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LEUKEMIA, MYELODYSPLASIA, AND TRANSPLANTATION Translating Knowledge into Therapeutic Progress in Myelodysplastic Syndromes CHAIR Olatoyosi Odenike, MD The University of Chicago Chicago, IL SPEAKERS Francesco Onida, MD University of Milan Milan, Italy Eric Padron, MD Moffitt Cancer Center Tampa, FL
ODENIKE, ONIDA, AND PADRON Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms: An Update on Risk Stratification, Molecular Genetics, and Therapeutic Approaches Including Allogeneic Hematopoietic Stem Cell Transplantation Olatoyosi Odenike, MD, Francesco Onida, MD, and Eric Padron, MD OVERVIEW Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and a variable propensity for leukemic transformation. In recent years there has been an explosion of information on the molecular genetic changes underlying these disorders. This information has substantial prognostic implications, and the influence on therapeutic approaches and the treatment of patients is evolving. Allogeneic hematopoietic stem cell transplantation (alloSCT) is the only known cure for these diseases, but appropriate patient selection is of utmost importance from a risk-benefit perspective. This review focuses on the factors influencing risk stratification in MDS and optimal choice of front-line therapy in the current era, including the interplay of clinical factors and molecular genetic factors, and factors that determine eligibility for alloSCT. The myelodysplastic/myeloproliferative diseases also will be discussed, including the increasing effort to understand the molecular genetics and natural history of these disorders and treatment approaches. The myelodysplastic syndromes are a clinically and molecularly heterogeneous group of clonal stem cell disorders with management options ranging from observation and growth-factor therapy to more intensive approaches, such as hypomethylating agent (HMA)–based therapies, intensive induction chemotherapy, and alloSCT. 1 During the last decade, rapid developments centered around highthroughput molecular technologies have resulted in remarkable advancement toward the understanding of MDS pathogenesis. 2-6 These technologies are anticipated to translate to innovative targeted agents that will radically affect the natural history of this disease. Presently, however, alloSCT remains the only curative treatment option in patients with MDS. 2,7-9 Even if substantially reduced during the last 20 years, mortality and morbidity risks associated with alloSCT continue to represent a major limit to the feasibility of such a therapeutic strategy in the large number of patients. 8,10,11 Therefore, the accurate selection of patients—together with optimal timing of transplantation—represent critical issues for maximum improvement of the alloSCT risk-benefıt ratio in MDS. As such, important advancements have been made toward the dissection of MDS clinical heterogeneity that have incorporated both clinical and molecular characteristics. In this review, we will discuss recent refınements to prognosis for patients with MDS based on clinical, cytogenetic, and molecular risk factors. We also will discuss the approach to the selection of front-line therapy in MDS, including a particular focus on alloSCT. Lastly, we will highlight myelodysplastic/ myeloproliferative neoplasms (MDS/MPNs), including recent insights into the molecular genetics and emerging therapeutic approaches in patients with these diseases. PROGNOSTIC STRATIFICATION IN MYELODYSPLASTIC SYNDROMES MDS is a disease found in older adults, with a median age at diagnosis of age 71. The estimated 3-year survival rate of patients with MDS is 45%, 12 although there is substantial variability in outcomes even within the same French-American- British (FAB) 13 classifıcation system and the more recent World Health Organization (WHO) morphologic subtypes. 14 This heterogeneity in outcomes underscores the need for accurate prognostication and has fuelled the evolution of various prognostic scoring models. From the Section of Hematology/Oncology, and the Comprehensive Cancer Center, The University of Chicago, Chicago, IL; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; Moffitt Cancer Center, Tampa, FL. Disclosures of potential conflicts of interest are found at the end of this article. Corresponding author: Olatoyosi Odenike, MD, Section of Hematology/Oncology and the Comprehensive Care Center, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637; email: todenike@medicine.bsd.uchicago.edu. © 2015 by American Society of Clinical Oncology. e398 2015 ASCO EDUCATIONAL BOOK | asco.org/edbook
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Controversies in Neoadjuvant Therap
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Managing Ovarian Cancer in the Olde
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2015 ASCO Annual Meeting Disclosure
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2015 Educational Book Expert Panel
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James Marshall, PhD Roswell Park Ca
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2015 Annual Meeting Supporters* MIS
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David Yurman Corporate Allies Conqu
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EGIDIO DEL FABBRO FIGURE 3. Mechani
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PROMISING STRATEGIES IN BLADDER CAN
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GYNECOLOGIC CANCER Cervical Cancer
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GYNECOLOGIC CANCER Managing Ovarian
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DUSKA, TEW, AND MOORE KEY POINTS A
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GYNECOLOGIC CANCER Treatment of the
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CHEMOTHERAPY FOR PATIENTS WITH BMOC
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PROGRESS IN HEAD AND NECK SQUAMOUS
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ISAACSSON VELHO, CASTRO JR, AND CHU
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HEALTH SERVICES RESEARCH AND QUALIT
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INDUSTRY AND ONCOLOGY KEY POINTS F
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INDUSTRY AND ONCOLOGY has been “l
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INDUSTRY AND ONCOLOGY by (covered)
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CANCER CARE QUALITY: CURRENT STATE
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MANAGING OLDER PATIENTS WITH ALL Th
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MANAGING OLDER PATIENTS WITH ALL TA
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MANAGING OLDER PATIENTS WITH ALL FI
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MANAGING OLDER PATIENTS WITH ALL FI
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MANAGING OLDER PATIENTS WITH ALL ra
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TREATMENT OF PHILADELPHIA CHROMOSOM
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BERNARDO H.L. GOULART every 6 month
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BERNARDO H.L. GOULART lung-cancer/l
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LUNG CANCER Updates in the Multimod
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WOODARD AND JABLONS section, becaus
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NASSER HANNA Current Standards and
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NASSER HANNA At the 2014 ASCO Annua
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NASSER HANNA culty of this task. Va
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LYMPHOMA AND PLASMA CELL DISORDERS
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NOWAKOWSKI AND CZUCZMAN sociated wi
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DAVID W. SCOTT 10. Shaffer AL 3rd,
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CHEAH, OKI, AND FANALE Novel Treatm
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STEPHEN ANSELL Disclosures of Poten
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LYMPHOMA AND PLASMA CELL DISORDERS
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MANAGEMENT OF CLL Up-Front Manageme
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MANAGEMENT OF CLL than 17p-/TP53mut
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MANAGEMENT OF CLL could be associat
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MANAGEMENT OF CLL tion by nonmalign
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MANAGEMENT OF CLL lymphocytic leuke
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PROGNOSTIC FACTORS AND ADJUVANT RAD
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MERKEL CELL CARCINOMA Merkel Cell C
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MERKEL CELL CARCINOMA tions in PIK3
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MERKEL CELL CARCINOMA 32. Leonard J
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PERFUSION AND INFUSION IN THE ERA O
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NEOADJUVANT THERAPY OF MELANOMA Neo
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SULLIVAN ET AL FIGURE 1. Relevant S
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SULLIVAN ET AL Resistance to BRAF i
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SULLIVAN ET AL 17. Halait H, Demart
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SULLIVAN ET AL NRAS-mutant melanoma
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KLEPIN, RODIN, AND HURRIA Treating
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KLEPIN, RODIN, AND HURRIA plication
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PERIPHERAL NEUROTOXICITY IN CANCER
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PARTRIDGE, JACOBSEN, AND ANDERSEN w
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PARTRIDGE, JACOBSEN, AND ANDERSEN v
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LESLIE R. SCHOVER Sexual Healing in
Page 782 and 783:
LESLIE R. SCHOVER tinuous ADT in pr
Page 784 and 785:
LESLIE R. SCHOVER 12. Potosky AL, H
Page 786 and 787:
CATHERINE H. VAN POZNAK TABLE 1. Wo
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CATHERINE H. VAN POZNAK (tamoxifen,
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CATHERINE H. VAN POZNAK TABLE 3. FD
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CATHERINE H. VAN POZNAK premenopaus
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SHARI GOLDFARB KEY POINTS Brea
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SHARI GOLDFARB and friction with va
Page 798 and 799:
SHARI GOLDFARB importance both duri
Page 800 and 801:
PATIENT AND SURVIVOR CARE Moving Su
Page 802 and 803:
MAYER ET AL TABLE 1. Quality Metric
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MAYER ET AL to enhance the quality
Page 806 and 807:
MAYER ET AL FIGURE 2. (A) Infertili
Page 808 and 809:
MAYER ET AL efıcial suggests that
Page 810 and 811:
PATIENT AND SURVIVOR CARE The Chall
Page 812 and 813:
BRUERA AND PAICE Choice of Opioid a
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BRUERA AND PAICE toxicity and proce
Page 816 and 817:
BRUERA AND PAICE effective. Basic s
Page 818 and 819:
PEDIATRIC ONCOLOGY Real-Time Molecu
Page 820 and 821:
CARROLL, RAETZ, AND MEYER KEY POINT
Page 822 and 823:
CARROLL, RAETZ, AND MEYER most are
Page 824 and 825:
CARROLL, RAETZ, AND MEYER markers a
Page 826 and 827:
PEDIATRIC ONCOLOGY Translating Surv
Page 828 and 829:
REDUCING THE BURDEN OF LATE EFFECTS
Page 830 and 831:
Page 832 and 833:
Page 834 and 835:
Page 836 and 837:
PROFESSIONAL DEVELOPMENT The Challe
Page 838 and 839:
ADVANCES IN WEBSITE INFORMATION RES
Page 840 and 841:
Page 842 and 843:
Page 844 and 845:
Page 846 and 847:
COMMUNICATION AND TECHNOLOGY: IT’
Page 848 and 849:
Page 850 and 851:
Page 852 and 853:
PATIENT-REPORTED OUTCOMES IN ONCOLO
Page 854 and 855:
PATIENT-REPORTED OUTCOMES IN ONCOLO
Page 856 and 857:
PROFESSIONAL DEVELOPMENT Trends, An
Page 858 and 859:
CLINICAL ONCOLOGY PRACTICE 2015 FIG
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CLINICAL ONCOLOGY PRACTICE 2015 (6.
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CLINICAL ONCOLOGY PRACTICE 2015 Pro
Page 864 and 865:
ADJUVANT/NEOADJUVANT MEDICAL THERAP
Page 866 and 867:
Page 868 and 869:
Page 870 and 871:
INDICATIONS FOR ADJUVANT RADIATION
Page 872 and 873:
Page 874 and 875:
Page 876 and 877:
Page 878 and 879:
SARCOMA Latest Advances in Systemic
Page 880 and 881:
SYSTEMIC THERAPY FOR OSTEOSARCOMA A
Page 882 and 883:
SYSTEMIC THERAPY FOR OSTEOSARCOMA A
Page 884 and 885:
RETHINKING TREATMENT FOR CHONDROSAR
Page 886 and 887:
Page 888 and 889:
Page 890 and 891:
Page 892 and 893:
BONE SARCOMAS IN ADULTS local disea
Page 894 and 895:
BONE SARCOMAS IN ADULTS structure a
Page 896 and 897:
SARCOMA Well-Differentiated and Ded
Page 898 and 899:
ABBAS MANJI ET AL ticular region. 7
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ABBAS MANJI ET AL MYXOID (ROUND CEL
Page 902 and 903:
ABBAS MANJI ET AL versus doxorubici
Page 904 and 905:
SHLUSH AND HERSHKOVITZ Clonal Evolu
Page 906 and 907:
SHLUSH AND HERSHKOVITZ FIGURE 1. Ti
Page 908 and 909:
TUMOR BIOLOGY New Strategies to Und
Page 910 and 911:
KNAPP, DHAWAN, AND OSTRANDER in dog
Page 912 and 913:
KNAPP, DHAWAN, AND OSTRANDER TABLE
Page 914 and 915:
KNAPP, DHAWAN, AND OSTRANDER 14. Fe
Page 916 and 917:
SOURBIER, SRINIVASAN, AND LINEHAN M
Page 918 and 919:
SOURBIER, SRINIVASAN, AND LINEHAN F
Page 920 and 921:
SOURBIER, SRINIVASAN, AND LINEHAN T
Page 922:
Author Index Abbas Manji, Gulam ...
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