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https://www.readbyqxmd.com/read/28389687/advances-in-the-treatment-of-relapsed-refractory-chronic-lymphocytic-leukemia
#1
REVIEW
C Shustik, I Bence-Bruckler, R Delage, C J Owen, C L Toze, S Coutre
Treatment of chronic lymphocytic leukemia (CLL) has advanced with the introduction of chemoimmunotherapy (CIT) agents that have improved the outcomes of frontline therapy. However, most treated patients will relapse and require subsequent therapy. This review focuses on recent advances in the treatment of relapsed or refractory CLL. Until recently, treatment options for relapsed CLL were of limited efficacy. Retreatment with fludarabine, cyclophosphamide, and rituximab (FCR) was recommended for patients with a durable response to first-line FCR, although acquired genetic aberrations, impaired marrow reserve, and comorbidities often made this suboptimal therapy for many patients...
April 7, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28340951/epstein-barr-virus-hemophagocytic-lymphohistiocytosis-related-to-rituximab-use-and-immunopathogenetic-insights
#2
Sotirios G Papageorgiou, Sotirios Tsiodras, Georgios Siakallis, Efthimia Bazani, Aris Spathis, Garyfalia Poulakou, Penelope Korkolopoulou, Ioannis Panayiotides, Vasiliki Pappa
Anti-CD20-based chemo-immunotherapeutic regimens have been suggested to assist in the management of Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis (HLH) and EBV-associated post-transplant lymphoproliferative disorders (EBV-PTLD), by reducing EBV viral load and EBV-induced inflammation. Herein we report a fatal EBV-related HLH in the context of Hodgkin lymphoma (HL)-like Richter's transformation of B chronic lymphocytic leukemia (B-CLL), two months after rituximab treatment. The complex balance between EBV driven T-cell stimulation and immunosuppressive therapy in the context of multiple immune deficits is discussed...
December 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28324286/prolymphocytic-leukemia-new-insights-in-diagnosis-and-in-treatment
#3
REVIEW
Aude Collignon, Anne Wanquet, Elsa Maitre, Edouard Cornet, Xavier Troussard, Thérèse Aurran-Schleinitz
PURPOSE OF REVIEW: We aimed to produce a comprehensive update on clinical and biological data regarding two rare lymphoid neoplasms, B and T prolymphocytic leukemias, and assess therapeutic management in the light of new molecular insights and the advent of targeted therapies. RECENT FINDINGS: B cell prolymphocytic leukemia (B-PLL) diagnosis remains challenging in the absence of clear immunophenotypic or cytogenetic signature and overlap with mantle cell lymphoma...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28295181/long-term-follow-up-of-patients-receiving-allogeneic-stem-cell-transplant-for-chronic-lymphocytic-leukaemia-mixed-t-cell-chimerism-is-associated-with-high-relapse-risk-and-inferior-survival
#4
Philip A Thompson, Francesco Stingo, Michael J Keating, William G Wierda, Susan M O'Brien, Zeev Estrov, Celina Ledesma, Katayoun Rezvani, Muzaffar Qazilbash, Nina Shah, Simrit Parmar, Uday Popat, Paolo Anderlini, Nieto Yago, Stefan O Ciurea, Partow Kebriaei, Richard Champlin, Elizabeth J Shpall, Chitra M Hosing
There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28287639/use-of-haploidentical-stem-cell-transplantation-continues-to-increase-the-2015-european-society-for-blood-and-marrow-transplant-activity-survey-report
#5
J R Passweg, H Baldomero, P Bader, C Bonini, R F Duarte, C Dufour, A Gennery, N Kröger, J Kuball, F Lanza, S Montoto, A Nagler, J A Snowden, J Styczynski, M Mohty
Hematopoietic stem cell transplantation (HSCT) is an established procedure for many acquired and congenital disorders of the hematopoietic system. A record number of 42 171 HSCT in 37 626 patients (16 030 allogeneic (43%), 21 596 autologous (57%)) were reported by 655 centers in 48 countries in 2015. Trends include continued growth in transplant activity over the last decade, with the highest percentage increase seen in middle-income countries but the highest absolute growth in the very-high-income countries in Europe...
March 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28112746/risk-factors-for-treatment-failure-after-allogeneic-transplantation-of-patients-with-cll-a-report-from-the-european-society-for-blood-and-marrow-transplantation
#6
J Schetelig, L C de Wreede, M van Gelder, N S Andersen, C Moreno, A Vitek, M Karas, M Michallet, M Machaczka, M Gramatzki, D Beelen, J Finke, J Delgado, L Volin, J Passweg, P Dreger, A Henseler, A van Biezen, M Bornhäuser, S O Schönland, N Kröger
For young patients with high-risk CLL, BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. Patients with a low risk of non-relapse mortality (NRM) but a high risk of failure of targeted therapy may benefit most from alloHCT. We performed Cox regression analyses to identify risk factors for 2-year NRM and 5-year event-free survival (using EFS as a surrogate for long-term disease control) in a large, updated EBMT registry cohort (n= 694). For the whole cohort, 2-year NRM was 28% and 5-year EFS 37%...
April 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27943415/flow-cytometry-minimal-residual-disease-after-allogeneic-transplant-for-chronic-lymphocytic-leukemia
#7
Caroline Algrin, Jean-Louis Golmard, Mauricette Michallet, Oumedaly Reman, Anne Huynh, Aurore Perrot, Anne Sirvent, Adriana Plesa, Véronique Salaun, Marie-Christine Béné, Dominique Bories, Olivier Tournilhac, Hélène Merle-Béral, Véronique Leblond, Magali Le Garff-Tavernier, Nathalie Dhedin
OBJECTIVES: This study investigates whether achieving complete remission (CR) with undetectable minimal residual disease (MRD) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL) affects outcome. METHODS: We retrospectively studied 46 patients transplanted for CLL and evaluated for post-transplant MRD by flow cytometry. RESULTS: At transplant time, 43% of the patients were in CR, including one with undetectable MRD, 46% were in partial response, and 11% had refractory disease...
December 10, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27941763/long-term-survival-of-patients-with-cll-after-allogeneic-transplantation-a-report-from-the-european-society-for-blood-and-marrow-transplantation
#8
M van Gelder, L C de Wreede, M Bornhäuser, D Niederwieser, M Karas, N S Anderson, M Gramatzki, P Dreger, M Michallet, E Petersen, D Bunjes, M Potter, D Beelen, J J Cornelissen, I Yakoub-Agha, N H Russell, J Finke, H Schoemans, A Vitek, Á Urbano-Ispízua, D Blaise, L Volin, P Chevallier, D Caballero, H Putter, A van Biezen, A Henseler, S Schönland, N Kröger, J Schetelig
Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population...
December 12, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27941287/adoptive-immunotherapy-utilizing-anti-cd19-chimeric-antigen-receptor-t-cells-for-b-cell-malignancies
#9
Iekuni Oh, Yukiko Oh, Ken Ohmine
Genetically modified T-cells with forced expression of anti-CD19 chimeric antigen receptor (CD19 CAR) have demonstrated promising clinical results for relapsed and refractory B cell malignancies in early clinical trial settings. The first beneficial tumor regressions were identified among approximately half of CLL patients in 2011. Similarly, CD19 CAR T-cells achieved remissions in about 80% of aggressive B-cell lymphomas in 2012. Furthermore, in 2013 this cellular therapy showed an extremely high rate of efficacy against refractory CD19 positive acute lymphoid leukemia, which had been regarded as the most difficult to treat hematologic disease...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27903679/the-bruton-tyrosine-kinase-btk-inhibitor-acalabrutinib-demonstrates-potent-on-target-effects-and-efficacy-in-two-mouse-models-of-chronic-lymphocytic-leukemia
#10
Sarah E M Herman, Arnau Montraveta, Carsten U Niemann, Helena Mora-Jensen, Michael Gulrajani, Fanny Krantz, Rose Mantel, Lisa L Smith, Fabienne McClanahan, Bonnie K Harrington, Dolors Colomer, Todd Covey, John C Byrd, Raquel Izumi, Allard Kaptein, Roger Ulrich, Amy J Johnson, Brian J Lannutti, Adrian Wiestner, Jennifer A Woyach
Purpose: Acalabrutinib (ACP-196) is a novel, potent, and highly selective Bruton tyrosine kinase (BTK) inhibitor, which binds covalently to Cys481 in the ATP-binding pocket of BTK. We sought to evaluate the antitumor effects of acalabrutinib treatment in two established mouse models of chronic lymphocytic leukemia (CLL).Experimental Design: Two distinct mouse models were used, the TCL1 adoptive transfer model where leukemic cells from Eμ-TCL1 transgenic mice are transplanted into C57BL/6 mice, and the human NSG primary CLL xenograft model...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27862308/alemtuzumab-consolidation-in-chronic-lymphocytic-leukaemia-a-phase-i-ii-multicentre-trial
#11
MULTICENTER STUDY
Othman Al-Sawaf, Kirsten Fischer, Carmen D Herling, Matthias Ritgen, Sebastian Böttcher, Jasmin Bahlo, Thomas Elter, Stephan Stilgenbauer, Barbara F Eichhorst, Raymonde Busch, Ute Elberskirch, Wolfgang Abenhardt, Michael Kneba, Michael Hallek, Clemens-Martin Wendtner
OBJECTIVE: Despite high rates of long-lasting remissions in patients with chronic lymphocytic leukaemia (CLL) treated with chemoimmunotherapy, none of the current therapeutic approaches is curative with the exception of allogeneic transplantation. One strategy to extend progression-free survival and long-term survival might be the establishment of consolidation therapies. METHODS: In this trial, patients with complete or partial second remission after fludarabine-based treatment received consolidation therapy with alemtuzumab...
March 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/27822100/the-danish-national-chronic-lymphocytic-leukemia-registry
#12
REVIEW
Caspar da Cunha-Bang, Christian Hartmann Geisler, Lisbeth Enggaard, Christian Bjørn Poulsen, Peter de Nully Brown, Henrik Frederiksen, Olav Jonas Bergmann, Elisa Jacobsen Pulczynski, Robert Schou Pedersen, Linda Højberg Nielsen, Ilse Christiansen, Carsten Utoft Niemann
AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate adherence to national guidelines and to provide source data for research purposes. STUDY POPULATION: All patients diagnosed with CLL in Denmark from 2008 onward are included in the registry...
2016: Clinical Epidemiology
https://www.readbyqxmd.com/read/27819687/impact-of-drug-development-on-the-use-of-stem-cell-transplantation-a-report-by-the-european-society-for-blood-and-marrow-transplantation-ebmt
#13
J R Passweg, H Baldomero, P Bader, C Bonini, S Cesaro, P Dreger, R F Duarte, C Dufour, J Kuball, D Farge-Bancel, A Gennery, N Kröger, F Lanza, A Nagler, A Sureda, M Mohty
Hematopoietic stem cell transplantation (HSCT) is used with increasing frequency in Europe with 40 000 transplants reported in 2014. Transplant-related mortality remains high in allogeneic HSCT (10-20%); high-dose chemotherapy is toxic and demanding for patients. Drug development is accelerating and with limited toxicity of some targeted drugs may replace HSCT, whereas others may function as a 'bridge to transplant'. We analyzed HSCT reported to the activity survey for selected diseases in which major advances in drug development have been made...
February 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27802969/ibrutinib-efficacy-and-tolerability-in-patients-with-relapsed-chronic-lymphocytic-leukemia-following-allogeneic-hct
#14
Christine E Ryan, Bita Sahaf, Aaron C Logan, Susan O'Brien, John C Byrd, Peter Hillmen, Jennifer R Brown, Martin J S Dyer, Anthony R Mato, Michael J Keating, Samantha Jaglowski, Fong Clow, Andrew R Rezvani, Lori Styles, Steven E Coutre, David B Miklos
Ibrutinib, a potent and irreversible small-molecule inhibitor of both Bruton's tyrosine kinase and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival. Here, we present 27 patients with relapsed CLL following allogeneic hematopoietic cell transplant (HCT) who subsequently received ibrutinib salvage therapy. Sixteen of these patients were part of multi-institutional clinical trials and achieved an overall response rate of 87...
December 22, 2016: Blood
https://www.readbyqxmd.com/read/27797975/long-term-follow-up-of-treatment-with-ibrutinib-and-rituximab-in-patients-with-high-risk-chronic-lymphocytic-leukemia
#15
Preetesh Jain, Michael J Keating, William G Wierda, Mariela Sivina, Philip A Thompson, Alessandra Ferrajoli, Zeev Estrov, Hagop Kantarjian, Susan O'Brien, Jan A Burger
Background: Ibrutinib is an active therapy with an acceptable safety profile for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del17p or with TP53 mutations. Ibrutinib is broadly indicated for the treatment of patients with CLL and specifically including those with 17p deletion. The optimal use of ibrutinib in combination with other agents remains controversial.Methods: We report the long-term outcome [median follow-up of 47 months (range, 36-51 months)] of 40 patients with high-risk CLL, treated on the first ibrutinib combination trial with rituximab (IR)...
October 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27757305/mono-and-dual-targeting-triplebodies-activate-natural-killer-cells-and-have-anti-tumor-activity-in-vitro-and-in-vivo-against-chronic-lymphocytic-leukemia
#16
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
https://www.readbyqxmd.com/read/27742075/tp53-dysfunction-in-cll-implications-for-prognosis-and-treatment
#17
Gera D Te Raa, Arnon P Kater
Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improve detection of TP53 defects and include next-generation sequencing (NGS) and functional assays...
March 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27742072/current-state-of-hematopoietic-cell-transplantation-in-cll-as-smart-therapies-emerge
#18
REVIEW
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
https://www.readbyqxmd.com/read/27742070/richter-s-syndrome-novel-and-promising-therapeutic-alternatives
#19
REVIEW
Davide Rossi
Richter's syndrome (RS) is the development of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL). The incidence rate for RS is ∼0.5% per year of observation. In the presence of clinical suspicious of RS, diagnosis of transformation and choice of the site of biopsy may take advantage of (18)FDG PET/CT. Molecular lesions of tumor suppression regulators (TP53), cell cycle (CDKN2A) and cell proliferation (NOTCH1, MYC) overall account for ∼90% of RS and may be responsible for its aggressive clinical phenotype...
March 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27728807/lyn-kinase-in-the-tumor-microenvironment-is-essential-for-the-progression-of-chronic-lymphocytic-leukemia
#20
Phuong-Hien Nguyen, Oleg Fedorchenko, Natascha Rosen, Maximilian Koch, Romy Barthel, Tomasz Winarski, Alexandra Florin, F Thomas Wunderlich, Nina Reinart, Michael Hallek
Survival of chronic lymphocytic leukemia (CLL) cells strictly depends on the support of an appropriate tumor microenvironment. Here, we demonstrate that LYN kinase is essential for CLL progression. Lyn deficiency results in a significantly reduced CLL burden in vivo. Loss of Lyn within leukemic cells reduces B cell receptor (BCR) signaling including BTK phosphorylation, but surprisingly does not affect leukemic cell expansion. Instead, syngeneic CLL transplantation of CLL cells into Lyn- or Btk-deficient recipients results in a strongly delayed leukemic progression and prolonged survival...
October 10, 2016: Cancer Cell
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