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https://www.readbyqxmd.com/read/29234595/ibrutinib-as-a-bridge-to-transplant-in-high-risk-chronic-lymphocytic-leukemia-a-case-report-and-review-of-the-literature
#1
Arcari Annalisa, Bassi Simona, Pochintesta Lara, Trabacchi Elena, Moroni Carlo Filippo, Rossi Angela, Zanlari Luca, Vallisa Daniele
The treatment landscape of chronic lymphocytic leukemia (CLL) has been challenged by the advent of novel classes of drugs, such as B-cell receptor (BCR)-inhibitors and BCL-2 antagonists. In selected high-risk patients, the choice to start allogeneic hematopoietic stem cell transplantation (alloHCT) or continue these agents is a matter of debate. Furthermore, published data about the impact on the feasibility of alloHCT and the optimal timing of administration are limited. Here we present a case of relapsed TP53 mutated CLL treated with ibrutinib as a bridge to alloHCT, discussing risks and benefits of different treatment options in a "real life" situation...
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/29226472/cost-utility-analysis-of-idelalisib-in-combination-with-rituximab-in-relapsed-or-refractory-chronic-lymphocytic-leukaemia
#2
Luis Felipe Casado, José Ángel Hernández, Isidro Jarque, María Echave, Miguel Angel Casado, Antonio Castro
OBJECTIVE: To evaluate the incremental cost-utility ratio (ICUR) of idelalisib in combination with rituximab (IR) versus rituximab monotherapy (R) in the treatment of patients with relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL), from the Spanish National Health System (NHS) perspective. METHODS: A partitioned survival Markov model for a lifetime horizon (30 years) was developed to estimate costs (€, 2016) and quality-adjusted life years (QALY) with IR and R...
December 11, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29225825/brain-biopsy-in-the-diagnosis-of-leptomeningeal-involvement-in-stage-i-chronic-lymphocytic-leukemia
#3
Eva Cervilla Muñoz, Pablo Demelo Rodríguez, Alejandra García García, Javier Menarguez Palanca, Jorge Del Toro Cervera
Leptomeningeal involvement of CLL is usually underdiagnosed as neurological symptoms are unspecific. It is important to carefully evaluate neurological status in these patients and consider this entity between the differential diagnosis of a neurological deterioration as adequate treatment improves the prognosis. Imaging techniques, analyses of cerebrospinal fluid, and brain biopsy are useful to establish a definitive diagnosis.
December 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/29222277/how-should-we-sequence-and-combine-novel-therapies-in-cll
#4
REVIEW
Matthew S Davids
With the recent approval of several effective and well-tolerated novel agents (NAs), including ibrutinib, idelalisib, venetoclax, and obinutuzumab, patients with chronic lymphocytic leukemia (CLL) have more therapeutic options than ever before. The availability of these agents is both an important advance for patients but also a challenge for practicing hematologist/oncologists to learn how best to sequence NAs, both with respect to chemoimmunotherapy (CIT) and to other NAs. The sequencing of NAs in clinical practice should be guided both by an individual patient's prognostic markers, such as FISH and immunoglobulin heavy chain variable region (IGHV)-mutation status, as well as the patient's medical comorbidities and goals of care...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222276/optimizing-frontline-therapy-of-cll-based-on-clinical-and-biological-factors
#5
REVIEW
Kirsten Fischer, Michael Hallek
The heterogeneity of the clinical course of chronic lymphocytic leukemia (CLL) ranges from an indolent course, where patients do not require therapy for many years, to a very aggressive disease, where treatment is required soon after diagnosis and relapses may occur early. The improved tools for prognostication allow predicting the outcome of patients with increasing reliability. Some markers also allow selecting more specific therapies with improved activity in the presence of certain genetic or clinical features of CLL...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222275/the-mutational-landscape-of-chronic-lymphocytic-leukemia-and-its-impact-on-prognosis-and-treatment
#6
REVIEW
Gianluca Gaidano, Davide Rossi
The typical genome of chronic lymphocytic leukemia (CLL) carries ∼2000 molecular lesions. Few mutations recur across patients at a frequency >5%, whereas a large number of biologically and clinically uncharacterized genes are mutated at lower frequency. Approximately 80% of CLL patients carry at least 1 of 4 common chromosomal alterations, namely deletion 13q14, deletion 11q22-23, deletion 17p12, and trisomy 12. Knowledge of the CLL genome has translated into the availability of molecular biomarkers for prognosis and treatment prediction...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222170/imprecision-and-dna-break-repair-biased-towards-incompatible-end-joining-in-leukemia
#7
Franz Josef Gassner, Maria Schubert, Stefan Rebhandl, Karina Spandl, Nadja Zaborsky, Kemal Catakovic, Stephanie Blaimer, Daniel Hebenstreit, Richard Greil, Roland Geisberger
Cancer is a genetic disease caused by mutations and chromosomal abnormalities which contribute to uncontrolled cell growth. In addition, cancer cells can rapidly respond to conventional and targeted therapies by accumulating novel and often specific genetic lesions leading to acquired drug resistance and relapsing disease. In chronic lymphocytic leukemia (CLL), however, diverse chromosomal aberrations often occur. In many cases, improper repair of DNA double strand breaks (DSBs) is a major source for genomic abnormalities...
December 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29214087/invasive-nontyphoidal-salmonella-infection-in-a-patient-with-early-stage-chronic-lymphocytic-leukemia
#8
Deepika Slawek, Yanina Dubrovskaya, Eddie Louie
We describe a case of a 72-year-old man with early-stage chronic lymphocytic leukemia (CLL) who presented with invasive nontyphoidal Salmonella (iNTS) infection, necrotizing pneumonia, and chronic infection of a hilar lymph node. Infection is a major cause of death in patients with CLL. Though few cases of iNTS infection associated with CLL have been described in the literature, to our knowledge this is the first reported case of iNTS-associated necrotizing pneumonia. Immunocompromised state in patients, even with early-stage CLL, likely predisposes them to invasive infection with intracellular organisms, such as Salmonella spp...
2017: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/29212732/the-role-of-rituximab-in-chronic-lymphocytic-leukemia-treatment-and-the-potential-utility-of-biosimilars
#9
REVIEW
Jennifer R Brown, Florence Cymbalista, Jeff Sharman, Ira Jacobs, Pilar Nava-Parada, Anthony Mato
Chronic lymphocytic leukemia (CLL) is managed with observation for asymptomatic or clinically silent disease; pharmacologic intervention is generally required for symptomatic patients with clinically significant adenopathy or cytopenia. In the front-line treatment of CLL, the current standard-of-care includes chemotherapy in combination with an anti-CD20 monoclonal antibody (e.g., rituximab, ofatumumab, or obinutuzumab) or ibrutinib as single agent. Despite the evolving treatment paradigm toward targeted therapy, it is likely that rituximab (plus chemotherapy), with or without targeted agents, will retain a significant role in CLL treatment...
December 6, 2017: Oncologist
https://www.readbyqxmd.com/read/29209431/combining-cytogenetic-and-epigenetic-approaches-in-chronic-lymphocytic-leukemia-improves-prognosis-prediction-for-patients-with-isolated-13q-deletion
#10
Cristina Bagacean, Christelle Le Dantec, Christian Berthou, Adrian Tempescul, Hussam Saad, Anne Bordron, Mihnea Zdrenghea, Victor Cristea, Nathalie Douet-Guilbert, Yves Renaudineau
Background: Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established. Methods: CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints])...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29207878/cd20-cd19-bispecific-car-t-cells-for-the-treatment-of-b-cell-malignancies
#11
Alexandra Martyniszyn, Ann-Christin Krahl, Maya C André, Andreas A Hombach, Hinrich Abken
The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected T cells with specificity for CD19 induced complete remissions in the majority of patients with a realistic hope for cure. However, recent follow-up data revealed a substantial risk of relapse through leukemic cells which lack the CAR targeted antigen. In this situation a bispecific CAR with binding domains for CD19 and CD20 is aimed at recognizing also leukemic cells with only one cognate antigen. The anti-CD20-CD19 bispecific CAR induced a full T cell response upon engagement of CD19 or CD20 on target cells showing a true "OR" gate recognition in redirecting T cell activation...
December 5, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29197349/granulomatous-interstitial-nephritis-due-to-chronic-lymphocytic-leukemia-a-case-report
#12
Yasuo Suzuki, Kan Katayama, Eiji Ishikawa, Shoko Mizoguchi, Keiko Oda, Yosuke Hirabayashi, Ayumi Haruki, Takayasu Ito, Mika Fujimoto, Tomohiro Murata, Masaaki Ito
BACKGROUND: Renal failure due to the infiltration of chronic lymphocytic leukemia (CLL) cells into the tubulointerstitial area of the kidney is uncommon. Furthermore, granulomatous interstitial nephritis (GIN) is a rare histological diagnosis in patients undergoing a renal biopsy. We herein report a case of GIN due to the diffuse infiltration of CLL cells in a patient who developed progressive renal failure. CASE PRESENTATION: The patient was a 55-year-old man who had been diagnosed with CLL 4 years earlier and who had been followed up without treatment...
December 2, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/29194741/-double-hit-chronic-lymphocytic-leukemia-an-aggressive-subgroup-with-17p-deletion-and-8q24-gain
#13
Elise Chapiro, Claude Lesty, Clémentine Gabillaud, Eric Durot, Simon Bouzy, Marine Armand, Magali Le Garff-Tavernier, Nadia Bougacha, Stéphanie Struski, Audrey Bidet, Elodie Laharanne, Carole Barin, Lauren Veronese, Nolwen Prié, Virginie Eclache, Baptiste Gaillard, Lucienne Michaux, Christine Lefebvre, Jean-Baptiste Gaillard, Christine Terré, Dominique Penther, Christian Bastard, Nathalie Nadal, Sandra Fert-Ferrer, Nathalie Auger, Catherine Godon, Laurent Sutton, Olivier Tournilhac, Santos A Susin, Florence Nguyen-Khac
Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL...
December 1, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29193006/a-single-institution-retrospective-cohort-study-of-first-line-r-epoch-chemoimmunotherapy-for-richter-syndrome-demonstrating-complex-chronic-lymphocytic-leukaemia-karyotype-as-an-adverse-prognostic-factor
#14
Kerry A Rogers, Ying Huang, Amy S Ruppert, Galena Salem, Deborah M Stephens, Nyla A Heerema, Leslie A Andritsos, Farrukh T Awan, John C Byrd, Joseph M Flynn, Kami J Maddocks, Jeffrey A Jones
Richter Syndrome, an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia (CLL), has a generally poor prognosis and anthracycline-based chemoimmunotherapy regimens designed to treat de novo diffuse large B-cell lymphoma achieve modest clinical benefit. R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) has demonstrated greater activity against aggressive B-cell histologies but has not been studied in Richter Syndrome. We conducted a retrospective cohort study of 46 Richter Syndrome patients treated with first-line R-EPOCH at our institution between 1 January 2006 and 31 May 2014...
November 28, 2017: British Journal of Haematology
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
#15
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/29173971/beyond-bystanders-myeloid-cells-in-chronic-lymphocytic-leukemia
#16
Bola S Hanna, Selcen Öztürk, Martina Seiffert
Tumor-promoting inflammation and escape from immune-mediated tumor destruction have been recognized as hallmarks of cancer, and myeloid cells are key players in these processes. By exploiting the tremendous plasticity of myeloid cells, tumors induce a variety of tumor-supportive and immunosuppressive cell phenotypes like tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). The relevance of these cell types in hematopoietic malignancies has only recently gained a stronger attention...
November 21, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29160119/a-review-of-the-infection-pathogenesis-and-prophylaxis-recommendations-in-patients-with-chronic-lymphocytic-leukemia
#17
Tamar Tadmor, Manfred Welslau, Iwoma Hus
The majority of patients with CLL will suffer from infections during their disease, accounting for approximately 60% of deaths in CLL. Patients are predisposed to infection due to immune defects related to the primary disease, and as a result of therapy. The range of infectious complications has evolved alongside therapeutic advances in the treatment of CLL. More recently several novel therapeutic compounds have been introduced in CLL, whose unique safety profiles will probably have an impact on the prophylaxis and management of infections in these patients...
November 27, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29159711/treatment-of-richter-s-syndrome
#18
REVIEW
Adalgisa Condoluci, Davide Rossi
Based on the available literature, mostly derived from retrospective or non-randomized phase I or II studies, it is difficult to define an optimized treatment approach for patients developing Richter's syndrome (RS). Early recognition of chronic lymphocytic leukemia (CLL) patients presenting clinical features suspected for a transformation is useful to avoid exposing them to multiple lines of therapy that, being targeted to CLL progression, have poor efficacy against RS. Because of the low specificity (~ 50-60%) of clinical signs of RS (such as rapid and discordant bulky localized lymphadenopathies, elevated LDH levels, emergent physical deterioration, and/or fever in the absence of infection), a 18FDG PET/CT and a biopsy are recommended to confirm RS...
November 21, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29156691/neutrophils-in-chronic-lymphocytic-leukemia-are-permanently-activated-and-have-functional-defects
#19
Gayane Manukyan, Tomas Papajik, Petr Gajdos, Zuzana Mikulkova, Renata Urbanova, Gabriela Gabcova, Milos Kudelka, Peter Turcsányi, Pavlina Ryznerova, Vit Prochazka, Eva Kriegova
A growing body of studies highlights involvement of neutrophils in cancer development and progression. Our aim was to assess the phenotypic and functional properties of circulating neutrophils from patients with chronic lymphocytic leukemia (CLL). The percentage of CD54+ and CD64+ neutrophils as well as CD54 expression on these cells were higher in CLL patients than in age-matched healthy controls. Neutrophils from CLL produced more reactive oxygen species (ROS) compared to controls in both resting and activated conditions...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155042/imaging-flow-cytometry-to-assess-chromosomal-abnormalities-in-chronic-lymphocytic-leukaemia
#20
Henry Hui, Kathryn A Fuller, Hun Chuah, James Liang, Hasib Sidiqi, Dejan Radeski, Wendy N Erber
Chronic Lymphocytic Leukaemia (CLL), the most common leukaemia in the Western world, has a characteristic phenotype and prognosis largely defined by the presence of cytogenetic aberrations. The gold standard for detecting these cytogenetic abnormalities is interphase fluorescence in situ hybridisation (FISH) performed on cell smears or tissue sections on glass slides. Fluorescently labelled DNA probes bind to specific chromosomal regions and the signal detected by fluorescent microscopy. Generally only 200 cells are assessed and the limit of sensitivity is 3% positive cells...
November 15, 2017: Methods: a Companion to Methods in Enzymology
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