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Relapsed b-cell lymphoma

J Prinz, Y d'Hargues, P Gödel, A Shimabukuro-Vornhagen, M Kochanek, B Böll
BACKGROUND: The development of chimeric antigen receptor (CAR) T‑cells has shown promising results in relapsed/refractory B‑cell acute lymphoblastic leukemia/lymphoma (B-ALL) and diffuse large cell B‑cell lymphoma. Complications, especially cytokine release syndrome (CRS) and CAR T‑cell related encephalopathy syndrome (CRES), can be life threatening. The management of both plays a key role in CAR T‑cell therapy. OBJECTIVES: Diagnosis, clinical presentation and development of complications in the treatment with CAR T‑cells...
December 13, 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Yaya Chu, Sanghoon Lee, Tishi Shah, Changhong Yin, Matthew Barth, Rodney R Miles, Janet Ayello, Erin Morris, Lauren Harrison, Carmella Van de Ven, Paul Galardy, Stanton C Goldman, Megan S Lim, Michelle Hermiston, Linda M McAllister-Lucas, Lisa Giulino-Roth, Sherrie L Perkins, Mitchell S Cairo
Pediatric and adult patients with recurrent/refractory Burkitt lymphoma (BL) continue to have poor outcomes, emphasizing the need for newer therapeutic agents. Bruton's tyrosine kinase (BTK) is activated following B-cell receptor stimulation and in part regulates normal B-cell development. Ibrutinib, a selective and irreversible BTK inhibitor, has been efficacious in chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenström's macroglobulinemia, and marginal zone lymphoma. In this study, we investigated the efficacy of ibrutinib alone and in selective adjuvant combinations against BL in-vitro and in a human BL xenografted immune-deficient NOD...
2019: Oncoimmunology
Xiang Meng Li, Hai Song Zhang, Xiao Li Dai, Jian Hong Shi
RATIONALE: Primary extra-nodal non-Hodgkin lymphoma (PE-NHL) arising in the region of the buttocks is rare. After reviewing the literature from the last 20 years, we found only 3 reported lymphomas originating from soft tissue of the buttocks. In our case, positron emission tomography/computed tomography (PET/CT) was performed for the first time, both before and after treatment, to determine the initial stage of PE-NHL and the curative effects of treatment. PATIENT CONCERNS: We report the case of a 71-year-old woman who was admitted to our hospital due to pain, skin redness, rising skin temperature, and swelling in the right hip...
December 2018: Medicine (Baltimore)
Shariful Islam, Andrew L Paek, Michael Hammer, Savithri Rangarajan, Robert Ruijtenbeek, Laurence Cooke, Eric Weterings, Daruka Mahadevan
Double-hit (DH) or double-expresser (DE) lymphomas are high-grade diffuse large B-cell lymphomas (DLBCL) that are mostly incurable with standard chemo-immunotherapy due to treatment resistance. The generation of drug-induced aneuploid/polyploid (DIAP) cells is a common effect of anti-DLBCL therapies (e.g. vincristine, doxorubicin). DIAP cells are thought to be responsible for treatment resistance, as they are capable of re-entering the cell cycle during off-therapy periods. Previously we have shown that combination of alisertib plus ibrutinib plus rituximab can partially abrogate DIAP cells and induce cell death...
November 13, 2018: Oncotarget
István Szegedi, Imre Gáspár, Katalin Gyurina, Zsuzsa Zele, Csongor Kiss
Classification, staging and treatment response criteria of pediatric NHL have been revised. Long-term survival reaches ~90% at the expense of severe acute toxicities. The outcome of refractory and relapsed cases is poor. The small number of patients hinders introduction of targeted therapies. Here we summarize principles and perspectives of pediatric NHL supported by results of a retrospective clinical survey. Twenty-five patients (21 boys, 4 girls; mean age: 11.9 years) were registered between 2009 and 2018: 11 Burkitt lymphomas, 4 diffuse large B-cell lymphomas, 5 T-cell lymphoblastic lymphomas, and 1-1 grey-zone lymphoma, anaplastic large-cell lymphoma, cutaneous T-cell lymphoma, angioimmunoblastic lymphoma, and Castleman disease...
December 12, 2018: Magyar Onkologia
Marissa L Cann, Laura E Herring, Lauren Haar, Thomas Sterns Karim Gilbert, Dennis Goldfarb, Kristy L Richards, Lee M Graves, David S Lawrence
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, with at least one-third of its patients relapsing after treatment with the current chemotherapy regimen, R-CHOP. By gene expression profiling, patients with DLBCL can be categorized into two clinically relevant subtypes: activated B-cell (ABC) and germinal center B-cell (GCB) DLBCL. Patients with the ABC subtype have a poorer prognosis than those with GCB, and are defined by chronic, overactive signaling through the B-cell receptor and NF-κB pathways...
December 12, 2018: Journal of Proteome Research
Richard J Lin, Caleb Ho, Patrick D Hilden, Juliet N Barker, Sergio A Giralt, Paul A Hamlin, Ann A Jakubowski, Hugo R Castro-Malaspina, Kevin S Robinson, Esperanza B Papadopoulos, Miguel-Angel Perales, Craig S Sauter
TP53 alterations portend extremely poor prognosis in patients with mantle cell lymphoma treated with standard treatment modalities. We reviewed outcomes of 42 patients with available TP53 status who had received a reduced-intensity or non-myeloablative allogeneic haematopoietic cell transplant at our institution. We demonstrated a 2-year overall survival and progression-free survival of 78% [95% confidence interval (CI) 60-88] and 61% (95% CI 43-75), respectively. The 2-year cumulative incidences of relapse and non-relapse mortality were 19% and 20%, respectively...
December 11, 2018: British Journal of Haematology
Jennifer E Hibma, Hagop M Kantarjian, Daniel J DeAngelo, Joseph P Boni
AIM: To characterize the effect of inotuzumab ozogamicin on QT interval in patients with B-cell malignancies. METHODS: Data were pooled from three clinical studies including 250 patients (N=2743) who received inotuzumab ozogamicin monotherapy. Patients with relapsed/refractory acute lymphoblastic leukaemia (NCT01564784 and NCT01363297) received 1.8 mg m-2 per cycle in divided doses (mean Cmax 371 ng ml-1 ; considered therapeutic) and patients with relapsed/refractory non-Hodgkin lymphoma (NCT00868608) received 1...
December 8, 2018: British Journal of Clinical Pharmacology
Gottfried von Keudell, Anas Younes
Hodgkin Lymphoma (HL) is a B-cell lymphoproliferative disorder with an excellent prognosis for the majority of patients who are treated with multi-agent chemotherapy, with or without radiation. A subset of patient, however, does not respond to therapy or relapses after accomplishing an initial response. Their outcome is poor and new treatment strategies are urgently needed for this patient population. Recent advances in the understanding of the tumour biology of HL and its microenvironment have ushered a new era of targeted- and immuno-therapies with remarkable activity...
December 11, 2018: British Journal of Haematology
Di Wang, Peng Liu, Yue Zhang, Hui-Ying Liu, Di Shen, Yi-Qun Che
Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin's lymphoma and is very likely to infiltrate the bone marrow. Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis. Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients. Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry...
2018: BioMed Research International
Rosa María Lacy-Niebla, Sonia Toussaint-Caire, María Estela Mares-Navarro
Introduction: T-cell lymphoid dyscrasia is a group of different, infrequent, epitheliotropic inflammatory dermatosis that precede cutaneous T-cell lymphomas. Treatment with ultraviolet radiation is safe and efficacious. Objective: To describe responses to treatment, secondary effects and complications. Method: Eleven patients with different T-cell lymphoid dyscrasias were treated. Two received psoralens plus ultraviolet A radiation (PUVA) and nine narrow band ultraviolet B radiation (NB-UVB)...
2018: Gaceta Médica de México
Kevin H Hall, Kelly Valla, Christopher R Flowers, Jonathon B Cohen
INTRODUCTION: Intrathecal chemoprophylaxis is often administered to patients with diffuse large B-cell lymphoma (DLBCL) to lower the rates of central nervous system (CNS) relapse, although its benefit has not been well-described. Prognostic models, including the CNS-International Prognostic Index (IPI), have been developed to aid in identifying patients at highest risk for CNS relapse. PATIENTS AND METHODS: We evaluated 112 patients diagnosed with DLBCL from 2009 to 2016 at Emory Healthcare and classified them as high (n = 44) or low risk (n = 68) for CNS relapse and compared CNS prophylaxis rates and relapse rates between groups...
November 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
Alessia Castellino, Jose S Pulido, Patrick B Johnston, Kay M Ristow, N Nora Bennani, David J Inwards, William R Macon, Ivana N M Micallef, Rebecca L King, Diva R Salomao, Thomas E Witzig, Thomas M Habermann, Grzegorz S Nowakowski
Vitreoretinal lymphoma (VRL) management remains a challenge. We present 72 patients with VRL, diagnosed at Mayo Clinic between 1990-2018. Three nondiffuse large B-cell lymphoma (DLBCL) histology cases were excluded. Among 69 DLBCL, 33 patients had primary VRL (PVRL), 18 concurrent intraocular and central nervous system (CNS) or systemic disease and 18 secondary VRL. Patients received intraocular chemotherapy (intraocular injections of rituximab or metothrexate or steroids or in combination), radiotherapy, systemic or combined systemic plus intraocular treatment in 9, 10, 35, and 15 cases, respectively...
December 5, 2018: American Journal of Hematology
Rueben Ganeshalingam, Paul Roach, Geoffrey Paul Schembri
Two patients with diffuse large B-cell lymphoma relapsing as neurolymphomatosis diagnosed on FDG PET/CT are presented. Both patients were treated initially with chemotherapy and had a complete metabolic response. Patient 1 represented with lower-limb pain. An FDG PET/CT demonstrated intense uptake throughout the sciatic nerves bilaterally extending distally with relapse confirmed on biopsy. Patient 2 represented to hospital with worsening mobility, neuropathic pain, and facial asymmetry. An FDG PET/CT demonstrated relapse within the spinal cord, left sciatic nerve, and facial nerve branches...
December 3, 2018: Clinical Nuclear Medicine
Mariadea Lavalle, Laura Maria Minordi, Stefan Hohaus, Riccardo Manfredi, Vittoria Rufini
A 75-year-old man, who had been diagnosed with small lymphocytic lymphoma with cervical localization, underwent F-FDG PET/CT with iodinated contrast medium due to the appearance of cervical swelling suspected of illness relapse. PET/CT revealed intense F-FDG uptake in multiple cervical and subdiaphragmatic lymph nodes and in the left parotid. Moreover, diffuse uptake and wall thickening of the colon were evident; endoscopy with biopsy revealed a diffuse large B-cell lymphoma. Transformation into a more aggressive lymphoma occurs in 2% to 8% of small lymphocytic lymphoma, the so-called Richter syndrome...
December 3, 2018: Clinical Nuclear Medicine
Mei Ming, Wenjun Wu, Bingqing Xie, Madina Sukhanova, Weige Wang, Sabah Kadri, Shruti Sharma, Jimmy Lee, Sharon Shacham, Yosef Landesman, Natalia Maltsev, Pin Lu, Y Lynn Wang
Inhibition of B-cell receptor (BCR) signaling through the BTK inhibitor, ibrutinib, has generated a remarkable response in mantle cell lymphoma (MCL). However, approximately one third of patients do not respond well to the drug, and disease relapse on ibrutinib is nearly universal. Alternative therapeutic strategies aimed to prevent and overcome ibrutinib resistance are needed. We compared and contrasted the effects of selinexor, a selective inhibitor of nuclear export, with ibrutinib in six MCL cell lines that display differential intrinsic sensitivity to ibrutinib...
December 2018: Molecular Cancer Therapeutics
Jonathon B Cohen
Most patients with aggressive non-Hodgkin lymphoma will be cured with initial chemoimmunotherapy; however, most patients with relapsed disease will not be cured and will die as a result of their disease. In these cases, continued treatment with conventional chemotherapy is typically not of benefit and can contribute to significant toxicities and decreased quality of life for patients. Fortunately, a number of therapies are currently available or under investigation for this group of patients, ranging from oral tyrosine kinase inhibitors targeting multiple pathways within the malignant cells to adoptive cellular therapies that harness the patient's immune system to fight disease...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Allison Rosenthal, Lisa Rimsza
The growing body of genomic information collected and applied to mature aggressive B-cell lymphoma diagnosis and management has exploded over the last few years due to improved technologies with high-throughput capacity, suitable for use on routine formalin-fixed, paraffin-embedded tissue biopsies, and decreasing costs. These techniques have made evaluation of complete DNA sequences, RNA-expression patterns, translocations, copy-number alterations, loss of heterozygosity, and DNA-methylation patterns possible on a genome-wide level...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Xi Wang, Bing Xia, Yi-Zhuo Zhang
Diffuse large B cell lymphoma(DLBCL)is the most common non-Hodgkin's lymphoma in adults,accounting for 30%-40% of non-Hodgkin's lymphoma in adults. The treatments of this lymphoma mainly include chemotherapy,radiotherapy and autologous hematopoietic stem cell transplantation. A large amount of studies show that autologous hematopoietic stem cell transplantation considered as the main treatmant approach can be used for primary high-risk young and relapsed or refractory DLBCL patients. Many scholars have evaluated the effectiveness of autologous hematopoietic stem cell transplantation for primarily high-risk young and relapsed or refractory DLBCL patients,and tried to improve the effectiveness of transplantation that showed some advantagcs for DLBCL patients...
December 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Stephen J Schuster, Michael R Bishop, Constantine S Tam, Edmund K Waller, Peter Borchmann, Joseph P McGuirk, Ulrich Jäger, Samantha Jaglowski, Charalambos Andreadis, Jason R Westin, Isabelle Fleury, Veronika Bachanova, S Ronan Foley, P Joy Ho, Stephan Mielke, John M Magenau, Harald Holte, Serafino Pantano, Lida B Pacaud, Rakesh Awasthi, Jufen Chu, Özlem Anak, Gilles Salles, Richard T Maziarz
BACKGROUND: Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. METHODS: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation...
December 1, 2018: New England Journal of Medicine
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