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https://www.readbyqxmd.com/read/28212806/clonal-evolution-as-detected-by-interphase-fluorescence-in-situ-hybridization-is-associated-with-worse-overall-survival-in-a-population-based-analysis-of-patients-with-chronic-lymphocytic-leukemia-in-british-columbia-canada
#1
Steven J Huang, Krystal Bergin, Adam C Smith, Alina S Gerrie, Helene Bruyere, Chinmay B Dalal, Daniele K Sugioka, Monica Hrynchak, Khaled M Ramadan, Aly Karsan, Tanya L Gillan, Cynthia L Toze
This study evaluates prognostic markers as predictors of clonal evolution (CE) and assesses the impact of CE on overall survival (OS) in a population-based cohort of 159 consecutive eligible patients with chronic lymphocytic leukemia (CLL) obtained from the British Columbia Provincial CLL Database. CE was detected by interphase fluorescence in situ hybridization (FISH) in 34/159 patients (21%) with 65% of CE patients acquiring deletion 17p or 11q. CD38 positive status (≥30%) on flow cytometry predicted 2...
January 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28212557/using-high-sensitivity-sequencing-for-the-detection-of-mutations-in-btk-and-plc%C3%AE-2-genes-in-cellular-and-cell-free-dna-and-correlation-with-progression-in-patients-treated-with-btk-inhibitors
#2
Adam Albitar, Wanlong Ma, Ivan DeDios, Jeffrey Estella, Inhye Ahn, Mohammed Farooqui, Adrian Wiestner, Maher Albitar
Patients with chronic lymphocytic leukemia (CLL) that develop resistance to Bruton tyrosine kinase (BTK) inhibitors are typically positive for mutations in BTK or phospholipase c gamma 2 (PLCγ2). We developed a high sensitivity (HS) assay utilizing wild-type blocking polymerase chain reaction achieved via bridged and locked nucleic acids. We used this high sensitivity assay in combination with Sanger sequencing and next generation sequencing (NGS) and tested cellular DNA and cell-free DNA (cfDNA) from patients with CLL treated with the BTK inhibitor, ibrutinib...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28203581/long-term-response-and-possible-cure-of-patients-with-b-cell-malignancies-with-dose-escalated-rituximab
#3
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/28203174/richter-s-syndrome-with-hypercalcemia-induced-by-tumor-associated-production-of-parathyroid-hormone-related-peptide
#4
Naoki Watanabe, Hajime Yasuda, Soji Morishita, Yasuo Aota, Junichi Tomomatsu, Masaru Tanaka, Akimichi Ohsaka, Norio Komatsu
Humoral hypercalcemia due to parathyroid hormone-related peptide (PTHrP) elevation is a well-known complication of various malignancies, but the situation is rare concerning hematological malignancies except for adult T-cell leukemia/lymphoma. We report a case of Richter's syndrome with humoral hypercalcemia, and demonstrate by reverse transcription polymerase chain reaction (RT-PCR) that peripheral blood PTHrP levels were 2,500-fold higher compared to healthy controls. PTHrP production by tumor cells in chronic lymphocytic leukemia (CLL) and Richter's syndrome has been previously demonstrated by nonquantitative methods such as immunohistochemistry and northern blot analysis, but this is the first report using the RT-PCR method...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28203169/recurrent-malignant-melanoma-presenting-as-isolated-pleural-metastases-in-a-patient-with-chronic-lymphocytic-leukemia
#5
Kartik Anand, Shashank Cingam, Prakash Peddi
Isolated pleural metastasis with pleural effusion is a rare occurrence in malignant melanoma. We report an unusual case of a patient with chronic lymphocytic leukemia (CLL) and recurrent pleural effusions. The pleural fluid cytology and immunohistochemistry profile were consistent with the diagnosis of CLL. However, chemotherapy with pentostatin, cyclophosphamide, and rituximab did not result in any meaningful clinical response. A video-assisted thoracoscopic surgery and biopsy of the affected nodular parietal layer of the pleura were consistent with malignant melanoma...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28202953/fully-human-cd19-specific-chimeric-antigen-receptors-for-t-cell-therapy
#6
D Sommermeyer, T Hill, S M Shamah, A I Salter, Y Chen, K M Mohler, S R Riddell
Impressive results have been achieved by adoptively transferring T-cells expressing CD19-specific CARs with binding domains from murine mAbs to treat B-cell malignancies. T-cell mediated immune responses specific for peptides from the murine scFv antigen-binding domain of the CAR can develop in patients and result in premature elimination of CAR-T-cells increasing the risk of tumor relapse. As fully human scFv might reduce immunogenicity, we generated CD19-specific human scFvs with similar binding characteristics as the murine FMC63-derived scFv using human Ab/DNA-libraries...
February 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28197963/a-concise-review-of-autoimmune-cytopenias-in-chronic-lymphocytic-leukemia
#7
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 14, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28195233/haematological-cancer-idelalisib-for-cll-risky-benefit
#8
Diana Romero
No abstract text is available yet for this article.
February 14, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28195098/biclonal-chronic-lymphocytic-leukemia-a-study-of-two-cases-and-review-of-literature
#9
Kiran Ashok Ghodke, Nikhil V Patkar, P G Subramanian, Sumeet Gujral, Pratibha Aamre Kadam, Prashant R Tembhare
Chronic lymphocytic leukemia (CLL) is a common, immunophenotypically well-defined mature B-cell neoplasm. Demonstration of more than 5000/μL CD5+ B-cell population with co-expression of CD23, weak expression of CD20, and one type of immunoglobin light chain (either kappa or lambda) is necessary for the diagnosis of CLL. However, CLL with two populations of B-cells expressing both kappa as well as lambda (biclonal) light chains are extremely rare and has not been reported from India. We report two cases of biclonal CLL presented with leukocytosis, typical morphological features, and distinct immunophenotype of CLL...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28195089/immunogenetics-of-chronic-lymphocytic-leukemia
#10
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/28192408/macrophages-confer-survival-signals-via-ccr1-dependent-translational-mcl-1-induction-in-chronic-lymphocytic-leukemia
#11
M H A van Attekum, S Terpstra, E Slinger, M von Lindern, P D Moerland, A Jongejan, A P Kater, E Eldering
Protective interactions with bystander cells in micro-environmental niches, such as lymph nodes (LNs), contribute to survival and therapy resistance of chronic lymphocytic leukemia (CLL) cells. This is caused by a shift in expression of B-cell lymphoma 2 (BCL-2) family members. Pro-survival proteins B-cell lymphoma-extra large (BCL-XL), BCL-2-related protein A1 (BFL-1) and myeloid leukemia cell differentiation protein 1 (MCL-1) are upregulated by LN-residing T cells through CD40L interaction, presumably via nuclear factor (NF)-κB signaling...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28191372/richter-transformation-of-chronic-lymphocytic-leukemia-a-review-of-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-and-molecular-diagnostics
#12
REVIEW
Faiq Shaikh, Amna Janjua, Frederick Van Gestel, Adeel Ahmad
Chronic lymphocytic leukemia (CLL) is a low-grade B-cell proliferative disease with a generally indolent course. In a few cases, it undergoes transformation and becomes a more aggressive malignancy, such as diffuse large B-cell lymphoma (DLBCL). This process, which is called Richter transformation (RT), is often detected too late and is associated with a poor prognosis. There are multiple molecular diagnostic approaches to detect RT in preexisting CLL. Metabolic imaging using 18-fluorine fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) can be a very useful tool for early detection of RT and which can hence allow for timely intervention, thereby improving the patient's chances of survival...
January 9, 2017: Curēus
https://www.readbyqxmd.com/read/28187524/phenotypic-characterization-of-trisomy-12-monoclonal-b-cell-lymphocytosis
#13
Marc Sorigue, Clara Maluquer, Jordi Junca
BACKGROUND: Trisomy 12 chronic lymphocytic leukemia (CLL) is phenotypically different from the rest of CLL cytogenetic subgroups. However, it is unknown whether this is also the case for trisomy 12 CLL-phenotype monoclonal B-cell lymphocytosis (MBL). METHODS: We analyzed the expression of several markers in a series of 89 cytogenetically characterized MBL (including 17 trisomy 12 cases). Additionally, we compared the expression of these markers between trisomy 12 MBL, trisomy 12 CLL and a series of cases with trisomy 12 but fulfilling only 3 of the 5 Moreau CLL diagnostic criteria...
February 10, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28187444/idelalisib-and-bendamustine-combination-is-synergistic-and-increases-dna-damage-response-in-chronic-lymphocytic-leukemia-cells
#14
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
#15
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/28183684/prognosis-biomarkers-evaluation-in-chronic-lymphocytic-leukemia
#16
Lorena Caixeta Gomes, Fernanda Cristina Gontijo Evangelista, Lirlândia Pires de Sousa, Sergio Schusterschitz da Silva Araujo, Maria das Graças Carvalho, Adriano de Paula Sabino
OBJECTIVE/BACKGROUND: From clinical and biological points of view, chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by a progressive accumulation of lymphocytes in the peripheral blood, bone marrow, and lymphoid organs. New prognostic markers in CLL may be useful to clinicians for predicting outcome and in clinical decision-making. The aim of this study was to evaluate the potential prognostic value of the apoptotic/survival-controlling proteins and protein tyrosine kinase ZAP-70 gene expression in CLL patients and control individuals, correlating such findings with patients' clinical data...
February 1, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28182141/obinutuzumab-in-chronic-lymphocytic-leukemia-design-development-and-place-in-therapy
#17
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
#18
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/28174663/chronic-lymphocytic-leukemia-with-clinical-debut-as-neurological-involvement-a-rare-phenomenon-and-the-need-for-better-predictive-markers
#19
Cristhiam M Rojas-Hernandez, Jacklyn Nemunaitis, Kristopher D Marjon, Daniel Bustamante, Qian-Yun Zhang, Jennifer M Gillette
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. The frequency of symptomatic central nervous system (CNS) involvement is unknown but thought to be a rare phenomenon. Currently there are no known risk factors for CNS involvement. CASE PRESENTATION: We describe a clinically staged low-risk CLL case that presented with symptomatic CNS involvement and progressed rapidly to death. Evaluation of the surface adhesion molecules identified a markedly altered expression pattern of the integrin, CD49d, and the tetraspanin, CD82, in the index case when compared to similar low-risk CLL cases...
2017: BMC Hematology
https://www.readbyqxmd.com/read/28171709/long-term-outcomes-for-patients-with-chronic-lymphocytic-leukemia-who-discontinue-ibrutinib
#20
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
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