Chronic Lymphocytic Leukemia
November 2019 Issue

Nearly every major medical breakthrough over the past 50 years can be attributed to new discoveries that were made possible through meticulous biomedical research. Many diseases and conditions that previously took a heavy toll on patients in terms of both morbidity and mortality are now either treatable or preventable thanks in large part to painstaking research that expanded the frontiers of scientific knowledge and moved the most promising basic research developments into tangible health benefits through human clinical trails. Ongoing research is also the key that will open the door to additional major medical advances and breakthroughs in the future.

Our staff at Medifocus is committed to keeping our subscribers to the Medifocus Digest Alert on Chronic Lymphocytic Leukemia abreast of the latest new research developments that have recently been published in the medical literature for this condition. In this issue of the Digest Alert, you will find a focused list of hand-picked journal article references that represent the latest advances in basic and clinical research for Chronic Lymphocytic Leukemia. These articles represent the current state-of-the-art of the research that will hopefully lead to additional major advances and breakthroughs in the clinical management of Chronic Lymphocytic Leukemia. You can access the summaries of each article referenced below by simply clicking on the article Title.

We will continue to update you with the latest scientific and clinical developments through the Medifocus Digest Alert on Chronic Lymphocytic Leukemia every 3 months. Thank you for your ongoing subscription to this publication.

Elliot Jacob, Ph.D.
Vice-President - Content, Inc.

1:Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized trials.
Authors:Zhou Y, Lu H, Yang M, Xu C
Institution:Department of Hematology, Jingzhou First People's Hospital, The First Affiliated Hospital of Yangtze University, Jingzhou.; Department of Cardiology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei, People's Republic of China.
Journal:Medicine (Baltimore). 2019 Aug;98(33):e16915. doi: 10.1097/MD.0000000000016915.

2:Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia.
Authors:Shanafelt TD, Wang XV, Kay NE, Hanson CA, O'Brien S, Barrientos J, Jelinek DF, Braggio E, Leis JF, Zhang CC, Coutre SE, Barr PM, Cashen AF, Mato AR, Singh AK, Mullane MP, Little RF, Erba H, Stone RM, Litzow M, Tallman M
Institution:From Stanford University, Stanford (T.D.S., S.E.C.), the University of California, Irvine, Medical Center, Orange (S.O.), and Kaiser Permanente National Cancer Institute Community Oncology Research Program (NCORP)-Permanente Medical Group, Oakland (C.C.Z.) - all in California; Dana-Farber Cancer Institute, Boston (X.V.W., R.M.S.); Mayo Clinic, Rochester (N.E.K., C.A.H., J.F.L., M.L.), and Minnesota Oncology, Burnsville (A.K.S.) - both in Minnesota; Northwell Health Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra-Northwell, Lake Success (J.B.), and University of Rochester, Rochester (P.M.B.) - both in New York; Mayo Clinic, Phoenix, AZ (D.F.J., E.B.); Washington University School of Medicine, St. Louis (A.F.C.); Memorial Sloan Kettering Cancer Center, New York (A.R.M., M.T.); Aurora Cancer Care, West Allis, WI (M.P.M.); National Cancer Institute, Bethesda, MD (R.F.L.); and the University of Alabama, Tuscaloosa (H.E.).
Journal:N Engl J Med. 2019 Aug 1;381(5):432-443. doi: 10.1056/NEJMoa1817073.

3:Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions.
Authors:Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, Robrecht S, Warburton S, Humphrey K, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Du K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Boettcher S, Tausch E, Humerickhouse R, Eichhorst B, Wendtner CM, Langerak AW, Kreuzer KA, Ritgen M, Goede V, Stilgenbauer S, Mobasher M, Hallek M
Institution:From Department I of Internal Medicine, Center for Integrated Oncology Aachen-Bonn-Cologne-Duesseldorf, University Hospital Cologne and University of Cologne (K.F., O.A.-S., J.B., A.-M.F., S. Robrecht, B.E., K.-A.K., M.H.), the Oncogeriatric Unit, Department of Geriatric Medicine, St. Marien Hospital (V.G.), CECAD (Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases) (M.H.), Center for Molecular Medicine Cologne (M.H.), Cologne, Department III of Internal Medicine, University Hospital Rostock, Rostock (S.B.), Department III of Internal Medicine, Ulm University, Ulm (E.T., S.S.), the Departments of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases, and Tropical Medicine, Klinikum Schwabing, Munich (C.-M.W.), Department II of Internal Medicine, Campus Kiel, University of Schleswig-Holstein, Kiel (M.R.), and the Department of Hematology, Oncology, and Rheumatology, Saarland University Medical School, Homburg (S.S.) - all in Germany; Roche Products, Welwyn Garden City, United Kingdom (M.T., M.D., S.W., K.H.); Regional Clinical Hospital N.A. Semashko, Nizhny Novgorod, Russia (O.S.); the Division of Onco-Hematology, Santa Maria Terni Hospital, University of Perugia, Perugia, Italy (A.M.L.); the Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.P.-I.); the Haematology Department, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia (S.O.); First Internal Department, Multiprofile Hospital for Active Treatment Hristo Botev, Vratsa, Bulgaria (L.S.); the Hematology Department, Clinique Victor Hugo, Le Mans, France (K.L.D.); Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil (L.M.F.); the Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen (C.U.N.); Wellington Blood and Cancer Centre, Capital and Coast District Health Board, and Malaghan Institute of Medical Research, Wellington, New Zealand (R.W.); Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada (S. Robinson); Moores Cancer Center, University of California San Diego, San Diego (T.J.K.), and Genentech, South San Francisco (M.M.) - both in California; AbbVie, North Chicago, IL (R.H.); and the Department of Immunology, Laboratory Medical Immunology, Erasmus MC, Rotterdam, the Netherlands (A.W.L.).
Journal:N Engl J Med. 2019 Jun 6;380(23):2225-2236. doi: 10.1056/NEJMoa1815281. Epub 2019 Jun 4.

4:Ibrutinib and Venetoclax for First-Line Treatment of CLL.
Authors:Jain N, Keating M, Thompson P, Ferrajoli A, Burger J, Borthakur G, Takahashi K, Estrov Z, Fowler N, Kadia T, Konopleva M, Alvarado Y, Yilmaz M, DiNardo C, Bose P, Ohanian M, Pemmaraju N, Jabbour E, Sasaki K, Kanagal-Shamanna R, Patel K, Jorgensen J, Garg N, Wang X, Sondermann K, Cruz N, Wei C, Ayala A, Plunkett W, Kantarjian H, Gandhi V, Wierda W
Institution:From the Departments of Leukemia (N.J., M. Keating, P.T., A.F., J.B., G.B., K.T., Z.E., T.K., M. Konopleva, Y.A., M.Y., C.D., P.B., M.O., N.P., E.J., K. Sasaki, K. Sondermann, N.C., C.W., A.A., H.K., W.W.), Lymphoma and Myeloma (N.F.), Hematopathology (R.K.-S., K.P., J.J.), Diagnostic Radiology (N.G.), Biostatistics (X.W.), and Experimental Therapeutics (W.P., V.G.), University of Texas M.D. Anderson Cancer Center, Houston.
Journal:N Engl J Med. 2019 May 30;380(22):2095-2103. doi: 10.1056/NEJMoa1900574.

5:Small Lymphocytic Lymphoma: Analysis of Two Cohorts Including Patients in Clinical Trials of the German Chronic Lymphocytic Leukemia Study Group (GCLLSG) or in "Real-Life" Outside of Clinical Trials.
Authors:Sachanas S, Pangalis GA, Fink AM, Bahlo J, Fischer K, Levidou G, Kyrtsonis MC, Bartzi V, Vassilakopoulos TP, Kalpadakis C, Koulieris E, Moschogiannis M, Yiakoumis X, Tsirkinidis P, Angelopoulou MK, Eichhorst B, Hallek M
Institution:Department of Haematology, Athens Medical Center-Psychikon Branch, Athens, Greece; Department of Haematology, Athens Medical Center-Psychikon Branch, Athens, Greece.; Department I of Internal Medicine & Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University Hospital Cologne, Cologne, Germany.; Pathology Department, University of Athens, Athens, Greece.; Pathology Department, Humanpathologie GmbH, Erlangen, Germany.
Journal:Anticancer Res. 2019 May;39(5):2591-2598. doi: 10.21873/anticanres.13382.

6:New Quinoline-Based Heterocycles as Anticancer Agents Targeting Bcl-2.
Authors:Hamdy R, Elseginy SA, Ziedan NI, Jones AT, Westwell AD
Institution:School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, Wales CF10 3NB, UK. Sharjah, P.O. Box 27272, Sharjah, UAE. Building, King Edward VII Avenue, Cardiff, Wales CF10 3NB, UK. Research Center, Dokki, Giza, P.O. Box 12622, Egypt. UK. Building, King Edward VII Avenue, Cardiff, Wales CF10 3NB, UK. Building, King Edward VII Avenue, Cardiff, Wales CF10 3NB, UK.
Journal:Molecules. 2019 Apr 2;24(7). pii: molecules24071274. doi: 10.3390/molecules24071274.

7:Venetoclax in the treatment of chronic lymphocytic leukemia.
Authors:Korycka-Wolowiec A, Wolowiec D, Kubiak-Mlonka A, Robak T
Institution:a Department of Hematology , Medical University of Lodz , Lodz , Poland.
Journal:Expert Opin Drug Metab Toxicol. 2019 May;15(5):353-366. doi: 10.1080/17425255.2019.1606211. Epub 2019 Apr 25.

8:Proteomics insights into the pathology and prognosis of chronic lymphocytic leukemia.
Authors:Alsagaby SA, Alhumaydhi FA
Institution:Department of Medical Laboratories Sciences, Faculty of Applied Medical Sciences, Majmaah University, Majmaah, Kingdom of Saudi Arabia. E-mail.
Journal:Saudi Med J. 2019 Apr;40(4):317-327. doi: 10.15537/smj.2019.4.23598.

9:Phase I study of tirabrutinib (ONO-4059/GS-4059) in patients with relapsed or refractory B-cell malignancies in Japan.
Authors:Munakata W, Ando K, Hatake K, Fukuhara N, Kinoshita T, Fukuhara S, Shirasugi Y, Yokoyama M, Ichikawa S, Ohmachi K, Gion N, Aoi A, Tobinai K
Institution:Department of Hematology, National Cancer Center Hospital, Tokyo, Japan. Foundation for Cancer Research, Tokyo, Japan. Medicine, Sendai, Japan. Foundation for Cancer Research, Tokyo, Japan. Medicine, Sendai, Japan. Ltd., Osaka, Japan.
Journal:Cancer Sci. 2019 May;110(5):1686-1694. doi: 10.1111/cas.13983. Epub 2019 Mar 28.

10:Oncology nurse phone calls halve the risk of reduced dose intensity of immunochemotherapy: results of the randomized FORTIS study in chronic lymphocytic leukemia.
Authors:Ysebaert L, Larcher M, Compaci G, Oberic L, Sahnes L, Banos A, Araujo C, Sommet A, Laurent G, Despas F
Institution:Department of Hematology, Toulouse University Hospital, Toulouse-Oncopole University Cancer Institute (IUCT-O), Toulouse, France.; University of Toulouse III Paul Sabatier, Toulouse, France.; INSERM UMR1037 (The French National Institute of Health and Medical Research), Cancer Research Center of Toulouse, Toulouse, France.; Service d'Hematologie, Institut Universitaire du Cancer de Toulouse, 1 Avenue Irene Joliot-Curie, 31059, Toulouse, France.; Hematology Department, Perpignan Hospital, Perpignan, France.
Journal:Ann Hematol. 2019 Apr;98(4):931-939. doi: 10.1007/s00277-019-03631-z. Epub 2019 Feb 18.

11:Low-dose fludarabine and cyclophosphamide combined with standard dose rituximab (LD-FCR) is an effective and safe regimen for elderly untreated patients with chronic lymphocytic leukemia: The Israeli CLL study group experience.
Authors:Herishanu Y, Tadmor T, Braester A, Bairey O, Aviv A, Rahimi-Levene N, Fineman R, Levi I, Yuklea M, Ruchlemer R, Shvidel L, Polliack A
Institution:Department of Hematology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. Galilee, Nahariya, Israel. University, Beer Sheba, Israel. Medical School, Jerusalem, Israel.
Journal:Hematol Oncol. 2019 Apr;37(2):185-192. doi: 10.1002/hon.2580. Epub 2019 Mar 12.

12:Relevance of TP53 for CLL diagnostics.
Authors:Catherwood MA, Gonzalez D, Donaldson D, Clifford R, Mills K, Thornton P
Institution:Haematology Department, Belfast Health and Social Care Trust, Belfast, UK Belfast, UK. Belfast, UK.
Journal:J Clin Pathol. 2019 May;72(5):343-346. doi: 10.1136/jclinpath-2018-205622. Epub 2019 Feb 2.

13:Effectiveness of the Combination of Rituximab and Standard Chemotherapeutic Regimens in Previously Untreated Patients with Chronic Lymphocytic Leukaemia in Real-Life: Results from a Noninterventional Study (CILI Study).
Authors:Szasz R, Altai E, Pal K, Dombi P, Ivanyi J, Jakucs J, Joni N, Illes A, Tarkanyi I, Szerafin L, Nagy Z, Farkas P, Nagy A, Piukovics K, Ujj G, Schneider T
Institution:Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary.; Veszprem County Csolnoky Ferenc Hospital, Korhaz u. 1, Veszprem, 8200, Hungary.; Fejer County Szent Gyorgy Hospital, Seregelyesi ut 3, Szekesfehervar, 8000, Hungary.; Department of Hematology, Szent Borbala Hospital, Dozsa Gyorgy ut 77, Tatabanya, 2800, Hungary.; Department of Hematology, Vas County Markusovszky Hospital, Markusovszky L. u. 5, Szombathely, 9700, Hungary.
Journal:Pathol Oncol Res. 2019 Apr;25(2):535-540. doi: 10.1007/s12253-018-0474-9. Epub 2018 Oct 25.

14:Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.
Authors:Fraser G, Cramer P, Demirkan F, Silva RS, Grosicki S, Pristupa A, Janssens A, Mayer J, Bartlett NL, Dilhuydy MS, Pylypenko H, Loscertales J, Avigdor A, Rule S, Villa D, Samoilova O, Panagiotidis P, Goy A, Pavlovsky MA, Karlsson C, Hallek M, Mahler M, Salman M, Sun S, Phelps C, Balasubramanian S, Howes A, Chanan-Khan A
Institution:Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada. fraserg@HHSC.CA. Study Group, University of Cologne, Cologne, Germany. University, Katowice, Poland. Hospital Brno, Jihlavska, Brno, Czech Republic. USA. Ukraine. Center, Tel-Hashomer and Sackler School of Medicine, University of Tel-Aviv, Tel-Aviv, Israel.
Journal:Leukemia. 2019 Apr;33(4):969-980. doi: 10.1038/s41375-018-0276-9. Epub 2018 Oct 12.

15:Severe arthritic syndrome due to ibrutinib use for chronic lymphocytic leukemia.
Authors:Dasanu CA
Institution:1 Lucy Curci Cancer Center, Eisenhower Medical Center, Rancho Mirage, CA, USA. Diego Health System, San Diego, CA, USA.
Journal:J Oncol Pharm Pract. 2019 Jun;25(4):1003-1005. doi: 10.1177/1078155218772327. Epub 2018 May 3.

16:Prolonged voriconazole treatment in a patient with chronic lymphocytic leukemia resulting in a litany of chronic overlapping toxicities.
Authors:Rausch CR, Kontoyiannis DP
Institution:1 Division of Pharmacy, MD Anderson Cancer Center, The University of Texas Houston, TX, USA. Anderson Cancer Center, The University of Texas Houston, TX, USA.
Journal:J Oncol Pharm Pract. 2019 Apr;25(3):747-753. doi: 10.1177/1078155218762624. Epub 2018 Mar 19.

17:Cryptococcal infections in two patients receiving ibrutinib therapy for chronic lymphocytic leukemia.
Authors:Stankowicz M, Banaszynski M, Crawford R
Institution:Southern Arizona VA Health Care System, Tucson, AZ, USA.
Journal:J Oncol Pharm Pract. 2019 Apr;25(3):710-714. doi: 10.1177/1078155217752078. Epub 2018 Jan 17.

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