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Therapeutic Advances in Hematology

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https://www.readbyqxmd.com/read/27904739/review-of-siltuximab-in-the-treatment-of-multicentric-castleman-s-disease
#1
REVIEW
Shayna Sarosiek, Ruchit Shah, Nikhil C Munshi
Castleman's disease (CD) is a rare lymphoproliferative disorder that has multiple histologic patterns, as well as two distinct clinical forms: unicentric or multicentric. Multicentric Castleman's disease (MCD) may have mild symptoms in some cases, but in others it can progress to severe pancytopenia, life-threatening infection, secondary malignancy, multiorgan failure, or death. Recent research has determined that the etiology of the disease signs and symptoms is related to elevated cytokines, including interleukin 6 (IL-6)...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27904738/recent-developments-in-the-management-of-invasive-fungal-infections-in-patients-with-oncohematological-diseases
#2
REVIEW
Markus Ruhnke, Stefan Schwartz
Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27904737/a-clinical-update-on-the-role-of-carfilzomib-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#3
REVIEW
B Franken, N W C J van de Donk, J C Cloos, S Zweegman, H M Lokhorst
Even though the prognosis of patients with multiple myeloma is continuing to improve, all patients eventually develop relapsed refractory disease. Several novel therapeutics have been developed in the last few years including the second-generation proteasome inhibitor carfilzomib which has been approved for patients with relapsed and refractory multiple myeloma in the United States since 2012. Recently data from several phase III studies have become available showing the promising efficacy of carfilzomib in combination with lenalidomide, which led to the renewed approval of carfilzomib in combination with lenalidomide and dexamethasone for relapsed myeloma in 2015...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27904736/the-biology-behind-b-cell-lymphoma-2-as-a-target-in-chronic-lymphocytic-leukemia
#4
REVIEW
Valentín Ortíz-Maldonado, Pablo Mozas, Julio Delgado
B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main 'hallmarks of cancer', BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27695619/the-potential-of-gene-therapy-approaches-for-the-treatment-of-hemoglobinopathies-achievements-and-challenges
#5
Michael A Goodman, Punam Malik
Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are a heterogeneous group of commonly inherited disorders affecting the function or levels of hemoglobin. Disease phenotype can be severe with substantial morbidity and mortality. Bone marrow transplantation is curative, but limited to those patients with an appropriately matched donor. Genetic therapy, which utilizes a patient's own cells, is thus an attractive therapeutic option. Numerous therapies are currently in clinical trials or in development, including therapies utilizing gene replacement therapy using lentiviruses and the latest gene editing techniques...
October 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27695618/treatment-of-multiple-myeloma-with-the-immunostimulatory-slamf7-antibody-elotuzumab
#6
REVIEW
Hermann Einsele, Martin Schreder
Elotuzumab is a humanized monoclonal antibody targeting the extracellular domain of signaling lymphocytic activation molecule F7 (SLAMF7) highly expressed in multiple myeloma cells. Upon binding to myeloma cells, elotuzumab exerts its cytotoxic effects through antibody-dependent cellular cytotoxicity, the antibody-induced selective lysis of tumor cells by activated natural killer (NK) cells. Furthermore, elotuzumab has been shown to directly induce NK-cell activation by binding to SLAMF7 expressed on NK cells and to indirectly modulate T-cell function by promoting the secretion of cytokines from NK cells...
October 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27695617/the-potential-of-venetoclax-abt-199-in-chronic-lymphocytic-leukemia
#7
REVIEW
Gilad Itchaki, Jennifer R Brown
Venetoclax (VEN, ABT-199/GDC-0199) is an orally bioavailable BH3-mimetic that specifically inhibits the anti-apoptotic B-cell lymphoma/leukemia 2 (BCL2) protein. Although BCL2 overexpression is not genetically driven in chronic lymphocytic leukemia (CLL), it is nearly universal and represents a highly important and prevalent mechanism of apoptosis evasion, making it an attractive therapeutic target. This review summarizes the role of BCL2 in CLL pathogenesis, the development path targeting its inhibition prior to VEN, and the preclinical and clinical data regarding the effectiveness and safety of VEN...
October 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27695616/recent-advances-and-novel-treatment-paradigms-in-acute-lymphocytic-leukemia
#8
REVIEW
Nikolaos Papadantonakis, Anjali S Advani
This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells...
October 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27695615/current-developments-in-molecular-monitoring-in-chronic-myeloid-leukemia
#9
Justine Ellen Marum, Susan Branford
Molecular monitoring plays an essential role in the clinical management of chronic myeloid leukemia (CML) patients, and now guides clinical decision making. Quantitative reverse-transcriptase-polymerase-chain-reaction (qRT-PCR) assessment of BCR-ABL1 transcript levels has become the standard of care protocol in CML. However, further developments are required to assess leukemic burden more efficiently, monitor minimal residual disease (MRD), detect mutations that drive resistance to tyrosine kinase inhibitor (TKI) therapy and identify predictors of response to TKI therapy...
October 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27493713/unusual-spontaneous-aneurysm-formation-in-a-patient-being-treated-with-ibrutinib-for-chronic-lymphocytic-leukemia
#10
Eric Wiedower, Felicia Hare, Adam Arthur, Jason Chandler, Michael G Martin
No abstract text is available yet for this article.
August 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27493712/ofatumumab-plus-chlorambucil-as-a-first-line-therapy-in-less-fit-patients-with-chronic-lymphocytic-leukemia-analysis-of-complement1-and-other-monoclonal-antibodies-association-data
#11
REVIEW
Anna Maria Frustaci, Alessandra Tedeschi, Paola Picardi, Maddalena Mazzucchelli, Roberto Cairoli, Marco Montillo
The management of patients with chronic lymphocytic leukemia (CLL) has radically improved over the last few years with the addition of anti-CD20 monoclonal antibodies (MoAbs) to chemotherapy. Chlorambucil has been considered for decades as a suitable therapeutic option for frail patients. Taking into account the advantage offered by the addition of MoAbs to chemotherapy, different studies up to now have explored the feasibility of chlorambucil-based chemoimmunotherapies in treatment-naïve CLL. COMPLEMENT1 is a prospective, randomized, open-label trial evaluating the efficacy and safety of ofatumumab added to chlorambucil, compared with chlorambucil in monotherapy, in the setting of untreated patients with CLL considered unsuitable for a fludarabine-based approach...
August 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27493711/a-comprehensive-review-of-lenalidomide-in-b-cell-non-hodgkin-lymphoma
#12
REVIEW
Mili Arora, Sonia Gowda, Joseph Tuscano
Lenalidomide, an immunomodulatory drug that the US Food and Drug Administration (FDA) approved for the treatment of multiple myeloma, 5q- myelodysplasia and mantle-cell lymphoma (MCL), has encouraging efficacy in other B-cell malignancies. Its unique mechanism of action is in part due to altering the tumor microenvironment and potentiating the activity of T and natural-killer (NK) cells. Impressive clinical activity and excellent tolerability allows broad applicability. Lenalidomide has been used in a wide range of B-cell malignancies for years, but in 2013, the FDA marked its approval as a single agent only in relapsed/refractory mantle-cell lymphoma...
August 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27493710/bortezomib-for-the-treatment-of-mantle-cell-lymphoma-an-update
#13
REVIEW
Bryan Hambley, Paolo F Caimi, Basem M William
Bortezomib is a first in class proteasome inhibitor, initially approved by the US Food and Drug Administration for the treatment of plasma cell myeloma. Bortezomib has been approved for the treatment of relapsed and refractory mantle cell lymphoma (MCL) and, more recently, in the upfront setting as well. Treatment algorithms for MCL have rapidly evolved over the past two decades, and the optimal regimen remains to be defined. The choice of treatment regimen is based on disease risk stratification models, the expected toxicity of antineoplastic agents, the perceived patient ability to tolerate the planned treatments and the availability of novel agents...
August 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27493709/elotuzumab-the-first-approved-monoclonal-antibody-for-multiple-myeloma-treatment
#14
REVIEW
Hila Magen, Eli Muchtar
Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor, expressed on normal and malignant plasma cells with a lower expression on other lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant antimyeloma activity when given as a single agent to patients with relapsed or refractory multiple myeloma (RRMM). However, when combined with other antimyeloma agents, it results in improved response and outcome. Owing to the results from the landmark ELOQUENT-2 phase III clinical trial, which compared lenalidomide and dexamethasone with or without elotuzumab in patients with RRMM, elotuzumab in combination with lenalidomide and dexamethasone was approved by the American Food and Drug Administration (FDA) in November 2015 for multiple myeloma (MM) patients who received one to three prior lines of therapy...
August 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27493708/ibrutinib-in-waldenstr%C3%A3-m-macroglobulinemia-latest-evidence-and-clinical-experience
#15
REVIEW
Jorge J Castillo, M Lia Palomba, Ranjana Advani, Steven P Treon
Ibrutinib is an oral Bruton's tyrosine kinase (BTK) inhibitor, which has recently gained approval by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with symptomatic Waldenström macroglobulinemia (WM). Herein, we review the role of BTK in the pathophysiology of WM, and present the results of the preclinical and clinical studies that led to the initial investigation and later approval of ibrutinib in WM. We also discuss aspects associated with ibrutinib therapy in WM patients, especially focusing on genomic profiling and the impact on response to ibrutinib, and the management of adverse events...
August 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27247757/mogamulizumab-for-the-treatment-of-cutaneous-t-cell-lymphoma-recent-advances-and-clinical-potential
#16
REVIEW
Madeleine Duvic, Mark Evans, Casey Wang
Mogamulizumab (KW-0761) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets CC chemokine receptor 4 (CCR4). It has shown promising therapeutic potential in phase I and II clinical trials and is currently being investigated for efficacy in treating cutaneous T-cell lymphoma (CTCL). We review the mechanism of action of mogamulizumab and its role in treating CTCL. We also discuss the results of major clinical trials.
June 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27247756/targeting-b-cell-receptor-signaling-kinases-in-chronic-lymphocytic-leukemia-the-promise-of-entospletinib
#17
REVIEW
Jeff Sharman, Julie Di Paolo
The B-cell receptor signaling pathway has emerged as an important therapeutic target in chronic lymphocytic leukemia and other B-cell malignancies. Novel agents have been developed targeting the signaling enzymes spleen tyrosine kinase (SYK), Bruton's tyrosine kinase, and phosphoinositide 3-kinase delta. This review discusses the rationale for targeting these enzymes, as well as the preclinical and clinical evidence supporting their role as therapeutic targets, with a particular focus on SYK inhibition with entospletinib...
June 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27247755/the-role-of-blinatumomab-in-patients-with-relapsed-refractory-acute-lymphoblastic-leukemia
#18
REVIEW
Jonathan E Benjamin, Anthony S Stein
Adults with relapsed/refractory B-acute lymphoblastic leukemia (ALL) have a complete remission (CR) rate of 20-45% and median overall survival of 3-9 months, depending on the duration of the first remission and number of lines of salvage therapy. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative option for adult patients with relapsed/refractory ALL, and achievement of CR is a crucial step before alloHSCT. Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct with dual specificity for CD19 and CD3, simultaneously binding CD3-positive cytotoxic T cells and CD19-positive B cells, resulting in T-cell-mediated serial lysis of normal and malignant B cells...
June 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27247754/reduced-intensity-conditioning-allogeneic-hematopoietic-cell-transplantation-for-older-patients-with-acute-myeloid-leukemia
#19
REVIEW
Gaurav Goyal, Krishna Gundabolu, Saraschandra Vallabhajosyula, Peter T Silberstein, Vijaya Raj Bhatt
Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis...
June 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27054026/the-evolving-role-of-response-adapted-pet-imaging-in-hodgkin-lymphoma
#20
REVIEW
Michael Coyle, Lale Kostakoglu, Andrew M Evens
(18)F-fluorodeoxyglucose positron emission tomography with (FDG-PET) has a well-established role in the pre- and post-treatment staging of Hodgkin lymphoma (HL), however its use as a predictive therapeutic tool via responded-adapted therapy continues to evolve. There have been a multitude of retrospective and noncontrolled clinical studies showing that early (or interim) FDG-PET is highly prognostic in HL, particularly in the advanced-stage setting. Response-adapted treatment approaches in HL are attempting to diminish toxicity for low-risk patients by minimizing therapy, and conversely, intensify treatment for high-risk patients...
April 2016: Therapeutic Advances in Hematology
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