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CLL, T-cell

Richard Colling, Daniel Royston, Elizabeth Soilleux
Clonality studies greatly assist in the diagnosis of challenging haematopathology cases. These robust and standardised tests aid the detection of clonal lymphoid populations and may assist in lymphocyte subtyping. In this case report, a gentleman presented with a high-grade transformation of a B cell neoplasm which histologically and immunophenotypically mimicked a T cell anaplastic large-cell lymphoma. With the aid of T cell and B cell receptor clonality studies, it was demonstrated that this tumour was in fact of B cell lineage...
September 2016: Journal of Hematopathology
Maulik Vyas, Ann-Charlott Schneider, Olga Shatnyeva, Katrin S Reiners, Samir Tawadros, Stephan Kloess, Ulrike Köhl, Michael Hallek, Hinrich P Hansen, Elke Pogge von Strandmann
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia that affects B lymphocytes in adults. Natural killer (NK) cells in CLL patients are intrinsically potent but display poor in situ effector functions. NKG2D is an activating receptor found on NK and CD8(+) T cells and plays a role in immunosurveillance of CLL. In this study, we developed mono- and dual-targeting triplebodies utilizing a natural ligand for human NKG2D receptor (ULBP2) to retarget NK cells against tumor cells. Triplebodies in both formats showed better ability to induce NK-cell-dependent killing of target cells compared to bispecific counterparts...
2016: Oncoimmunology
A Prica, F Baldassarre, L K Hicks, K Imrie, T Kouroukis, M Cheung
Rituximab is the first monoclonal antibody to be approved for use by the US Food and Drug Administration in cancer. Its role in the treatment of non-Hodgkin lymphoma, including chronic lymphocytic leukaemia (CLL), has evolved significantly. We aimed to systematically review and update the literature on rituximab in lymphoma and CLL, and provide evidence-based consensus guidelines for its rational use. Validated methodology from the Cancer Care Ontario Program in Evidence-based Care was used. A comprehensive literature search was completed by a methodologist from the Hematology Disease Site Group of Cancer Care Ontario...
October 13, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
Mohamed A Kharfan-Dabaja, Jessica El-Asmar, Farrukh T Awan, Mehdi Hamadani, Ernesto Ayala
Novel therapies targeting various kinases downstream of the B-cell receptor have emerged along with monoclonal antibodies and BCL-2 antagonists, and are changing the therapeutic landscape of chronic lymphocytic leukemia. However, cure remains unattainable unless eligible patients are offered an allogeneic hematopoietic cell transplant. Access to allogeneic hematopoietic cell transplantation has expanded considerably with availability of reduced intensity conditioning regimens which is capable offering durable remissions even in poor-risk disease...
March 2016: Best Practice & Research. Clinical Haematology
Emili Montserrat, Tycho Bauman, Julio Delgado
Medicine has been 'personalized' (i.e. centred in persons) since its foundation. Recently, however, the term 'personalized medicine' (or, better, 'precision medicine') has been introduced to define 'a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease'. This concept has gained momentum thanks to next-generation-sequencing (NGS) techniques that allow identification of molecular characteristics unique to the patient and to the tumour...
March 2016: Best Practice & Research. Clinical Haematology
Agata A Filip, Anna Grenda, Sylwia Popek, Dorota Koczkodaj, Małgorzata Michalak-Wojnowska, Michał Budzyński, Ewa Wąsik-Szczepanek, Szymon Zmorzyński, Agnieszka Karczmarczyk, Krzysztof Giannopoulos
Expression of microRNAs is altered in cancer. Circulating miRNA level assessed in body fluids commonly reflects their expression in tumor cells. In leukemias, however, both leukemic and nonleukemic cells compose circulating miRNA expression profile of peripheral blood. The latter contribution to extracellular miRNA pool may result in specific microenvironmental signaling, which promotes proliferation and survival. In our study, we used qT-PCR to assay peripheral blood serum of 22 chronic lymphocytic leukemia (CLL) patients for the expression of 84 miRNAs associated with activation and differentiation of B and T lymphocytes...
October 12, 2016: Annals of Hematology
Supriya V Vartak, Mahesh Hegde, Divyaanka Iyer, Snehal Gaikwad, Vidya Gopalakrishnan, Mrinal Srivastava, Subhas S Karki, Bibha Choudhary, Pritha Ray, T R Santhoshkumar, Sathees C Raghavan
Antiapoptotic protein BCL2, serves as an excellent target for anticancer therapy owing to its increased level in cancers. Previously, we have described characterization of a novel BCL2 inhibitor, Disarib, which showed selective cytotoxicity in BCL2 'high' cancer cells and CLL patient cells. Here, we have investigated the mechanism of Disarib-induced cytotoxicity, and compared its efficacy with a well-established BCL2 inhibitor, ABT199. We show that Disarib administration caused tumor regression in mouse allograft and xenograft models, exhibited platelet sparing property and did not exhibit significant side effects...
September 29, 2016: Biochemical Pharmacology
G Galletti, F Caligaris-Cappio, M T S Bertilaccio
The development and progression of chronic B-cell tumors depend on a complex microenvironmental network of cells that include monocyte-derived macrophages. In chronic lymphocytic leukemia (CLL) the survival of malignant cells is supported in vitro by nurse-like cells, which differentiate from CD14(+) monocytes and have been identified as tumor-associated macrophages (TAMs). The role of the monocyte/macrophage lineage in CLL has been extensively studied in vitro, but only recently has been investigated in in vivo models...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Staci L Haney, Garland M Upchurch, Jana Opavska, David Klinkebiel, Adams Kusi Appiah, Lynette M Smith, Tayla B Heavican, Javeed Iqbal, Shantaram Joshi, Rene Opavsky
Cytosine methylation of DNA is an epigenetic modification involved in the repression of genes that affect biological processes including hematopoiesis. It is catalyzed by DNA methyltransferases, one of which -DNMT3A- is frequently mutated in human hematologic malignancies. We have previously reported that Dnmt3a inactivation in hematopoietic stem cells results in chronic lymphocytic leukemia (CLL) and CD8-positive peripheral T cell lymphomas (PTCL) in EμSRα-tTA;Teto-Cre;Dnmt3a(fl/fl); Rosa26LOXP(EGFP/EGFP) (Dnmt3a(Δ/Δ)) mice...
September 28, 2016: Scientific Reports
Larry Mansouri, Daniel Noerenberg, Emma Young, Elena Mylonas, Maysaa Abdulla, Mareike Frick, Fazila Asmar, Viktor Ljungström, Markus Schneider, Kenichi Yoshida, Aron Skaftason, Tatjana Pandzic, Blanca Gonzalez, Anna Tasidou, Nils Waldhueter, Alfredo Rivas-Delgado, Maria Angelopoulou, Marita Ziepert, Christopher Maximilian Arends, Lucile Couronné, Dido Lenze, Claudia D Baldus, Christian Bastard, Jessica Okosun, Jude Fitzgibbon, Bernd Dörken, Hans G Drexler, Damien Roos-Weil, Clemens A Schmitt, Helga Duverger Munch-Petersen, Thorsten Zenz, Martin-Leo Hansmann, Jonathan C Strefford, Gunilla Enblad, Olivier A Bernard, Elisabeth Ralfkiaer, Martin Erlanson, Penelope Korkolopoulou, Magnus Hultdin, Theodora Papadaki, Kirsten Grønbæk, Armando Lopez-Guillermo, Seishi Ogawa, Ralf Küppers, Kostas Stamatopoulos, Niki Stavroyianni, George Kanellis, Andreas Rosenwald, Elias Campo, Rose-Marie Amini, German Ott, Theodoros P Vassilakopoulos, Michael Hummel, Richard Rosenquist, Frederik Damm
We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBϵ, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, hence we screened a large patient cohort (n=1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal-zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary CNS lymphoma (3-4%)...
September 26, 2016: Blood
Ewelina Grywalska, Anna Hymos, Izabela Korona-Głowniak, Marcin Pasiarski, Agnieszka Stelmach-Gołdyś, Stanisław Góźdź, Anna Malm, Jacek Rolinski
INTRODUCTION: Since 2012, both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23) have been recommended for pneumococcal infection prevention in patients with chronic lymphocytic leukemia (CLL). Available literature data indicate that leukemic cells may respond to the presence of pathogens through specific Toll-like receptors (TLR). OBJECTIVES: The aim of the study was to assess the effect of in vitro PPV23 stimulation of peripheral blood mononuclear cells (PBMCs) on expression of TLR-2, TLR-4, CD25, CD69, and CD95 on the surface of CD3+ T cells and CD19+ B cells in CLL patients...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
Mohamed A Kharfan-Dabaja, Ambuj Kumar, Mehdi Hamadani, Stephan Stilgenbauer, Paolo Ghia, Claudio Anasetti, Peter Dreger, Emili Montserrat, Miguel-Angel Perales, Edwin P Alyea, Farrukh T Awan, Ernesto Ayala, Jacqueline C Barrientos, Jennifer R Brown, Januario Castro, Richard R Furman, John Gribben, Brian T Hill, Mohamad Mohty, Carol Moreno, Susan O'Brien, Steven Z Pavletic, Javier Pinilla-Ibarz, Nishitha M Reddy, Mohamed Sorror, Christopher Bredeson, Paul Carpenter, Bipin N Savani
We sought to establish clinical practice recommendations to redefine the role of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with chronic lymphocytic leukemia (CLL) in an era of highly active targeted therapies. We performed a systematic review to identify prospective randomized controlled trials comparing allo-HCT against novel therapies for treatment of CLL at various disease stages. In the absence of such data, we invited physicians with expertise in allo-HCT and/or CLL to participate in developing these recommendations...
September 19, 2016: Biology of Blood and Marrow Transplantation
Fahimeh Asadi-Amoli, Zohreh Nozarian, Hirbod Nasiri Bonaki, Vahid Mehrtash, Samaneh Entezari
BACKGROUND: The most common type of ocular lymphoma is non-Hodgkin lymphoma (NHL), categorized into two groups: indolent (slow growing) and aggressive (rapid growing). Differentiating benign reactive lymphoid hyperplasia (RLH) from malignant ocular adnexal lymphoma (OAL) is challenging. Histopathology, immunohistochemistry (IHC) and ow cytometry have been used as diagnostic tools in such cases. MATERIALS AND METHODS: In this retrospective case series, from 2002 to 2013 at Farabi Eye Center, 110 patients with ocular lymphoproliferative disease were enrolled...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
David Killock
No abstract text is available yet for this article.
October 2016: Nature Reviews. Clinical Oncology
Anthony R Mato, Chadi Nabhan, Paul M Barr, Chaitra S Ujjani, Brian T Hill, Nicole Lamanna, Alan P Skarbnik, Christina Howlett, Jeffrey J Pu, Alison R Sehgal, Lauren E Strelec, Alexandra Vandegrift, Danielle M Fitzpatrick, Clive S Zent, Tatyana Feldman, Andre Goy, David F Claxton, Spencer Henick Bachow, Gurbakhash Kaur, Jakub Svoboda, Sunita Dwivedy Nasta, David Porter, Daniel J Landsburg, Stephen J Schuster, Bruce D Cheson, Pavel Kiselev, Andrew M Evens
B Cell receptor (BCR) kinase inhibitor (KI) therapy represents a paradigm shift in Chronic Lymphocytic Leukemia (CLL) management, but data on practice patterns after KI discontinuation and optimal sequencing are limited. We conducted a multicenter, retrospective, comprehensive analysis on 178 CLL patients (ibrutinib=143; idelalisib=35) who discontinued KI therapy. We examined responses, toxicity, post-KI therapies, and overall survival (OS). Patients had a median of 3 prior therapies (range 0-11); del17p (34%), p53 mutation (27%), del11q (33%), and complex karyotype (29%)...
September 6, 2016: Blood
I F Khouri, D Sui, E J Jabbour, B I Samuels, F Turturro, G Alatrash, P Anderlini, S Ahmed, B Oran, S O Ciurea, D Marin, A Olson, K K Patel, U R Popat, C Ledesma, T M Kadia, A Ferrajoli, J A Burger, J L Jorgensen, L J Medeiros, R L Bassett, A M Gulbis
Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution...
September 5, 2016: Bone Marrow Transplantation
Mark B Geyer, Renier J Brentjens
The past several years have been marked by extraordinary advances in clinical applications of immunotherapy. In particular, adoptive cellular therapy utilizing chimeric antigen receptor (CAR)-modified T cells targeted to CD19 has demonstrated substantial clinical efficacy in children and adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and durable clinical benefit in a smaller subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or B-cell non-Hodgkin lymphoma (B-NHL)...
November 2016: Cytotherapy
Nannan Pang, Rui Zhang, Jinhua Li, Zhenghao Zhang, Hailong Yuan, Gang Chen, Fang Zhao, Lei Wang, Haizhou Cao, Jianhua Qu, Jianbing Ding
OBJECTIVE: This study is to investigate the association between the Treg/Th17 cells and prognosis of chronic lymphocytic leukemia (CLL). METHODS: Totally 50 CLL patients and 20 Health controls were included in this study. Regulatory T (Treg) cells and the cell subset secreting IL-17 (Th17) in peripheral blood were detected with flow cytometry. Serum levels of IL-10 and IL-17 were determined with ELISA, and expression of Foxp3 and RORγt was assessed with quantitative real-time PCR...
August 29, 2016: International Immunopharmacology
Efstratios Koutroumpakis, Montgomery Lobe, Lezah McCarthy, Syed Mehdi
BACKGROUND: Hypercalcemia due to malignancy is well described in the literature and a common paraneoplastic finding in certain solid tumors. Hematologic malignancies, however, are less frequently associated with hypercalcemia with the exception of myelomas and T-cell lymphomas. CASE REPORT: This case report describes a patient with B-cell chronic lymphocytic leukemia (B-CLL) who developed symptomatic hypercalcemia. None of the pathogenetic mechanisms of malignancy-associated hypercalcemia already described in the literature could explain the pathogenesis of hypercalcemia in our patient...
September 2016: In Vivo
Jana Zemanova, Ondrej Hylse, Jana Collakova, Pavel Vesely, Alexandra Oltova, Marek Borsky, Kristina Zaprazna, Marie Kasparkova, Pavlina Janovska, Jan Verner, Jiri Kohoutek, Marta Dzimkova, Vitezslav Bryja, Zuzana Jaskova, Yvona Brychtova, Kamil Paruch, Martin Trbusek
Treatment options for TP53-mutated lymphoid tumors are very limited. In experimental models, TP53-mutated lymphomas were sensitive to direct inhibition of checkpoint kinase 1 (Chk1), a pivotal regulator of replication. We initially tested the potential of the highly specific Chk1 inhibitor SCH900776 to synergize with nucleoside analogs (NAs) fludarabine, cytarabine and gemcitabine in cell lines derived from B-cell malignancies. In p53-proficient NALM-6 cells, SCH900776 added to NAs enhanced signaling towards Chk1 (pSer317/pSer345), effectively blocked Chk1 activation (Ser296 autophosphorylation), increased replication stress (p53 and γ-H2AX accumulation) and temporarily potentiated apoptosis...
August 19, 2016: Oncotarget
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