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https://www.readbyqxmd.com/read/28811872/current-and-emerging-treatment-options-for-mantle-cell-lymphoma
#1
REVIEW
Bita Fakhri, Brad Kahl
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with typically aggressive behavior. The genetic signature is the chromosomal translocation t(11;14)(q13;q32) resulting in overexpression of cyclin D1. Asymptomatic newly diagnosed MCL patients with low tumor burden can be closely observed, deferring therapy to the time of disease progression. Although MCL classically responds to upfront chemotherapy, it remains incurable with standard approaches. For patients in need of frontline therapy, the initial decision is whether to proceed with an intensive treatment strategy or a non-intensive treatment strategy...
August 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28800491/survival-for-patients-with-rare-haematologic-malignancies-changes-in-the-early-21st-century
#2
Dianne Pulte, Janick Weberpals, Lina Jansen, Sabine Luttmann, Bernd Holleczek, Alice Nennecke, Meike Ressing, Alexander Katalinic, Hermann Brenner
INTRODUCTION: Population-level survival has improved for common haematologic malignancies in the early 21st century. However, relatively few population-level data are available for rare haematologic malignancies. METHODS: Data were extracted from 12 cancer registries in Germany and the Surveillance, Epidemiology and End Results database in the United States (US). Cases of haematologic malignancies with an incidence of less than 1 per 100,000 were selected for analysis...
August 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28797244/a-lowered-26s-proteasome-activity-correlates-with-mantle-lymphoma-cell-lines-resistance-to-genotoxic-stress
#3
Khaoula Ben Younes, Simon Body, Élodie Costé, Pierre-Julien Viailly, Hadjer Miloudi, Clémence Coudre, Fabrice Jardin, Fatma Ben Aissa-Fennira, Brigitte Sola
BACKGROUND: Mantle cell lymphoma (MCL) is a B-cell hemopathy characterized by the t(11;14) translocation and the aberrant overexpression of cyclin D1. This results in an unrestrained cell proliferation. Other genetic alterations are common in MCL cells such as SOX11 expression, mutations of ATM and/or TP53 genes, activation of the NF-κB signaling pathway and NOTCH receptors. These alterations lead to the deregulation of the apoptotic machinery and resistance to drugs. We observed that among a panel of MCL cell lines, REC1 cells were resistant towards genotoxic stress...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28797213/surveillance-imaging-in-mantle-cell-lymphoma-in-first-remission-lacks-clinical-utility
#4
Daniel M Guidot, Jeffrey M Switchenko, Loretta J Nastoupil, Jean L Koff, Kristie A Blum, Joseph Maly, Christopher R Flowers, Jonathon B Cohen
Mantle cell lymphoma (MCL) is a heterogeneous disease with high relapse rates. Limited data guide the use of surveillance imaging following treatment. We constructed a retrospective cohort from two academic institutions of patients with MCL who completed first-line therapy and underwent follow-up for relapse, analyzing the effect of surveillance imaging on survival. Of 217 patients, 102 had documented relapse, with 38 (37%) diagnosed by surveillance imaging and 64 (63%) by other methods. Relapse diagnosis by surveillance imaging had no significant advantage in overall survival from diagnosis date (hazard ratio [HR] = 0...
August 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28797193/exposure-response-evaluations-of-venetoclax-efficacy-and-safety-in-patients-with-non-hodgkin-lymphoma
#5
Apurvasena Parikh, Sathej Gopalakrishnan, Kevin J Freise, Maria E Verdugo, Rajeev M Menon, Sven Mensing, Ahmed Hamed Salem
Exposure-response analyses were performed for a venetoclax monotherapy study in 106 patients with varying subtypes of non-Hodgkin lymphoma (NHL) (NCT01328626). Logistic regression, time-to-event, and progression-free survival (PFS) analyses were used to evaluate the relationship between venetoclax exposure, NHL subtype and response, PFS, or occurrence of serious adverse events. Trends for small increases in the probability of response with increasing venetoclax exposures were identified, and became more evident when assessed by NHL subtype...
August 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28791403/complex-analysis-of-the-tp53-tumor-suppressor-in-mantle-cell-and-diffuse-large-b-cell-lymphomas
#6
Lenka Zlamalikova, Mojmir Moulis, Barbora Ravcukova, Kvetoslava Liskova, Jitka Malcikova, David Salek, Jiri Jarkovsky, Miluse Svitakova, Renata Hrabalkova, Jan Smarda, Jana Smardova
Mutations and deletions of the tumor suppressor TP53 gene are the most frequent genetic alterations detected in human tumors, though they are rather less frequent in lymphomas. However, acquisition of the TP53 mutation was demonstrated to be one of the characteristic markers in mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) and prognostic value of the TP53 status has been recognized for these diseases. We present the complex analysis of the TP53 aberrations in 57 cases of MCL and 131 cases of DLBCL...
August 8, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28791187/ibrutinib-treatment-of-mantle-cell-lymphoma-relapsing-at-central-nervous-system-a-case-report-and-literature-review
#7
Donato Mannina, Barbara Loteta
Mantle cell lymphoma (MCL) accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement). Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL) and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD)...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28775119/incidence-and-management-of-toxicity-associated-with-ibrutinib-and-idelalisib-a-practical-approach
#8
Iris de Weerdt, Suzanne M Koopmans, Arnon P Kater, Michel van Gelder
The use of novel B cell receptor signaling inhibitors results in high response rates and long progression-free survival in patients with indolent B cell malignancies, such as chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma and Waldenstroms macroglobulinemia. Ibrutinib, the first-in-class inhibitor or Bruton's tyrosine kinase, and idelalisib, the first-in-class inhibitor of phosphatidylinositol 3-kinase δ have recently been approved for several indolent B cell malignancies. These drugs especially foresee in previously unmet needs for patients with relapsed or refractory disease, high-risk cytogenetic or molecular abnormalities or with comorbidities...
August 3, 2017: Haematologica
https://www.readbyqxmd.com/read/28771673/activity-of-lenalidomide-in-mantle-cell-lymphoma-can-be-explained-by-nk-cell-mediated-cytotoxicity
#9
Patrick R Hagner, Hsiling Chiu, Maria Ortiz, Benedetta Apollonio, Maria Wang, Suzana Couto, Michelle F Waldman, Erin Flynt, Alan G Ramsay, Matthew Trotter, Anita K Gandhi, Rajesh Chopra, Anjan Thakurta
Lenalidomide is an immunomodulatory agent that has demonstrated clinical benefit for patients with relapsed or refractory mantle cell lymphoma (MCL); however, despite this observed clinical activity, the mechanism of action (MOA) of lenalidomide has not been characterized in this setting. We investigated the MOA of lenalidomide in clinical samples from patients enrolled in the CC-5013-MCL-002 trial (NCT00875667) comparing single-agent lenalidomide versus investigator's choice single-agent therapy and validated our findings in pre-clinical models of MCL...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28768446/comparison-of-two-doses-of-intravenous-temsirolimus-in-patients-with-relapsed-refractory-mantle-cell-lymphoma
#10
Wojciech Jurczak, Sundra Ramanathan, Pratyush Giri, Alessandra Romano, Heidi Mocikova, Jill Clancy, Mariajose Lechuga, Michelle Casey, Joseph Boni, Agnieszka Giza, Georg Hess
Temsirolimus 175 mg once-weekly for 3 weeks, followed by 75 mg once-weekly intravenously dosed (175/75 mg) is approved in the European Union for treatment of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored whether similar efficacy, but improved safety could be achieved with 75 mg without 175 mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75 mg (n = 47) or 75 mg (n = 42). Treatment continued until objective disease progression...
August 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28760309/autologous-stem-cell-transplant-still-the-standard-for-fit-patients-with-mantle-cell-lymphoma
#11
REVIEW
Ashley D Staton, Amelia A Langston
Mantle cell lymphoma is a relatively rare malignancy, comprising fewer than 10% of all non-Hodgkin lymphomas. It is a heterogeneous disease, and although most patients experience an aggressive clinical course, some have a more indolent disease and may not require immediate therapy. There are currently few reliable prognostic markers, making it difficult to accurately predict which patients require early intensive treatment. We argue that consolidative autologous stem cell transplantation in first remission remains the standard of care for the young and fit patient population, based on long-term data from phase II and III trials demonstrating that early transplantation extends both progression-free and overall survival...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28758825/rationale-for-targeting-tumor-cells-in-their-microenvironment-for-mantle-cell-lymphoma-treatment
#12
Antonin Papin, Steven Le Gouill, David Chiron
Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma associated with poor prognosis, and despite recent improvements in the therapeutic strategies for treating MCL, its management remains challenging. While improvements in next generation sequencing technology have greatly increased our understanding of the intrinsic abnormalities of MCL, the role of extrinsic signaling remains largely unknown. Recent studies have highlighted the central role of the MCL microenvironment in tumor cell survival, drug resistance and proliferation...
July 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28752619/spectrum-and-immunophenotyping-of-653-patients-with-b-cell-chronic-lymphoproliferative-disorders-in-china-a-single-centre-analysis
#13
Yi Miao, Lei Cao, Qian Sun, Xiao-Tong Li, Yan Wang, Chun Qiao, Li Wang, Rong Wang, Hai-Rong Qiu, Wei Xu, Jian-Yong Li, Yu-Jie Wu, Lei Fan
The incidence of B-cell chronic lymphoproliferative disorders (B-CLPDs) is significantly lower in China than that in western countries. There have been studies involving small cohorts with conflicting results regarding the spectrum of B-CLPDs in China, and the types and immunophenotyping of B-CLPDs in China remain largely unexplored. We conducted a retrospective analysis of 653 cases of B-CLPDs seen in our centre from 2011 to 2015. Four-colour flow cytometry was used to determine the expression of each immunological marker, and the diagnostic values of the immunological markers were also investigated...
July 28, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28751558/characterization-of-atrial-fibrillation-adverse-events-reported-in-ibrutinib-randomized-controlled-registration-trials
#14
Jennifer R Brown, Javid Moslehi, Susan O' Brien, Paolo Ghia, Peter Hillmen, Florence Cymbalista, Tait D Shanafelt, Graeme Fraser, Simon Rule, Thomas J Kipps, Steven Coutre, Marie-Sarah Dilhuydy, Paula Cramer, Alessandra Tedeschi, Ulrich Jaeger, Martin Dreyling, John C Byrd, Angela Howes, Michael Todd, Jessica Vermeulen, Danelle F James, Fong Clow, Lori Styles, Rudy Valentino, Mark Wildgust, Michelle Mahler, Jan A Burger
The first-in-class Bruton's tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation has been reported in 6-16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize atrial fibrillation with ibrutinib and its management. Atrial fibrillation incidence was 6.5% (95% CI: 4.8, 8.5) for ibrutinib at 16.6-months (vs. 1.6% [95% CI: 0...
July 27, 2017: Haematologica
https://www.readbyqxmd.com/read/28751356/sox11-holds-mantle-cell-lymphoma-s-key-to-home
#15
David Dominguez-Sola
No abstract text is available yet for this article.
July 27, 2017: Blood
https://www.readbyqxmd.com/read/28742622/rational-therapeutic-choice-for-older-patients-with-lymphoma
#16
Dominique Bron, Pierre Soubeyran
PURPOSE OF REVIEW: The choice for an optimal treatment in older lymphoma patients is a real challenge for hemato-oncologists. They have to treat a potentially curative lymphoma, and concomitantly protect their patients from unacceptable toxicities. Some recommendations are provided for the major subtypes of lymphomas including the antitumoral treatment and primarily the optimal supportive care. RECENT FINDINGS: All the recent literature data converge to say that the approach of an older patient with a malignant hemopathy is a multistep procedure...
July 22, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28733439/implementation-of-a-model-based-design-in-a-phase-1b-study-of-combined-targeted-agents
#17
Nolan A Wages, Craig A Portell, Michael E Williams, Mark R Conaway, Gina R Petroni
In recent years, investigators have recognized the rigidity of single agent, safety only, traditional designs, rendering them ineffective for conducting contemporary early-phase clinical trials, such as those involving combinations and /or biological agents.  Novel approaches are required to address these research questions, such as those posed in trials involving targeted therapies. We describe the implementation of a model-based design for identifying an optimal treatment combination, defined by low toxicity and high efficacy, in an early-phase trial evaluating a combination of two oral targeted inhibitors in relapsed / refractory mantle cell lymphoma...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28733266/long-term-results-of-high-dose-therapy-and-autologous-stem-cell-transplantation-for-mantle-cell-lymphoma-effectiveness-of-maintenance-rituximab
#18
Matthew G Mei, Thai M Cao, Lu Chen, Joo Song, Tanya Siddiqi, Ji-Lian Cai, Leonardo T Farol, Monzr M Al Malki, Amandeep Salhotra, Ibrahim Aldoss, Joycelynne Palmer, Alex F Herrera, Jasmine Zain, Leslie L Popplewell, Robert W Chen, Steven T Rosen, Stephen J Forman, Larry Kwak, Auayporn P Nademanee, Lihua E Budde
High-dose therapy followed by autologous stem cell transplantation (ASCT) can improve outcomes for mantle cell lymphoma (MCL) but is associated with a high incidence of relapse. A retrospective study of 191 MCL patients who underwent ASCT at City of Hope was performed to examine prognostic factors for outcomes after ASCT. For all patients the 5-year overall survival (OS) was 71% (95% confidence interval [CI], 63% to 77%) and progression-free survival (PFS) was 53% (95% CI, 45% to 60%). The 5-year cumulative incidence of relapse was 41% (95% CI, 34% to 48%) with a continuous pattern of relapse events occurring at a median of 2...
July 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28724540/targeting-bcl-2-in-b-cell-lymphomas
#19
Matthew S Davids
The B-cell leukemia/lymphoma-2 (BCL-2) family of proteins governs the intrinsic pathway of mitochondrial apoptosis. Dysregulation of BCL-2 has long been known to be a crucial part of the pathophysiology of B-cell lymphomas, yet several early attempts to target this pathway therapeutically were unsuccessful due to toxicity, lack of efficacy, or both. Recently, a highly potent and selective oral BCL-2 antagonist, venetoclax, was approved in chronic lymphocytic leukemia (CLL), where it has proven to be highly active, even in patients with high risk del(17p) disease...
July 19, 2017: Blood
https://www.readbyqxmd.com/read/28720472/mantle-cell-lymphoma-involving-the-esophagus-evaluated-by-magnifying-endoscopy-with-narrow-band-imaging
#20
Haruka Toyonaga, Masashi Fukushima, Tetsuro Inokuma, Yukihiro Imai
No abstract text is available yet for this article.
July 15, 2017: Gastrointestinal Endoscopy
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