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https://www.readbyqxmd.com/read/29415938/-acquisition-of-igh-ccnd1-translocation-during-the-natural-disease-course-in-a-patient-with-chronic-lymphocytic-leukemia
#1
Kosuke Arai, Fumisato Takagi, Saeko Sonokawa, Sayaka Suzuki, Eisaku Ito, Kengo Takeuchi, Takashi Kumagai
A 69-year-old man visited a doctor because of systemic lymphadenopathy. Peripheral blood examination revealed leukocytosis, anemia, and decreased platelet count (WBC, 103,060/µl; lymph, 92.2%; Hb, 8.9 g/dl; and Plt, 4.1×10 4 /µl). Bone marrow biopsy revealed that approximately 70% of nucleated cells were small, mature lymphoid cells with positive immunostaining for CD5, CD20, and CD23. He was diagnosed with chronic lymphocytic leukemia (CLL). The IgH/CCND1 translocation and ATM locus loss in 20% and 95% peripheral cells, respectively, were detected by fluorescence in situ hybridization...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29343153/cryptococcal-infections-in-two-patients-receiving-ibrutinib-therapy-for-chronic-lymphocytic-leukemia
#2
Matthew Stankowicz, Megan Banaszynski, Russell Crawford
Cryptococcal infections are responsible for significant morbidity and mortality in immunocompromised patients. Reports of these infections in patients on small molecular kinase inhibitors have not been widely reported in clinical trials. We describe one case of cryptococcal meningoencephalitis and one case of cryptococcal pneumonia in two patients who were receiving ibrutinib for chronic lymphocytic leukemia. Despite different sites of cryptococcal infection, both patients had similar presentations of acute illness...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29317454/casein-kinase-1-is-a-therapeutic-target-in-chronic-lymphocytic-leukemia
#3
Pavlina Janovska, Jan Verner, Jiri Kohoutek, Lenka Bryjova, Michaela Gregorova, Marta Dzimkova, Hana Skabrahova, Tomasz Radaszkiewicz, Petra Ovesna, Olga Vondalova Blanarova, Tereza Nemcova, Zuzana Hoferova, Katerina Vasickova, Lucie Smyckova, Alexander Egle, Sarka Pavlova, Lucie Poppova, Karla Plevova, Sarka Pospisilova, Vitezslav Bryja
Casein kinase (CK) 1δ/ε is a key component of non-canonical Wnt signaling pathways, which were shown previously to drive pathogenesis of chronic lymphocytic leukemia (CLL). In this study we investigated thoroughly the effects of CK1δ/ε inhibition on the primary CLL cells and analyzed the therapeutic potential in vivo using two murine model systems based on the Eµ-TCL1-induced leukemia (syngeneic adoptive transfer model and spontaneous disease development), which resemble closely the human CLL. We can demonstrate that CK1δ/ε inhibitor PF-670462 significantly blocks microenvironmental interactions - chemotaxis, invasion and communication with stromal cells in primary CLL cells in all major subtypes of CLL...
January 9, 2018: Blood
https://www.readbyqxmd.com/read/29305552/venetoclax-for-patients-with-chronic-lymphocytic-leukemia-who-progressed-during-or-after-idelalisib-therapy
#4
Steven Coutre, Michael Choi, Richard R Furman, Herbert Eradat, Leonard Heffner, Jeffrey A Jones, Brenda Chyla, Lang Zhou, Suresh Agarwal, Tina Waskiewicz, Maria Verdugo, Rod A Humerickhouse, Jalaja Potluri, William G Wierda, Matthew S Davids
B-cell receptor pathway inhibitors (BCRi) have transformed treatment for chronic lymphocytic leukemia (CLL); however, efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRi is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi prior to enrollment...
January 5, 2018: Blood
https://www.readbyqxmd.com/read/29191916/duvelisib-a-novel-oral-dual-inhibitor-of-pi3k-%C3%AE-%C3%AE-is-clinically-active-in-advanced-hematologic-malignancies
#5
Ian W Flinn, Susan O'Brien, Brad Kahl, Manish Patel, Yasuhiro Oki, Francine F Foss, Pierluigi Porcu, Jeffrey Jones, Jan A Burger, Nitin Jain, Virginia M Kelly, Kerstin Allen, Mark Douglas, Jennifer Sweeney, Patrick Kelly, Steven Horwitz
Duvelisib (IPI-145) is a novel, oral, dual inhibitor of phosphoinositide 3-kinase (PI3K)-δ and PI3K-γ in late-stage clinical development for treatment of hematologic malignancies. This Phase 1 study (registered as NCT01476657 at ClinicalTrials.gov) evaluated the maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of duvelisib in 210 patients with advanced hematologic malignancies. In the Dose Escalation Phase (n=31), duvelisib 8 to 100 mg BID was administered, with MTD determined to be 75 mg BID...
November 30, 2017: Blood
https://www.readbyqxmd.com/read/29122300/using-prognostic-models-in-cll-to-personalize-approach-to-clinical-care-are-we-there-yet
#6
REVIEW
Alain Mina, Jose Sandoval Sus, Elsa Sleiman, Javier Pinilla-Ibarz, Farrukh T Awan, Mohamed A Kharfan-Dabaja
Four decades ago, two staging systems were developed to help stratify CLL into different prognostic categories. These systems, the Rai and the Binet staging, depended entirely on abnormal exam findings and evidence of anemia and thrombocytopenia. Better understanding of biologic, genetic, and molecular characteristics of CLL have contributed to better appreciating its clinical heterogeneity. New prognostic models, the GCLLSG prognostic index and the CLL-IPI, emerged. They incorporate biologic and genetic information related to CLL and are capable of predicting survival outcomes and cases anticipated to need therapy earlier in the disease course...
October 28, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29108368/phase-i-clinical-trial-of-the-base-excision-repair-inhibitor-methoxyamine-in-combination-with-fludarabine-for-patients-with-advanced-hematologic-malignancies
#7
Paolo F Caimi, Brenda W Cooper, Basem M William, Afshin Dowlati, Paul M Barr, Pingfu Fu, John Pink, Yan Xu, Hillard M Lazarus, Marcos de Lima, Stanton L Gerson
Purpose: We determined the safety, pharmacokinetics, pharmacodynamics and recommended phase II dose of the base excision repair blocker methoxyamine combined with fludarabine. Materials and Methods: This was a phase I study with intravenous fludarabine (25 mg/m2, days 1-5), and methoxyamine (15 mg/m2-120 mg/m2, once). A maximum of six cycles were given. Adult patients with relapsed/refractory hematologic malignancies, excluding acute myeloid leukemia, were eligible...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29081197/-clinical-features-and-prognosis-of-17-patients-with-primary-cold-agglutinin-disease
#8
Y Y Wu, X X Cao, H Cai, L Zhang, D B Zhou, J Li
Objective: To explore the clinical characteristics, treatment and prognosis in 17 patients with primary cold agglutinin disease (CAD) . Methods: Clinical data, treatment and survival status of 17 patients diagnosed with primary cold agglutinin disease in Peking Union Medical College Hospital during April 2007 to October 2016 were retrospectively analyzed. The MYD88(L265P) mutation was tested in 4 patients. Results: The median age of 17 patients was 67 years (range, 51-86 years) , and male- to female ratio was 1...
September 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28945711/venetoclax-management-and-care-for-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukemia%C3%A2
#9
Heather Brumbaugh Paradis, Debbie Alter, Diane Llerandi
BACKGROUND: Venetoclax (Venclexta™) is a potent, selective, orally available, small-molecule B-cell lymphoma 2 inhibitor that achieves response rates of about 80% and has an acceptable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL).
. OBJECTIVES: The aim was to describe treatment management considerations when caring for patients using venetoclax.
. METHODS: A review was done of safety and management considerations based on current clinical practice and 240 patients with CLL who received venetoclax monotherapy on clinical trials from 2011-2016...
October 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28871936/xanthoma-like-skin-changes-in-an-elderly-woman-with-a-normal-lipid-profile
#10
Piotr Nockowski, Zdzisław Woźniak, Adam Reich, Joanna Maj
Dear Editor, An 83-year-old woman developed yellow-brownish infiltrates, nodules, and tumors mimicking xanthomas, mostly involving the periorbital and chest area within three months (Figure 1). She had no abnormalities in serum cholesterol or triglycerides levels. A detailed laboratory analysis revealed the presence of mild monoclonal gammopathy with a presence of immunoglobulin G (IgG) kappa light chains; however, according to hematologist consultation, it did not require medical intervention. Imaging assessment and ultrasound examination did not show any specific involvement of internal organs...
July 2017: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/28708231/ibrutinib-treatment-of-a-patient-with-relapsing-chronic-lymphocytic-leukemia-and-sustained-remission-of-richter-syndrome
#11
Elisa Albi, Stefano Baldoni, Patrizia Aureli, Erica Dorillo, Beatrice Del Papa, Stefano Ascani, Mauro Di Ianni, Franca Falzetti, Paolo Sportoletti
PURPOSE: Richter syndrome (RS) is a rare event in chronic lymphocytic leukemia (CLL) that is influenced by biological factors and prior CLL treatments. Ibrutinib is a Bruton tyrosine kinase inhibitor that has shown remarkable efficacy in CLL; however, little is known about its relationship to RS. We report a case of ibrutinib efficacy against CLL in a patient with prolonged remission of RS. METHODS: The patient was diagnosed with CLL in 2003. Biological findings at onset included absent ZAP70 expression, mutated IGVH, and NOTCH1 mutation...
July 5, 2017: Tumori
https://www.readbyqxmd.com/read/28670081/treatment-of-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-presenting-simultaneously-with-acquired-hemophilia-and-warm-autoimmune-hemolytic-anemia
#12
Chelsea Williams, Christian Cable, Julia Choi
Since both acquired factor VIII inhibitor in non-hemophiliac patients and warm autoimmune hemolytic anemia are uncommon disorders with no case-controlled trials, managing these diseases can be challenging. We present a case of a 75-year-old man in whom both diseases were present simultaneously with life-threatening bleeding. This case is an example of the successful initial management and long-term treatment of acquired hemophilia A, warm autoimmune hemolytic anemia, and chronic lymphocytic leukemia/small lymphocytic lymphoma with rituximab, prednisone, and cyclophosphamide...
July 2017: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/28580841/safety-and-efficacy-of-ofatumumab-in-chronic-lymphocytic-leukemia-a-systematic-review-and-meta-analysis
#13
Yougen Wu, Yang Wang, Yuting Gu, Ju Xia, Xiaoyang Kong, Qingqing Qian, Yang Hong
OBJECTIVES: Increasing numbers of clinical studies have been carried out to investigate the therapeutic effect of Ofatumumab for patients with chronic lymphocytic leukemia (CLL) but no studies have yet reported a pooled estimate of the treatment effect. We performed a meta-analysis of evidence from 13 clinical trials to assess effectiveness and safety of Ofatumumab-based therapy in patients with CLL. METHODS: Relevant publications from PubMed, Web of Science, Embase, and ClinicalTrials...
June 3, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28477093/clinical-and-serological-autoimmune-complications-in-chronic-lymphocytic-leukemia
#14
Cengiz Demir, Ömer Ekinci
BACKGROUND: Autoimmune disorders often develop during the course of chronic lymphocytic leukemia (CLL). The aim of our study was to investigate the incidence of autoimmune complications (AIC) and serological autoantibodies, and to assess the relationship of these to patient characteristics. METHODS: We prospectively collected screenings of AIC and serological markers from a total of 192 patients. RESULTS: AIC was observed in 18 (9.4%) patients...
May 5, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28473690/clinical-and-laboratory-features-of-cd5-negative-chronic-lymphocytic-leukemia
#15
Cengiz Demir, Erdal Kara, Ömer Ekinci, Senar Ebinç
BACKGROUND Chronic lymphocytic leukemia (CLL) usually expresses CD5 antigen. However, 7-20% of patients are CD5 negative. We report here a series of 19 CD5-negative B-CLL cases. MATERIAL AND METHODS We reviewed 19 consecutive CD5-negative B-CLL cases seen in our medical center from 2009 to 2015 and compared them with 105 CD5-positive B-CLL cases. The two groups were compared in terms of clinical parameters, laboratory parameters, and survival characteristics. RESULTS Lymphadenopathy was present in 31.5% of the CD5-negative group and 51...
May 5, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28469947/successful-long-term-use-of-eltrombopag-in-a-patient-with-refractory-severe-thrombocytopenia-associated-with-chronic-lymphocytic-leukemia-that-allowed-oral-anticoagulant-treatment-for-severe-cardiomyopathy
#16
Juárez Salcedo Luis Miguel, Gil-Fernández Juan José
Autoimmune cytopenias (AICs) are frequently associated with chronic lymphocytic leukemia (CLL). The most common of these AICs is autoimmune hemolytic anemia (AIHA); the second most is immune thrombocytopenia (ITP). Here, we report on a patient with CLL-associated ITP, with thrombocytopenia refractory to corticosteroids and intravenous immunoglobulins, in which continuous oral treatment with Eltrombopag allowed initiation and maintenance of an oral anticoagulation treatment with Acenocoumarol that was indicated because of a severe arrhythmogenic cardiomyopathy...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28468797/selective-inhibition-of-nuclear-export-with-selinexor-in-patients-with-non-hodgkin-lymphoma
#17
MULTICENTER STUDY
John Kuruvilla, Michael Savona, Rachid Baz, Paul Morten Mau-Sorensen, Nashat Gabrail, Ramiro Garzon, Richard Stone, Michael Wang, Lynn Savoie, Peter Martin, Ian Flinn, Meagan Jacoby, Thaddeus J Unger, Jean-Richard Saint-Martin, Tami Rashal, Sharon Friedlander, Robert Carlson, Michael Kauffman, Sharon Shacham, Martin Gutierrez
Patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) have a poor prognosis and limited treatment options. We evaluated selinexor, an orally bioavailable, first-in-class inhibitor of the nuclear export protein XPO1, in this phase 1 trial to assess safety and determine a recommended phase 2 dose (RP2D). Seventy-nine patients with various NHL histologies, including diffuse large B-cell lymphoma, Richter's transformation, mantle cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia, were enrolled...
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28302090/characterizing-and-prognosticating-chronic-lymphocytic-leukemia-in-the-elderly-prospective-evaluation-on-455-patients-treated-in-the-united-states
#18
Chadi Nabhan, Anthony Mato, Christopher R Flowers, David L Grinblatt, Nicole Lamanna, Mark A Weiss, Matthew S Davids, Arlene S Swern, Shriya Bhushan, Kristen Sullivan, E Dawn Flick, Pavel Kiselev, Jeff P Sharman
BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is > 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites...
March 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28197963/a-concise-review-of-autoimmune-cytopenias-in-chronic-lymphocytic-leukemia
#19
REVIEW
Mazie Tsang, Sameer A Parikh
Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune complications such as autoimmune hemolytic anemia, immune thrombocytopenia, pure red cell aplasia, and autoimmune granulocytopenia. It is critical to diagnose cytopenias from these secondary complications of CLL accurately, since prognosis and therapy are substantially different from patients who have cytopenias due to extensive bone marrow infiltration by CLL. The pathogenesis of autoimmune cytopenias in CLL is complex; and it involves antigen presentation by CLL cells to polyclonal B cells resulting in production of autoantibody, and alteration of the T cell milieu tilting the balance in favor of an autoimmune response...
February 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28126962/safety-and-efficacy-of-abexinostat-a-pan-histone-deacetylase-inhibitor-in-non-hodgkin-lymphoma-and-chronic-lymphocytic-leukemia-results-of-a-phase-ii-study
#20
Vincent Ribrag, Won Seog Kim, Reda Bouabdallah, Soon Thye Lim, Bertrand Coiffier, Arpad Illes, Bernard Lemieux, Martin J S Dyer, Fritz Offner, Zakia Felloussi, Ioana Kloos, Ying Luan, Remus Vezan, Thorsten Graef, Franck Morschhauser
Histone deacetylase inhibitors are members of a class of epigenetic drugs that have proven activity in T-cell malignancies, but little is known about their efficacy in B-cell lymphomas. Abexinostat is an orally available hydroxamate-containing histone deacetylase inhibitor that differs from approved inhibitors; its unique pharmacokinetic profile and oral dosing schedule, twice daily four hours apart, allows for continuous exposure at concentrations required to efficiently kill tumor cells. In this phase II study, patients with relapsed/refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia received oral abexinostat at 80 mg BID for 14 days of a 21-day cycle and continued until progressive disease or unacceptable toxicity...
May 2017: Haematologica
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