymphocytic leukemia with alemtuzumab, alone or in combination with fludarabine

    Directory of Open Access Journals (Sweden)

    E. V. Kataeva

    2014-07-01

    Full Text Available In present study the immediate and long-term therapy results of 14 patients with refractory chronic lymphocytic leukemia (CLL are analyzed. Treatment program included alemtuzumab alone or in combination with fludarabine.

  19. Treatment of patients with refractory chronic lymphocytic leukemia with alemtuzumab, alone or in combination with fludarabine

    Directory of Open Access Journals (Sweden)

    E. V. Kataeva

    2011-01-01

    Full Text Available In present study the immediate and long-term therapy results of 14 patients with refractory chronic lymphocytic leukemia (CLL are analyzed. Treatment program included alemtuzumab alone or in combination with fludarabine.

  20. Impaired removal of Vβ8(+) lymphocytes aggravates colitis in mice deficient for B cell lymphoma-2-interacting mediator of cell death (Bim).

    Science.gov (United States)

    Leucht, K; Caj, M; Fried, M; Rogler, G; Hausmann, M

    2013-09-01

    We investigated the role of B cell lymphoma (BCL)-2-interacting mediator of cell death (Bim) for lymphocyte homeostasis in intestinal mucosa. Lymphocytes lacking Bim are refractory to apoptosis. Chronic colitis was induced in Bim-deficient mice (Bim(-/-) ) with dextran sulphate sodium (DSS). Weight loss and colonoscopic score were increased significantly in Bim(-/-) mice compared to wild-type mice. As Bim is induced for the killing of autoreactive cells we determined the role of Bim in the regulation of lymphocyte survival at mucosal sites. Upon chronic dextran sulphate sodium (DSS)-induced colitis, Bim(-/-) animals exhibited an increased infiltrate of lymphocytes into the mucosa compared to wild-type mice. The number of autoreactive T cell receptor (TCR) Vβ8(+) lymphocytes was significantly higher in Bim(-/-) mice compared to wild-type controls. Impaired removal of autoreactive lymphocytes in Bim(-/-) mice upon chronic DSS-induced colitis may therefore contribute to aggravated mucosal inflammation.

  1. Prognostic significance of new immunohistochemical markers in refractory classical Hodgkin lymphoma: a study of 59 cases.

    Directory of Open Access Journals (Sweden)

    Danielle Canioni

    Full Text Available Although most classical Hodgkin lymphoma patients are cured, a significant minority fail after primary therapy and may die as result of their disease. To date, there is no consensus on biological markers that add value to usual parameters (which comprise the International Prognostic Score used at diagnosis to predict outcome. We evaluated 59 patients (18 with primary refractory or early relapse disease and 41 responders for bcl2, Ki67, CD20, TiA1 and c-kit expression by semi-quantitative immunohistochemical study and correlated the results with the response to treatment.The results showed that expression of bcl2 and CD20 in Hodgkin and Reed Sternberg cells, and expression of TiA1 in micro-environmental lymphocytes, and c-kit positive mast cells in microenvironment, were independent prognostic markers. These novel cHL markers could be used in association with clinical parameters to identify newly diagnosed patients with favorable or unfavorable prognosis and to better tailor treatment for different risk groups.

  2. [Outpatient reinduction therapy with gemcitabine, dexamethasone, Cisplatin (GDP) for patients with relapsed and refractory lymphoma].

    Science.gov (United States)

    Aota, Yasuo; Tanaka, Masaru; Watanabe, Naoki; Tomomatu, Jyunichi; Gotoh, Akihiko; Komatu, Norio

    2015-01-01

    For younger patients with relapsed or refractory lymphomas who respond to salvage therapy, autologous stem cell trans- plantation(ASCT)is the standard of care. Recently, it was demonstrated that the gemcitabine/dexamethasone/cisplatin (GDP) regimen for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) prior to ASCT was not inferior to the standard dexamethasone/cytarabine/cisplatin (DHAP) regimen for patients with relapsed and refractory aggressive lymphoma. In Japan, most patients who receive CDDP-containing regimens are hospitalized because of the substantial transfusions required for preventing renal dysfunction. We initiated GDP therapy combined with a short period of hydration and the administration of a magnesium agent and mannitol for 5 patients with relapsed and refractory aggressive lymphoma. In 4 cases, GDP was safely administered on an outpatient basis. Furthermore, peripheral blood stem cells were successfully collected in 2 patients. After stem cell harvest, ASCT was performed in a patient with diffuse large B-cell lymphoma, with the patient remaining in complete remission (CR) after ASCT.

  3. Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia

    Science.gov (United States)

    2014-06-16

    Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  4. A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Tucker DL

    2015-06-01

    Full Text Available David L Tucker, Simon A Rule Department of Haematology, Plymouth Hospitals NHS Trust, Plymouth, UK Abstract: Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL and chronic lymphocytic leukemia (CLL, small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase, which functions by irreversible inhibition of the downstream signaling pathway of the B-cell receptor, which normally promotes cell survival and proliferation. Early clinical trials have demonstrated excellent tolerability and a modest side-effect profile even in elderly and multiply pretreated patient cohorts. Although the majority of disease responses tend to be partial, efficacy data have also been encouraging with more than two-thirds of patients with CLL and MCL demonstrating a durable response, even in the high-risk disease setting. Resistance mechanisms are only partially understood and appear to be multifactorial, including the binding site mutation C481S, and escape through other common cell-signaling pathways. This article appraises the currently available data on safety and efficacy from clinical trials of ibrutinib in the management of MCL and CLL, both as a single agent and in combination with other therapies, and considers how this drug is likely to be used in future clinical practice. Keywords: ibrutinib, mantle cell lymphoma, chronic lymphocytic leukemia, Bruton’s tyrosine kinase, lymphoproliferative disorders

  5. Morphologic studies of lymphocyte nuclei in follicular and diffuse mixed small- and large-cell (lymphocytic-histiocytic) lymphoma.

    Science.gov (United States)

    Dardick, I; Caldwell, D R; Moher, D; Jabi, M

    1988-08-01

    Twelve examples of mixed small- and large-cell lymphoma (eight follicular, one follicular and diffuse, and three diffuse) were investigated morphometrically using plastic-embedded tissue in order to study nuclear characteristics of lymphocyte populations in this form of non-Hodgkin's lymphoma (NHL) and to test morphologic bases for current NHL classification systems. This study illustrates that there are many inaccuracies, illusions, and misconceptions in the morphologic criteria currently used to classify mixed small- and large-cell lymphoma. A principal finding was that lymphocyte nuclear profiles in mixed-cell lymphomas tend to be smaller in size (P less than .005) and more irregular in shape (P = .0001) than the morphologically similar counterparts in germinal centers of lymph nodes with reactive hyperplasia. Intercase comparison of mixed small- and large-cell lymphomas revealed a considerable range of mean nuclear area values, some of which were within the size range of normal, small lymphocytes. At the magnifications used for morphometric assessment, a high proportion of lymphocyte nuclear profiles had shallow invaginations, but only a limited number of profiles (4% to 14%) had deep (cleaved) indentations. Contrary to current definitions for this subtype of NHL, lymphocytes with "small" nuclei had the same proportion of the nuclear diameter occupied by nuclear invaginations as lymphocytes with "large" nuclei and, in fact, mean nuclear invagination depth was shallower in "small" nuclei than in "large" nuclei. Furthermore, regardless of whether it is nuclear area or shape that is evaluated, lymphocytes in mixed-cell lymphoma do not separate into two populations of small-cleaved and large noncleaved cells. Morphometry reveals that only four of the 12 examples of mixed small- and large-cell lymphoma had a proportion of the lymphocytes in the size range of fully transformed germinal center lymphocytes that exceeded 25%, and none of the cases approached 50% even

  6. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

    Science.gov (United States)

    Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

    2017-01-01

    Summary Background Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Methods Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200–600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2–6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Findings Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1–2 toxicities

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

    Science.gov (United States)

    2017-01-31

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

  8. SMALL LYMPHOCYTIC LYMPHOMAS WITH PREDOMINANT SPLENOMEGALY - A COMPARISON OF IMMUNOPHENOTYPES WITH CASES OF PREDOMINANT LYMPHADENOPATHY

    NARCIS (Netherlands)

    HOLLEMA, H; VISSER, L; POPPEMA, S

    1991-01-01

    In this study, we compared small lymphocytic lymphomas with predominant lymphadenopathy with those with predominant splenomegaly and found differences in morphology and immunophenotype as well as clinical features. Cases with lymphadenopathy were characterized by widespread disease, CLL type

  9. DNAM-1 mediates epithelial cell-specific cytotoxicity of aberrant intraepithelial lymphocyte lines from refractory celiac disease type II patients.

    Science.gov (United States)

    Tjon, Jennifer M-L; Kooy-Winkelaar, Yvonne M C; Tack, Greetje J; Mommaas, A Mieke; Schreurs, Marco W J; Schilham, Marco W; Mulder, Chris J; van Bergen, Jeroen; Koning, Frits

    2011-06-01

    In refractory celiac disease (RCD), intestinal epithelial damage persists despite a gluten-free diet. Characteristic for RCD type II (RCD II) is the presence of aberrant surface TCR-CD3(-) intraepithelial lymphocytes (IELs) that can progressively replace normal IELs and eventually give rise to overt lymphoma. Therefore, RCD II is considered a malignant condition that forms an intermediate stage between celiac disease (CD) and overt lymphoma. We demonstrate in this study that surface TCR-CD3(-) IEL lines isolated from three RCD II patients preferentially lyse epithelial cell lines. FACS analysis revealed that DNAM-1 was strongly expressed on the three RCD cell lines, whereas other activating NK cell receptors were not expressed on all three RCD cell lines. Consistent with this finding, cytotoxicity of the RCD cell lines was mediated mainly by DNAM-1 with only a minor role for other activating NK cell receptors. Furthermore, enterocytes isolated from duodenal biopsies expressed DNAM-1 ligands and were lysed by the RCD cell lines ex vivo. Although DNAM-1 on CD8(+) T cells and NK cells is known to mediate lysis of tumor cells, this study provides, to our knowledge, the first evidence that (pre)malignant cells themselves can acquire the ability to lyse epithelial cells via DNAM-1. This study confirms previous work on epithelial lysis by RCD cell lines and identifies a novel mechanism that potentially contributes to the gluten-independent tissue damage in RCD II and RCD-associated lymphoma.

  10. Lenalidomide, as a single agent, induces complete remission in a refractory mantle cell lymphoma

    OpenAIRE

    Tempescul, Adrian; Ianotto, Jean-Christophe; Morel, Frederic; Morel, Frédéric; Marion, Veronique; De Braekeleer, Marc; Berthou, Christian

    2009-01-01

    Lenalidomide, as a single agent, induces complete remission in a refractory mantle cell lymphoma phone: +33-298-223504 (Tempescul, Adrian) (Tempescul, Adrian) Department of Clinical Hematology, Institute of Cancerology and Hematology, CHU Morvan - Avenue Foch - 29609 - Brest - FRANCE (Tempescul, Adrian) Department of Clinical Hematology, Institute of Cancerology and Hematology, CHU Morvan - Avenue Foch - 29609 - Brest - FRANCE (Ianotto, Jean-Christophe) ...

  11. Intraepithelial lymphocytes in refractory celiac disease : lost in transition

    NARCIS (Netherlands)

    Schmitz, Frederike

    2014-01-01

    Refractory coeliac disease type II (RCDII) is a severe complication of coeliac disease. Whereas celiac disease can successfully be treated by the strict avoidance of gluten, refractory celiac patients show no remission despite a gluten-free diet. The pathology of RCDII is only partially understood,

  12. Intraepithelial lymphocytes in refractory celiac disease : lost in transition

    NARCIS (Netherlands)

    Schmitz, Frederike

    2014-01-01

    Refractory coeliac disease type II (RCDII) is a severe complication of coeliac disease. Whereas celiac disease can successfully be treated by the strict avoidance of gluten, refractory celiac patients show no remission despite a gluten-free diet. The pathology of RCDII is only partially understood,

  13. Primary Non-Hodgkin’s Lymphoma of the thyroid with lymphocytic thyroiditis

    OpenAIRE

    Raviprakash, C. S.; Joseph, Cherian; Xavier, Saju; Raj, Girish

    2005-01-01

    Primary Lymphoma of the thyroid is one of the very rare entities accounting to less than 2% of thyroid malignancies. We present a case of primary Non-Hodgkin’s Lymphoma of the thyroid with lymphocytic thyroiditis in a 60 year old woman. The patient presented with a rapidly growing nodular mass in the thyroid. The histological and immune marker features of the tumour were consistent with Primary Non-Hodgkin’s Lymphoma of the thyroid with associated thyroiditis.

  14. Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

    Science.gov (United States)

    2016-08-01

    ; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Renal Cell Cancer; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin 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; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  15. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) after treatment for Hodgkin's lymphoma.

    Science.gov (United States)

    Mashima, Kyoko; Suzuki, Shigeaki; Mori, Takehiko; Shimizu, Toshihiko; Yamada, Satoshi; Hirose, Shigemichi; Okamoto, Shinichiro; Suzuki, Norihiro

    2015-12-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system (CNS) disorder with distinct radiological features. However, CLIPPERS may mimic CNS lymphoma, and several cases in which CLIPPERS occurred premonitory to CNS lymphoma have been reported. We report a 31-year-old man presenting with progressive gait ataxia and the characteristic MRI features of CLIPPERS. He was diagnosed with stage II Hodgkin's lymphoma at the age of 15, and we considered the possibility of newly emerged CNS lymphoma occurring in the immunosuppressive condition after the treatment of Hodgkin's lymphoma. Histological findings showed no evidence of CNS lymphoma and the neurological symptoms were resolved by steroids. Although CLIPPERS developed in the reverse order in this case, CLIPPERS should be considered in different diagnosis for CNS lymphoma.

  16. Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

    Science.gov (United States)

    A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

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

    Science.gov (United States)

    2016-09-15

    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

  18. Chronic lymphocytic leukemia/small lymphocytic lymphoma: another neoplasm related to the B-cell follicle?

    Science.gov (United States)

    Tandon, Bevan; Swerdlow, Steven H; Hasserjian, Robert P; Surti, Urvashi; Gibson, Sarah E

    2015-01-01

    Although there has been increased attention paid to the critical nature of nodal involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the B-cell compartment it is most closely related to and its relationship to the follicle remain uncertain. A clinicopathologic investigation of 60 extramedullary biopsies of LEF1+ CLL/SLL, including 29 cases with perifollicular/follicular (PF/F) growth, was therefore performed. A subset of PF/F cases demonstrated inner mantle zone preservation or intra-mantle zone growth. All PF/F and 16/31 other cases contained CD21+ follicular dendritic cells. No cytogenetic, IGHV mutational or gene usage differences were seen between PF/F and diffuse cases. PF/F cases were more often kappa positive (p<0.03) and had fewer involved nodal sites (p=0.0004). These findings suggest that at least a subset of bona fide CLL/SLL is related to the follicle, most likely the outer mantle zone, and that at least a subset of the diffuse cases may represent "later" disease.

  19. Granulomatous interstitial nephritis secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma.

    Science.gov (United States)

    Nasr, Samih H; Shanafelt, Tait D; Hanson, Curtis A; Fidler, Mary E; Cornell, Lynn D; Sethi, Sanjeev; Chaffee, Kari G; Morris, Joseph; Leung, Nelson

    2015-06-01

    Granulomatous interstitial nephritis (GIN) is an uncommon pathologic lesion encountered in 0.5% to 5.9% of renal biopsies. Drugs, sarcoidosis, and infections are responsible for most cases of GIN. Malignancy is not an established cause of GIN. Here, we report a series of 5 patients with GIN secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients were mostly elderly white males with an established history of CLL/SLL who presented with severe renal impairment (median peak serum creatinine, 7.3 mg/dL), leukocyturia, and mild proteinuria. One had nephromegaly. In 2 patients, the development and relapse of renal insufficiency closely paralleled the level of lymphocytosis. Kidney biopsy in all patients showed GIN concomitant with CLL/SLL leukemic interstitial infiltration. Granulomas were nonnecrotizing and epithelioid and were associated with giant cells. One biopsy showed granulomatous arteritis. One patient had a granulomatous reaction in lymph nodes and skin. Steroids with/without CLL/SLL-directed chemotherapy led to partial improvement of kidney function in all patients except 1 who had advanced cortical scarring on biopsy. In conclusion, we report an association between CLL/SLL and GIN. Patients typically present with severe renal failure due to both GIN and leukemic interstitial infiltration, which tends to respond to steroids with/without CLL/SLL-directed chemotherapy. The pathogenesis of GIN in this clinical setting is unknown but may represent a local hypersensitivity reaction to the CLL/SLL tumor cells.

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

    Science.gov (United States)

    2015-12-07

    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

  1. Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

    Science.gov (United States)

    2016-09-12

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Central Nervous System Lymphoma; Intraocular Lymphoma; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Recurrent Adult Diffuse Large Cell Lymphoma; Retinal Lymphoma

  2. Clinical Options in Relapsed or Refractory Hodgkin Lymphoma: An Updated Review

    Directory of Open Access Journals (Sweden)

    Roberta Fedele

    2015-01-01

    Full Text Available Hodgkin lymphoma (HL is a potentially curable lymphoma, and modern therapy is expected to successfully cure more than 80% of the patients. Second-line salvage high-dose chemotherapy and autologous stem cell transplantation (auto-SCT have an established role in the management of refractory and relapsed HL, leading to long-lasting responses in approximately 50% of relapsed patients and a minority of refractory patients. Patients progressing after intensive treatments, such as auto-SCT, have a very poor outcome. Allogeneic SCT represents the only strategy with a curative potential for these patients; however, its role is controversial. Based on recent knowledge of HL pathology, biology, and immunology, antibody-drug conjugates targeting CD30, small molecule inhibitors of cell signaling, and antibodies that inhibit immune checkpoints are currently explored. This review will discuss the clinical results regarding auto-SCT and allo-SCT as well as the current role of emerging new treatment strategies.

  3. Clinical Options in Relapsed or Refractory Hodgkin Lymphoma: An Updated Review

    Science.gov (United States)

    Fedele, Roberta; Martino, Massimo; Recchia, Anna Grazia; Irrera, Giuseppe; Gentile, Massimo; Morabito, Fortunato

    2015-01-01

    Hodgkin lymphoma (HL) is a potentially curable lymphoma, and modern therapy is expected to successfully cure more than 80% of the patients. Second-line salvage high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) have an established role in the management of refractory and relapsed HL, leading to long-lasting responses in approximately 50% of relapsed patients and a minority of refractory patients. Patients progressing after intensive treatments, such as auto-SCT, have a very poor outcome. Allogeneic SCT represents the only strategy with a curative potential for these patients; however, its role is controversial. Based on recent knowledge of HL pathology, biology, and immunology, antibody-drug conjugates targeting CD30, small molecule inhibitors of cell signaling, and antibodies that inhibit immune checkpoints are currently explored. This review will discuss the clinical results regarding auto-SCT and allo-SCT as well as the current role of emerging new treatment strategies. PMID:26788526

  4. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    Science.gov (United States)

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

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

    Science.gov (United States)

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

    2016-10-01

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

  6. Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kim, Youn H; Duvic, Madeleine; Obitz, Erik

    2007-01-01

    The efficacy and safety of zanolimumab in patients with refractory cutaneous T-cell lymphoma (CTCL) have been assessed in two phase 2, multicenter, prospective, open-label, uncontrolled clinical studies. Patients with treatment refractory CD4(+) CTCL (mycosis fungoides [MF], n = 38; Sézary syndrome...

  7. Obinutuzumab for relapsed or refractory indolent non-Hodgkin’s lymphomas

    Science.gov (United States)

    Gabellier, Ludovic; Cartron, Guillaume

    2016-01-01

    The use of anti-CD20 monoclonal antibodies (mAbs), such as rituximab, in CD20-positive B-cell malignancies has dramatically improved the outcome of chronic lymphoid leukemia and non-Hodgkin’s lymphomas (NHL). However, the occurrence of relapse and development of rituximab-refractory disease highlight the need to develop novel anti-CD20 mAbs, with improved mechanisms of action. Obinutuzumab is the first humanized type II glycoengineered anti-CD20 mAb. In vitro and in vivo data suggested several differences compared with rituximab, including a low level of complement-dependent cytotoxicity and an increased direct nonapoptotic cell death. Moreover, the glycoengineered Fc-linked nonfucosylated oligosaccharide enhanced the Fc–Fcγ receptor (FcγR) IIIa interaction, resulting in improved antibody-dependent cellular cytotoxicity and phagocytosis. Preclinical models suggested that these differences translate into superior survival in murine lymphoma models. Phase I/II trials in monotherapy in relapsed or refractory B-cell NHL demonstrated that obinutuzumab has an acceptable safety profile, infusion-related reactions being the most common adverse event. In rituximab-refractory indolent NHL, the recent randomized phase III GADOLIN study demonstrated an improved median progression-free survival for patients treated with obinutuzumab plus bendamustine rather than bendamustine alone. Further trials are ongoing to determine the role of obinutuzumab as a first-line agent in the treatment of follicular lymphoma. PMID:27054024

  8. Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma.

    Science.gov (United States)

    Dhillon, Sohita

    2017-03-21

    Obinutuzumab (Gazyva(®), Gazyvaro(®)) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the primary analysis of the large, phase III GADOLIN study, induction therapy with obinutuzumab plus bendamustine followed by obinutuzumab maintenance prolonged progression-free survival (PFS) to a statistically significant extent relative to induction with bendamustine monotherapy in patients with indolent non-Hodgkin's lymphoma (iNHL). The improvement in PFS was largely driven by the subgroup of patients with follicular lymphoma, who also had prolonged overall survival (OS) in a planned updated analysis. Obinutuzumab had a generally manageable tolerability profile in these patients; mild to moderate infusion-related reactions (IRRs) were the most common treatment-emergent adverse events (AEs) and neutropenia the most common grade 3 or 4 treatment-related AEs. Although additional studies and longer-term data are needed to further assess treatment benefits with obinutuzumab, current evidence indicates that obinutuzumab is a useful treatment option for patients with rituximab-refractory or -relapsed follicular lymphoma.

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

    Science.gov (United States)

    2016-08-22

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

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

    Science.gov (United States)

    2015-08-12

    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; Stage I Adult Burkitt Lymphoma; 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 Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin 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 IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Childhood Anaplastic Large

  11. Combination therapy with brentuximab vedotin and cisplatin/cytarabine in a patient with primarily refractory anaplastic lymphoma kinase positive anaplastic large cell lymphoma.

    Science.gov (United States)

    Heidegger, Simon; Beer, Ambros J; Geissinger, Eva; Rosenwald, Andreas; Peschel, Christian; Ringshausen, Ingo; Keller, Ulrich

    2014-01-01

    Anaplastic large cell lymphoma (ALCL) is a common subtype of the heterogeneous group of peripheral T-cell lymphomas, which is characterized by large pleomorphic cells with strong expression of CD30. Translocations involving ALK, the anaplastic lymphoma kinase gene, are associated with a favorable clinical outcome. Such ALK-positive ALCLs are usually responsive to a multidrug chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). However, there is no general consensus on the optimal therapy for relapsed or refractory ALCL. We report the case of a 24-year-old male suffering from ALK-positive ALCL with an uncommon manifestation of only extranodal disease in the gastric cardia region that showed primary refractoriness to standard CHOP chemotherapy. A combination therapy consisting of the anti-CD30 drug conjugate, brentuximab vedotin, and classical lymphoma salvage regimen DHAP (cisplatin, high-dose cytarabine and dexamethasone) was administered. Following two treatment cycles in 21-day intervals, the lymphoma showed considerable regression based on imaging diagnostics and no evidence of vital lymphoma in a subsequent biopsy. We did not observe any increase in toxicity; in particular, polyneuropathy and febrile neutropenia were not observed. In summary, we report that the antibody-drug conjugate brentuximab vedotin and a classical regimen used for aggressive lymphoma, DHAP, could be combined as salvage therapy in a case of refractory ALK-positive ALCL. Phase I/II studies will be required for safety and efficacy analysis.

  12. Combination therapy with brentuximab vedotin and cisplatin/cytarabine in a patient with primarily refractory anaplastic lymphoma kinase positive anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Heidegger S

    2014-06-01

    Full Text Available Simon Heidegger,1 Ambros Beer,2 Eva Geissinger,3 Andreas Rosenwald,3 Christian Peschel,1 Ingo Ringshausen,1 Ulrich Keller11III Medical Department, 2Nuclear Medicine Department, Technische Universität München, Munich, Germany; 3Institute of Pathology, University of Würzburg, Würzburg, GermanyAbstract: Anaplastic large cell lymphoma (ALCL is a common subtype of the heterogeneous group of peripheral T-cell lymphomas, which is characterized by large pleomorphic cells with strong expression of CD30. Translocations involving ALK, the anaplastic lymphoma kinase gene, are associated with a favorable clinical outcome. Such ALK-positive ALCLs are usually responsive to a multidrug chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone. However, there is no general consensus on the optimal therapy for relapsed or refractory ALCL. We report the case of a 24-year-old male suffering from ALK-positive ALCL with an uncommon manifestation of only extranodal disease in the gastric cardia region that showed primary refractoriness to standard CHOP chemotherapy. A combination therapy consisting of the anti-CD30 drug conjugate, brentuximab vedotin, and classical lymphoma salvage regimen DHAP (cisplatin, high-dose cytarabine and dexamethasone was administered. Following two treatment cycles in 21-day intervals, the lymphoma showed considerable regression based on imaging diagnostics and no evidence of vital lymphoma in a subsequent biopsy. We did not observe any increase in toxicity; in particular, polyneuropathy and febrile neutropenia were not observed. In summary, we report that the antibody-drug conjugate brentuximab vedotin and a classical regimen used for aggressive lymphoma, DHAP, could be combined as salvage therapy in a case of refractory ALK-positive ALCL. Phase I/II studies will be required for safety and efficacy analysis.Keywords: anaplastic large cell lymphoma (ALCL, refractory/relapsed lymphoma, anti-CD30 drug conjugate, DHAP

  13. Primary CD56+ NK/T-cell lymphoma of the rectum accompanied with refractory ulcerative colitis.

    Science.gov (United States)

    Kakimoto, Kazuki; Inoue, Takuya; Nishikawa, Takashi; Ishida, Kumi; Kawakami, Ken; Kuramoto, Takanori; Abe, Yosuke; Morita, Eijiro; Murano, Naoko; Toshina, Ken; Murano, Mitsuyuki; Umegaki, Eiji; Egashira, Yutaro; Okuda, Junji; Tanigawa, Nobuhiko; Hirata, Ichiro; Katsu, Ken-Ichi; Higuchi, Kazuhide

    2008-01-01

    A case of primary NK/T-cell lymphoma of the rectum accompanied with ulcerative colitis (UC) in a 73-year-old man is reported. He had a 6-year history of repeated admission to our hospital for UC. Total colonoscopy performed 4 months after resolution of refractory UC complicated by cytomegalovirus colitis showed a markedly submucosal tumor in the rectum, which was histologically diagnosed as malignant lymphoma. The findings of computed tomography of the chest and abdomen, gallium scintigraphy, abdominal ultrasonography, and upper gastrointestinal endoscopy showed no abnormal lesions. Therefore, based on a diagnosis of localized rectal lymphoma with UC, proctocolectomy was performed. The resected specimen showed three submucosal tumors in the rectum with local nodal involvement. Histologically, the tumors were characterized by diffusely infiltrating sheets of large atypical lymphoid cells, which were negative for CD4, CD8, and CD20 but were positive for CD56, CD3, and granzyme B. The presence of Epstein-Barr virus (EBV) infection in neoplastic cells was shown by in situ hybridization for EBV-encoded early small RNA1 (EBER-1). Based on these findings, the patient was diagnosed with primary CD56+ NK/T-cell lymphoma of the rectum (stage IIE). This is the first case report of primary rectal NK/T-cell lymphoma accompanied with UC.

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

    Science.gov (United States)

    2016-08-22

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

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

    Science.gov (United States)

    2016-04-19

    Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; 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 Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic 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 Multiple Myeloma; Stage I Small Lymphocytic Lymphoma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Untreated Hairy Cell Leukemia; Waldenström Macroglobulinemia

  16. Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin’s Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Knecht, Hans, E-mail: hans.knecht@usherbrooke.ca [Division d‘Hématologie, Département de Médecine, CHUS, Université de Sherbrooke, Québec, J1H 5N4 (Canada); Manitoba Institute of Cell Biology, The Genomic Centre for Cancer Research and Diagnosis, University of Manitoba, Winnipeg, Manitoba, R3E 0V9 (Canada); Righolt, Christiaan [Manitoba Institute of Cell Biology, The Genomic Centre for Cancer Research and Diagnosis, University of Manitoba, Winnipeg, Manitoba, R3E 0V9 (Canada); Department of Imaging Science and Technology, Delft University of Technology, 2628 CJ Delft (Netherlands); Mai, Sabine [Manitoba Institute of Cell Biology, The Genomic Centre for Cancer Research and Diagnosis, University of Manitoba, Winnipeg, Manitoba, R3E 0V9 (Canada)

    2013-06-05

    In classical Hodgkin’s lymphoma (HL) the malignant mononuclear Hodgkin (H) and multinuclear, diagnostic Reed-Sternberg (RS) cells are rare and generally make up <3% of the total cellular mass of the affected lymph nodes. During recent years, the introduction of laser micro-dissection techniques at the single cell level has substantially improved our understanding of the molecular pathogenesis of HL. Gene expression profiling, comparative genomic hybridization analysis, micro-RNA expression profiling and viral oncogene sequencing have deepened our knowledge of numerous facets of H- and RS-cell gene expression deregulation. The question remains whether disturbed signaling pathways and deregulated transcription factors are at the origin of refractory/relapsing Hodgkin’s lymphoma or whether these hallmarks are at least partially related to another major factor. We recently showed that the 3D nuclear organization of telomeres and chromosomes marked the transition from H- to RS-cells in HL cell lines. This transition is associated with progression of telomere dysfunction, shelterin disruption and progression of complex chromosomal rearrangements. We reported analogous findings in refractory/relapsing HL and identified the shelterin proteins TRF1, TRF2 and POT1 as targets of the LMP1 oncogene in post-germinal center B-cells. Here we summarize our findings, including data not previously published, and propose a model in which progressive disruption of nuclear integrity, a form of genomic instability, is the key-player in refractory/relapsing HL. Therapeutic approaches should take these findings into account.

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

    Science.gov (United States)

    2016-04-18

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

  18. Rate of primary refractory disease in B and T-cell non-Hodgkin's lymphoma: correlation with long-term survival.

    Directory of Open Access Journals (Sweden)

    Corrado Tarella

    Full Text Available BACKGROUND: Primary refractory disease is a main challenge in the management of non-Hodgkin's Lymphoma (NHL. This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients. METHODS: Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%, intensive therapy with autograft (16.9%, or other therapies (19.9%. Among B-cell NHL, 1,356 (47.8% received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months. RESULTS: Overall, 690 (22.2% patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001. Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001. Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001. CONCLUSION: Chemosensitivity to primary

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

    Science.gov (United States)

    2017-01-27

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

  20. Salvage Therapy for Refractory Aids-Related Primary Central Nervous System Lymphoma

    Science.gov (United States)

    Ferro, Hugo; Parino, Eduardo

    2012-01-01

    A 27-year-old male patient presented with speech disorders and multiple brain masses on MRI evaluation. He tested positive for HIV. A sterotactic biopsy diagnosed primary central nervous system lymphoma (diffuse large B-cell lymphoma). After two cycles of high-dose metotrexate (HD-MTX-)-based chemotherapy, the tumor progressed. He underwent whole brain radiotherapy achieving complete response. Six cycles of consolidating immunochemotherapy with rituximab-temozolomide were administered after radiation. Forty-three months after remission, he has not recurred and his neurological status is optimal. Younger HIV patients with refractory PCNSL and preserved immune function can face salvage therapy successfully achieving long term remissions with no remarkable neurotoxicity. PMID:23029628

  1. Non-Hodgkin lymphoma

    Science.gov (United States)

    Lymphoma - non-Hodgkin; Lymphocytic lymphoma; Histiocytic lymphoma; Lymphoblastic lymphoma; Cancer - non-Hodgkin lymphoma ... National Cancer Institute: PDQ adult non-Hodgkin lymphoma treatment. Bethesda, MD: National Cancer Institute. Updated ... . Accessed ...

  2. Effect of dendritic cell vaccine therapy on lymphocyte subpopulation in refractory primary brain tumor

    Directory of Open Access Journals (Sweden)

    J Niu

    2015-01-01

    Full Text Available BACKGROUND: Dendritic cell (DC-based immunotherapy has the potential to induce an antitumor response within the immunologically privileged brain. AIMS: The aim of this study was to evaluate the short-term effect of DC vaccine therapy on lymphocyte subsets in patients with refractory primary brain tumor. MATERIALS AND METHODS: Eighteen cases with refractory primary brain tumor who refused any treatment against tumor within 6 months of the therapy, were referred to one medicine center, from January 2011 to October 2012. All patients received 1 × 107 tumor lysate–pulsed DC vaccinations both intradermal injection and intravenous infusion 3 times/week. RESULTS: There were increases of lymphocytes CD8+ (P = 0.002 and CD56+ (P = 4.207E-10, but no change of lymphocytes CD3+ (P = 0.651. Six patients were positive response of delayed-type hypersensitivity. There were improving of appetite in 14 cases and increasing of physical strength 17 cases. CONCLUSIONS: DC vaccine has the potential for inducing an immune cytotoxic effect directed toward tumor cells.

  3. Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

    Science.gov (United States)

    2013-07-01

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Medulloepithelioma; Childhood Meningioma; Childhood Mixed Glioma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Oligodendroglioma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  4. A Chinese patient with relapsed and refractory Hodgkin lymphoma treated with brentuximab vedotin

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang Cao; Hong-Wei Zhou; Chao-Jin Peng; Mo Liu; Yu Du; Qing-Ming Yang

    2013-01-01

    At present, approximately 20% of Hodgkin lymphomas (HL) are relapsed and refractory, and therapeutic methods including chemotherapy, radiotherapy, and even stem cell transplantation are unsatisfactory. Brentuximab vedotin, composed of CD30 antibody and a chemotherapeutic agent, is a new targeted drug that eradicates tumor cel s by binding to the CD30 antigen on their surface. In clinical trials, the response rate and complete remission rate of this drug were 73% and 40%, respectively, for relapsed and refractory HL. Here we report a case of CD30-positive relapsed and refractory HL that was treated with brentuximab. Before the treatment with brentuximab, the patient underwent chemotherapy, radiotherapy, and autologous stem cell transplantation. However, the disease continued to progress, affecting multiple organs and prompting symptoms such as persistent fever. After the treatment with brentuximab, the patient′s condition improved. Body temperature returned to normal after 4 days. Lung nodules were reduced in size and number after a single course of treatment, and PET/CT showed partial remission and complete remission after 3 and 6 courses of treatment, respectively. The entire treatment process progressed smoothly, though the patient experienced some symptoms due to chemotherapy, including peripheral neuritis of the limbs, irritating dry cough, and mild increase in aminotransferase. No serious adverse effects were observed. The current general condition of the patient is good;the continuous complete remission has amounted to 6 months.

  5. Pilot experience with continuous infusion alemtuzumab in patients with fludarabine-refractory chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Wierda, William G; LaPushin, Ruth; O'Brien, Susan M; Faderl, Stefan; Browning, Mary L; Keating, Michael J

    2008-04-01

    We evaluated the activity and tolerability of alemtuzumab given as a continuous infusion for 7 d followed by subcutaneous administration for 11 wk as salvage therapy for 10 patients with fludarabine-refractory chronic lymphocytic leukemia. The continuous infusion of alemtuzumab was well tolerated. The typical infusion reaction seen with intravenous alemtuzumab was abolished. Two patients achieved a partial response with an overall response rate of 20%. Alemtuzumab levels were measured in four patients and detectable levels were obtained in three. Clinical activity needs to be confirmed in a larger patient population.

  6. Study on effectiveness of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related non-Hodgkin's lymphoma.

    Science.gov (United States)

    Zhong, Dong Ta; Shi, Chun Mei; Chen, Qiang; Huang, Jing Ze; Liang, Jian Gang

    2012-11-01

    Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. Even though NHL is commonly chemosensitive to primary treatment, failure or relapse still occurs in a large number of patients. We conducted this retrospective study to evaluate the efficacy and safety of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related NHL (AIDS-NHL). Forty-eight patients with relapsed or refractory AIDS-NHL were treated with intravenous combination chemotherapy with GDP. The overall objective response rate was 54.1% (95% confidence interval, CI, 40.1-68.3%), with 10 complete responses and 16 partial responses. The 2-year overall survival rate (OS) was 70.8% (95% CI 58.0-83.7%), and the 5-year OS was 41.7% (95% CI 27.7-55.6%). The 2-year progression-free survival rate (PFS) was 37.5% (95% CI 23.8-51.2%), and the 5-year PFS was 25.0% (95% CI 12.8-37.3%). The median progression-free survival was 8.8 months (95% CI 0-20.3 months), and the median overall survival was 40.6 months (95% CI 22.6-58.6 months). Patients with B cell tumors who relapsed but had no B symptoms were clinical stage I/II, had infiltration fewer than two extranodal sites, had CD4⁺ counts >200 cells/μL, and had lactate dehydrogenase (LDH) less than the upper limit of normal benefited from GDP. The level of LDH had a significant impact on the response rate to chemotherapy with GDP (P = 0.015). Myelosuppression was the main side effect; the incidence of grade 3-4 anemia was 8.3%; leukopenia, 37.5%; and thrombocytopenia, 48.3%. Univariate and multivariate analyses were performed to determine variables for OS and PFS. This study confirms that GDP is an effective and safe salvage regimen in relapsed or refractory AIDS-NHL, was associated with modest declines in CD4⁺ lymphocyte counts, and did not promote HIV-1 viral replication.

  7. Lymphocyte Rich Hodgkin's Lymphoma Presented with Warm Hemolytic Anemia: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Jorge M. Hurtado-Cordovi

    2011-01-01

    Full Text Available Hodgkin's lymphoma accounts for ten percent of all lymphomas. In the United States, there are about 8000 new cases every year. This paper describes a case of lymphocyte-rich Hodgkin's lymphoma (LRHL manifested by autoimmune hemolytic anemia (AIHA. A 27-year-old Israeli male presented with dizziness associated with one month of low-grade fevers and night sweats; he also complained of persistent cough, pruritus, and ten-pound weight lost during this time. The CBC revealed hemoglobin of 5.9 gm/dL, and direct Coomb's test detected multiple nonspecific antibodies consistent with the diagnosis of AIHA. Chest, abdomen, and pelvic CT scan showed mediastinal lymphadenopathy and splenomegaly. Lymph node biopsy revealed classic LRHL. AIHA resolved after completion of the first cycle of chemotherapy with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD; after six cycles, he went into complete remission. Although infrequent, AIHA can be responsible for the presenting symptoms of HL.

  8. Sjogren syndrome complicated by mucosa-associated lymphoid tissue lymphoma and lymphocytic interstitial pneumonia

    Directory of Open Access Journals (Sweden)

    Fatma eAhmed

    2015-08-01

    Full Text Available Sjogren Syndrome (SS is an autoimmune disease with exocrine glands dysfunction and multiorgan involvement. It is associated with increased risk of lymphoproliferative disorders, especially B-cell marginal zone lymphoma. While the role of F-18 Flurodoxyglucose position emission tomography/CT (F-18 FDG PET/CT for evaluation of lymphoma has been established, its use in patients with a chronic history of SS to evaluate for possible lymphoproliferative disorders or multiorgan involvement is limited. We present a case of chronic SS in which F-18 FDG PET/CT demonstrated FDG avid intraparotid and cervical lymph nodes pathologically proven to be Mucosa-associated lymphoid tissue (MALT lymphoma. In addition, the patient had bibasilar cystic changes consistent with lymphocytic interstitial pneumonia (LIP.

  9. Febrile cholestatic disease as an initial presentation of nodular lymphocyte-predominant Hodgkin lymphoma

    Institute of Scientific and Technical Information of China (English)

    Anna; Mrzljak; Slavko; Gasparov; Ika; Kardum-Skelin; Vesna; Colic-Cvrlje; Slobodanka; Ostojic; Kolonic

    2010-01-01

    Febrile cholestatic liver disease is an extremely unusual presentation of Hodgkin lymphoma(HL).The liver biopsy of a 40-year-old man with febrile episodes and cholestatic laboratory pattern disclosed an uncommon subtype of HL,a nodular lymphocyte-predominant HL(NLPHL).Liver involvement in the early stage of the usually indolent NLPHL's clinical course suggests an aggressiveness and unfavorable outcome.Emphasizing a liver biopsy early in the diagnostic algorithm enables accurate diagnosis and appropriate tre...

  10. Performance of FDG PET/CT at initial diagnosis in a rare lymphoma: nodular lymphocyte-predominant Hodgkin lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Grellier, Jean Francois; Weinmann, Pierre [AP-HP- Hopital Europeen Georges Pompidou, Service de medecine nucleaire, Paris (France); Vercellino, Laetitia; Merlet, Pascal; Toubert, Marie-Elisabeth; Berenger, Nathalie [AP-HP- Hopital Saint-Louis, Service de medecine nucleaire, Paris (France); Leblanc, Thierry [Hopital Saint-Louis, Service d' immuno-hematologie, Paris (France); Thieblemont, Catherine [Universite Paris Diderot, Sorbonne Paris Cite - INSERM UMR-S1165, AP-HP- Hopital Saint-Louis, Service d' hemato-Oncologie, Paris (France); Briere, Josette [AP-HP- Hopital Saint-Louis, Service de pathologie, Paris (France); Brice, Pauline [AP-HP- Hopital Saint-Louis, Service d' hemato-Oncologie, Paris (France)

    2014-11-15

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare Hodgkin lymphoma distinguished from classical Hodgkin lymphoma (cHL) by the nature of the neoplastic cells which express B-cell markers. We wanted to determine the diagnostic performance of FDG PET/CT in initial assessment and its therapeutic impact on staging. We retrospectively studied a population of 35 patients with NLPHL (8 previously treated for NLHPL, 27 untreated). All patients underwent an initial staging by pretherapeutic FDG PET/CT. The impact on initial stage or relapse stage was assessed by an independent physician. In a per-patient analysis, the sensitivity of the pretherapeutic FDG PET/CT was 100 %. In a per-site analysis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of pretherapeutic FDG PET/CT were 100 %, 99 %, 97 %, 100 % and 99 %, respectively. Pretherapeutic FDG PET/CT led to a change in the initial stage/relapse stage in 12 of the 35 patients (34 %). In contrast to previous results established without FDG PET/CT, 20 % of patient had osteomedullary lesions. Pretherapeutic FDG PET/CT has excellent performance for initial staging or relapse staging of NLPHL. (orig.)

  11. CD57+ T-cells are a subpopulation of T-follicular helper cells in nodular lymphocyte predominant Hodgkin lymphoma

    NARCIS (Netherlands)

    Sattarzadeh, Ahmad; Diepstra, Arjan; Rutgers, Bea; van den Berg, Anke; Visser, Lydia

    2015-01-01

    BACKGROUND: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is characterized by lymphocyte-predominant (LP) cells in a background of CD4+ CD57+ T-cells. These cells are normally present in the germinal center of lymphoid tissues. The cells rosetting LP cells are described to be PD-1 and

  12. CD57+ T-cells are a subpopulation of T-follicular helper cells in nodular lymphocyte predominant Hodgkin lymphoma

    NARCIS (Netherlands)

    Sattarzadeh, Ahmad; Diepstra, Arjan; Rutgers, Bea; van den Berg, Anke; Visser, Lydia

    2015-01-01

    BACKGROUND: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is characterized by lymphocyte-predominant (LP) cells in a background of CD4+ CD57+ T-cells. These cells are normally present in the germinal center of lymphoid tissues. The cells rosetting LP cells are described to be PD-1 and BCL-

  13. The spectrum of coincident entities with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL diagnosed by cytology

    Directory of Open Access Journals (Sweden)

    Kastenbaum Hannah

    2010-01-01

    Full Text Available Background: The cytologic diagnosis of Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL often relies on finding a small lymphoid population with the characteristic immunoprofile by ancillary testing. There are only a few reports of other processes identified with SLL/CLL. The aim of this study was to review the fine needle aspiration (FNA and touch prep (TP diagnoses of SLL/CLL in order to identify any coincident entities. Materials and Methods: We retrospectively reviewed all FNA and TP cytology cases between January 2005 and May 2009 with a diagnosis of SLL/CLL to determine the presence of any coincident process. Results: We identified 29 cases, including 23 FNAs and six TPs, from 23 patients. Ancillary studies were utilized in 97% of the cases, including flow cytometry (FC, 79%, immunohistochemistry (IHC, 55%, fluorescent in situ hybridization studies (24% and special stains (7%. Coincident entities were identified in nine cases (31% and included seven (28% neoplastic entities (Hodgkin lymphoma [HL], adenocarcinoma, squamous cell carcinoma, seminoma and two (7% non-neoplastic entities (infection and immunoglobulin containing cells. Six cases (21% suspicious for large cell transformation were also identified. Conclusion: In our review of SLL/CLL, coincident entities were present in 31% of the cases and included a spectrum of non-neoplastic and neoplastic processes. FC was the most frequently utilized ancillary test, but IHC provided important information by excluding a mantle cell lymphoma or confirming a coincident process. Thus, cytomorphologic evaluation in these patients is important due to the high risk of a coincident process that may not be apparent by FC alone and may require clinical management.

  14. Lenalidomide Therapy for Patients With Relapsed and/or Refractory, Peripheral T-Cell Lymphomas

    Science.gov (United States)

    2012-04-18

    Peripheral T-cell Lymphomas; Adult T-cell Leukemia; Adult T-cell Lymphoma; Peripheral T-cell Lymphoma Unspecified; Angioimmunoblastic T-cell Lymphoma; Anaplastic Large Cell Lymphoma; T/Null Cell Systemic Type; Cutaneous t-Cell Lymphoma With Nodal/Visceral Disease

  15. Alemtuzumab in the treatment of fludarabine refractory B-cell chronic lymphocytic leukemia (CLL

    Directory of Open Access Journals (Sweden)

    Marco Montillo

    2008-03-01

    Full Text Available Marco Montillo, Francesca Ricci, Sara Miqueleiz, Alessandra Tedeschi, Enrica MorraDepartment of Oncology/Hematology, Division of Hematology and Bone Marrow Transplant Unit, Niguarda Ca’ Granda Hospital, Milan, ItalyAbstract: The introduction of immunotherapeutic agents has provided renewed hope for Chronic lymphocytic leukemia fludarabine-refractory patients. Several clinical trials have shown that alemtuzumab is a more effective option compared to combination chemotherapy for treatment of patients who have relapsed or who are refractory to fludarabine, including those with poor prognostic factors. Although there are significant potential toxicities associated with alemtuzumab, such as infusional reactions and the risk of cytomegalovirus (CMV reactivation, most are manageable. Pre-treatment anti-pyretics and anti-histamines are recommended to prevent or mitigate the acute infusional reactions associated with intravenous infusion. Recent use of alemtuzumab via the subcutaneous route has been shown to be well tolerated and has yielded similar response rates to the infusional method of administration. Prophylaxis with thrimethoprim/sulphamethoxazole (TMP/SMZ as well as valacyclovir or a similar anti-viral can prevent many of the opportunistic infections seen in early trials. Reactivation of CMV infection can be effectively managed with monitoring and early treatment. Chemo-immunotherapy combination with alemtuzumab has been tested and demonstrated unprecedented clinical results in relapsed and refractory patients. The use of this agent earlier in the algorithm of patients with these characteristics should be considered. Future areas of research will include the use of alemtuzumab in combination with other monoclonal antibodies and other targeted therapies.Keywords: chronic lymphocytic leukemia, fludarabine, alemtuzumab

  16. Mouse rosettes and surface immunoglobulin in small lymphocytic lymphoma. Importance in immunophenotyping and differential diagnosis.

    Science.gov (United States)

    Batata, A; Shen, B

    1992-02-15

    Cell suspensions from lymphoid tissue of 82 small lymphocytic lymphoma (SLL), 8 intermediate lymphocytic lymphoma (ILL), 286 other B-non-Hodgkin's lymphoma (B-NHL), and 248 reactive lymphadenopathy (RLA) cases were analyzed to evaluate the diagnostic significance of mouse-rosette (M-rosette) assay, and surface immunoglobulin clonality (SIg) and level of expression. In SLL, 55 were M-rosette positive (67.07%) and 72 SIg positive (87.8%), with weak fluorescence in 63 and strong fluorescence in 9 cases. Of 10 SIg-negative cases, 9 were M-rosette positive; of 27 M-rosette-negative cases, 26 were SIg positive. Seven of the nine cases with strong fluorescence were M-rosette positive. In other B-NHL, 252 were M-rosette negative (88.11%) and 245 SIg positive (85.66%), with strong fluorescence in 211 and weak fluorescence in 34 cases. Thirty-two of the 34 cases with weak fluorescence were M-rosette negative. Of the RLA cases, 213 were M-rosette negative (85.89%) and 1 SIg positive (0.4%). The study demonstrated the independent expression of M-rosettes and SIg in SLL and their complementary role in diagnosis. It showed that positive results for M-rosettes and weak fluorescence are characteristic of SLL, that M-rosette negativity and strong fluorescence are characteristic of other B-NHL, and that M-rosette negativity and polyclonal SIg are characteristic of RLA. In 26 cases with paired data for CD5, M-rosettes, and SIg, a positive result for M-rosettes was superior to CD5 in differentiating SLL from other B-NHL. Intermediate lymphocytic lymphoma frequently showed weak SIg fluorescence and M-rosette negativity.

  17. Treatment Options for Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Lymphoma Treatment AIDS-Related Lymphoma Treatment Chronic Lymphocytic Leukemia Treatment (small lymphocytic lymphoma) Mycosis Fungoides (Including Sézary Syndrome) Treatment (cutaneous T-cell lymphoma) Primary CNS Lymphoma Treatment Non-Hodgkin lymphoma ...

  18. Stages of Adult Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Lymphoma Treatment AIDS-Related Lymphoma Treatment Chronic Lymphocytic Leukemia Treatment (small lymphocytic lymphoma) Mycosis Fungoides (Including Sézary Syndrome) Treatment (cutaneous T-cell lymphoma) Primary CNS Lymphoma Treatment Non-Hodgkin lymphoma ...

  19. Comparison of Outcomes of HLA-Matched Related, Unrelated, or HLA-Haploidentical Related Hematopoietic Cell Transplantation following Nonmyeloablative Conditioning for Relapsed or Refractory Hodgkin Lymphoma

    National Research Council Canada - National Science Library

    Burroughs, Lauri M; O'Donnell, Paul V; Sandmaier, Brenda M; Storer, Barry E; Luznik, Leo; Symons, Heather J; Jones, Richard J; Ambinder, Richard F; Maris, Michael B; Blume, Karl G; Niederwieser, Dietger W; Bruno, Benedetto; Maziarz, Richard T; Pulsipher, Michael A; Petersen, Finn B; Storb, Rainer; Fuchs, Ephraim J; Maloney, David G

    2008-01-01

    ...) for patients with relapsed or refractory Hodgkin lymphoma (HL) based on donor cell source. Ninety patients with HL were treated with nonmyeloablative conditioning followed by HCT from HLA-matched related, n=38, unrelated, n...

  20. Primary Refractory and Relapsed Classical Hodgkin Lymphoma - Significance of Differential CD15 Expression in Hodgkin-Reed-Sternberg Cells

    Directory of Open Access Journals (Sweden)

    Daniel Benharroch, Shai Pilosof, Jacob Gopas, Itai Levi

    2012-01-01

    Full Text Available We recognized a few possible complications of classical Hodgkin lymphoma therapy in a cohort of 209 patients: 8 developed a primary refractory disease (primary progression, 36 showed an early relapse and 21 showed a late relapse. Sialyl-CD15 expression in Hodgkin-Reed-Sternberg cells was significantly more positive in primary refractory Hodgkin lymphoma, which confirms our previously published findings. Bcl-2 showed a significantly lower level of expression in primary refractory disease than in the other follow-up groups. This is in contrast with a previous finding of Bcl-2, associated with a poor prognosis in primary refractory illness. Another category of variables, old age and advanced stages, was significantly different in the various complications but this finding is probably to be expected. We could not demonstrate a difference between the sequels and the control group with regard to several clinical and immunohistochemical markers. Sialyl-CD15 and Bcl-2 expression, in contrast, were confirmed as prognostic factors, mainly of tumor progression into primary refractory disease.

  1. Emperipolesis-like invasion of neoplastic lymphocytes into hepatocytes in feline T-cell lymphoma.

    Science.gov (United States)

    Suzuki, M; Kanae, Y; Kagawa, Y; Ano, N; Nomura, K; Ozaki, K; Narama, I

    2011-05-01

    Twelve cases of feline malignant lymphoma with emperipolesis-like invasion of neoplastic lymphocytes were examined microscopically, immunohistochemically and ultrastructurally. Intracytoplasmic invasion of neoplastic cells varied in severity between the cases, between hepatic lobules and between areas within the lobules. The number of infiltrating neoplastic cells ranged from one to several per hepatocyte. Neoplastic cells exhibited widely varying morphology from case-to-case and cell-to-cell within each case, and contained eosinophilic cytoplasmic granules in four cases. Immunohistochemical examination revealed that neoplastic cells in 11 of the 12 cases expressed one or both T-cell markers (CD3 and TIA-1). Diagnosis of T-cell lymphoma was also confirmed by assessment of clonality by polymerase chain reaction. Ultrastructural analysis revealed that the neoplastic lymphocytes were contained within an invagination of the cell membrane of the hepatocyte, rather than directly infiltrating into the cytoplasm of the cell. There was no evidence that the invasive neoplastic lymphocytes had a cytotoxic effect.

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

    Science.gov (United States)

    Goede, Valentin; Klein, Christian; Stilgenbauer, Stephan

    2015-01-01

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

  3. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations

    DEFF Research Database (Denmark)

    Farooqui, Mohammed Z H; Valdez, Janet; Martyr, Sabrina

    2015-01-01

    BACKGROUND: Patients with chronic lymphocytic leukaemia (CLL) with TP53 aberrations respond poorly to first-line chemoimmunotherapy, resulting in early relapse and short survival. We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53...

  4. Nodular lymphocyte predominant Hodgkin lymphoma in Sweden between 2000 and 2014: an analysis of the Swedish Lymphoma Registry.

    Science.gov (United States)

    Molin, Daniel; Linderoth, Johan; Wahlin, Björn E

    2017-05-01

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent CD20(+) lymphoma. Its scarcity has made clinical trials difficult and there is no consensus on first-line treatment. We conducted a population-based study of all patients diagnosed with NLPHL in Sweden between 2000 and 2014 (N = 158; 41 women and 117 men), focusing on clinical features, therapy and overall survival. The median female and male age was 59 and 44 years, respectively (P = 0·002). In early-stage disease, there was little mortality and no survival differences between therapies. In patients with advanced-stage disease, mortality was relatively high in patients who did not receive first-line rituximab but absent in those who did (10-year survival, 55% vs. 100%; P = 0·033); there were no imbalances of prognostic factors between those two groups. In advanced stages, first-line rituximab use increased markedly between 2000-2004 and 2005-2014 (7% vs. 67%; P < 0·00005), as did 10-year survival, 53% vs. 72% (multivariate P = 0·027). Although all patients were diagnosed in the 2000s, this is the longest-followed (and largest) population-based cohort. We report a hitherto unreported 15-year median age difference between sexes, increasing rituximab use and improved survival. © 2017 John Wiley & Sons Ltd.

  5. Infused autograft lymphocyte to monocyte ratio predicts survival in classical Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Porrata LF

    2015-02-01

    Full Text Available Luis F Porrata, David J Inwards, Stephen M Ansell, Ivana N Micallef, Patrick B Johnston, William J Hogan, Svetomir N Markovic Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA Abstract: The infused autograft lymphocyte to monocyte ratio (A-LMR as a surrogate marker of host immunity (ie, absolute lymphocyte count and CD14+ HLA-DRlow/neg immunosuppressive monocytes (ie, absolute monocyte count is a prognostic factor for patients with diffuse large B-cell lymphoma after autologous peripheral hematopoietic stem cell transplantation (APHSCT. Thus, we set out to investigate if A-LMR can also affect survival post-APHSCT in classical Hodgkin lymphoma. From 1994 to 2012, 183 patients with classical Hodgkin lymphoma who underwent APHSCT were studied. The patients were randomly divided into a training set (n=122 and a validation set (n=61. The receiver operating characteristic and area under the curve identified an A-LMR ≥1 as the best cut-off value and validated by the k-fold cross-validation in the training set. Multivariate analysis showed A-LMR to be an independent prognostic factor for survival in the training set. Patients with an A-LMR ≥1.0 experienced a superior overall survival (OS versus patients with an A-LMR <1.0 (median OS not reached versus 40.4 months, 5-year OS rates of 86% [95% CI 72–93] versus 43% [95% CI 28–58], P<0.0001, respectively in the training set. In the validation set, an A-LMR ≥1 showed a median OS of not reached versus 41.4 months for an A-LMR ,1, 5-year OS rates of 90% (95% CI 73–97 versus 48% (95% CI 28–68; P<0.0001. A-LMR provides a platform to engineer an autograft versus tumor effect to improve clinical outcomes in patients with classical Hodgkin lymphoma undergoing APHSCT. Keywords: autograft absolute lymphocyte to monocyte count ratio, survival, autologous peripheral hematopoietic stem cell transplantation, classical Hodgkin lymphoma

  6. Nonmyeloablative Allogeneic Stem Cell Transplantation in Relapsed/Refractory Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Khouri, Issa F.; Bassett, Roland; Poindexter, Nancy; O'Brien, Susan; Bueso-Ramos, Carlos E.; Hsu, Yvonne; Ferrajoli, Alessandra; Keating, Michael J.; Champlin, Richard; Fernandez-Vina, Marcelo

    2015-01-01

    BACKGROUND The role of nonmyeloablative allogeneic stem cell transplantation (NST) in the treatment of chronic lymphocytic leukemia (CLL) is not well established. The authors report on long-term experience with NST in relapsed/refractory CLL and define prognostic factors associated with outcome. METHODS The authors reviewed the outcome of 86 patients with relapsed/relapsed CLL enrolled in sequential NST protocols. RESULTS The median patient age was 58 years. Patients were heavily pretreated before transplantation, and 43 required immunomanipulation after NST for persistent or recurrent disease. Immunomanipulation included withdrawal of immunosuppression, rituximab, and step-wise donor lymphocyte infusions. Of 43 patients receiving immunomanipulation, 20 (47%) experienced a complete remission. Patients with human leukocyte antigen (HLA) genotype A1+/A2−/B44− were more likely to experience a complete remission (P ¼ .0009), with rates of 9%, 36%, 50%, and 91%, respectively, for 0, 1, 2, and 3 of these HLA factors. This resulted in significant improvement in progression-free-survival rates of 68.2% at 5 years for patients with all 3 HLA factors. Overall, the estimated 5-year survival rate was 51%. In a multivariate model, a CD4 count of <100/mm3 and a below normal serum immunoglobulin G level at study entry were associated with a short survival duration (P < .0001). CONCLUSIONS These results confirm the potential cure of relapsed/refractory CLL with NST and provide the first evidence that immunoglobulin G and CD4 levels are predictive of overall survival after NST in CLL and that human leukocyte antigen alleles predict response to immunomanipulation. PMID:21455998

  7. Chronic lymphocytic lymphoma and concomitant renal cell carcinoma (Clear Cell Type: Review of the literature

    Directory of Open Access Journals (Sweden)

    Burak Uz

    2016-01-01

    Full Text Available In the present report, a 73 years-old male patient who developed clear cell type renal cell carcinoma (RCC 5 years after the diagnosis of chronic lymphocytic lymphoma (CLL and plausible explanations for this association were discussed by the authors. The incidence of CLL and RCC occurring in the same patient is higher than that expected in the general population. Various explicative hypotheses of this concurrence include treatment-related development of a second malignancy, immunomodulatory mechanisms, viral aetiology, cytokine (interleukin 6 release from a tumor, and common genetic mutations. Further investigations are warranted.

  8. Diffuse Lymphocytic Lymphoma in a Feline’s Ileum: Clinical and Pathologic Report

    Directory of Open Access Journals (Sweden)

    José Fernando Ortiz Álvarez

    2015-09-01

    Full Text Available The case of a domestic, shorthaired male cat, neutered, of three and a half years of age, with a current health plan that is presenting weight loss and digestive signology is presented. After performing the necessary diagnostic tests, an intestinal mass was found and it tested positive for viral feline leukemia; after the diagnosis, and following the request of the owners, the cat was euthanized. Following the necropsy and the histopathology results, it was found that the intestinal mass was a diffuse lymphocytic lymphoma, presumably of B cells with metastases in mesenteric lymph nodes and the liver.

  9. Correction: Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia and lymphoma.

    Science.gov (United States)

    2016-09-01

    An article in the July 2016 issue, "Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia and lymphoma" by Gaurav Varma, MSPH, Tyler P. Johnson, MD, and Ranjana H. Advani, MD, described ONO/GS-4059 as a "reversible" inhibitor of BTK when it is in fact an "irreversible" inhibitor. We have made the correction to pages 546 and 552 of the online version at www.hematologyandoncology.net. Many thanks to an astute reader for pointing out the error. This corrects the article pmid:27379948.

  10. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Lee, Bang-Ning; Schlette, Ellen J; O'Brien, Susan M; Gao, Hui; Wen, Sijin; Wierda, William G; Estrov, Zeev; Faderl, Stefan; Cohen, Evan N; Li, Changping; Reuben, James M; Keating, Michael J

    2008-06-01

    This study investigated the activity of lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Lenalidomide was given at 10 mg daily with dose escalation up to 25 mg daily. Three patients (7%) achieved a complete response (CR), one a nodular partial remission, and 10 patients a partial remission (PR), for an overall response (OR) rate of 32%. Treatment with lenalidomide was associated with an OR rate of 31% in patients with 11q or 17p deletion, of 24% in patients with unmutated V(H), and of 25% in patients with fludarabine-refractory disease. The most common toxicity was myelosuppression, and the median daily dose of lenalidomide tolerated was 10 mg. Plasma levels of angiogenic factors, inflammatory cytokines, and cytokine receptors were measured at baseline, day 7, and day 28. There was a dramatic increase in median interleukin (IL)-6, IL-10, IL-2, and tumor necrosis factor receptor-1 levels on day 7, whereas no changes were observed in median vascular endothelial growth factor levels (20 patients studied). According to our experience, lenalidomide given as a continuous treatment has antitumor activity in heavily pretreated patients with CLL.

  11. The Spectrum of Kidney Pathology in B-Cell Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma: A 25-Year Multicenter Experience

    Science.gov (United States)

    Poitou-Verkinder, Anne-Laure; Francois, Arnaud; Drieux, Fanny; Lepretre, Stéphane; Legallicier, Bruno; Moulin, Bruno; Godin, Michel; Guerrot, Dominique

    2015-01-01

    Background Chronic lymphocytic leukemia and small lymphocytic lymphoma are 2 different presentations of the most common B-cell neoplasm in western countries (CLL/SLL). In this disease, kidney involvement is usually silent, and is rarely reported in the literature. This study provides a clinicopathological analysis of all-cause kidney disease in CLL/SLL patients. Methods Fifteen CLL/SLL patients with kidney biopsy were identified retrospectively. Demographic, clinical, pathological and laboratory data were assessed at biopsy, and during follow-up. Results At biopsy 11 patients presented impaired renal function, 7 patients nephrotic syndrome, 6 patients dysproteinemia, and 3 patients cryoglobulinemia. Kidney pathology revealed CLL/SLL-specific monoclonal infiltrate in 10 biopsies, glomerulopathy in 9 biopsies (5 membranoproliferative glomerulonephritis, 2 minimal change disease, 1 glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits, 1 AHL amyloidosis). Five patients presented interstitial granulomas attributed to CLL/SLL. After treatment of the hematological disease, improvement of renal function was observed in 7/11 patients, and remission of nephrotic syndrome in 5/7 patients. During follow-up, aggravation of the kidney disease systematically occurred in the absence of favorable response to hematological treatment. Conclusions A broad spectrum of kidney diseases is associated with CLL/SLL. In this setting, kidney biopsy can provide important information for diagnosis and therapeutic guidance. PMID:25811382

  12. Clinical efficacy and safety in relapsed/refractory mantle cell lymphoma: a systematic literature review.

    Science.gov (United States)

    Njue, Annete; Colosia, Ann; Trask, Peter C; Olivares, Robert; Khan, Shahnaz; Abbe, Adeline; Police, Rachel; Wang, Jianmin; Ruiz-Soto, Rodrigo; Kaye, James A; Awan, Farrukh

    2015-01-01

    A systematic literature review was performed to collect and review information on the clinical efficacy and safety of treatments for relapsed/refractory (R/R) mantle cell lymphoma (MCL), with a meta-analysis, if possible. PubMed, Embase, and the Cochrane Library were searched for studies published in English from January 1, 1997, to August 2, 2012. Conference proceedings, bibliographic reference lists of included articles, recent reviews, and ClinicalTrials.gov were searched for phase II to IV studies displaying results. Studies were included if they reported on patients with R/R MCL who were ineligible to receive high-dose chemotherapy with stem cell transplant. Studies of patients with several non-Hodgkin lymphoma subtypes were only included if they reported MCL outcomes separately. We identified 59 studies in R/R MCL. Forty distinct treatment regimens were evaluated. Thirty studies included more than 15 patients with R/R MCL. Six studies were comparative (including 5 randomized controlled trials [RCTs]); 53 were single-arm. There were no common treatments among the RCTs; therefore, a meta-analysis was not feasible. Thirty-one of 59 studies reported baseline data for patients with R/R MCL. Of the 30 studies with > 15 patients with R/R MCL, 30 reported overall response rate data, 14 reported progression-free survival (PFS), and 12 reported overall survival (OS). The small number of RCTs in R/R MCL precludes identifying an optimal treatment. Small sample sizes, infrequent reporting of OS and PFS, and limited information on patient characteristics made a comparison of results difficult. High-quality comparative studies of novel therapies that have the potential to demonstrate OS advantages in R/R MCL are needed.

  13. A novel immunomodulatory and molecularly targeted strategy for refractory Hodgkin's lymphoma

    Science.gov (United States)

    McGuire, Mary F.; Buryanek, Jamie; Janku, Filip; Younes, Anas; Hong, David

    2014-01-01

    Although Hodgkin's lymphoma (HL) was one of the first human cancers to be cured by chemotherapy, no new agents other than brentuximab vedotin (Adcetris®, CD 30 directed antibody drug conjugate) have received US Food and Drug Administration (FDA) approval for HL since 1977. Subsets of young adult patients with HL continue to relapse, even after stem cell transplantation, warranting new approaches. Against this background, we report a dramatic response in a young patient with advanced HL refractory to the standard treatment who responded to the combination of a pan-histone deacetylase inhibitor (vorinostat, suberoylanilide hydroxamic acid, SAHA) and mammalian target of rapamycin (mTOR) inhibitor therapy (sirolimus,rapamume). In-depth immunohistochemical and morphoproteomic analyses of this exceptional responder to targeted therapy have yielded potential insights into the biology of advanced HL. The PI3K/AKT/mTOR pathway is a commonly activated pathway in multiple tumor types including HL. The patient was treated using therapy based on mechanistic in vitro data demonstrating that combined histone deacetylase (HDAC) and mTOR inhibition act together on this pathway, resulting in inhibition of reciprocal feedback networks, leading to better anti-proliferative activity. The in vivo response signature from this patient's tissue sample sheds light on immune dysregulation in HL. We describe the response signature achieved from targeting immune dysregulation in addition to targeting the key oncogenic PI3K/AKT/mTOR pathway. We also expand on the role of rapamycin analogs in oncology. This study supports a role for an immune-type pathogenesis that is amenable to immune modulating targeted therapy in refractory HL. Significance: We report an exceptional responder to molecularly targeted and immune modulator therapy in advanced Hodgkin's lymphoma. The morphoproteomic/morphometric findings in this “unusual responder” patient's relapsed HL that correlate best, as a response

  14. Three Years Sustained Complete Remission Achieved in a Primary Refractory ALK-Positive Anaplastic T Large Cell Lymphoma Treated with Crizotinib

    Science.gov (United States)

    Mahuad, Carolina Valeria; Repáraz, María de los Ángeles Vicente; Zerga, Marta E.; Aizpurua, María Florencia; Casali, Claudia; Garate, Gonzalo

    2016-01-01

    The prognosis of the primary refractory anaplastic lymphoma kinase (ALK+) anaplastic T large cell lymphoma is ominous. The identification of molecular targets with potential to drive oncogenesis remains a cornerstone for the designing of new selective cancer therapies. Crizotinib is a selective ATP-competitive inhibitor for ALK, approved for its use in lung cancer with rearrangements on ALK gene. The reported cases describe the use of crizotinib as a bridging strategy prior to allotransplantation; there are no reported prolonged survivals under monotherapy with Crizotinib. We report a case of a primary refractory ALK+ anaplastic large-cell lymphoma that sustains complete response after 3 years of crizotinib monotherapy. PMID:27441079

  15. PET/CT before autologous stem cell transplantation predicts outcome in refractory/relapsed follicular lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Alcantara, Marion; Tilly, Herve [Universite de Rouen, Service d' Hematologie, Centre Henri Becquerel, Rouen (France); Dupuis, Jehan; Haioun, Corinne [CHU Henri Mondor et Universite Paris-Est, Assistance Publique - Hopitaux de Paris, Unite Hemopathies Lymphoides, Marechal de Lattre de Tassigny (France); Mareschal, Sylvain; Dubois, Sydney [Centre Henri Becquerel, IRIB, Unite Inserm U918, Rouen (France); Julian, Anne [CHU Purpan, Service de Medecine Nucleaire, Toulouse (France); Cottereau, Anne Segolene; Becker, Stephanie [Centre Henri Becquerel, Service de Medecine Nucleaire, Rouen (France); Oberic, Lucie; Huynh, Anne; Laurent, Guy; Ysebaert, Loic [IUCT-Oncopole, Departement d' Hematologie, Toulouse (France); Meignan, Michel [CHU Henri-Mondor, Service de Medecine Nucleaire, Paris (France)

    2014-09-20

    Salvage of young patients with follicular lymphoma (FL) after R-CHOP includes salvage immunochemotherapy followed by autologous stem cell transplantation (ASCT). Previous studies dealing with relapsed Hodgkin lymphoma have shown the prognostic value of PET/CT prior to ASCT. We retrospectively analysed 59 patients with refractory/relapsed FL after first-line R-CHOP who were chemosensitive (as evaluated by CT) to the salvage treatment and who proceeded to ASCT. The role of PET/CT in this setting to define chemosensitivity is not definitely established. So we focused on the prognostic value of PET/CT performed after salvage treatment, before ASCT. The estimated 3-year progression-free survival (PFS) and overall survival were 63.1 % (50.9-78.3 %) and 90.5 % (82.8 - 98.8 %), respectively, and did not differ significantly according to their Follicular Lymphoma International Prognostic Index at relapse, conditioning regimen, or type of salvage. PFS was significantly lower in PET/CT-positive patients, according to the International Harmonization Project revised response criteria, with a 3-year PFS of 45.5 % (26.6 - 77.8 %) versus 72.6 % (58.5 - 90.0 %; p = 0.039). To better refine prognosis, we applied two types of thresholds: a Deauville five-point scale positive threshold of ≥3 (3-year PFS of 74.9 %, range 61.0 - 92.1 % %, versus 42.8 %, range 24.7 - 74.4 %; p = 0.02), and a ≥70 % ∇SUV{sub max} threshold between presalvage and pre-ASCT PET/CT (3-year PFS of 72.4 %, range 57.5 - 91.3 % versus 13.3 %, 2.2 - 81.7 %; p < 10{sup -3}). The PET/CT findings before ASCT were independently correlated with PFS in our series. PET/CT negativity before ASCT is a desirable and achievable goal in the management of chemosensitive FL relapsing after first-line R-CHOP. (orig.)

  16. Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

    Science.gov (United States)

    Moccia, Alden A; Hitz, Felicitas; Hoskins, Paul; Klasa, Richard; Power, Maryse M; Savage, Kerry J; Shenkier, Tamara; Shepherd, John D; Slack, Graham W; Song, Kevin W; Gascoyne, Randy D; Connors, Joseph M; Sehn, Laurie H

    2017-02-01

    The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

  17. Pretreatment T lymphocyte numbers are contributing to the prognostic significance of absolute lymphocyte numbers in B-cell non-Hodgkins lymphomas.

    Science.gov (United States)

    Gergely, Lajos; Váncsa, Andrea; Miltényi, Zsófia; Simon, Zsófia; Baráth, Sándor; Illés, Árpád

    2011-06-01

    Targeted immuno-chemotherapy resulted in greatly improved survival of B cell lymphoma patients. Several prognostic markers are investigated, amongst them the pretreatment absolute lymphocyte numbers. We investigated lymphocyte subpopulations and correlated this data with prognosis of patients. 88 patients (mean age: 56 years, 18-88, median follow up 32 months) with B cell lymphomas were investigated. There were 51 DLBCL, 16 Follicular NHL, 4 MALT, 7 Marginal Zone NHL, 10 Small lymphocytic cases were investigated. Our data showed that overall survival was statistically significant up to the 0.9 G/l absolute lymphocyte numbers as dividers between the subgroups. The CD19+ B cell numbers, or the CD56+/CD3- NK cell numbers did not represent any significant differences between subgroups. However CD3+, CD4+ and CD8+ T cells were differentiating statistically significant subgroups. Pretreatment CD3+ cell number less than 700/ul and CD8+ cell number less than 200/ul were corresponding with significantly inferior overall survival. These could be verified in the bad prognostic IPI group as well. Our data further support the importance of pretreatment lymphocyte numbers and highlight CD3+ and CD8+ lymphocytes to be the key factors in predicting outcome.

  18. B-small lymphocytic lymphoma/chronic lymphocytic leukemia in cranio-orbital region with osteolytic performance

    Directory of Open Access Journals (Sweden)

    Jie QIAO

    2016-08-01

    Full Text Available Objective To report a case of B-small lymphocytic lymphoma (SLL/chronic lymphocytic leukemia (CLL with osteolytic performance invading the intracranial and orbital part, and to analyze the clinical manifestations, imaging features, histological patterns and immunohistochemical phenotypes, diagnosis and treatment strategies of this disease combined with review of literatures.  Methods and Results A 60-year-old female presented with left orbital swelling with intermittent headache. Head MRI showed space-occupying lesions invading left frontotemporal lobe, left greater wing of sphenoid bone, left lateral wall of sphenoid sinus, left lateral and upper orbital wall. Three-dimensional reconstructed CT showed extensive bone destruction in left frontal, temporal and sphenoid bone. The patient underwent tumor resection under general anesthesia. Histologically, the tumor cells were diffusely distributed. The nuclei were small, round and hyperchromatic, with sparse nucleoli and cytoplasm. The membrane of tumor cells were diffusely positive for CD5, positive for CD20 and CD43, partially positive for CD23, focally positive for CD138, sparsely positive for CD38 and sporadically positive for MUM1. The membrane and cytoplasm of tumor cells were positive for epithelial membrane antigen (EMA. The cytoplasm was positive for immunoglobulin κ-chain. Cyclin D1, CD10, CD56, Bcl-6, glial fibrillary acidic protein (GFAP, synaptophysin (Syn and immunoglobulin λ-chain were negative. Ki-67 labeling index was about 70% . Final pathological diagnosis was B-SLL/CLL. The patient was treated by postoperative chemotherapy, and the 6-month follow-up showed a fine survival.  Conclusions The clinical manifestations of central nervous system (CNS lymphomas are various, and the imaging features are atypical. A definite diagnosis depends on histopathological diagnosis. B-SLL/CLL should be differentiated from CNS metastatic tumors, other primary CNS tumors and other hematological

  19. Autologous hematopoietic stem cell transplantation in lymphoma patients is associated with a decrease in the double strand break repair capacity of peripheral blood lymphocytes.

    Science.gov (United States)

    Lacoste, Sandrine; Bhatia, Smita; Chen, Yanjun; Bhatia, Ravi; O'Connor, Timothy R

    2017-01-01

    Patients who undergo autologous hematopoietic stem cell transplantation (aHCT) for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML). Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC), which is thought to influence the effect chemotherapeutic treatments have on the patient's stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals. Initially, we investigated the cell model in healthy individuals (primary lymphocytes and/or lymphoblastoid cell lines) that would be appropriate to measure genetically determined DRC using host-cell reactivation assays. We present evidence that interindividual differences in DRC double-strand break repair (by non-homologous end-joining [NHEJ] or single-strand annealing [SSA]) are better preserved in non-induced primary lymphocytes. In contrast, lymphocytes induced to proliferate are required to assay base excision (BER) or nucleotide excision repair (NER). We established that both NHEJ and SSA DRCs in lymphocytes of healthy individuals were inversely correlated with the age of the donor, indicating that DSB repair in lymphocytes is likely not a constant feature but rather something that decreases with age (~0.37% NHEJ DRC/year). To investigate the predictive value of pre-aHCT DRC on outcome in patients, we then applied the optimized assays to the analysis of primary lymphocytes from lymphoma patients and found that individuals who later developed t-MDS/AML (cases) were indistinguishable in their DRC from controls who never developed t-MDS/AML. However, when DRC was investigated shortly after aHCT in the same individuals (21.6 months later on average), aHCT patients (both cases and controls) showed a significant decrease in DSB repair measurements. The average decrease of 6.9% in NHEJ DRC observed among aHCT patients was much higher

  20. Autologous hematopoietic stem cell transplantation in lymphoma patients is associated with a decrease in the double strand break repair capacity of peripheral blood lymphocytes

    Science.gov (United States)

    Lacoste, Sandrine; Bhatia, Smita; Chen, Yanjun; Bhatia, Ravi; O’Connor, Timothy R.

    2017-01-01

    Patients who undergo autologous hematopoietic stem cell transplantation (aHCT) for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML). Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC), which is thought to influence the effect chemotherapeutic treatments have on the patient’s stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals. Initially, we investigated the cell model in healthy individuals (primary lymphocytes and/or lymphoblastoid cell lines) that would be appropriate to measure genetically determined DRC using host-cell reactivation assays. We present evidence that interindividual differences in DRC double-strand break repair (by non-homologous end-joining [NHEJ] or single-strand annealing [SSA]) are better preserved in non-induced primary lymphocytes. In contrast, lymphocytes induced to proliferate are required to assay base excision (BER) or nucleotide excision repair (NER). We established that both NHEJ and SSA DRCs in lymphocytes of healthy individuals were inversely correlated with the age of the donor, indicating that DSB repair in lymphocytes is likely not a constant feature but rather something that decreases with age (~0.37% NHEJ DRC/year). To investigate the predictive value of pre-aHCT DRC on outcome in patients, we then applied the optimized assays to the analysis of primary lymphocytes from lymphoma patients and found that individuals who later developed t-MDS/AML (cases) were indistinguishable in their DRC from controls who never developed t-MDS/AML. However, when DRC was investigated shortly after aHCT in the same individuals (21.6 months later on average), aHCT patients (both cases and controls) showed a significant decrease in DSB repair measurements. The average decrease of 6.9% in NHEJ DRC observed among aHCT patients was much

  1. ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases

    Directory of Open Access Journals (Sweden)

    Ungur R

    2015-10-01

    Full Text Available Rodica Ungur,1,2 Adrian Tempescul,3 Christian Berthou,3 Cristina Bagacean,1,2 Doinel Radeanu,1 Adriana Muresan,1 Mihnea Zdrenghea1,21Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, 2Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania; 3Department of Clinical Hematology, Institute of Cancerology and Hematology, Brest Teaching Hospital, Brest, FranceAbstract: Primary central nervous system non-Hodgkin’s lymphoma is a rare presentation, almost always of diffuse large B-cell type. Although there is no consensus regarding therapy for this condition, induction regimens are based on high-dose methotrexate and consolidation whole-brain radiotherapy, or, more preferred recently, blood–brain barrier penetrating drugs such as etoposide, cytarabine, and alkylating agents like temozolomide, ifosfamide, and lomustine. We present here four cases of relapsed/refractory primary central nervous system lymphoma treated with ESHAP (etoposide, solumedrol, high-dose cytarabine, and platinum chemotherapy to complete remission, with the eligible patients proceeding to autologous transplantation. We want to draw attention to this interesting, relatively well tolerated, underused therapeutic option, in a setting where treatment options are scarce and evidence-based recommendations are lacking.Keywords: cerebral lymphoma, PCNSL, refractory, relapsed, platinum

  2. T-Cell Lymphoma

    Science.gov (United States)

    Getting the Facts T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). T-cell lymphomas account for ...

  3. General Information about Adult Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Lymphoma Treatment AIDS-Related Lymphoma Treatment Chronic Lymphocytic Leukemia Treatment (small lymphocytic lymphoma) Mycosis Fungoides (Including Sézary Syndrome) Treatment (cutaneous T-cell lymphoma) Primary CNS Lymphoma Treatment Non-Hodgkin lymphoma ...

  4. Treatment Option Overview (Adult Non-Hodgkin Lymphoma)

    Science.gov (United States)

    ... Lymphoma Treatment AIDS-Related Lymphoma Treatment Chronic Lymphocytic Leukemia Treatment (small lymphocytic lymphoma) Mycosis Fungoides (Including Sézary Syndrome) Treatment (cutaneous T-cell lymphoma) Primary CNS Lymphoma Treatment Non-Hodgkin lymphoma ...

  5. Nodular lymphocyte predominant hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma--endpoints of a spectrum of one disease?

    Directory of Open Access Journals (Sweden)

    Sylvia Hartmann

    Full Text Available In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL, T cell/histiocyte rich large B cell lymphoma (THRLBCL is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants of NLPHL with considerable histopathologic overlap compared to THRLBCL. Especially THRLBCL-like NLPHL, a diffuse form of NLPHL, often presents a histopathologic pattern similar to THRLBCL, suggesting a close relationship between both lymphoma entities. To corroborate this hypothesis, we performed gene expression profiling of microdissected tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. In unsupervised analyses, the lymphomas did not cluster according to their entity. Moreover, even in supervised analyses, very few consistently differentially expressed transcripts were found, and for these genes the extent of differential expression was only moderate. Hence, there are no clear and consistent differences in the gene expression of the tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. Based on the gene expression studies, we identified BAT3/BAG6, HIGD1A, and FAT10/UBD as immunohistochemical markers expressed in the tumor cells of all three lymphomas. Characterization of the tumor microenvironment for infiltrating T cells and histiocytes revealed significant differences in the cellular composition between typical NLPHL and THRLBCL cases. However, THRLBCL-like NLPHL presented a histopathologic pattern more related to THRLBCL than NLPHL. In conclusion, NLPHL and THRLBCL may represent a spectrum of the same disease. The different clinical behavior of these lymphomas may be strongly influenced by differences in the lymphoma microenvironment, possibly related to the immune status of the patient at the timepoint of diagnosis.

  6. Salvage chemotherapy of gemcitabine, dexamethasone, and cisplatin (GDP) for patients with relapsed or refractory peripheral T-cell lymphomas: a consortium for improving survival of lymphoma (CISL) trial.

    Science.gov (United States)

    Park, Byeong-Bae; Kim, Won Seog; Suh, Cheolwon; Shin, Dong-Yeop; Kim, Jeong-A; Kim, Hoon-Gu; Lee, Won Sik

    2015-11-01

    There is no standard salvage chemotherapy for relapsed or refractory peripheral T-cell lymphomas (PTCLs). Gemcitabine combined with cisplatin has been known as an effective regimen for lymphoma treatment in the salvage setting. We investigated the efficacy and toxicity of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory PTCLs in search of a more effective and less toxic therapy. Patients with relapsed or refractory PTCLs with more than one previous regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4, and cisplatin 70 mg/m(2) i.v. on day 1, and then every 21 days. Patients could proceed to autologous stem cell transplantation (ASCT) after four cycles of GDP or receive up to six treatment cycles. Twenty-five eligible patients were evaluated for toxicity and response. The diagnoses of participants included 14 cases of PTCL-not otherwise specified (NOS) (56 %) and four cases of angioimmunoblastic T-cell lymphoma (16 %) among others. The median age of the patients was 59 years (range 20-75 years). After treatments with GDP, which delivered a median of four GDP cycles, there were 12 patients with complete responses (CR; 48 %) and six with partial responses (PR; 24 %). The overall response rate (RR) was 72 %. Four patients preceded to ASCT, and three patients finally achieved CR. The median progression free survival was 9.3 months (95 % confidence interval (CI); 4.1-14.6) with a median follow-up duration of 27.1 months. In a total of 86 cycles of GDP, grade 3 or 4 neutropenia and thrombocytopenia occurred in 16.3 and 12.8 % of cycles, respectively. Three patients (3.3 %) experienced febrile neutropenia. GDP is a highly effective and optimal salvage regimen for relapsed or refractory PTCLs and can be administered with acceptable toxicity.

  7. Emergence of Bruton's tyrosine kinase-negative Hodgkin lymphoma during ibrutinib treatment of chronic lymphocytic leukaemia.

    Science.gov (United States)

    Glavey, Siobhan; Quinn, John; McCloy, Mary; Sargent, Jeremy; McCartney, Yvonne; Catherwood, Mark; Marafioti, Teresa; Leader, Mary; Murphy, Philip; Thornton, Patrick

    2017-10-01

    Chronic lymphocytic leukaemia (CLL) is a chronic B-cell lympho-proliferative disorder in which lymphomatous transformations occur in 5%-15% of patients. Histologically these cases resemble diffuse large B-cell lymphoma, or Richter's transformation, in over 80% of cases. Rare cases of transformation to Hodgkin lymphoma (HL) have been reported in the literature with an estimated prevalence of 0.4%. We report a case of a 67-year-old female with CLL treated with the novel Bruton's tyrosine kinase (Btk) inhibitor, ibrutinib, who subsequently presented with intractable fevers. Bone marrow trephine, and lymph node biopsy revealed classical HL with negative immuno-histochemistry for Btk in HL cells, on a backdrop of CLL. The patient commenced treatment with Adriamycin, Vinblastine and Dacarbazine (AVD), which resulted in an excellent response. Hodgkin transformation of CLL is rare with a single retrospective study of 4121 CLL patients reporting only 18 cases. Btk expression in HL cells is recently recognised in classical HL; however, the majority of HLs are Btk negative. Given that Btk inhibitors have recently been shown to induce genomic instability in B cells, in the context of their widespread use, such emerging cases are increasingly relevant. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Ispinesib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Lymphoma

    Science.gov (United States)

    2013-01-15

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Unspecified Childhood Solid Tumor, Protocol Specific

  9. Refractory Classical Hodgkin Lymphoma Presenting with Atypical Cutaneous Involvement and Diagnosis of ZZ Phenotype Alpha-1 Antitrypsin Deficiency

    Directory of Open Access Journals (Sweden)

    Mohamad Khawandanah

    2014-01-01

    Full Text Available Cutaneous Hodgkin lymphoma is a rare condition. Specific neoplastic involvement can be primary (confined to the skin or secondary to systemic involvement (metastatic. Cutaneous involvement by HL usually occurs late in the course and is associated with poor prognosis; however in some cases it can exhibit indolent behavior. Skin involvement with nonspecific cutaneous findings may represent a paraneoplastic syndrome. We describe a case of 46-year-old white male patient presented with rash and lymphadenopathy which led to the diagnosis of stage IVE mixed cellularity classical Hodgkin lymphoma with skin involvement. His disease was refractory to multiple lines of chemotherapy including (1 AVD (doxorubicin/bleomycin/dacarbazine, (2 brentuximab, and (3 bendamustine, he later achieved complete remission with (4 GCD (gemcitabine/carboplatin/dexamethasone salvage regimen. Bleomycin was not given secondary to poor pulmonary function tests. His treatment was complicated after AVD with multiple pneumothoraces which unmasked the diagnosis of ZZ phenotype alpha-1 antitrypsin (ATT deficiency. Simultaneous existence of Hodgkin lymphoma and ATT is rarely reported.

  10. Therapeutic Efficacy of L-asparaginase in the Treatment of Refractory Midfacial Peripheral T-Cell Non-Hodgkin's Lymphoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To improve the efficacy of refractory midfacial peripheral T-cell non-Hodgkin's lymphoma (MPTC-NHL) with L-asparaginase (L-ASP) based salvage chemotherapy. Methods: 21 patients with refractory MPTC-NHL were analyzed. 11patients (L-ASP group) received L-asparaginase based salvage chemotherapy consisting of L-asparaginase, vincristine and dexame-thosone. 10 patients (control group) received salvage combination chemotherapy without L-asparaginase. Results: Complete remission rates were 45.6% for L-ASP group and 0.0% for control group (p<0.05). Overall response rates (CR+PR) were 63.6% for L-ASP group and 10.0% for control group, respectively (p<0.05). 2-year survival rates were 45.5% for L-ASP group and 0.0% for control group (p<0.05). The major adverse effects of L-ASP were leukopenia, elevation of serum bilirubin and hyperglycemia. Conclusion: The preliminary clinical study shows that the L-ASP based salvage chemotherapy may improve the response rate and 2-year survival rate of the patients with refractory MPTC-NHL. It is necessary to continue the study further.

  11. An approach for conjugation of 177 Lu- DOTA-SCN- Rituximab (BioSim & its evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins lymphoma patients

    Directory of Open Access Journals (Sweden)

    Parul Thakral

    2014-01-01

    Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim in patients of relapsed and refractory non Hodgkin′s lymphoma can be considered.

  12. 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.

    Science.gov (United States)

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

    2017-08-26

    Although most classical Hodgkin lymphomas (CHL) 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 CHL are positive for these antigens. We investigated the utility of J chain and 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 (BCLU, DLBCL/CHL) compared to OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHL and were negative in 43/43 (100%) CHL. 14/15 (93%) PMBL and 4/4 (100%) TCRLBL were MEF2B-positive, while 67% of PMBL and 50% of TCRLBL were J chain-positive. 3/3 BCLU, DLBCL/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. Published by Elsevier Inc.

  13. Clinical role of obinutuzumab in the treatment of naive patients with chronic lymphocytic leukemia

    OpenAIRE

    Cerquozzi S; Owen C

    2015-01-01

    Sonia Cerquozzi,1 Carolyn Owen2 1Department of Hematology, University of Calgary, 2Department of Hematology, Tom Baker Cancer Centre, Calgary, AB, Canada Abstract: The introduction of targeted therapy against CD20+ with the monoclonal antibody rituximab has dramatically improved the survival of B-cell non-Hodgkin lymphoma including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma. Unfortunately, CLL remains incurable with chemoimmunotherapy, with many patients having refractory ...

  14. Immunoarchitectural patterns of progressive transformation of germinal centers with and without nodular lymphocyte-predominant Hodgkin lymphoma.

    Science.gov (United States)

    Hartmann, Sylvia; Winkelmann, Ria; Metcalf, Ryan A; Treetipsatit, Jitsupa; Warnke, Roger A; Natkunam, Yasodha; Hansmann, Martin-Leo

    2015-11-01

    Progressive transformation of germinal centers (PTGC) has been frequently described in association with Hodgkin lymphoma, particularly nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). The aim of this study was to evaluate morphologic features of PTGC for better delineation of PTGC from early involvement by NLPHL. A total of 160 cases of PTGC were evaluated and included in the following 3 groups: 93 patients with PTGC who never developed a lymphoma, 23 patients with synchronous PTGC and NLPHL, and 44 patients with PTGC with antecedent or subsequent history of lymphoma. By histopathologic evaluation, 5 patterns of PTGC that reflected progressive dismantling of germinal centers were identified. There was no difference in the distribution of patterns 1 to 4 among the 3 groups of PTGC; however, in patients showing synchronous involvement of PTGC and NLPHL, pattern 5, which resembles a naïve B-cell follicle, was significantly more frequently observed (14/23) when compared with patients with PTGC who never developed a lymphoma (30/93; P = .0161). Furthermore, recognition of the spectrum of immunoarchitectural patterns of PTGC, including architectural and cytologic features, was helpful to better differentiate nodules involved by PTGC from NLPHL.

  15. Outpatient-Based Therapy of Oral Fludarabine and Subcutaneous Alemtuzumab for Asian Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    William Y. K. Hwang

    2009-01-01

    Full Text Available Background. Intravenous alemtuzumab and fludarabine are effective in combination for the treatment of chronic lymphocytic leukemia (CLL, but require hospital visits for intravenous injection. We performed a pilot study to assess the safety and efficacy of outpatient-based oral fludarabine with subcutaneous alemtuzumab (OFSA for the treatment of relapsed/refractory CLL. Results. Depending on their response, patients were given two to six 28-day cycles of subcutaneous alemtuzumab 30 mg on days 1,3, and 5 and oral fludarabine 40 mg/m2/day for 5 days. Median patient age was 74. The lymphocyte counts of all five patients fell after the 1st cycle of treatment and reached normal/low levels on completion of 2 to 6 cycles of therapy. Platelet counts and hemoglobin were unaffected. All five patients achieved complete hematological remission, while two attained minimal residual disease negativity on 4-color flow cytometry. Conclusions. Our OFSA regimen was effective in elderly Asian patients with relapsed/refractory CLL, and it should be investigated further.

  16. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    Getting the Facts Peripheral T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma and ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Peripheral T-cell lymphoma (PTCL) ...

  17. Ocular Adnexal Lymphoma Presenting as Refractory Unilateral Open-angle Glaucoma.

    Science.gov (United States)

    Sears, Nathaniel C; Singh, Annapurna; Singh, Arun D

    2016-08-01

    We report a single case of masquerade glaucoma caused by increased episcleral venous pressure from adnexal lymphoma. The patient presented as a referral for unilateral glaucoma with intraocular pressures (IOPs) consistently >40 mm Hg (right eye). We present data conclusively demonstrating extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in the involved eye, and provide an account of the treatment of the tumor with sustained regression and complete resolution of his elevated IOP. We conclude with a discussion of the proposed mechanism. This case serves as a reminder that unilateral open-angle glaucoma can be a sign of indolent ocular adnexal lymphoma. The case also provides a useful model for increased IOP with orbital lesions.

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

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Yolanda D., E-mail: ydt2@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts (United States); Ng, Andrea [Department of Radiation Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2015-01-01

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

  19. Atypical variants of nodular lymphocyte-predominant Hodgkin lymphoma show low microvessel density and vessels of distention type.

    Science.gov (United States)

    Scheidt, Victoria; Hansmann, Martin-Leo; Schuhmacher, Bianca; Döring, Claudia; Hartmann, Sylvia

    2017-02-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) presents different histopathologic growth patterns, including atypical forms showing overlapping histopathologic and clinical features with T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL). Because growth patterns are associated with vessel distribution, the aim of the present study was to compare angiogenesis in different NLPHL patterns with THRLBCL as well as other lymphomas. Atypical variants of NLPHL and THRLBCL (n=10 per group) both showed a low microvessel density (MVD; 1.16-1.31/μm(2)) with a diffuse vessel distribution. In contrast, in typical NLPHL (n=10), follicular areas with low MVD were retained, whereas an increase in vessels in the interfollicular areas was observed (MVD 1.35/μm(2)). THRLBCL and typical NLPHL could additionally be distinguished by differences in their molecular angiogenesis signature. Furthermore, the number of intravascular T cells was significantly reduced in THRLBCL (0.0028 T cells/mm(2) vessel area) when compared with typical NLPHL (0.0059 T cells/mm(2) vessel area), potentially reflecting the different composition of the microenvironment in these 2 lymphoma entities. The results of our study reveal a similar vascular pattern and angiogenesis behavior in atypical NLPHL variants and THRLBCL in contrast to the retained follicular pattern in typical NLPHL. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Occupation and risk of non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

    Science.gov (United States)

    Zheng, Tongzhang; Blair, Aaron; Zhang, Yawei; Weisenburger, Dennis D; Zahm, Shelia H

    2002-05-01

    To investigate the association between occupation and the risk of non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), and to test whether the associations may vary by histological type of NHL, we analyzed data from two population-based, case-control studies of NHL performed in Kansas and Nebraska. A total of 555 incident NHL cases, 56 CLL cases, and 2380 population-based controls were included in the analysis. Information on occupation and other confounding factors was collected through telephone interviews. Study pathologists reviewed slides of tumor tissues in all cases. In men, we found an increased risk of NHL and CLL for those working in agricultural, forestry, and logging industries (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2 to 2.1). The OR was 1.9 (95% CI, 1.4 to 2.6) for those producing crops. An increased risk was also observed for industries involving metalworking machinery and equipment (OR, 8.4; 95% CI, 1.4 to 50.6), motor vehicles and motor vehicle equipment (OR, 4.2; 95% CI, 1.3 to 13.9), and telephone communications (OR, 3.1; 95% CI, 1.2 to 8.0), and for teachers (OR, 2.5; 95% CI, 1.0 to 6.5), farmers (OR, 2.0; 95% CI, 1.5 to 2.8), and welders and solderers (OR, 2.9; 95% CI, 1.2 to 6.9). The risks for these associations increased by duration of employment and seem to vary by histological type. Work in the printing and publishing industry was also associated with an increased risk of NHL among women. These data suggest that the workers employed in these industries or occupations experienced an increased risk of NHL and CLL, and the risks associated with these industries or occupations may vary by histological type of NHL.

  1. Hodgkin Lymphoma: Diagnosis and Treatment.

    Science.gov (United States)

    Ansell, Stephen M

    2015-11-01

    Hodgkin lymphoma is a rare B-cell malignant neoplasm affecting approximately 9000 new patients annually. This disease represents approximately 11% of all lymphomas seen in the United States and comprises 2 discrete disease entities--classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Within the subcategorization of classical Hodgkin lymphoma are defined subgroups: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich Hodgkin lymphoma. Staging of this disease is essential for the choice of optimal therapy. Prognostic models to identify patients at high or low risk for recurrence have been developed, and these models, along with positron emission tomography, are used to provide optimal therapy. The initial treatment for patients with Hodgkin lymphoma is based on the histologic characteristics of the disease, the stage at presentation, and the presence or absence of prognostic factors associated with poor outcome. Patients with early-stage Hodgkin lymphoma commonly receive combined-modality therapies that include abbreviated courses of chemotherapy followed by involved-field radiation treatment. In contrast, patients with advanced-stage Hodgkin lymphoma commonly receive a more prolonged course of combination chemotherapy, with radiation therapy used only in selected cases. For patients with relapse or refractory disease, salvage chemotherapy followed by high-dose treatment and an autologous stem cell transplant is the standard of care. For patients who are ineligible for this therapy or those in whom high-dose therapy and autologous stem cell transplant have failed, treatment with brentuximab vedotin is a standard approach. Additional options include palliative chemotherapy, immune checkpoint inhibitors, nonmyeloablative allogeneic stem cell transplant, or participation in a clinical trial testing novel agents.

  2. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study.

    Science.gov (United States)

    Cartron, Guillaume; de Guibert, Sophie; Dilhuydy, Marie-Sarah; Morschhauser, Franck; Leblond, Veronique; Dupuis, Jehan; Mahe, Beatrice; Bouabdallah, Reda; Lei, Guiyuan; Wenger, Michael; Wassner-Fritsch, Elisabeth; Hallek, Michael

    2014-10-02

    GAUGUIN evaluated the safety and efficacy of obinutuzumab (GA101) monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). In phase 1 (dose escalation), 13 patients received obinutuzumab 400 to 1200 mg (days 1 and 8 of cycle 1; day 1 of cycles 2-8). In phase 2, 20 patients received a fixed dose of 1000 mg (days 1, 8, and 15 of cycle 1; day 1 of cycles 2-8). Infusion-related reactions occurred in nearly all patients, but few were grade 3/4. Grade 3/4 neutropenia occurred in 7 patients in phase 1 (but was not dose-related) and in 4 patients in phase 2. Overall end-of-treatment response (all partial responses) was 62% (phase 1) and 15% (phase 2); best overall response was 62% and 30%, respectively. Phase 2 median progression-free survival was 10.7 months and median duration of response was 8.9 months. In summary, obinutuzumab monotherapy is active in patients with heavily pretreated relapsed/refractory CLL.

  3. Randomized controlled trials in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis.

    Science.gov (United States)

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

    2015-04-01

    This systematic literature review with meta-analysis was conducted on the clinical efficacy and safety of interventions used in the treatment of chronic lymphocytic leukemia (CLL). We systematically searched databases (PubMed, Cochrane Library, and Embase; 1997 to August 2, 2012), conference abstracts, bibliographic reference lists, recent reviews, and Clinicaltrials.gov. Primary efficacy outcomes were objective response rate, progression-free survival, and overall survival. Safety end points were Grade 3/4 toxicities, serious adverse events, withdrawals because of toxicity, and deaths due to toxicity. Studies were selected if they were randomized controlled trials (RCTs) reporting on the efficacy or safety of relapsed or refractory CLL and if outcomes for CLL were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 6 RCTs of pharmacologic treatment for relapsed/refractory CLL. The most common drugs investigated (alone or in combination) were fludarabine and cyclophosphamide. When reported, median overall survival ranged from 27.3 to 52.9 months, and overall response rate from 58% to 82%. Although meta-analysis of efficacy results was considered, details are not presented because only 3 studies qualified and the common comparator treatment was not clinically relevant. The relatively small number of RCTs, few overlapping treatment arms, and variability in end points studied make it difficult to formally compare therapies for relapsed/refractory CLL. Significant variability in RCT features presents a further challenge to meaningful comparisons. Additional well-designed RCTs are needed to fully understand the relative efficacy and safety of older and more recently developed therapies.

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

    Directory of Open Access Journals (Sweden)

    Wilfred Delacruz

    2016-01-01

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

  5. Clinical efficacy and safety in relapsed/refractory diffuse large B-cell lymphoma: a systematic literature review.

    Science.gov (United States)

    Colosia, Ann; Njue, Annete; Trask, Peter C; Olivares, Robert; Khan, Shahnaz; Abbe, Adeline; Police, Rachel; Wang, Jianmin; Ruiz-Soto, Rodrigo; Kaye, James A; Awan, Farrukh

    2014-10-01

    This systematic literature review was designed to assess information on the clinical efficacy and safety of interventions used in the treatment of refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL) and to perform a meta-analysis if possible. We searched databases (PubMed, EMBASE, and Cochrane Library for articles from 1997 to August 2, 2012 reported in English), conference abstracts, bibliographic reference lists, and the ClinicalTrials.gov database for phase II to IV studies with results. Studies had to report on patients with R/R DLBCL who were not eligible to receive high-dose therapy (HDT) with stem cell transplantation (SCT) (autologous or allogeneic). Mixed-type non-Hodgkin lymphoma (NHL) studies were required to report R/R DLBCL outcomes separately. We identified 55 studies that presented outcomes data separately for patients with R/R DLBCL. Of 7 comparative studies, only 4 were randomized controlled trials (RCTs). In the 2 RCTs with a common regimen, the patient populations differed too greatly to perform a valid meta-analysis. The 48 single-arm studies identified were typically small (n < 50 in most), with 31% reporting median progression-free survival (PFS) or overall survival (OS) specifically for the R/R DLBCL population. In these studies, median OS ranged from 4 to 13 months. The small number of RCTs in R/R DLBCL precludes identifying optimal treatments. Small sample size, infrequent reporting of OS and PFS separated by histologic type, and limited information on patient characteristics also hinder comparison of results. Randomized studies are needed to demonstrate which current therapies have advantages for improving survival and other important clinical outcomes in patients with R/R DLBCL.

  6. Management of Nodular Lymphocyte Predominant Hodgkin Lymphoma in the Modern Era

    Energy Technology Data Exchange (ETDEWEB)

    King, Martin T., E-mail: mking1@stanford.edu [Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California (United States); Donaldson, Sarah S. [Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California (United States); Link, Michael P. [Department of Pediatrics, Stanford Cancer Institute, Stanford, California (United States); Natkunam, Yasodha [Department of Pathology, Stanford Cancer Institute, Stanford, California (United States); Advani, Ranjana H. [Department of Medicine, Stanford Cancer Institute, Stanford, California (United States); Hoppe, Richard T. [Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California (United States)

    2015-05-01

    Purpose: To analyze treatment outcomes for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) at a single institution. Patients and Methods: Patients with newly diagnosed NLPHL between 1996 and 2013 were reviewed retrospectively. Patients treated before 1996 were excluded because the majority received extended field radiation therapy (RT) alone. Results: Fifty-five patients (22 ≤ 21 years old) were identified. The median follow-up time was 6.8 years. Among 37 patients with limited-stage (I-II) disease, treatments included involved field RT at a median dose of 36 Gy (n=9), rituximab monotherapy (n=9), observation (n=3), and response-adaptive therapy (n=16), in which the RT dose was reduced from 25.5 Gy to 15 Gy or was eliminated based on interim imaging after chemotherapy. The 5-year progression-free survival (PFS) was 76.4% (95% confidence interval [CI], 63.1-92.4). Nine patients experienced progression, including 5 receiving rituximab, 2 undergoing observation, and 2 receiving response-adaptive therapy. Rituximab was associated with an inferior PFS compared with RT alone (P=.02). The difference in PFS between response-adaptive therapy and RT alone was not statistically significant (P=.39). Among 18 patients with advanced-stage (III-IV) disease, treatments included chemotherapy alone (n=3), combined modality therapy (CMT) (n=2), response-adaptive therapy (n=2), rituximab (n=7), and observation (n=4). The 5-year PFS was 29.9% (CI, 13.3-67.4). Twelve patients experienced progression, including 1 receiving chemotherapy, 1 receiving CMT, 6 receiving rituximab, and 4 undergoing observation. There was no significant PFS difference between rituximab and non-rituximab therapies (P=.19) within the caveat of small sample sizes. In the entire cohort, 9 patients (3 with limited disease, 6 with advanced disease) experienced large cell transformation (LCT). Seven patients died; of those, 5 died with LCT. Conclusions: For limited disease, response-adaptive therapy

  7. Angioimmunoblastic T-Cell Lymphoma

    Science.gov (United States)

    Angioimmunoblastic T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Cancerous lymphocytes can travel to ...

  8. SOLITARY T-CELL HEPATIC LYMPHOMA WITH LARGE GRANULAR LYMPHOCYTE MORPHOLOGY IN A CAPTIVE CHEETAH (ACINONYX JUBATUS).

    Science.gov (United States)

    Lindemann, Dana M; Carpenter, James W; Almes, Kelli M; Schumacher, Loni; Ryseff, Julia K; Hallman, Mackenzie

    2015-06-01

    A 13-yr-old male cheetah (Acinonyx jubatus) presented for an acute history of lateral recumbency and anorexia. Upon physical examination under general anesthesia, severe icterus was noted. A serum biochemical profile confirmed markedly elevated total bilirubin and alanine transaminase. Based on ultrasound-guided liver aspirates and cytology, a presumptive diagnosis of large granular lymphocyte hepatic lymphoma was reached. Abdominal and thoracic radiographs did not assist in reaching an antemortem diagnosis. Postmortem examination and histopathology provided a definitive diagnosis of hepatic lymphoma with acute massive hepatocelluar necrosis and hemorrhage, as well as concurrent lesions of gastric ulcers, ulcerative and sclerosing enteritis, myocardial hypertrophy, and splenic myelolipomas. Immunohistochemistry of the liver yielded CD-3 positive and CD-20 negative results, confirming lymphocytes of a T-cell lineage. Due to concern for possible retrovirus-associated disease, enzyme-linked immunosorbent assays for feline leukemia virus and feline immunodeficiency virus were performed retrospectively on a banked serum sample and yielded negative results, thus diminishing concern for the male conspecific housed in the same exhibit.

  9. Phase I study of bryostatin 1 and fludarabine in patients with chronic lymphocytic leukemia and indolent (non-Hodgkin's) lymphoma.

    Science.gov (United States)

    Roberts, John D; Smith, Mitchell R; Feldman, Eric J; Cragg, Louise; Millenson, Michael M; Roboz, Gail J; Honeycutt, Connie; Thune, Rose; Padavic-Shaller, Kristin; Carter, W Hans; Ramakrishnan, Viswanathan; Murgo, Anthony J; Grant, Steven

    2006-10-01

    Preclinical studies suggested that bryostatin 1 might potentiate the therapeutic effects of fludarabine in the treatment of hematologic malignancies. We undertook a phase I study to identify appropriate schedules and doses of bryostatin 1 and fludarabine to be used in phase II studies. Patients with chronic lymphocytic leukemia (CLL) or indolent lymphoma received fludarabine daily for 5 days and a single dose of bryostatin 1 via a 24-hour continuous infusion either before or after the fludarabine course. Doses were escalated in successive patients until recommended phase II doses for each sequence were identified on the basis of dose-limiting toxic events. Bryostatin 1 can be administered safely and tolerably with full dose fludarabine (25 mg/m(2)/d x 5). The recommended bryostatin 1 phase II dose is 50 microg/m(2) for both sequences, bryostatin 1 --> fludarabine and fludarabine --> bryostatin 1. The combination is active against both CLL and indolent lymphomas with responses seen in patients who had been previously treated with fludarabine. Correlative studies do not support the hypothesis that bryostatin 1 potentiates fludarabine activity through down-regulation of protein kinase C in target cells. Bryostatin 1 can be administered with full dose fludarabine, and the combination is moderately active in patients with persistent disease following prior treatment. In view of the activity of monoclonal antibodies such as the anti-CD20 monoclonal antibody rituximab in the treatment of CLL and indolent lymphomas, the concept of combining bryostatin 1 and fludarabine with rituximab warrants future consideration.

  10. Mogamulizumab for the treatment of relapsed or refractory adult T-cell leukemia-lymphoma.

    Science.gov (United States)

    Winsett, Frank T; Lewis, Daniel J; Duvic, Madeleine

    2017-09-01

    Adult T-cell leukemia-lymphoma (ATL) is an aggressive variant of peripheral T-cell lymphoma of CD4+ T-malignant cells caused by human T-lymphotropic virus type-1. Despite aggressive treatment with multidrug combination chemotherapies, ATL confers a poor prognosis and commonly develops resistance to conventional treatments. Areas covered: Mogamulizumab is a humanized, defucosylated monoclonal antibody that acts by targeting the CC chemokine receptor 4 (CCR4) on malignant cells of ATL. In phase I and II clinical trials, it has achieved overall response rates of 31-50% in CCR4+ malignancies. The most commonly observed hematologic and non-hematologic adverse events included lymphocytopenia, neutropenia, leukocytopenia, infusion reaction, rash, and pyrexia. Expert commentary: Mogamulizumab has shown significant efficacy in treating ATL with moderately high response rates and has been approved in Japan for use in ATL. It may serve as a bridge therapy to achieve disease control prior to allogeneic hematopoietic stem cell transplantation. It also offers potential for use in combination with conventional chemotherapy. Determining the optimal combination of mogamulizumab with conventional and novel therapies remains an important strategy to improve the prognosis of patients with ATL.

  11. Lenalidomide induced good clinical response in a patient with multiple relapsed and refractory Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Kolonic Slobodanka

    2010-05-01

    Full Text Available Abstract Background A 24-year-old female patient was diagnosed with classic Hodgkin's lymphoma in clinical stage II, and combination chemotherapy followed by radiotherapy was initiated. During the following 5 years, the disease progressed despite several standard therapeutic approaches, including autologous and allogeneic stem cell transplantation. Methods Lenalidomide (25 mg daily treatment was then initiated in a continuous dosing schedule. Positron emission tomography scans were performed before and during lenalidomide treatment. Hematologic and laboratory values, as well as physical condition were also assessed before and during lenalidomide treatment. Results Four months after continuous lenalidomide treatment, tumor load was significantly reduced, B symptoms had resolved, and the patient's physical condition had improved, allowing her to resume normal daily-living activities. Evaluations after 15 months of lenalidomide treatment indicated limited disease progression. Nevertheless, the patient was feeling well and maintaining a normal active life. Treatment was well tolerated, allowing the patient to remain on continuous dosing, which has now been maintained for 18 months. Conclusion Daily, long-term lenalidomide treatment provided clinical benefit and was well tolerated in a patient with relapsed, advanced classic Hodgkin's lymphoma.

  12. Case Study in RefractoryNon-Hodgkin’s Lymphoma: Successful Treatment with Plerixafor

    Directory of Open Access Journals (Sweden)

    Hamdy Abdel Azim

    2011-09-01

    Full Text Available The present case study describes our experience in treating a young woman diagnosed with a relapsing case of diffuse large cell lymphoma, who was heavily pre-treated with chemotherapy and radiotherapy. Our only chance to improve her survival was by using high-dose chemotherapy, followed by peripheral stem cell rescue. Unfortunately, in this patient, collecting sufficient stem cells for bone marrow transplantation proved to be very difficult since she had already been heavily treated with chemotherapy and radiotherapy. Currently, granulocyte colony-stimulating factor (G-CSF alone or G-CSF plus chemotherapy are the most commonly used treatments for stem cell mobilization. However, 5–30% of patients do not respond to these agents. Plerixafor is a new hematopoietic stem cell-mobilizing drug that antagonizes the binding of chemokine stromal cell-derived factor-1α to CXC chemokine receptor 4. It is indicated in combination with G-CSF to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma [Kessans et al.: Pharmacotherapy 2010;30:485–492; Jantunen: Expert Opin Biol Ther 2011;11:1241–1248]. Based on our findings, we consider plerixafor to be a very efficient and practical solution to mobilize and collect stem cells among all patients in such a situation, enabling us to proceed to autologous bone marrow transplantation and peripheral stem cell rescue in order to improve the patients’ overall survival.

  13. Efficacy of lenalidomide in relapsed/refractory chronic lymphocytic leukemia patient: a systematic review and meta-analysis.

    Science.gov (United States)

    Liang, Liang; Zhao, Ming; Zhu, Yuan-Chao; Hu, Xin; Yang, Li-Ping; Liu, Hui

    2016-09-01

    Therapeutic results of relapsed/refractory chronic lymphocytic leukemia (CLL) are very disappointing at present. Lenalidomide has been proved to be effective for relapsed/refractory CLL as a single agent or in combination with various chemo-immunotherapeutic regimens. However, current clinical experience in its usage is still limited. Because of existing considerable variability in different studies, a systematic review and meta-analysis was conducted to describe overall response rate (ORR) of lenalidomide in patients with relapsed/refractory CLL. Pooled estimate of cumulative prevalence of total ORR was 42.23 % (95 % confidence interval [CI], 32.49-52.61 %), while pooled ORR in regimen with lenalidomide plus anti-CD20 monoclonal antibody (mAbs) and lenalidomide mono-therapy were 60.01 % (95 % CI, 53.86-65.86 %) and 24.38 % (95 % CI, 16.15-35.06 %), respectively. There was no significant difference between L + R (lenalidomide plus rituximab) group and L + O (lenalidomide plus ofatumumab) group, with pooled ORR of 66.38 % (95 % CI, 57.96-73.87 %) and 57.40 % (95 % CI, 46.46-67.65 %), respectively. When co-administrated with anti-CD20 mAbs, dosage of lenalidomide was not the key factor of ORR in combination therapy. Pooled ORR of patient with high-risk cytogenetic in L + anti-CD20 mAbs group was 56.74 % (95 % CI, 45.53-67.30 %). In comparison with patients without high-risk cytogenetic receiving the same treatment regimen, no significant difference was observed, with relative risk (RR) of 0.87 (95 % CI 0.68-1.11). Our finding demonstrated that lenalidomide plus anti-CD20 mAbs could be an efficient therapy regimen for relapsed/refractory CLL patients, especially for those with high-risk cytogenetic factor.

  14. NK cell function is markedly impaired in patients with chronic lymphocytic leukaemia but is preserved in patients with small lymphocytic lymphoma.

    Science.gov (United States)

    Parry, Helen M; Stevens, Tom; Oldreive, Ceri; Zadran, Bassier; McSkeane, Tina; Rudzki, Zbigniew; Paneesha, Shankara; Chadwick, Caroline; Stankovic, Tatjana; Pratt, Guy; Zuo, Jianmin; Moss, Paul

    2016-10-18

    Chronic lymphocytic leukemia (B-CLL) and small lymphocytic lymphoma (SLL) are part of the same disease classification but are defined by differential distribution of tumor cells. B-CLL is characterized by significant immune suppression and dysregulation but this is not typical of patients with SLL. Natural killer cells (NK) are important mediators of immune function but have been poorly studied in patients with B-CLL/SLL. Here we report for the first time the NK cell phenotype and function in patients with B-CLL and SLL alongside their transcriptional profile. We show for the first time impaired B-CLL NK cell function in a xenograft model with reduced activating receptor expression including NKG2D, DNAM-1 and NCRs in-vitro. Importantly, we show these functional differences are associated with transcriptional downregulation of cytotoxic pathway genes, including activating receptors, adhesion molecules, cytotoxic molecules and intracellular signalling molecules, which remain intact in patients with SLL. In conclusion, NK cell function is markedly influenced by the anatomical site of the tumor in patients with B-CLL/SLL and lymphocytosis leads to marked impairment of NK cell activity. These observations have implications for treatment protocols which seek to preserve immune function by limiting the exposure of NK cells to tumor cells within the peripheral circulation.

  15. Severe Acute Pulmonary Toxicity Associated with Brentuximab in a Patient with Refractory Hodgkin’s Lymphoma

    Directory of Open Access Journals (Sweden)

    Yasmin Sabet

    2016-01-01

    Full Text Available Acute pulmonary toxicity associated with brentuximab appears to be a rare but serious adverse effect that can be potentially fatal. We report the case of a twenty-nine-year-old female with Hodgkin’s lymphoma who was treated with brentuximab and later presented with severe acute pulmonary toxicity; she improved after the discontinuation of brentuximab and administration of antibiotics and glucocorticoid therapy. Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique.

  16. Single-institution long-term outcomes for patients receiving nonmyeloablative conditioning hematopoeitic cell transplantation for chronic lymphocytic leukemia and follicular lymphoma

    DEFF Research Database (Denmark)

    Mortensen, Bo K; Petersen, Søren; Kornblit, Brian;

    2012-01-01

    Non-myeloablative conditioning hematopoietic cell transplantation (NMC-HCT) has improved the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). In a cohort of 85 patients (45 with CLL and 40 with FL), we observed 5-yr overall survival (OS) and progression-free survival ...

  17. Phase II study of palliative low-dose local radiotherapy in disseminated indolent non-Hodgkin's lymphoma and chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Jóhannsson, Jakob; Specht, Lena; Mejer, Johannes

    2002-01-01

    Indolent non-Hodgkin's lymphoma (INHL) and chronic lymphocytic leukemia (CLL) are highly sensitive to radiotherapy (RT). Previous retrospective studies have shown high response rates after local palliative RT of 4 Gy in 2 fractions, which prompted this prospective Phase II trial of the palliative...

  18. Intravascular large B-cell lymphoma presenting with fulminant pseudomembranous colitis.

    Science.gov (United States)

    Wang, Tao; Ghaffar, Hasan; Grin, Andrea

    2013-05-01

    Intravascular large B-cell lymphoma is a rare entity that usually presents in late stages with non-specific symptoms. We present a case of an incidentally discovered intravascular large B-cell lymphoma in a 78-year-old man who underwent colectomy for medically refractory pseudomembranous colitis. The malignant lymphocytes were preferentially localized to small colonic submucosal vasculature, without any evidence of an extravascular tumor mass. The gastrointestinal system is an exceeding rare initial diagnostic site for intravascular lymphoma, and presentation with pseudomembranous colitis has not been previously reported. We discuss the current definition of intravascular lymphoma, clinicopathological variants, differential diagnoses, as well as current therapy.

  19. Histopathological features and their prognostic impact in nodular lymphocyte-predominant Hodgkin lymphoma--a matched pair analysis from the German Hodgkin Study Group (GHSG).

    Science.gov (United States)

    Hartmann, Sylvia; Eichenauer, Dennis A; Plütschow, Annette; Mottok, Anja; Bob, Roshanak; Koch, Karoline; Bernd, Heinz-Wolfram; Cogliatti, Sergio; Hummel, Michael; Feller, Alfred C; Ott, German; Möller, Peter; Rosenwald, Andreas; Stein, Harald; Hansmann, Martin-Leo; Engert, Andreas; Klapper, Wolfram

    2014-10-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity. We performed a matched-pair analysis to evaluate the prognostic impact of several histopathological features in this distinct Hodgkin lymphoma subtype. Lymph node samples of NLPHL patients were tested for CD15, IgD, phosphorylated STAT6, ICOS and Epstein-Barr virus status of the malignant lymphocyte-predominant cells as well as epithelioid cell clusters and activated T cells in the microenvironment. None of these features was associated with a particular clinical outcome. However, patients presenting with epithelioid cell clusters showed a non-significant trend towards a lower relapse rate, justifying further evaluation of this marker. © 2014 John Wiley & Sons Ltd.

  20. Combination of bendamustine and rituximab in the management of relapsed and refractory chronic lymphocytic leukemia: the results of retrospective study

    Directory of Open Access Journals (Sweden)

    S. V. Semochkin

    2015-01-01

    Full Text Available Efficacy and safety results of rituximab and bendamustine combination (Scheme BR in patients with relapsed and refractory chronic lymphocytic leukemia (CLL are presented. From 01.2012 to 04.2013, the treatment was initiated in 43 patients (21 with relapses are sensitive to the last line of therapy; 22 – with refractory CLL. Median age at start of therapy was 63.5 years (range from 43 to 81 years. In 40 patients response was evaluated according to NCI-WG criteria (1996. Complete remission (CR is documented in 5 (12.5 % cases, partial (PR or nodular partial remission (nPR in 17 (42.5 % cases. MRD-negative CR was achieved in 1 (20.0 % of 5 patients with CR. With 23.5 months of median follow-up for surviving patients 2-year progression-free survival (PFS was 47.2 ± 8.5 % (median – 18.5 months, overall survival (OS – 66.9 ± 7.9 % (median not achieved. Hematological toxicity Grade 3–4 occurred in 15 (34.9 % cases, same degree infectious complicationsin 5 (11.6 % cases. Patients received 3 or more therapy lines before this treatment (37.5 ± 16.1 % against 74.7 ± 8.3 %; p = 0.016, with «bulky disease» more than 10 cm (0.0 % vs. 75.4 ± 7.5 %; p < 0.001 and received rituximab in combination with chemotherapy in the previous lines, compared to the «naive» cases (44.1 ± 10.5 % against 92.9 ± 6.9 %; p = 0.009 have significantly worsened 2-year OS.

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

    Science.gov (United States)

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

    2017-03-01

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

  2. Refractory Celiac Disease

    Directory of Open Access Journals (Sweden)

    K Khatami

    2014-04-01

    Full Text Available Refractory celiac disease (RCD is when malabsorption symptoms and villous atrophy persist despite strict adherence to a gluten free diet (GFD for more than 12 months and other causes of villous atrophy have been ruled out.  RCD is considered a rare disease and almost exclusively occurs in adults. Persistent diarrhea, abdominal pain, weight loss are the most common symptoms in RCD. Also, anemia, fatigue, malaise, thromboembolic events and coexisting autoimmune disorders are frequent. Diagnosis of RCD is based on other causes of unresponsiveness to the GFD, particularly collagenous sprue, ulcerative jejunitis, and enteropathy-associated T-cell lymphoma. Many disorders such as autoimmune enteropathy, tropical sprue, common variable immunodeficiency, and intolerance to non-gluten dietary proteins may have similar histological findings but not necessarily identical with CD and therefore should be excluded. Repeat intestinal biopsy may help to differentiate causes of non-responsive CD associated with ongoing villous atrophy (e.g., gluten contamination, small-bowel bacterial overgrowth, RCD. There are 2 subtypes of RCD according to absence (type I or presence (type II of an abnormal intraepithelial lymphocyte population. RCD type 1 usually becomes better with a combination of aggressive nutritional support, adherence to GFD, and pharmacologic therapies such as prednisone, budesonide and azathioprine. For RCD type 2, more aggressive therapeutic approach is needed since clinical response to therapies is less certain and may evolve into aggressive enteropathy associated T-cell lymphoma and the prognosis is poor.   Key words: Celiac Disease, Refractory.  

  3. The Coexistence of an Intrasellar Adenoma, Lymphocytic Hypophysitis, and Primary Pituitary Lymphoma in a Patient with Acromegaly

    Directory of Open Access Journals (Sweden)

    Jose Hernan Martinez

    2011-01-01

    Full Text Available The concomitant presence of three histopathologically different entities in the pituitary gland is a rare occurrence. Most publications identify at least two distinct pathologies, mainly, a pituitary adenoma coexisting with a second intrasellar lesion. We present a case of a 71-year-old female referred for evaluation and treatment of acromegaly. Questioning revealed she was experiencing facial palsy, visual disturbances, and syncopal spells for several weeks. When laboratory evaluation showed elevated somatomedin (IGF-I levels and an oral glucose tolerance test failed to demonstrate any suppression of her growth hormone (GH values, an MRI of the pituitary revealed a sellar mass. A presumptive diagnosis of pituitary adenoma was established. The patient underwent transsphenoidal resection of the sellar mass, which proved to be a large B-cell lymphoma (Stage I-E associated with areas of adenoma and lymphocytic hypophysitis.

  4. Malt1-dependent RelB cleavage promotes canonical NF-kappaB activation in lymphocytes and lymphoma cell lines.

    Science.gov (United States)

    Hailfinger, Stephan; Nogai, Hendrik; Pelzer, Christiane; Jaworski, Maike; Cabalzar, Katrin; Charton, Jean-Enno; Guzzardi, Montserrat; Décaillet, Chantal; Grau, Michael; Dörken, Bernd; Lenz, Peter; Lenz, Georg; Thome, Margot

    2011-08-30

    The protease activity of the paracaspase Malt1 contributes to antigen receptor-mediated lymphocyte activation and lymphomagenesis. Malt1 activity is required for optimal NF-κB activation, but little is known about the responsible substrate(s). Here we report that Malt1 cleaved the NF-κB family member RelB after Arg-85. RelB cleavage induced its proteasomal degradation and specifically controlled DNA binding of RelA- or c-Rel-containing NF-κB complexes. Overexpression of RelB inhibited expression of canonical NF-κB target genes and led to impaired survival of diffuse large B-cell lymphoma cell lines characterized by constitutive Malt1 activity. These findings identify a central role for Malt1-dependent RelB cleavage in canonical NF-κB activation and thereby provide a rationale for the targeting of Malt1 in immunomodulation and cancer treatment.

  5. Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000).

    Science.gov (United States)

    Radford, John; Davies, Andrew; Cartron, Guillaume; Morschhauser, Franck; Salles, Gilles; Marcus, Robert; Wenger, Michael; Lei, Guiyuan; Wassner-Fritsch, Elisabeth; Vitolo, Umberto

    2013-08-15

    The safety and activity of obinutuzumab (GA101) plus chemotherapy in relapsed/refractory follicular lymphoma was explored in 56 patients. Participants received obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP; every 3 weeks for 6 to 8 cycles) or obinutuzumab plus fludarabine and cyclophosphamide (G-FC; every 4 weeks for 4 to 6 cycles). Patients were randomly assigned to either obinutuzumab 1600 mg on days 1 and 8 of cycle 1 followed by 800 mg on day 1 of subsequent cycles or 400 mg for all doses. Treatment responders were eligible for obinutuzumab maintenance every 3 months for up to 2 years. Grade 1/2 infusion-related reactions (IRRs) were the most common treatment-related adverse event (AE) (all grades: G-CHOP, 68%; G-FC, 82%). Grade 3/4 IRRs were rare (7%) and restricted to the first infusion. All patients received the planned obinutuzumab dose. Neutropenia was the most common treatment-related hematologic AE for G-CHOP (43%) and G-FC (50%). At induction end, 96% (27/28) of patients receiving G-CHOP (complete response [CR], 39% [11/28]) and 93% (26/28) receiving G-FC (CR, 50% [14 of 28]) achieved responses. G-CHOP and G-FC had an acceptable safety profile with no new or unexpected AEs, but G-FC was associated with more AEs than G-CHOP. Obinutuzumab plus chemotherapy resulted in 93% to 96% response rates, supporting phase 3 investigation. This trial was registered at www.clinicaltrials.gov as #NCT00825149.

  6. DNA methylation profiling of transcription factor genes in normal lymphocyte development and lymphomas.

    Science.gov (United States)

    Ivascu, Claudia; Wasserkort, Reinhold; Lesche, Ralf; Dong, Jun; Stein, Harald; Thiel, Andreas; Eckhardt, Florian

    2007-01-01

    Transcription factors play a crucial role during hematopoiesis by orchestrating lineage commitment and determining cellular fate. Although tight regulation of transcription factor expression appears to be essential, little is known about the epigenetic mechanisms involved in transcription factor gene regulation. We have analyzed DNA methylation profiles of 13 key transcription factor genes in primary cells of the hematopoietic cascade, lymphoma cell lines and lymph node biopsies of diffuse large B-cell- and T-cell-non-Hodgkin lymphoma patients. Several of the transcription factor genes (SPI1, GATA3, TCF-7, Etv5, c-maf and TBX21) are differentially methylated in specific cell lineages and stages of the hematopoietic cascade. For some genes, such as SPI1, Etv5 and Eomes, we found an inverse correlation between the methylation of the 5' untranslated region and expression of the associated gene suggesting that these genes are regulated by DNA methylation. Differential methylation is not limited to cells of the healthy hematopoietic cascade, as we observed aberrant methylation of c-maf, TCF7, Eomes and SPI1 in diffuse large B-cell lymphomas. Our results suggest that epigenetic remodelling of transcription factor genes is a frequent mechanism during hematopoietic development. Aberrant methylation of transcription factor genes is frequently observed in diffuse large B-cell lymphomas and might have a functional role during tumorigenesis.

  7. Using Health Care Claims Data to Assess the Prevalence of Hodgkin Lymphoma and Relapsed or Refractory Hodgkin Lymphoma in the United States.

    Science.gov (United States)

    Lin, Jay; Siegartel, Lisa R; Lingohr-Smith, Melissa; Menges, Brandy; Makenbaeva, Dinara

    2017-02-01

    Although most patients with Hodgkin lymphoma (HL) respond to primary therapy, some patients experience relapses or are refractory to treatment (RR-HL). The objectives of this study were to investigate the prevalence of HL and RR-HL in the United States by using a large health care claims database. Patients with ≥1 diagnosis for HL between January 1, 2013, and September 30, 2014 (prevalence assessment period), in the MarketScan Commercial and Medicare databases were identified. RR-HL patients were identified as any HL patient with any record for either an autologous stem cell transplantation (ASCT) or brentuximab vedotin (BV) treatment between January 1, 2010, and September 30, 2014 (entire study period). Prevalence rates of HL and RR-HL were calculated as the number of patients with HL or RR-HL divided by the total number of persons with insurance enrollment during the prevalence assessment period (January 1, 2013-September 30, 2014) in the MarketScan databases. Age- and sex-specific prevalence rates for HL and RR-HL were estimated. The estimated prevalence rates based on the claims database analysis were applied to the US national population estimates from the US Census Bureau to project the national prevalence of HL and RR-HL in the United States. Of persons with any insurance enrollment in the MarketScan databases during the prevalence assessment period (N = 58,968,235), 24,812 (0.04%) were identified as having HL (mean age, 48.6 years) between January 1, 2013, and September 30, 2014. Of this HL population, 712 (2.87%) were identified as RR-HL patients, with 432 (1.74%) having received ASCT, 199 (0.80%) having received BV, and 81 (0.33%) having received both ASCT and BV treatments during the study period. According to the national projection according to the US Census population estimate, the overall number of persons with HL in the United States was estimated at 149,615 (469.2 per 1 million) in 2014, with 2.72% (N = 4077; 12.8 per 1 million) having RR

  8. Prognostic value of pretransplant FDG-PET in refractory/relapsed Hodgkin lymphoma treated with autologous stem cell transplantation: systematic review and meta-analysis.

    Science.gov (United States)

    Adams, Hugo J A; Kwee, Thomas C

    2016-04-01

    This study aimed to systematically review the prognostic value of pretransplant (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in refractory/relapsed Hodgkin lymphoma treated with autologous stem cell transplantation (SCT). MEDLINE was systematically searched for appropriate studies. Included studies were methodologically appraised. Results of individual studies were meta-analyzed, if possible. Eleven studies, comprising a total of 745 refractory/relapsed Hodgkin lymphoma patients who underwent FDG-PET before autologous SCT, were included. The overall methodological quality of these studies was moderate. The proportion of pretransplant FDG-PET positive patients ranged between 25 and 65.2 %. Progression-free survival ranged between 0 and 52 % in pretransplant FDG-PET positive patients, and between 55 and 85 % in pretransplant FDG-PET negative patients. Overall survival ranged between 17 and 77 % in pretransplant FDG-PET positive patients, and between 78 and 100 % in FDG-PET negative patients. Based on five studies that provided sufficient data for meta-analysis, pooled sensitivity and specificity of pretransplant FDG-PET in predicting treatment failure (i.e., either progressive, residual, or relapsed disease) were 67.2 % (95 % confidence interval [CI] 58.2-75.3 %) and 70.7 % (95 % CI 64.2-76.5 %), respectively. Based on two studies that provided sufficient data for meta-analysis, pooled sensitivity and specificity of pretransplant FDG-PET in predicting death during follow-up were 74.4 % (95 % CI 58.8-86.5 %) and 58.0 % (95 % CI 49.3-66.3 %), respectively. In conclusion, the moderate quality evidence suggests pretransplant FDG-PET to have value in predicting outcome in refractory/relapsed Hodgkin lymphoma patients treated with autologous SCT. Nevertheless, a considerable proportion of pretransplant FDG-PET positive patients remains disease free and a considerable proportion of pretransplant FDG-PET negative patients develops disease relapse

  9. Relevance of monitoring metabolic reduction in patients with relapsed or refractory follicular and mantle cell lymphoma receiving bendamustine: a multicenter study.

    Science.gov (United States)

    Tateishi, Ukihide; Tatsumi, Mitsuaki; Terauchi, Takashi; Ishizawa, Kenichi; Ogura, Michinori; Tobinai, Kensei

    2011-02-01

    The aim of the present study was to investigate the relevance of monitoring metabolic reduction evaluated by (18) F-fluorodeoxyglucose ((18) F-FDG) PET/CT in relapsed or refractory patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) who received bendamustine. We conducted a phantom study of 18F-FDG PET/CT to ensure quality control for performing a multicenter clinical study. We analyzed 49 patients with relapsed or refractory FL and MCL who received bendamustine (120 mg/m(2)) on days 1-2 of a 21-day cycle for up to six cycles as a licensing phase II study. 18F-FDG PET/CT scans were acquired before the first and after the last cycle. In a total of 175 target lesions, the maximum perpendicular diameter (Max PD), minimum PD (Min PD), sum of the products of the Max PD (SPD), maximum standardized uptake value (SUVmax), and the percentage reduction rates of Max PD (%Max PD), SPD (%SPD) and SUVmax (%SUVmax) were evaluated for the response to treatment. The therapeutic response was assessed after the last cycle of treatment according to the revised response criteria for malignant lymphoma (revised RC). We evaluated 134 lesions in 39 patients (76%) achieving complete response (CR) and 41 lesions in 10 patients (24%) not achieving CR. The Max PD, Min PD, SPD and SUVmax of the lesions after the last cycle were significantly higher in patients with non-CR than in patients with CR. The %MPD, %SPD and %SUVmax of the lesions were significantly greater in patients with CR than in patients with non-CR (P < 0.0001). Metabolic reduction was observed in all target lesions of relapsed or refractory patients with FL and MCL who achieved CR after bendamustine therapy.

  10. Leucemia linfóide crônica e linfoma linfocítico de pequenas células Chronic lymphocytic leukemia and small lymphocytic lymphoma

    Directory of Open Access Journals (Sweden)

    Lucia M. R. Silla

    2005-12-01

    Full Text Available O linfoma linfocítico de pequenas células (LLPC é considerado uma variante tumoral da leucemia linfocítica crônica e, por conseguinte, a mesma doença. Existem similaridades clínicas, morfológicas, imunofenotípicas e genéticas que parecem resistir até mesmo a uma análise mais aprofundada com o instrumental técnico atualmente disponível para o estudo da biologia molecular. Talvez o refinamento das técnicas de análise da expressão de multiplos genes, incluindo genes para microRNAs, tanto das células malignas quanto das remanescentes benignas do microambiente, e os avanços no conhecimento de determinantes da diferenciação celular possam, em um futuro próximo, esclarecer afinal se LLPC e LLC são doenças diferentes.Small lymphocytic lymphoma (SLL and chronic lymphocytic leukemia (CLL are thought to be different expressions of the same disease. There are clinical, morphological, immuno-phenotypical and genotypical similarities that seem to resist even to advanced molecular biology techniques. It still needs to be defined, through a more refined understanding of the gene profile expression and microRNA biology of the malignant and surrounding micro-environment benign cells and a better understanding of the new paradigms of cell differentiation relativity, if SLL and CLL are different diseases.

  11. Combined assay of surface immunoglobulin intensity and mouse rosettes. A practical parameter in the differential diagnosis of small lymphocytic and follicular center cell lymphomas.

    Science.gov (United States)

    Batata, A; Shen, B

    1993-03-01

    Cell suspensions from the lymph nodes of small lymphocytic lymphoma (n = 94) and nodular and diffuse follicular center cell lymphomas (n = 330) were analyzed to evaluate the diagnostic significance of the surface immunoglobulin (SIg) intensity and mouse rosette assay (MR). In small lymphocytic lymphoma, SIg was monoclonal in 65 cases (69.15%), with weak fluorescence in 59 (90.77%). It was not detected in 29 cases (30.85%). The MR findings were positive in 68 cases (72.34%) and negative in 26 (27.66%). The combined results of these two assays showed the following: weak SIg/MR+, 35 (37.23%); weak SIg/MR-, 24 (25.53%); strong SIg/MR+, 6 (6.38%); strong SIg/MR-, 0; undetected SIg/MR+, 27 (28.72%); and undetected SIg/MR-, 2 (2.13%). By performing the assays for these two markers and accepting weak SIg/MR+, weak SIg/MR-, strong SIg/MR+, or undetected SIg/MR+ as sufficient for diagnosis, 92 cases (97.87%) were diagnosed. In diffuse follicular center cell lymphomas, SIg was monoclonal in 287 cases (86.97%), with strong fluorescence in 258 (89.9%) and weak fluorescence in 29 (10.1%). It was not detected in 43 cases (13.03%). The MR results were positive in 34 cases (10.3%) and negative in 296 (89.7%). The combined findings of these two assays showed that strong SIg/MR- was present in 244 cases (73.94%). The diagnostic value of the combined assay in the differential diagnosis between small lymphocytic lymphoma and diffuse follicular center cell lymphomas was proved using five statistical parameters.

  12. Minimal renal toxicity after Rituximab DHAP with a modified cisplatin application scheme in patients with relapsed or refractory diffuse large B-cell lymphoma

    OpenAIRE

    Lisenko, Katherina; McClanahan, F.; Schöning, Tilman; Schwarzbich, Mark Alexander; Cremer, Martin; Dittrich, Tobias; Ho, Anthony D; Witzens-Harig, Mathias

    2016-01-01

    Background: Rituximab (R) in combination with DHAP is a widely accepted salvage regimen for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). A common adverse effect of this protocol is renal toxicity which may result in treatment discontinuation. Assuming that a lower single dose of cisplatin over several days would reduce renal toxicity, our institution has chosen to administer cisplatin in a dosage of 25 mg/m2 per day as a 3-h infusion over 4 consecutive days. M...

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

    Science.gov (United States)

    2016-08-10

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

  14. Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma.

    Science.gov (United States)

    Akhtar, Saad; Rauf, Shahzad M; Elhassan, Tusneem A M; Maghfoor, Irfan

    2016-09-01

    High-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage many patients with relapsed or refractory Hodgkin's lymphoma (HL). We are reporting the outcome of HDC auto-SCT and the impact of 21 prognostic factors in relapsed and refractory adolescent (14-21 years) and young adult (>21-30 years) (AYA) HL patients. We used Fine and Gray's competing risk analysis method and regression model for outcome analysis. From 1996 to 2013, 290 consecutive patients with biopsy-proven HL underwent HDC auto-SCT for relapsed/refractory HL; 216 patients (74.5 %) were AYA at the time of auto-SCT. Male/female were equal, median age at auto-SCT was 22.4 years, and there were 94 adolescent (43.5 %) and 122 young adults (56.5 %). There was refractory disease in 121 (56 %) patients, relapsed in 95 (44 %). Median follow-up was 72.6 months. The Kaplan-Meier method estimated that 5-year overall survival is 62.7 % (adolescents (63.5 %), young adults (62 %)) and event-free survival was 51.3 %. Five-year cumulative incidence of disease-specific death (DS-death) is 33 % and that of DS-event is 45 %. For DS-death, the multivariate analysis identified complete remission (CR) duration of young adults.

  15. A Rare Case of Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma with Light Chain Discrepancy between B Lymphocyte Population and Serum Paraprotein.

    Science.gov (United States)

    Kim, Hyun Jeong; Hur, Mina; Kim, Hanah; Moon, Hee-Won; Yun, Yeo-Min; Kim, Sung Yong; Lee, Mark Hong

    2015-01-01

    Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma with bone marrow involvement, monotypic immunoglobulin (Ig) M and a light chain of neoplastic cells. A 68-year-old woman presented with fever, nausea, vomiting, and pancytopenia. Her serum albumin/globulin ratio was reversed, and monoclonal gammopathy of IgM, lambda type (23.20%, 1.58 g/dL) was detected. In her bone marrow, increased small lymphocytes were admixed with plasmacytoid lymphocytes and plasma cells. She was diagnosed as having lymphoplasmacytic variant of WM. Immunohistochemical stains and flow cytometic analysis revealed two distinct populations; monoclonal B cells (kappa+) and abnormal plasma cells (CD19-/CD56+/lambda+). She expired 19 days after admission due to septic shock. This is a rare case of WM exhibiting a light chain discrepancy between monoclonal B lymphocytes and paraprotein-secreting plasma cells. Light chain restriction may occur distinctly between lymphocyte and plasma cell populations in WM.

  16. Helical Irradiation of the Total Skin with Dose Painting to Replace Total Skin Electron Beam Therapy for Therapy-Refractory Cutaneous CD4+ T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Chen-Hsi Hsieh

    2013-01-01

    Full Text Available A 36-year-old woman was diagnosed with a therapy-refractory cutaneous CD4+ T-cell lymphoma, T3N0M0B0, and stage IIB. Helical irradiation of the total skin (HITS and dose painting techniques, with 30 Gy in 40 fractions interrupted at 20 fractions with one week resting, 4 times per week were prescribed. The diving suit was dressed whole body to increase the superficial dose and using central core complete block (CCCB technique for reducing the internal organ dose. The mean doses of critical organs of head, chest, and abdomen were 2.1 to 29.9 Gy, 2.9 to 8.1 Gy, and 3.6 to 15.7 Gy, respectively. The mean dose of lesions was 84.0 cGy. The dosage of left side pretreated area was decreased 57%. The tumor regressed progressively without further noduloplaques. During the HITS procedure, most toxicity was grade I except leukocytopenia with grade 3. No epitheliolysis, phlyctenules, tumor lysis syndrome, fever, vomiting, dyspnea, edema of the extremities, or diarrhea occurred during the treatment. HITS with dose painting techniques provides precise dosage delivery with impressive results, sparing critical organs, and offering limited transient and chronic sequelae for previously locally irradiated, therapy-refractory cutaneous T-cell lymphoma.

  17. Role of Salvage Radiation Therapy for Patients With Relapsed or Refractory Hodgkin Lymphoma Who Failed Autologous Stem Cell Transplant

    Energy Technology Data Exchange (ETDEWEB)

    Goda, Jayant S. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Massey, Christine [Department of Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Kuruvilla, John [Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Keating, Armand; Crump, Michael [Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Tsang, Richard W., E-mail: richard.tsang@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)

    2012-11-01

    Purpose: To analyze, through chart review, the efficacy of salvage radiation therapy (sRT) for relapsed or progressive Hodgkin lymphoma (HL) patients who failed autologous stem cell transplant (ASCT). Patients and Methods: Among 347 patients with recurrent/refractory HL who received ASCT from 1986-2006, 163 had post-ASCT progression or relapse. Of these, 56 received sRT and form the basis of this report. Median age at sRT was 30 years (range, 17-59 years). Disease was confined to lymph nodes in 27 patients, whereas 24 had both nodal and extranodal disease. Salvage radiation therapy alone was given in 34 patients (61%), and sRT plus chemotherapy was given in 22 (39%). Median interval from ASCT to sRT was 0.8 years (range, 0.1-5.6 years). The median dose was 35 Gy (range, 8-40.3 Gy). The sRT technique was extended-field in 14 patients (25%) and involved-field in 42 (75%). Results: The median follow-up from sRT was 31.3 months (range, 0.2-205.5 months). Overall response rate was 84% (complete response: 36%; partial response: 48%). The median overall survival was 40.8 months (95% confidence interval, 34.2-56.3 months). The 5-year overall survival was 29% (95% confidence interval, 14%-44%). The 2-year progression-free survival (PFS) was 16%; the 2-year local PFS was 65%, whereas the 2-year systemic PFS was 17%. The 1-year PFS was higher in patients in whom all diseased sites were irradiated (49%) compared with those in whom only the symptomatic site was treated (22%, P=.07). Among 20 alive patients, 5 were disease free (at 6.4, 6.8, 7.4, 7.9, and 17.1 years). Conclusion: For patients with HL who fail ASCT, a selective use of RT provides a durable local control rate of 65% at 2 years and should be considered as part of the standard management plan for the palliation of incurable HL. Occasionally irradiation of truly localized disease can lead to long-term survival.

  18. Characteristics and Outcomes of Patients With Nodular Lymphocyte-Predominant Hodgkin Lymphoma Versus Those With Classical Hodgkin Lymphoma: A Population-Based Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Naamit K. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Atoria, Coral L.; Elkin, Elena B. [Department of Epidemiology and Biostatistics, Health Outcomes Research Group, New York, New York (United States); Yahalom, Joachim, E-mail: yahalomj@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2015-05-01

    Purpose: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is rare, comprising approximately 5% of all Hodgkin lymphoma (HL) cases. Patients with NLPHL tend to have better prognoses than those with classical HL (CHL). Our goal was to assess differences in survival between NLPHL and CHL patients, controlling for differences in patient and disease characteristics. Methods and Materials: Using data from the population-based Surveillance, Epidemiology and End Results (SEER) cancer registry program, we identified patients diagnosed with pathologically confirmed HL between 1988 and 2010. Results: We identified 1,162 patients with NLPHL and 29,083 patients with CHL. With a median follow-up of 7 years, 5- and 10-year overall survival (OS) rates were 91% and 83% for NLPHL, respectively, and 81% and 74% for CHL, respectively. After adjusting for all available characteristics, NLPHL (vs CHL) was associated with higher OS (hazard ratio [HR]: 0.62, P<.01) and disease-specific survival (DSS; HR: 0.48, P<.01). The male predominance of NLPHL, compared to CHL, as well as the more favorable prognostic features in NLPHL patients are most pronounced in NLPHL patients <20 years old. Among all NLPHL patients, younger patients were less likely to receive radiation, and radiation use has declined by 40% for all patients from 1988 to 2010. Receipt of radiation was associated with better OS (HR: 0.64, P=.03) and DSS (HR: 0.45, P=.01) in NLPHL patients after controlling for available baseline characteristics. Other factors associated with OS and DSS in NLPHL patients are younger age and early stage. Conclusions: Our results in a large population dataset demonstrated that NLPHL patients have improved prognosis compared to CHL patients, even after accounting for stage and baseline characteristics. Use of radiation is declining among NLPHL patients despite an association in this series between radiation and better DSS and OS. Unique treatment strategies for NLPHL are warranted in both

  19. Effect of antilymphoma antibody, 131I-Lym-1, on peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma.

    Science.gov (United States)

    Schillaci, Orazio; DeNardo, Gerald L; DeNardo, Sally J; Goldstein, Desiree S; Kroger, Linda A; O'Donnell, Robert T; Lamborn, Kathleen R

    2007-08-01

    Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled 90Y-ibritumomab (Zevalin, Biogen Idec Inc., Cambridge, MA) and 131I-tositumomab (Bexxar; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 (131I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received 131I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last 131I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last 131I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or 131I dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of 131I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after 131I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes.

  20. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma

    DEFF Research Database (Denmark)

    Hagenbeek, Anton; Gadeberg, Ole Vestergaard; Johnson, Peter

    2008-01-01

    Ofatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cells with low CD20-antigen density and high expression of complement inhibitory molecules...... and profound B-cell depletion, and 65% of patients reverted to negative BCL2 status. Clinical response rates ranged from 20% to 63%. Median time to progression for all patients/responders was 8.8/32.6 months, and median duration of response was 29.9 months at a median/maximum follow-up of 9.2/38.6 months...

  1. Methylation changes of SIRT1, KLF4, DAPK1 and SPG20 in B-lymphocytes derived from follicular and diffuse large B-cell lymphoma.

    Science.gov (United States)

    Frazzi, Raffaele; Zanetti, Eleonora; Pistoni, Mariaelena; Tamagnini, Ione; Valli, Riccardo; Braglia, Luca; Merli, Francesco

    2017-06-01

    Diffuse large-B cell lymphomas (DLBCL) and follicular lymphomas (FL) are the most represented subtypes among mature B-cell neoplasms and originate from malignant B lymphocytes. Methylation represents one of the major epigenetic mechanisms of gene regulation. Silent information regulator 1 (SIRT1) is a class III lysine-deacetylase playing several functions and considered to be a context-dependent tumor promoter. We present the quantitative methylation, gene expression and tissue distribution of SIRT1 and some key mediators related to lymphoma pathogenesis in B lymphocytes purified from biopsies of follicular hyperplasias, FL and DLBCL. SIRT1 mRNA levels are higher in FL than follicular hyperplasias and DLBCL. B cell lymphoma 6 (BCL6) positively correlates with SIRT1. SIRT1 promoter shows a methylation decrease in the order: follicular hyperplasia - FL - DLBCL. Kruppel-like factor 4 (KLF4), Death-associated protein kinase 1 (DAPK1) and Spastic Paraplegia 20 (SPG20) methylation increase significantly in FL and DLBCL compared to follicular hyperplasias. Gene expression of DAPK1 and SPG20 inversely correlates with their degree of methylation. Our findings evidence a positive correlation between SIRT1 and BCL6 expression increase in FL. SIRT1 methylation decreases in FL and DLBCL accordingly and this parallels the increase of KLF4, DAPK1 and SPG20 methylation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. T-cell population of primary and secondary cutaneous B-cell lymphomas does not express the cutaneous lymphocyte-associated antigen (CLA).

    Science.gov (United States)

    Marti, R M; Hausmann, G; Estrach, T; Cid, M C; Palou, J; Herrero, C; Mascaro, J M

    1997-05-01

    Primary cutaneous B-cell lymphomas (CBCL) are a group of malignant lymphomas with apparently distinct clinicopathological and immunophenotypical features. As in other B-cell lymphomas, the accompanying benign cell population in CBCL includes a variable number of T lymphocytes whose role is not well understood. In the present study we characterized the immunophenotype of these T cells and compared it with that of the reactive T-cell population in specific skin involvement by noncutaneous B-cell malignancies. Our results indicated that most T cells in both primary and secondary B-cell lymphomas were CLA+ memory/effector helper T cells which differed from the currently known CLA+ memory/effector helper T lymphocytes of the skin-associated lymphoid tissue (SALT) system. However, the endothelial CLA ligand, E-selectin, was expressed on dermal vessels. These results suggest that a B cell environment and/or a lack of epidermal involvement promote(s) the recruitment into the skin of a different, apparently less specific, subset of memory helper T cells from those seen in T-cell-mediated dermatoses.

  3. Increased percentage of CD8 CD28– suppressor lymphocytes in peripheral blood and skin infiltrates correlates with advanced disease in patients with cutaneous T-cell lymphomas

    Directory of Open Access Journals (Sweden)

    Donata Urbaniak-Kujda

    2009-07-01

    Full Text Available Introduction: T cells with the CD8 CD28– phenotype are CD8 lymphocytes with regulatory function. Their increased numbers were observed in infections, autoimmune and neoplastic diseases, and in elderly healthy individuals. CD8 CD28– lymphocyte levels in patients with cutaneous T-cell lymphoma (CTCL has not yet been described. The aim of the study was to determine their levels in these patients’ peripheral blood and cutaneous infiltrates and their relation to the clinical stage of disease.Material/Methods: Forty-one untreated patients, 26 males and 15 females, with CTCL were enrolled in the study. CD8 CD28– lymphocyte levels were determined by flow cytometry in peripheral blood and by immunochemistry in skin infiltrates.Results: The percentage of CD8 CD28– lymphocytes in the peripheral blood of the patients was significantly higher than in the controls. Patients with advanced disease displayed a higher percentage of CD8 CD28– lymphocytes in the peripheral blood and skin than did the individuals with early stages of the disease. Moreover, positive correlations between CD8 CD28– lymphocyte level in peripheral blood and age, clinical stage, and the levels in the skin infiltrates was revealed. Additionally, the percentage of CD8 CD28– T cells in the skin infiltrates correlated positively with age and clinical stage of the disease.Conclusions: These data suggest that CD8 CD28– lymphocytes play an important role in the development of immunotolerance in the progression of cutaneous T-cell lymphoma.

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

    Science.gov (United States)

    2017-01-26

    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. High dose chemotherapy and autologous stem cell transplantation in relapsed or refractory Hodgkin lymphoma: Emerging questions, newer agents, and changing paradigm.

    Science.gov (United States)

    Akhtar, Saad

    2017-06-13

    Primary treatment for adult and pediatric patients with Hodgkin lymphoma (HL) using current multiagent anthracycline-based chemotherapy with or without radiation therapy will cure approximately >70% of the patients; >95% for early stage with a favorable risk profile and 70-75% with advanced stage and high risk features. Managing refractory and relapsed disease, however, remains a challenge. High dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage 40-70% of patients with relapsed or refractory HL. Two randomized trials in relapsed and refractory patients showed superior progression free survival. This presentation addresses some of the salient differences and changes in the management that have evolved over the last decade and have either already affected, or are likely to affect the outcome of HDC auto-SCT. The following will discussed. 1. Historic trials and other emerging issues impacting the outcome of HDC auto-SCT. 2. Changes in the primary treatment and response adapted therapy. 3. Evaluation and validation of prognostic factors at the time of first failure. 4. Selection of salvage chemotherapy. 5. Conditioning regimens. 6. Consolidation after HDC auto-SCT. 7. Management of failures of HDC auto-SCT. 8. Availability of financial resources in various healthcare systems. Enrolment in clinical trials should be encouraged. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  6. Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified.

    Science.gov (United States)

    Qi, Fei; Dong, Mei; He, Xiaohui; Li, Yexiong; Wang, Weihu; Liu, Peng; Yang, Jianliang; Gui, Lin; Zhang, Changgong; Yang, Sheng; Zhou, Shengyu; Shi, Yuankai

    2017-02-01

    Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2-8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL-NOS.

  7. Multiparameter flow cytometry to detect hematogones and to assess B-lymphocyte clonality in bone marrow samples from patients with non-Hodgkin lymphomas

    Directory of Open Access Journals (Sweden)

    Giovanni Carulli

    2014-06-01

    Full Text Available Hematogones are precursors of B-lymphocytes detected in small numbers in the bone marrow. Flow cytometry is the most useful tool to identify hematogones and, so far, 4-color methods have been published. In addition, flow cytometry is used in the diagnosis and follow-up of lymphomas. We developed a flow cytometric 7-color method to enumerate hematogones and to assess B-lymphocyte clonality for routine purposes. We evaluated 171 cases of B-cell non-Hodgkin lymphomas, either at diagnosis or in the course of follow-up. By our diagnostic method, which was carried out by the combination K/l/CD20/CD19/CD10/CD45/CD5, we were able to detect hematogones in 97.6% of samples and to distinguish normal B-lymphocytes, neoplastic lymphocytes and hematogones in a single step. The percentage of hematogones showed a significant inverse correlation with the degree of neoplastic infiltration and, when bone marrow samples not involved by disease were taken into consideration, resulted higher in patients during follow-up than in patients evaluated at diagnosis.

  8. Prognostic role of pretreatment neutrophil-lymphocyte ratio in patients with diffuse large B-cell lymphoma treated with RCHOP

    Science.gov (United States)

    Wang, Jing; Zhou, Min; Xu, Jing-Yan; Yang, Yong-Gong; Zhang, Qi-Guo; Zhou, Rong-Fu; Chen, Bing; Ouyang, Jian

    2016-01-01

    Abstract This study aims to investigate whether neutrophil to lymphocyte ratio (NLR) is an independent predictor in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Data from newly diagnosed DLBCL patients at Nanjing Drum Tower Hospital from 2006 to 2015 were retrospectively reviewed. We used the receiver operating characteristic (ROC) curve analysis to generate the optimal cutoff value for NLR. Among those 156 patients enrolled, the NLR was < 3.0 in 46.8% (73/156) of the patients, and the remaining 53.2% (83/156) had an NLR ≥ 3.0. Patients with higher pretreatment NLR were found to correlate with poorer OS and PFS than these with lower NLR (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.43–4.97, P = 0.002 and HR = 1.79, 95% CI = 1.05–3.07, P = 0.034, respectively). The multivariate Cox proportional hazard model analysis further showed that high NLR was found independently predictive of poor OS (HR = 0.40; CI = 0.19–0.84, P = 0.015) and PFS (HR = 0.57; CI = 0.33–0.98, P = 0.042). Consequently, pretreatment NLR was an independent prognostic predictor in patients with DLBCL in the rituximab era. PMID:27661033

  9. Non-Hodgkin's lymphoma, poorly differentiated lymphocytic and mixed cell types. Results of sequential staging procedures, response to therapy, and survival of 100 patients

    Energy Technology Data Exchange (ETDEWEB)

    Bitran, J.D.; Golomb, H.M.; Ultmann, J.E.

    1978-07-01

    The results of sequential staging procedures including laparotomy, radiotherapy, and combination chemotherapy are reported for 100 patients with poorly differentiated lymphocytic (PDL) and mixed cell (MC) non-Hodgkin's lymphoma (NHL). Twelve patients were found to have localized disease, pathologic stage (PS) I or II; 88 patients had PS III or IV disease. Bone marrow biopsy showed a high incidence of involvement and advanced 34% of the patients from PS I, II, and III to PS IV. Staging laparotomy has a very limited role in the evaluation of these patients. All of 12 patients with PS I and II NHL were treated with radiotherapy; at 5 years, they had 100% survival, 80% being disease-free. Fifteen patients with PS III disease were treated with total nodal radiotherapy (TNRT) alone and had a median disease-free survival of 41 months. The remaining patients with PS III and IV disease were treated with chemotherapy consisting of vincristine and prednisone (V and P); cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (COPP); cyclophosphamide, vincristine (Oncovin), adriamycin, and prednisone (COPA); or palliative therapy consisting of chlorambucil and prednisone. Two-year and 4-year survivals for patients with diffuse lymphoma were 93% and 60%, respectively; for patients with +2 nodular lymphoma, 80% and 30%; and for patients with nodular lymphomas, 76 to 93% and 50%, respectively. Treatment with COPP showed no advantage over V and P, palliative therapy, or TNRT for patients with +2 nodular and nodular disease. The likelihood of cure appears most promising for patients in complete remission (CR) with diffuse lymphoma; patients in CR with nodular lymphoma show a high rate of relapse over 5 years of observation. We conclude that staging laparotomy in PDL and MC NHL is of limited value, and that the role of aggressive chemotherapy for patients with +2 nodular and nodular lymphoma needs to be redefined.

  10. Whole exome sequencing of relapsed/refractory patients expands the repertoire of somatic mutations in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Mareschal, Sylvain; Dubois, Sydney; Viailly, Pierre-Julien; Bertrand, Philippe; Bohers, Elodie; Maingonnat, Catherine; Jaïs, Jean-Philippe; Tesson, Bruno; Ruminy, Philippe; Peyrouze, Pauline; Copie-Bergman, Christiane; Fest, Thierry; Jo Molina, Thierry; Haioun, Corinne; Salles, Gilles; Tilly, Hervé; Lecroq, Thierry; Leroy, Karen; Jardin, Fabrice

    2016-03-01

    Despite the many efforts already spent to enumerate somatic mutations in diffuse large B-cell lymphoma (DLBCL), previous whole-genome and whole-exome studies conducted on patients of mixed outcomes failed at characterizing the 30% of patients who will relapse or resist current immunochemotherapies. To address this issue, we performed whole-exome sequencing of normal/tumoral DNA pairs in 14 relapsed/refractory (R/R) patients subclassified by full-transcriptome arrays (six activated B-cell like, three germinal center B-cell like, and five primary mediastinal B-cell lymphomas), from the LNH-03 LYSA clinical trial program. Aside from well-known DLBCL features, gene and pathway level recurrence analyses proposed several interesting leads including TBL1XR1 and activating mutations in IRF4 or in the insulin regulation pathway. Sequencing-based copy number analysis defined 23 short recurrently altered regions involving genes such as REL, CDKN2A, HYAL2, and TP53. Moreover, it highlighted mutations in genes such as GNA13, CARD11, MFHAS1, and PCLO as associated with secondary variant allele amplification events. The five primary mediastinal B-cell lymphomas (PMBL), while unexpected in a R/R cohort, showed a significantly higher mutation rate (P = 0.003) and provided many insights on this classical Hodgkin lymphoma related subtype. Novel genes such as XPO1, MFHAS1, and ITPKB were found particularly mutated, along with various cytokine-based signaling pathways. Among these analyses, somatic events in the NF-κB pathway were found preponderant in the three DLBCL subtypes, confirming its major implication in DLBCL aggressiveness and pinpointing several new candidate genes.

  11. Analysis of Efficacy of DICE (Dexamethasone, Ifosfamide,Cisplatin and Etoposide) Regimen on Recurrent and Refractory Intermediate and High Grade Non-Hodgkin's Lymphoma

    Institute of Scientific and Technical Information of China (English)

    Lei Yang; Zhucheng Song; Xiaohong Xu; Jinzhi Wei; Qinghe Tan; Zhirong Cong; Chunlei Peng

    2009-01-01

    OBJECTIVE Thus far there is no standard salvage regimen for patients with recurrent and refractory intermediate and high grade non-Hodgkin's lymphoma (NHL). This study intends to investigate the therapeutic efficacy of the DICE (dexamethasone, isofosfamide, cisplatin and etoposide) regimen on the recurrent and refractory NHL, and to observe the related adverse effects. METHODS Clinical records of 22 patients with recurrent and refractory NHL, who failed to achieve a remission from the CHOP [cyclophosphamide, hydroxydaunomycin/doxorubicin (adriamycin), oncovin, prednisone] regimen within 2 to 6 cycles of treatment, were reviewed. DICE, as a salvage regimen with a median course of treatment of 4 cycles (ranging from 2 to 7 cycles), was now used, and evaluation of the therapeutic efficacy and adverse effect of DICE was conducted in all the patients. Of the 22 NHL cases, 8 were of T-cell origin and the other 14 B-cell origin. Salvage treatment was performed in the patients, with appraisal, prevention and treatment of the toxic reactions. RESULTS Following DICE treatment in the 22 patients, the total effective rate of the regimen was 63.6%, and the complete remission (CR) rate was 40.9%. The effective rates of DICE on the T and B-cell sourced NHL were 75.0% and 57.1%, and the CR rate were 37.5%, 42.9%, respectively (P > 0.05). An increase of the lactate dehydrogenase (LDH) level accompanied by a giant lump was the short-term effect on patients with recurrence (mean P < 0.05) who were drug resistant. Myelosuppression, digestive system reaction and alopecia were the commonly-seen complications in the patients who Received DICE regimen. All patients recovered after treatment, and no chemotherapy-related death occurred. CONCLUSION DICE regimen is effective in treating refractory and recurrent NHL.

  12. Gemcitabine and treatment of diffuse large B-cell lymphoma in relapsed or refractory elderly patients: A prospective randomized trial in Algeria

    Directory of Open Access Journals (Sweden)

    Aribi Mourad

    2010-01-01

    Full Text Available Context: Support for non-Hodgkin′s lymphoma (NHL with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria. Aim: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine regimen. Materials and Methods: Ninety-six patients in the age group of 60-70 years were volunteers for a prospective randomized single-blind study, carried out for three years. Patients were divided into two groups by the drawing of lots. The first group (GA, n = 48, relapse; n = 27 [56.3%], refractory; n = 21 [43.7%] received treatment with ESHAP protocol and the second one (GB, n = 48, relapse; n = 28 [58%], refractory; n = 20 [42%] with GPD (gemcitabine, dexamethasone, cisplatine protocol. Results: The overall response rates and mean survival at three years were significantly higher among patients subjected to GPD treatment compared with those subjected to ESHAP treatment (63% vs. 55%, P = 0.01 and 20.5% [95% CI 16.5-24.5] vs. 11.8% [8.9-14.6], respectively. Additionally, three-year progression-free and event-free survival rates were 20.5% (16.3-24 and 19.7% (15.9-23.5, respectively, for the GPD regimen and 10.9% (8.2-13.7 and 11.1% (95% CI 8.5-13.7, respectively, for the ESHAP regimen. Moreover, the GPD regimen was associated with improving overall survival (RR=2.02, 95% CI 1.59-2.56; P = 0.000, event-free survival (2.03, 1.64-2.52; P < 0.001 and progression-free survival (1.86, 1.46-2.37; P < 0.001. Conclusion: In cases of contra-indication for high-dose chemotherapy for elderly patients with DLBCL, without complete remission, the Gemcitabine

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

    Science.gov (United States)

    2016-08-24

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

  14. Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma.

    Science.gov (United States)

    Chen, Robert; Palmer, Joycelynne M; Martin, Peter; Tsai, Nicole; Kim, Young; Chen, Bihong T; Popplewell, Leslie; Siddiqi, Tanya; Thomas, Sandra H; Mott, Michelle; Sahebi, Firoozeh; Armenian, Saro; Leonard, John; Nademanee, Auayporn; Forman, Stephen J

    2015-12-01

    This multicenter prospective phase II study examines the activity and tolerability of brentuximab vedotin as second-line therapy in patients with Hodgkin lymphoma that was relapsed or refractory after induction therapy. Brentuximab vedotin (1.8 mg/kg) was administered i.v. on day 1 of a 21-day cycle for a total of 4 cycles. Patients then proceeded to autologous hematopoietic cell transplantation (AHCT), if eligible, with or without additional salvage therapy, based on remission status after brentuximab vedotin. The primary endpoint was overall response rate (ORR). Secondary endpoints were safety, stem cell mobilization/collection, AHCT outcomes, and association of CD68(+) with outcomes. Of 37 patients, the ORR was 68% (13 complete remission, 12 partial remission). The regimen was well tolerated with few grade 3/4 adverse events, including lymphopenia (1), neutropenia (3), rash (2), and hyperuricemia (1). Thirty-two patients (86%) were able to proceed to AHCT, with 24 patients (65%) in complete remission at time of AHCT. Thirteen patients in complete remission, 4 in partial remission, and 1 with stable disease (49%) received AHCT without salvage combination chemotherapy. CD68 expression did not correlate with response to brentuximab vedotin. The median number of stem cells mobilized was 6.0 × 10(6) (range, 2.6 to 34), and median number of days to obtain minimum collection (2 × 10(6)) was 2 (range, 1 to 6). Brentuximab vedotin as second-line therapy is active, well tolerated, and allows adequate stem cell collection and engraftment. For Hodgkin lymphoma patients with relapsed/refractory disease after induction therapy, second-line brentuximab vedotin, followed by combination chemotherapy for residual disease, can effectively bridge patients to AHCT.

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

    Science.gov (United States)

    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.

  16. B-cell transcription factors Pax-5, Oct-2, BOB.1, Bcl-6, and MUM1 are useful markers for the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma.

    Science.gov (United States)

    Herbeck, Rosemarie; Teodorescu Brînzeu, D; Giubelan, Marioara; Lazăr, Elena; Dema, Alis; Ioniţă, Hortensia

    2011-01-01

    In some instances, the overlap in morphologic features and antigen expression between nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (cHL) can cause confusion in the diagnosis. In these cases, the transcription factors (TFs) B-cell specific activator protein (BSAP)/Pax-5, octamer binding protein-2 (Oct-2), B-lymphocyte-specific co-activator BOB.1/OBF.1, Bcl-6 protein and multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF-4) may aid in clarifying the diagnosis. Twenty-two cases of NLPHL were studied for the immunohistochemical expression of Pax-5, Oct-2, BOB.1, Bcl-6 protein and MUM1/IRF-4. Our results sustain the usefulness of the selected set of TFs to diagnose and distinguish NLPHL from cHL since Pax-5, Oct-2, BOB.1 and Bcl-6 are consistently expressed by lymphocyte predominant (LP) cells and reported by others to be often unexpressed in Hodgkin and Reed-Sternberg cells. By contrast, MUM1/IRF-4 protein scored negative in the majority of LP cells, but is reported to be expressed in almost all cases of cHL. Thus, although the expression of transcription factors is very heterogeneous, their simultaneous implementation for positive and differential diagnosis may be useful.

  17. [Combination of etoposide, cisplatin and ifosfamide (VPH) in the salvage chemotherapy of relapsing or refractory aggressive malignant lymphoma. Study of 51 patients].

    Science.gov (United States)

    Eghbali, H; Catry-Thomas, I; Soubeyran, P; Bonnel, C; Hoerni, B

    1994-09-01

    Fifty-one patients with non-Hodgkin's lymphoma refractory or relapsing after CHOP-like regimen, underwent a salvage chemotherapy by VPH: etoposide 100 mg/m2/d, D1 to D3, cisplatin 20 mg/m2/d, D1 to D5, ifosfamide 1 g/m2/d D1 to D5, mesna 1.2 g/m2/d D1 to D5, every 4 weeks. Among 46 evaluable patients for efficacy, 21 (45.6%) achieved complete or partial response according to WHO criteria and 25 (54.3%) failed, while five cases (9.8% of all patients) were not evaluable (two initial complete remission before VPH, two early toxic deaths and one confusional syndrome). Thirty-five patients (68.6%) died of lymphoma, three (5.8%) of acute toxicity and 13 (25.5%) are alive: five in complete remission. The toxicity is mainly myelo-suppression, digestive and renal but could be managed as usually. Although the follow-up is short, this regimen appears effective in these circumstances after CHOP failure but it should be used early, before overt chemoresistance. It does not hinder a bone marrow transplantation programme.

  18. Cyclosporine,prednisone,and high-dose immunoglobulin treatment of angioimmunoblastic T-cell lymphoma refractory to prior CHOP or CHOP-like regimen

    Institute of Scientific and Technical Information of China (English)

    Xing-Gui Chen; He Huang; Ying Tian; Cheng-Cheng Guo; Chao-Yong Liang; Yao-Ling Gong; Ben-Yan Zou; Rui-Qing Cai; Tong-Yu Lin

    2011-01-01

    Angioimmunoblastic T-cell lymphoma(AITL) is a rare,distinct subtype of peripheral T-cell lymphoma,possessing an aggressive course and poor prognosis with no standard therapy.Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine(CsA),prednisone(PDN),and monthly,high-dose intravenous immunoglobulin (HI?IVIG).The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function.All patients were examined for response,toxicity and survival.The most significant toxicities insomnia(16.7%).Discontinuation of treatment occurred in one patient(8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection.Treatment-related death was not observed.The overall response rate was 75.0%(complete response,33.3%; partial response,41.7%).With a median follow-up of 25.5 months,the median duration of response was 20 months (range,12 to 49 months) and the median progression-free survival(PFS) was 25.5 months(range,10 to 56 months).The 2-year PFS rate was 81.5%.Our findings indicate the combination of CsA,PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.

  19. Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.

    Science.gov (United States)

    Herrera, Alex F; Mei, Matthew; Low, Lawrence; Kim, Haesook T; Griffin, Gabriel K; Song, Joo Y; Merryman, Reid W; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R; Budde, Lihua E; Chan, Wing C; Chen, Robert; Davids, Matthew S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric D; Jacobson, Caron A; LaCasce, Ann S; Murata-Collins, Joyce; Nademanee, Auayporn P; Palmer, Joycelynne M; Pihan, German A; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R; Zain, Jasmine; Rosen, Steven T; Kwak, Larry W; Weinstock, David M; Forman, Stephen J; Weisenburger, Dennis D; Kim, Young; Rodig, Scott J; Krishnan, Amrita; Armand, Philippe

    2017-01-01

    Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

  20. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma.

    Science.gov (United States)

    Feldman, Tatyana; Mato, Anthony R; Chow, Kar F; Protomastro, Ewelina A; Yannotti, Kara M L; Bhattacharyya, Pritish; Yang, Xiao; Donato, Michele L; Rowley, Scott D; Carini, Carolanne; Valentinetti, Marisa; Smith, Judith; Gadaleta, Gabriella; Bejot, Coleen; Stives, Susan; Timberg, Mary; Kdiry, Sabrina; Pecora, Andrew L; Beaven, Anne W; Goy, Andre

    2014-07-01

    Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction. We conducted a Phase I/II trial of lenalidomide plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) (RICER) as a salvage regimen for first-relapse or primary refractory DLBCL. Dose-escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER, patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] followed by autologous stem cell transplantation (autoSCT). Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months. No dose-limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE. Grade 3/4 haematological toxicities resolved appropriately, and planned dose density and dose intensity of RICER were preserved. No lenalidomide or RICE dose reductions were required in any of the three cycles. After two cycles of RICER, nine of 15 patients (60%) achieved a complete response, and two achieved a partial response (13%). Combining lenalidomide with RICE is feasible, and results in promising response rates (particularly complete response rates) in high-risk DLBCL patients.

  1. Proteomic analysis identifies galectin-1 as a predictive biomarker for relapsed/refractory disease in classical Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Kamper, Peter; Ludvigsen, Maja; Bendix, Knud

    2011-01-01

    Considerable effort has been spent identifying prognostic biomarkers in classic Hodgkin lymphoma (cHL). The aim of our study was to search for possible prognostic parameters in advanced-stage cHL using a proteomics-based strategy. A total of 14 cHL pretreatment tissue samples from younger, advanced...

  2. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung-Ju

    2017-01-01

    Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refra...

  3. Treatment Options for Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... Hodgkin lymphoma. Lymphocyte-depleted Hodgkin lymphoma. Epstein-Barr virus infection increases the risk of childhood Hodgkin lymphoma. ... about health care. Reviewers and Updates Editorial Boards write the PDQ cancer information summaries and keep them ...

  4. 2D ultrasonography and contrast enhanced ultrasound for the evaluation of cavitating mesenteric lymph node syndrome in a patient with refractory celiac disease and enteropathy T cell lymphoma

    Directory of Open Access Journals (Sweden)

    Pojoga Cristina

    2013-02-01

    Full Text Available Abstract Background The cavitating mesenteric lymph node syndrome (CMLNS is a rare manifestation of celiac disease, with an estimated mortality rate of 50%. Specific infections and malignant lymphoma may complicate its clinical course and contribute to its poor prognosis. Diagnosing the underlying cause of CMLNS can be challenging. This is the first report on contrast enhanced ultrasound (CEUS findings in enteropathy associated T-cell lymphoma (EATL complicating CMLNS in a gluten-free compliant patient with persistent symptoms and poor outcome. Case presentation We present the case of a 51-year old Caucasian male patient, diagnosed with celiac disease and CMLNS. Despite his compliance to the gluten-free diet the symptoms persisted and we eventually considered the possible development of malignancy. No mucosal changes suggestive of lymphoma were identified with capsule endoscopy. Low attenuation mesenteric lymphadenopathy, without enlarged small bowel segments were seen on computed tomography. CEUS revealed arterial rim enhancement around the necrotic mesenteric lymph nodes, without venous wash-out. No malignant cells were identified on laparoscopic mesenteric lymph nodes biopsies. The patient died due to fulminant liver failure 14 months later; the histopathological examination revealed CD3/CD30-positive atypical T-cell lymphocytes in the liver, mesenteric tissue, spleen, gastric wall, kidney, lung and bone marrow samples; no malignant cells were present in the small bowel samples. Conclusions CEUS findings in EATL complicating CMLNS include arterial rim enhancement of the mesenteric tissue around the cavitating lymph nodes, without venous wash-out. This vascular pattern is not suggestive for neoangiogenesis, as arteriovenous shunts from malignant tissues are responsible for rapid venous wash-out of the contrast agent. CEUS failed to provide a diagnosis in this case.

  5. Relapsed/refractory paediatric T cell lymphoblastic leukaemia and lymphoma. | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available IA. A.3.2Name or abbreviated title of the trial where available NK cells in leukemia / lymphoma Células NK en leucemia...a de rescate en pacientes con leucemia aguda linfoblástica/linfoma linfoblástico (LLT) en recaída o refracta...HIV serology 1. Pacientes de edad comprendida entre 0 y 21 años diagnosticados de leucemia aguda linfoblásti

  6. Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci

    Science.gov (United States)

    Law, Philip J.; Sud, Amit; Mitchell, Jonathan S.; Henrion, Marc; Orlando, Giulia; Lenive, Oleg; Broderick, Peter; Speedy, Helen E.; Johnson, David C.; Kaiser, Martin; Weinhold, Niels; Cooke, Rosie; Sunter, Nicola J.; Jackson, Graham H.; Summerfield, Geoffrey; Harris, Robert J.; Pettitt, Andrew R.; Allsup, David J.; Carmichael, Jonathan; Bailey, James R.; Pratt, Guy; Rahman, Thahira; Pepper, Chris; Fegan, Chris; von Strandmann, Elke Pogge; Engert, Andreas; Försti, Asta; Chen, Bowang; Filho, Miguel Inacio Da Silva; Thomsen, Hauke; Hoffmann, Per; Noethen, Markus M.; Eisele, Lewin; Jöckel, Karl-Heinz; Allan, James M.; Swerdlow, Anthony J.; Goldschmidt, Hartmut; Catovsky, Daniel; Morgan, Gareth J.; Hemminki, Kari; Houlston, Richard S.

    2017-01-01

    B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10-9) with opposing effects between CLL (P = 1.97 × 10-8) and HL (P = 3.31 × 10-3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10-12) was associated with increased CLL and HL risk (P = 4.68 × 10-12), and reduced MM risk (P = 1.12 × 10-2), and Gly70 in HLA-DQB1 (P = 3.15 × 10-10) showed opposing effects between CLL (P = 3.52 × 10-3) and HL (P = 3.41 × 10-9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs.

  7. Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci

    Science.gov (United States)

    Law, Philip J.; Sud, Amit; Mitchell, Jonathan S.; Henrion, Marc; Orlando, Giulia; Lenive, Oleg; Broderick, Peter; Speedy, Helen E.; Johnson, David C.; Kaiser, Martin; Weinhold, Niels; Cooke, Rosie; Sunter, Nicola J.; Jackson, Graham H.; Summerfield, Geoffrey; Harris, Robert J.; Pettitt, Andrew R.; Allsup, David J.; Carmichael, Jonathan; Bailey, James R.; Pratt, Guy; Rahman, Thahira; Pepper, Chris; Fegan, Chris; von Strandmann, Elke Pogge; Engert, Andreas; Försti, Asta; Chen, Bowang; Filho, Miguel Inacio da Silva; Thomsen, Hauke; Hoffmann, Per; Noethen, Markus M.; Eisele, Lewin; Jöckel, Karl-Heinz; Allan, James M.; Swerdlow, Anthony J.; Goldschmidt, Hartmut; Catovsky, Daniel; Morgan, Gareth J.; Hemminki, Kari; Houlston, Richard S.

    2017-01-01

    B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10−9) with opposing effects between CLL (P = 1.97 × 10−8) and HL (P = 3.31 × 10−3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10−12) was associated with increased CLL and HL risk (P = 4.68 × 10−12), and reduced MM risk (P = 1.12 × 10−2), and Gly70 in HLA-DQB1 (P = 3.15 × 10−10) showed opposing effects between CLL (P = 3.52 × 10−3) and HL (P = 3.41 × 10−9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs. PMID:28112199

  8. Treatment of severe refractory autoimmune hemolytic anemia in B-cell chronic lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody).

    Science.gov (United States)

    Karlsson, C; Hansson, L; Celsing, F; Lundin, J

    2007-03-01

    Progressive B-cell chronic lymphocytic leukemia (B-CLL) is often complicated by autoimmune hemolytic anemia (AIHA), which in some cases may be refractory to conventional therapy such as corticosteroids, rituximab and splenectomy. We report here on 5 patients (median age 66 years, range 59-69) with advanced B-CLL, all of whom developed severe transfusion-dependent AIHA resistant to conventional therapy and received subcutaneous (SC) or intravenous (IV) alemtuzumab, a humanized monoclonal antibody that targets the CD52 antigen as salvage treatment for AIHA. Alemtuzumab was well tolerated with only minor 'first dose' reactions. All 5 patients responded with a >or=2.0 g/dl rise in hemoglobin (Hb) concentration, in the absence of further transfusions, after a median time of 5 weeks (range 4-7), and the mean Hb increased from 7.2 g/dl at baseline to 11.9 g/dl at end of treatment. All patients remained stable, without further AIHA episodes, after a median follow-up time of 12 months with a mean Hb of 12.5 g/dl (range 12.2-12.9). For patients with severe, refractory CLL-related AIHA, who have not previously responded to conventional therapy, alemtuzumab is an effective agent.

  9. Occurrence of nodular lymphocyte-predominant hodgkin lymphoma in hermansky-pudlak type 2 syndrome is associated to natural killer and natural killer T cell defects.

    Directory of Open Access Journals (Sweden)

    Luisa Lorenzi

    Full Text Available Hermansky Pudlak type 2 syndrome (HPS2 is a rare autosomal recessive primary immune deficiency caused by mutations on β3A gene (AP3B1 gene. The defect results in the impairment of the adaptor protein 3 (AP-3 complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56(brightCD16(- Natural Killer (NK cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-γ production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients.

  10. Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: clinical characteristics and treatment outcome - a report from the SFCE & CCLG groups.

    Science.gov (United States)

    Shankar, Ananth G; Roques, Gaelle; Kirkwood, Amy A; Lambilliotte, Anne; Freund, Katja; Leblanc, Thierry; Hayward, Janis; Abbou, Samuel; Ramsay, Alan D; Schmitt, Claudine; Gorde-Grosjean, Stephanie; Pacquement, Hélène; Haouy, Stephanie; Boudjemaa, Sabah; Aladjidi, Nathalie; Hall, Georgina W; Landman-Parker, Judith

    2017-04-01

    Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non-Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression-free survival events). The median time to progression for those who progressed was 21 months (5·9-73·8). The median time since last diagnosis is 87·3 months (8·44-179·20). Thirty-six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi-agent chemotherapy as first line treatment seems to be a reasonable therapeutic option. © 2017 John Wiley & Sons Ltd.

  11. CD47 agonist peptides induce programmed cell death in refractory chronic lymphocytic leukemia B cells via PLCγ1 activation: evidence from mice and humans.

    Directory of Open Access Journals (Sweden)

    Ana-Carolina Martinez-Torres

    2015-03-01

    Full Text Available Chronic lymphocytic leukemia (CLL, the most common adulthood leukemia, is characterized by the accumulation of abnormal CD5+ B lymphocytes, which results in a progressive failure of the immune system. Despite intense research efforts, drug resistance remains a major cause of treatment failure in CLL, particularly in patients with dysfunctional TP53. The objective of our work was to identify potential approaches that might overcome CLL drug refractoriness by examining the pro-apoptotic potential of targeting the cell surface receptor CD47 with serum-stable agonist peptides.In peripheral blood samples collected from 80 patients with CLL with positive and adverse prognostic features, we performed in vitro genetic and molecular analyses that demonstrate that the targeting of CD47 with peptides derived from the C-terminal domain of thrombospondin-1 efficiently kills the malignant CLL B cells, including those from high-risk individuals with a dysfunctional TP53 gene, while sparing the normal T and B lymphocytes from the CLL patients. Further studies reveal that the differential response of normal B lymphocytes, collected from 20 healthy donors, and leukemic B cells to CD47 peptide targeting results from the sustained activation in CLL B cells of phospholipase C gamma-1 (PLCγ1, a protein that is significantly over-expressed in CLL. Once phosphorylated at tyrosine 783, PLCγ1 enables a Ca2+-mediated, caspase-independent programmed cell death (PCD pathway that is not down-modulated by the lymphocyte microenvironment. Accordingly, down-regulation of PLCγ1 or pharmacological inhibition of PLCγ1 phosphorylation abolishes CD47-mediated killing. Additionally, in a CLL-xenograft model developed in NOD/scid gamma mice, we demonstrate that the injection of CD47 agonist peptides reduces tumor burden without inducing anemia or toxicity in blood, liver, or kidney. The limitations of our study are mainly linked to the affinity of the peptides targeting CD47

  12. Primary refractory and early-relapsed Hodgkin's lymphoma: strategies for therapeutic targeting based on the tumour microenvironment.

    Science.gov (United States)

    Carbone, Antonino; Gloghini, Annunziata; Castagna, Luca; Santoro, Armando; Carlo-Stella, Carmelo

    2015-09-01

    Classical Hodgkin's lymphoma (cHL), a distinct disease entity with characteristic clinical and pathological features, accounts for approximately 10% of all malignant lymphomas. cHL can be considered a prototype model for how the tumour microenvironment influences cancer pathogenesis. Cellular components of the cHL microenvironment express molecules involved in cancer cell growth and survival, such as CD30L or CD40L. Moreover, several signal transduction pathways that are critical for the proliferation and survival of neoplastic Hodgkin Reed-Sternberg (HRS) cells, including NF-κB, JAK-STAT, PI3K-AkT and ERK, are deregulated in cHL. Although most patients can be cured with modern treatment strategies, approximately a quarter experience either primary or secondary chemorefractoriness or disease relapse, thus requiring novel treatments. Preclinical and clinical evidence has elucidated a complex crosstalk between malignant HRS cells and the reactive cells of the microenvironment, which suggests that novel therapeutic approaches capable of targeting HRS cells along with reactive cells might overcome chemorefractoriness. In the near future, these novel therapies will also be tested in chemosensitive patients, to reduce the long-term toxicity of chemo-radiotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. Emerging role of checkpoint blockade therapy in lymphoma

    Science.gov (United States)

    Galanina, Natalie; Kline, Justin; Bishop, Michael R.

    2017-01-01

    Following the successful application of immune checkpoint blockade therapy (CBT) in refractory solid tumors, it has recently gained momentum as a promising modality in the treatment of relapsed lymphoma. This significant therapeutic advance stems from decades of research that elucidated the role of immune regulation pathways and the mechanisms by which tumors can engage these critical pathways to escape immune detection. To date, two main pathways, the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1), have emerged as key targets of CBT demonstrating unprecedented activity particularly in heavily pretreated relapsed/refractory Hodgkin lymphoma and some forms of non-Hodgkin disease. Herein we provide a brief discussion of checkpoint blockade in the context of lymphoma biology with a specific focus on novel checkpoint inhibitors and their therapeutic activity. We discuss current clinical trials and the landscape of CBT to underscore both the remarkable progress and foreseeable limitations of this novel treatment strategy. In particular, we build upon state-of-the-art knowledge and clinical insights gained from the early trials to review potential approaches to how CBT may be integrated with other treatment modalities, including chemoimmunotherapy to improve patient outcomes in the future. Finally, as the role of CBT evolves to potentially become a cornerstone of therapy in refractory/relapsed lymphoma, we briefly emphasize the importance of predictive biomarkers in an effort to select appropriate patients who are most likely to derive benefit from CBT. PMID:28203344

  14. Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial

    Directory of Open Access Journals (Sweden)

    Francine Foss

    2016-03-01

    Full Text Available Abstract Background Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD. Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130, including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD. Methods Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m2 romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months. Results Of the 32 patients (25 % with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment. The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m2 on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated. Conclusions We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses. Trial registration NCT00426764

  15. Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 1b study from GELTAMO group.

    Science.gov (United States)

    Martín, Alejandro; Redondo, Alba M; Dlouhy, Iván; Salar, Antonio; González-Barca, Eva; Canales, Miguel; Montes-Moreno, Santiago; Ocio, Enrique M; López-Guillermo, Armando; Caballero, Dolores

    2016-04-01

    Diffuse large B-cell lymphoma (DLBCL) patients failing rituximab-containing therapy have a poor outcome with the current salvage regimens. We conducted a phase 1b trial to determine the maximum tolerated dose (MTD) of lenalidomide in combination with R-ESHAP (rituximab, etoposide, cisplatin, cytarabine, methylprednisolone) (LR-ESHAP) in patients with relapsed or refractory DLBCL. Efficacy data were collected as a secondary objective. Subjects received 3 cycles of lenalidomide at escalating doses (5, 10 or 15 mg) given on days 1-14 of every 21-day cycle, in combination with R-ESHAP. Responding patients received BEAM (carmustine, etoposide, cytarabine, melphalan) followed by autologous stem-cell transplantation. Lenalidomide 10 mg/d was identified as the MTD because, in the 15 mg cohort, one patient experienced dose-limiting toxicity (grade 3 angioedema) and two patients had mobilization failure. A total of 19 patients (3, 12 and 4 in the 5, 10 and 15 mg cohorts, respectively) were evaluable. All toxicities occurring during LR-ESHAP cycles resolved appropriately and no grade 4-5 non-haematological toxicities were observed. The complete remission and overall response rates were 47·4% and 78·9%, respectively. With a median follow-up of 24·6 (17·4-38·2) months, the 2-year progression-free survival and overall survival were 44% and 63%, respectively. In conclusion, the LR-ESHAP regimen is feasible and yields encouraging outcomes.

  16. Safety and efficacy of rituximab plus bendamustine in relapsed or refractory diffuse large B-cell lymphoma patients: an Italian retrospective multicenter study.

    Science.gov (United States)

    Arcari, Annalisa; Chiappella, Annalisa; Spina, Michele; Zanlari, Luca; Bernuzzi, Patrizia; Valenti, Vanessa; Tani, Monica; Marasca, Roberto; Cabras, Maria Giuseppina; Zambello, Renato; Santagostino, Alberto; Ilariucci, Fiorella; Carli, Giuseppe; Musto, Pellegrino; Savini, Paolo; Marino, Dario; Ghio, Francesco; Gentile, Massimo; Cox, Maria Christina; Vallisa, Daniele

    2016-08-01

    Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not suitable for high dose chemotherapy with autologous stem cell transplantation (ASCT) has a dismal prognosis and no standard therapy. We designed an Italian multicenter retrospective study aimed at evaluating the safety and efficacy of rituximab plus bendamustine (R-B) as salvage treatment in patients not eligible for ASCT because of age and/or comorbidity or in patients with post-ASCT recurrence. Fifty-five patients with a median age of 76 years were included. The overall response rate was 50%, including 28% complete remission and 22% partial remission. The median overall survival (OS) was 10.8 months. The median progression free survival (PFS) was 8.8 months. Eleven patients are still alive and in complete remission at last follow-up (12-71 months). Toxicity was moderate, mainly grades 1 and 2. R-B showed promising efficacy results with an acceptable toxicity profile and should be further investigated, possibly in combination with novel drugs.

  17. Phase-I and randomized phase-II trial of panobinostat in combination with ICE (ifosfamide, carboplatin, etoposide) in relapsed or refractory classical Hodgkin lymphoma.

    Science.gov (United States)

    Hu, Bei; Younes, Anas; Westin, Jason R; Turturro, Francesco; Claret, Linda; Feng, Lei; Fowler, Nathan; Neelapu, Sattva; Romaguera, Jorge; Hagemeister, Fredrick B; Rodriguez, Maria Alma; Samaniego, Felipe; Fayad, Luis E; Copeland, Amanda R; Nastoupil, Loretta J; Nieto, Yago; Fanale, Michelle A; Oki, Yasuhiro

    2017-08-09

    This phase-I/phase-II study evaluated panobinostat in combination with ifosfamide, carboplatin, etoposide (P-ICE) in relapsed/refractory classical Hodgkin lymphoma. During phase I, panobinostat was given daily on Monday/Wednesday/Friday starting one week prior to Cycle 1 (C1) of ICE and during two weeks of C1-2 of ICE (Schedule A). No DLT was observed at 30 mg. However, frequent (84%) grade-4 thrombocytopenia during second week prompted us to omit the second week of panobinostat 30 mg (Schedule B) for phase II, where this regimen was compared to ICE. In the randomized phase-II study, CR was seen in 9/11 (82%) and 8/12 (67%) for P-ICE and ICE, respectively (p = .64). Grade-4 neutropenia (55% vs. 8%) and thrombocytopenia (100% vs. 33%) were more common in P-ICE. In summary, combination therapy using panobinostat produced high CR rate at the cost of greater bone marrow toxicity. Investigation of panobinostat with less myelosuppressive agents is of interest.

  18. Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia

    Science.gov (United States)

    Castro, JE; Sandoval-Sus, JD; Bole, J; Rassenti, L; Kipps, TJ

    2017-01-01

    We examined the clinical response of fludarabine-refractory CLL patients treated with high-dose methylprednisolone (HDMP) and rituximab. Fourteen patients were treated with three cycles of rituximab (375mg/m2 weekly for 4 weeks) in combination with HDMP (1gm/m2 daily for 5 days). All patients were refractory to fludarabine and 86% had high-risk disease by the modified Rai classification. In all, 79% of the patients had CLL cells that expressed ZAP-70 and three patients had poor prognostic cytogenetics. The overall response rate was 93% and the complete remission rate was 36%. The median time-to-progression was 15 months and the median time-to-next treatment was 22 months. Median survival has not been reached after a median follow up of 40 months. Four patients have died of progressive disease. Patients tolerated the treatment well and serious adverse events were rare. This allowed patients to receive all planned treatments on schedule with no dose modifications. All but one patient responded to treatment and the overall survival and time-to-progression were superior to those of other published salvage regimens. PMID:18754025

  19. Potential role of enzastaurin in the treatment of patients with relapsed or refractory advanced cutaneous T-cell lymphomas: a review

    Directory of Open Access Journals (Sweden)

    Katz DA

    2012-06-01

    Full Text Available Deborah A Katz, Janet MD Plate, Sunita Nathan, Lydia UshaDivision of Hematology and Oncology, Rush University Medical Center, Chicago, IL, USAAbstract: Cutaneous T-cell lymphomas (CTCLs are rare extranodal non-Hodgkin lymphomas characterized by neoplastic T-lymphocyte accumulation in the skin. The two most common types of CTCLs are mycosis fungoides and the leukemic variant, Sézary syndrome. Prognosis of CTCLs depends on the stage, with a poor prognosis in advanced-stage disease. A number of agents have recently been developed for the treatment of CTCLs: chemotherapeutic agents such as pralatrexate, interferon-alpha, retinoids such as bexarotene, monoclonal antibodies such as alemtuzumab, and histone deacetylase inhibitors such as vorinostat and romidepsin. Nevertheless, there is no cure for CTCLs except for allogeneic stem cell transplant. A promising new drug is enzastaurin. Enzastaurin is a novel serine/threonine kinase inhibitor that binds to protein kinase C-β (PKC-β and inhibits the phosphoinositide-3 kinase (PI3K/AKT/phosphatase and tensin homolog (PTEN signaling pathway. Enzastaurin induces apoptosis and inhibits angiogenesis; it was also shown to suppress growth of CTCL cell lines in vitro. Given its low toxicity, enzastaurin has been tested against both solid tumors and hematologic malignancies. This article is focused on the potential role of enzastaurin in the treatment of CTCLs. A phase II multicenter trial evaluated enzastaurin monotherapy in patients with CTCLs. However, the results from this study were disappointing, demonstrating that enzastaurin had only modest clinical activity. Hence, enzastaurin is not currently developed for treating CTCLs. Potential strategies to improve enzastaurin efficacy against CTCLs are discussed: validation of enzastaurin targets such as PKC-β expression in CTCL lesions and or/blood; measurement of serum vascular endothelial growth factor levels; dose optimization; combining enzastaurin with

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

    Science.gov (United States)

    2014-01-06

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

  1. 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

    Science.gov (United States)

    2010-08-05

    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 Non-Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; 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; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  2. Population Pharmacokinetics of Obinutuzumab (GA101) in Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma and Exposure-Response in CLL.

    Science.gov (United States)

    Gibiansky, E; Gibiansky, L; Carlile, D J; Jamois, C; Buchheit, V; Frey, N

    2014-10-29

    Treatment regimens involving obinutuzumab (GA101) demonstrated increased efficacy to rituximab in clinical trials for non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). However, the pharmacokinetic (PK) properties and the exposure-response relationships of obinutuzumab still need to be fully described. Data from four clinical trials of obinutuzumab were analyzed to describe the PK properties in patients with NHL or CLL and the pharmacodynamic (PD) properties in patients with CLL. A population PK model with linear time-dependent clearance described the obinutuzumab concentration-time course. Diagnosis, baseline tumor size (BSIZ), body weight, and gender were the main covariates affecting obinutuzumab exposure. In patients with CLL, exposure was not associated with safety but showed positive trends of correlation with efficacy. Although efficacy correlated positively with exposure, since both efficacy and exposure correlated negatively with BSIZ, it was not possible to determine with certainty whether it would be beneficial to adjust the dose according to BSIZ.

  3. Prognostic performance of lymphocyte-to-monocyte ratio in diffuse large B-cell lymphoma: an updated meta-analysis of eleven reports

    Directory of Open Access Journals (Sweden)

    Sun HL

    2016-05-01

    Full Text Available Hui-Ling Sun,1,* Yu-Qin Pan,1,* Bang-Shun He,1 Zhen-Lin Nie,2 Kang Lin,1 Hong-Xin Peng,1,3 William C Cho,4 Shu-Kui Wang1 1Central Laboratory, 2Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, 3Medical College, Southeast University, Nanjing, 4Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, People’s Republic of China *These authors contributed equally to this work Purpose: The findings on the prognostic value of lymphocyte-to-monocyte ratio (LMR in diffuse large B-cell lymphoma (DLBCL are inconsistent. This meta-analysis was conducted to more precisely evaluate the prognostic significance of LMR in DLBCL. Methods: This analysis combined eleven studies with 4,578 patients aiming to assess the association of LMR with overall survival (OS and progression-free survival (PFS in DLBCL. Data from studies directly reporting a hazard ratio (HR with 95% corresponding confidence interval (CI in multivariate analysis were pooled to estimate the effect. Results: Our results suggested that patients with decreased LMR had shorter OS (HR =1.79, 95% CI =1.54–2.08, P<0.001 and PFS (HR =2.21, 95% CI =1.80–2.72, P<0.001 in DLBCL. Stratified analyses indicated that each confounder showed consistent prognostic value in DLBCL. There was no significant heterogeneity for PFS (PH=0.192 and OS (PH=0.212 among the enrolled studies. Conclusion: This meta-analysis indicated that decreased LMR might be a marker in the prediction of poor prognosis for patients with DLBCL. Keywords: diffuse large B-cell lymphoma, lymphocyte-to-monocyte ratio, meta-analysis, prognosis

  4. A 20-year population-based study on the epidemiology, clinical features, treatment, and outcome of nodular lymphocyte predominant Hodgkin lymphoma.

    Science.gov (United States)

    Strobbe, L; Valke, L L F G; Diets, I J; van den Brand, M; Aben, K; Raemaekers, J M M; Hebeda, K M; van Krieken, J H J M

    2016-02-01

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma characterized by a unique clinical and histological presentation. Because of the rare nature of this disease, few large-scale studies are available. We conducted a cohort study in which patients were identified in the Netherlands Cancer Registry in the Southeast of the Netherlands between 1990 and 2010. Of these patients, we collected all clinical characteristics and re-reviewed pathologic material to confirm NLPHL diagnosis. Seventy-three histologically confirmed cases of NLPHL were analyzed with a median follow-up of 65 months (range 4-257 months). Median age at diagnosis was 43 years (range 1-87); 84.9 % of the patients were male; B symptoms were present in 5.5 %; and stage I/II disease was most common (75.4 %). Patients were primarily treated with radiotherapy (50.7 %), chemotherapy (26 %), combined modality (radiotherapy and chemotherapy) (11 %), or surgical excision with careful watch-and-wait (12.3 %). Relapses occurred in seven patients (9.6 %) after a median of 26 months (21-74 months). Six patients (8.2 %) developed histologic transformation to large cell lymphoma. Five patients (6.8 %) died during follow-up due to progression of NLPHL (n = 1), histologic transformation (n = 2) and intercurrent deaths (n = 2). The estimated 10-year overall survival was 94.0 % and the 10-year progression-free survival 75.8 %. Our study confirms the distinct characteristics of NLPHL with a relatively good long-term prognosis. It may be possible to reduce treatment intensity in early stage NLPHL without affecting long-term outcome.

  5. Fluorescence immunophenotyping and interphase cytogenetics (FICTION) detects BCL6 abnormalities, including gene amplification, in most cases of nodular lymphocyte-predominant Hodgkin lymphoma.

    Science.gov (United States)

    Bakhirev, Alexei G; Vasef, Mohammad A; Zhang, Qian-Yun; Reichard, Kaaren K; Czuchlewski, David R

    2014-04-01

    BCL6 translocations are a frequent finding in B-cell lymphomas of diverse subtypes, including some cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). However, reliable analysis of BCL6 rearrangements using fluorescence in situ hybridization is difficult in NLPHL because of the relative paucity of neoplastic cells. Combined immunofluorescence microscopy and fluorescence in situ hybridization, or fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION), permits targeted analysis of neoplastic cells. To better define the spectrum of BCL6 abnormalities in NLPHL using FICTION analysis. We performed an optimized FICTION analysis of 24 lymph nodes, including 11 NLPHL, 5 follicular hyperplasia with prominent progressive transformation of germinal centers, and 8 follicular hyperplasia without progressive transformation of germinal centers. BCL6 rearrangement was identified in 5 of 11 cases of NLPHL (46%). In addition, BCL6 gene amplification, with large clusters of BCL6 signals in the absence of chromosome 3 aneuploidy, was detected in 3 of 11 cases of NLPHL (27%). One NLPHL showed extra copies of BCL6 present in conjunction with multiple copies of chromosome 3. Altogether, we detected BCL6 abnormalities in 9 of 11 cases of NLPHL (82%). None of the progressive transformation of germinal centers or follicular hyperplasia cases showed BCL6 abnormalities by FICTION. To our knowledge, this is the first report of BCL6 gene amplification in NLPHL. Our optimized protocol for FICTION permits detection of cytogenetic abnormalities in most NLPHL cases and may represent a useful ancillary diagnostic technique.

  6. Quantitative miR analysis in chronic lymphocytic leukaemia/small lymphocytic lymphoma - proliferation centres are characterized by high miR-92a and miR-155 and low miR-150 expression.

    Science.gov (United States)

    Szurián, Kinga; Csala, Irén; Piurkó, Violetta; Deák, Linda; Matolcsy, András; Reiniger, Lilla

    2017-07-01

    Proliferation centres (PCs) are histological hallmarks of lymph nodes in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). Chromosomal abnormalities have already been described to accumulate preferably in the PCs as opposed to the intervening small cell areas. To further characterize the pathogenic role of PCs, the expression levels of 17 selected miRs known to be involved in the development of CLL/SLL were compared in the PCs and the intervening small cell areas in lymph nodes of 15 patients with CLL/SLL. The miR expression levels were also compared to the cytogenetic alterations defined by FISH analysis. Our results show that two known oncomiRs, miR-155 and -92a were upregulated and the tumour suppressor miR-150 was downregulated in the PCs. Low expression of miR-150 was also associated with loss of 11q. In summary we found significantly higher expression of oncomiRs and lower expression of a tumour suppressor miR in PCs of CLL/SLL lymph nodes, which support the hypothesis that the PCs may drive the disease and play a role in progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

  8. Phase I-II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints.

    Science.gov (United States)

    Winqvist, Maria; Mozaffari, Fariba; Palma, Marzia; Eketorp Sylvan, Sandra; Hansson, Lotta; Mellstedt, Håkan; Österborg, Anders; Lundin, Jeanette

    2017-01-01

    This phase I-II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1-16) and alemtuzumab (weeks 5-16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1-29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2.5 mg/day was not efficient, and maximum tolerated dose was 5 mg/day. Grade 3-4 neutropenia and thrombocytopenia occurred in 84 and 55%, 30% had febrile neutropenia, and CMV-reactivation requiring valganciclovir occurred in 30% of patients. The frequency of proliferating (Ki67(+)) CD8(+) T cells was increased at week 4, with further increase in both the CD4(+) and CD8(+) subsets (p low-dose lenalidomide and alemtuzumab induced major perturbations of T cells, including increased proliferative activity and cytotoxic potential.

  9. Improved outcomes after autologous bone marrow transplantation for children with relapsed or refractory Hodgkin lymphoma: twenty years experience at a single institution.

    Science.gov (United States)

    Garfin, Phillip M; Link, Michael P; Donaldson, Sarah S; Advani, Ranjana H; Luna-Fineman, Sandra; Kharbanda, Sandhya; Porteus, Matthew; Weinberg, Kenneth I; Agarwal-Hashmi, Rajni

    2015-02-01

    The purpose of this study is to evaluate the survival of pediatric patients undergoing autologous bone marrow transplantation (auBMT) for relapsed or refractory Hodgkin lymphoma (rrHL) and to identify factors that might contribute to their outcome. We reviewed the records and clinical course of 89 consecutive rrHL patients ≤ 21 years old who underwent auBMT at Stanford Hospitals and Clinics and the Lucile Packard Children's Hospital, Stanford between 1989 and 2012. We investigated, by multiple analyses, patient, disease, and treatment characteristics associated with outcome. Endpoints were 5-year overall and event-free survival. Our findings include that cyclophosphamide, carmustine, and etoposide (CBV) as a conditioning regimen for auBMT is effective for most patients ≤ 21 years old with rrHL (5-year overall survival, 71%). Transplantation after the year 2001 was associated with significantly improved overall survival compared with our earlier experience (80% compared with 65%). Patients with multiply relapsed disease or with disease not responsive to initial therapy fared less well compared with those with response to initial therapy or after first relapse. Administration of post-auBMT consolidative radiotherapy (cRT) also appears to contribute to improved survival. We are able to conclude that high-dose chemotherapy with CBV followed by auBMT is effective for the treatment of rrHL in children and adolescents. Survival for patients who undergo auBMT for rrHL has improved significantly. This improvement may be because of patient selection and improvements in utilization of radiotherapy rather than improvements in chemotherapy. Further investigation is needed to describe the role of auBMT across the entire spectrum of patients with rrHL and to identify the most appropriate preparative regimen with or without cRT therapy in the treatment of rrHL in young patients.

  10. Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program.

    Science.gov (United States)

    Perrot, Aurore; Monjanel, Hélène; Bouabdallah, Réda; Quittet, Philippe; Sarkozy, Clémentine; Bernard, Marc; Stamatoullas, Aspasia; Borel, Cécile; Bouabdallah, Krimo; Nicolas-Virelizier, Emmanuelle; Fournier, Marion; Morschhauser, Franck; Brice, Pauline

    2016-04-01

    Brentuximab vedotin was reported to be effective and safe against refractory/relapsed Hodgkin lymphoma in cohorts of between 12 to 102 patients. Herein we report our retrospective analysis of the French experience with brentuximab vedotin used alone to treat 240 refractory/relapsed Hodgkin lymphoma patients enrolled in a named patient program between 2011 and 2013. All patients had histologically documented CD30+ Hodgkin lymphoma; 74% had refractory disease or early relapses. After a median of 3 lines of chemotherapy, brentuximab vedotin was infused intravenously (1.8 mg/kg every 3 weeks). The primary endpoint was best response. Response at the end of treatment, its duration, survival data and toxicity profile were secondary endpoints. Patients received a median of 6 cycles; 68 underwent a consolidation thereafter. The best response was observed after a median of 4 cycles in 145 (60.4%) patients: 33.8% complete response/unconfirmed complete response, 26.7% partial response. Objective responses were observed as decreased (39.3%) in the 28 patients >60 years. The median response duration was 8.4 months. With median follow-up at 16.1 months, median progression-free survival was 6.8 months and this was significantly longer for patients transplanted after brentuximab vedotin (a median of 18,8 months); median overall survival was not reached. No death has been linked to brentuximab vedotin toxicity. The most common adverse events were peripheral sensory neuropathy (29.3%) and hematological toxicity. The results of this analysis support the previously reported brentuximab vedotin efficacy with manageable toxicity. Because of the short-term responses in most patients, a high-dose therapy with stem cell transplantation for responders should be considered as quickly as possible.

  11. Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program

    Science.gov (United States)

    Perrot, Aurore; Monjanel, Hélène; Bouabdallah, Réda; Quittet, Philippe; Sarkozy, Clémentine; Bernard, Marc; Stamatoullas, Aspasia; Borel, Cécile; Bouabdallah, Krimo; Nicolas-Virelizier, Emmanuelle; Fournier, Marion; Morschhauser, Franck; Brice, Pauline

    2016-01-01

    Brentuximab vedotin was reported to be effective and safe against refractory/relapsed Hodgkin lymphoma in cohorts of between 12 to 102 patients. Herein we report our retrospective analysis of the French experience with brentuximab vedotin used alone to treat 240 refractory/relapsed Hodgkin lymphoma patients enrolled in a named patient program between 2011 and 2013. All patients had histologically documented CD30+ Hodgkin lymphoma; 74% had refractory disease or early relapses. After a median of 3 lines of chemotherapy, brentuximab vedotin was infused intravenously (1.8 mg/kg every 3 weeks). The primary endpoint was best response. Response at the end of treatment, its duration, survival data and toxicity profile were secondary endpoints. Patients received a median of 6 cycles; 68 underwent a consolidation thereafter. The best response was observed after a median of 4 cycles in 145 (60.4%) patients: 33.8% complete response/unconfirmed complete response, 26.7% partial response. Objective responses were observed as decreased (39.3%) in the 28 patients >60 years. The median response duration was 8.4 months. With median follow-up at 16.1 months, median progression-free survival was 6.8 months and this was significantly longer for patients transplanted after brentuximab vedotin (a median of 18,8 months); median overall survival was not reached. No death has been linked to brentuximab vedotin toxicity. The most common adverse events were peripheral sensory neuropathy (29.3%) and hematological toxicity. The results of this analysis support the previously reported brentuximab vedotin efficacy with manageable toxicity. Because of the short-term responses in most patients, a high-dose therapy with stem cell transplantation for responders should be considered as quickly as possible. PMID:26768687

  12. Improving outcomes of refractory celiac disease – current and emerging treatment strategies

    Directory of Open Access Journals (Sweden)

    Woodward J

    2016-08-01

    Full Text Available Jeremy Woodward Department of Gastroenterology and Clinical Nutrition, Addenbrooke’s Hospital, Cambridge, UK Abstract: Intestinal inflammation and symptoms of celiac disease (CD usually respond well to gluten withdrawal, but rare cases are refractory to diet. Two types of refractory CD are discriminated on the basis of the presence or absence of an atypical population of mucosal lymphocytes that may progress to enteropathy-associated T-cell lymphoma. Challenges remain in the secure diagnosis of both types of refractory disease, and evidence on which to base treatment recommendations is flawed by the small numbers of reported patients and the use of different diagnostic strategies. Recent advances in our understanding of the mechanisms of the condition in conjunction with the development of immunomodulatory agents for managing other inflammatory diseases are helping to shape future approaches to targeted therapy. Progression will depend on collaboration and recruitment to trials. In the meantime, there is evidence to suggest that earlier diagnosis and better follow-up and management of CD may prevent the development of refractoriness. Keywords: celiac disease, gluten, small intestine, lymphoma, lymphocytes

  13. Prognostic value of the age-adjusted International Prognostic Index in chemosensitive recurrent or refractory non-Hodgkin's lymphomas treated with high-dose BEAM therapy and autologous stem cell transplantation.

    Science.gov (United States)

    Jabbour, E; Peslin, N; Arnaud, P; Ferme, C; Carde, P; Vantelon, J M; Bocaccio, C; Bourhis, J H; Koscielny, S; Ribrag, V

    2005-06-01

    High-dose therapy (HDT) is now recommended for patients under 60 years of age with chemosensitive relapsed aggressive non-Hodgkin's lymphoma. However, approximately half of these patients will be cured by HDT. Prognostic factors are needed to predict which patients with chemosensitive lymphoma to second-line therapy could benefit from HDT. We retrospectively investigated the prognostic value of the widely used age-adjusted International Prognostic Index (AA-IPI) calculated at the time of relapse (35 patients) or just before second-line salvage therapy for primary refractory disease (5 patients). The median age was 51 years (range 18-64 years). Thirty-six patients had diffuse large B-cell lymphoma. Salvage cytoreductive therapy before HDT was DHAP/ESHAP (cytarabine, cysplatin, etoposide, steroids) in 17 patients, VIM3-Ara-c/MAMI (high-dose cytarabine, ifosfamide, methyl-gag, amsacrine) in 17 patients, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or reinforced CHOP in 4 patients, high-dose cyclophosphamide and etoposide in 2 patients. The HDT regimen consisted of BEAM (carmusine, cytarabine, etoposide, melphalan) in all cases. Eleven patients were in partial remission and 29 in complete remission at the time of HDT. Ten patients had an IPI >1, 16 had relapsed early (6 months after first-line chemotherapy) (P=1), but the AA-IPI >1 was associated with a poor outcome (P=0.03). In conclusion, the AA-IPI could have a prognostic value in patients with chemosensitive recurrent lymphoma treated with BEAM HDT.

  14. Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy

    Science.gov (United States)

    Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

    2012-01-01

    Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to

  15. Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin's lymphoma responding to prior salvage therapy.

    Science.gov (United States)

    Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

    2012-07-01

    High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin's lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin's lymphoma. We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin's lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed

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

    Science.gov (United States)

    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

  17. Update on the Diagnosis and Management of Refractory Coeliac Disease

    Directory of Open Access Journals (Sweden)

    Petula Nijeboer

    2013-01-01

    Full Text Available A small subset of coeliac disease (CD patients experiences persisting or recurring symptoms despite strict adherence to a gluten-free diet (GFD. When other causes of villous atrophy have been excluded, these patients are referred to as refractory celiac disease (RCD patients. RCD can be divided in two types based on the absence (type I or presence (type II of an, usually clonal, intraepithelial lymphocyte population with aberrant phenotype. RCDI usually runs a benign course and may be difficult to be differentiated from uncomplicated, slow responding CD. In contrast, RCDII can be defined as low-grade intraepithelial lymphoma and frequently transforms into an aggressive enteropathy associated T-cell lymphoma with dismal prognosis. This paper describes the clinical characteristics of RCDI and RCDII, diagnostic approach, and the latest insights in treatment options.

  18. Lymphomas of large cells.

    Science.gov (United States)

    Staples, W G; Gétaz, E P

    1977-09-03

    Historial aspects of the classification of large-cell lymphomas are described. Immunological characterization of the lymphomas has been made possible by identification of T and B lymphocytes according to their cell membrane surface characteristics. The pathogenesis of lymphomas has been clarified by the germinal (follicular) centre cell concepts of Lennert and Lukes and Collins. The various classifications are presented and compared. Whether these subdivisions will have any relevance in the clinical context remains to be seen.

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

    Science.gov (United States)

    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

  20. Bendamustine in the treatment of non-Hodgkin’s lymphomas

    Directory of Open Access Journals (Sweden)

    Fredrick Hagemeister

    2009-12-01

    Full Text Available Fredrick Hagemeister1, George Manoukian21Department of Lymphoma/Myeloma, The University of Texas M.D. Anderson Cancer Center Houston, TX, USA; 2Department of Internal Medicine, The University of Texas Health Science Center, Houston, TX, USAPurpose: To review available data using bendamustine alone and in combination with other chemotherapeutic agents in treatment of patients with non-Hodgkin’s lymphomas.Methods: Internet database searches and literature review.Results: Bendamustine was approved in March 2008 by the United States Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia. Many trials have been performed over the last decade using bendamustine not only as monotherapy, but also in combination with other agents including rituximab, vincristine, mitoxantrone, fludarabine, and other agents as therapy for patients with relapsed non-Hodgkin’s lymphomas, and recently was approved for use in therapy of patients with relapsed indolent lymphomas considered refractory to rituximab therapy. As monotherapy, bendamustine induces good responses with only minor side effects. In combination with other agents, efficacy improves, especially when given in combination with rituximab. The drug has also been studied in combination with rituximab as initial therapy for indolent lymphomas, and has excellent activity with less toxicity than R-CHOP (rituximab – cyclophosphamide, hydroxydaunorubicin [Adriamycin], Oncovin [vincristine], and prednisone/prednisolone.Conclusion: Overall, bendamustine has demonstrated promising results as therapy for non-Hodgkin’s lymphomas and should be included in the armamentarium of agents used to treat relapsed indolent non-Hodgkin’s lymphomas and may prove valuable as initial therapy for these diseases. Further studies are being conducted to demonstrate the efficacy of this drug in combination with other agents.Keywords: bendamustine, non-Hodgkin’s lymphomas, relapsed lymphoma

  1. 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

    Science.gov (United States)

    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

  2. Absolute Monocyte Count and Lymphocyte-Monocyte Ratio Predict Outcome in Nodular Sclerosis Hodgkin Lymphoma: Evaluation Based on Data From 1450 Patients.

    Science.gov (United States)

    Tadmor, Tamar; Bari, Alessia; Marcheselli, Luigi; Sacchi, Stefano; Aviv, Ariel; Baldini, Luca; Gobbi, Paolo G; Pozzi, Samantha; Ferri, Paola; Cox, Maria Christina; Cascavilla, Nicola; Iannitto, Emilio; Federico, Massimo; Polliack, Aaron

    2015-06-01

    To verify whether absolute monocyte count (AMC) and lymphocyte- monocyte ratio (LMR) at diagnosis are valid prognostic parameters in classical Hodgkin lymphoma (cHL). Data were collected from 1450 patients with cHL treated in Israel and Italy from January 1, 1988, through December 31, 2007. The median age of the patients was 33 years (range, 17-72 years), and 70% (1017) of the patients had nodular sclerosis (NS); the median follow-up duration was 87 months. The best cutoff value for AMC was 750 cells/mm(3), and the best ratio for LMR was 2.1. The adverse prognostic impact of an AMC of more than 750 cells/mm(3) was confirmed for the entire cohort, and its clinical significance was particularly evident in patients with NS histology. The progression-free survival (PFS) at 10 years for an AMC of more than 750 cells/mm(3) was 65% (56%-72%), and the PFS at 10 years for an AMC of 750 cells/mm(3) or less was 81% (76%-84%; PHR], 1.54, P=.006, and HR, 1.50, P=.006) after adjusting for the international prognostic score, whereas the impact on OS was confirmed (HR, 1.56; P=.04) only in patients with NS and an AMC of more than 750 cells/mm(3). This study confirms that AMC has prognostic value in cHL that is particularly significant in patients with NS subtype histology. This finding links the known impact of macrophages and monocytes in Hodgkin lymphoma with routine clinical practice. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  3. A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

    Science.gov (United States)

    2016-10-18

    Ewing Sarcoma; Gastrointestinal Tumor; Germ Cell Tumor; Hepatic Tumor; Lymphoma; Wilms Tumor; Rhabdoid Tumor; Clear Cell Carcinoma; Renal Cell Carcinoma; Melanoma; Neuroblastoma; Rhabdomyosarcoma; Non-rhabdomyosarcoma

  4. Collision tumor of primary merkel cell carcinoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, diagnosed on ultrasound-guided fine-needle aspiration biopsy: a unique case report and review of literature.

    Science.gov (United States)

    Li, Zhonghua; Yang, Jing-Jing; Wu, Maoxin

    2015-01-01

    We report an extremely rare case of skin collision tumor between primary Merkel cell carcinoma (MCC) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) first diagnosed on ultrasound-guided fine-needle aspiration biopsy (US-FNA). A 95-year-old female with a history of CLL presented with a slow growing left malar mass was referred to our clinic for US-FNA. US scan showed a well-defined subcutaneous mass (2.78 cm) with complex echogenicity. On-site assessment showed a cellular aspiration which was interpreted as small blue round cell tumor. On further examination, smears and cell block showed dimorphic populations of relatively larger cells with neuroendocrine features and smaller lymphoid cells. Immunocytochemical studies of cell block sections revealed that the larger cells were positive for CD56, Chromogranin, Synaptophysin, CK8/18, CK20 (dot-like pattern); and the smaller cells were positive for CD45. Flow cytometric analysis showed a majority of CD16/CD56 positive cells, 17% of monoclonal B-cells, and 14% of reactive T cells. The immunophenotype of the monoclonal B cells were of CLL/SLL. The diagnosis of a collision tumor composed of primary MCC and CLL/SLL was confirmed. Surgical resection of the mass one month later concurred with the FNA cytological diagnosis. The fact that surgical specimen displayed a solid tumor with both CLL/SLL and MCC components ruled out the possibility that the FNA merely had MCC with peripheral leukemic blood contaminant. No additional MCC lesion was found in the patient, which ruled out the possibility of metastatic MCC to a lymphomatous lymph node. © 2014 Wiley Periodicals, Inc.

  5. The microenvironment of Hodgkin lymphoma : Composition and interaction

    NARCIS (Netherlands)

    Sattarzadeh, Ahmad

    2016-01-01

    Hodgkin lymphoma (HL) as a type of lymphoma with two subtypes including classical Hodgkin lymphoma (cHL) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). HL is a unique type of lymphoma with a population of neoplastic cells which consist less than1% of the total cell population- in a

  6. Neuroendocrine function in survivors of childhood acute lymphocytic leukemia and non-Hodgkins lymphoma: a study of pulsatile growth hormone and gonadotropin secretions

    Energy Technology Data Exchange (ETDEWEB)

    Mauras, N.; Sabio, H.; Rogol, A.D.

    To assess the neuroendocrine function of long-term survivors of childhood hematologic malignancies, 10 patients who had acute lymphocytic leukemia and two who had non-Hodgkins lymphoma (NHL) (mean age 13.5 +/- 1 year) were studied, who were treated with similar chemotherapeutic regimens with or without 2400 rads of prophylactic cranial irradiation. Pharmacologic growth hormone (GH) stimulation tests and three graded doses of the GH-releasing hormone (1-40-OH-GRH, 0.1, 0.3, and 1 microgram/kg) were administered. Venous sampling for GH and gonadotropin determinations was done at 20-min intervals for 24 h, and a new computerized pulse detection algorithm was used to analyze pulses. All the patients who had neuroendocrine abnormalities were in the cranially irradiated group. Two of the 12 patients were GH deficient, and had abnormal 24-h secretory profiles, blunted GH responses to pharmacologic stimuli, and minimal responses to the three doses of GRH. The pulsatile properties of luteinizing hormone (LH) were normal in 10 of the 12 nongonadally irradiated patients, irrespective of previous cranial irradiation and pubertal stage, when compared with available normative data.

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

    Science.gov (United States)

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

    2014-05-01

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

  8. Barriers to the Access and Use of Rituximab in Patients with Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia: A Physician Survey

    Directory of Open Access Journals (Sweden)

    William H. Baer II

    2014-05-01

    Full Text Available Biologics such as rituximab are an important component of oncology treatment strategies, although access to such therapies is challenging in countries with limited resources. This study examined access to rituximab and identified potential barriers to its use in the United States, Mexico, Turkey, Russia, and Brazil. The study also examined whether availability of a biosimilar to rituximab would improve access to, and use of, rituximab. Overall, 450 hematologists and oncologists completed a survey examining their use of rituximab in patients with non-Hodgkin’s lymphoma (NHL and chronic lymphocytic leukemia (CLL. Less than 40% of physicians considered rituximab as easy to access from a cost perspective. Furthermore, many physicians chose not to treat, were unable to treat, or had to modify treatment with rituximab despite guidelines recommending its use in NHL and CLL patients. Insurance coverage, reimbursement, and cost to patient were commonly reported as barriers to the use of rituximab. Across all markets, over half of physicians reported that they would increase use of rituximab if a biosimilar was available. We conclude that rituximab use would increase across all therapy types and markets if a biosimilar was available, although a biosimilar would have the greatest impact in Brazil, Mexico, and Russia.

  9. S-phase induction by interleukin-6 followed by chemotherapy in patients with chronic lymphocytic leukemia and non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Brown, P D; Diamant, Marcus; Jensen, P O

    1999-01-01

    Interleukin-6 (IL-6) has in vitro demonstrated growth regulatory effects on tumor cells from patients with chronic lymphocytic leukemia (CLL) and lymphoma. The proliferation rate of these cells is usually very low and this is thought to be one of the reasons for the lack of a curative potential...... of cytostatic chemotherapy in CLL and low grade NHL. Recombinant human (rh) IL-6 might increase the in vivo proliferation rate leading to a higher sensitivity for chemotherapy. We tested this hypothesis by administering rhIL-6 to 9 CLL patients and 3 NHL patients in doses of 2.5 micrograms/kg, 5 micrograms....../kg and 10 micrograms/kg s.c. daily for 5 days followed by CHOP chemotherapy on the last day of rhIL-6 injection. Six patients had two treatment cycles. The proportion of cells in S-phase was determined by the bromodeoxyuridine labeling index (LI). Three patients achieved a partial remission, one patient had...

  10. Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease : Report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's disease

    NARCIS (Netherlands)

    Diehl, [No Value; Sextro, M; Franklin, J; Hansmann, ML; Harris, N; Jaffe, E; Poppema, S; Harris, M; Franssila, K; van Krieken, J; Marafioti, T; Anagnostopoulos, [No Value; Stein, H

    1999-01-01

    Purpose: Recent studies have suggested that lymphocyte-predominant Hodgkin's disease (LPHD) is both clinically and pathologically distinct from or her forms of Hodgkin's disease, including classical Hodgkin's disease (CHD), However, large-scale clinical studies were tacking, This multicenter, retros

  11. GDP (Gemcitabine, Dexamethasone, and Cisplatin) Is Highly Effective and Well-Tolerated for Newly Diagnosed Stage IV and Relapsed/Refractory Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type.

    Science.gov (United States)

    Wang, Jing-Jing; Dong, Mei; He, Xiao-Hui; Li, Ye-Xiong; Wang, Wei-Hu; Liu, Peng; Yang, Jian-Liang; Gui, Lin; Zhang, Chang-Gong; Yang, Sheng; Zhou, Sheng-Yu; Shi, Yuan-Kai

    2016-02-01

    This study was conducted to evaluate the effectiveness and tolerance of GDP (gemcitabine, dexamethasone, and cisplatin) regimen in patients with newly diagnosed stage IV and relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKTL).The study enrolled 41 ENKTL patients who received GDP regimen at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2008 and January 2015.The disease status was newly diagnosed stage IV in 15 patients and relapsed/refractory in 26 patients. The median number of cycles of chemotherapy per patient was 6 (range, 2-8 cycles). The overall response rate and complete-remission rate were 83.0% (34/41) and 41.5% (17/41), respectively. After a median follow-up of 16.2 months, 1-year progression-free survival rate and 1-year overall survival rate for the whole cohort were 54.5% and 72.7%. Grade 3 to 4 adverse events included neutropenia (34.1%), thrombocytopenia (19.5%), and anemia (14.6%).Our study has suggested high efficacy and low toxicity profile of GDP regimen in patients with newly diagnosed stage IV and relapsed/refractory ENKTL.

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

    Science.gov (United States)

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

    2017-05-01

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

  13. Health-related quality of life and symptoms in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated in the phase III GADOLIN study with obinutuzumab plus bendamustine versus bendamustine alone.

    Science.gov (United States)

    Cheson, Bruce D; Trask, Peter C; Gribben, John G; Dimier, Natalie; Kimby, Eva; Lugtenburg, Pieternella J; Thieblemont, Catherine; Wassner-Fritsch, Elisabeth; Launonen, Aino; Sehn, Laurie H

    2017-02-01

    We present health-related quality of life (HRQoL) data from GADOLIN, comparing bendamustine (B) alone or combined with obinutuzumab (G-B) in rituximab-refractory indolent non-Hodgkin lymphoma patients. The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) questionnaire was administered on day 1 of cycles 1, 3, and 5 during treatment, at end of induction (EOI), bi-monthly for 2 years during maintenance/follow-up, and annually during extended follow-up until progression/death. Time to first ≥6-point worsening from baseline in the FACT-Lym trial outcome index (TOI) was estimated. Minimally important differences at individual subscale and total score level were used to define the proportion of patients reporting improvement on the FACT-Lym lymphoma-specific subscale (≥3 points), FACT-Lym TOI (≥6 points), and FACT-Lym total score (≥7 points). Overall, 396 patients were randomized. Analysis was conducted when 175 Independent Review Committee-assessed progression-free survival (PFS) events were observed. Questionnaire completion rates were generally balanced between arms at baseline, EOI, and final follow-up. Median time to ≥6-point worsening from baseline on the FACT-Lym TOI was 8.0 months in the G-B arm and 4.6 months in the B arm (HR 0.74; 95% CI 0.56-0.98). More G-B patients reported meaningful improvements on the FACT-Lym questionnaire subscales. Results were similar when follicular lymphoma patients were analyzed separately. The delayed time to worsening and greater proportion of patients reporting meaningful improvement in HRQoL in the G-B arm suggest that benefit in PFS is not at the expense of an increase in treatment-related toxicity that could lead to reduced HRQoL.

  14. Clinical role of obinutuzumab in the treatment of naive patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Cerquozzi, Sonia; Owen, Carolyn

    2015-01-01

    The introduction of targeted therapy against CD20(+) with the monoclonal antibody rituximab has dramatically improved the survival of B-cell non-Hodgkin lymphoma including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma. Unfortunately, CLL remains incurable with chemoimmunotherapy, with many patients having refractory or relapsing disease after rituximab-containing therapy. Obinutuzumab (GA101) is a novel humanized Type II anti-CD20 monoclonal antibody that has been investigated and compared to rituximab. Here, we provide an overview of obinutuzumab, including its mechanisms of action, preclinical data, and Phase I to III clinical studies. Preclinical data illustrate obinutuzumab's higher potency compared to rituximab through antibody-dependent cellular cytotoxicity and direct cell death. Recently, the CLL11 study presented a significant benefit from obinutuzumab chemoimmunotherapy and supports its use for treatment-naive unfit CLL patients. Herein, we review that obinutuzumab is both a safe and effective alternative to rituximab.

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

    Science.gov (United States)

    2016-10-11

    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

  16. CAR-pNK Cell Immunotherapy in CD7 Positive Leukemia and Lymphoma

    Science.gov (United States)

    2016-12-04

    Acute Myeloid Leukemia; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; T-cell Prolymphocytic Leukemia; T-cell Large Granular Lymphocytic Leukemia; Peripheral T-cell Lymphoma, NOS; Angioimmunoblastic T-cell Lymphoma; Extranodal NK/T-cell Lymphoma, Nasal Type; Enteropathy-type Intestinal T-cell Lymphoma; Hepatosplenic T-cell Lymphoma

  17. Expression of apoptosis markers on peripheral blood lymphocytes from patients with cutaneous T-cell lymphoma during extracorporeal photochemotherapy.

    Science.gov (United States)

    Osella-Abate, S; Zaccagna, A; Savoia, P; Quaglino, P; Salomone, B; Bernengo, M G

    2001-01-01

    The mechanisms of extracorporeal photochemotherapy (ExP) therapeutic activity in cutaneous T-cell lymphomas (CTCLs) are not yet well understood, even though it has been suggested that a major mechanism may be induction of apoptosis. In vitro studies demonstrate that UVA-induced apoptosis is mediated by CD95-Fas expression and inhibited by Bcl-2 up-regulation and that UVA irradiation is able to down-regulate Bcl-2 expression. High-resolution multiparameter flow-cytometric analyses were used to evaluate Bcl-2/CD95-Fas expression on phenotypically identifiable circulating clonal T cells from 7 patients with CTCL (4 with Sézary syndrome and 3 with mycosis fungoides with peripheral involvement) before and during ExP, in an attempt to ascertain whether Bcl-2/CD95-Fas status can be related to the hematologic response. A Bcl-2 normal phenotype before ExP or a normalization in Bcl-2 expression during ExP were related to a better clinical response, whereas a persistent Bcl-2 high expression was a negative prognostic factor. On the other hand, no response was found in patients with a CD95-Fas-negative phenotype, whereas the expression of CD95-Fas was associated with hematologic remission. Although further studies are needed to confirm these preliminary results, this study suggests that Bcl-2 and CD95-Fas expression could be evaluated, together with the other known clinical and immunologic factors, as additional parameters related to clinical response in patients with CTCL undergoing ExP.

  18. Pediatric lymphomas in Brazil

    Directory of Open Access Journals (Sweden)

    Gabriela Gualco

    2010-01-01

    Full Text Available OBJECTIVE: This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. METHODS: A retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. We believe that it represents the largest series of pediatric lymphomas presented from Brazil. RESULTS: Non-Hodgkin lymphomas represented 68% of the cases, including those of precursor (36% and mature (64% cell origin. Mature cell lymphomas comprised 81% of the B-cell phenotype and 19% of the T-cell phenotype. Hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. The geographic distribution showed 38.4% of the cases in the Southeast region, 28.7% in the Northeast, 16.1% in the South, 8.8% in the North, and 8% in the Central-west region. The distribution by age groups was 15-18 years old, 33%; 11-14 years old, 26%; 6-10 years old, 24%; and 6 years old or younger, 17%. Among mature B-cell lymphomas, most of the cases were Burkitt lymphomas (65%, followed by diffuse large B-cell lymphomas (24%. In the mature T-cell group, anaplastic large cell lymphoma, ALK-positive was the most prevalent (57%, followed by peripheral T-cell lymphoma, then not otherwise specified (25%. In the group of classic Hodgkin lymphomas, the main histological subtype was nodular sclerosis (76%. Nodular lymphocyte predominance occurred more frequently than in other series. CONCLUSION: Some of the results found in this study may reflect the heterogeneous socioeconomical status and environmental factors of the Brazilian population in different regions.

  19. TP53 Staining in Tissue Samples of Chronic Lymphocytic Lymphoma Cases: An Immunohistochemical Survey of 51 Cases

    Directory of Open Access Journals (Sweden)

    İbrahim Kulaç

    2017-03-01

    Full Text Available Objective: Chronic lymphocytic leukemia (CLL is the most common lymphoproliferative disease in adults. The aim of this study is to find out if the extent of proliferation centers or the immunohistochemical expression of p53 is related to disease prognosis. Materials and Methods: In the scope of this study, 54 biopsy specimens from 51 patients (50 of lymph nodes; the others of spleen, tonsil, orbit, and liver diagnosed with CLL at the Hacettepe University Department of Pathology in 2000-2013 were reevaluated. The clinical and demographic data of the patients were obtained from our patient database. Biopsy samples were assessed semi-quantitatively for the percentage of proliferation center/total biopsy area (PC/TBA and an immunohistochemical study was performed on representative blocks of tissues for p53 expression. Results: When the patients were divided into two categories according to Rai stage as high and low (stages 0, 1, and 2 vs. stages 3 and 4, it was seen that patients with low Rai stage had a better prognosis than those with high stages (p=0.030. However, there was no statistically significant correlation between overall survival and PC/TBA ratio or p53 expression levels. Conclusion: In our cohort, PC/TBA ratio and immunopositivity of p53 did not show correlations with overall survival.

  20. Day 100 Peripheral Blood Absolute Lymphocyte/Monocyte Ratio and Survival in Classical Hodgkin's Lymphoma Postautologous Peripheral Blood Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Luis F. Porrata

    2013-01-01

    Full Text Available Day 100 prognostic factors of postautologous peripheral blood hematopoietic stem cell transplantation (APBHSCT to predict clinical outcome in classical Hodgkin lymphoma (cHL patients have not been evaluated. Thus, we studied if the day 100 peripheral blood absolute lymphocyte/monocyte ratio (Day 100 ALC/AMC affects clinical outcomes by landmark analysis from day 100 post-APBHSCT. Only cHL patients achieving a complete remission at day 100 post-APBHSCT were studied. From 2000 to 2010, 131 cHL consecutive patients qualified for the study. The median followup from day 100 was 4.1 years (range: 0.2–12.3 years. Patients with a Day 100 ALC/AMC ≥ 1.3 experienced superior overall survival (OS and progression-free survival (PFS compared with Day 100 ALC/AMC < 1.3 (from day 100: OS, median not reached versus 2.8 years; 5 years OS rates of 93% (95% CI, 83%–97% versus 35% (95% CI, 19%–51%, resp., P<0.0001; from day 100: PFS, median not reached versus 1.2 years; 5 years PFS rates of 79% (95% CI, 69%–86% versus 27% (95% CI, 14%–45%, resp., P<0.0001. Day ALC/AMC ratio was an independent predictor for OS and PFS. Thus, Day 100 ALC/AMC ratio is a simple biomarker that can help to assess clinical outcomes from day 100 post-APBHSCT in cHL patients.

  1. Role of ofatumumab in treatment of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Veliz M

    2011-05-01

    Full Text Available Marays Veliz, Javier Pinilla-IbarzH Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USAAbstract: The management of chronic lymphocytic leukemia (CLL has dramatically improved in the past decade with the addition of anti-CD20 monoclonal antibodies to the treatment armamentarium. Ofatumumab is a novel anti-CD20 monoclonal antibody recently approved in the US and Europe for the treatment of CLL refractory to alemtuzumab and fludarabine. Preclinical data showed improved complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity compared with rituximab. Clinical studies have shown single-agent activity for ofatumumab in CLL and in other low-grade non-Hodgkin's lymphomas. Combination studies are being conducted to enhance the therapeutic efficacy of ofatumumab. This paper reviews some of the key clinical studies that led to approval of ofatumumab, and future directions.Keywords: ofatumumab, chronic lymphocytic leukemia, efficacy, safety

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

    Science.gov (United States)

    2017-01-26

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

  3. Effect of MINE-ESHAP regimen in treatment of refractory or relapsed non-Hodgkin lymphoma%MINE-ESHAP联合方案治疗难治或复发性非霍奇金淋巴瘤28例

    Institute of Scientific and Technical Information of China (English)

    冯国安; 邢正云

    2010-01-01

    目的 探讨MINE-ESHAP联合方案治疗难治性或复发性非霍奇金淋巴瘤(NHL)的疗效.方法 采用MINE-ESHAP联合方案治疗难治性或复发性NHL 28例.结果 28例患者中,CR 11例(39.3%),PR 6例(21.4%),SD 5例(17.9%),进展或恶化5例(17.9%),中位生存时间28.5个月.1例死于骨髓抑制期感染(3.6%).不良反应主要为消化道症状和骨髓抑制.结论 MINE-ESHAP方案对部分难治性或复发性NHL患者有效,不良反应可以耐受,可用于对其他化疗方案无效的难治性或复发性NHL.%Objective To evaluate the efficacy of MINE-ESHAP regimen in treatment of refractory and relapsed non-Hodgkin lymphoma (NHL). Methods Twenty-eight patients with refractory and relapsed NHL were treated with MINE-ESHAP regimen. Results The rate of complete remission was 39.3 %(11/28),of partial remission 21.4 %(6/28),of stable disease 17.9 %(5/28),and of progression 17.94 %(5/28). The midsurvival time was 28.5 months. One patient died of infection during marrow restrain period. The main toxicities included gastrointestinal symptoms and myelosuppression. Conclusion MINE-ESHAP regimen is sate and could be employed in treatment of the patients with refractory and relapsed NHL.

  4. Refractory duodenal ulcer

    Directory of Open Access Journals (Sweden)

    Al Freihi Hussein

    1995-01-01

    Full Text Available Refractory or intractable ulcer is defined as an ulcer that fails to heal completely after eight to twelve weeks, despite appropriate treatment with a modern antiulcer therapy in a compliant patient. Refractory ulcer should be suspected in individuals diagnosed to have peptic ulcer if their symptoms persist longer than usual: occurrence of complications or simply their ulcers fail to heal, since up to 25% of such patients remain asymptomatic. Conditions associated with refractory ulcer include noncompliance, continuous consumption of nonsteroidal anti-inflam-matory drugs, acid hypersecretion, smoking. male gender and other factors with questionable role like advanced age, large ulcer size, prolonged duration of symptoms and the presence of complication like bleeding. Nonpeptic ulcers like tuberculosis, malignancy, Crohn′s disease and primary intestinal lymphoma should always be considered in the differential diagnosis. Colonization with H. pylori which is well-known as a cause of frequent recurrences, has not been linked with refractoriness. Patients with refractory ulcers must undergo thorough re-evaluation including repeated endoscopies, obtaining biopsies for microbiology and histology and determination of serum-gastrin level. Once diseases with identifiable etiologies have been ruled out, aggressive medical management with single or multiple antiulcer drugs should be instituted. Such treatments will virtually heal all refractory ulcers. Surgery should be reserved for patients whose ulcers fail to respond to optimal medical therapy or those who develop com-plications necessitating surgical intervention.

  5. A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma

    NARCIS (Netherlands)

    F. Morschhauser; J.F. Seymour; H.C. Kluin-Nelemans (Hanneke); A. Grigg; M. Wolf; M. Pfreundschuh (Michael); H. Tilly (Herve); J. Raemaekers; M.B. van 't Veer (Mars); N. Milpied; G. Cartron; A. Pezzutto; A. Spencer; F. Reyes; M. Dreyling (Martin)

    2008-01-01

    textabstractBackground: Protein kinase C beta (PKCβ), a pivotal enzyme in B-cell signaling and survival, is overexpressed in most cases of mantle cell lymphoma (MCL). Activation of PI3K/AKT pathway is involved in pathogenesis of MCL. Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses

  6. A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma

    NARCIS (Netherlands)

    Morschhauser, F.; Seymour, J. F.; Kluin-Nelemans, H. C.; Grigg, A.; Wolf, M.; Pfreundschuh, M.; Tilly, H.; Raemaekers, J.; van 't Veer, M. B.; Milpied, N.; Cartron, G.; Pezzutto, A.; Spencer, A.; Reyes, F.; Dreyling, M.

    2008-01-01

    Background: Protein kinase C beta (PKC beta), a pivotal enzyme in B-cell signaling and survival, is overexpressed in most cases of mantle cell lymphoma (MCL). Activation of PI3K/AKT pathway is involved in pathogenesis of MCL. Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses signali

  7. Excellent Outcome of Immunomodulation or Bruton's Tyrosine Kinase Inhibition in Highly Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type.

    Science.gov (United States)

    Gupta, Eva; Accurso, Joseph; Sluzevich, Jason; Menke, David M; Tun, Han W

    2015-12-29

    Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare diffuse large B-cell lymphoma confined to the skin of the legs. The typical presentation is characterized by solitary or multiple growing plaques, usually confined to one leg. We report a case of PCDLBCL-LT of activated B-cell subtype characterized by multiple local relapses in the legs, initially, and systemic relapses about seven years after the diagnosis. Local relapses were sensitive to radiation therapy. Cutaneous and systemic relapses responded well to immunomodulatory therapy with lenalidomide followed by Bruton's tyrosine kinase inhibition with ibrutinib. Ibrutinib is the only treatment that resulted in long-lasting complete remission. Lenalidomide and especially ibrutinib appear to have a significant activity against this lymphoma and should be incorporated in the treatment of this resistant and aggressive lymphoma. To our knowledge, this is the first case of PCDLBCL-LT reported in the literature exhibiting a complete response to ibrutinib.

  8. [Plasmablastic lymphoma].

    Science.gov (United States)

    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.

  9. Lomustine (chloroethylnitrosourea [CCNU]), ifosfamide, bleomycin, vincristine, and cisplatin (CIBO-P) is an effective regimen for patients with poor prognostic refractory or multiple disease recurrent aggressive non-Hodgkin lymphoma.

    Science.gov (United States)

    Musolino, Antonino; Perrone, Maria Antonietta; Michiara, Maria; Delnevo, Daniela; Franciosi, Vittorio; Di Blasio, Beatrice; Ceci, Guido; Camisa, Roberta; Ardizzoni, Andrea; Cocconi, Giorgio

    2005-05-15

    The current study was designed to assess the activity and safety of a novel combination therapy for patients with recurrent or refractory aggressive non-Hodgkin lymphoma (NHL). Forty-three consecutive patients with recurrent or refractory aggressive NHL were treated with lomustine (chloroethylnitrosourea [CCNU]; 60 mg/m2 on Day 1), ifosfamide (1.5 g/m(2 on Days 1, 2 and 21, 22), bleomycin (5 mg/m2 on Days 1, 5 and 21, 25), vincristine (1.4 mg/m2 on Days 1, 8 and 21, 28), and cisplatin (25 mg/m2 on Days 3, 4, 5 and 23, 24, 25), every 42 days (CIBO-P regimen). Thirty-nine patients (91%) were evaluable for response. The median patient age was 63 years. Thirty-five percent of the patients had received > or = 2 lines of previous chemotherapy and 40% had elevated lactate dehydrogenase levels at the time of treatment initiation. The overall objective response rate was 77% (95% confidence interval [95% CI], 63-90%), including 19 (49%) complete (CR) and 11 (28%) partial responses. CIBO-P induced responses in primary refractory disease and in patients treated for second or subsequent disease recurrences. A CR with previous therapy was the most important factor associated with a significantly higher CR rate. The median duration of response was 6 months (95% CI, 4.4-7.7 months) and the median survival duration was 10.7 months (95% CI, 5.9-18.1 months). Five patients (11.6%) remained disease free for > or = 24 months. By multivariate analysis, a CR with previous therapy and average dose intensity of CIBO-P drugs were independent prognostic factors for time-to-treatment failure, whereas a CR with previous therapy and serum lactate dehydrogenase were independent predictors for survival. Myelosuppression was the most frequent serious complication of this regimen. However, none of the patients had hemorrhage with thrombocytopenia, and only 2 patients (5%) had febrile neutropenia. In the current study, CIBO-P was a novel, highly active, and safe combination therapy for patients with

  10. Safety and efficacy of different lenalidomide starting doses in patients with relapsed or refractory chronic lymphocytic leukemia: results of an international multicenter double-blinded randomized phase II trial.

    Science.gov (United States)

    Wendtner, Clemens M; Hallek, Michael; Fraser, Graeme A M; Michallet, Anne-Sophie; Hillmen, Peter; Dürig, Jan; Kalaycio, Matt; Gribben, John G; Stilgenbauer, Stephan; Buhler, Andreas; Kipps, Thomas J; Purse, Brendan; Zhang, Jennie; De Bedout, Sabine; Mei, Jay; Chanan-Khan, Asher

    2016-01-01

    The objective of this study was to evaluate the safety and efficacy of different lenalidomide starting doses in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). CLL patients were randomized to receive lenalidomide at initial doses of 5, 10, or 15 mg/d (N = 103). Doses were escalated by 5 mg every 28-d up to a maximum of 25 mg/d; dose reductions in up to 5 mg decrements were permitted. The most common grade ≥3 adverse events (AEs) were neutropenia and thrombocytopenia. Ten patients died during therapy (four deaths considered as related to lenalidomide); 12 patients experienced second primary malignancies. The most common cause for treatment discontinuation was AEs. Overall response rates were similar across arms. Progression-free survival and overall survival rates were longer in patients who escalated treatment (to 15 or 20 mg/d) versus those who did not. Lower starting doses allowed subsequent dose escalation of lenalidomide while maintaining an acceptable tolerability profile in patients with relapsed/refractory CLL.

  11. Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors

    Science.gov (United States)

    2017-03-16

    Childhood Brain Stem Neoplasm; Childhood Lymphoma; Childhood Solid Neoplasm; Pineal Region Neoplasm; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Visual Pathway Glioma; Refractory Central Nervous System Neoplasm

  12. SMILE方案治疗复发难治NK/T细胞淋巴瘤的初步临床报告%Preliminary outcomes of patients with relapsed or refractory NK/T-cell lymphoma treated by SMILE regimen

    Institute of Scientific and Technical Information of China (English)

    周颖; 蔡清清; 林旭滨; 高岩; 卜庆; 王潇潇; 黄慧强

    2009-01-01

    severe side effect. Conclusion SMILE may be an effective regimen for relapsed or refractory NK/T-cell lymphoma while significant toxicities were observed. Further investigation is requried before SMILE become a standard combination for relapsed or refractory NK/T-cell lymphoma.

  13. Presentation and long-term follow-up of refractory celiac disease: comparison of type I with type II.

    Science.gov (United States)

    Malamut, Georgia; Afchain, Pauline; Verkarre, Virginie; Lecomte, Thierry; Amiot, Aurélien; Damotte, Diane; Bouhnik, Yoram; Colombel, Jean-Frédéric; Delchier, Jean-Charles; Allez, Matthieu; Cosnes, Jacques; Lavergne-Slove, Anne; Meresse, Bertrand; Trinquart, Ludovic; Macintyre, Elizabeth; Radford-Weiss, Isabelle; Hermine, Olivier; Brousse, Nicole; Cerf-Bensussan, Nadine; Cellier, Christophe

    2009-01-01

    Refractory celiac disease (RCD) was recently subdivided into 2 subtypes (RCD I and II) based on a normal or abnormal phenotype of intraepithelial lymphocytes (IELs), respectively. It is not clear, however, if these 2 entities differ in their presentation at diagnosis or long-term outcome. We compared the clinical and biological characteristics of RCD I and RCD II at diagnosis, the risk of developing an overt lymphoma, and the predictive factors of survival. Medical files of 14 patients with RCD I and 43 with RCD II were analyzed retrospectively. Predictive factors of overt lymphoma and survival were studied in univariate and multivariate analyses. At diagnosis, malnutrition, ulcerative jejunitis, and lymphocytic gastritis were more common in patients with RCD II than RCD I (PRCD I and 16 with RCD II. In the univariate analysis, abnormal IEL phenotype and increased age at diagnosis of RCD were predictive factors for overt lymphoma. Abnormal IEL phenotype (PRCD I and 44% with RCD II. RCD II has a much more severe presentation and prognosis than patients with RCD I; RCD II survive 5 years after diagnosis. Abnormal IEL phenotype is a predictive factor but not a necessary condition for the development of overt lymphoma.

  14. Reduced Intensity Conditioning With Clofarabine, Antithymocyte Globulin (ATG), Total Lymphoid Irradiation (TLI) Followed by Allogeneic Stem Cell Transplant

    Science.gov (United States)

    2016-01-21

    Acute Myeloid Leukemia; Myelodysplastic Syndrome; Acute Lymphocytic Leukemia; Relapsed/Refractory Chronic Lymphocytic Leukemia; Relapsed/Refractory Non Hodgkin's Lymphoma; Hodgkins Disease; Relapsed Refractory Multiple Myeloma

  15. Clinical Comparative Study of the Effect of MINE and ICE Regimen on Relapsed and Refractory Lymphoma%MINE与ICE方案治疗复发难治性淋巴瘤的疗效比较

    Institute of Scientific and Technical Information of China (English)

    郝杰; 李雪莲; 李良群; 关爽; 王黎

    2012-01-01

    Objective To compare the effect and safety of MINE and ICE Regimen in the treatment of relapsed and refractory lymphoma. Methods 56 patients with relapsed or refractory non-Hodgkin' s lymphoma( NHL )were treated by MINE ( n = 28 ) or ICE( n = 28 ) Regimen. Short - term effect, quality of life and main toxicities were compared and analyzed after chemotherapy treatments. Results The effective rate for the two group were 60. 7% and 67. 9% ,respectively ( P > 0.05 ). After chemotherapy treatment, the score of Karnofsky in MINE group improved more remarkedly than those in ICE group ( P 0.05 ), while the gastrointestinal symptoms in MINE group was significantly lower than that in ICE group ( P < 0. 05 ). Conclusion MINE and ICE Regimen have similar effect for NHL. MINE Regimen has certain superiority on the improvement of quality of life and reduction of gastrointestinal symptoms, so it can be used as a first remedial program after first-line drug resistance.%目的 比较分析MINE与ICE方案治疗复发难治性淋巴瘤的临床疗效及安全性.方法 对56例复发难治性非霍奇金淋巴瘤(NHL)患者,分别采用MINE与ICE 2种不同的方案化疗,每组各28例.比较2组患者的近期疗效、生活质量状况及不良反应.结果 MINE组和ICE组的有效率分别为60.7%和67.9%,差异无统计学意义(P>0.05);MINE组Karnofsky评分改善情况显著优于ICE组,差异均有统计学意义;2组骨髓抑制与脱发无显著性差异,而MINE组的胃肠道反应较 ICE组轻,差异有统计学意义(P<0.05).结论 MINE与ICE 2种化疗方案的近期疗效相当,但MINE在改善患者生活质量及减轻消化道副反应方面有一定的优势,可作为一线方案耐药后的首选补救方案.

  16. Lymphoma-associated dysimmune polyneuropathies.

    Science.gov (United States)

    Stübgen, Joerg-Patrick

    2015-08-15

    Lymphoma consists of a variety of malignancies of lymphocyte origin. A spectrum of clinical peripheral neuropathy syndromes with different disease mechanisms occurs in about 5% of lymphoma patients. There exists a complex inter-relationship between lymphoproliferative malignancies and autoimmunity. An imbalance in the regulation of the immune system presumably underlies various immune-mediated neuropathies in patients with lymphoma. This article reviews lymphoma and more-or-less well-defined dysimmune neuropathy subgroups that are caused by humoral and/or cell-mediated immune disease mechanisms directed against known or undetermined peripheral nerve antigens.

  17. Autologous stem cell transplantation for patients aged 60 years or older with refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

    Science.gov (United States)

    Stamatoullas, A; Brice, P; Gueye, M S; Mareschal, S; Chevallier, P; Bouabdallah, R; Nguyenquoc, S; Francois, S; Turlure, P; Ceballos, P; Monjanel, H; Bourhis, J-H; Guillerm, G; Mohty, M; Biron, P; Cornillon, J; Belhadj, K; Bonmati, C; Dilhuydy, M-S; Huynh, A; Bernard, M; Chrétien, M-L; Peffault de Latour, R; Tilly, H

    2016-07-01

    This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity.

  18. Gemcitabine, Fludarabine, and Melphalan for Reduced-Intensity Conditioning and Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma.

    Science.gov (United States)

    Anderlini, Paolo; Saliba, Rima M; Ledesma, Celina; Plair, Tamera; Alousi, Amin M; Hosing, Chitra M; Khouri, Issa F; Nieto, Yago; Popat, Uday R; Shpall, Elizabeth J; Fanale, Michelle A; Hagemeister, Frederick B; Oki, Yasuhiro; Neelapu, Saatva; Romaguera, Jorge E; Younes, Anas; Champlin, Richard E

    2016-07-01

    Forty patients (median age, 31 years; range, 20 to 63) with Hodgkin lymphoma underwent an allogeneic stem cell transplant with the gemcitabine-fludarabine-melphalan reduced-intensity conditioning regimen. Thirty-one patients (77%) had undergone a prior autologous stem cell transplant, with a median time to progression after transplant of 6 months (range, 1 to 68). Disease status at transplant was complete remission/complete remission, undetermined (n = 23; 57%), partial remission (n = 14; 35%), and other (n = 3; 8%). Twenty-six patients (65%) received brentuximab vedotin before allotransplant. The overall complete response rate before allotransplant was 65% in brentuximab-treated patients versus 42% in brentuximab-naive patients (P = .15). At the latest follow-up (October 2015) 31 patients were alive. The median follow-up was 41 months (range, 5 to 87). Transplant-related mortality rate at 3 years was 17%. Pulmonary, skin toxicities, and nausea were seen in 13 (33%), 11 (28%), and 37 (93%) patients, respectively. At 3 years, estimates for overall and progression-free survival were 75% (95% CI, 57% to 86%) and 54% (95% CI, 36% to 70%). Overall incidence for disease progression was 28% (95% CI, 16% to 50%). We believe the gemcitabine-fludarabine-melphalan regimen allows moderate dose intensification with acceptable morbidity and mortality. The inclusion of gemcitabine affected nausea, pulmonary, and likely skin toxicity. Exposure to brentuximab vedotin allowed more patients to reach allogeneic stem cell transplantation in complete remission. With over 50% of patients progression-free at 3 years, allogeneic stem cell transplantation with reduced-intensity conditioning remains an effective and relevant treatment option for Hodgkin lymphoma in the brentuximab vedotin era.

  19. Prediagnostic immunoglobulin E levels and risk of chronic lymphocytic leukemia, other lymphomas and multiple myeloma-results of the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Nieters, Alexandra; Luczynska, Anna; Becker, Susen; Becker, Nikolaus; Vermeulen, Roel; Overvad, Kim; Aleksandrova, Krasimira; Boeing, Heiner; Lagiou, Pagona; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Krogh, Vittorio; Masala, Giovanna; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, Bas; Jeurnink, Suzanne M.; Weiderpass, Elisabete; Ardanaz, Eva; Chirlaque, Maria-Dolores; Sanchez, Maraia-Jose; Sanchez, Soledad; Borgquist, Signe; Butt, Salma; Melin, Beatrice; Spaeth, Florentin; Rinaldi, Sabina; Brennan, Paul; Kelly, Rachel S.; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolf

    2014-01-01

    Previous epidemiological studies suggest an inverse association between allergies, marked by elevated immunoglobulin (Ig) E levels, and non-Hodgkin lymphoma (NHL) risk. The evidence, however, is inconsistent and prospective data are sparse. We examined the association between prediagnostic total (lo

  20. Feline epitheliotropic intestinal malignant lymphoma: 10 cases (1997-2000).

    Science.gov (United States)

    Carreras, Janet K; Goldschmidt, Micheal; Lamb, Martin; McLear, Robert C; Drobatz, Kenneth J; Sørenmo, Karin U

    2003-01-01

    The clinical, histopathologic, and immunohistochemical features of 10 cats with epitheliotropic intestinal malignant lymphoma (EIL) are described. Intestinal biopsy samples were reviewed by 3 pathologists to confirm the diagnosis of EIL. These samples (n = 10) were compared to the intestinal biopsies of normal cats (n = 11), cats with inflammatory bowel disease (IBD; n = 7), and cats with non-EIL (n = 9) for quantification and immunophenotyping of intraepithelial lymphocytes. Immunophenotypic studies were performed with CD3 and CD79a antibody stains to assess for T- and B-cell immunoreactivity, respectively. EIL biopsies had markedly more intraepithelial lymphocytes than normal intestine (NRL) and samples from cats with IBD. However, no marked difference was observed in the number of intraepithelial lymphocytes in cats with non-EIL compared to cats with EIL. Regardless of the histologic diagnosis, the intraepithelial lymphocytes in all cats were small- to intermediate-sized T cells. Clinical findings and imaging studies in the cats identified minimal or nonspecific findings in affected cats. Most cats fit the typical profile of cats with IBD or alimentary malignant lymphoma. Nine of 10 cats with EIL were treated with prednisone with or without additional chemotherapy. Four cats were refractory to chemotherapy and were euthanized within 3.5 months. The remaining 5 cats had long-term survival times of 11 months or greater. The median survival time was 11 months. Additional studies are warranted to better characterize EIL and its relationship to IBD in cats and non-EIL and to identify optimal treatment strategies for this disease.

  1. Primary leptomeningeal lymphoma

    Science.gov (United States)

    Taylor, Jennie W.; Flanagan, Eoin P.; O'Neill, Brian P.; Siegal, Tali; Omuro, Antonio; DeAngelis, Lisa; Baehring, Joachim; Nishikawa, Ryo; Pinto, Fernando; Chamberlain, Marc; Hoang-Xuan, Khe; Gonzalez-Aguilar, Alberto; Batchelor, Tracy; Blay, Jean-Yves; Korfel, Agnieszka; Betensky, Rebecca A.; Lopes, Maria-Beatriz S.

    2013-01-01

    Objective: To evaluate clinical presentation, optimal diagnostic evaluation and treatment, and outcome in primary leptomeningeal lymphoma, a rare form of primary CNS lymphoma without parenchymal or systemic involvement. Methods: The International Primary CNS Lymphoma Collaborative Group, a multidisciplinary group of physicians with a particular interest in primary CNS lymphoma, retrospectively identified cases of lymphoma isolated to the leptomeninges as diagnosed by CSF cytology, flow cytometry, or biopsy, without systemic or parenchymal brain/spinal cord lymphoma or immunodeficiency. Results: Forty-eight patients were identified, with median age at diagnosis of 51 years and median Eastern Cooperative Oncology Group performance status of 2. Presenting symptoms were multifocal in 68%. Leptomeningeal enhancement was seen in 74% and CSF profile was abnormal in all cases. CSF cytology detected malignant lymphocytes in 67%. Flow cytometry identified monoclonal population in 80%, as did receptor gene rearrangement studies in 71%. Sixty-two percent had B-cell lymphoma, 19% T-cell, and 19% unclassified. Treatment varied and included fractionated radiotherapy (36%), systemic chemotherapy (78%), and intra-CSF chemotherapy (66%), with 66% receiving ≥2 modalities. Seventy-one percent had a favorable clinical response; ultimately, 44% received salvage treatment. Median overall survival was 24 months, with 11 patients still alive at 50 months follow-up. Conclusion: Primary leptomeningeal lymphoma is a rare form of primary CNS lymphoma. Patients usually present with multifocal symptoms, with evidence of leptomeningeal enhancement and diagnostic CSF analysis. Although treatment is highly variable, patients have a better prognosis than previously reported and a subset may be cured. PMID:24107866

  2. Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial.

    Science.gov (United States)

    Sharman, Jeff P; Farber, Charles M; Mahadevan, Daruka; Schreeder, Marshall T; Brooks, Heather D; Kolibaba, Kathryn S; Fanning, Suzanne; Klein, Leonard; Greenwald, Daniel R; Sportelli, Peter; Miskin, Hari P; Weiss, Michael S; Burke, John M

    2017-02-01

    Ibrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti-CD20 monoclonal antibody with single-agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2-6. Response assessments were completed at cycles 3 and 6; patients then continued on ibrutinib monotherapy per standard of care. Forty-one of 45 enrolled patients were evaluable for efficacy. Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event. Combination therapy resulted in an overall response rate (ORR) of 88% at 6 months. In the 20 patients with high-risk features (17p or 11q deletions or TP53 mutation) and evaluable for efficacy, the ORR was 95%, with three patients (15%) achieving negative minimal residual disease. Median time to response was 8 weeks. Ublituximab in combination with ibrutinib resulted in rapid and high response rates. The long-term clinical benefit of ublituximab will be defined by an ongoing phase 3 trial (NCT 02301156).

  3. Primary thyroid lymphoma: A rare disease

    Directory of Open Access Journals (Sweden)

    Deepti Verma

    2014-01-01

    Full Text Available Primary thyroid lymphomas are rare neoplasms comprising of 1-5% of thyroid malignancies. These are predominantly B-cell in origin. Here, we report a case of 60 years lady, a known case of lymphocytic thyroiditis, diagnosed as thyroid lymphoma (diffuse large B-cell on fine needle aspiration and confirmed histopathogically and immunohistochemically. She presented with a sudden increase in thyroid swelling. Fine needle aspiration performed showed highly cellular smears comprising predominantly of the monomorphic population of medium to large sized lymphoid cells with high nuclear/cytoplasmic ratio and scant cytoplasm. A possibility of thyroid lymphoma possibly diffuse large B-cell lymphoma was suggested which was later confirmed on biopsy. Fine needle aspiration provides an easy mode for diagnosing large cell lymphoma like diffuse large B-cell. Hence, an early diagnosis is possible for a timely intervention. Also, cases of lymphocytic thyroiditis should be regularly followed for the development of lymphoma.

  4. Recent advances in refractory coeliac disease: a review.

    Science.gov (United States)

    Ho-Yen, C; Chang, F; van der Walt, J; Mitchell, T; Ciclitira, P

    2009-06-01

    Coeliac disease (CD) is an immune-mediated disease of the small intestine caused by intolerance to gluten. Removal of gluten from the diet results in a return to normal health for the majority of patients. A significant proportion of patients do not respond to a gluten-free diet and are considered to be suffering from refractory coeliac disease (RCD). Two types of RCD are now recognized: type 1 RCD is characterized by a polyclonal population of intraepithelial lymphocytes (IELs) with a normal immunophenotype, and type 2 RCD shows monoclonal IELs with an aberrant immunoprofile. Patients with RCD have a high risk of complications such as ulcerative jejunitis (UJ) and enteropathy-type T-cell lymphoma (ETTL). RCD2 may represent an early stage in the development of overt lymphoma. The diagnosis of RCD, therefore, has important implications, but remains a challenging area. In this paper we review the latest developments in RCD, including the diagnostic approach and a discussion of the key clinical, histological, immunohistochemical and molecular features of RCD and its complications.

  5. High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation for Adults ≥ 60 Years Old with Relapsed or Refractory B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Gopal, Ajay K.; Rajendran, Joseph G.; Gooley, Ted; Pagel, John M.; Fisher, Darrell R.; Petersdorf, Stephen; Maloney, David G.; Eary, Janet F.; Appelbaum, Frederick R.; Press, Oliver W.

    2007-04-10

    Purpose: The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet they are often denied potentially curative high-dose therapy and autologous stem cell transplants (ASCT) due to the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy. Methods: Patients over age 60 with relapsed B-NHL received infusions of tositumomab anti-CD20 antibody labeled with 5-10mCi I-131 tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of I-131-tositumomab (median 525 mCi, range 328-1154 mCi) to deliver 25-27Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy. Results: Twenty-four patients with a median age of 64 (range 60-76) who had received a median of four prior regimens (range 2-14) were treated. Thirteen (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survivals were 59% and 51%, respectively with a median follow-up of 2.9 years (range 1-6 years). All patients experienced expected myeloablation with engraftment of platelets (≥20K/µL) and neutrophils (≥500/µL) occurring a median of 9 and 15 days, respectively following ASCT. There were no treatment-related deaths, and only two patients experienced grade 4 non-hematologic toxicity. Conclusions: Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL.

  6. Gemcitabina e ifosfamida no tratamento do linfoma de Hodgkin refratário ou recidivado após múltiplas terapias Gemcitabine and ifosfamide in the treatment of Hodgkin's lymphoma refractory to or relapsed after multiple therapies

    Directory of Open Access Journals (Sweden)

    Luís Fernando Pracchia

    2007-12-01

    Full Text Available Patients with Hodgkin's lymphoma relapsed after or refractory to multiple therapies (rHL have a dismal prognosis. Monotherapy with gemcitabine can promote an overall response rate of about 40% in these patients and its association with alkylating agents can provide better results. We retrospectively evaluated 17 rHL cases. All were treated with the combination of gemcitabine (1.0 g/m²; D1 and D8 and ifosfamide (1.0 g/m²; D1 to D5 in a 21-day cycle. Treatment response was evaluated according to the Cotswolds criteria. Toxicity was evaluated according to WHO criteria. The median age of all patients was 34 years (18-53. Nine of them (53% were men and eight (47% had Stage III/IV. The median number of previous treatments was 2 (2-3; two patients had already been treated with autologous stem cell transplant. Overall response rate to the combined regimen was 62.5% (95% CI = 38.8% - 86.2% and the median progression-free survival was 15 months (95% CI = 4 - 24 months. Fifty-six cycles were evaluated for toxicity. The most frequent toxicities observed by cycle were: hepatic Grade I/II in 48.2% of the cycles and Grade III/IV in 1.8%; anemia Grade I/II in 45%; neutropenia Grade I/II in 36% and Grade III/IV 16%. Grade III/IV renal toxicity on any degree of haematuria were not observed. Combined therapy with Gemcitabine and Ifosfamide promoted responses in more than half of the evaluated patients with an acceptable toxicity profile.

  7. Richter Syndrome With Plasmablastic Lymphoma at Primary Diagnosis: A Case Report With a Review of the Literature.

    Science.gov (United States)

    Ronchi, Andrea; Marra, Laura; Frigeri, Ferdinando; Botti, Gerardo; Franco, Renato; De Chiara, Annarosaria

    2017-07-01

    Richter syndrome (RS) is considered as the rare development of an aggressive lymphoid malignancy in a preexisting small lymphocytic lymphoma/chronic lymphocytic leukemia. The most common aggressive lymphoma developing in this setting is diffuse large B-cell lymphoma, but classical Hodgkin lymphoma and other much rarer entities such as prolymphocytic lymphoma and dendritic cell sarcoma are also described, most frequently in the progression of the disease over time. A clonal relation between the 2 neoplastic proliferations can be frequently found, whereas clonally unrelated cases are commonly considered as independent tumors, probably due to a variable combination of multiple causes, responsible independently for the 2 neoplasms. RS with plasmablastic lymphoma is reported very rarely, during the clinical course of the small lymphocytic lymphoma/chronic lymphocytic leukemia. Herein, an unusual case of RS with the coexistence of plasmablastic lymphoma and B-small lymphocytic lymphoma in the same lymph node at the time of first diagnosis is described.

  8. Managing Risk in Hodgkin Lymphoma.

    Science.gov (United States)

    Armitage, James O; Chen, Robert W; Moskowitz, Craig H; Sweetenham, John

    2015-02-01

    Approximately 90% of patients with limited-stage Hodgkin lymphoma are cured. The cure rate in advanced-stage Hodgkin lymphoma is dramatically better than it once was, but it is still lower than the rate in patients with limited disease. The choice of treatment is based on several factors, including symptoms, disease stage, extent of tumor burden, and prognosis. Positron emission tomography scanning can be used to assess the patient's stage of disease, which can allow further individualization of therapy. Traditional frontline treatment options include doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and, for high-risk patients, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). Autologous stem cell transplantation cures approximately 50% of patients. The antibody-drug conjugate brentuximab vedotin is very active in relapsed/refractory Hodgkin lymphoma. Data presented at the 2014 meeting of the American Society of Hematology (ASH) showed that brentuximab vedotin was beneficial in several settings, including as consolidation therapy posttransplant in patients at high risk for relapse, as first-line salvage therapy in relapsed/refractory Hodgkin lymphoma prior to autologous hematopoietic cell transplantation, and in combination with bendamustine in relapsed/refractory disease. The ASH meeting also offered promising data on novel agents, such as the programmed cell death 1 (PD-1) inhibitors. In this monograph, 4 experts in the management of Hodgkin lymphoma discuss various aspects of the disease and provide their perspectives on the new data presented at the ASH meeting.

  9. European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease : histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes

    NARCIS (Netherlands)

    Anagnostopoulos, [No Value; Hansmann, ML; Franssila, K; Harris, M; Harris, NL; Jaffe, ES; van Krieken, JM; Poppema, S; Marafioti, T; Franklin, J; Sextro, M; Diehl, [No Value; Stein, H

    2000-01-01

    Paraffin blocks and clinical data from 521 patients with lymphocyte predominance Hodgkin disease (LPHD) diagnosed between 1970 and 1994 were collected from 16 European and United States oncological centers to establish the pathologic and clinical characteristics of a large patient cohort, to determi

  10. Refractory vasculitis

    NARCIS (Netherlands)

    Rutgers, Bram; Kallenberg, Cees G. M.

    2011-01-01

    Refractory vasculitis occurs in 4-5% of patients with anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Differences between therapies used for refractory disease are mostly reflected in the percentages of complete and partial remissions, but also in the number of serious side effects

  11. Refractory vasculitis

    NARCIS (Netherlands)

    Rutgers, Bram; Kallenberg, Cees G. M.

    Refractory vasculitis occurs in 4-5% of patients with anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Differences between therapies used for refractory disease are mostly reflected in the percentages of complete and partial remissions, but also in the number of serious side

  12. 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

    Science.gov (United States)

    2017-06-06

    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

  13. Lymphoma Remissions Caused by Anti-CD19 Chimeric Antigen Receptor T Cells Are Associated With High Serum Interleukin-15 Levels.

    Science.gov (United States)

    Kochenderfer, James N; Somerville, Robert P T; Lu, Tangying; Shi, Victoria; Bot, Adrian; Rossi, John; Xue, Allen; Goff, Stephanie L; Yang, James C; Sherry, Richard M; Klebanoff, Christopher A; Kammula, Udai S; Sherman, Marika; Perez, Arianne; Yuan, Constance M; Feldman, Tatyana; Friedberg, Jonathan W; Roschewski, Mark J; Feldman, Steven A; McIntyre, Lori; Toomey, Mary Ann; Rosenberg, Steven A

    2017-03-14

    Purpose T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 (CAR-19) have potent activity against acute lymphoblastic leukemia, but fewer results supporting treatment of lymphoma with CAR-19 T cells have been published. Patients with lymphoma that is chemotherapy refractory or relapsed after autologous stem-cell transplantation have a grim prognosis, and new treatments for these patients are clearly needed. Chemotherapy administered before adoptive T-cell transfer has been shown to enhance the antimalignancy activity of adoptively transferred T cells. Patients and Methods We treated 22 patients with advanced-stage lymphoma in a clinical trial of CAR-19 T cells preceded by low-dose chemotherapy. Nineteen patients had diffuse large B-cell lymphoma, two patients had follicular lymphoma, and one patient had mantle cell lymphoma. Patients received a single dose of CAR-19 T cells 2 days after a low-dose chemotherapy conditioning regimen of cyclophosphamide plus fludarabine. Results The overall remission rate was 73% with 55% complete remissions and 18% partial remissions. Eleven of 12 complete remissions are ongoing. Fifty-five percent of patients had grade 3 or 4 neurologic toxicities that completely resolved. The low-dose chemotherapy conditioning regimen depleted blood lymphocytes and increased serum interleukin-15 (IL-15). Patients who achieved a remission had a median peak blood CAR(+) cell level of 98/μL and those who did not achieve a remission had a median peak blood CAR(+) cell level of 15/μL ( P = .027). High serum IL-15 levels were associated with high peak blood CAR(+) cell levels ( P = .001) and remissions of lymphoma ( P < .001). Conclusion CAR-19 T cells preceded by low-dose chemotherapy induced remission of advanced-stage lymphoma, and high serum IL-15 levels were associated with the effectiveness of this treatment regimen. CAR-19 T cells will likely become an important treatment for patients with relapsed lymphoma.

  14. HIV-1-related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4⁺ T-cell lymphocytes

    DEFF Research Database (Denmark)

    Bohlius, Julia; Schmidlin, Kurt; Boué, François;

    2011-01-01

    The risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4⁺ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1-infected...... lost 98 CD4 cells (95% CI, -159 to -36 cells), whereas controls gained 35 cells (95% CI, 24-46 cells; P HIV-1 replication on cART may harbor HL....

  15. Phase II study of palliative low-dose local radiotherapy in disseminated indolent non-Hodgkin's lymphoma and chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Jóhannsson, Jakob; Specht, Lena; Mejer, Johannes

    2002-01-01

    of the palliative effect of this regimen in patients with disseminated INHL or CLL. METHODS AND MATERIALS: Twenty-two patients (11 men, 11 women, median age 62 years, range 30-89) with disseminated INHL (n = 15) or CLL (n = 7) were treated with local low-dose RT, 2 Gy x 2 within 3 days, with the aim of achieving...... at 22 months. None of the patients had significant side effects from the treatment. CONCLUSION: Low-dose RT (4 Gy in 2 fractions) is a highly effective palliative treatment of localized lymphoma masses in patients with disseminated INHL and CLL. The treatment has minimal side effects....

  16. Pathobiology of Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Pier Paolo Piccaluga

    2011-01-01

    Full Text Available Despite its well-known histological and clinical features, Hodgkin's lymphoma (HL has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics, histogenesis, and possible mechanisms of lymphomagenesis. There is complete consensus on the B-cell derivation of the tumor in most cases, and on the relevance of Epstein-Barr virus infection and defective cytokinesis in at least a proportion of patients. The REAL/WHO classification recognizes a basic distinction between lymphocyte predominance HL (LP-HL and classic HL (cHL, reflecting the differences in clinical presentation and behavior, morphology, phenotype, and molecular features. cHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, with mixed cellularity, and lymphocyte depleted. The borders between cHL and anaplastic large-cell lymphoma have become sharper, whereas those between LP-HL and T-cell-rich B-cell lymphoma remain ill defined. Treatments adjusted to the pathobiological characteristics of the tumor in at-risk patients have been proposed and are on the way to being applied.

  17. Radioimmunotherapy with Tenarad, a {sup 131}I-labelled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Aloj, Luigi [Istituto Nazionale Tumori ' ' Fondazione G. Pascale' ' - IRCCS, Struttura Complessa di Medicina Nucleare, Napoli (Italy); D' Ambrosio, Laura; Aurilio, Michela; Morisco, Anna; Caraco' , Corradina; Di Gennaro, Francesca; Lastoria, Secondo [Istituto Nazionale Tumori ' ' Fondazione G. Pascale' ' - IRCCS, Struttura Complessa Medicina Nucleare, Napoli (Italy); Frigeri, Ferdinando; Capobianco, Gaetana; Pinto, Antonio [Istituto Nazionale Tumori ' ' Fondazione G. Pascale' ' - IRCCS, Struttura Complessa di Ematologia Oncologica, Napoli (Italy); Giovannoni, Leonardo; Menssen, Hans D. [Philogen, SpA, Siena (Italy); Neri, Dario [Institute of Pharmaceutical Sciences, ETH, Zurich (Switzerland)

    2014-05-15

    The extra-domain A1 of tenascin-C (TC-A1) is highly expressed in the extracellular matrix of tumours and on newly formed blood vessels and is thus a valuable target for radionuclide therapy. Tenarad is a fully human miniantibody or small immunoprotein (SIP, molecular weight 80 kDa) labelled with {sup 131}I that is derived from a TC-A1-binding antibody. Previous phase I/II studies with a similar compound ({sup 131}I-L19SIP) used for radioimmunotherapy (RIT) have shown preliminary efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad was administered to patients with recurrent Hodgkin's lymphoma (HL) refractory to conventional treatments. Eight patients (four men, four women; age range 19 - 41) were enrolled between April 2010 and March 2011. All patients had received a median of three previous lines of chemotherapy (range three to six) and seven had also undergone autologous stem cell transplantation (ASCT) or bone marrow transplantation. In addition, seven patients received external beam radiation. All patients had nodal disease, constitutional B symptoms and some showed extranodal disease in skeletal bone (four patients), lung (three), liver (two) and spleen (one). Baseline assessments included whole-body FDG PET with contrast-enhanced CT and diagnostic Tenarad planar and SPECT studies. Patients were considered eligible to receive a therapeutic dose of Tenarad (2.05 GBq/m{sup 2}) if tumour uptake was more than four times higher than that of muscle. All patients were eligible and received the therapeutic dose of Tenarad. Only one patient developed grade 4 thrombocytopenia and leucocytopenia, requiring hospitalization and therapeutic intervention. All other patients had haematological toxicity of grade 3 or lower, which resolved spontaneously. At the first response assessment (4 - 6 weeks after therapy), one patient showed a complete response, one showed a partial response (PR) and five had disease stabilization (SD). Five patients

  18. Clinical staging and survival in refractory celiac disease: a single center experience.

    Science.gov (United States)

    Rubio-Tapia, Alberto; Kelly, Darlene G; Lahr, Brian D; Dogan, Ahmet; Wu, Tsung-Teh; Murray, Joseph A

    2009-01-01

    Refractory celiac disease (RCD) occurs when both symptoms and intestinal damage persist or recur despite strict adherence to a gluten-free diet. In RCD, the immunophenotype of intraepithelial lymphocytes may be normal and polyclonal (RCD I) or abnormal and monoclonal (RCD II). The aim is to describe the clinical characteristics, treatment, and long-term outcome in a large single-center cohort of patients with RCD. We compared the clinical characteristics and outcome in 57 patients with RCD: 42 with RCD I and 15 with RCD II. Fifteen of 57 patients died during follow-up (n=8 with RCD I and n=7 with RCD II), each within the first 2 years after RCD diagnosis. The overall 5-year cumulative survival is 70%, 80%, and 45% for the entire cohort, RCD I, and RCD II, respectively. The refractory state itself and enteropathy-associated T-cell lymphoma (EATL) were the most common causes of death, respectively. A new staging system is proposed based on the cumulative effect of 5 prognostic factors investigated at the time of the refractory state diagnosis: for patients in stages I, II, and III, the 5-year cumulative survival rate was 96%, 71%, and 19%, respectively (PRCD is associated with high mortality with RCD II having an especially poor prognosis because of the development of EATL. A new staging model is proposed that may improve the precision of prognosis in patients with RCD.

  19. A multi-center open-labeled study of recombinant erythropoietin-beta in the treatment of anemic patients with multiple myeloma, low-grade non-Hodgkin's lymphoma, or chronic lymphocytic leukemia in Chinese population.

    Science.gov (United States)

    Yang, Shen; Jun, Ma; Hong-Li, Zhu; Jian-Min, Wang; Chun, Wang; Lu-Gui, Qiu; Yong-Qiang, Zhao; Jun, Zhu; Jian, Hou; Zhi-Xiang, Shen

    2008-09-01

    The purpose of this study is to investigate the efficacy and safety of recombinant erythropoietin-beta in the treatment of anemic patients with multiple myeloma (MM), low-grade non-Hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL). From December 2005 to November 2006, the patients with MM, low-grade NHL, and CLL were enrolled in this study, male or female, aged > or = 18 years, transfusion-dependant, and receiving anti-neoplasia chemotherapy. Recombinant human erythropoietin-beta was used in this study with the dose initiated at 150 IU/kg, thrice a week, subcutaneously. The total treatment duration was 12 weeks. The primary endpoint of the study is response rate (RR), which is defined as hemoglobin increasing > or = 2 g/dL comparing to baseline level, or returning to normal range, without any transfusion within 6 weeks of evaluation. Fifty out of 82 (64.6%) patients enrolled in this study responded to the treatment and 29 patients had no response. Hypertension (12.2%) is the most common adverse effect; however, all the adverse events were mild, categorized in NCI grade I or II. We conclude that recombinant erythropoietin-beta was effective in the treatment of anemia of the patients with MM, NHL, and CLL, as well as it is well-tolerated.

  20. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  1. HIV-1-related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4⁺ T-cell lymphocytes

    DEFF Research Database (Denmark)

    Bohlius, Julia; Schmidlin, Kurt; Boué, François;

    2011-01-01

    The risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4¿ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1-infected...... patients (median age, 36 years; 70% male; median CD4 cell count, 234 cells/µL) from 16 European cohorts were observed during 159 133 person-years; 78 patients developed HL. The incidence was 49.0 (95% confidence interval [CI], 39.3-61.2) per 100,000 person-years, and similar on cART and not on cART (P...... = .96). The risk of HL declined as the most recent (time-updated) CD4 count increased: the adjusted hazard ratio comparing more than 350 with less than 50 cells/µL was 0.27 (95% CI, 0.08-0.86). Sixty-one HL cases diagnosed on cART were matched to 1652 controls: during the year before diagnosis, cases...

  2. Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma.

    Science.gov (United States)

    Gualco, Gabriela; Weiss, Lawrence M; Bacchi, Carlos E

    2008-10-01

    Immunohistochemical determination of p63 protein is frequently used in the pathologic diagnosis of nonhematological solid tumors. In malignant hematological disease, p63 expression has been reported in 22% of follicular lymphoma, about 35% of diffuse large B-cell lymphoma, 23% of chronic lymphocytic leukemia, and in some cases of blast crisis of chronic myelogenous leukemia. Anaplastic large cell lymphoma is a rare disease that accounts for less than 5% of all cases of non-Hodgkin's lymphoma. There is little information concerning p63 expression in this specific type of lymphoma. In some cases, the morphological and phenotypic features between anaplastic large cell lymphoma and classical Hodgkin's lymphoma are similar, making this differential diagnosis challenging. We studied p63 expression using a tissue microarray approach in 154 cases of anaplastic large cell lymphoma, including 38% anaplastic large cell kinase positive and 62% anaplastic large cell kinase negative, and 58 Hodgkin's lymphoma cases. Sixty-eight cases of anaplastic large cell lymphoma (44%) showed p63 nuclear positivity (41% of anaplastic large cell kinase positive and 47% of anaplastic large cell kinase negative). Of 130 cases of systemic-anaplastic large cell lymphoma, 42% showed p63 positivity. The neoplastic cells expressed p63 in 38% of the cases of CD45-negative/anaplastic large cell kinase-negative null cell-type anaplastic large cell lymphoma, a subgroup that offers the most difficulties in the differential diagnosis with classical Hodgkin's lymphoma. In contrast, none of the cases of classical Hodgkin's lymphoma demonstrated any p63 expression. These results demonstrate that p63 protein expression is frequently expressed in a subset of anaplastic large cell lymphoma cases and may be used as a potential tool in the differential diagnosis between anaplastic large cell lymphoma and classical Hodgkin's lymphoma.

  3. Antemortem diagnosis with multiple random skin biopsies and transbronchial lung biopsy in a patient with intravascular large B-cell lymphoma, the so-called Asian variant lymphoma.

    Science.gov (United States)

    Nishizawa, Tomotaka; Saraya, Takeshi; Ishii, Haruyuki; Goto, Hajime

    2014-03-14

    A 59-year-old, previously healthy man presented to our hospital, with a 3-month history of high fever, nocturnal sweating and exertional dyspnoea. Aggressive diagnostic procedures such as multiple random skin biopsies and transbronchial lung biopsy (TBLB) led to an antemortem diagnosis of intravascular large B-cell lymphoma (IVLBCL), which showed abundant CD20 atypical lymphocytes aggregated in lumina of small vessels. The 29 cases diagnosed with IVLBCL during their lifetime by TBLB were reviewed. Their clinical features included respiratory symptoms (hypoxaemia, dyspnoea and dry cough) and persistent fever. IVLBCL patients show various radiological patterns (ground glass opacities, multiple centrilobular nodules, interlobular septal thickening, interstitial shadows and thickening of bronchovascular bundles), suggesting lymphatic or haematological spread. Antemortem diagnosis of IVLBCL is difficult, but a multidisciplinary approach, with aggressive multiple random skin biopsies and/or TBLB, should be considered in patients with respiratory symptoms that are refractory to antibiotics or prednisolone treatment.

  4. The absolute lymphocyte/monocyte ratio recovery during ABVD treatment cycles is not significantly impacted by the use of myeloid growth factors and predicts clinical outcomes in classical Hodgkin lymphoma regardless of their use

    Directory of Open Access Journals (Sweden)

    Kaufman GP

    2014-07-01

    Full Text Available Gregory P Kaufman,1 Kay M Ristow,1,2 Svetomir N Markovic,1,2 Luis F Porrata1,2 1Department of Internal Medicine, 2Division of Hematology, Mayo Clinic, Rochester, MN, USA Abstract: Risk stratification of patients with classical Hodgkin lymphoma (cHL remains suboptimal. The ratio of the absolute lymphocyte count (ALC to absolute monocyte count (AMC both at diagnosis and during subsequent recovery from serial cycles of chemotherapy predicts survival in cHL, and possesses advantages over other commonly used prognostic markers. Myeloid growth factors (MGFs, while not strongly recommended for use in adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD treatment cycles, are not uncommonly used to prevent the negative consequences of neutropenia. The effect that MGFs have on the ALC/AMC ratio during ABVD treatment cycles, if any, remains unclear. We retrospectively evaluated 208 patients with cHL, who were diagnosed, treated, and followed at Mayo Clinic Rochester between 1990 and 2014, and who had quantifiable records for the use of MGFs during ABVD treatment cycles. Having an ALC/AMC ratio <1.1 during all treatment cycles was confirmed as being a negative predictor of overall and progression free survival (hazard ratio [HR] 0.06, 95% confidence interval [CI] 0.03–0.14 and HR 0.08, 95% CI 0.04–0.17, respectively. Data on both the ALC/AMC ratio and use of MGFs were available for 1,979 half treatment cycles. When stratified to whether or not MGFs were given, the change in the ALC/AMC ratio as compared to the prior half cycle was found to be statistically insignificant (P=0.3445. No survival advantage was found with the administration of MGFs in any cycle of therapy (log rank P=0.5713. Our data validate the prognostic significance of having an ALC/AMC ratio of ≥1.1 regardless of the use of MGFs. Keywords: myeloid growth factors, classical Hodgkin lymphoma, survival ALC/AMC ratio, ABVD chemotherapy

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

    Science.gov (United States)

    2016-08-18

    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

  6. PATHOBIOLOGY OF HODGKIN LYMPHOMA

    Directory of Open Access Journals (Sweden)

    Claudio Agostinelli

    2014-06-01

    Full Text Available Hodgkin’s lymphoma is a lymphoid tumour that represents about 1% of all de novo neoplasms occurring every year worldwide. Its diagnosis is based on the identification of characteristic neoplastic cells within an inflammatory milieu. Molecular studies have shown that most, if not all cases, belong to the same clonal population, which is derived from peripheral B-cells. The relevance of Epstein-Barr virus infection at least in a proportion of patients was also demonstrated. The REAL/WHO classification recognizes a basic distinction between nodular lymphocyte predominance  HL (NLPHL and classic HL (CHL, reflecting the differences in clinical presentation, behavior, morphology, phenotype, molecular features as well as in the composition of their cellular background. CHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, mixed cellularity and lymphocyte depleted. Despite its well known histological and clinical features, Hodgkin's lymphoma (HL has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics and possible mechanisms of lymphomagenesis.

  7. Clinical role of obinutuzumab in the treatment of naive patients with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Cerquozzi S

    2015-02-01

    Full Text Available Sonia Cerquozzi,1 Carolyn Owen2 1Department of Hematology, University of Calgary, 2Department of Hematology, Tom Baker Cancer Centre, Calgary, AB, Canada Abstract: The introduction of targeted therapy against CD20+ with the monoclonal antibody rituximab has dramatically improved the survival of B-cell non-Hodgkin lymphoma including chronic lymphocytic leukemia (CLL/small lymphocytic lymphoma. Unfortunately, CLL remains incurable with chemoimmunotherapy, with many patients having refractory or relapsing disease after rituximab-containing therapy. Obinutuzumab (GA101 is a novel humanized Type II anti-CD20 monoclonal antibody that has been investigated and compared to rituximab. Here, we provide an overview of obinutuzumab, including its mechanisms of action, preclinical data, and Phase I to III clinical studies. Preclinical data illustrate obinutuzumab's higher potency compared to rituximab through antibody-dependent cellular cytotoxicity and direct cell death. Recently, the CLL11 study presented a significant benefit from obinutuzumab chemoimmunotherapy and supports its use for treatment-naive unfit CLL patients. Herein, we review that obinutuzumab is both a safe and effective alternative to rituximab. Keywords: CLL, GA101, antibody, CD20 

  8. Hodgkin Lymphoma (For Teens)

    Science.gov (United States)

    ... Can I Help Someone Who's Being Bullied? Volunteering Hodgkin Lymphoma KidsHealth > For Teens > Hodgkin Lymphoma Print A ... to check for disease, including lymphoma. What Is Hodgkin Lymphoma? Hodgkin lymphoma is a type of cancer ...

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

    Science.gov (United States)

    Barrientos, Jacqueline C

    2016-01-01

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

  10. Lymphocyte 'homing' and chronic inflammation.

    Science.gov (United States)

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

    Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV-like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV-like vessel-mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.

  11. Role of bendamustine in the treatment of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Saad Jamshed

    2009-03-01

    Full Text Available Saad Jamshed, Bruce D ChesonGeorgetown University Hospital, Lombardi Comprehensive Cancer Center, Washington, DC, USAAbstract: Major advances in the management of patients with chronic lymphocytic leukemia (CLL include an enhanced ability to make an accurate diagnosis and define clinically meaningful prognostic groups, while improving outcome through more effective therapeutic regimens and supportive care. Nevertheless, CLL remains an incurable disorder and new, active agents are needed. Bendamustine, a unique cytotoxic agent with structural similarities to both alkylating agents and antimetabolites, was recently approved by the US Food and Drug Administration for treatment of CLL and rituximab-refractory indolent non-Hodgkin’s lymphoma. In a randomized trial, bendamustine was superior to chlorambucil, with comparable toxicity. Combinations with other active agents including rituximab and lenalidomide are in development. Nevertheless, numerous questions concerning the ideal use of this agent remain to be addressed, including the optimal dose and schedule and mechanisms of resistance. The availability of bendamustine provides another effective treatment option for patients with lymphoproliferative disorders. Rational development of combination regimens will improve the outlook for patients with CLL.Keywords: bendamustine, chemotherapy, chronic lymphocytic leukemia

  12. TCRβ clonality improves diagnostic yield of TCRγ clonality in refractory celiac disease.

    Science.gov (United States)

    Perfetti, Vittorio; Brunetti, Laura; Biagi, Federico; Ciccocioppo, Rachele; Bianchi, Paola I; Corazza, Gino R

    2012-09-01

    Refractory celiac disease (RCD) is a preneoplastic condition as many patients develop an enteropathy-type T-cell lymphoma, a mature T-cell receptor α-β lymphoma arising in the gut with an ominous outcome. Recently, research focused on a population of intraepithelial intestinal lymphocytes expressing the same lymphoma T-cell receptor variable region (V)γ, as shown by polymerase chain reaction (PCR) analysis and sequencing. Meanwhile, the Biomedicine and Health-2 Concerted Action has made available standardized, highly specific, and sensitive PCR assays not only for Vγ but also for Vβ. We verified whether analyzing both rearrangements in duodenal biopsies from RCD patients increases the diagnostic accuracy of this method. Duodenal biopsies were analyzed from 15 RCD patients, 21 negative controls, and 2 positive controls (enteropathy-type T-cell lymphoma complicating celiac disease). Multiplex clonality analyses were performed according to the Biomedicine and Health-2 protocols. PCR products were cloned and sequenced. Monoclonal rearrangements were found in 5/15 samples from patients with RCD (both rearrangements in 2 cases, Vβ only in 2, and only 1 solitary Vγ clonality). Monoclonality was found in 4/8 of the RCD patients who subsequently died, whereas only 1/7 of the patients still alive presented a monoclonal rearrangement. Positive controls revealed both monoclonal rearrangements; rearrangements were not detected in 20 of 21 negative controls. Sequencing of the amplified fragments confirmed the results. The combined analysis of both rearrangements allowed recognition of monoclonal populations in otherwise negative patients, with detection rates from 20% (Vγ only) to 33% (Vγ and Vβ), thus raising the likelihood of early identification of RCD patients at high risk of death.

  13. Adoptive Cell Transfer Therapy Following Non-Myeloablative but Lymphodepleting Chemotherapy for the Treatment of Patients With Refractory Metastatic Melanoma

    National Research Council Canada - National Science Library

    Mark E. Dudley; John R. Wunderlich; James C. Yang; Richard M. Sherry; Suzanne L. Topalian; Nicholas P. Restifo; Richard E. Royal; Udai Kammula; Don E. White; Sharon A. Mavroukakis; Linda J. Rogers; Gerald J. Gracia; Stephanie A. Jones; David P. Mangiameli; Michelle M. Pelletier; Juan Gea-Banacloche; Michael R. Robinson; David M. Berman; Armando C. Filie; Andrea Abati; Steven A. Rosenberg

    2005-01-01

    We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma...

  14. HEPATITIS C VIRUS INFECTION AND LYMPHOMA

    Directory of Open Access Journals (Sweden)

    Emmanuel Bachy

    2010-03-01

    Full Text Available Apart from its well known role as an etiological agent for non-A and non-B viral hepatitis, there is growing evidence that hepatitis C virus is associated to B-cell non-Hodgkin lymphoma. The association between HCV and lymphoproliferative disorders has been recently postulated based on epidemiological data, biological studies and clinical observations. Although various subtypes of lymphomas appear to be associated to HCV, diffuse large B-cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia and marginal zone lymphoma appeared to be particularly represented among HCV-positive patients.  The causative role of HCV in those disorders has been further supported by the response to anti-viral therapy. Despite a better understanding of pathophysiological processes at stake leading from HCV infection to overt lymphoma, many issues still need to be further elucidated. Although HCV has been demonstrated to directly infect peripheral blood mononuclear cells both in vitro and, in some cases, in vivo, a strong body of evidence rather supports the hypothesis of an indirect transformation mechanism by which sustained antigenic stimulation leads from oligoclonal to monoclonal expansion and sometimes to lymphoma, probably through secondary oncogenic events. Here, we review epidemiological and biological studies, as well as clinical data on antiviral therapy, linking HCV-infection to B-cell non-Hodgkin lymphoma.

  15. Malignant lymphoma and the thyroid gland

    Energy Technology Data Exchange (ETDEWEB)

    Becker, W.; Reiners, C.; Boerner, W.; Mueller, H.A.; Wuensch, P.H.; Schaeffer, R.; Gunzer, U.

    1983-04-01

    Among 4325 goiter patients first examined in the period from February 1980 to April 1982, 5 cases of lymphoma appearing primarily in the thyroid gland were discovered incidentally. During the same period 13 patients with anaplastic thyroid carcinoma were observed. 5 of 23 systematically examined patients who had already known extrahyroidal malignant non-Hodgkin's lymphomas and lymphoma patient examined by chance exhibited a secondary thyroid gland lymphoma, that is, a secondary infiltration of the enlarged thyroid. Altogether, 29 patients with malignant non-Hodgkin's lymphoma (Kiel classification) were examined. Of 8 Hodgkin's disease patients none showed clinical or cytological evidence of thyroid infiltration. The clinical symptoms of primary lymphoma of the thyroid gland corresponded to those of anaplastic thyroid carcinoma. A positive differential diagnosis of the two tumours succeeded cytologically. The secondary lymphoma of the thyroid also could only be diagnosed cytologically. Patients with Hodgkin's lymphoma and non-Hodgkin's lymphoma were always found to be euthyroid. Autoimmunological phenomena (antimicrosomal and antithyreoglobulin autoantibodies) as an indicator of lymphocytic thyroiditis could only be examined among 11 patients. Two patients with secondary lymphoma of the thyroid showed positive titers. A small cell anaplastic thyroid carcinoma could not be diagnosed in any of 37 patients with anaplastic thyroid cancer out of an enlarged patient collective (period under consideration: 1976-1982).

  16. Targeting the CD20 and CXCR4 pathways in non-hodgkin lymphoma with rituximab and high-affinity CXCR4 antagonist BKT140.

    Science.gov (United States)

    Beider, Katia; Ribakovsky, Elena; Abraham, Michal; Wald, Hanna; Weiss, Lola; Rosenberg, Evgenia; Galun, Eithan; Avigdor, Abraham; Eizenberg, Orly; Peled, Amnon; Nagler, Arnon

    2013-07-01

    Chemokine axis CXCR4/CXCL12 is critically involved in the survival and trafficking of normal and malignant B lymphocytes. Here, we investigated the effect of high-affinity CXCR4 antagonist BKT140 on lymphoma cell growth and rituximab-induced cytotoxicity in vitro and in vivo. In vitro efficacy of BKT140 alone or in combination with rituximab was determined in non-Hodgkin lymphoma (NHL) cell lines and primary samples from bone marrow aspirates of patients with NHL. In vivo efficacy was evaluated in xenograft models of localized and disseminated NHL with bone marrow involvement. Antagonizing CXCR4 with BKT140 resulted in significant inhibition of CD20+ lymphoma cell growth and in the induction of cell death, respectively. Combination of BKT140 with rituximab significantly enhanced the apoptosis against the lymphoma cells in a dose-dependent manner. Moreover, rituximab induced CXCR4 expression in lymphoma cell lines and primary lymphoma cells, suggesting the possible interaction between CD20 and CXCR4 pathways in NHL. Primary bone marrow stromal cells (BMSC) further increased CXCR4 expression and protected NHL cells from rituximab-induced apoptosis, whereas BKT140 abrogated this protective effect. Furthermore, BKT140 showed efficient antilymphoma activity in vivo in the xenograft model of disseminated NHL with bone marrow involvement. BKT140 treatment inhibited the local tumor progression and significantly reduced the number of NHL cells in the bone marrow. Combined treatment of BKT140 with rituximab further decreased the number of viable lymphoma cells in the bone marrow, achieving 93% reduction. These findings suggest the possible role of CXCR4 in NHL progression and response to rituximab and provide the scientific basis for the development of novel CXCR4-targeted therapies for refractory NHL. ©2013 AACR.

  17. 含美罗华联合方案治疗复发耐药B细胞性非霍奇金淋巴瘤%Preliminary outcome of rituximab-containing salvage regimens on relapsed or refractory B-cell non-Hodgkin's lymphoma: single institution experience

    Institute of Scientific and Technical Information of China (English)

    王步飞; 黄慧强; 卜庆

    2006-01-01

    Objective: The prognosis of relapsed or refractory B-cell lymphoma is poor, with a short-term survival after conventional second-line chemotherapy. Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like chemotherapy may improve both disease free survival (DFS) and overall survival (OS) of naive patients, but its role in the second-line therapy for relapsed non-Hodgkin's Lymphoma (NHL) remains to be defined. This study aimed to evaluate the efficacy of rituximab-containing salvage regimens for relapsed or refractory NHL, and observe the toxicities. Methods: The clinical data of 54 patients, who were with relapsed or refractory NHL and treated in the Cancer Center of Sun Yat-sen University, were analyzed retrospectively. Of the 54 patients, 29 were man, 25 were women, with a median age of 52.5 years old (range 18 to75); 50 patients (92.6%) scored 0-1 for the ECOG performance status; for second-line international prognostic index (slPI), 21(38.9%) scored 0-1, 30 (55.6%) scored 2 to 3, and 3 (5.6%) scored 4-5; 40 cases were diffuse large B-cell lymphoma (DLBCL),accounting for 74.1% of all subtypes. Rituximab was administered intravenously at a dose of 375 mg/m2 at the day before each chemotherapy cycle. The second or third-line salvage regimens included EPOCH, CHOP, DHAP, DICE, IVAC, IMVP-16 and FND. Results: Of the 54 patients, 49 received retuximab-containing salvage regimens. The objective response rate of the 45 evaluable cases was 68.8%, with a complete remission (CR) rate of 37.7%; 3 patients achieved CR after radiotherapy following rituximab-based regimens and 3 achieved CR after autologous hematopoietic stem cell transplantation. The most frequent adverse events were leucopenia, nausea and alopecia. The addition of rituximab to chemotherapy only elevated the occurrence of mild infusion-related reactions, such as chills, fever and pruritus. The median follow-up time was 18 months (range 2-86 months); 5 patients were lost, 24 were dead (23

  18. False Negative Fine Needle Aspiration Biopsy Results in Primary Thyroid Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Joong; Kim, Eun Kyung; Koh, Myoung Ju; Kwak, Jin Young; Moon, Hee Jung [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-06-15

    Ultrasonography-guided fine needle aspiration biopsy (US-FNA) is one of the methods used to diagnose thyroid lymphoma, but it has a relatively high false-negative rate. The authors report a case of a primary thyroid lymphoma associated with underlying lymphocytic thyroiditis that was initially misdiagnosed as lymphocytic thyroiditis based on US-FNA findings

  19. Lymphocytic Interstitial Pneumonia.

    Science.gov (United States)

    Panchabhai, Tanmay S; Farver, Carol; Highland, Kristin B

    2016-09-01

    Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum of benign pulmonary lymphoproliferative disorders. LIP is frequently associated with connective tissue diseases or infections. Idiopathic LIP is rare; every attempt must be made to diagnose underlying conditions when LIP is diagnosed. Computed tomography of the chest in patients with LIP may reveal ground-glass opacities, centrilobular and subpleural nodules, and randomly distributed thin-walled cysts. Demonstrating polyclonality with immunohistochemistry is the key to differentiating LIP from lymphoma. The 5-year mortality remains between 33% and 50% and is likely to vary based on the underlying disease process.

  20. Chimeric antigen receptor T-cell therapies for lymphoma.

    Science.gov (United States)

    Brudno, Jennifer N; Kochenderfer, James N

    2017-08-31

    New therapies are needed for patients with Hodgkin or non-Hodgkin lymphomas that are resistant to standard therapies. Indeed, unresponsiveness to standard chemotherapy and relapse after autologous stem-cell transplantation are indicators of an especially poor prognosis. Chimeric antigen receptor (CAR) T cells are emerging as a novel treatment modality for these patients. Clinical trial data have demonstrated the potent activity of anti-CD19 CAR T cells against multiple subtypes of B-cell lymphoma, including diffuse large-B-cell lymphoma (DLBCL), follicular lymphoma, mantle-cell lymphoma, and marginal-zone lymphoma. Importantly, anti-CD19 CAR T cells have impressive activity against chemotherapy-refractory lymphoma, inducing durable complete remissions lasting >2 years in some patients with refractory DLBCL. CAR-T-cell therapies are, however, associated with potentially fatal toxicities, including cytokine-release syndrome and neurological toxicities. CAR T cells with novel target antigens, including CD20, CD22, and κ-light chain for B-cell lymphomas, and CD30 for Hodgkin and T-cell lymphomas, are currently being investigated in clinical trials. Centrally manufactured CAR T cells are also being tested in industry-sponsored multicentre clinical trials, and will probably soon become a standard therapy. Herein, we review the clinical efficacy and toxicity of CAR-T-cell therapies for lymphoma, and discuss their limitations and future directions with regard to toxicity management, CAR designs and CAR-T-cell phenotypes, conditioning regimens, and combination therapies.

  1. Recognising and Managing Refractory Coeliac Disease: A Tertiary Centre Experience

    Science.gov (United States)

    Nasr, Ikram; Nasr, Iman; Beyers, Carl; Chang, Fuju; Donnelly, Suzanne; Ciclitira, Paul J.

    2015-01-01

    Refractory coeliac disease (RCD) is a rare complication of coeliac disease (CD) and involves malabsorption and villous atrophy despite adherence to a strict gluten-free diet (GFD) for at least 12 months in the absence of another cause. RCD is classified based on the T-cells in the intra-epithelial lymphocyte (IEL) morphology into type 1 with normal IEL and type 2 with aberrant IEL (clonal) by PCR (polymerase chain reaction) for T cell receptors (TCR) at the β/γ loci. RCD type 1 is managed with strict nutritional and pharmacological management. RCD type 2 can be complicated by ulcerative jejunitis or enteropathy associated lymphoma (EATL), the latter having a five-year mortality of 50%. Management options for RCD type 2 and response to treatment differs across centres and there have been debates over the best treatment option. Treatment options that have been used include azathioprine and steroids, methotrexate, cyclosporine, campath (an anti CD-52 monoclonal antibody), and cladribine or fluadribine with or without autologous stem cell transplantation. We present a tertiary centre’s experience in the treatment of RCD type 2 where treatment with prednisolone and azathioprine was used, and our results show good response with histological recovery in 56.6% of treated individuals. PMID:26633478

  2. Recognising and Managing Refractory Coeliac Disease: A Tertiary Centre Experience

    Directory of Open Access Journals (Sweden)

    Ikram Nasr

    2015-12-01

    Full Text Available Refractory coeliac disease (RCD is a rare complication of coeliac disease (CD and involves malabsorption and villous atrophy despite adherence to a strict gluten-free diet (GFD for at least 12 months in the absence of another cause. RCD is classified based on the T-cells in the intra-epithelial lymphocyte (IEL morphology into type 1 with normal IEL and type 2 with aberrant IEL (clonal by PCR (polymerase chain reaction for T cell receptors (TCR at the β/γ loci. RCD type 1 is managed with strict nutritional and pharmacological management. RCD type 2 can be complicated by ulcerative jejunitis or enteropathy associated lymphoma (EATL, the latter having a five-year mortality of 50%. Management options for RCD type 2 and response to treatment differs across centres and there have been debates over the best treatment option. Treatment options that have been used include azathioprine and steroids, methotrexate, cyclosporine, campath (an anti CD-52 monoclonal antibody, and cladribine or fluadribine with or without autologous stem cell transplantation. We present a tertiary centre’s experience in the treatment of RCD type 2 where treatment with prednisolone and azathioprine was used, and our results show good response with histological recovery in 56.6% of treated individuals.

  3. Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

    OpenAIRE

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

    1987-01-01

    This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, im...

  4. Obinutuzumab for the treatment of indolent lymphoma.

    Science.gov (United States)

    Edelmann, Jennifer; Gribben, John G

    2016-08-01

    Obinutuzumab is a humanized, type II anti-CD20 monoclonal antibody designed for strong induction of direct cell death and antibody-dependent cell-mediated cytotoxicity. The Phase III GADOLIN trial tested the clinical efficacy of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy in rituximab-refractory indolent non-Hodgkin lymphoma versus treatment with bendamustine alone. It demonstrated significantly longer progression-free survival for the obinutuzumab-containing regimen in this difficult to treat patient group. Based on the results of this trial, US FDA approval was most recently granted for obinutuzumab in the treatment of follicular lymphoma that has relapsed after or was refractory to a rituximab-containing regimen. This article summarizes the available data on chemistry, pharmacokinetics, clinical efficacy and safety of obinutuzumab in the treatment of indolent non-Hodgkin lymphoma.

  5. Fludarabine combined with pirarubicin chemotherapy for patients with relapsed or refractory indolent non-Hodgldn lymphoma%氟达拉滨联合吡柔比星治疗复发难治性惰性非霍奇金淋巴瘤

    Institute of Scientific and Technical Information of China (English)

    王华庆; 郝希山; 邱立华; 钱正子; 李维; 孟祥睿; 侯芸; 宋拯; 赵静; 崔秀珍

    2009-01-01

    Objective To evaluate the efficacy and safety of fludarabine and pirarubicin (FT) regimen in the treatment of refractory or relapsed indolent non-Hodgkin lymphoma (NHL). Methods A total of 40 patients with relapsed or refractory indolent NHL were treated with FT regimen, one cycle for 28 days, total 6 cycles. The data of indolent NHL patients treated with fludarabine, noventrene and dexamethasone (FND) regimen were collected as control. Results 40 patients were given 228 cycles chemotherapy, overall response rate was 62.5 %, median progression-free survival was more than 20 months and 2 years overall survival rate was 70.0 %. The main toxicities was leucopenia (80.0 %), but the incidence of WHO Ⅲ-Ⅳ leucopenia and pneumonia was less than that of in the control group, the rate were 12.5 % vs 29.0 % and 2.5 % vs 23.0 % respectively (P 0.05);不良反应以中性粒细胞减少(80.0%)最为常见,但Ⅲ~Ⅳ度中性粒细胞减少症和肺炎的发生率均低于对照组,分别为12.5%、29.0%和2.5%、23.0%(P<0.05).结论 FT方案治疗复发难治惰性NHL安全有效,骨髓抑制轻,感染发生率低.

  6. Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

    Science.gov (United States)

    2017-02-14

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Indolent Non-Hodgkin Lymphoma; Malignant Lymphoma, Large Cell Type; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Recurrent Chronic Lymphocytic Leukemia; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Non-Hodgkin Lymphoma

  7. Peripheral T-cell lymphoma.

    Science.gov (United States)

    Rosenberg, Benjamin

    2005-12-30

    A 32-year-old man presented with a 5-year history of cutaneous nodules on his head and a diffuse, lichenified eruption. Histopathologic examination showed an atypical lymphocytic infiltrate. Immunophenotyping studies determined that the lymphocyte population to be CD4-positive, with partial loss of CD3 and CD7, and immunogenotyping studies showed a clonal rearrangement of the T-cell receptor. A positron-emission tomography scan showed increased uptake in cervical, axillary, and inguinal lymph nodes. A diagnosis of peripheral T-cell lymphoma was made, and the patient is undergoing chemotherapy.

  8. Radiation therapy of follicular lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Koguchi, Masahiko; Nakamura, Naoki; Tsubokura, Takuji; Gomi, Koutarou; Yamashita, Takashi [Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital; Shikama, Naoto

    2001-09-01

    The follicular lymphoma, exactly, the cancer of follicular center and germinal center B lymphocytes, is reviewed on its immunological, pathological and genetic diagnoses, epidemiology, clinical symptoms, prognosis factors, therapy and assessment of therapy effects together with respective therapy of follicular small cleaved and follicular mixed small cleaved and large cell lymphoma of grade I, II; and of follicular large cell lymphoma of grade III. The therapy is essentially the radiotherapy combined with chemotherapy and others, of which effect is mainly assessed by CT. In clinical application grade II, III, irradiation of X- and electron rays and their combination is done in a fractionated manner with the maximal dose of around 35 Gy. In clinical disease grade II, III, regimen of irradiation is not fixed. In III, IV, chemotherapy and immunotherapy are major. In recurrence and malignant transformation, there is a report of large dose chemotherapy + whole body irradiation + bone marrow transplantation. (K.H.)

  9. Efficacy of Arsenic Trioxide combined with GDP regimen for patients with aggressive relapsed or refractory non-Hodgkin's lymphoma%亚砷酸联合GDP方案治疗难治性或复发性非霍奇金淋巴瘤的疗效观察

    Institute of Scientific and Technical Information of China (English)

    丁富强; 乔红梅; 李晓霞; 李恩孝

    2011-01-01

    目的:观察亚砷酸(三氧化二砷,As2O3)联合GDP方案(吉西他滨,顺铂,地塞米松)治疗难治性或复发性非霍奇金淋巴瘤(non-hodgkin's lymphoma,NHL)的有效率.方法:23例难治性或复发性非霍奇金淋巴瘤(NHL),给予吉西他滨1000mg/m2,第1和第8天,顺铂25mg/m2 第1-3天,地塞米松 20mg/m2,第1-5天,As2O310mg/d,第1-14天.21天为1个周期.结果:完全缓解9例,部分缓解6例,总有效率65.22%.肿瘤中位进展时间6个月,1年生存率39.13%.不良反应主要为血液学毒性.结论:亚砷酸联合GDP方案是治疗难治性或复发性非霍奇金淋巴瘤较为安全有效的化疗方案.%Objective:To evaluate the efficacy and safety of chemotherapy regimen with arsenic trioxide ( As2 O3 )combined with GDP ( gemcitabine, cisplatin and dexamethasone ) for patients with aggressive relapsed or refractory NHL. Methods: All 23 patients with relapsed or refractory NHL were observed,23 patients were treated by gemcitabine 1000 mg/m2 on d1 ,8, cisplatin 25 mg/m2 on d1-3 and dexamethasone 25 mg/m2 on d1-5, Arsenic oxide 10mg/d on d1-14。 21 days for a cycle. Results: Of experimental group all response rate was 65.22% ,including 9 complete response and 6 partial response. Median time to progression was 6 months, and 1 year survival rate was 39.13%.The major adverse reaction was toxicity of bone marrow. Conclusion: Arsenic trioxide combined with GDP regimen is effective and safe for patients with aggressive relapsed or refractory non - Hodgkin's lymphoma.

  10. Gastric lymphoma

    Directory of Open Access Journals (Sweden)

    Sravani Padala

    2016-06-01

    Full Text Available Gastrointestinal lymphomas represent 5-20% of extra nodal lymphomas and mainly occur in the stomach and small intestine. Clinical findings are not specific, thus often determining a delay in the diagnosis. Imaging features at conventional and cross-sectional imaging must be known by the radiologist since he/she plays a pivotal role in the diagnosis and disease assessment, thus assisting in the choice of the optimal treatment to patients. This review focuses on the wide variety of imaging presentation of esophageal, gastric, and small and large bowel lymphoma presenting their main imaging appearances at conventional and cross-sectional imaging, mainly focusing on computed tomography and magnetic resonance, helping in the choice of the best imaging technique for the disease characterization and assessment and the recognition of potential complications. Gastrointestinal tract is the most common extra nodal site involved by lymphoma. 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. [Int J Res Med Sci 2016; 4(6.000: 2481-2486

  11. Pediatric lymphoma diagnosis: role of FNAC, biopsy, immunohistochemistry and molecular diagnostics.

    Science.gov (United States)

    Iyer, Venkateswaran K

    2013-09-01

    Peripheral lymphadenopathy in the pediatric age group is screened using fine needle aspiration cytology (FNAC). Cases found to have features suspicious for lymphoma on FNAC need to undergo biopsy with immunohistochemistry for characterization and typing. In pediatric age group, peripheral lymph nodes are common in Hodgkin's lymphoma for which biopsy is needed for subtyping. Distinction of classical Hodgkin's lymphoma of lymphocyte rich type from nodular lymphocyte predominant Hodgkin's lymphoma needs biopsy evaluation and a panel of immunostains. T lymphoblastic lymphomas and Burkitt's lymphoma are the common types of non Hodgkin's lymphoma seen in the pediatric age group. All lymphomas require a biopsy evaluation with immunohistochemistry and analysis of molecular genetic markers for proper characterization and selection of optimal treatment which are discussed in detail in this review.

  12. Hodgkin lymphoma - children

    Science.gov (United States)

    Lymphoma - Hodgkin - children; Hodgkin disease - children; Cancer - Hodgkin lymphoma - children; Childhood Hodgkin lymphoma ... In children, Hodgkin lymphoma is more likely to occur between ages 15 to 19 years. The cause of this type of ...

  13. Hodgkin Lymphoma (For Kids)

    Science.gov (United States)

    ... Too Tall or Too Short All About Puberty Hodgkin Lymphoma KidsHealth > For Kids > Hodgkin Lymphoma Print A ... of the cool things he's missed. What Is Hodgkin Lymphoma? Lymphoma (say: lim-FOH-mah) is cancer ...

  14. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma

    Directory of Open Access Journals (Sweden)

    Kayo Tokeji

    2016-01-01

    Full Text Available We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case.

  15. Breast lymphoma

    African Journals Online (AJOL)

    Expression of oestrogen receptor protein as determined by ... lymphomas. While this classification has been fairly widely accepted, a ... minimum a full history and physical examination, chest radiographs ... and hepatic function. A number ...

  16. Hodgkin's Lymphoma

    Science.gov (United States)

    ... for information in your local library and on the Internet. Start your information search with the National Cancer ... www.mayoclinic.org/diseases-conditions/hodgkins-lymphoma/basics/definition/CON-20030667 . Mayo Clinic Footer Legal Conditions and ...

  17. Novel agents in classical Hodgkin lymphoma.

    Science.gov (United States)

    Borchmann, Sven; von Tresckow, Bastian

    2017-10-01

    Classical Hodgkin lymphoma (cHL) is the most common hematological malignancy in young adults and can be cured in most cases. However, relapsed and refractory Hodgkin lymphoma, certain patient groups, such as elderly patients, and toxicity of first-line treatment still pose significant challenges. Consequently, new treatment options are needed. Recently, many new treatment concepts have been evaluated in clinical trials. Targeted drug-antibody conjugates and immune checkpoint inhibitors have decisively changed treatment approaches. This review aims to give a comprehensive overview of novel agents in Hodgkin lymphoma that have been recently or are currently being evaluated in clinical trials. In addition to dedicated sections on brentuximab vedotin (BV) and immune checkpoint inhibitors, other emerging substances and concepts are discussed. In doing so, this review compares trial results regarding safety and efficacy. A special focus lies on the effect novel agents will have on the different treatment settings faced by clinicians involved in the treatment of Hodgkin lymphoma.

  18. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  19. Case presentation – thyroid lymphoma

    Directory of Open Access Journals (Sweden)

    Belkisa Izić

    2011-11-01

    Full Text Available Malignant tumors of the thyroid gland account for about 1% of thenewly diagnosed malignant tumors each year, and their incidence inwomen is twice the incidence in men. According to the WHO classification (2004 thyroid tumors are divided into: carcinoma of the thyroid, adenoma and similar tumors, and other thyroid tumors which include: teratomas, angiosarcomas, paragangliomas and others, as well as primary lymphomas and plasmacytomas. Primary thyroid lymphomasare defined as lymphomas which originate in the thyroid gland. This study presents the case of a 68-year-old patient with a thyroid lymphoma, which caused compression of the airways. In the patientpresented there was reduced activity of the thyroid gland. The dominant symptoms were: breathing difficulties, hoarse voice and the enlargement of the thyroid. An ultrasound examination was performedbefore surgery on the neck, which showed a multinodular thyroid,with compromised and compressed trachea to the right and rear. Anemergency surgical procedure was performed to reduce the tumor.Pathohistological diagnosis confirmed diffuse large B cell lymphoma.The aim of the study was to present a patient with a thyroid lymphoma, who had previously not had any immunological changes to the gland,that is, she had not had any chronic lymphocyte thyroiditis, but due to the compressive syndrome it was necessary to perform an emergencysurgical procedure to reduce the tumor.

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

    Science.gov (United States)

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

    2014-08-01

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

  1. Perforin expression in feline epitheliotropic cutaneous lymphoma.

    Science.gov (United States)

    Neta, Michal; Naigamwalla, Dinaz; Bienzle, Dorothee

    2008-11-01

    Cutaneous lymphomas are uncommon in people and companion animals. The tumors can be broadly categorized into epitheliotropic and nonepitheliotropic forms, which appear to have different biological behaviors. The present case describes a feline cutaneous epitheliotropic lymphoma. Masses in a 9-year-old cat were first identified on the tail. The cat was treated with chemotherapy, but additional skin masses developed on the flank, face, and ears. Local radiation induced transient tumor regression, but eventual dissemination prompted euthanasia 13 months after initial tumor appearance. Granular lymphocytes were consistently detected on blood smears, and histologically, the tumor involved the skin and superficial subcutis. Tumor lymphocytes expressed cluster of differentiation 3 (CD3) and perforin molecules, suggestive of a cytotoxic phenotype. Location, histopathological features, and perforin expression were similar to a distinct entity in human medicine designated primary cutaneous, CD8-positive, epidermotropic, cytotoxic, T-cell lymphoma.

  2. Obinutuzumab in follicular lymphoma.

    Science.gov (United States)

    Martinez-Calle, N; Figueroa-Mora, R; Villar-Fernandez, S; Marcos-Jubilar, M; Panizo, C

    2016-12-01

    The CD20 marker continues to be exploited as a therapeutic target for non-Hodgkin's lymphoma. Obinutuzumab is part of a new generation of anti-CD20 monoclonal antibodies, which are synthesized using molecular engineering technology, resulting in novel target epitopes and unprecedented optimization of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Rituximab is the current gold standard for anti-CD20 therapy, yet despite outstanding results published over the past decade, many patients continue to relapse after anti-CD20 regimens. Obinutuzumab is slowly positioning itself in the treatment of CD20+ B-cell neoplasms. On the basis of favorable results from the phase III GADOLIN trial, obinutuzumab was recently approved by the U.S. Food and Drug Administration in combination with bendamustine followed by obinutuzumab maintenance, for the treatment of follicular lymphoma (FL) patients who relapsed or are refractory to a rituximab-containing regimen. Additional phase III trials are underway to test obinutuzumab as a first-line anti-CD20 agent in FL with good preliminary results (GALLIUM trial); thus, it is likely that obinutuzumab will soon achieve a first-line indication. It is plausible that obinutuzumab will replace rituximab as the gold standard for chemoimmunotherapy in FL, although some safety concerns still need to be resolved. This review will address the preclinical pharmacology and the main aspects of the clinical development of obinutuzumab for the treatment of FL.

  3. RNA-binding protein VICKZ is expressed in a germinal center associated pattern among lymphoma subtypes

    DEFF Research Database (Denmark)

    Natkunam, Y.; Vainer, G.; Zhao, S.C.;

    2005-01-01

    to the cytoplasm. Among 868 non-Hodgkin and Hodgkin lymphomas tested by immunohistochemistry on tissue microarrays, staining for VICKZ protein was present in 76% (126/165) of follicular lymphoma, 78% (155/200) of DLBCL, 90% (9/10) of mediastinal large B-cell lymphoma, and 100% (2/2) of Burkitt lymphoma. A subset...... of mantle cell lymphoma (11%, 2/19), extranodal (8%, 2/25), and nodal (20%, 1/5) marginal zone lymphoma and lymphoblastic lymphoma (25%, 4/13), showed VICKZ staining. The majority of lymphocyte predominant Hodgkin (92%, 12/13) and classical Hodgkin (94%, 101/108) lymphoma were found to be positive. Among T......Recent effort in the molecular characterization of diffuse large B-cell lymphoma (DLBCL) has led to the recognition that patients with DLBCL of germinal center origin exhibit a better overall survival. Thus, identification and characterization of markers of germinal center derivation...

  4. Bryostatin and Vincristine in B-Cell Malignancies

    Science.gov (United States)

    2013-01-10

    Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Multiple Myeloma

  5. Lymphoma cytogenetics.

    Science.gov (United States)

    Dave, Bhavana J; Nelson, Marilu; Sanger, Warren G

    2011-12-01

    Lymphomas are a heterogeneous group of neoplasms with distinct morphologic, immunologic, and cytogenetic characteristics. Overlapping morphologic and immunophenotypic features often makes accurate diagnosis difficult. Cytogenetics helps simplify the diagnostic complexities presented in transforming and progressive lymphoid malignancies. Genetic studies using technical advances such as fluorescence in situ hybridization and the newer approaches of array comparative genomic hybridization and gene expression profiling play a critical and often defining role in the diagnosis, progression, prognosis, and therapeutic stratification. This article reviews characteristic cytogenetic abnormalities in specific subtypes of lymphomas at diagnosis, disease progression, and prognosis.

  6. Expression of DNA mismatch repair proteins in transformed non-Hodgkin's lymphoma: relationship to smoking

    DEFF Research Database (Denmark)

    Nandi, S; Yu, J; Reinert, Line

    2006-01-01

    It has been hypothesized that defects in DNA-mismatch repair are associated with smoking in certain types of transformed non-Hodgkin lymphoma (NHL). We have analyzed biopsy samples from two indolent B-cell lymphomas, follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic...... leukemia (CLL/SLL), that have transformed to diffuse-large B-cell lymphoma (DLBCL). We correlated the presence or absence of DNA-mismatch repair enzymes by immunostaining as well as the p53 status to smoking history. Of all patients (n = 30), 37% showed negative immunostaining of MLH1, 16% showed negative...

  7. Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL.

    Science.gov (United States)

    Barr, Paul M; Saylors, Gene B; Spurgeon, Stephen E; Cheson, Bruce D; Greenwald, Daniel R; O'Brien, Susan M; Liem, Andre K D; Mclntyre, Rosemary E; Joshi, Adarsh; Abella-Dominicis, Esteban; Hawkins, Michael J; Reddy, Anita; Di Paolo, Julie; Lee, Hank; He, Joyce; Hu, Jing; Dreiling, Lyndah K; Friedberg, Jonathan W

    2016-05-19

    Although agents targeting B-cell receptor signaling have provided practice-changing results in relapsed chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), they require prolonged administration and provide incomplete responses. Given synergistic preclinical activity with phosphatidylinositol 3-kinase δ and spleen tyrosine kinase inhibition, this phase 2 study evaluated the safety and efficacy of the combination of idelalisib and entospletinib. Eligible patients with relapsed or refractory CLL or NHL underwent intrapatient dose escalation with each agent. With a median treatment exposure of 10 weeks, 60% and 36% of patients with CLL or follicular lymphoma, respectively, achieved objective responses. However, the study was terminated early because of treatment-emergent pneumonitis in 18% of patients (severe in 11 of 12 cases). Although most patients recovered with supportive measures and systemic steroids, 2 fatalities occurred and were attributed to treatment-emergent pneumonitis. Increases of interferon-γ and interleukins 6, 7, and 8 occurred over time in patients who developed pneumonitis. Future studies of novel combinations should employ conservative designs that incorporate pharmacodynamics/biomarker monitoring. These investigations should also prospectively evaluate plasma cytokine/chemokine levels in an attempt to validate biomarkers predictive of response and toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01796470.

  8. GDP方案治疗复发和难治性弥漫性大B细胞淋巴瘤的疗效分析%GDP regimen in Treatment of relapsed and refractory diffuse large B-cell lymphoma and its efficacy

    Institute of Scientific and Technical Information of China (English)

    刘永钟; 梁淑仪; 彭杰文; 梁汉霖; 殷兆锋; 贺景焕

    2011-01-01

    目的 探讨GDP方案(吉西他滨、顺铂、氟美松)治疗复发和难治性弥漫性大B细胞淋巴瘤(DLBCL)的近期疗效和毒副反应.方法 26例复发和难治性弥漫性大B细胞淋巴瘤采用GDP方案治疗:吉西他滨1000 mg/m2静脉滴注,第1、8天;顺铂25 mg/m2静脉滴注,第1~3天;氟美松40mg/d 口服,第1~4天,21 d为1个周期.观察疗效和毒副反应,并随访疾病进展情况.结果 26例均能评价疗效,复发组18例总缓解率(RR)为66.7% (12/18),中位肿瘤进展时间(TTP)为7.3个月(4.5 ~11.2个月),难治组8例总缓解率(RR)为62.5% (5/8),中位肿瘤进展时间(TTP)为6.5个月(2.9~10.1个月),经统计学检验两组间RR及中位TTP差异均无统计学意义;且毒副反应程度较轻,毒副反应主要为白细胞和血小板减少,但均为可逆,未出现因化疗毒性而死亡患者.结论 GDP方案是治疗复发和难治性弥漫性大B细胞淋巴瘤安全有效的可行解救方案,缓解率高,化疗耐受性好.%Objective To evaluate the short-term effect and side effects of GDP regimen treating the patients with relapsed and refractory diffuse large B-cell lymphoma( DLBCL) . Method Twenty-six patients with relapsed and refractory DLBCL were treated with GDP regimen, GDP regimen: gemcitabine ( GEM ) 1 000 mg/m2 IVD on day 1 and 8;cisplatine( DDP) 25mg/m2 IVD on day 1 to 3 ; dexamethasone( DXM) 40 mg/d P. O. On day 1 to 4; Treatment was repeated Every 3 weeks. Result The response rate ( RR) of relapsed group was 66. 7% ( 12/18) ,the median time to progression ( m-TTP) was 7. 3 months( ranged 4. 5-11.2 months) ;The response rate( RR)of refractory group was 62. 5% (5/8) ,m-TTP was 6. 5 months( ranged 2. 9-10. 1 months). There were no statistical signification between relapsed group and refractory group in the RR and m-TTP;The main side effects were marrow suppression including of leucopenia and thrombocytope-nia,no patients dead for toxic reactions of chemotherapy. Conclusion GDP

  9. Targeted therapy for Hodgkin lymphoma and systemic anaplastic large cell lymphoma: focus on brentuximab vedotin

    Directory of Open Access Journals (Sweden)

    Chen X

    2013-12-01

    Full Text Available Xueyan Chen, Lorinda A Soma, Jonathan R FrommDepartment of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USAAbstract: Despite the relative success of chemotherapy for Hodgkin lymphoma (HL and systemic anaplastic large cell lymphoma (ALCL, novel therapeutic agents are needed for refractory or relapsed patients. Targeted immunotherapy has emerged as a novel treatment option for these patients. Although unconjugated anti-cluster of differentiation (CD30 antibodies showed minimal antitumor activity in early clinical trials, development of antibody–drug conjugates (ADCs appears promising. Brentuximab vedotin is an ADC composed of an anti-CD30 antibody linked to a potent microtubule-disrupting agent monomethyl auristatin E (MMAE. It has the ability to target CD30-positive tumor cells and, once bound to CD30, brentuximab vedotin is internalized and MMAE is released to induce cell cycle arrest and apoptosis. In two phase II trials, objective response was reported in 75% and 86% of patients with refractory or relapsed HL and systemic ALCL, respectively, with an acceptable toxicity profile. Based on these studies, the US Food and Drug Administration (FDA granted accelerated approval of brentuximab vedotin in August 2011 for the treatment of refractory and relapsed HL and ALCL. We review the key characteristics of brentuximab vedotin, clinical data supporting its therapeutic efficacy, and current ongoing trials to explore its utility in other CD30-positive malignancies.Keywords: classical Hodgkin lymphoma, systemic anaplastic large cell lymphoma, CD30, brentuximab vedotin, SGN-35

  10. Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma

    NARCIS (Netherlands)

    D. van Baarle (Debbie); F. Miedema (Frank); E. Hovenkamp (Egbert); M.F.C. Callan (Margareth); K.C. Wolthers (Katja); S. Kostense; L.C. Tan; H.G.M. Niesters (Bert); A.D.M.E. Osterhaus (Albert); A.J. McMichael (Andrew); M.H.J. van Oers (Marinus)

    2001-01-01

    textabstractAcquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfu

  11. Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma

    NARCIS (Netherlands)

    van Baarle, D; Hovenkamp, E; Callan, M F; Wolthers, K C; Kostense, S; Tan, L C; Niesters, H G; Osterhaus, A D; McMichael, A J; van Oers, M H; Miedema, F

    2001-01-01

    Acquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfunction of EB

  12. Open-Capsule Budesonide for Refractory Celiac Disease.

    Science.gov (United States)

    Mukewar, Saurabh S; Sharma, Ayush; Rubio-Tapia, Alberto; Wu, Tsung-Teh; Jabri, Bana; Murray, Joseph A

    2017-06-01

    Refractory celiac disease (RCD) is a rare condition often associated with poor prognosis. Various immunosuppressive medications (IMs) have been used with modest success. We describe outcomes in patients treated with open-capsule budesonide (OB), including those for whom IM treatment failed. We identified RCD patients treated with OB at Mayo Clinic, Rochester, Minnesota from 2003 to 2015. Demographic, serologic, and clinical variables were analyzed. We identified 57 patients who received OB for suspected RCD. Based on clonal T-cell receptor gamma gene rearrangement or aberrant phenotype of intraepithelial lymphocytes (IELs), 13 patients (23%) were classified as having RCD-2 and 43 (75%) as RCD-1. In one patient (2%) TCR gene rearrangement status was unknown. Most patients were women (69%), mean (s.d.) age was 60.5 (3.5) years and body mass index was 28.4 (4.5) kg/m(2). The majority had diarrhea (72%), with median of 6 bowel movements per day (range, 4-25). IM treatment (azathioprine, systemic corticosteroids, or regular budesonide) had failed in nearly half. Twenty-four patients (42%) had anemia and 12 (21%) had hypoalbuminemia. All had Marsh 3 lesions on biopsy: 3a (19%), 3b (46%), and 3c (35%). After OB therapy, the majority had clinical (92%) and histologic (89%) improvement. Follow-up biopsy in 7 out of 13 patients with RCD-2 (53%) showed an absence of clonal TCR gamma gene rearrangement/aberrant IEL phenotype previously seen. On follow-up, 2 patients (4%) died of enteropathy-associated T-cell lymphoma. Most patients with RCD show clinical and histopathologic improvement with OB therapy, including those with failure of IMs. OB is a promising therapeutic option for management of RCD.

  13. Angioimmunoblastic T Cell Lymphoma Mimicking Chronic Urticaria

    Directory of Open Access Journals (Sweden)

    Mohleen Kang

    2016-01-01

    Full Text Available Angioimmunoblastic T cell lymphoma (AITL is a rare but distinct type of T cell lymphoma with an aggressive course and high mortality. Most patients are diagnosed late in the disease and usually present with generalized lymphadenopathy. A minority have skin lesions at the time of diagnosis, more commonly in the form of nonspecific maculopapular rash with or without pruritus. We report a rare case of AITL presenting with chronic, recurrent angioedema and urticaria-like lesions and no palpable peripheral adenopathy. Primary Care physicians, dermatologists, and allergists must maintain a high index of suspicion for cutaneous manifestations of lymphoma, especially if the skin lesions are refractory to standard treatment. Timely diagnosis is essential to improve survival.

  14. Study on the expression of T, B lymphocyte antigen and platelet antibodies in patients with platelet transfusion refractoriness%血小板输注无效患者T、B淋巴细胞抗原和血小板抗体表达的研究

    Institute of Scientific and Technical Information of China (English)

    杜春红; 黄海涛; 苑广洋; 赵国生; 李红学; 张元; 孙亚军; 徐慧民; 董守智

    2016-01-01

    Objective To explore whether T lymphocytes subgroup,B lymphocytes,platelet antigen CD41a,CD61 or platelet antibodies are involved in the platelet transfusion refractoriness.Methods Forty-seven patients diagnosed as platelet transfusion refractoriness and 32 patients that achieved effective platelet therapy were ennolled in this study.Flow cytometry was performed to detect the proportion of cytotoxic T cell (CD3+CD4-CD8+),helper T cell (CD3+CD4+CD8) and B lymphocytes (CD19+),and the expression of platelet glycoproteins,including CD41a and CD61,while platelet antibodies were also measured by solid-phase agglutination.Results The significant lower level of helper T cell (36.60% vs 48.53%),higher level of cytotoxic T cell (53.26% vs 44.02%) and lower cytotoxic/helper T cell ratio (0.85 vs 1.31) were observed in platelet refractoriness group when compared with effective platelet therapy group (P<0.05).However,the significant difference was not observed in B lymphocytes between the two group (3.02% vs 2.85%,P>0.05).Platelet glycoproteins CD41 a and CD61 and antibodies were both expressed at high levels in platelet refractoriness group (88.10% vs 51.69%,88.36% vs 51.83%,85.37% vs 14.82%,respectively,P<0.05).Conclusions Activation of cytotoxic T cells,suppression of helper T cells,higher expression level of platelet glycoproteins CD41a and CD61 as well as the development of anti-platelet antibodies are involved in the immunologic mechanism of platelet refractoriness.%目的 探讨T、B淋巴细胞,血小板膜糖蛋白和血小板抗体在血小板输注无效中作用.方法 选择41例临床确诊血小板输注无效患者为研究对象,以27例血小板输注有效患者为对照组,采用流式细胞术检测两组患者外周血细胞毒性T淋巴细胞(CD3+CD4-CD8+)、辅助性T淋巴细胞(CD3+CD4+CD8)、B淋巴细胞(CD19+)比例和血小板膜糖蛋白CD41a、CD61的表达,采用固相凝集法检测两组患者血

  15. Extranodal lymphoplasmacytoid lymphoma: spectrum of disease

    Energy Technology Data Exchange (ETDEWEB)

    Guermazi, Ali [Department of Radiology, University of California at San Francisco, 350 Parnassus Avenue, Suite 150, San Francisco, CA 94117 (United States); Department of Radiology, Saint Louis University Hospital, AP-HP, Paris (France); Meignin, Veronique [Department of Pathology, Saint Louis University Hospital, AP-HP, Paris (France); Brice, Pauline [Department of Hematology, Saint Louis University Hospital, AP-HP, Paris (France)

    2003-04-01

    Lymphoplasmacytoid lymphomas (LPL) are non-Hodgkin's lymphomas characterized by a proliferation of lymphoplasmacytoid cells or plasma cells with intracytoplasmic monoclonal Ig. The LPL are low-grade B-cell neoplasms close to B chronic lymphocytic leukemia with plasmacytoid differentiation. They show an indolent course, typically affect older men, and present as a disseminated disease with predominantly nodal involvement. Nevertheless, localized forms, some of them extranodal, have been described. The cases that best represent the range of radiographic findings on X-ray, CT, and MR imaging are presented. (orig.)

  16. Spinal epidural compression in chronic lymphocytic leukemia.

    Science.gov (United States)

    Michalevicz, R; Burstein, A; Razon, N; Reider, I; Ilie, B

    1989-11-01

    Spinal epidural compression is a rare neurologic complication in patients with lymphoma. It occurs mostly in those with intermediate-grade to high-grade malignancy disease. This type of neurologic involvement has not been described in chronic lymphocytic leukemia (CLL). A patient with a long, stable CLL course developed spinal epidural compression and consequently died. The frequency of spinal epidural compression in lymphoma, according to the histologic subtypes and the considerations in making the right choice of therapy are discussed in light of the presented case.

  17. Lymphoma of the eyelid

    DEFF Research Database (Denmark)

    Svendsen, Frederik H; Heegaard, Steffen

    2017-01-01

    Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B-cell lymph......Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B...... chemotherapy with or without adjuvant treatment is the treatment of choice for high-grade or disseminated lymphomas. The majority of subtypes, especially low-grade subtypes, have a good prognosis with few recurrences or progression. Some subtypes, including mycosis fungoides, have a poorer prognosis...

  18. 表面增强激光解吸/电离-飞行时间质谱技术检测不同来源淋巴瘤细胞株及健康人外周淋巴细胞的差异蛋白质%Detection of protein expression in lymphoma cell lines and peripheral blood lymphocyte of health persons by SELDI-TOF-MS

    Institute of Scientific and Technical Information of China (English)

    张健; 陶朝晖; 景莉; 韩丽英

    2010-01-01

    Objective To look for different expression of proteins between T and B lymphoma cell lines and normal peripheral blood lymphocytes by surface enhanced laser desorption/ionization-time of flightmass spectrometry (SELDI-TOF-MS) technology. Methods T and B lymphoma cells were conventionally cultivated, and logarithmic phase cells were collected for experiment. The normal lymphocytes were separated from peripheral blood of healthy persons. Proteins were extracted from the total protein of various cells, and were detected by SELDI-TOF-MS technology. SPSS 13.0 statistical software was used to statistical analysis and P <0.05 was considered as statistically difference. Results There are six differentially expressed proteins between T/B lymphoma cell lines and health human peripheral lymphocyte. There are seven differentially expressed proteins between B and T lymphoma cell lines. Conclusion The levels of proteomics were significantly different among T, B lymphoma cell line and normal lymphocyte. Application of SELDI-TOF-MS technology probably is some benefit on screening molecular markers of lymphoma. Moreover it is possible to lay the preliminary foundation for pathogenesis and targeted treatment of lymphoma.%目的 应用表面增强激光解吸/电离-飞行时间质谱(SELDI-TOF-MS)技术对体外培养的人类T、B淋巴瘤细胞株和健康人外周血淋巴细胞的蛋白质进行检测,寻找差异蛋白.方法 常规培养人类T、B淋巴瘤细胞株,并从健康人外周血中分离出淋巴细胞培养,取对数生长期的细胞进行试验,使用蛋白提取液提取蛋白质,应用SELDI-TOF-MS技术进行检测,采用SPSS 13.0统计软件包进行统计学分析.结果 T、B淋巴瘤细胞株与健康人外周淋巴细胞比较,均有6个差异蛋白质.T淋巴瘤细胞株与B淋巴瘤细胞株比较有7个差异蛋白质.结论 T、B淋巴瘤细胞间及二者与健康人外周淋巴细胞比较,蛋白质组学水平均有差异.应用SELDl-TOF-MS技

  19. Does tumoral {sup 111}In-ibritumomab accumulation correlate with therapeutic effect and outcome in relapsed or refractory low-grade B-cell lymphoma patients undergoing {sup 90}Y-ibritumomab radioimmunotherapy?

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Koichiro; Shinozaki, Kenji [National Kyushu Cancer Center, National Hospital Organization, Department of Radiology, Minami-ku, Fukuoka (Japan); Choi, Ilseung; Uike, Naokuni [National Kyushu Cancer Center, National Hospital Organization, Division of Hematology, Minami-ku, Fukuoka (Japan); Nakagawa, Makoto [PET Imaging Center, Koga Hospital 21, Kurume (Japan)

    2014-12-15

    The aim of this study was to determine whether tumoral {sup 111}In-ibritumomab accumulation on pre-treatment imaging correlates with therapeutic responses and progression-free survival (PFS) in patients with non-Hodgkin's lymphoma (NHL) undergoing {sup 90}Y-ibritumomab radioimmunotherapy (RIT). This was a retrospective study of 39 patients with low-grade B-cell NHL treated with RIT. We classified the patients into positive and negative groups according to the presence or absence of tumoral {sup 111}In-ibritumomab accumulation on pre-treatment {sup 111}In-ibritumomab examinations. We then determined the correlation between the {sup 111}In-ibritumomab imaging findings and the patients' therapeutic responses and PFS. Tumoral {sup 111}In-ibritumomab accumulation was positive in 64.1 % and negative in 35.9 % of the patients. The {sup 111}In-positive patients had a significantly higher overall response rate (ORR) compared to the {sup 111}In-negative patients (100.0 % vs. 78.6 %, p = 0.02). The {sup 111}In-negative patients with advanced disease (stages III/IV) had a significantly lower ORR (40 %) and a significantly higher rate of progressive disease (40.0 %) compared to those of the {sup 111}In-negative patients with limited disease (stages I/II) (100 % and 0 %, p = 0.009 each). However, these two groups had similar 2-year PFS rates (65.0 % vs. 50.0 %, p = 0.80). {sup 111}In-ibritumomab imaging findings seem to correlate with ORR and the progressive disease rate after RIT, but not with PFS. (orig.)

  20. Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

    Science.gov (United States)

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

    1987-07-01

    This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, immune perturbation demonstrated by excessive previous skin diseases and phenylbutazone use, and viral involvement shown by links with infectious diseases and multiple sclerosis.

  1. Lymphoma with large-plaque parapsoriasis treated with PUVA.

    Science.gov (United States)

    Tamagawa, Risa; Katoh, Norito; Shimazaki, Chihiro; Okano, Akira; Yamada, Shinya; Ichihashi, Kaori; Masuda, Koji; Kishimoto, Saburo

    2005-01-01

    We report on a 78-year-old Japanese woman with a 50-year history of large-plaque parapsoriasis that had evolved into cutaneous T-cell lymphoma. Her large-plaque parapsoriasis had been treated with psoralen plus ultraviolet A for 10 years. Subsequently an isolated nodule appeared on her right lower leg. Prior or concurrent patches or plaques were absent. Histology revealed a diffuse nonepidermotropic infiltrate of large lymphocytes in the dermis, which had enlarged nuclei and prominent nucleoli. A diagnosis of CD30- cutaneous large T-cell lymphoma was made. Following systemic chemotherapy, there was clinical improvement. No evidence of recurrence or systemic lymphoma has subsequently been found.

  2. B-cell lymphomas with features intermediate between distinct pathologic entities. From pathogenesis to pathology.

    Science.gov (United States)

    Carbone, Antonino; Gloghini, Annunziata; Aiello, Antonella; Testi, Adele; Cabras, Antonello

    2010-05-01

    Published in September 2008, the updated World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues introduces provisional borderline categories for lymphoma cases that demonstrate overlapping clinical, morphological, and/or immunophenotypic features between well-established entities. These overlapping features pose real diagnostic challenges especially in identifying atypical cases of diffuse large B-cell lymphoma, Hodgkin lymphoma, and Burkitt lymphoma. Lymphoma cases showing borderline features between T-cell/histiocyte-rich large B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma are not included within the borderline categories provisionally recognized by the updated classification. Within the borderline categories, there are cases combining features of primary mediastinal large B-cell lymphoma and classical Hodgkin lymphoma. Many of these cases resemble classical Hodgkin lymphoma but have a large number of tumor cells expressing CD20, CD45, and B-cell transcription factors. Alternatively, these cases may resemble primary mediastinal large B-cell lymphoma but contain tumor cells resembling Reed-Sternberg cells and displaying an aberrant phenotype such as CD20(-), CD15(-/+) CD45(+), CD30(+), Pax5(+), OCT2(+/-), and BOB1(+/-). Another new borderline category defining B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, represents a biologically heterogeneous group. Cases with morphologic features intermediate and with CD10/BCL6 coexpression should be placed in diffuse large B-cell lymphoma/Burkitt lymphoma category if tumor cells also show strong BCL2 staining and/or a Ki67 proliferation index of less than 90%. When MYC rearrangements are present in these cases, the lymphomas often have atypical features, including concurrent rearrangements of BCL2 and/or BCL6 genes (so-called double/triple-hit lymphomas) and more aggressive behavior. For the

  3. Predicting factors for refractory kawasaki disease.

    Science.gov (United States)

    Do, Young-Sun; Kim, Ki-Won; Chun, Jin-Kyong; Cha, Byung Ho; Namgoong, Mee Kyung; Lee, Hae Yong

    2010-05-01

    About 10-15% of Kawasaki disease (KD) is refractory to intravenous immunoglobulin (IVIG) therapy. This study was designed to investigate the predicting factors for refractory KD. We reviewed retrospectively the clinical records of 77 patients with typical KD admitted at Wonju Christian Hospital from January, 2005, to December, 2008. The variance of laboratory and demographic parameters between the IVIG-responsive group and IVIG-resistant group were analyzed. Thirteen patients with urinary tract infections were randomly collected as a febrile control group. Among 77 patients diagnosed with complete KD, 13 patients (16.9%) were IVIG-resistant. The febrile period and hospital days were significantly longer in the IVIG-resistant group than IVIG-responsive group (pIVIG-resistant group (p=0.025). The Kobayashi score could differentiate these two groups (p=0.015). Fewer lymphocytes was observed during the subacute phase in the IVIG-resistant group (p=0.032). Coronary arterial dilatations (CADs) were observed in 10.9% (7/64) of IVIG-responders and 38.5% (5/13) of IVIG-resistant patients (p=0.038). The percentage of neutrophils and lymphocytes in patients with KD, in addition to known risk factors for refractory KD, may help predict IVIG-resistance in patients with KD.

  4. Testicular lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; d'Amore, F; Christensen, Bjarne Egelund

    1994-01-01

    In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases...... were diffuse (65% diffuse centroblastic type). Of the 27 tested, 11% were of T- and 89% of B-immunophenotype. In localised cases, where surgery was supplemented by combination chemotherapy (CCT), the relapse rate was 15.4%. The relapse rate for cases with localised disease treated with other regimens...

  5. Approach to patients with refractory coeliac disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Ikram Nasr

    2016-10-01

    Full Text Available Refractory coeliac disease (RCD is a recognised complication, albeit very rare, of coeliac disease (CD. This condition is described when individuals with CD continue to experience enteropathy and subsequent or ongoing malabsorption despite strict adherence to a diet devoid of gluten for at least 12 months and when all other causes mimicking this condition are excluded. Depending on the T-cell morphology and T-cell receptor (TCR clonality at the β/γ loci, RCD can be subdivided into type 1 (normal intra-epithelial lymphocyte morphology, polyclonal TCR population and type 2 (aberrant IELs with clonal TCR. It is important to differentiate between the two types as type 1 has an 80% survival rate and is managed with strict nutritional and pharmacological management. RCD type 2 on the other hand has a 5-year mortality of 50% and can be complicated by ulcerative jejunitis or enteropathy-associated T-cell lymphoma (EATL. Management of RCD type 2 has challenged many experts, and different treatment approaches have been adopted with variable results. Some of these treatments include immunomodulation with azathioprine and steroids, methotrexate, cyclosporine, alemtuzumab (an anti CD-52 monoclonal antibody, and cladribine or fludarabine sometimes with autologous stem cell transplantation. In this article, we summarise the management approach to patients with RCD type 2.

  6. NKT Cell Responses to B Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Junxin Li

    2014-04-01

    Full Text Available Natural killer T (NKT cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer, resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.

  7. Monoclonal antibodies in chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Faderl, Stefan; Keating, Michael J

    2006-09-01

    Multiple options are now available for the treatment of chronic lymphocytic leukemia. Over the last 10 years, monoclonal antibodies have become an integral part of the management of this disease. Alemtuzumab has received approval for use in patients with fludarabine-refractory chronic lymphocytic leukemia. Rituximab has been investigated extensively in chronic lymphocytic leukemia both as a single agent and in combination with chemotherapy and other monoclonal antibodies. Epratuzumab and lumiliximab are newer monoclonal antibodies in the early phase of clinical development. This article will review the monoclonal antibodies more commonly used to treat chronic lymphocytic leukemia, the results obtained with monoclonal antibodies as single agents and in combination with chemotherapy, and other biological agents and newer compounds undergoing clinical trials.

  8. Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg cells and normal B-lymphocytes.

    Science.gov (United States)

    Faumont, Nathalie; Chanut, Aurélie; Benard, Alan; Cogne, Nadine; Delsol, Georges; Feuillard, Jean; Meggetto, Fabienne

    2009-03-01

    In Epstein-Barr virus-associated Hodgkin's lymphomas, neoplastic Reed-Sternberg cells and surrounding non-tumor B-cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-cells. Twelve LMP1 natural variants from Reed-Sternberg cells, non-tumor B-cells of Hodgkin's lymphomas and from B-cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 cells to search for relationships between LMP1 cellular origin and oncogenic properties as well as nuclear factor-kappaB activation, and apoptosis protection. LMP1 variants of Reed-Sternberg cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg cells, but inconstantly for LMP1-variants from non-tumor B-cells. Analysis of LMP1 variants from both normal B-cells and Reed-Sternberg cells indicates that protection against apoptosis through activation of nuclear factor-kappaB - whatever the cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. Taken together, our results demonstrate that preserved nuclear factor-kappaB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor cells in Hodgkin's lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg cells.

  9. Developing Refractories for Exporting

    Institute of Scientific and Technical Information of China (English)

    PANShang-xin

    1996-01-01

    The total output of China refractory products and export volume of China refractory raw materials rank the first in the world,In future the task is to improve the quality of the products to enlarge the variety and to expand export.

  10. Silica Refractory Bricks

    Institute of Scientific and Technical Information of China (English)

    Yu Lingyan; Peng Xigao

    2011-01-01

    @@ 1.Scope This standard specifies the classification,technical requirements,test methods,quality appraisal procedures,packing,marking,transportation,storage,and quality certificate of silica refractory bricks.This standard is applicable to silica refractory bricks with single weight≤40 kg.

  11. Stages of Adult Hodgkin Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  12. Stages of Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  13. T-Cell Lymphomas Presenting as Colon Ulcers and Eosinophilia

    Directory of Open Access Journals (Sweden)

    Ping-Hsiu Wu

    2015-07-01

    Full Text Available Primary gastrointestinal T-cell lymphoma is an uncommon entity and primary colon T-cell lymphoma is even rarer. The majority of enteropathy-associated T-cell lymphomas present predominantly as ulcers or strictures in the endoscopic examinations, while primary B-cell lymphomas commonly present as exophytic lesions. Ulcerative colon T-cell lymphoma may mimic Crohn's disease (CD, which is a chronic inflammatory disease of the intestines with ulcer and fistula formations difficult for clinicians to diagnose based on endoscopic observations alone. Like CD, T-cell lymphoma may be characterized by the presence of multiple skipped ulcers distributed from the terminal ileum to the descending colon. Furthermore, it is difficult to diagnose this unusual lymphoma by a single endoscopic biopsy. Typically, the histological composition of T-cell lymphoma is made of medium to large atypical cells located in the base of the ulcer with extension to the muscle layer and the adjacent mucosa. However, it is common that biopsy specimens show only mixed inflammatory changes where the lymphoma cells are hard to be identified. The differential diagnosis of malignant lymphoma must be considered when clinically diagnosed CD is refractory to the medical treatment or when its clinical behavior becomes aggressive. The current study presents a rare case of primary colon T-cell lymphoma in a 56-year-old male with marked recent weight loss, watery diarrhea and bilateral neck lymphadenopathy, who received a laboratory checkup and endoscopic workup for colon biopsy. The initial pathological report was consistent with mucosal inflammation and benign colon ulcers. Interestingly, the blood test showed a prominent eosinophilia. A biopsy of the enlarged neck lymph nodes done approximately 1 month after the colon biopsy unexpectedly showed T-cell lymphoma, which led to a review of the initial colonic biopsy specimens. Additional immunohistochemical stains were used accordingly, which

  14. Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association

    Science.gov (United States)

    Sarkozy, Clémentine; Molina, Thierry; Ghesquières, Hervé; Michallet, Anne-Sophie; Dupuis, Jehan; Damotte, Diane; Morsschauser, Franck; Parrens, Marie; Martin, Laurent; Dartigues, Peggy; Stamatoullas, Aspasia; Hirsch, Pierre; Fabiani, Bettina; Bouabdallah, Krimo; da Silva, Maria Gomes; Maerevoet, Marie; Laurent, Camille; Coiffier, Bertrand; Salles, Gilles; Traverse-Glehen, Alexandra

    2017-01-01

    Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been well described in the literature. We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. Cases were defined as classical Hodgkin lymphoma-like morphology (64.6%) with primary mediastinal B-cell lymphoma immunophenotype, primary mediastinal B-cell lymphoma-like morphology (30.3%) with classical Hodgkin lymphoma or composite (5.1%) (synchronous occurrence of classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma). The median age was 32 years (13–83 years); 55% were women. Thirteen of 81 evaluable cases (16%) were Epstein-Barr virus-positive. Twenty-eight percent of patients presented primary refractory disease (progression under first-line treatment or relapse within one year). The 3-year event-free and overall survival rates were 63% and 80%, respectively. Patients treated with a standard regimen (RCHOP/ABVD) had worse event-free survival (P=0.003) and overall survival (P=0.02) than those treated with a dose-intensive chemotherapy (high-dose RCHOP/escalated BEACOPP). Rituximab added to chemotherapy was not associated with better event-free survival (P=0.55) or overall survival (P=0.88). Radiotherapy for patients in complete remission had no impact on event-free survival. In multivariate prognostic analysis, ECOG-PS and anemia were the strongest factors associated with a shorter event-free survival and overall survival, respectively. In conclusion, this report describes the largest series of mediastinal gray zone lymphoma. Our data suggest that a dose-intensive treatment might improve the outcome of this rare and aggressive disease. PMID:27758822

  15. Development of improved refractories

    Energy Technology Data Exchange (ETDEWEB)

    Wereszczak, A.A.; Ferber, M.K.; Liu, K.C. [Oak Ridge National Lab., TN (United States); Moore, R.E. [Univ. of Missouri, Rolla, MO (United States)

    1997-04-01

    The goal of the proposed project is to provide expertise and facilities for the high temperature mechanical properties characterization of refractory materials which are of interest to the US DOE`s Office of Industrial Technologies Advanced Industrial Materials Project. Initially the project would establish dedicated refractory testing facilities which would be capable of generating representative engineering creep and high temperature modulus of elasticity (MOE) data to a temperature of 3300{degrees}F (1815{degrees}C) in ambient air. The generated engineering creep and MOE data would serve R&D requirements of refractories-manufacturers and its glass-manufacturer end-users and designers. The relevance of this effort to the refractory and glass-making industries would be ensured by coordinating the research activities through a membership with Alfred University`s Center for Glass Research (CGR) Satellite Center at the University of Missouri-Rolla (UMR), an NSF Center. Valid engineering creep and high temperature MOE data currently do not exist for almost all commercial refractories. Refractory end-users such as glass-manufacturers require such data for efficient and economical design of their various glass-melting furnace superstructures (e.g., furnace crowns). Refractories in glass production furnaces may be subjected to extreme temperatures as high as 3200{degrees}F (1760{degrees}C). With the simultaneous imposition of mechanical and thermal stresses, creep deformation of the refractory material will assuredly occur as a consequence. Designers must ensure that the structural integrity is maintained, so these high temperature deformations must be considered for successful glass furnace superstructure design. These criteria can only be satisfied with the utilization of representative engineering creep and high temperature MOE data for the refractory materials that are chosen for the design of the refractory superstructures.

  16. Influência do CD 20 na refratariedade do linfoma de Hodgkin clássico ao tratamento inicial com o esquema ABVD, no Ceará, Brasil Influence of CD 20 antigen expression in the refractoriness of classical Hodgkin lymphoma in the first line treatment with ABVD protocol in Ceará state, Brazil

    Directory of Open Access Journals (Sweden)

    Rogério Pinto Giesta

    2009-06-01

    Full Text Available INTRODUÇÃO: A significância prognóstica do marcador imunológico CD 20 no linfoma de Hodgkin clássico (LHc ainda é incerta, particularmente no que se refere à refratariedade ao tratamento inicial. OBJETIVOS: Avaliar a influência da positividade do marcador CD 20 na refratariedade do LHc ao tratamento poliquimioterápico inicial, com o esquema doxorubicina 25 mg/m², bleomicina 10 mg/m², vinblastina 6 mg/m² e dacarbazina 375 mg/m² (ABVD, no Ceará, Brasil. MATERIAL E MÉTODOS: Estudo analítico incluindo 97 pacientes com diagnóstico de LHc firmado entre janeiro de 2000 e dezembro de 2004. A análise foi realizada avaliando variáveis demográficas, clínicas e laboratoriais. RESULTADOS: Foi evidenciada uma positividade do CD 20 em 38,1% dos pacientes. Na análise bivariada, CD 20 positivo (razão de chance [RC] = 4,02; intervalo de confiança [IC] = 1,09 - 8,54; p = 0,02, a presença de sintomas B (RC = 4,02; IC = 1,18-17,51; p = 0,01 e a elevação da desidrogenase lática (mediana não-refratários 248,5 [200,5 - 389,5]; mediana refratários 356 [208,5 - 545]; p = 0,03 apresentaram relação de pior prognóstico quanto à refratariedade. Na regressão logística, o CD 20 positivo (RC ajustada = 3,6; IC = 0,99 - 13,09; p = 0,05 e a presença de sintomas B (RC ajustada = 5,41; IC = 1,16 - 25,34; p = 0,03 continuaram apresentando pior prognóstico. DISCUSSÃO: Esses dados coincidem com a literatura, em que a positividade do marcador CD 20 está relacionada com pior resposta ao tratamento com ABVD. CONCLUSÃO: Os nossos dados indicam que o tratamento com ABVD não é completamente adequado para a abordagem terapêutica inicial deste subgrupo de pacientes e novas pesquisas precisam ser realizadas no sentido de aperfeiçoar o tratamento destes pacientes.INTRODUCTION: The prognostic value of CD20 antigen expression in classical Hodgkin lymphoma (cHL is uncertain, particularly regarding the refractoriness to first-line treatment. OBJECTIVES

  17. New drugs for follicular lymphoma.

    Science.gov (United States)

    Sorigue, Marc; Ribera, Josep-Maria; Motlló, Cristina; Sancho, Juan-Manuel

    2016-10-01

    Despite the improvement in prognosis since the advent of rituximab, follicular lymphoma is still incurable and remains the cause of death of most afflicted patients. With the expanding knowledge of the pathogenesis of B-cell malignancies, in the last few years a plethora of new therapies acting through a variety of mechanisms have shown promising results. This review attempts to analyze the evidence available on these new drugs, which include new monoclonal antibodies and immunoconjugates, the anti-angiogenic and immunomodulatory agent lenalidomide, the proteasome inhibitor bortezomib, inhibitors of B-cell receptor pathway enzymes, such as ibrutinib, idelalisib, duvelisib and entospletinib, BCL2 inhibitors and checkpoint inhibitors. We conclude that despite the high expectations around the new therapeutic options for patients with refractory disease, these new drugs have side effects that require caution with their use, particularly in light of the still short follow up and the lack of both randomized trials and data on combination regimens.

  18. Chidamide in the treatment of peripheral T-cell lymphoma

    Science.gov (United States)

    Chan, Thomas S; Tse, Eric; Kwong, Yok-Lam

    2017-01-01

    Mature T-cell lymphomas are aggressive malignancies. Treatment outcome is poor with conventional chemotherapy. They are about twice as common in Asia as compared with other non-Asian countries. Histone proteins form the basic structure of chromatin, and their acetylation at lysine residues relaxes chromatin structure, facilitating gene transcription. Conversely, histone deacetylation, catalyzed by histone deacetylases, compacts chromatin and represses gene transcription. Histone deacetylase inhibitors are an important class of antineoplastic agents. Chidamide is a novel orally active benzamide-type histone deacetylase inhibitor that has shown in vitro activities against a wide array of neoplasms. In Phase I trials, chidamide showed preferential efficacy in mature T-cell lymphomas. In a pivotal Phase II trial of chidamide in 79 patients with relapsed or refractory mature T-cell lymphomas, an overall response rate of 28% (complete remission/complete remission unconfirmed: 14%) was achieved, with most responses occurring within the first 6 weeks of treatment. The median duration of response (DOR) was 9.9 (1.1–40.8) months. Of 22 responders, 19 patients (86%) had a DOR of ≥3 months and eight patients (36%) had a DOR of >12 months. Angioimmunoblastic T-cell lymphoma and anaplastic large cell lymphoma (anaplastic lymphoma kinase-negative) showed better response rates, with the most durable responses observed in angioimmunoblastic T-cell lymphoma patients. Safety profile was favorable, with very few cases of grade 3/4 toxicities observed. Chidamide is approved by the China Food and Drug Administration for the treatment of relapsed and refractory peripheral T-cell lymphomas. PMID:28138258

  19. B-cell-rich T-cell lymphoma associated with Epstein-Barr virus-reactivation and T-cell suppression following antithymocyte globulin therapy in a patient with severe aplastic anemia

    Directory of Open Access Journals (Sweden)

    Nobuyoshi Hanaoka

    2015-09-01

    Full Text Available B-cell lymphoproliferative disorder (B-LPD is generally characterized by the proliferation of Epstein-Barr virus (EBV-infected B lymphocytes. We here report the development of EBV-negative B-LPD associated with EBV-reactivation following antithymocyte globulin (ATG therapy in a patient with aplastic anemia. The molecular autopsy study showed the sparse EBV-infected clonal T cells could be critically involved in the pathogenesis of EBV-negative oligoclonal B-LPD through cytokine amplification and escape from T-cell surveillances attributable to ATG-based immunosuppressive therapy, leading to an extremely rare B-cell-rich T-cell lymphoma. This report helps in elucidating the complex pathophysiology of intractable B-LPD refractory to rituximab.

  20. Cyclic adenosine monophosphate signal pathway in targeted therapy of lymphoma

    Institute of Scientific and Technical Information of China (English)

    DOU Ai-xia; WANG Xin

    2010-01-01

    Objective To review the role of cyclic adenosine monophosphate (cAMP) signal pathway in the pathogenesis oflymphoma and explore a potential lymphoma therapy targeted on this signaling pathway.Data sources The data cited in this review were mainly obtained from the articles listed in Medline and PubMed,published from January 1995 to June 2009. The search terms were "cAMP" and "lymphoma".Study selection Articles regarding the role of the cAMP pathway in apoptosis of lymphoma and associated cells and itspotential role in targeted therapy of lymphoma.Results In the transformation of lymphocytic malignancies, several signal pathways are involved. Among of them, thecAMP pathway has attracted increasing attention because of its apoptosis-inducing role in several lymphoma cells. cAMPpathway impairment is found to influence the prognosis of lymphoma. Targeted therapy to the cAMP pathway seems tobe a new direction for lymphoma treatment, aiming at restoring the cAMP function.Conclusions cAMP signal pathway has different effects on various lymphoma cells. cAMP analogues andphosphodiesterase 4B (PDE4B) inhibitors have potential clinical significance. However, many challenges remain inunderstanding the various roles of such agents.

  1. The Evolving Role of Medical Imaging in Lymphoma Management: The Clinician's Perspective.

    Science.gov (United States)

    Svoboda, Jakub; Schuster, Stephen J

    2012-01-01

    Hodgkin and non-Hodgkin lymphomas are a heterogeneous group of hematologic neoplasms which arise from malignant lymphocytes. Imaging plays an important role in management of lymphoma patients during diagnosis, staging, and response assessment. Functional imaging may also provide prognostic information and improve the ability to detect extranodal disease. This article provides an overview of the evolving role of various imaging techniques in lymphoma from the clinician's perspective. It serves as an introduction to the other articles in this issue that focus on specific areas of lymphoma imaging.

  2. Primary osseous Burkitt lymphoma with nodal and intracardiac metastases in a child

    Directory of Open Access Journals (Sweden)

    Lina Cadavid, MD

    2017-03-01

    Full Text Available Burkitt lymphoma (BL is the most frequent non-Hodgkin lymphoma in pediatric patients, accounting for approximately 34% of the cases of lymphoma in children. This subtype of non-Hodgkin lymphoma was first described in 1958 as a monoclonal proliferation of B cell lymphocytes. Cardiac involvement of BL in association with osseous compromise and lymphadenopathy is rare and poorly documented. We report a case of femur primary BL in an 8-year-old boy with metastatic cardiac involvement, retroperitoneal and iliofemoral lymphadenopathy, and hepatosplenomegaly. We highlight the diagnostic challenge in a patient with clinical nonspecific findings and systemic disease.

  3. International Lymphoma Epidemiology Consortium

    Science.gov (United States)

    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.

  4. Non-Hodgkin's Lymphoma

    Science.gov (United States)

    ... These include the lymphatic vessels, tonsils, adenoids, spleen, thymus and bone marrow. Occasionally, non-Hodgkin's lymphoma involves ... understand the possible link between pesticides and the development of non-Hodgkin's lymphoma. Older age. Non-Hodgkin's ...

  5. Clinical research on chemotherapy of recurrent and refractory non-Hodgkin lymphoma directed by ATP bioluminescence chemosensitivity assay in vitro%三磷酸腺苷生物荧光法体外药敏试验指导复发或难治性非霍奇金淋巴瘤化疗的临床研究

    Institute of Scientific and Technical Information of China (English)

    杨磊; 宋诸臣; 徐小红; 蒋斌; 彭春雷; 魏金芝

    2011-01-01

    Objective To investigate the clinical value of ATP bioluminescence tumor chemosensitivity assay (ATP-TCA) for recurrent and refractory non-Hodgkin lymphoma (NHL) specimens in vitro.Methods Thirty-four freshly taken recurrent and refractory NHL specimens were tested in vitro for cancer chemosensitivity by ATP-TCA.Results Drug sensitivity of NHL specimens had heterogeneity.Different drugs had different tumor growth inhibition ratio in vitro.Response rate (RR) of the patients receiving chemotherapy according to in vitro assay was 82.4 % (28/34),complete response rate (CR) was 52.9 % (18/34).In DICE group RR was 60.0 % (18/30),CR rate was 33.3 % (10/30).In GDP group RR was 62.3 % (33/53),CR rate was 26.4 % (14/53).In ATP-TCA group RR was significantly higher than those in DICE and GDP groups (x2 =3.93,P =0.047; x2 =3.98,P =0.046).Conclusion The results of ATP-TCA assay are correlated well with clinical treatment responses.The assay may be an important and useful method for individual-based chemotherapy of cancers.%目的 探讨三磷酸腺苷生物荧光法(ATP-TCA)体外药敏试验在复发或难治非霍奇金淋巴瘤( NHL)治疗中的临床应用价值.方法 应用ATP-TCA技术对复发或耐药淋巴瘤患者术后新鲜组织标本共34例进行体外药敏试验,观察用敏感药物化疗疗效.结果 淋巴瘤标本的药物敏感性具有个体差异性,不同化疗药物的体外抑瘤活性不同.药敏试验组总有效率(RR)为82.4%(28/34),完全缓解(CR)率为52.9%(18/34);DICE化疗组RR为60.0%( 18/30),CR率为33.3%(10/30);GDP化疗组RR为62.3%(33/53),CR率为26.4%(14/53).药敏试验组的RR与DICE组及GDP组相比,差异有统计学意义(x2=3.93,P=0.047; x2=3.98,P=0.046).结论 ATP-TCA体外药敏检测结果与临床治疗反应有很好的相关性,是开展肿瘤个体化化疗的一种重要的体外药物筛选方法.

  6. Fireclay Refractory Bricks

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiaohui

    2010-01-01

    @@ 1 Scope This standard specifies the classification,brand,shape,dimension,technical requirements,test methods,quality appraisal procedures,packing,marking,transportation,storage,and quality certificate of fireclay refractory bricks.

  7. On the aetiology of Hodgkin lymphoma.

    Science.gov (United States)

    Hjalgrim, Henrik

    2012-07-01

    decreased risk of EBV-positive Hodgkin lymphoma associated with HLA-A*01 and HLA-A*02 alleles, respectively. The increased risk of EBV-positive Hodgkin lymphoma after infectious mononucleosis was not explained by the two HLA class I alleles, but HLA-A*02 abrogated its effect. This led to an immunological model for EBV-positive Hodgkin lymphoma according to which the level of circulating EBV infected lymphocyte regulated by cytotoxic T-cell responses is a critical determinant of disease risk. Overall, the studies included in the thesis favour that EBV infection is causally associated with development of EBV-positive Hodgkin lymphoma. The circumstances under which the ubiquitous infection leads to lymphoma development must be explored in future studies, which should include analyses of gene-environment interactions. Meanwhile, the aetiology of EBV-negative Hodgkin lymphoma remains elusive. Possible clinical implications of the aetiological heterogeneity should also be considered and assessed.

  8. Ocular Adnexal Follicular Lymphoma

    DEFF Research Database (Denmark)

    Rasmussen, Peter K; Coupland, Sarah E; Finger, Paul T

    2014-01-01

    , and 31 (45%) had stage IIE lymphoma. Patients with disseminated lymphoma had stage IIIE (9 of 19 [47%]) and stage IV (10 of 19 [53%]) disease, whereas patients with a relapse of systemic lymphoma presented with stage IE (8 of 10 [80%]), stage IIE (1 of 10 [10%]), and stage IIIE (1 of 10 [10%]) disease...

  9. Brentuximab vedotin in children and adolescents with Hodgkin’s lymphoma and anaplastic large cell lymphoma – literature review and own experience

    Directory of Open Access Journals (Sweden)

    N. V. Myakova

    2016-01-01

    Full Text Available Despite significant advances in the treatment of lymphomas in children remain a small proportion of patients with refractory or recurrent disease. An effective approach to the treatment of such patients – not only is the second line chemotherapy, but the use of the new targeted therapies. An example of this approach is the use of brentuximab vedotin (antibody-drug conjugate directed to the CD30 in relapsed Hodgkin’s lymphoma and anaplastic large cell lymphoma. Literature review and own experience of using this drug in children are describes in this article.

  10. Plasmablastic lymphoma

    Science.gov (United States)

    Han, Xiao; Duan, Minghui; Hu, Lixing; Zhou, Daobin; Zhang, Wei

    2017-01-01

    Abstract Background: Plasmablastic lymphoma (PBL) is a B-cell malignancy associated with human immunodeficiency virus (HIV). PBL could also influence the HIV-negative patients. The study aimed to identify prognostic factors for survival among Chinese PBL patients. Materials and methods: Eligible patients from literature and Peking Union Medical College Hospital (PUMCH) were included in this study. Clinical characteristics and immunophenotypic data were extracted. Kaplan–Meier curve was used to describe the survival status. Cox regression was used for multivariate analysis. Results: A total of 60 Chinese PBL patients were included, including 54 patients from 36 published articles and 6 new patients that have not been reported. The median overall survival was 7 months (95% confidence interval 3.853–10.147 months). An overwhelming majority (79.31%) of the included cases were Ann Arbor stage IV patients. All the Chinese PBL patients were HIV-negative; 46.81% were Epstein-Barr virus-positive. CD38, CD138, or MUM1 was positively expressed in more than 80% of patients; CD20 expression was also found in 22.03% of cases. Kaplan–Meier curve revealed obvious differences in patient survival between patients in primary stages and advanced stages, as well as between patients with kidney involvement and those without kidney involvement. Cox regression analysis indicated that stage and age were 2 prognostic factors for patient survival. Conclusions: Advanced stage might be associated with poor prognosis among PBL HIV-negative patients in Chinese. PMID:28248855

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

    Science.gov (United States)

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

    2015-02-01

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

  12. Studies of lymphocyte growth and differentiation. Progress report, September 1, 1975--July 31, 1976

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, A.D.

    1976-01-01

    Studies were continued on ribonuclear protein synthesis and the assembly of ribosomes in resting and stimulated lymphocytes. We demonstrated the interdependency of protein synthesis and RNA synthesis in the formation and processing of nascent ribonuclear protein particles. We further explored lymphocyte nuclei in a cell-free system. By isolating lymphocyte chromatin we showed a direct effect of PHA on the ability of this nuclear structure to incorporate radioactivity into acid precipitable RNA. We returned to our previous studies on the delayed response of chronic lymphocytic leukemia (CLL) lymphocytes to PHA. We traced this alternate response identifying it as a characteristic of the CLL cell. The evidence questioned the generally accepted conclusion that CLL represents a B cell malignancy. We went on further to describe delayed reacting lymphocytes in the circulation of patients with nodular lymphoma and acute lymphoblastic leukemia (ALL). The ALL, unlike the lymphoma and CLL cells, showed a normal magnitude of response, even though it was delayed. We described the technique which might be employed as a diagnostic test for detecting abnormal lymphocytes in patients with lymphocytic lymphoma and leukemia and could help distinguish these diseases from benign lymphoid hyperplasia and other forms of non-lymphocytic leukemia.

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

    Science.gov (United States)

    2016-02-02

    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

  14. THE IMMUNOHISTOCHEMISTRY AND QUANTITATIVE MORPHOMETRIC STUDY OF MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT) LYMPHOMA IN STOMACH

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To invetigate the Immunohistochemistry characters and quantitative nmorphometric significance for the mucosa associated lymphoid tissue (MALT) lymphoma of stomach in 14 patients. Methods: The routine paraffin slides were cut, stained with H.E., and immunochemically by ABC method. The morphologic appearance of nuclei of lymphoma cells were measured with HPIAS-1000 color pathology picture analysis system. Results of the 14 cases, 9 was centrocyte like (CCL) cell lymphoma, 2 CCL with large cell lymphoma, 1 small no cleaved cell lymphoma, 1 large no cleaved cell lymphoma, 1 T immunoblastic malignant lymphoma. The morphologic measurement results showed that there were great significant differences (P<0.001) for the 15 items of morphology parameters between the nuclei of MALT lymphoma cells and those of normal control lymphocytes in stomach. There were great significance differences (P<0.001) or significance (P<0.05) for the most of the 15 items of morphologic parameters of nuclei among the 5 types of MALT lymphoma. Especially, that the values of area, circumference, equivalent diameter, area volume, circumference volume, long diameter, short diameter, practical area were increasing as the malignant degree of classification was rising, which reflect the increasing malignancy of the tumor. Conclusion: It was suggested that with the quantitative morphology measurement method, man could make accurate diagnosis for MALT lymphoma. It offered us a new method to make the diagnosis, so that it had significance. It might be also practicable with morphology measurement method to make the sub classification of MALT lymphoma.

  15. Skin fragility syndrome in a cat with multicentric follicular lymphoma.

    Science.gov (United States)

    Crosaz, Odile; Vilaplana-Grosso, Federico; Alleaume, Charline; Cordonnier, Nathalie; Bedu-Leperlier, Anne-Sophie; Marignac, Geneviève; Hubert, Blaise; Rosenberg, Dan

    2013-10-01

    An 11-year-old, spayed female domestic shorthair cat was presented for a right flank wound. On clinical examination, a single non-painful skin tear lesion with irregular edges was detected. During the examination, star-shaped cigarette paper-like skin lesions appeared spontaneously. An abdominal mass was also palpated. Feline skin fragility syndrome (FSFS) was suspected and a multicentric lymphoma was diagnosed by fine needle aspiration. The cat's condition declined and it died spontaneously. Post-mortem examination confirmed the diagnosis of lymphoma. Neoplastic lymphocytes were not observed in the skin. Histological analysis of the skin was consistent with the morphological aspects of FSFS. A possible direct link between the two conditions remains a matter of speculation, but this case report provides the first description of FSFS associated with multicentric follicular lymphoma. Thus, multicentric follicular lymphoma should be considered as a differential diagnosis in cats presenting with FSFS.

  16. The clinical features, management and prognosis of primary and secondary indolent lymphoma of the bone: a retrospective study of the International Extranodal Lymphoma Study Group (IELSG #14 study).

    Science.gov (United States)

    Govi, Silvia; Christie, David; Mappa, Silvia; Marturano, Emerenziana; Bruno-Ventre, Marta; Messina, Carlo; Medina, Elías A Gracia; Porter, David; Radford, John; Heo, Dae Seog; Park, Yeon; Pro, Barbara; Jayamohan, Jayasingham; Pavlakis, Nick; Zucca, Emanuele; Gospodarowicz, Mary; Ferreri, Andrés J M

    2014-08-01

    Indolent lymphomas primarily involving the skeleton (iPBL) represent management and prognosis have not been previously described. Patients with primary and secondary iPBL were selected from an international database of 499 patients with a histopathological diagnosis of non-Hodgkin lymphoma and skeleton involvement, and clinical features, management and prognosis were analyzed. Twenty-six (5%) patients had an iPBL. Ten patients had small lymphocytic lymphoma, 10 had follicular lymphoma and six had lymphoplasmacytic lymphoma. Eleven patients had limited stage and 15 had advanced disease. The overall response rate was 73% (95% confidence interval [CI] = 57-89%). Median follow-up was 58 months, and the 5- and 10-year progression-free survival (PFS) rates were 37 ± 10% and 25 ± 12%, respectively. Nine patients are alive, with 5- and 10-year overall survival (OS) rates of 46 ± 10% and 29 ± 11%, respectively. Patients with small lymphocytic lymphoma showed significantly better outcome than patients with follicular lymphoma. Performance status and stage of disease were independently associated with OS. The prognosis of patients with primary bone lymphoplasmacytic or follicular lymphoma was less favorable.

  17. Cholecalciferol in Improving Survival in Patients With Newly Diagnosed Cancer With Vitamin D Insufficiency

    Science.gov (United States)

    2016-12-20

    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

  18. Efficacy of lenalidomide in patients with chronic lymphocytic leukemia with high-risk cytogenetics.

    Science.gov (United States)

    Sher, Taimur; Miller, Kena C; Lawrence, David; Whitworth, Amy; Hernandez-Ilizaliturri, Francisco; Czuczman, Myron S; Miller, Austin; Lawrence, William; Bilgrami, Syed Ali; Sood, Raman; Wood, Margaret T; Block, Annemarie W; Lee, Kelvin; Chanan-Khan, Asher Alban

    2010-01-01

    Patients with chronic lymphocytic lymphoma (CLL) with high-risk cytogenetics [del(11q)(q22.3) or del(17p)(p13.1)] have limited therapeutic options and their prognosis remains poor. This analysis was conducted to determine the clinical activity of lenalidomide in patients with high-risk disease. Relapsed/refractory patients with CLL enrolled in a phase II clinical trial who had del(11q)(q22.3) or del(17p)(p13.1) were included in this analysis. Patients received single agent lenalidomide for 21 days of the 4 week treatment cycle. The overall response rate among patients with high-risk cytogenetics was 38%, with 19% of patients achieving a complete response. Median progression-free survival was 12.1 months, which is higher than demonstrated with other agents in comparable patient populations. In addition, the estimated 2-year survival probability was 58%, demonstrating that the responses achieved with lenalidomide are durable, even in patients with CLL with high-risk disease with poor risk cytogenetics.

  19. Harnessing the immune system through programmed death-1 blockade in the management of Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Oncale MB

    2017-02-01

    Full Text Available Melody B Oncale, Hossein Maymani, Loretta J Nastoupil Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Immunotherapy is a rapidly evolving therapeutic option in the treatment of lymphoma. Neoplastic cells evade immune recognition through the programmed death (PD-1/PD-ligand immune checkpoint pathway. Several novel agents have been developed to restore the immune system’s ability to recognize and destroy cancer cells. Nivolumab and pembrolizumab are two anti-PD-1 antibodies that have demonstrated success in the treatment of refractory Hodgkin lymphoma. Harnessing the immune system’s ability to target neoplastic cells, ideally without the use of cytotoxic chemotherapeutic agents, is one way in which these novel agents are changing the therapeutic landscape in the treatment of lymphomas. Here, we review the emerging data regarding checkpoint inhibitors in the management of Hodgkin lymphoma, the unique adverse effects encountered with the use of these agents, and a practical approach to the management of these adverse effects. Additionally, we discuss upcoming trials that will further assess the promising future developments of checkpoint inhibition in the treatment of not only Hodgkin lymphoma but also other B cell lymphomas and myeloma. These agents offer immense promise of a future where many lymphomas can be treated without the toxic effects of chemotherapeutic agents. Keywords: Hodgkin lymphoma, programmed death-1, nivolumab, pembrolizumab, lymphoma

  20. Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Benjamin Arthurs, MD

    2017-01-01

    Full Text Available We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus. Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

  1. Prevalence and clinical manifestation of lymphomas in North Eastern Nigeria

    Directory of Open Access Journals (Sweden)

    Mava Yakubu

    2015-01-01

    Full Text Available BACKGROUND: Lymphomas are one of the commonest childhood malignancies. Due to varied clinical features many patients are misdiagnosed and treated for other diseases. It is imperative to keep health workers informed about the current trend of lymphomas in northeastern Nigeria to facilitate prompt diagnosis and treatment. OBJECTIVE: To evaluate the extent of lymphomas at presentation and to define the pattern of presentation in relation to gender and site. MATERIALS AND METHODS: Retrospective analysis of cases of lymphomas over a 15 year period was conducted. Structured questionnaires were used to document demographic characteristics and clinical features. The non-Hodgkin's lymphoma (NHL and Hodgkin's lymphoma (HL cases were categorized using standard classification schemes. Data were analyzed using the Statistical Package for Social Sciences (SPSS software version 16, Illinois, Chicago, USA. Spearman's correlation and Student's t-test were applied where appropriate. A P value < 0.05 was considered significant. RESULTS: Fifty cases of lymphoma, 10 (20% belong to HL and 40 (80% belong to NHL. Lymphoma is common in male, though the male to female preponderance was not significant in both the cases (P = 0.107 and 0.320, respectively. Maxilla was the commonest site of primary malignancy (36% and late presentation of patients were observed. New trend was noticed, the NHL patients present commonly with severe symptoms than HL (P = 0.038. HL was dominated by lymphocytic predominant type, while NHL was dominated by the small non cleaved cells (Burkitt's lymphoma (70%. CONCLUSION: Childhood lymphoma in northeastern Nigeria has a slight shift in varied clinical presentation in favor of NHL. Patients in this study had late presentation.

  2. The cost effectiveness of treating paediatric cancer in low-income and middle-income countries: a case-study approach using acute lymphocytic leukaemia in Brazil and Burkitt lymphoma in Malawi.

    Science.gov (United States)

    Bhakta, Nickhill; Martiniuk, Alexandra L C; Gupta, Sumit; Howard, Scott C

    2013-02-01

    Approximately 90% of children with cancer reside in low-income and middle-income countries (LMIC) where healthcare resources are scarce and allocation decisions difficult. The cost effectiveness of treating childhood cancers in these settings is unknown. The objective of the present work was to determine cost-effectiveness thresholds for common paediatric cancers using acute lymphoblastic leukaemia (ALL) in Brazil and Burkitt lymphoma (BL) in Malawi as examples. Disability-adjusted life years (DALYs) prevented by treatment were compared to the gross domestic product (GDP) per capita of each country to define cost-effectiveness thresholds using WHO-CHOICE ('CHOosing Interventions that are Cost-Effective') guidelines. The case examples were selected due to the data available and because ALL and BL both have the potential to yield significant health gains at a low cost per patient treated. The key findings were as follows: the 3:1 cost/DALY prevented to GDP/capita ratio for ALL in Brazil was US $771,225; expenditures below this threshold were cost effective. Costs below US $257,075 (1:1 ratio) were considered very cost effective. Analogous thresholds for BL in Malawi were US $42,729 and US $14,243. Actual costs were far less. In Brazil, US $16,700 was spent to treat each patient while in Malawi total drug costs were less than US $50 per child. In summary, treatment of certain paediatric cancers in LMIC is very cost effective. Future research should evaluate actual treatment and infrastructure expenditures to help guide policymakers.

  3. Alemtuzumab in refractory Sézary syndrome*

    Science.gov (United States)

    Reifs, Carmen María Alcántara; Salido-Vallejo, Rafael; Garnacho-Saucedo, Gloria María; la Corte-Sánchez, Sofía De; González-Menchen, Alberto; García-Nieto, Antonio Vélez

    2016-01-01

    Sézary syndrome is a primary cutaneous T-cell lymphoma characterized by the triad of erythroderma, lymphadenopathy and circulating atypical cells. The emergence of new molecular targets has enabled the development of drugs such as alemtuzumab, an anti-CD52 monoclonal antibody, which has shown promising results in the treatment of this entity. We report the case of a 70-year-old male with refractory Sézary syndrome in whom treatment with alemtuzumab achieved an 80% skin lesion clearance with complete haematologic and radiologic response. The treatment was discontinued after 4 months due to adverse effects, with the patient showing a sustained response without disease progression after 13 months of follow-up. PMID:27828640

  4. Malignant lymphoma of the conjunctiva

    DEFF Research Database (Denmark)

    Kirkegaard, Marina M; Coupland, Sarah E; Prause, Jan U;

    2015-01-01

    Conjunctival lymphomas constitute 25% of all ocular adnexal lymphomas. The majority are B-cell non-Hodgkin lymphomas (NHLs) (98%), whereas conjunctival T-cell NHLs are rare (2%). The most frequent subtype of conjunctival B-cell lymphoma is extranodal marginal zone lymphoma (EMZL; 81%), followed b...

  5. Lenalidomide and Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Pilar González-Rodríguez

    2013-01-01

    Full Text Available Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS and tumor flare reaction (TFR, that make its management different from other hematologic malignancies.

  6. RHI Refractories Opens Dalian Plant

    Institute of Scientific and Technical Information of China (English)

    Stefan Pirker

    2004-01-01

    @@ End of November the opening ceremony of the RHI Refractories Dalian plant took place in the presence of 250 guests from China and Europe. RHI Refractories welcomed highly official guests from the Dalian City and the Dalian Development Area, the Supervisory Board of RHI, the company's biggest shareholder, the Board of Management, representatives of customers in China as well as Professors of China's refractory academic field. The ceremony' s highlight was the speech of Professor Zhong Xiangchong from Zhengzhou University, member of the China Academy of Science, who pointed out RHI Refractories' long and successful history of refractory innovations during the last decades and the future possibilities of collaboration with RHI Refractories.

  7. Peripheral T-cell lymphomas of follicular helper T-cell type frequently display an aberrant CD3(-/dim)CD4(+) population by flow cytometry: an important clue to the diagnosis of a Hodgkin lymphoma mimic.

    Science.gov (United States)

    Alikhan, Mir; Song, Joo Y; Sohani, Aliyah R; Moroch, Julien; Plonquet, Anne; Duffield, Amy S; Borowitz, Michael J; Jiang, Liuyan; Bueso-Ramos, Carlos; Inamdar, Kedar; Menon, Madhu P; Gurbuxani, Sandeep; Chan, Ernest; Smith, Sonali M; Nicolae, Alina; Jaffe, Elaine S; Gaulard, Philippe; Venkataraman, Girish

    2016-10-01

    Nodal follicular helper T-cell-derived lymphoproliferations (specifically the less common peripheral T-cell lymphomas of follicular type) exhibit a spectrum of histologic features that may mimic reactive hyperplasia or Hodgkin lymphoma. Even though angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma of follicular type share a common biologic origin from follicular helper T-cells and their morphology has been well characterized, flow cytometry of peripheral T-cell lymphomas of follicular type has not been widely discussed as a tool for identifying this reactive hyperplasia/Hodgkin lymphoma mimic. We identified 10 peripheral T-cell lymphomas of follicular type with available flow cytometry data from five different institutions, including two cases with peripheral blood evaluation. For comparison, we examined flow cytometry data for 8 classical Hodgkin lymphomas (including 1 lymphocyte-rich classical Hodgkin lymphoma), 15 nodular lymphocyte predominant Hodgkin lymphomas, 15 angioimmunoblastic T-cell lymphomas, and 26 reactive nodes. Lymph node histology and flow cytometry data were reviewed, specifically for the presence of a CD3(-/dim)CD4(+) aberrant T-cell population (described in angioimmunoblastic T-cell lymphomas), besides other T-cell aberrancies. Nine of 10 (90%) peripheral T-cell lymphomas of follicular type showed a CD3(-/dim)CD4(+) T-cell population constituting 29.3% (range 7.9-62%) of all lymphocytes. Five of 10 (50%) had nodular lymphocyte predominant Hodgkin lymphoma or lymphocyte-rich classical Hodgkin lymphoma-like morphology with scattered Hodgkin-like cells that expressed CD20, CD30, CD15, and MUM1. Three cases had a nodular growth pattern and three others exhibited a perifollicular growth pattern without Hodgkin-like cells. Epstein-Barr virus was positive in 1 of 10 cases (10%). PCR analysis showed clonal T-cell receptor gamma gene rearrangement in all 10 peripheral T-cell lymphomas of follicular type. By flow cytometry, 11 of 15 (73

  8. Infectious agents as causes of non-Hodgkin lymphoma.

    Science.gov (United States)

    Engels, Eric A

    2007-03-01

    Among exposures presently viewed as possible etiologic factors in non-Hodgkin lymphoma (NHL), infections are close to being regarded as established causes. Infectious agents causing NHL can be classified, according to mechanism, into three broad groups. First, some viruses can directly transform lymphocytes. Lymphocyte-transforming viruses include Epstein Barr virus (linked to Burkitt's lymphoma, NHLs in immunosuppressed individuals, and extranodal natural killer/T-cell NHL), human herpesvirus 8 (primary effusion lymphoma), and human T lymphotropic virus type I (adult T-cell leukemia/lymphoma). Second, human immunodeficiency virus is unique in causing profound depletion of CD4+ T lymphocytes, leading to acquired immunodeficiency syndrome and an associated high risk for some NHL subtypes. Third, recent evidence suggests that some infections increase NHL risk through chronic immune stimulation. These infections include hepatitis C virus as well as certain bacteria that cause chronic site-specific inflammation and seem to increase risk for localized mucosa-associated lymphoid tissue NHLs. Establishing that an infectious agent causes NHL depends on showing that the agent is present in persons with NHL as well as laboratory experiments elucidating the mechanisms involved. Only epidemiologic studies can provide evidence that infection is actually a risk factor by showing that infection is more frequent in NHL cases than in controls. Given the range of mechanisms by which infections could plausibly cause NHL and our growing molecular understanding of this malignancy, this field of research deserves continued attention.

  9. Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia.

    OpenAIRE

    Yang, W. I.; Zukerberg, L R; Motokura, T.; Arnold, A.; Harris, N. L.

    1994-01-01

    Mantle cell (centrocytic) lymphoma (MCL) and occasional cases of B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (B-SLL/CLL) show a characteristic translocation, t(11:14)(q13;q32) involving rearrangement of the Bcl-1 region. Recently it was shown that the key Bcl-1 region oncogene is cyclin D1/PRAD1; cyclin D1 mRNA was shown to be overexpressed in cases of MCL. We examined cyclin D1 protein expression in low-grade B-cell lymphomas and reactive lymphoid hyperplasias using polycl...

  10. XK469R in Treating Patients With Refractory Hematologic Cancer

    Science.gov (United States)

    2013-02-07

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); 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 With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); 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 Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Refractory peptic ulcer disease.

    Science.gov (United States)

    Napolitano, Lena

    2009-06-01

    Refractory PUD is a diagnostic and therapeutic challenge. Optimal management of severe or refractory PUD requires a multidisciplinary team approach, using primary care providers, gastroenterologists, and general surgeons. Medical management has become the cornerstone of therapy. Identification and eradication of H pylori infection combined with acid reduction regimens can heal ulceration and also prevent recurrence. Severe, intractable or recurrent PUD and associated complications mandates a careful and methodical evaluation and management strategy to determine the potential etiologies and necessary treatment (medical or surgical) required.

  12. Lymphoma in acquired generalized lipodystrophy.

    Science.gov (United States)

    Brown, Rebecca J; Chan, Jean L; Jaffe, Elaine S; Cochran, Elaine; DePaoli, Alex M; Gautier, Jean-Francois; Goujard, Cecile; Vigouroux, Corinne; Gorden, Phillip

    2016-01-01

    Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression.

  13. Dynamic Testing of Gasifier Refractory

    Energy Technology Data Exchange (ETDEWEB)

    Michael D. Mann; Wayne S. Seames; Devdutt Shukla; Xi Hong; John P. Hurley

    2005-12-01

    The University of North Dakota (UND) Chemical Engineering Department in conjunction with the UND Energy & Environmental Research Center (EERC) have initiated a program to examine the combined chemical (reaction and phase change) and physical (erosion) effects experienced by refractory materials under slagging coal gasification conditions. The goal of this work is to devise a mechanism of refractory loss under these conditions. The controlled-atmospheric dynamic corrodent application furnace (CADCAF) was utilized to simulate refractory/slag interactions under dynamic conditions that more realistically simulate the environment in a slagging coal gasifier than any of the static tests used previously by refractory manufacturers and researchers. High-alumina and high-chromia refractory bricks were tested using slags obtained from two solid fuel gasifiers. Testing was performed at 1475 C in a reducing atmosphere (2% H{sub 2} in N{sub 2}) The CADCAF tests show that high-chrome refractories have greater corrosion resistance than high-aluminum refractories; coal slag readily diffuses into the refractory through its grain boundaries; the refractory grains are more stable than the matrix in the tests, and the grains are the first line of defense against corrosion; calcium and alkali in the slag are more corrosive than iron; and silicon and calcium penetrate the deepest into the refractory. The results obtained from this study are preliminary and should be combined with result from other research programs. In particular, the refractory corrosion results from this study should be compared with refractories removed from commercial gasifiers.

  14. Refractory Minerals in Henan Province

    Institute of Scientific and Technical Information of China (English)

    JIN Qinguo; LI Jing; LIU Jiehua; LIU Yanjun

    2004-01-01

    Henan province is very rich in refractory minerals of many varieties including silica, dolomite, graphite,pearlite, sepiolite, olivine, and sillimanite group minerals, besides the abundant reserves of fireclay and bauxite,which lay a good foundation for the development of the refractories industry of the province. The paper introduces the reserves, distribution and character of the refractory minerals in Henan province.

  15. Monoamine oxidase A is highly expressed in classical Hodgkin lymphoma.

    Science.gov (United States)

    Li, Pei Chuan; Siddiqi, Imran N; Mottok, Anja; Loo, Eric Y; Wu, Chieh Hsi; Cozen, Wendy; Steidl, Christian; Shih, Jean Chen

    2017-10-01

    Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines and produces H2 O2 . It facilitates the progression of gliomas and prostate cancer, but its expression and functional relevance have not been studied in lymphoma. Here, we evaluated MAOA in 427 cases of Hodgkin and non-Hodgkin lymphoma and in a spectrum of reactive lymphoid tissues by immunohistochemistry on formalin-fixed, paraffin-embedded specimens. MAOA was expressed by Hodgkin Reed-Sternberg (HRS) cells in the majority of classical Hodgkin lymphomas (cHLs) (181/241; 75%), with 34.8% showing strong expression. Weak MAOA was also noted in a minority of primary mediastinal large B-cell lymphomas (8/47; 17%) and in a mediastinal gray-zone lymphoma. In contrast, no MAOA was found in non-neoplastic lymphoid tissues, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL; 0/8) or any other non-Hodgkin lymphomas studied (0/123). MAOA was more common in Epstein-Barr virus (EBV)-negative compared to EBV-positive cHL (p Hodgkin-lymphoma-derived cell lines did not. The MAOA inhibitor clorgyline reduced the growth of L1236 cells and U-HO1 cells, and shRNA knockdown of MAOA reduced the growth of L1236 cells. Conversely, ectopic overexpression of MAOA increased the growth of MAOA-negative HDLM2 cells. Combined treatment with clorgyline and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) was more effective in reducing cell growth than either regimen alone. In summary, MAOA is highly expressed in cHL and may reflect the distinct biology of this lymphoma. Further studies on the potential utility of MAOA as a diagnostic marker and therapeutic target are warranted. 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.

  16. Lymphoma Microenvironment and Immunotherapy.

    Science.gov (United States)

    Xu, Mina L; Fedoriw, Yuri

    2016-03-01

    Understanding of the lymphoma tumor microenvironment is poised to expand in the era of next-generation sequencing studies of the tumor cells themselves. Successful therapies of the future will rely on deeper appreciation of the interactions between elements of the microenvironment. Although the phenotypic, cytogenetic, and molecular characterization of tumor cells in lymphomas has progressed faster than most other solid organ tumors, concrete advancements in understanding the lymphoma microenvironment have been fewer. This article explores the composition of the lymphoma tumor microenvironment; its role in immune surveillance, evasion, and drug resistance; and its potential role in the development of targeted therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Bilateral primary breast lymphoma

    Institute of Scientific and Technical Information of China (English)

    Jung Im Yi; Byung Joo Chae; Ja Seong Bae; Bong Joo Kang; Ahwon Lee; Byung Joo Song; Sang Seol Jung

    2010-01-01

    @@ Primary breast lymphoma (PBL) is rare, accounting for 0.04%-0.50% of breast malignancies and 1.7% of extranodal lymphoma.1,2 The originally described diagnostic criteria for PBL2 remains the standard definition for this disease. These criteria are breast location as the clinical site of presentation, absence of history of previous lymphoma or evidence of widespread disease at diagnosis, close association of lymphoma with breast tissue in pathologic specimens, and involvement of ipsilateral lymph nodes if they develop simultaneously with PBL.

  18. Primary gastrointestinal lymphoma

    Institute of Scientific and Technical Information of China (English)

    Prasanna Ghimire; Guang-Yao Wu; Ling Zhu

    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.

  19. Bilateral Primary Intraocular Lymphoma

    Directory of Open Access Journals (Sweden)

    Mehrdad Karimi

    2011-01-01

    Full Text Available Purpose: To report a case of bilateral primary intraocular lymphoma. Case report: A 33-year-old man presented with bilateral blurred vision since two years ago. Examination revealed large keratic precipitates, anterior chamber reaction, posterior subcapsular cataracts, and vitreous infiltration. After a short trial of topical and periocular steroids, diagnostic 25-gauge pars plana vitrectomy was performed and cytologic evaluation of the aspirate confirmed a diagnosis of intraocular lymphoma. The patient was subsequently managed with intravitreal methotrexate in both eyes and responded favorably. Central nervous system workup for lymphoma was negative. Conclusion: Primary intraocular lymphoma should be considered in young adults suffering from chronic recalcitrant panuveitis.

  20. Tissue-Specific Enrichment of Lymphoma Risk Loci in Regulatory Elements.

    Science.gov (United States)

    Hayes, James E; Trynka, Gosia; Vijai, Joseph; Offit, Kenneth; Raychaudhuri, Soumya; Klein, Robert J

    2015-01-01

    Though numerous polymorphisms have been associated with risk of developing lymphoma, how these variants function to promote tumorigenesis is poorly understood. Here, we report that lymphoma risk SNPs, especially in the non-Hodgkin's lymphoma subtype chronic lymphocytic leukemia, are significantly enriched for co-localization with epigenetic marks of active gene regulation. These enrichments were seen in a lymphoid-specific manner for numerous ENCODE datasets, including DNase-hypersensitivity as well as multiple segmentation-defined enhancer regions. Furthermore, we identify putatively functional SNPs that are both in regulatory elements in lymphocytes and are associated with gene expression changes in blood. We developed an algorithm, UES, that uses a Monte Carlo simulation approach to calculate the enrichment of previously identified risk SNPs in various functional elements. This multiscale approach integrating multiple datasets helps disentangle the underlying biology of lymphoma, and more broadly, is generally applicable to GWAS results from other diseases as well.

  1. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Afonso José Pereira Cortez

    2011-02-01

    Full Text Available BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not

  2. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    Science.gov (United States)

    Cortez, Afonso José Pereira; Dulley, Frederico Luiz; Saboya, Rosaura; Mendrone Júnior, Alfredo; Amigo Filho, Ulisses; Coracin, Fabio Luiz; Buccheri, Valéria; Linardi, Camila da Cruz Gouveia; Ruiz, Milton Artur; Chamone, Dalton de Alencar Fischer

    2011-01-01

    Background Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. Objectives To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. Methods A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. Results The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. Conclusion Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported

  3. Status epilepticus: Refractory and super-refractory.

    Science.gov (United States)

    Dubey, Deepanshu; Kalita, Jayantee; Misra, Usha K

    2017-01-01

    Status epilepticus (SE) is an important neurological emergency. It is defined as seizures lasting for 5 minutes or more or recurrent seizures without recovery of consciousness to baseline between the attacks. Refractory SE (RSE) is defined as SE persisting despite sufficient dose of benzodiazepines and at least one antiepileptic drug (AED), irrespective of time. Super refractory SE (SRSE) is defined as SE that continues for 24 hours or more after the use of anesthetic therapy, including cases that recur on weaning of the anesthestic agent. RSE occurs in 23%-48% of the patients and SRSE in approximately 22% of the patients with SE. In general, RSE occurs in patients with new-onset seizures rather than in patients with chronic epilepsy. The etiology of RSE in developing countries is dominated by central nervous system (CNS) infections and head injury compared to stroke and drug withdrawal in the developed countries. The treatment of RSE and SRSE is not evidence based. Following benzodiazepines, the second line antiepileptic drugs include sodium valproate, phenytoin, levetiracetam, and anesthetic drugs such as midazolam, phenobarbital, and propofol. Most intravenous anesthetic drugs produce hypotension and respiratory suppression; therefore, patients with RSE are managed in intensive care units (ICUs). In RSE patients, electroencephalogram (EEG) burst suppression with interburst interval of 2-20 s or even flat EEG has been tried. Recently, concerns have been raised on the safety of burst suppression in RSE and SRSE. The paucity of ICUs in developing countries limits the use of these management protocols. There is a need to explore intravenous AEDs with safer cardiovascular and respiratory profile for the management of SE.

  4. Renal involvement in non-Hodgkin lymphoma: proven by renal biopsy.

    Science.gov (United States)

    Li, Shi-Jun; Chen, Hui-Ping; Chen, Ying-Hua; Zhang, Li-hua; Tu, Yuan-Mao; Liu, Zhi-hong

    2014-01-01

    To determine the spectrum of renal lesions in patients with kidney involvement in non-Hodgkin's lymphoma (NHL) by renal biopsy. The clinical features and histological findings at the time of the renal biopsy were assessed for each patient. We identified 20 patients with NHL and renal involvement, and the diagnosis of NHL was established following the kidney biopsy in 18 (90%) patients. The types of NHL include the following: chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 8), diffuse large B-cell lymphoma (n = 4), T/NK cell lymphoma (n = 3), lymphoplasmacytic lymphoma (n = 2), cutaneous T-cell lymphoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1) and mantle cell lymphoma (n = 1). All presented with proteinuria, and 15 patients had impaired renal function. The pathological findings included (1) membranoproliferative glomerulonephritis-like pattern in seven patients; (2) crescent glomerulonephritis in four; (3) minimal-change disease in three, and glomeruli without specific pathological abnormalities in three; (4) intraglomerular large B-cell lymphoma in one; (5) intracapillary monoclonal IgM deposits in one; (6) primary diffuse large B-cell lymphoma of the kidneys in one; and (7) lymphoma infiltration of the kidney in eight patients. A wide spectrum of renal lesions can be observed in patients with NHL, and NHL may be first proven by renal biopsies for evaluation of kidney injury or proteinuria. Renal biopsy is necessary to establish the underlying cause of renal involvement in NHL.

  5. Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide

    NARCIS (Netherlands)

    Enting, Roeline; Demopoulos, A; DeAngelis, LM; Abrey, LE

    2004-01-01

    The authors evaluated the efficacy of a combination of rituximab and temozolomide for recurrent or refractory primary CNS lymphoma (PCNSL). Fifteen patients with a median age of 69 years had a 53% objective response rate with acceptable toxicity. Median overall survival is 14 months and median progr

  6. Autologous stem cell transplantation in treatment of aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke

    2002-01-01

    There is no doubt that autologous stem cell transplantation is useful for patients with relapsed aggressive non-Hodgkin's lymphoma if they are responsive to the chemotherapy given before the transplantation. A small subset of patients with primary refractory disease still profits from this high dose

  7. Refractory headache: classification and nomenclature.

    Science.gov (United States)

    Levin, Morris

    2008-06-01

    There are a number of reasons to attempt to define and classify refractory headache disorders. Particularly important are the potential benefits in the areas of research, treatment, and medical cost reimbursement. There are challenges in attempting to classify refractory forms of headaches, including the lack of biological or other objective markers and a lack of consensus among practitioners as to what qualifies as refractoriness, or even if a separate category for refractory migraine and other refractory headaches needs to be established. A definition of refractory migraine has been proposed by Schulman et al in this issue ("Defining Refractory Migraine [RM] and Refractory Chronic Migraine [RCM]: Proposed Criteria for the Refractory Headache Special Interests Section of the American Headache Society"), which should be tested for validity and usefulness. It seems reasonable to consider adding this defined syndrome to the International Classification of Headache Disorders, second edition (ICHD-II). In this article, options for adding refractory headache syndromes to the ICHD are discussed with pros and cons for each. Two "best" options for adding the disorder "refractory migraine" to the ICHD are presented along with an illustrative case example.

  8. [Molecular abnormalities in lymphomas].

    Science.gov (United States)

    Delsol, G

    2010-11-01

    Numerous molecular abnormalities have been described in lymphomas. They are of diagnostic and prognostic value and are taken into account for the WHO classification of these tumors. They also shed some light on the underlying molecular mechanisms involved in lymphomas. Overall, four types of molecular abnormalities are involved: mutations, translocations, amplifications and deletions of tumor suppressor genes. Several techniques are available to detect these molecular anomalies: conventional cytogenetic analysis, multicolor FISH, CGH array or gene expression profiling using DNA microarrays. In some lymphomas, genetic abnormalities are responsible for the expression of an abnormal protein (e.g. tyrosine-kinase, transcription factor) detectable by immunohistochemistry. In the present review, molecular abnormalities observed in the most frequent B, T or NK cell lymphomas are discussed. In the broad spectrum of diffuse large B-cell lymphomas microarray analysis shows mostly two subgroups of tumors, one with gene expression signature corresponding to germinal center B-cell-like (GCB: CD10+, BCL6 [B-Cell Lymphoma 6]+, centerine+, MUM1-) and a subgroup expressing an activated B-cell-like signature (ABC: CD10-, BCL6-, centerine-, MUM1+). Among other B-cell lymphomas with well characterized molecular abnormalies are follicular lymphoma (BCL2 deregulation), MALT lymphoma (Mucosa Associated Lymphoid Tissue) [API2-MALT1 (mucosa-associated-lymphoid-tissue-lymphoma-translocation-gene1) fusion protein or deregulation BCL10, MALT1, FOXP1. MALT1 transcription factors], mantle cell lymphoma (cycline D1 [CCND1] overexpression) and Burkitt lymphoma (c-Myc expression). Except for ALK (anaplastic lymphoma kinase)-positive anaplastic large cell lymphoma, well characterized molecular anomalies are rare in lymphomas developed from T or NK cells. Peripheral T cell lymphomas not otherwise specified are a heterogeneous group of tumors with frequent but not recurrent molecular abnormalities

  9. Occupational exposure to ethylene oxide and risk of lymphoma.

    Science.gov (United States)

    Kiran, Sibel; Cocco, Pierluigi; Mannetje, Andrea't; Satta, Giannina; D'Andrea, Ileana; Becker, Nikolaus; de Sanjosé, Silvia; Foretova, Lenka; Staines, Anthony; Kleefeld, Silke; Maynadié, Marc; Nieters, Alexandra; Brennan, Paul; Boffetta, Paolo

    2010-11-01

    Ethylene oxide, a high-volume commodity, is an established human carcinogen, although the relevant epidemiologic evidence is limited. We explored the association between occupational exposure to ethylene oxide and risk of lymphoma in a case-control study, including 2347 lymphoma cases first diagnosed in 1998-2004 and 2463 controls, from 6 European countries. The diagnosis of lymphoma was based on the 2001 World Health Organization Classification of lymphoma. Occupational exposure to ethylene oxide was retrospectively assessed by industrial hygienists and occupational physicians based on detailed self-reported information. We modeled risk of lymphoma with unconditional logistic regression analysis as a function of various exposure measures, adjusting for age, sex, and participating center. Thirty-one cases and 27 controls (1.2% of the total study population) were defined as ever having been exposed to ethylene oxide (odds ratio = 1.3 [95% confidence interval [CI] = 0.7-2.1]). Lymphoma risk showed a 4.3-fold increase associated with medium-high frequency of exposure to ethylene oxide (95% CI = 1.4-13). Among major subtypes, chronic lymphocytic leukemia was consistently associated with ethylene oxide exposure, related in a dose-response manner to probability, frequency, and duration of exposure, as well as to cumulative exposure and (less definitively) with exposure intensity. Our results add to the evidence that ethylene oxide is a human carcinogen.

  10. Sarcoidosis Occurring After Lymphoma

    Science.gov (United States)

    London, Jonathan; Grados, Aurélie; Fermé, Christophe; Charmillon, Alexandre; Maurier, François; Deau, Bénédicte; Crickx, Etienne; Brice, Pauline; Chapelon-Abric, Catherine; Haioun, Corinne; Burroni, Barbara; Alifano, Marco; Le Jeunne, Claire; Guillevin, Loïc; Costedoat-Chalumeau, Nathalie; Schleinitz, Nicolas; Mouthon, Luc; Terrier, Benjamin

    2014-01-01

    Abstract Sarcoidosis is a granulomatous disease that most frequently affects the lungs with pulmonary infiltrates and/or bilateral hilar and mediastinal lymphadenopathy. An association of sarcoidosis and lymphoproliferative disease has previously been reported as the sarcoidosis-lymphoma syndrome. Although this syndrome is characterized by sarcoidosis preceding lymphoma, very few cases of sarcoidosis following lymphoma have been reported. We describe the clinical, biological, and radiological characteristics and outcome of 39 patients presenting with sarcoidosis following lymphoproliferative disease, including 14 previously unreported cases and 25 additional patients, after performing a literature review. Hodgkin lymphoma and non-Hodgkin lymphoma were equally represented. The median delay between lymphoma and sarcoidosis was 18 months. Only 16 patients (41%) required treatment. Sarcoidosis was of mild intensity or self-healing in most cases, and overall clinical response to sarcoidosis was excellent with complete clinical response in 91% of patients. Sarcoidosis was identified after a follow-up computerized tomography scan (CT-scan) or 18fluorodeoxyglucose-positron emission tomography/computerized tomography (18FDG-PET/CT) evaluation in 18/34 patients (53%). Sarcoidosis is therefore a differential diagnosis to consider when lymphoma relapse is suspected on a CT-scan or 18FDG-PET/CT, emphasizing the necessity to rely on histological confirmation of lymphoma relapse. PMID:25380084

  11. Diagnostic algorithm to differentiate lymphoma from inflammation in feline small intestinal biopsy samples.

    Science.gov (United States)

    Kiupel, M; Smedley, R C; Pfent, C; Xie, Y; Xue, Y; Wise, A G; DeVaul, J M; Maes, R K

    2011-01-01

    Differentiating between inflammatory bowel disease (IBD) and small intestinal lymphoma in cats is often difficult, especially when only endoscopic biopsy specimens are available for evaluation. However, a correct diagnosis is imperative for proper treatment and prognosis. A retrospective study was performed using surgical and endoscopic intestinal biopsy specimens from 63 cats with a history of chronic diarrhea or vomiting or weight loss. A diagnosis of lymphoma or inflammation was based on microscopic examination of hematoxylin and eosin (HE)-stained sections alone, HE-stained sections plus results of immunohistochemical labeling (IHC) for CD3e and CD79a, and HE staining, immunophenotyping, and polymerase chain reaction (PCR) results for B and/or T cell clonality. In addition, various histomorphologic parameters were evaluated for significant differences between lymphoma and IBD using Fisher's exact test. The sensitivity and specificity of each parameter in the diagnosis of lymphoma were also determined. Results of Bayesian statistical analysis demonstrated that combining histologic evaluation of small intestinal biopsy specimens with immunophenotyping and analysis of clonality of lymphoid infiltrates results in more accurate differentiation of neoplastic versus inflammatory lymphocytes. Important histologic features that differentiated intestinal lymphoma from IBD included lymphoid infiltration of the intestinal wall beyond the mucosa, epitheliotropism (especially intraepithelial nests and plaques), heterogeneity, and nuclear size of lymphocytes. Based on the results of this study, a stepwise diagnostic algorithm that first uses histologic assessment, followed by immunophenotyping and then PCR to determine clonality of the lymphocytes, was developed to more accurately differentiate between intestinal lymphoma and IBD.

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

    Science.gov (United States)

    2016-09-06

    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; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  13. Biomarkers for lymphoma

    Science.gov (United States)

    Zangar, Richard C.; Varnum, Susan M.

    2014-09-02

    A biomarker, method, test kit, and diagnostic system for detecting the presence of lymphoma in a person are disclosed. The lymphoma may be Hodgkin's lymphoma or non-Hodgkin's lymphoma. The person may be a high-risk subject. In one embodiment, a plasma sample from a person is obtained. The level of at least one protein listed in Table S3 in the plasma sample is measured. The level of at least one protein in the plasma sample is compared with the level in a normal or healthy subject. The lymphoma is diagnosed based upon the level of the at least one protein in the plasma sample in comparison to the normal or healthy level.

  14. [Secondary orbital lymphoma].

    Science.gov (United States)

    Basanta, I; Sevillano, C; Álvarez, M D

    2015-09-01

    A case is presented of an 85 year-old Caucasian female with lymphoma that recurred in the orbit (secondary ocular adnexal lymphoma). The orbital tumour was a diffuse large B-cell lymphoma according to the REAL classification (Revised European-American Lymphoma Classification). Orbital lymphomas are predominantly B-cell proliferations of a variety of histological types, and most are low-grade tumours. Patients are usually middle-aged or elderly, and it is slightly more common in women. A palpable mass, proptosis and blepharoptosis are the most common signs of presentation. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  15. Hodgkin lymphoma: Evolution and dilemma in radiation treatments; Evolution et dilemmes dans les traitements du lymphome de Hodgkin

    Energy Technology Data Exchange (ETDEWEB)

    Girinsky, T.; Ghalibafian, M.; Paumier, A. [Institut Gustave-Roussy, Dept. des Radiations, 94 - Villejuif (France); Ghalibafian, M. [Hopital Marak, Dept. des radiations, Teheran (Iran, Islamic Republic of)

    2009-10-15

    Multiple new developments in the treatments of patients with Hodgkin lymphoma have occurred in the last 10 years. Radiation treatments have become extremely precise in localized Hodgkin lymphomas, on the other hand, they have almost completely disappeared in advanced stages. For patients with refractory or recurrent disease, it is strongly advocated, whenever feasible, to deliver a mantle field radiation treatment after an autologous stem cell transplant to avoid any further recurrence of the disease. (authors)

  16. Refractory gastroesophageal reflux disease

    OpenAIRE

    Joaquim Prado P. Moraes-Filho

    2012-01-01

    CONTEXT: Gastroesophageal reflux disease (GERD) is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Its pathophysiology, diagnosis and treatment have frequently been analyzed but it is interesting to review some aspects of the GERD refractory patients to the proton pump inhibitors treatment. The treatment encompasses behavioral measures and pharmacological therapy. The majority of the patients respond well to proton pump inhibito...

  17. Colectomy for refractory constipation

    DEFF Research Database (Denmark)

    Raahave, Dennis; Loud, Franck Bjørn; Christensen, Elsebeth;

    2010-01-01

    OBJECTIVE: This study evaluated the type of colectomy, postoperative complications, functional results, and satisfaction in patients with constipation refractory to conservative therapy. Further, colonic transit time (CTT), faecal load (coprostasis), and colon length (redundancies) were compared...... had at hemicolectomy, 11 patients a subtotal colectomy and 3 patients an ileostomy. Two patients had an anastomotic leak and one died. In 11 patients, further surgery was necessary, because of recurrent constipation. Abdominal pain disappeared and defecation patterns improved significantly to 1-4 per...

  18. Dynamics of occurrence of refractory coeliac disease and associated complications over 25 years.

    Science.gov (United States)

    Eigner, W; Bashir, K; Primas, C; Kazemi-Shirazi, L; Wrba, F; Trauner, M; Vogelsang, H

    2017-01-01

    Refractory coeliac disease, enteropathy associated T-cell lymphoma and small bowel adenocarcinoma are rare but prognostically important complications in coeliac disease. To analyse potential changes in occurrence of complicated coeliac disease over the last 25 years. One thousand one hundred and thirty eight patients were included and evaluated based on their time of first presentation at the Medical University of Vienna, Austria. Occurrences of refractory coeliac disease and associated malignancies were evaluated for 5-year intervals from January 1990 until December 2014 and were compared over time. 2.6% (n = 29) were diagnosed with refractory coeliac disease (females 65.6%, mean age at diagnosis 62.8 years). The proportion of those patients was 2.6%, 3.1%, 3.3%, 2.7% and 0.5% for the 5 year intervals from 1990 onwards. Thus, the number of refractory cases has been decreasing since 2000 (P = 0.024). The number of patients presenting with lymphoma (n = 7) was 0.6%, 0.4%, 1.1%, 0.8% and 0% from 1990 to 2014. Similarly the number of patients with adenocarcinoma (n = 4) decreased to 0% until 2014. Overall mortality in patients suffering from refractory disease was 48%. Of all patients diagnosed with lymphoma 71.4% died with a 5-year survival rate of 28.6%. Over the past 15 years the occurrence of complicated coeliac disease has been decreasing. This possibly reflects a higher awareness of coeliac disease and optimised diagnosis and treatment with avoidance of long-term immunological disease activity. Symptomatic disease and a delay in diagnosis are risk factors for refractory coeliac disease and related cancer. © 2016 John Wiley & Sons Ltd.

  19. Refractory status epilepticus

    Directory of Open Access Journals (Sweden)

    Sanjay P Singh

    2014-01-01

    Full Text Available Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED, i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.

  20. An overview of cutaneous T cell lymphomas [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Nooshin Bagherani

    2016-07-01

    Full Text Available Cutaneous T cell lymphomas (CTCLs are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are characterized by a cutaneous infiltration of malignant monoclonal T lymphocytes. They typically afflict adults with a median age of 55 to 60 years, and the annual incidence is about 0.5 per 100,000. Mycosis fungoides, Sézary syndrome, and primary cutaneous peripheral T cell lymphomas not otherwise specified are the most important subtypes of CTCL. CTCL is a complicated concept in terms of etiopathogenesis, diagnosis, therapy, and prognosis. Herein, we summarize advances which have been achieved in these fields.

  1. [Primary Meckel's cave lymphoma. A case and review of the literature].

    Science.gov (United States)

    Artico, M; Salvati, M; Raco, A; Innocenzi, G; Delfini, R

    1992-01-01

    A rare case of Meckel's cavity lymphoma is presented. Only two other cases of identical localization have been presented in the literature. The symptoms consisted of sensorimotor impairment of the Vth nerve associated with slight exophthalmos. C.T. scan showed a hyperdense lesion in Meckel's cavity. After total surgical removal, histological analysis diagnosed a B-lymphocyte non-Hodgkin's lymphoma. The patient received both radiotherapy and chemotherapy and at one year follow up, the clinical course was good. The lesion had no clinical or radiological specificity. Its prognosis appears to be identical to that of other intracranial lymphomas.

  2. Non-Hodgkin's lymphomas; Lymphomes malins non hodgkiniens

    Energy Technology Data Exchange (ETDEWEB)

    Drouet, F.; Mahe, M.A. [Service de radiotherapie du centre Rene-Gauducheau, CRLCC Nantes-Atlantique, 44 - Saint-Herblain (France); Cahu, X. [Service d' hematologie clinique CHU de Rennes, hopital Pontchaillou, 35 - Rennes (France); Pointreau, Y. [Service de radiotherapie, centre regional universitaire de cancerologie Henry-S.-Kaplan CHU de Tours, Hpital Bretonneau, 37 - Tours (France); Denis, F. [Centre Jean-Bernard, Service de radiotherapie 72 - Le Mans (France)

    2010-07-01

    With approximately 10000 cases per year in France, non-Hodgkin's lymphoma (NHL) represents the most frequent hematological malignancy, and 5 to 10 % of new cases of cancers. NHLs constitute a heterogeneous group of lympho-proliferative diseases, including entities with very different epidemiological and evolutive characteristics, as well as prognosis and treatments. Several classifications exist, but in practice, we individualize aggressive NHL including Diffuse Large B-Cell Lymphomas (DLBCL) which is the most common lymphoma, and indolent NHL including follicular lymphomas and mucosa-associated lymphoid tissue (MALT) lymphomas. The role of the radiotherapy in the management of NHLs varies according to the specific sub-type of lymphoma, but it has become increasingly limited over time. Overall it finds indications with curative intent only in situations of localized LMNH: either associated with chemotherapy as part of a combined modality therapy as for the treatment of localized DLBCL, or as exclusive treatment specially in the rare situations of localized follicular lymphomas. Moreover, lymphocytes being extremely radiosensitive cells, radiotherapy retains excellent indications with palliative intent for the management of symptomatic bulky tumor masses, and that whatever the sub-type of NHLs may be. It is important to remember that even today the 'Involved Field' irradiation type remains the gold standard for the treatment of nodal NHLs, even if we witness at present the emergence of new types of irradiation, which aim to reduce the amount of irradiated tissues to try to limit the risks of delayed radio-induced complications. The purpose of this article is to clarify the specific aspects (epidemiological, radio-anatomical and prognostic characteristics) of each NHLs'sub-types (except primary central nervous system lymphomas), as well as the practical modalities of the irradiation (illustrated by a clinical case record) when an indication of

  3. T-Cell Lymphomas in South America and Europe

    Directory of Open Access Journals (Sweden)

    Monica Bellei

    2012-01-01

    Full Text Available Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic, nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies.

  4. Checkpoint Inhibition in Hodgkin Lymphoma: Saving the Best for Last?

    Science.gov (United States)

    Lin, Richard J; Diefenbach, Catherine S

    2016-10-15

    Hodgkin lymphoma is a unique disease entity characterized by a low number of neoplastic tumor cells surrounded by an inflammatory microenvironment composed of dysfunctional immune cells. Recent molecular and genetic studies have revealed that upregulation of the immune checkpoint pathway programmed death 1/programmed death ligand 1 is a key oncogenic driver of Hodgkin lymphoma. Corroborating these mechanistic studies, early-phase clinical trials using the checkpoint inhibitors nivolumab and pembrolizumab in treatment regimens for relapsed and/or refractory Hodgkin lymphoma have demonstrated impressive response rates, a promising durability of response, and a favorable side-effect profile. Given its targeted mechanism of action, acceptable safety, and clinically meaningful activity, the checkpoint inhibitor nivolumab was recently approved by the US Food and Drug Administration as therapy for classical Hodgkin lymphoma that has relapsed or progressed after autologous stem cell transplantation (ASCT) and post-ASCT consolidation therapy with brentuximab vedotin. In this article we review the scientific rationale, preclinical evidence, and most recent clinical data for the use of checkpoint inhibitor therapy in patients with relapsed Hodgkin lymphoma.

  5. RETREATMENT WITH FLUDARABINE AND CYCLOSPORINE FOR ONE CASE OF REFRACTORY PURE RED CELL APLASIA

    Institute of Scientific and Technical Information of China (English)

    Guang-sheng He; Xiang Zhang; De-pei Wu; Ai-ning Sun; Miao Miao; Xiu-li Wang; Zheng-ming Jin

    2008-01-01

    @@ MANY cases of pure red cell aplasia (PRCA) were mediated by over-function of immune cells, and responded well to immunosuppres-sive therapy.1 Sometimes refractory cases also arose. Fludara-bine is an analogue of adenosine resistant to deamination which is widely used for B-chronic lymphocytic leukemia (CLL) and other hematological malignancies.

  6. Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Sterry, W.; Pullmann, H.; Steigleder, G.K.

    1981-01-01

    To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of /sup 3/H-thymidine-labeled infiltrating cells (/sup 3/H-index). A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the /sup 3/H-index is moderately elevated in stage I and high in stage III. The /sup 3/H-index is within normal range in dermal infiltrate of Sezary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis. In parapsoriasis en plaques two groups can be distinguished: in the small plaque variant (chronic superficial dermatitis) the /sup 3/H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity. Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas.

  7. Critical appraisal of pralatrexate in the management of difficult-to-treat peripheral T cell lymphoma

    Directory of Open Access Journals (Sweden)

    Casanova M

    2011-10-01

    Full Text Available M Casanova, A Medina-Pérez, M Moreno-Beltran, M Mata-Vazquez, A RuedaOncohematology Service, Hospital Costa del Sol, Marbella, SpainAbstract: Aggressive T cell lymphomas are a subgroup of lymphomas with a particularly poor prognosis. This is especially true for patients with recurrent or refractory disease, who typically have limited response to salvage therapy and extremely poor overall survival. For this reason, there is a strong need to develop potentially active drugs for these malignancies. Pralatrexate is a novel antifolate designed to have high affinity for reduced folate carrier type 1. Preclinical and clinical studies have demonstrated that pralatrexate has significant activity against T cell lymphomas. The dose-limiting toxicity for pralatrexate is mucositis, which can be abrogated with folic acid and vitamin B12 supplementation. Pralatrexate is the first single agent approved for the treatment of patients with relapsed or refractory peripheral T cell lymphoma. This approval was based on an overall objective response rate observed in the pivotal study. The overall response rate was 29%, with a median duration of 10.1 months. This article reviews the biochemistry, preclinical experience, metabolism, and pharmacokinetics of pralatrexate, including the clinical experience with this agent in lymphoma. Future areas of development are now focused on identifying synergistic combinations of pralatrexate with other agents and the evaluation of predictive markers for clinical benefit.Keywords: pralatrexate, peripheral T cell lymphoma

  8. Pembrolizumab in classical Hodgkin's lymphoma.

    Science.gov (United States)

    Maly, Joseph; Alinari, Lapo

    2016-09-01

    Pembrolizumab is a humanized monoclonal antibody directed against programmed cell death protein 1 (PD-1), a key immune-inhibitory molecule expressed on T cells and implicated in CD4+ T-cell exhaustion and tumor immune-escape mechanisms. Classical Hodgkin's lymphoma (cHL) is a unique B-cell malignancy in the sense that malignant Reed-Sternberg (RS) cells represent a small percentage of cells within an extensive immune cell infiltrate. PD-1 ligands are upregulated on RS cells as a consequence of both chromosome 9p24.1 amplification and Epstein-Barr virus infection and by interacting with PD-1 promote an immune-suppressive effect. By augmenting antitumor immune response, pembrolizumab and nivolumab, another monoclonal antibody against PD-1, have shown significant activity in patients with relapsed/refractory cHL as well as an acceptable toxicity profile with immune-related adverse events that are generally manageable. In this review, we explore the rationale for targeting PD-1 in cHL, review the clinical trial results supporting the use of checkpoint inhibitors in this disease, and present future directions for investigation in which this approach may be used.

  9. Primary pediatric gastrointestinal lymphoma

    Directory of Open Access Journals (Sweden)

    Ranjana Bandyopadhyay

    2011-01-01

    Full Text Available Background: Primary non-Hodgkin′s lymphoma (NHL of the gastrointestinal (GI tract is the most common extranodal lymphoma in pediatric age group. Yet, the overall incidence is very low. The rarity of the disease as well as variable clinical presentation prevents early detection when the possibility of cure exists. Materials and Methods: We studied six cases of primary GI NHL in pediatric age group with reference to their clinical presentation, anatomic distribution and histopathologic characteristics. Results: All were males except one. Intestinal obstruction was the presenting feature in 50%. Half the cases showed ileocaecal involvement, while large bowel was involved in 16%. Histology showed four cases of diffuse large B-cell lymphoma (DLBCL, one case of Burkitt lymphoma, and one Burkitt-like lymphoma. Immunohistochemistry for Tdt, CD20, CD3, CD30, bcl2, bcl6 confirmed the morphological diagnosis. Conclusion: Pediatric GI lymphoma commonly involves the ileocaecal region and presents with intestinal obstruction. A higher prevalence of DLBCL is found compared to other series. A high proliferative index is useful in differentiating Burkitt-like lymphoma from DLBCL.

  10. Spondylarthritis in the absence of B lymphocytes.

    Science.gov (United States)

    Baeten, Dominique; Kruithof, Elli; Breban, Maxime; Tak, Paul P

    2008-03-01

    The highly effective treatment of rheumatoid arthritis by B cell depletion and the presence of B cells in the peripheral and axial lesions of patients with spondylarthritis (SpA) raise the question as to whether B lymphocytes could also be an appropriate therapeutic target in the latter disease. We describe 2 male HLA-B27-positive patients who had active SpA despite absence of B cells. One patient developed SpA with sacroiliitis and asymmetric oligoarthritis after having been diagnosed as having severe Bruton agammaglobulinemia. Since extensive investigations excluded an infectious origin of the SpA, this case illustrates that functional B cells and/or gamma globulins are not strictly required for SpA pathogenesis. The second patient had severe axial and peripheral SpA that was treated successfully with etanercept. After discontinuation of etanercept treatment because of non-Hodgkin's B cell lymphoma, both axial and peripheral SpA symptoms relapsed rapidly, and this exacerbation of articular disease activity was not modulated by successful B cell depletion therapy for the lymphoma. Although case reports have obvious limitations, our clinical observations provide evidence that active SpA can occur in the absence of functional mature B cells and thus emphasize the need for systematic studies of the exact role and function of B lymphocytes in this disease.

  11. Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

    1980-07-01

    The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable.

  12. Identification of highly methylated genes across various types of B-cell non-hodgkin lymphoma.

    Directory of Open Access Journals (Sweden)

    Nicole Bethge

    Full Text Available 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.

  13. CT findings of lymphoma with peritoneal, omental and mesenteric involvement: Peritoneal lymphomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Karaosmanoglu, Devrim [Department of Radiology, Hacettepe University School of Medicine, Ankara (Turkey); Karcaaltincaba, Musturay [Department of Radiology, Hacettepe University School of Medicine, Ankara (Turkey)], E-mail: musturayk@yahoo.com; Oguz, Berna; Akata, Deniz; Ozmen, Mustafa; Akhan, Okan [Department of Radiology, Hacettepe University School of Medicine, Ankara (Turkey)

    2009-08-15

    Purpose: We aimed to describe computed tomography (CT) findings in patients with peritoneal, omental and mesenteric lymphoma involvement. Materials and methods: We searched our archive retrospectively to find out patients with peritoneal, omental and mesen