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https://www.readbyqxmd.com/read/28916311/lenalidomide-maintenance-after-first-line-therapy-for-high-risk-chronic-lymphocytic-leukaemia-cllm1-final-results-from-a-randomised-double-blind-phase-3-study
#1
Anna Maria Fink, Jasmin Bahlo, Sandra Robrecht, Othman Al-Sawaf, Ali Aldaoud, Holger Hebart, Kathleen Jentsch-Ullrich, Steffen Dörfel, Kirsten Fischer, Clemens-Martin Wendtner, Thomas Nösslinger, Paolo Ghia, Francesc Bosch, Arnon P Kater, Hartmut Döhner, Michael Kneba, Karl-Anton Kreuzer, Eugen Tausch, Stephan Stilgenbauer, Matthias Ritgen, Sebastian Böttcher, Barbara Eichhorst, Michael Hallek
BACKGROUND: The combined use of genetic markers and detectable minimal residual disease identifies patients with chronic lymphocytic leukaemia with poor outcome after first-line chemoimmunotherapy. We aimed to assess lenalidomide maintenance therapy in these high-risk patients. METHODS: In this randomised, double-blind, phase 3 study (CLLM1; CLL Maintenance 1 of the German CLL Study Group), patients older than 18 years and diagnosed with immunophenotypically confirmed chronic lymphocytic leukaemia with active disease, who responded to chemoimmunotherapy 2-5 months after completion of first-line therapy and who were assessed as having a high risk for an early progression with at least a partial response after four or more cycles of first-line chemoimmunotherapy, were eligible if they had high minimal residual disease levels or intermediate levels combined with an unmutated IGHV gene status or TP53 alterations...
September 12, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28864095/minimal-residual-disease-in-chronic-lymphocytic-leukaemia
#2
REVIEW
José Antonio García Vela, José Antonio García Marco
Minimal residual disease (MRD) assessment is an important endpoint in the treatment of chronic lymphocytic leukaemia (CLL). It is highly predictive of prolonged progression-free survival (PFS) and overall survival and could be considered a surrogate for PFS in the context of chemoimmunotherapy based treatment. Evaluation of MRD level by flow cytometry or molecular techniques in the era of the new BCR and Bcl-2 targeted inhibitors could identify the most cost-effective and durable treatment sequencing. A therapeutic approach guided by the level of MRD might also determine which patients would benefit from an early stop or consolidation therapy...
August 29, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28859185/salvage-chemoimmunotherapy-with-inotuzumab-ozogamicin-combined-with-mini-hyper-cvd-for-patients-with-relapsed-or-refractory-philadelphia-chromosome-negative-acute-lymphoblastic-leukemia-a-phase-2-clinical-trial
#3
Elias Jabbour, Farhad Ravandi, Partow Kebriaei, Xuelin Huang, Nicholas J Short, Deborah Thomas, Koji Sasaki, Michael Rytting, Nitin Jain, Marina Konopleva, Guillermo Garcia-Manero, Richard Champlin, David Marin, Tapan Kadia, Jorge Cortes, Zeev Estrov, Koichi Takahashi, Yogin Patel, Maria R Khouri, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Hagop Kantarjian
Importance: The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has single-agent activity in R/R ALL. Objective: To evaluate the efficacy and safety of inotuzumab ozogamicin plus low-intensity chemotherapy in patients with R/R ALL. Design, Setting, and Participants: A single-arm, phase 2 study of adults with R/R B-cell ALL conducted at The University of Texas MD Anderson Cancer Center, Houston...
August 31, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28845710/combination-therapy-with-the-type-ii-anti-cd20-antibody-obinutuzumab
#4
Christian Klein, Marina Bacac, Pablo Umana, Günter Fingerle-Rowson
Obinutuzumab is a novel humanized type II glycoengineered anti-CD20 antibody approved for first-line treatment of chronic lymphocytic leukemia (CLL) in combination with chlorambucil and for treatment of rituximab-refractory follicular lymphoma (FL). Areas covered: We describe current preclinical and clinical evidence supporting the combination of obinutuzumab with not only chemotherapy but also novel targeted therapies for B-cell hematologic malignancies, and its application in chemoimmunotherapy. We also provide an overview of the current clinical trial landscape investigating novel combination therapies based on obinutuzumab...
August 26, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28841210/alternative-splicing-discriminates-molecular-subtypes-and-has-prognostic-impact-in-diffuse-large-b-cell-lymphoma
#5
S-K Leivonen, M Taskinen, A Cervera, M-L Karjalainen-Lindsberg, J Delabie, H Holte, R Lehtonen, S Hautaniemi, S Leppä
Effect of alternative splicing (AS) on diffuse large B-cell lymphoma (DLBCL) pathogenesis and survival has not been systematically addressed. Here, we compared differentially expressed genes and exons in association with survival after chemoimmunotherapy, and between germinal center B-cell like (GCB) and activated B-cell like (ABC) DLBCLs. Genome-wide exon array-based screen was performed from samples of 38 clinically high-risk patients who were treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis...
August 25, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28831584/clinical-outcomes-in-patients-with-diffuse-large-b-cell-lymphoma-with-a-partial-response-to-first-line-r-chop-chemotherapy-prognostic-value-of-secondary-international-prognostic-index-scores-and-deauville-scores
#6
Hyewon Lee, Yu Ri Kim, Soo-Jeong Kim, Yong Park, Hyeon-Seok Eom, Sung Yong Oh, Hyo Jung Kim, Hye Jin Kang, Won-Sik Lee, Joon Ho Moon, Young-Woong Won, Tae-Sung Kim, Jin Seok Kim
After introducing a rituximab-containing chemoimmunotherapy (R-CHOP) for diffuse large B cell lymphoma (DLBCL), a partial response (PR) which is regarded as treatment failure is still observed. To investigate the prognostic factors for the DLBCL patients with a PR to R-CHOP, we retrospectively evaluated 758 newly diagnosed DLBCL patients. After R-CHOP, 88 (11.6%) achieved a PR. Three-year progression-free and overall survival rates measured from the date of PR achievement (PFS2 and OS2) were 57.4 and 67.8%, respectively...
August 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28819011/tp53-mutations-identify-younger-mantle-cell-lymphoma-patients-who-do-not-benefit-from-intensive-chemoimmunotherapy
#7
Christian W Eskelund, Christina Dahl, Jakob W Hansen, Maj Westman, Arne Kolstad, Lone B Pedersen, Carmen P Montano-Almendras, Simon Husby, Catja Freiburghaus, Sara Ek, Anja Pedersen, Carsten Niemann, Riikka Räty, Peter Brown, Christian H Geisler, Mette K Andersen, Per Guldberg, Mats Jerkeman, Kirsten Grønbæk
Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable and we are still unable to identify patients who will not benefit from the current standard-of-care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger MCL patients from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) and CDKN2A (20%) were significantly associated with inferior outcomes (together with MIPI, MIPI-c, Blastoid morphology and Ki67>30%); however, in multivariate analyses only TP53 mutations (HR=6...
August 17, 2017: Blood
https://www.readbyqxmd.com/read/28798068/consolidation-treatment-with-lenalidomide-following-front-line-or-salvage-chemoimmunotherapy-in-chronic-lymphocytic-leukemia
#8
Paolo Strati, Michael J Keating, Jan A Burger, Susan M O'Brien, William G Wierda, Zeev Estrov, Gracy Zacharian, Alessandra Ferrajoli
No abstract text is available yet for this article.
August 10, 2017: Haematologica
https://www.readbyqxmd.com/read/28782884/chronic-lymphocytic-leukemia-2017-update-on-diagnosis-risk-stratification-and-treatment
#9
REVIEW
Michael Hallek
DISEASE OVERVIEW: Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B cells. DIAGNOSIS: The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen and B-cell markers...
September 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28780145/what-is-the-role-of-chemotherapy-in-patients-with-chronic-lymphocytic-leukemia
#10
REVIEW
Bruce D Cheson
The current standard treatment for patients with chronic lymphocytic leukemia who require therapy is chemoimmunotherapy. However, the availability of an increasing number of targeted agents and combination warrants a reassessment of that approach. The high rate of durable responses with ibrutinib in relapsed refractory patients has established its role in this setting; however, because of its impressive efficacy as initial treatment, it should be considered as part of the algorithm in appropriate patients. There is virtually no role for chemotherapy in the relapsed or refractory setting, but, instead, consideration of active agents including idelalisib plus rituximab, or, particularly venetoclax...
July 12, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28750119/minimal-residual-disease-in-chronic-lymphocytic-leukemia-in-the-era-of-novel-agents-a-review
#11
Meghan Thompson, Danielle Brander, Chadi Nabhan, Anthony Mato
Importance: The landscape of chronic lymphocytic leukemia (CLL) treatment has changed considerably since the first reported assessment of minimal residual disease (MRD) by flow cytometry in 1992. Chemoimmunotherapy (CIT) combinations have become the standard of care for most patients, and novel targeted agents are rapidly being incorporated into the front-line and relapsed settings. Minimal residual disease status has been shown to be a predictor of both progression-free survival (PFS) and overall survival (OS) at the time of response assessment following CIT, but less is known about the relationship between MRD and outcomes after novel oral therapeutics...
July 27, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28749548/c-myc-positive-relapsed-and-refractory-diffuse-large-b-cell-lymphoma-impact-of-additional-hits-and-outcomes-with-subsequent-therapy
#12
Narendranath Epperla, Kami J Maddocks, Mohammed Salhab, Julio C Chavez, Nishitha Reddy, Reem Karmali, Elvira Umyarova, Veronika Bachanova, Cristiana Costa, Martha Glenn, Oscar Calzada, Ana C Xavier, Zheng Zhou, Nasheed M Hossain, Francisco J Hernandez-Ilizaliturri, Zeina Al-Mansour, Stefan K Barta, Saurabh Chhabra, Frederick Lansigan, Amitkumar Mehta, Michael V Jaglal, Andrew Evans, Christopher R Flowers, Jonathon B Cohen, Timothy S Fenske, Mehdi Hamadani, Luciano J Costa
BACKGROUND: The impact of MYC proto-oncogene, basic helix-loop-helix (MYC) translocations (with or without additional rearrangements involving the B-cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary treatment failure is not well defined. METHODS: This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy...
July 27, 2017: Cancer
https://www.readbyqxmd.com/read/28748453/patterns-of-failure-of-diffuse-large-b%C3%A2-cell-lymphoma-patients-after-involved-site-radiotherapy
#13
Eva Holzhäuser, Maximilian Berlin, Daniel Wollschläger, Thomas Bezold, Arnulf Mayer, Georg Heß, Heinz Schmidberger
PURPOSE: Radiotherapy (RT) in combination with chemoimmunotherapy is highly efficient in the treatment of diffuse large B‑cell lymphoma (DLBCL). This retrospective analysis evaluated the efficacy of the treatment volume and the dose concept of involved-site RT (ISRT). PATIENTS AND METHODS: We identified 60 histologically confirmed stage I-IV DLBCL patients treated with multimodal cytotoxic chemoimmunotherapy and followed by consolidative ISRT from 2005-2015. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method...
July 26, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28745332/impact-of-gender-on-outcome-after-chemoimmunotherapy-in-patients-with-chronic-lymphocytic-leukemia-a-meta-analysis-by-the-german-cll-study-group
#14
O Al-Sawaf, S Robrecht, J Bahlo, A M Fink, P Cramer, J von Tresckow, C Maurer, M Bergmann, T Seiler, E Lange, M Kneba, S Stilgenbauer, H Döhner, M G Kiehl, U Jäger, C M Wendtner, K Fischer, V Goede, M Hallek, B Eichhorst, G Hopfinger
No abstract text is available yet for this article.
July 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28742455/chemoimmunotherapy-is-not-dead-yet-in-chronic-lymphocytic-leukemia
#15
Jennifer R Brown, Neil E Kay
No abstract text is available yet for this article.
September 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28720054/impact-of-novel-agents-on-patient-relevant-outcomes-in-patients-with-previously-untreated-chronic-lymphocytic-leukemia-who-are-not-eligible-for-fludarabine-based-therapy
#16
Moushmi Singh, Stuart Mealing, Simona Baculea, Sarah Cote, Jo Whelan
BACKGROUND: Chronic lymphocytic leukemia (CLL) is an orphan disease that primarily affects the elderly. The majority of symptomatic patients eligible for frontline treatment are unfit for fludarabine based chemoimmunotherapy. Historical treatment includes chlorambucil (Chl), bendamustine/rituximab (BR), and chlorambucil/rituximab/ChlR combination. Clinical guidelines now recommend the use of novel agents, such as ibrutinib (Ibr), in both frontline and relapse settings and other novel agents, such as idelalisib (with rituximab), in relapse settings...
August 9, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28713366/intratumoral-lentivector-mediated-tgf-%C3%AE-1-gene-downregulation-as-a-potent-strategy-for-enhancing-the-antitumor-effect-of-therapy-composed-of-cyclophosphamide-and-dendritic-cells
#17
Joanna Rossowska, Natalia Anger, Agnieszka Szczygieł, Jagoda Mierzejewska, Elżbieta Pajtasz-Piasecka
Vaccination with dendritic cells (DCs) stimulated with tumor antigens can induce specific cellular immune response that recognizes a high spectrum of tumor antigens. However, the ability of cancer cells to produce immunosuppressive factors drastically decreases the antitumor activity of DCs. The main purpose of the study was to improve the effectiveness of DC-based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and DCs by application of lentivectors (LVs)-encoding short hairpin RNA specific for TGF-β1 (shTGFβ1 LVs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28707314/nodular-lymphocyte-predominant-hodgkin-s-lymphoma-in-daily-practice-a-multicenter-experience
#18
Aliihsan Gemici, Ismet Aydogdu, Hatice Terzi, Mehmet Sencan, Alma Aslan, Ali Hakan Kaya, Mehmet Sinan Dal, Meltem Olga Akay, Mehmet Hilmi Dogu, Orhan Ayyildiz, Fahri Sahin, Gulsum Akgun Cagliyan, Mehmet Yilmaz, Zafer Gokgoz, Yusuf Bilen, Cengiz Demir, Omur Gokmen Sevindik, Serdal Korkmaz, Bulent Eser, Fevzi Altuntas
Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin's lymphoma. In this study, we aimed to investigate the clinical features and therapeutic outcomes of patients with NLPHL who were diagnosed at different institutes in Turkey. We retrospectively reviewed the records of the patients diagnosed with NLPHL. Adult patients who were diagnosed after 2005 with histological confirmation were selected for the study. Forty-three patients were included in the study. Median age of patients was 37...
July 14, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28698783/lenalidomide-and-temozolomide-combination-in-a-very-elderly-patient-with-cns-relapse-of-diffuse-large-b-cell-lymphoma
#19
Emanuele Cencini, Alberto Fabbri, Umberto Arrigucci, Alfonso Cerase, Monica Bocchia
Central nervous system (CNS) relapse is an infrequent but severe complication for DLBCL patients, associated with poor prognosis. Intravenous prophylaxis with high-dose methotrexate has shown promising results but is rarely feasible in elderly and/or nephropathic patients. A 83 years old woman with CNS relapse occurred 6 months after chemoimmunotherapy. The patient was defined ineligible for radiotherapy (RT) and started oral Temozolomide 250mg daily for 5 consecutive days without any improvement after 1st cycle...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28696801/analysis-of-the-risk-of-infection-in-patients-with-chronic-lymphocytic-leukemia-in-the-era-of-novel-therapies
#20
AnnaLynn M Williams, Andrea M Baran, Philip J Meacham, Megan M Feldman, Hugo E Valencia, Catherine Newsom-Stewart, Nealansh Gupta, Michelle C Janelsins, Paul M Barr, Clive S Zent
We studied the risk of infections in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Major infections were defined as requiring hospital admission or intravenous antimicrobial treatment. Incidence rate (IR) ratios (IRR) were used to compare infection rates. Of 263 CLL patients followed for 936.9 person-years, 60% required treatment for progressive CLL (66 received ibrutinib). Infections occurred in 71.9% patients (IR 92.4/100 person-years) with 31.9% having major infections (IR 20...
July 11, 2017: Leukemia & Lymphoma
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