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https://www.readbyqxmd.com/read/28203581/long-term-response-and-possible-cure-of-patients-with-b-cell-malignancies-with-dose-escalated-rituximab
#1
Lauren M Jacobs, Peter H Wiernik, Janice P Dutcher, Pablo Muxi
Rituximab (R), a chimeric monoclonal antibody targeting CD20 antigen on B-cells, has become a standard of care in the treatment of B-cell malignancies, most often in conjunction with cytotoxic chemotherapy. Activity has been demonstrated in many subtypes of B-cell lymphoma, including diffuse large cell lymphoma, follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), lymphocyte-predominant Hodgkin lymphoma, and Waldenström macroglobulinemia (WM). Additionally, dose escalation of R as a single agent has demonstrated improved activity in previously treated/poor prognosis CLL...
January 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28195089/immunogenetics-of-chronic-lymphocytic-leukemia
#2
Nikhil Patkar, Nikhil Rabade, Pratibha Amare Kadam, Falguni Mishra, Aditi Muranjan, Prashant Tembhare, Shruti Chaudhary, Swapnali Joshi, Hasmukh Jain, Uma Dangi, Bhausaheb Bagal, Navin Khattry, Hari Menon, Sumeet Gujral, Manju Sengar, P G Subramanian
INTRODUCTION: Cytogenetic aberrations as well as presence of IGVH mutations are the underlying reason for clinical heterogeneity in Chronic Lymphocytic Leukemia (CLL). The presence of IGVH mutations as well as the predominant gene usage shows geographical variations. However, there is no study from India addressing immunogenetics of CLL. In a first Indian study we document the immunogenetics of CLL in a large tertiary hospital. METHODS: We analyzed IGVH mutation status, VH gene usage, cytogenetic abnormalities using FISH, immunophenotyping data and correlated them with standard clinical variables in 84 patients of CLL...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28187444/idelalisib-and-bendamustine-combination-is-synergistic-and-increases-dna-damage-response-in-chronic-lymphocytic-leukemia-cells
#3
Prexy Modi, Kumudha Balakrishnan, Qingshan Yang, William G Wierda, Michael J Keating, Varsha Gandhi
Idelalisib is a targeted agent that potently inhibits PI3Kδ which is exclusively expressed in hematological cells. Bendamustine is a well-tolerated cytotoxic alkylating agent which has been extensively used for treatment of chronic lymphocytic leukemia (CLL). Both these agents are FDA-approved for CLL. To increase the potency of idelalisib and bendamustine, we tested their combination in primary CLL lymphocytes. While each compound alone produced a moderate response, combination at several concentrations resulted in synergistic cytotoxicity...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185174/current-treatment-of-chronic-lymphocytic-leukemia
#4
REVIEW
Krzysztof Jamroziak, Bartosz Puła, Jan Walewski
A number of new treatment options have recently emerged for chronic lymphocytic leukemia (CLL) patients, including the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3-kinase (PI3K) delta isoform inhibitor idelalisib combined with rituximab, the Bcl-2 antagonist venetoclax, and the new anti-CD20 antibodies obinutuzumab and ofatumumab. Most of these agents are already included into treatment algorithms defined by international practice guidelines, but more clinical investigations are needed to answer still remaining questions...
January 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28182141/obinutuzumab-in-chronic-lymphocytic-leukemia-design-development-and-place-in-therapy
#5
REVIEW
Othman Al-Sawaf, Kirsten Fischer, Anja Engelke, Natali Pflug, Michael Hallek, Valentin Goede
For decades, treatment of chronic lymphocytic leukemia (CLL) has been based on chemotherapy. This changed when the first CD20 antibody rituximab was introduced. Since 2008, the combination of chemotherapy and CD20 antibodies has become the standard of care for most patients, and a significant fraction of patients had very long-lasting remissions after chemoimmunotherapy. Despite the improvement of response rates and overall survival (OS) by the use of chemoimmunotherapy, most CLL patients will relapse eventually...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28180067/-hemophagocytic-lymphohistiocytosis-after-ebv-reactivation-and-ibrutinib-treatment-in-relapsed-refractory-chronic-lymphocytic-leukemia
#6
Maurizio Cavallari, Maria Ciccone, Simonetta Falzoni, Francesco Cavazzini, Luca Formigaro, Francesco Di Virgilio, Antonella Rotola, Gian Matteo Rigolin, Antonio Cuneo
Hemophagocytic Lymphohistiocytosis (HLH) is a rare syndrome characterized by ineffective T-cell and NK response. We report the clinical course of a patient with relapsed CLL who developed acute symptoms soon after starting ibrutinib. Hyperpyrexia, splenomegaly, hyperferritinemia, hypertriglyceridemia, cytopenias, and a typical cytokine pattern, i.e. high interleukin (IL)-6, IL10 and IL18, were consistent with a diagnosis of HLH. Coexistent Epstein Barr virus reactivation was documented. Ibrutinib-induced impairment of NK degranulation, associated with EBV reactivation and CLL-related immunodeficiency may have contributed to the development of HLH in our patient...
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/28171709/long-term-outcomes-for-patients-with-chronic-lymphocytic-leukemia-who-discontinue-ibrutinib
#7
Preetesh Jain, Philip A Thompson, Michael Keating, Zeev Estrov, Alessandra Ferrajoli, Nitin Jain, Hagop Kantarjian, Jan A Burger, Susan O'Brien, William G Wierda
BACKGROUND: Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported. METHODS: Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively analyzed...
February 7, 2017: Cancer
https://www.readbyqxmd.com/read/28169240/synergistic-induction-of-apoptosis-in-b-cell-chronic-lymphocytic-leukemia-cells-after-treatment-with-all-trans-retinoic-acid-in-combination-with-interleukin-21-and-rituximab
#8
Kazem Abbaszadeh-Goudarzi, Fazel Shokri, Mostafa Hosseini, Farhad Jadidi-Niaragh, Ghasem Ghalamfarsa, Ali Akbar Saboor-Yaraghi
AIM: B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western world and characterized by the progressive expansion of malignant B lymphocytes in peripheral blood. In spite of advances in sciences to recognize the number of effective agents for the treatment of chronic lymphocytic leukemia (CLL), this leukemia is thought as incurable one. Introducing a new therapy that has a direct effect on B-CLL lymphocytes and no cytotoxic effects on the other cells is a great wish...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28160756/receptor-tyrosine-kinase-like-orphan-receptor-1-ror-1-an-emerging-target-for-diagnosis-and-therapy-of-chronic-lymphocytic-leukemia
#9
REVIEW
Leili Aghebati-Maleki, Mahdi Shabani, Behzad Baradaran, Morteza Motallebnezhad, Jafar Majidi, Mehdi Yousefi
Chronic lymphocytic leukemia (CLL) is characterized by reposition of malignant B cells in the blood, bone marrow, spleen and lymph nodes. It remains the most common leukemia in the Western world. Within the recent years, major breakthroughs have been made to prolong the survival and improve the health of patients. Despite these advances, CLL is still recognized as a disease without definitive cure. New treatment approaches, based on unique targets and novel drugs, are highly desired for CLL therapy. The Identification and subsequent targeting of molecules that are overexpressed uniquely in malignant cells not normal ones play critical roles in the success of anticancer therapeutic strategies...
February 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28160213/a-multicenter-single-arm-phase-ii-clinical-trial-of-bendamustine-monotherapy-in-patients-with-chronic-lymphocytic-leukemia-in-japan
#10
Yoshiaki Ogawa, Koji Izutsu, Toru Kiguchi, Ilseung Choi, Yoshifusa Takatsuka, Kiyoshi Ando, Junji Suzumiya
The present study was intended to examine the efficacy and safety of bendamustine monotherapy in patients with previously untreated chronic lymphocytic leukemia (CLL) for whom treatment with fludarabine (FLU) was not suitable, and in FLU-naïve patients with relapsed/refractory CLL. We intravenously administered bendamustine 100 mg/m(2)/day on days 1 and 2 of each 28-day cycle to 10 patients (eight previously untreated; two relapsed/refractory) up to six cycles. The primary endpoint was overall response rate (ORR: partial remission or better) according to the 2008 International Workshop on the CLL guidelines...
February 3, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28159928/a-meta-analysis-of-hla-peptidome-composition-in-different-hematological-entities-entity-specific-dividing-lines-and-pan-leukemia-antigens
#11
Linus Backert, Daniel Johannes Kowalewski, Simon Walz, Heiko Schuster, Claudia Berlin, Marian Christoph Neidert, Mirle Schemionek, Tim H Brümmendorf, Vladan Vucinic, Dietger Niederwieser, Lothar Kanz, Helmut Rainer Salih, Oliver Kohlbacher, Katja Weisel, Hans-Georg Rammensee, Stefan StevanoviÄ, Juliane Sarah Walz
Hematological malignancies (HM) are highly amenable targets for immunotherapeutic intervention and may be effectively treated by antigen-specific T-cell based treatment. Recent studies demonstrate that physiologically occurring anti-cancer T-cell responses in certain HM entities target broadly presented non-mutated epitopes. HLA ligands are thus implied as prime targets for broadly applicable and antigen-specific off-the-shelf compounds. With the aim of assessing the presence of common targets shared among different HM which may enable addressing a larger patient collective we conducted a meta-analysis of 83 mass spectrometry-based HLA peptidome datasets (comprising 40,361 unique peptide identifications) across four major HM (19 AML, 16 CML, 35 CLL, and 13 MM/MCL samples) and investigated similarities and differences within the HLA presented antigenic landscape...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28157628/characterization-of-treatment-and-outcomes-in-a-population-based-cohort-of-patients-with-chronic-lymphocytic-leukemia-referred-for-cytogenetic-testing-in-british-columbia-canada
#12
Steven J Huang, Lauren J Lee, Alina S Gerrie, Tanya L Gillan, Helene Bruyere, Monica Hrynchak, Adam C Smith, Aly Karsan, Khaled M Ramadan, Kavisha S Jayasundara, Cynthia L Toze
This study evaluates outcomes in chronic lymphocytic leukemia (CLL) based on first-line therapy in a large consecutive population-based cohort of 669 patients with fluorescence in-situ hybridization (FISH) data in British Columbia, Canada during the period when chemoimmunotherapy was standard first-line treatment. When analyzed as a time-dependent variable, patients who required treatment (n=336) had a 4.7 times higher hazard of death than patients who did not (95% confidence interval 2.8-7.9, P<0.001). The majority of patients received fludarabine-rituximab (FR) in front-line...
January 15, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28156016/severe-pneumonia-associated-with-ibrutinib-monotherapy-for-cll-and-lymphoma
#13
Natalia Kreiniz, Jacob Bejar, Aaron Polliack, Tamar Tadmor
In recent years, there have been major advances in the treatment of chronic lymphocytic leukemia (CLL) particularly since the development of novel therapeutic agents, mostly "biological drugs." One of the obvious advantages of these agents is the decreased rate of infectious complications occurring during the course of therapy, compared to the use of standard immuno-chemotherapy regimens. Here, we describe 3 patients with CLL and 1 with mantle cell lymphoma who developed severe life-threatening pneumonias, during monotherapy with ibrutinib...
February 3, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28155013/targeted-therapy-in-chronic-lymphocytic-leukemia-cll
#14
REVIEW
Erin M Pettijohn, Shuo Ma
The standard of care for the treatment of chronic lymphocytic leukemia (CLL) has traditionally been chemoimmunotherapy. For patients who are unable to tolerate chemotherapy and those with high risk 17p deletions, there were previously few feasible or efficacious treatment options. Novel targeted agents for the treatment of CLL have the potential to offer long-term, durable remissions and offer promising treatment options for those in previously challenging population groups. Current targeted agents in CLL are directed against B cell receptor-associated tyrosine kinases such as BTK and SYK, the downstream PI3-kinase pathway, as well as the antiapoptotic protein BCL-2...
February 2, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28152957/real-world-treatment-patterns-and-health-care-resource-utilization-hru-among-patients-with-chronic-lymphocytic-leukemia-cll-by-regimen
#15
Lorie Ellis, Stephanie Korrer, Stacey DaCosta Byfield
: 15 Background: Few studies examine HRU of CLL, the most common hematologic malignancy in adults. This study describes HRU by the most common regimens among CLL patients (pts). METHODS: A retrospective study using a large, national U.S. claims database from 1/2007-10/2013 was conducted. Adult CLL pts (≥2 claims for CLL) with ≥1 claim for systemic anticancer therapy (SACT) were identified; first SACT claim date was the index date. Pts had to have a CLL diagnosis ≤3 months (m) prior to the index date and be continuously enrolled (CE) in the health plan for 24m pre- and ≥6m post-index date...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152789/does-oncology-patient-reported-healthcare-experience-vary-by-site-of-care-soc
#16
Adrianne Waldman Casebeer, Sari Hopson, Joseph Dye, Zhuliang Tao, Andrew M Howe, Stephen Stemkowski, Jeffrey Patton, Art Small, Anthony Masaquel
: 71 Background: Patients with cancer are increasingly receiving chemotherapy infusions in a hospital outpatient (HO) as compared to the physician practice setting (PO). Previous research has focused on SOC differences in economic measures, such as healthcare costs, in commercially insured populations. This study investigates SOC differences in patients' reported healthcare experience for a mostly Medicare population. METHODS: A convenience sample of 2,604 Humana members with cancer of the breast, lung, colon/rectum or NHL/CLL and treated in 2014 received a survey by mail to capture patient reported healthcare experiences...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152748/patient-activation-measures-distress-levels-and-causes-of-distress-in-chronic-lymphocytic-leukemia
#17
Emily Van Laar, Uma Borate, Bradford E Jackson, Maria Pisu, Pamela M Peters, Thomas Wayne Butler, Randall S Davis, Amitkumar Mehta, Aras Acemgil, Sara J Knight, Monika M Safford, Gabrielle Betty Rocque
: 201 Background: Patients with chronic lymphocytic leukemia (CLL) reporting high levels of distress due to knowledge gaps and emotional concerns can have negative outcomes and suffer from lower quality of life. Understanding patients' activation levels, causes of distress, knowledge gaps, and psychosocial needs are crucial in high quality care. Optimally activated, educated and empowered patients are better positioned to communicate effectively with providers regarding selection of, and adherence to, CLL treatment protocols and long-term care plans, and potentially improving quality of life...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152701/shared-decision-making-in-chronic-lymphocytic-leukemia-preferences-and-perceptions-of-patients-providers-and-navigators
#18
Emily Van Laar, Uma Borate, Karina I Halilova, Pamela M Peters, Bradford E Jackson, Maria Pisu, Thomas Wayne Butler, Randall S Davis, Amitkumar Mehta, Aras Acemgil, Sara J Knight, Monika M Safford
: 221 Background: In recent years, new treatments for chronic lymphocytic leukemia (CLL) with excellent response rates and varying toxicity profiles have emerged. In the setting of multiple available options, shared decision-making is critical. Developing strategies to enhance shared decision-making requires better understanding of how patients and providers make treatment decisions. METHODS: Patients with CLL and health care providers within the University of Alabama at Birmingham Health System Cancer Community Network were to assess how treatment decisions are made...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28138560/leukemia-cell-proliferation-and-death-in-chronic-lymphocytic-leukemia-patients-on-therapy-with-the-btk-inhibitor-ibrutinib
#19
Jan A Burger, Kelvin W Li, Michael J Keating, Mariela Sivina, Ahmed M Amer, Naveen Garg, Alessandra Ferrajoli, Xuelin Huang, Hagop Kantarjian, William G Wierda, Susan O'Brien, Marc K Hellerstein, Scott M Turner, Claire L Emson, Shih-Shih Chen, Xiao-Jie Yan, Dominik Wodarz, Nicholas Chiorazzi
BACKGROUND. Ibrutinib is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL) that inhibits Bruton's tyrosine kinase (BTK), a kinase involved in B cell receptor signaling. METHODS. We used stable isotopic labeling with deuterated water ((2)H2O) to measure directly the effects of ibrutinib on leukemia cell proliferation and death in 30 patients with CLL. RESULTS. The measured average CLL cell proliferation ("birth") rate before ibrutinib therapy was 0.39% of the clone per day (range 0...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28130399/constitutive-phosphorylation-of-stat3-by-the-ck2-blnk-cd5-complex
#20
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Ivo Veletic, Alessandra Ferrajoli, Jan Burger, Susan O'Brien, Prithviraj Bose, Philip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
: In chronic lymphocytic leukemia (CLL), STAT3 is constitutively phosphorylated on serine 727 and plays a role in the pathobiology of CLL. However, what induces constitutive phosphorylation of STAT3 is currently unknown. Mass spectrometry was used to identify casein kinase 2 (CK2), a serine/threonine kinase that co-immunoprecipitated with serine phosphorylated STAT3 (pSTAT3). Furthermore, activated CK2 incubated with recombinant STAT3 induced phosphorylation of STAT3 on serine 727. Although STAT3 and CK2 are present in normal B- and T-cells, STAT3 is not constitutively phosphorylated in these cells...
January 27, 2017: Molecular Cancer Research: MCR
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