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Best Practice & Research. Clinical Haematology

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https://www.readbyqxmd.com/read/30213403/integrating-novel-systemic-therapies-for-the-treatment-of-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#1
REVIEW
H Miles Prince, Christiane Querfeld
Novel systemic therapies are generally prescribed to patients with advanced-stage disease or those with early-stage disease refractory to skin-directed therapies. In general, systemic chemotherapy should be reserved for patients who fail to respond to biological agents. Such biological agents include interferon alfa, bexarotene, histone deacetylase inhibitors (vorinostat, romidepsin), brentuximab vedotin and mogamulizumab. Extracorporeal photopheresis is particularly effective for patients with Sézary Syndrome...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213402/extranodal-nk-t-cell-lymphoma-updates-in-biology-and-management-strategies
#2
REVIEW
Motoko Yamaguchi, Masahiko Oguchi, Ritsuro Suzuki
Extranodal NK/T-cell lymphoma, nasal type (ENKL), is a rare lymphoma subtype of peripheral T/NK-cell lymphoma that is very common in East Asia and Latin America. Two-thirds of patients have localized disease in the nasal cavity or adjacent sites. Large retrospective studies have revealed the clinicopathologic features of ENKL patients, identified risk factors for short survival time, and developed prognostic models. Next-generation sequencing studies have provided a comprehensive list of recurrent mutations in ENKL...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213401/peripheral-t-cell-lymphoma-are-we-making-progress
#3
REVIEW
Niloufer Khan, Neval Ozkaya, Alison Moskowitz, Ahmet Dogan, Steven Horwitz
Peripheral T cell lymphoma (PTCL) is a rare subtype of non-Hodgkin lymphoma. PTCLs are heterogeneous in terms of biology, but generally have more aggressive features and poorer outcomes than aggressive B-cell lymphomas when treated with combination chemotherapy. While the best long-term results are still seen with intensive chemotherapeutic approaches, significant progress has been made with molecular profiling identifying genetic drivers of PTCL that could serve as therapeutic targets. Tailoring therapy to different subtypes of PTCL may lead to more individualized approaches with the hope of improved outcomes...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213400/immunotherapy-in-aggressive-b-cell-lymphomas
#4
REVIEW
Caron A Jacobson, Philippe Armand
The idea that the immune system could be co-opted to treat cancer is not new; it has existed for centuries. However, what is new is the advancement of our understanding of how the immune system is regulated and how a tumor evolves to evade an immune response. This knowledge, combined with modern technologies to manipulate the immune system, both pharmacologically and genetically, has led to the realization of immuno-oncology as a new frontier in cancer therapeutics. This review will focus on pharmacologic immunotherapies in aggressive B cell lymphomas: checkpoint inhibition and bispecific antibodies...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213399/the-promise-of-car-t-cell-therapy-in-aggressive-b-cell-lymphoma
#5
REVIEW
Ranjit Nair, Sattva S Neelapu
Relapsed or refractory aggressive B-cell lymphoma has an extremely poor prognosis and efforts to develop novel therapies for these patients have failed for almost four decades until the advent of chimeric antigen receptor (CAR) T-cell therapy. Within the last one year, two anti-CD19 CAR T-cell therapy products, axicabtagene ciloleucel and tisagenlecleucel, were approved by the United States Food and Drug Administration for the treatment of relapsed or refractory large B-cell lymphoma after at least two lines of systemic therapy based on multicenter single-arm phase two clinical trials...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213398/monitoring-clinical-outcomes-in-aggressive-b-cell-lymphoma-from-imaging-studies-to-circulating-tumor-dna
#6
REVIEW
Christopher Melani, Wyndham H Wilson, Mark Roschewski
Recent guidelines have de-emphasized the role of routine surveillance computed tomography (CT) scans for diffuse large B-cell lymphoma (DLBCL) patients who achieve a complete response to front-line therapy. This shift in practice recommendations was prompted by retrospective studies that failed to demonstrate clear clinical utility for surveillance CT in unselected DLBCL patients. Controversy remains, however, over the role of routine surveillance CT in the highest risk patients for treatment failure who would remain candidates for aggressive salvage therapies...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213397/burkitt-lymphoma-a-rare-but-challenging-lymphoma
#7
REVIEW
Carla Casulo, Jonathan W Friedberg
Burkitt lymphoma (BL) is a rare, aggressive subtype of non-Hodgkin lymphoma affecting approximately 1500 patients per year. Three forms of BL exist (sporadic, endemic, immunodeficiency associated) and the endemic form was first discovered as being driven by the Epstein Barr virus in areas of the world where malaria is prevalent. BL has the characteristic t8; 14 cytogenetic translocation that leads to constitutive activation of the MYC gene, which drives BL cell division. Therapy of BL has resulted in cure for many patients but significant toxicity and treatment related complications remains problematic in the approach to BL therapy...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213396/evolving-treatment-strategies-in-mantle-cell-lymphoma
#8
REVIEW
Natasha Catherine Edwin, Brad Kahl
Mantle cell lymphoma is an incurable, moderately aggressive B cell lymphoma. While a small proportion of patients with indolent disease can be managed expectantly, most patients require treatment. The therapeutic approach is driven by physician recommendation, patient choice, age, fitness and comorbidities. Young, fit patients often receive combination chemoimmunotherapy, including high dose cytarabine, with autologous stem cell transplant. Recent data has indicated benefit from maintenance rituximab following autologous stem cell transplant...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213395/improving-outcomes-in-primary-cns-lymphoma
#9
REVIEW
Maya S Graham, Lisa M DeAngelis
Primary central nervous system lymphoma (PCNSL) is an aggressive disease with previously poor prognosis. The advent of high-dose methotrexate-based induction regimens as well as use of consolidation therapy has greatly improved this prognosis in recent decades, but durable remission still eludes half of patients. In this review, we summarize the progress made in the treatment of PCNSL as well as the challenges that remain, with a focus on defining optimal induction and consolidation regimens, including the promise of developing biotherapies...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213394/an-update-in-treating-transformed-lymphoma
#10
REVIEW
James Godfrey, Michael J Leukam, Sonali M Smith
Indolent lymphomas typically have a prolonged course and favorable prognosis. Recent data support survival times that can reach several decades, even if periodic treatment is needed to manage symptoms or stabilize disease. However, all indolent lymphomas have the potential to undergo transformation to an aggressive phenotype, clinically characterized by a rapid progression of adenopathy, new-onset constitutional symptoms, or laboratory abnormalities, and the immediate need for therapeutic intervention. The most common scenario is transformation of follicular lymphoma to either diffuse large B-cell lymphoma or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations; however, other indolent subtypes such as marginal zone lymphoma, lymphoplasmacytic lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, or even nodular lymphocyte predominant Hodgkin lymphoma, can undergo similar histologic transformation...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213393/the-unique-biology-and-treatment-of-primary-mediastinal-b-cell-lymphoma
#11
REVIEW
Alessandro Broccoli, Pier Luigi Zinzani
The unique biological features of primary mediastinal large B-cell lymphoma are offering suggestions for the development and application of innovative drugs in patients who do not respond to first-line regimens or relapse. This lymphoma, in fact, is characterised by high rates of curability with standard anthracycline-containing chemoimmunotherapy regimens, but still displays a severe prognosis if adequate responses are not rapidly achieved or if the disease recurs. Radiotherapy has proved to be effective to consolidate responses after induction, but it may be safely avoided in certain cases, especially when a metabolic complete response is obtained, as to reduce the incidence of radiation-induced long-term sequelae...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213392/double-hit-lymphoma-how-do-we-define-it-and-how-do-we-treat-it
#12
REVIEW
Brídgín Merron, Andrew Davies
Double/triple hit lymphoma is recognised as a distinct entity within the heterogeneous group of high grade B-cell lymphomas, accounting for between 5 and 10% of cases of diffuse large B-cell lymphoma. Under the WHO 2016 it is now known as high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6. When treated with standard chemotherapy it has a poor outcome. There is currently no standard of care for the management of this condition. Diagnosing double hit lymphoma requires identification of translocations of MYC and BCL2 and/or BCL6...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213391/successful-role-of-radiation-therapy-account-for-every-single-gray-and-make-every-single-gray-count
#13
REVIEW
Bouthaina Shbib Dabaja
Combined-modality treatment involving immuno-chemotherapy with or without radiation has become the mainstay of treatment for aggressive lymphomas such as diffuse large B-cell lymphoma (DLBCL). Long-term goals in the treatment of DLBCL are to keep improving the therapeutic ratio and to extend survival; these goals have been accomplished largely by (a) gaining insight into disease biology and developing biologically based criteria to guide choice of therapy, (b) avoiding unnecessarily long courses of chemotherapy, and (c) reducing both the size of the radiation fields and the radiation dose...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213390/management-of-relapsed-refractory-dlbcl
#14
REVIEW
Clémentine Sarkozy, Laurie H Sehn
Diffuse large B cell lymphoma represents the most common type of non-Hodgkin lymphoma. Although the curability rate is high, around 40% of patients will relapse or exhibit refractory disease. To obtain long-term disease-free survival after relapse, an intensive salvage regimen followed by autologous steam cell transplant remains the standard of care. However, more than 60% of patients will be transplant ineligible, presenting a therapeutic challenge. In this setting, there is no definitive standard approach, as management should be individualized according to patient tolerance...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213389/optimizing-initial-therapy-in-dlbcl
#15
REVIEW
Catherine Thieblemont, Sophie Bernard, Michel Meignan, Thierry Molina
Diffuse large B-cell lymphoma (DLBCL) is a group of lymphomas comprising heterogeneous molecular and biological subtypes, reflected in a broad range of clinical outcomes. With the standard R-CHOP regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab administered every 21 days, the treatment failure rate remains unacceptably high in certain DLBCL subsets. Here we review possible avenues for optimizing initial therapy. The role of functional imaging and biological features, such as double-hit lymphomas, defined by the dual translocation of MYC and BCL2, and dual protein-expresser lymphomas, defined by the overexpression of MYC and BCL2, activated B-cell (ABC)-like DLBCL, to better define these high-risk patient subsets, and their use to guide and personalize treatment decisions are discussed...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213388/dissecting-aggressive-b-cell-lymphoma-through-genomic-analysis-what-is-clinically-relevant
#16
REVIEW
David W Scott, Lisa M Rimsza
The aggressive B-cell lymphomas are a diverse collection of cancers grouped together based on clinical behavior and derivation from B lymphocytes. Genomic analyses on these tumours are now translating into improved classification systems and identification of underpinning targetable biology. Simple karyotyping revealed key translocations involving MYC, BCL2, and BCL6 that have impacted lymphoma classification in the World Health Organization classification scheme. Subsequently, gene expression profiling identified molecular subgroups within the most common lymphoma, diffuse large B-cell lymphoma (DLBCL): activated B-cell-like and germinal centre B-cell-like...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213387/editor-s-introduction
#17
EDITORIAL
Laurie H Sehn
No abstract text is available yet for this article.
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909918/advances-in-the-use-of-natural-receptor-or-ligand-based-chimeric-antigen-receptors-cars-in-haematologic-malignancies
#18
REVIEW
Joana M Murad, David J Graber, Charles L Sentman
Chimeric antigen receptors (CAR)-T cell therapy has recently made promising advances towards treatment of B-cell malignancies. This approach makes use of an antibody-derived single chain variable fragment (scFv)-based CAR to target the CD19 antigen. Currently scFvs are the most common strategy for creation of CARs, but tumor cells can also be targeted using non-antibody based approaches with designs focused on the interaction between natural receptors and their ligands. This emerging strategy has been used in unique ways to target multiple tumor types, including solid and haematological malignancies...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909917/off-the-shelf-t-cell-therapies-for-hematologic-malignancies
#19
REVIEW
Bruce J McCreedy, Vladimir V Senyukov, Kim T Nguyen
Adoptive transfer of autologous CAR-T cells can induce durable remissions in patients with relapsed/refractory hematologic malignancies. However, multiple challenges exist for manufacturing CAR-T cells from patients with advanced disease including inability to manufacture a product, disease progression or death while waiting for the CAR-T product to be available, and heterogeneity among autologous CAR-T products that contributes to unpredictable and variable clinical activity. Healthy donor T cells can provide a source for production of universal CAR-T cells when combined with gene editing to prevent expression of endogenous TCRs and avoid generation of GvHD in HLA mismatched recipients...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909916/toxicities-associated-with-immunotherapies-for-hematologic-malignancies
#20
REVIEW
Mark B Leick, Marcela V Maus
Immunotherapy has generated tremendous hope for patients with cancer that is refractory to standard approaches. Hematologic malignancies have taken the lead in harnessing the most recent advances in cell-based immunotherapies, such as CAR T cells, and some patients have achieved durable remissions. However, these T-cell-engaging therapies are associated with a new set of toxicities which need to be managed by caretakers, oncologists, nurses, and healthcare staff. In this review we provide an overview of the toxicity of some of these revolutionary agents including bispecific T cell engagers, checkpoint inhibitors, chimeric antigen receptor T-cells...
June 2018: Best Practice & Research. Clinical Haematology
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