Chronic myelogenous leukemia (CML) accounts for 15% to 20% of newly
diagnosed leukemia in adults. The disease follows a triphasic course,
with the majority of patients (85%) presenting in the chronic phase
(the accelerated and blastic phases represent the later progressive
course of the disease). CML has been studied in great detail, and the
molecular and cytogenetic abnormalities that are the hallmarks of the
disease are well characterized. CML is caused by abnormal cellular
signaling that transforms normal hematopoietic progenitor cells into
malignant cells. The underlying molecular abnormality is the
Philadelphia chromosome, a chromosomal anomaly caused by the
translocation of genetic material between chromosomes 9 and 22, which
produces the bcr-abl fusion gene responsible for the increased proliferation of blood cells in CML.
A recent study published in Blood (2004) and updated at
the American Society of Hematology (ASH) Annual Meeting in 2004
demonstrated that treatment of patients with chronic phase CML with
imatinib mesylate, a selective inhibitor of the Bcr-Abl tyrosine
kinase, induced high rates of cytogenetic and hematologic responses in
patients in whom previous interferon-α–based therapy had failed.
Another clinical trial published in the New England Journal of Medicine
(2003), which was also updated at ASH 2004, demonstrated that imatinib
mesylate therapy produced superior responses vs interferon-α +
cytarabine in newly diagnosed patients with CML, radically changing the
paradigm of CML treatment in a short period of time. Additionally,
imatinib mesylate has shown efficacy in patients with accelerated and
blastic phase CML, patient populations generally considered difficult
to treat. Both of these trials led the National Comprehensive Cancer
Network to update the current treatment algorithm to recommend imatinib
mesylate as first-line therapy for patients newly diagnosed with CML.
Long-term follow-up of these trials provides critical data for
evaluating the real-world impact of a treatment on a patient's quality
of life and survival. Data on targeted therapies continue to evolve
rapidly and suggest that there is potential for a further increase in
efficacy as treatment options are optimized, specifically with regard
to new methods for monitoring responses and residual disease as well as
monitoring and managing the use of imatinib mesylate. New cytogenetic
and quantitative molecular techniques offer improvement over
traditional hematologic and cytogenetic approaches for tracking
responses and for detecting the presence of minimal residual disease.
Indeed, quantitative molecular results from the TIDEL and RIGHT
studies, presented at the ASH 2004 and American Society of Clinical
Oncology (ASCO) 2005 meetings, respectively, have demonstrated that
higher doses of imatinib mesylate result in more frequent and robust
molecular responses. Despite the impressive activity of imatinib
mesylate in patients with CML, long-term follow-up data from the IRIS
trial show that some patients will develop resistance. To address this
issue, novel targeted therapies such as dasatinib and AMN107 are in
development. Promising phase I/II data from these agents were reported
at the ASH 2004 and ASCO 2005 meetings. It is important that medical
hematologists and oncologists are aware of such new data in order to
make informed decisions about how best to care for patients with CML.
This program will convene thought leaders to present the latest data
for dynamic discussion and evaluation.
Target Audience
The target audience for this activity includes academic and
community-based medical hematologists, oncologists,
hematologist/oncologists, and other health care providers who treat or
manage patients with hematologic disorders.
Learning Objectives
At the conclusion of this educational activity, participants should be better able to
Discuss the molecular pathogenesis of CML and the progression of therapeutic options developed to treat patients with CML
Differentiate the advantages and disadvantages of current
methods for testing and monitoring (cytogenetic and molecular) patients
with CML
Evaluate current issues surrounding the use of available
targeted agents, such as potential resistance and managing disease
progression
Review the latest clinical developments evaluating the use of
targeted therapies, such as signal transduction inhibitors, for the
treatment of patients with CML
Assess current therapeutic approaches to maximizing patient
response to and compliance with targeted therapies while minimizing
side effects and tolerability issues
Accreditation/Designation of Credit Statement
The Health Science Center for Continuing Medical Education is
accredited by the Accreditation Council for Continuing Medical
Education (ACCME) to provide continuing medical education for
physicians.
The Health Science Center for Continuing Medical Education designates this educational activity for a maximum of 3.25 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
If you previously completed and received credit for the live
symposium on December 9, 2005, in Atlanta, Georgia or CD-ROM (released:
February 28, 2006) entitled "Expanding Treatment Options in the
Hematologic Malignancies: New Therapies, New Findings, New Clinical
Insights," please note that you will not receive credit for completing
this activity. Participants who take part in an identical activity,
even in order to validate learning or to clarify specific topics,
cannot claim, nor will the Health Science Center for Continuing Medical
Education award, duplicate credit for the activity. While learning
benefits may be accrued by revisiting learning materials presented in
Internet-based, self-directed activities, ultimately participants are
still satisfying the activity's learning objectives for which they were
originally awarded credit.
Chairperson
Francis J. Giles, MD, FRCPI, FRCPath Professor of Medicine
Chief, Section of Developmental Therapeutics
Department of Leukemia
University of Texas MD Anderson Cancer Center
Houston, Texas
Francis J. Giles, MD, FRCPI, FRCPath, is a professor of medicine and
chief of the Section of Developmental Therapeutics at the University of
Texas MD Anderson Cancer Center in Houston, Texas. He earned his
medical degree at the National University of Ireland in Galway and
completed fellowships in hematology/oncology at St. James Hospital,
Dublin, Ireland, and University College and Middlesex Hospitals in
London, England. He subsequently joined the faculty at the University
of North Carolina at Chapel Hill, followed by the University of
California, Los Angeles. Dr. Giles's primary research interests are in
the area of developmental therapeutics. He is currently involved in the
development of numerous novel anticancer agents, particularly for
patients with hematologic malignancies, with a focus on targeted
therapies including tyrosine kinase inhibitors, epigenetic modifiers,
checkpoint inhibitors, apoptosis modifiers, heat shock protein
modifiers, monoclonal antibodies, antisense agents, and small
interfering RNAs.
Faculty
James D. Griffin, MD Chairman, Department of Medical Oncology
Dana-Farber Cancer Institute
Boston, Massachusetts
James D. Griffin, MD, is a professor of medicine at Harvard
Medical School and an attending physician at the Dana-Farber Cancer
Institute in Boston, Massachusetts. He earned his master's degree at
Brown University in Providence, Rhode Island, and his medical degree at
Harvard Medical School. Dr. Griffin completed an internship and
residency in medicine at Johns Hopkins Hospital in Baltimore, Maryland.
Afterwards, he completed a clinical and research fellowship in
hematology at Massachusetts General Hospital in Boston and a research
fellowship in tumor virology and a clinical fellowship in medical
oncology at the Dana-Farber Cancer Institute.
Dr. Griffin's primary research interests are in the regulation of
hematopoiesis, the biology of myeloid leukemias, leukemia oncogenes as
targets for drug development, and notch receptor function. He is a
leading contributor to the field of leukemia biology and therapy. In
the early 1980s, he developed panels of monoclonal antibodies that
recognize acute myelogenous leukemia (AML) cells; these are now in
general use as diagnostic reagents throughout the world. He was the
first to identify CD33 using monoclonal antibody and to use this
antibody for therapy to deplete leukemic cells during autologous bone
marrow transplantation. Another important contribution was his
discovery that patients receiving granulocyte-macrophage
colony-stimulating factor had transient mobilization of stem cells from
the bone marrow to the blood. It was found that these "mobilized" stem
cells could be collected and used in place of marrow in bone marrow
transplantation. For the last decade, Dr. Griffin has studied the
function of tyrosine kinase oncogenes that cause AML and chronic
myelogenous
leukemia (CML), including Flt3 and bcr-abl. He has been
a leader in studying signaling pathways activated by the oncogenes.
This work, and the model systems he devised to do these studies, have
contributed to the development of small-molecule tyrosine kinase
inhibitors currently used for therapy in both CML and AML.
Dr. Griffin is a member of several professional organizations,
including the American Society of Hematology, the American Society of
Clinical Investigation, the International Society of Experimental
Hematology, and the American Society for Cancer Research. He has
authored or co-authored numerous articles in journals such as Blood, Clinical Cancer Research, Cancer Cell, and the Journal of Biological Chemistry.
François Guilhot, MD Oncology, Hematology, and Cell Therapy
CHU de Poitiers
Poitiers, France
François Guilhot, MD, is head of the Department of Oncology,
Hematology, and Cell Therapy and the Bone Marrow Transplant Unit at the
Centre Hospitalier Universitaire (CHU) de Poitiers, France. Dr. Guilhot
received his undergraduate degree at the University of Paris, CHU
Cochin, Port Royal, France. He received a degree in hematology, a
master's degree in human biology and hematology, and a medical
doctorate at the University of Paris, CHU Saint Louis, France. In 1989,
Dr. Guilhot earned a diploma of advanced studies and in 1990 he became
a professor of clinical hematology at the College of Medical Studies in
Poitiers, France.
Dr. Guilhot received the first award of the French Society of
Hematology for clinical research in 1997. He has been president of the
Chronic Myelogenous Leukemia French Group since 2000 and director of
the Clinical Research Center at CHU de Poitiers, France, since 2003. He
is a member of the American Society of Hematology, the American Society
of Clinical Oncology, the European Hematology Association, and the
European Group for Bone Marrow Transplantation. Dr. Guilhot has
published over 380 communications and articles appearing in journals
such as Blood, Leukemia & Lymphoma, Cancer Research, Seminars in Hematology, and the New England Journal of Medicine.
Timothy Hughes, MD, MBBS Associate Professor, Hematology
University of Adelaide
Adelaide, South Australia, Australia
Timothy Hughes, MD, MBBS, is director of research in the Division of
Haematology at the Hanson Centre for Cancer Research and a consultant
hematologist at the Institute of Medical and Veterinary Science in
Adelaide, South Australia. He is also a clinical associate professor of
medicine at the University of Adelaide. Dr. Hughes is a fellow of the
Royal Australasian College of Physicians and the Royal College of
Pathologists of Australia. He is a member of the Haematology Society of
Australia and New Zealand, for which he served as president from 2001
to 2003, and the Australasian Leukaemia and Lymphoma Group (ALLG), for
which he served as vice chairman from 2000 to 2005. He is the current
chairman of the Chronic Myeloid Leukemia (CML) Study Group within ALLG.
His current research interests focus on molecular monitoring as a guide
to clinical management of CML, new therapies for CML, and biomarkers in
CML.
Oliver G. Ottmann, MD Medizinische Klinik II, Abt. Hämatologie und Onkologie
Johann Wolfgang Goethe Universität
Frankfurt, Germany
Oliver G. Ottmann, MD, was born in Columbus, Ohio, on June 28,
1958. He received his medical training at Heinrich Heine University in
Düsseldorf, Germany, from 1977 to 1984.
He was a postdoctoral research fellow at Memorial
Sloan-Kettering Cancer Center in New York from 1985 to 1987 (Dr.
Mildred Scheel Foundation scholarship), and trained in internal
medicine at the Johann Wolfgang Goethe University, Frankfurt, from 1987
to 1995. He received his board
certification in internal medicine in 1996 and in hematology and
oncology in 2002, and earned his Habilitation in 2002.
Since 1995, Dr. Ottmann has been chief physician (Oberarzt) and head of
the Laboratory for Experimental Hematology in the Department of
Hematology/Oncology, Medizinische Klinik II, at Johann Wolfgang Goethe
University, Frankfurt, Germany.
Dr. Ottmann's professional interests focus on the clinical
application of signal transduction modulators and transcriptional
regulators, as well as the biology of normal and leukemic stem cells.
He is also researching signal transduction by growth factor receptors
in leukemia and the role of leukemogenic fusion proteins in human
leukemia.
Dr. Ottmann is a member of the American Society of Hematology, the
International Society for Experimental Hematology, the American
Association for Cancer Research, the European Hematology Association,
and the German Society of Hematology and Oncology (DGHO). He has
published 130 original articles in peer-reviewed journals, 32 reviews,
and 11 book chapters.
Faculty Disclosure Summary
In accordance with ACCME Standards for Commercial Support of Continuing Medical Education and the Health Science Center for Continuing Medical Education Disclosure Policy for CME Activities,
faculty members have been asked to disclose any relationship they may
have with commercial supporters of this CME activity or with companies
providing drugs, medical equipment, etc, that may have relevance to the
content of their presentations. Such disclosure is intended to provide
participants with sufficient information to evaluate whether any given
presentation has been influenced by the faculty's relationship(s) or
financial interests with said companies.
The following faculty reported no significant relationships:
François Guilhot, MD
The following faculty have reported receiving something of
value* from the commercial supporter(s) of this activity or from a
corporate organization whose product(s) may have relevance to the
content of their presentations:
Francis J. Giles, MD, FRCPI, FRCPath
Amgen: received grants/research support
Bristol-Myers Squibb Company: received grants/research support
Merck & Co., Inc.: received grants/research support
Novartis: received grants/research support
Pfizer Inc: received grants/research support
James D. Griffin, MD
Novartis: consultant, received grants/research support
Timothy Hughes, MD, MBBS
Bristol-Myers Squibb Company: received grants/research support
Novartis: honoraria, received grants/research support
Oliver G. Ottmann, MD
Bristol-Myers Squibb Company: honoraria
Novartis: consultant, honoraria, received grants/research support
*Something of value refers to any equity position, receipt of
royalties/honoraria, funding of a research grant, consultantships, or
to any other relationship with a company that provides sufficient
reason for disclosure, in keeping with the spirit of the stated policy.
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