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Best Practice & Research. Clinical Haematology

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https://www.readbyqxmd.com/read/29909918/advances-in-the-use-of-natural-receptor-or-ligand-based-chimeric-antigen-receptors-cars-in-haematologic-malignancies
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/29909915/cars-and-other-t-cell-therapies-for-mm-the-clinical-experience
#4
REVIEW
Sophia Danhof, Michael Hudecek, Eric L Smith
Harnessing the endogenous immune system to eliminate malignant cells has long been an intriguing approach. After considerable success in the treatment of B-cell acute lymphoblastic leukemia, chimeric antigen receptor (CAR)-modified T cells have entered early clinical evaluation in the field of multiple myeloma (MM). The choice of suitable non-CD19 target antigens is challenging and a variety of myeloma-associated surface molecules have been under preclinical investigation. Most recent clinical protocols have focused on targeting B-cell maturation antigen (BCMA), and early results are promising...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909914/car-t-cell-therapy-for-b-cell-lymphomas
#5
REVIEW
Julio C Chavez, Frederick L Locke
B-cell non-Hodgkin's lymphoma (NHLs)is a very heterogonous malignancy with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) as the most common subtypes. Standard treatment with anti-CD20 based chemoimmunotherapy is usually very effective for disease control. However a significant proportion of patients with high-risk features (double hit lymphoma, transformed lymphomas or early relapses) will become refractory to standard therapies and will have limited alternatives for cure. Adoptive therapy with chimeric antigen receptor (CAR) T-cells is a new paradigm for effective treatment of poor prognosis lymphomas...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909913/gmp-car-t-cell-production
#6
REVIEW
Adrian P Gee
The clinical success achieved using CD19-directed CAR-T cells has stimulated many academic institutions to explore the feasibility of manufacturing these, and other CAR-T cells, in-house. This article reviews the issues that must be addressed in order to achieve this goal. It includes the manufacturing infrastructure, the regulatory environment, practical aspects of production, and the costs involved.
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909912/pre-clinical-development-of-chimeric-antigen-receptor-t-cell-immunotherapy-implications-of-design-for-efficacy-and-safety
#7
REVIEW
Leena Halim, Adam Ajina, John Maher
Following the landmark approvals by the United States Food and Drug Administration, the adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells has now entered mainstream clinical practice for patients with chemotherapy-resistant or refractory B-cell malignancies. These approvals have followed on from a prolonged period of pre-clinical evaluation, informing the design of clinical trials that have demonstrated unprecedented efficacy in this difficult to treat patient population. However, the delivery of autologous CAR-engineered T-cell therapy is complex, costly and not without significant risk...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909911/car-t-cells-immunologic-and-cellular-therapies-in-hematologic-malignancies
#8
EDITORIAL
Renier Brentjens, Marco L Davila
No abstract text is available yet for this article.
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452672/what-is-the-optimal-initial-management-of-the-older-mcl-patient
#9
REVIEW
Johanna C Kluin-Nelemans, Jeanette K Doorduijn
The current first line treatment of a patient with mantle cell lymphoma (MCL) is often considered as too toxic for elderly patients. The elderly, however, comprise the majority of the patients with MCL. The results of several recent studies have shown that the outcome of this patient group is not as dismal as in the past. Indeed, if patients are not considered frail, and can tolerate rituximab and moderate intensive chemotherapy such as R-CHOP followed by rituximab maintenance or R-bendamustine, a 4-year overall survival of >80% can be achieved...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452671/what-is-the-optimal-initial-management-of-the-younger-mantle-cell-lymphoma-patient
#10
REVIEW
Rory McCulloch, Simon Rule
The last 20 years has seen considerable advances made in the management of younger patients with mantle cell lymphoma. The use of high dose cytarabine and rituximab in induction therapy, usually followed by autologous stem cell transplant consolidation, has become established practice and the median overall survival now exceeds 10 years. However, this high intensity upfront approach is not necessarily appropriate for all newly diagnosed patients. A minority exhibit disease that behaves in an indolent fashion with no proven benefit from early intervention, and at the opposite end of the spectrum a high-risk group exists who do poorly with conventional treatment...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452670/what-is-the-optimal-management-of-older-cll-patients
#11
REVIEW
Jennifer A Woyach
CLL is the most common leukemia in older adults with a median age at diagnosis of 71. Therefore, management of patients with this disease must take into account the older age of most patients and consequences of this in terms of functional status and organ function. This review will discuss the management of CLL with regards to observation prior to the initiation of therapy, functional status, and initial treatment. We will discuss criteria for the initiation of therapy, and how initial therapy is different between older and younger patients...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452669/optimal-management-of-the-young-patient-cll-patient
#12
REVIEW
John N Allan, Richard R Furman
The emergence of targeted therapy for patients with chronic lymphocytic leukemia (CLL) has permanently altered the therapeutic landscape. In both upfront and relapsed settings, safe and effective oral kinase inhibitors are available which rival the responses and durability seen with standard chemo immunotherapy regimens. In 2016, ibrutinib was granted Federal Drug Administration approval for first-line therapy in patients with CLL. While its role as initial therapy for older, unfit or deleted 17p CLL patients is less controversial, its role as first-line treatment for younger fit patients is less clear, begging the question, what is the optimal treatment for these patients, novel agents or standard CIT strategies? In this review, we aim to provide guidance for what we believe is the optimal management of young fit patients with CLL...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452668/should-rituximab-replace-splenectomy-in-the-management-of-splenic-marginal-zone-lymphoma
#13
REVIEW
Christina Kalpadakis, Gerassimos A Pangalis, Maria K Angelopoulou, Sotirios Sachanas, Theodoros P Vassilakopoulos
SMZL is a relatively rare low grade B-cell lymphoma, characterized usually by an indolent clinical behavior. Since there is no prospective randomized trials to establish the best treatment approach, decision on therapeutic management should be based on the available retrospective series. Based on these data, rituximab and splenectomy appear to be the most effective. Splenectomy represented the standard treatment modality until early 2000s. More than 90% of the patients present quick amelioration of splenomegaly related symptoms along with improvement of cytopenias related to hypersplenism...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452667/overview-on-the-management-of-non-gastric-malt-lymphomas
#14
REVIEW
Irene Defrancesco, Luca Arcaini
Extranodal marginal zone B-cell lymphomas (EMZLs) of the mucosa-associated lymphoid tissue (MALT) are indolent lymphomas which can present at any extranodal site. The most frequent localizations (other than stomach) are ocular adnexa, salivary gland, skin, lung and thyroid. Chronic inflammation and antigenic stimulation are a potential risk for the development of MALT lymphomas. While Helicobacter Pylori (HP) is known to be associated with gastric MALT lymphoma and antibiotic therapy is effective in the setting of HP-positive, other microorganisms (such as Chlamydophila Psittaci, Campylobacter Jejiuni, Borrelia Burgdoferi) have been implicated in the pathogenesis of non-gastric MALT lymphomas...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452666/transformation-of-follicular-lymphoma-why-does-it-happen-and-can-it-be-prevented
#15
REVIEW
Brian K Link
Follicular lymphoma is a clinical disease with a multitude of presentations and behaviors. Although infrequent, transformation of follicular lymphoma to a more aggressive behaving subtype - prototypically diffuse large B-cell lymphoma - confers a substantially adverse prognosis. There is no consensus for optimal management after transformation is recognized. Historically considered a distinct clinical event, this review highlights the multiple subclinical transformational events that either variably or cumulatively result in clinical recognition of transformed follicular lymphoma...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452665/novel-agents-for-relapsed-and-refractory-follicular-lymphoma
#16
REVIEW
Chan Yoon Cheah, Nathan H Fowler
Follicular lymphoma is one of the most common non-Hodgkin's lymphomas. Although current frontline regimens are associated with high response rates, most patients still relapse. When progression is discovered, re-establishing the diagnosis and ruling out transformation in paramount. The outcomes following relapse have been improving due to the activity and increasing availability of novel agents with various mechanisms of action. Despite these advances, single agent activity is limited and the disease remains incurable in the majority of cases...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452664/the-role-of-stem-cell-transplantation-in-follicular-lymphoma
#17
REVIEW
Georg Hess
With the introduction of novel treatments paradigms to if or when to use transplantation strategies for patients with follicular lymphoma have changed substantially. Autologous transplantation has been intensively evaluated as consolidation after first induction treatment with positive effects, however the introduction of Rituximab led to comparable improvements and HDT has been moved to relapse treatment. In this indication HDT was frequently use already at first relapse, but now is dominantly used in patients with a highrisk profile, e...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452663/management-of-untreated-advanced-stage-follicular-lymphoma-role-of-patient-discernment
#18
REVIEW
Jayadev Manikkam Umakanthan, Mathew A Lunning
Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Advanced stage disease is common at diagnosis. The timing of treatment for follicular lymphoma is best approached by considering the combination of presence or absence of symptoms along with estimation of tumor burden. Upfront treatment strategies should take into initial presentation variables, pace of disease progression and goals of care after discussion with the patient. Treatment approaches remain diverse and patient discernment is paramount...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452662/pathogenesis-of-follicular-lymphoma
#19
REVIEW
Tracy Lackraj, Rashmi Goswami, Robert Kridel
Follicular lymphoma (FL) is presented as a germinal centre B cell lymphoma that is characterized by an indolent clinical course, but remains - paradoxically - largely incurable to date. The last years have seen significant progress in our understanding of FL lymphomagenesis, which is a multi-step process beginning in the bone marrow with the hallmark t(14;18)(q32;q21) translocation. The pathobiology of FL is complex and combines broad somatic changes at the level of both the genome and the epigenome, the latter evidenced by highly recurrent mutations in chromatin-modifying genes such as KMT2D and CREBBP...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452661/risk-stratification-in-follicular-lymphoma
#20
REVIEW
Carla Casulo
Advances in the understanding of FL biology, molecular characteristics and clinical risk factors are further highlighting the heterogeneity of this disease. Historically used prognostic factors were broadly based on clinical and laboratory features at the time of diagnosis. However novel prognostic factors are emerging that can be studied at the time of diagnosis, and relapse, and use a variety of tools including gene alterations and diagnostic imaging. These novel discoveries are being implemented into daily practice with the ultimate goal of providing a precise, individualized approach to every patient with FL...
March 2018: Best Practice & Research. Clinical Haematology
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