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https://www.readbyqxmd.com/read/28096698/burkitt-lymphoma-in-adolescents-and-young-adults-management-challenges
#1
REVIEW
Massimo Dozzo, Francesca Carobolante, Pietro Maria Donisi, Annamaria Scattolin, Elena Maino, Rosaria Sancetta, Piera Viero, Renato Bassan
About one-half of all Burkitt lymphoma (BL) patients are younger than 40 years, and one-third belong to the adolescent and young adult (AYA) subset, defined by an age between 15 and 25-40 years, based on selection criteria used in different reports. BL is an aggressive B-cell neoplasm displaying highly characteristic clinico-diagnostic features, the biologic hallmark of which is a translocation involving immunoglobulin and c-MYC genes. It presents as sporadic, endemic, or epidemic disease. Endemicity is pathogenetically linked to an imbalance of the immune system which occurs in African children infected by malaria parasites and Epstein-Barr virus, while the epidemic form strictly follows the pattern of infection by HIV...
2017: Adolescent Health, Medicine and Therapeutics
https://www.readbyqxmd.com/read/28088906/epratuzumab-and-blinatumomab-as-therapeutic-antibodies-for-treatment-of-pediatric-acute-lymphoblastic-leukemia-current-status-and-future-perspectives
#2
Raffaella Franca, Diego Favretto, Marilena Granzotto, Giuliana Decorti, Marco Rabusin, Gabriele Stocco
BACKGROUND: More than 85% of children affected by acute lymphoblastic leukemia (ALL) are successfully treated; however relapse remains a remarkable clinical concern, with 50-60% of relapsing patients facing a fatal outcome. Management of relapsed patients includes standardized intensive risk-adapted regimens based on conventional drugs, and hematopoietic stem cells transplantation for patients with unfavourable features. Biological drugs, in particular the monoclonal antibody epratuzumab and the bi-functional recombinant single chain peptide blinatumomab, have been recently recognized as novel potential agents to be integrated in salvage ALL therapy to further improve rescue outcome...
January 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28028314/redirecting-t-cells-to-eradicate-b-cell-acute-lymphoblastic-leukemia-bispecific-t-cell-engagers-and-chimeric-antigen-receptors
#3
REVIEW
I Aldoss, R C Bargou, D Nagorsen, G R Friberg, P A Baeuerle, S J Forman
Recent advances in antibody technology to harness T-cells for cancer immunotherapy, particularly in the difficult-to-treat setting of relapsed or refractory acute lymphoblastic leukemia (r/r ALL), has led to innovative methods for directing cytotoxic T-cells to specific surface antigens on cancer cells. One approach involves administration of soluble bispecific (or dual-affinity) antibody-based constructs that temporarily bridge T-cells and cancer cells. Another approach infuses ex vivo-engineered T-cells that express a surface plasma membrane-inserted antibody construct called a chimeric antigen receptor (CAR)...
December 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27998223/phase-i-phase-ii-study-of-blinatumomab-in-pediatric-patients-with-relapsed-refractory-acute-lymphoblastic-leukemia
#4
Arend von Stackelberg, Franco Locatelli, Gerhard Zugmaier, Rupert Handgretinger, Tanya M Trippett, Carmelo Rizzari, Peter Bader, Maureen M O'Brien, Benoît Brethon, Deepa Bhojwani, Paul Gerhardt Schlegel, Arndt Borkhardt, Susan R Rheingold, Todd Michael Cooper, Christian M Zwaan, Phillip Barnette, Chiara Messina, Gérard Michel, Steven G DuBois, Kuolung Hu, Min Zhu, James A Whitlock, Lia Gore
Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II)...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27990053/blinatumomab-for-lymphoblastic-leukaemia
#5
REVIEW
(no author information available yet)
No abstract text is available yet for this article.
December 2016: Australian Prescriber
https://www.readbyqxmd.com/read/27987201/treatment-of-acute-lymphoblastic-leukemia-in-adults-applying-lessons-learned-in-children
#6
REVIEW
Ibrahim T Aldoss, Guido Marcucci, Vinod Pullarkat
Although pediatric acute lymphoblastic leukemia (ALL) has cure rates of over 90%, adult ALL remains a challenging disease to treat, with cure rates roughly half those seen in children. The inferior outcomes in adults can be attributed mainly to adverse genetic features, as well as the inability-particularly of older adults-to tolerate chemotherapy. Modest improvements have been seen in outcomes for adolescents and young adults; these can largely be attributed to the use of pediatric-type combination chemotherapy regimens in patients aged 50 years or younger...
December 15, 2016: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/27935578/comment-on-blinatumomab-vs-historical-standard-therapy-of-adult-relapsed-refractory-acute-lymphoblastic-leukemia
#7
W H Tong
No abstract text is available yet for this article.
December 9, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27913530/cytokine-release-syndrome-with-novel-therapeutics-for-acute-lymphoblastic-leukemia
#8
Noelle V Frey, David L Porter
T-cell-engaging immunotherapies are exciting new approaches to treat patients with acute lymphoblastic leukemia (ALL). These unique agents, which include blinatumomab, a CD3/CD19 bispecific antibody, and chimeric antigen receptor (CAR) modified T cells targeted to CD19 have shown unprecedented remission rates in the relapsed, refractory ALL setting. Cytokine release syndrome (CRS), resulting from the high magnitude of immune activation by these therapies, is the most significant treatment-related toxicity. CRS manifests with fever and malaise and can progress to life-threatening capillary leak with hypoxia and hypotension...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27908880/an-anti-cd3-anti-cll-1-bispecific-antibody-for-the-treatment-of-acute-myeloid-leukemia
#9
Steven R Leong, Siddharth Sukumaran, Maria Hristopoulos, Klara Totpal, Shannon Stainton, Elizabeth Lu, Alfred Wong, Lucinda Tam, Robert Newman, Brian R Vuillemenot, Diego Ellerman, Chen Gu, Mary Mathieu, Mark S Dennis, Allen Nguyen, Bing Zheng, Crystal Zhang, Genee Lee, Yu-Waye Chu, Rodney A Prell, Kedan Lin, Steven T Laing, Andrew G Polson
Acute myeloid leukemia (AML) is major unmet medical need. Most patients have poor long-term survival and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T-cells by binding to CD3, the signaling component of the T-cell receptor, and a tumor target have shown clinical activity. Notably, blinatumomab is approved to treat relapsed/refractory acute lymphoid leukemia. Here we describe the design, discovery, pharmacological activity, pharmacokinetics, and safety of a CD3 T-cell-dependent bispecific (TDB) full-length human IgG1 therapeutic antibody targeting CLL-1 that could potentially be used in humans to treat AML...
December 1, 2016: Blood
https://www.readbyqxmd.com/read/27873237/estimating-long-term-survival-of-adults-with-philadelphia-chromosome-negative-relapsed-refractory-b-precursor-acute-lymphoblastic-leukemia-treated-with-blinatumomab-using-historical-data
#10
Arie Barlev, Vincent W Lin, Aaron Katz, Kuolung Hu, Ze Cong, Beth Barber
INTRODUCTION: Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(-) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years. METHODS: The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset...
November 21, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27872741/novel-drugs-in-follicular-lymphoma
#11
REVIEW
Antonella Anastasia, Giuseppe Rossi
Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of achieving a definite cure, have prompted investigations into the possible role of more active and less toxic strategies with innovative therapeutic agents. Recently Casulo et al. demonstrated that approximately 20% of patients with FL relapse within two years after achieving remission with R-CHOP and have a poor prognosis...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27820973/emerging-biological-therapies-to-treat-acute-lymphoblastic-leukemia
#12
Françoise Huguet, Suzanne Tavitian
Various settings of acute lymphoblastic leukemia (ALL) represent unmet medical needs: first remission at high risk of relapse, such as persistent minimal residual disease (MRD); relapse/refractoriness (R/R); elderly patients. Biological therapies targeting widely-shared antigens of blast cells have entered the clinic in B-cell precursor (BCP)-ALL. Area covered: Results of phase II/III trials of monoclonal antibodies (MoAbs) and phase I/II trials of adoptive cell therapy by chimeric antigen receptor-engineered T cells (CAR-T cells) are presented...
December 25, 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27816725/blinatumomab-provoked-fatal-heart-failure
#13
REVIEW
Behrad Darvishi, Leila Farahmand, Neda Jalili, Keivan Majidzadeh-A
Mentioned in Blinatumomab (Blincyto®) clinical safety report, a 5 year old boy with acute lymphoblastic leukemia (ALL) receiving Blincyto® with the concentration of 30μg/m(2)/day on the fourth day of therapy developed both Cytokine Release Syndrome (CRS) and Tumor Lysis Syndrome (TLS). Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Bilirubin peaks were 18, 7 and 8 folds more than upper normal limit (UNL) respectively. However, albumin was reduced to approximately half of the lower Normal limit (LNL)...
December 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27799606/successful-reintroduction-of-blinatumomab-in-a-patient-with-relapsed-refractory-acute-lymphoblastic-leukemia-following-grade-4-cytokine-release-syndrome
#14
Bernard L Marini, Yihan Sun, Patrick W Burke, Anthony J Perissinotti
Relapsed/refractory acute lymphoblastic leukemia poses a clinical challenge due to its poor prognosis and lack of effective treatment. Blinatumomab, a novel immunotherapy, has demonstrated excellent efficacy in relapsed/refractory acute lymphoblastic leukemia; however, life-threatening toxicities such as cytokine release syndrome have been reported in pivotal clinical trials. In this report, we describe the safe reintroduction of blinatumomab in an adult patient with relapsed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia after experiencing grade 4 blinatumomab-induced cytokine release syndrome using a unique dosing strategy and a very diligent monitoring approach...
October 31, 2016: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/27784674/resistance-to-anti-cd19-cd3-bite-in-acute-lymphoblastic-leukemia-may-be-mediated-by-disrupted-cd19-membrane-trafficking
#15
Friederike Braig, Anna Brandt, Mariele Goebeler, Hans-Peter Tony, Anna-Katharina Kurze, Peter Nollau, Thomas Bumm, Sebastian Böttcher, Ralf C Bargou, Mascha Binder
The CD19 antigen is a promising target for immunotherapy of acute lymphoblastic leukemia (ALL), but CD19-negative relapses remain a major challenge in about 10-20% of patients. Here, we analyzed four CD19-negative ALL relapses after treatment with the CD19/CD3 bispecific T-cell engager blinatumomab. Three were on-drug relapses, with the CD19-negative escape variant first detected after only two treatment courses. In one patient, the CD19-negative clone appeared as a late relapse 19 months after completion of blinatumomab treatment...
October 26, 2016: Blood
https://www.readbyqxmd.com/read/27761200/catch-me-if-you-can-leukemia-escape-after-cd19-directed-t-cell-immunotherapies
#16
REVIEW
Marco Ruella, Marcela V Maus
Immunotherapy is the revolution in cancer treatment of this last decade. Among multiple approaches able to harness the power of the immune system against cancer, T cell based immunotherapies represent one of the most successful examples. In particular, biotechnological engineering of protein structures, like the T cell receptor or the immunoglobulins, allowed the generation of synthetic peptides like chimeric antigen receptors and bispecific antibodies that are able to redirect non-tumor specific T cells to recognize and kill leukemic cells...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27759440/treating-adults-with-acute-lymphocytic-leukemia-new-pharmacotherapy-options
#17
Xavier Thomas, Caroline Le Jeune
Advances in acute lymphocytic leukemia (ALL) therapy has led to long-term survival rates in children. However, only 30%-40% of adults achieve long-term disease-free survival. After relapse, the outcome of salvage chemotherapy is very disappointing with less than 10% of long survival. Novel agents are therefore desperately required to improve response rates and survival, but also the quality of life of patients. Areas covered: The following review is a comprehensive summary of various novel options reported over the past few years in the therapeutic area of adult ALL...
December 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27742613/blinatumomab-has-activity-in-pediatric-patients-with-advanced-bcp-all
#18
(no author information available yet)
Blinatumomab was active across age and risk groups in patients with relapsed or refractory BCP-ALL.
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27713846/advancements-in-therapy-for-acute-lymphoblastic-leukemia-blinatumomab
#19
REVIEW
Lindsay Hladnik, Kristan Augustin, Sean DeFrates
No abstract text is available yet for this article.
January 2016: Journal of the Advanced Practitioner in Oncology
https://www.readbyqxmd.com/read/27708227/t-cell-responses-against-cd19-pediatric-acute-lymphoblastic-leukemia-mediated-by-bispecific-t-cell-engager-bite-are-regulated-contrarily-by-pd-l1-and-cd80-cd86-on-leukemic-blasts
#20
Judith Feucht, Simone Kayser, David Gorodezki, Mohamad Hamieh, Michaela Döring, Franziska Blaeschke, Patrick Schlegel, Hans Bösmüller, Leticia Quintanilla-Fend, Martin Ebinger, Peter Lang, Rupert Handgretinger, Tobias Feuchtinger
T-cell immunotherapies are promising options in relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We investigated the effect of co-signaling molecules on T-cell attack against leukemia mediated by CD19/CD3-bispecific T-cell engager. Primary CD19+ ALL blasts (n≥10) and physiologic CD19+CD10+ bone marrow precursors were screened for 20 co-signaling molecules. PD-L1, PD-1, LAG-3, CD40, CD86, CD27, CD70 and HVEM revealed different stimulatory and inhibitory profiles of pediatric ALL compared to physiologic cells, with PD-L1 and CD86 as most prominent inhibitory and stimulatory markers...
September 30, 2016: Oncotarget
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