OVERVIEW

Navigating the Evolving Therapeutic Landscape of CLL: Strategies for the Optimal Application of Emerging Agents and Combinations in Practice is organized by Healthcare Made Practical (HMP) Communications LLC and will be held from Oct 31, 2018 - Oct 31, 2019.

Target Audience:
Designed for hematologists and hematologic oncologists, medical, radiation, and surgical oncologists, and other healthcare professionals (e.g., physicians, physicians-in-training, oncology nurses, nurse practitioners, pharmacists, physician assistants) who are involved and/or interested in the treatment of patients with hematologic malignancies.

Accreditation:

CME 2.25
CNE 2.25
CPE 2.25

Course Overview:
An individualized approach to Chronic Lymphocytic Leukemia (CLL) management is now possible with the targeted therapies and current clinical guidelines to recommend treatment options for the first-line or relapsed/refractory setting based on patient age and genetic biomarkers. However, the diversity of these targeted therapies, with even agents that belong to the same therapeutic class exhibiting differences in their precise mechanisms of action, efficacy, dosing, and adverse effect profiles, also generates new challenges for their appropriate use and optimal placement in therapeutic paradigms. Moreover, the data pool surrounding targeted CLL therapy is continually evolving, featuring expanded indications for first-line therapy or specific relapsed/refractory patient populations; next-generation agents with improved efficacy and safety profiles that are poised to further advance outcomes for patients with CLL.

This on-demand web archive is initiated to address knowledge and practice gaps among physicians, NPs, and PAs pertaining to this rapidly changing treatment landscape for CLL.

Course Objectives:
• Distinguish among the full array of available and emerging targeted therapies for CLL, highlighting both between-class and within-class distinctions in mechanisms of action, efficacy, adverse effect profiles, and indications
• Evaluate current and emerging clinical trial data surrounding newer agents and combination strategies that may impact the CLL management paradigm
• Address barriers to the optimal implementation of targeted CLL therapies through strategies to improve adherence, persistence, and adverse effect management

Additional details will be posted as soon as they are available.

FACULTY

Jennifer R. Brown

MD, PhDOncology, Haematology, Internal Medicine

John C. Byrd

MDHaematology

Kanti Roop Rai

MDOncology, Haematology

Neil E. Kay

MDHaematology, Internal Medicine

Peter Hillmen

MD, MB ChB, PhDHaematology

SPECIALITIES

HaematologyOncology

REVIEWS (1)

Signification of p-53 Protein Isoform in Chronic Lymphocytic Leukemia Aurelian Udristioiu¹, aurelianu2007@yahoo.com, Manole Cojocaru¹, mancojocaru@yahoo.com, Delia Nica-Badea², nicabadeadelia@yahoo.com, ¹Faculty of Medicine, Titu Maiorescu University, Bucharest, Romania, ²Constantin Brancusi University, Faculty of Medical Science and Behaviors, Târgu Jiu, Romania Corresponding author, Aurelian Udristioiu, aurelianu2007@yahoo.com Abstract This work of research investigated the diagnosed cases with Chronic Lymphocytic Leukemia (CLL) with possible mutations or translocations of the P-53 gene in the human B lymphocyte genome. By ELISA technique, was analyzed the frequency of p-53 protein expression to 20 patients diagnosed with CLL, in the relationship of this protein to the disease status, in stage I/II-III/IV. Was calculated the frequency of increased expressed p-53 protein in type B-CLL, in 15% per cent. The mean value of p-53 protein concentration, in 17 cases of the 20, was calculated at 16.76 ?g / dl, CV = 0.5%, and probability index p = 0.034 value. The percentage of p53 positive isoform proteins increased above the normal values, with disease progression, 15% + -2, in stage 1-2 as compared to 100% in stage 3-4. In this context of CLL-B, this method, ELISA, has proven to be a useful prognostic tool and has been able to identify the patients with p-53 isoforms, which may be considered candidates for personalized treatment in CLL-B. Keywords: apoptosis, p-53 monoclonal antibody, chronic lymphocytic leukemia, p-53 protein, TP-53 gene, ZAP-70, CD 38 receptor. Short presentation of the project, mentioning the proposed targets to be achieved by implementing the project In recent years, the technique of gene analysis, chromosome rearrangement, cross reactivity, or multiplication in the human genome affected by a variety of genetic diseases has been used. It has been demonstrated that the best techniques for investigating malignant lymphocytes are flow cytometry and in situ hybridization fluorescence (FISH). The latter method, FISH, is used as an alternative to chromosomal bandage, a conventional application in molecular medicine and can detect gene deletions, chromosomal and complex rearrangements of various genes in malignant diseases such as chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia) or multiple myeloma (MM). In particular, the identification of P53 gene deletions and mutations in chromosome 17 regions in hematological malignancies is important because these genetic events have an impact on the clinical management of patients. Completing personal research using the FISH molecular technique could contribute to a new breakthrough in treating cancer, especially in CLL, the most common form of adult leukemia. Identifying different mutations is important because these mutations have an impact on patients' clinical course and require an appropriate adjustment of the therapeutic attitude. High concentrations of anaerobic ATP may affect CLL apoptosis. Further studies are needed to detect in patients with high concentrations of ATP mutations or translocations deletions of the p53 gene using complex molecular technologies to discover the complete mechanism in the carcinogenesis process (Udri?tioiu A, Florescu C, Popescu AM, Cojocaru M. High concentration of anaerobic ATP involved in aborted apoptosis from CLL, Lab. Med 41: 2010: 203-8). Current state of the research topic In the country, Romania The application of ELISA and FISH technology in highly specialized laboratories from research institutions funded by European programs in cases of malignant patients resistant to conventional classical therapy, chemotherapy has not been published in scientific papers in the country. The subsequent recently published the significance of p-53 proteins in triggering malignant hematopoiesis, (Udristioiu Aurelian, Nica-Badea Delia. Biomedicine & Pharmacotherapy. Significance of protein p-53 isoforms and immune therapeutic success in chronic lymphocytic leukemia. Volume 106, October 2018, pages 50-53; Indexing in the PubMed Web of Science (WOS). In abroad: In international studies. expression of unchanged immunoglobulin heavy chain variable (IGHV) genes, ZAP-70 proteins, CD38 receptor, and chromosomal anomalies such as 17p deletions have been associated with poor prognosis for non-Hodgkin's lymphomas. In addition, mutations in tumor suppressor genes, such as P-53 and ATM, have been associated with resistance to conventional chemotherapeutic agents. Modifications of micro-RNA expression and aberrant methylation patterns in genes that are specifically deregulated in CLL, including the BCL-2, TCL1 and ZAP-70 genes, have also been encountered and related to distinguished clinical parameters. Specific chromosomal abnormalities and genetic mutations can serve as diagnostic and prognostic indicators for disease progression and survival. The effectiveness of new therapists should be tested for the presence of these molecular lesions in CLL patients. P53 mutations are the most common genetic abnormalities of cancer. They have been extensively studied in various mature B cell malignancies, including CLL. In recent years, more attention has been paid to the importance of the p53expressed protein in CLL, and a combination with low survival and non-response to classical conventional chemotherapy and radiotherapy therapy has been observed in a number of cases of CLL with the p-53 protein mutant or absence as a consequence of P-53 gene deletion. -Aurelian Udristioiu, M.D, Primary Physician Laboratory Medicine, City Targu Jiu, -Romania. -National Academy of Biochemical Chemistry NACB/AACC Member, Washington D.C, USA -PhD in Molecular Biology, Titu Maiorescu University, General Medicine Faculty, Bucharest, Romania. -Man of medical year/2015, Award, International Bibliographic Center, Cambridge, UK. -Aurelian Udristioiu, Certificate as Award Academic, IBC, International Bibliographic Centre, Cambridge, UK, 2017. -” Marquis Who's Who” Lifetime /2018, 300 Connell Drive, Suite 2000, Berkeley Heights, N0: 07922 USA1-908-673-1000 , www.marquiswhoswho.com -Membership of Cancer Epigenetics Society. Membership ID number is: 786. Web: https://ces.b2sg.org/, Union for Internatio