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Malignancies: Causes, Symptoms, Diagnosis, and Treatment



Chaired by Andrew D. Zelenetz, MD, PhD, from Memorial Sloan Kettering Cancer Center, the Congress featured panel discussions with world-renowned experts, interactive presentations, and challenging patient cases that highlight recent updates to the NCCN Guidelines, new and emerging therapeutic agents, and practical management strategies for patients with hematologic malignancies. The agenda included topics designed to meet the educational needs of oncologists, hematologists, nurse practitioners, nurses, pharmacists, physician assistants, and other health care professionals who manage patients with hematologic malignancies.




malignancies



The expert physician investigators in our division are leading innovative research aimed at expanding treatment options for patients with malignancies and hematologic disorders. Fellows train alongside experts in a dynamic, state-of-the-art environment.


Investigators are also focused on ways to alter and interfere with immune cell reactions to improve outcomes in bone marrow transplant patients and to pursue immune therapy strategies for cancers of the blood and lymph/immune cells. Their research is resulting in novel strategies for adult and pediatric hematologic malignancies and many noncancer diseases, including aplastic anemia, certain genetic diseases and sickle cell disease.


Our world-renowned laboratory scientists and clinical investigators strive daily to make further paradigm-changing discoveries that improve outcomes for patients with blood cancers. CHM is designed to accelerate scientific discovery, to support investigations into new research directions, and to serve as a node for translational research between laboratory and clinical investigators with a shared interest in hematologic malignancies.


Layout table for study information Study Type : Interventional (Clinical Trial) ActualEnrollment : 185 participants Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment Official Title: A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands Actual Study Start Date : December 1, 2011 Actual Primary Completion Date : June 14, 2021 Estimated Study Completion Date : November 23, 2023 Resource links provided by the National Library of Medicine MedlinePlus Genetics related topics: Breast cancer Melanoma Genetic and Rare Diseases Information Center resources: Pancreatic Cancer Neuroendocrine Tumor Neuroepithelioma Esophageal Cancer U.S. FDA Resources Arms and Interventions Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Arm Intervention/treatment Experimental: LGK974LGK974 Drug: LGK974Other Name: WNT974 Experimental: LGK974 in combination with PDR001LGK in combination with PDR001 Drug: LGK974Other Name: WNT974 Biological: PDR001 Outcome Measures Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Primary Outcome Measures : Maximum Tolerated Dose or Recommended Dose for Expansion of LGK974 as a single agent or in combination with PDR001 in patients treated [ Time Frame: 34 months ]Determine the Maximum Tolerated Dose (MTD) or Recommended Dose for Expansion (RDE) of LGK974 as a single agent and in combination with PDR001 when administered orally to adult patients with malignancies dependent on Wnt ligands. Secondary Outcome Measures : Type and category of study drug related adverse events (AE) [ Time Frame: 61 months ]The incidence of treatment-emergent adverse events (new or worsening from baseline) will be summarized by primary system organ class, severity based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, type of AE, relationship to study drug by dose group. Absorption and plasma concentrations of LGK974 [ Time Frame: 61 months ]Evaluate pharmacokinetic (PK) parameters such as AUClast, AUCtau, Cmax, the apparent elimination T1/2 and Racc for LGK974 and its pharmacologically metabolite. PD related to the Wnt pathway [ Time Frame: 61 months ]Assessing percent change from baseline to post-treatment of PD related to the Wnt pathway. Overall response rate of tumor [ Time Frame: 61 months ]Patients with an Overall Response Rate(ORR), complete response (CR) or partial response (PR) rate and duration of response (DOR) assessed by RECIST 1.1 for single agent LGK974 and by RECIST1.1 and irRC for LGK974+PDR001. Absorportion and plasma concentrations of PDR001 [ Time Frame: 61 months ]Evaluate pharmacokinetic (PK) parameters such as AUClast, AUCtau, Cmax, the apparent elimination T1/2 and Racc for LGK974, its pharmacologically metabolite and PDR001. Eligibility CriteriaGo to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. Layout table for eligibility information Ages Eligible for Study: 18 Years and older (Adult, Older Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: No Criteria Inclusion Criteria:


Tania Brandstoetter, Johannes Schmoellerl, Reinhard Grausenburger, Sebastian Kollmann, Eszter Doma, Jani Huuhtanen, Thorsten Klampfl, Thomas Eder, Florian Grebien, Gregor Hoermann, Johannes Zuber, Satu Mustjoki, Barbara Maurer, Veronika Sexl; SBNO2 is a critical mediator of STAT3-driven hematological malignancies. Blood 2023; blood.2022018494. doi:


Gain-of-function mutations in the STAT3 gene are recurrently identified in patients suffering from large granular lymphocytic leukemia (LGLL) and some cases of T/NK and adult T-cell leukemia/lymphoma. To understand the consequences and molecular mechanisms contributing to disease development and oncogenic transformation we developed murine hematopoietic stem and progenitor cell models expressing mutated STAT3Y640F. The cells show accelerated proliferation and enhanced self-renewal potential. We integrated gene expression analyses and chromatin occupancy profiling of STAT3Y640F-transformed cells with T-LGLL patient data. This approach uncovered a conserved set of direct transcriptional targets of STAT3Y640F. Among those, the strawberry notch homolog 2 (SBNO2) represents an essential transcriptional target which was identified by a comparative genome-wide CRISPR/Cas9-based loss-of-function (LOF) screen. The STAT3-SBNO2 axis is also present in NK-cell leukemia, T-cell non Hodgkin-lymphoma (T-NHL) and NPM-ALK-rearranged T-anaplastic large cell lymphoma (T-ALCL), which are driven by STAT3-hyperactivation/mutation. In NPM-ALK T-ALCL patients, high SBNO2 expression correlates with shorter relapse-free- and overall survival. Our findings identify SBNO2 as potential therapeutic intervention site for STAT3-driven hematopoietic malignancies.


Mukherjee S, Sathanoori M, Ma Z, et al. Addition of chromosomal microarray and next generation sequencing to FISH and classical cytogenetics enhances genomic profiling of myeloid malignancies. Cancer Genet. 2017;216-217:128-141.


The Chronic Malignancies Working Party promotes and conduct educational activities and clinical investigations on the role of hematopoietic cell transplantation in chronic malignancies such as chronic leukaemias, myelodysplastic syndromes, myeloproliferative and plasma cell disorders.


Hematologic malignancies are cancers that begin in blood-forming tissue, such as the bone marrow, or in the cells of the immune system. There are three main types of hematologic malignancies: leukemia, lymphoma and multiple myeloma.


A recent EU review of Xgeva has added into the product information the risk of new primary malignancy when used for the prevention of skeletal-related events in adults with advanced malignancies involving bone. A letter has been sent to healthcare professionals about this risk.


In a pooled analysis of four phase III studies in patients with advanced malignancies involving bone, new primary malignancy was reported more frequently in patients treated with Xgeva (denosumab 120 mg, once a month) compared to zoledronic acid (4 mg, once a month) during the primary double-blind treatment phases of these studies.


To provide effective care for patients with these cancer conditions, our hematology malignancies program offers patients state-of-the-art medical treatment with the help of progressive technologies and our compassionate staff members. Some of the treatments that we offer include infusion of blood components or medications for benign and malignant conditions, and chemotherapy for blood cancers like leukemia and lymphoma. We also provide radiation therapy treatments for malignancies, including therapies that use advanced technologies like TomoTherapy, a form of image-guided, intensity-modulated radiation (IMRT).


The Secretary, acting as appropriate through the Director of the Centers for Disease Control and Prevention and the Director of the National Institutes of Health, shall study environmental and other risk factors for childhood cancers (including skeletal malignancies, leukemias, malignant tumors of the central nervous system, lymphomas, soft tissue sarcomas, and other malignant neoplasms) and carry out projects to improve outcomes among children with childhood cancers and resultant secondary conditions, including limb loss, anemia, rehabilitation, and palliative care. Such projects shall be carried out by the Secretary directly and through awards of grants or contracts. 2ff7e9595c


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