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Novel Biospecific Agents for the Treatment of Myelodysplastic Syndromes

Jason Gotlib and Peter L. Greenberg

Levels of treatment for patients with myelodysplastic syndromes (MDS) fall within 3 broad categories: supportive care, low- and high-intensity therapy. Most approaches remain experimental, and supportive care remains the standard of treatment in MDS. In parallel with the growing knowledge of the multiple pathobiologic abnormalities in MDS, increasing numbers of low-intensity, biospecific agents that target these pathogenetic lesions have entered clinical trial testing. Although the term “biospecific” has been applied to many of these investigational drugs, they often exert pleiotropic effects, many of which remain to be identified. An ongoing challenge will be to more fully characterize the mechanisms of action of these drugs and to characterize biologic correlates of response. With these data in hand, it will be increasingly feasible to treat patients with combinations of biospecific drugs with non-overlapping actions and toxicities, a therapeutic approach that is likely required to effectively overcome the barriers posed by the biologic heterogeneity of MDS. This review focuses on recent therapeutic approaches using such biologic response modifiers to treat MDS.

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Cancer-Related Fatigue

Ann M. Berger, Amy Pickar Abernethy, Ashley Atkinson, Andrea M. Barsevick, William S. Breitbart, David Cella, Bernadine Cimprich, Charles Cleeland, Mario A. Eisenberger, Carmen P. Escalante, Paul B. Jacobsen, Phyllis Kaldor, Jennifer A. Ligibel, Barbara A. Murphy, Tracey O'Connor, William F. Pirl, Eve Rodler, Hope S. Rugo, Jay Thomas, and Lynne I. Wagner

Overview Fatigue is a common symptom in patients with cancer and is nearly universal in those undergoing cytotoxic chemotherapy, radiation therapy, bone marrow transplantation, or treatment with biologic response modifiers. 1 – 10 The symptom

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Cancer-Related Fatigue

St. Jude Children's Research Hospital

Fatigue is a common symptom in patients with cancer and is nearly universal in those undergoing cytotoxic chemotherapy, radiation therapy, bone marrow transplantation, or treatment with biologic response modifiers. The problem, which affects 70% to 100% of cancer patients, has been exacerbated by the increased use of fatigue-inducing multimodal treatments and dose-dense, dose-intense protocols. In patients with metastatic disease, the prevalence of cancer-related fatigue exceeds 75%, and cancer survivors report that fatigue is a disruptive symptom months or even years after treatment ends. Patients perceive fatigue to be the most distressing symptom associated with cancer and its treatment, more distressing even than pain or nausea and vomiting, which, for most patients, can generally be managed with medications.

For the most recent version of the guidelines, please visit NCCN.org

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Liver Transplantation for Hepatocellular Carcinoma: An Update

Jean F. Botha and Alan N. Langnas

responsible for tumor surveillance in man: effects of radiotherapy, chemotherapy, and biologic response modifiers . Adv Immun Cancer Ther 1985 ; 1 : 1 – 28 . 31. Azoulay D Astarcioglu I Bismuth H . Split-liver transplantation. The Paul Brousse

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Contemporary Intravesical Treatment Options for Urothelial Carcinoma of the Bladder

Stephen A. Brassell and Ashish M. Kamat

. Zlotta AR Schulman CC . Biological response modifiers for the treatment of superficial bladder tumors . Eur Urol 2000 ; 37 : 10 – 15 . 50. Elsässer-Beile U Leiber C Wolf P . Adjuvant intravesical treatment of superficial bladder cancer

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Survivorship: Fatigue, Version 1.2014

Crystal S. Denlinger, Jennifer A. Ligibel, Madhuri Are, K. Scott Baker, Wendy Demark-Wahnefried, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Grace H. Ku, Elizabeth Kvale, Terry S. Langbaum, Kristin Leonardi-Warren, Mary S. McCabe, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Javid J. Moslehi, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Muhammad Raza, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole McMillian, and Deborah Freedman-Cass

a common symptom in patients with cancer and is nearly universal in those receiving cytotoxic chemotherapy, radiation therapy, bone marrow transplantation, or treatment with biological response modifiers. 2 - 4 According to a survey of 1569 patients

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Myelodysplastic Syndromes

Peter L. Greenberg, Eyal Attar, John M. Bennett, Clara D. Bloomfield, Carlos M. De Castro, H. Joachim Deeg, James M. Foran, Karin Gaensler, Guillermo Garcia-Manero, Steven D. Gore, David Head, Rami Komrokji, Lori J. Maness, Michael Millenson, Stephen D. Nimer, Margaret R. O'Donnell, Mark A. Schroeder, Paul J. Shami, Richard M. Stone, James E. Thompson, and Peter Westervelt

-intensity therapy includes the use of low-intensity chemotherapy or biologic response modifiers. Although this type of treatment is mainly provided in the outpatient setting, certain treatments may require supportive care or occasional hospitalization afterwards (e

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Myelodysplastic Syndromes

Peter L. Greenberg, Eyal Attar, John M. Bennett, Clara D. Bloomfield, Uma Borate, Carlos M. De Castro, H. Joachim Deeg, Olga Frankfurt, Karin Gaensler, Guillermo Garcia-Manero, Steven D. Gore, David Head, Rami Komrokji, Lori J. Maness, Michael Millenson, Margaret R. O’Donnell, Paul J. Shami, Brady L. Stein, Richard M. Stone, James E. Thompson, Peter Westervelt, Benton Wheeler, Dorothy A. Shead, and Maoko Naganuma

experience a response to (or who relapsed after) immunosuppressive therapy. Biologic Response Modifiers and Immunosuppressive Therapy The currently available nonchemotherapy low-intensity agents (biologic response modifiers) include antithymocyte

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Myelodysplastic Syndromes, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

Peter L. Greenberg, Richard M. Stone, Aref Al-Kali, Stefan K. Barta, Rafael Bejar, John M. Bennett, Hetty Carraway, Carlos M. De Castro, H. Joachim Deeg, Amy E. DeZern, Amir T. Fathi, Olga Frankfurt, Karin Gaensler, Guillermo Garcia-Manero, Elizabeth A. Griffiths, David Head, Ruth Horsfall, Robert A. Johnson, Mark Juckett, Virginia M. Klimek, Rami Komrokji, Lisa A. Kujawski, Lori J. Maness, Margaret R. O'Donnell, Daniel A. Pollyea, Paul J. Shami, Brady L. Stein, Alison R. Walker, Peter Westervelt, Amer Zeidan, Dorothy A. Shead, and Courtney Smith

-intensity chemotherapy or biologic response modifiers. Although this type of treatment is mainly provided in the outpatient setting, supportive care or occasional hospitalization (eg, for treatment of infections) may be needed. Hypomethylating Agents: The DNA

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Cancer-Related Fatigue, Version 2.2015

Ann M. Berger, Kathi Mooney, Amy Alvarez-Perez, William S. Breitbart, Kristen M. Carpenter, David Cella, Charles Cleeland, Efrat Dotan, Mario A. Eisenberger, Carmen P. Escalante, Paul B. Jacobsen, Catherine Jankowski, Thomas LeBlanc, Jennifer A. Ligibel, Elizabeth Trice Loggers, Belinda Mandrell, Barbara A. Murphy, Oxana Palesh, William F. Pirl, Steven C. Plaxe, Michelle B. Riba, Hope S. Rugo, Carolina Salvador, Lynne I. Wagner, Nina D. Wagner-Johnston, Finly J. Zachariah, Mary Anne Bergman, and Courtney Smith

Fatigue is a common symptom in patients with cancer. It is nearly universal in those receiving cytotoxic chemotherapy, radiation therapy, bone marrow transplantation, or treatment with biologic response modifiers. 1 – 3 According to a survey of 1569