CME

Controversies in the Management of CML

Authors: Chairperson: Stephen D. Nimer, MD; Faculty: Rainer F. Storb, MD; Hagop M. Kantarjian, MD; Brian J. Druker, MD; Rüdiger Hehlmann, MD; John F. DiPersio, MD, PhD; Sergio Giralt, MD; Richard A. Larson, MD; Charles Schiffer, MD; Francois Guilhot, MD
THIS ACTIVITY HAS EXPIRED

Target Audience and Goal Statement

The goal of this educational symposium is to provide oncologists and hematologists with current developments in the treatment of patients with chronic myeloid leukemia (CML); debate controversies involving those new developments relative to current therapeutic options; and provide an update on CML treatment algorithms.

On completion of this CME offering, participants will be able to:

Understand new developments in stem cell transplantation for CML.
Assess therapeutic utility of interferon-alpha and bone marrow transplantation.
Address current data on molecularly targeted therapy, imatinib mesylate, for CML.
Gain awareness of controversies in the treatment of CML.
Explore the impact of new developments in treatment of CML.
Communicate optimal treatment strategies for the management of Philadelphia chromosome-positive leukemias.

Author(s)

John F DiPersio, MD, PhD

Professor of Medicine, Pediatrics, and Pathology/Immunology, Washington University School of Medicine, St. Louis, MO; Chief of the Division of Oncology, Director of the Section of Bone Marrow Transplantation and Leukemia, and Deputy Director of the Siteman Cancer Center, Washington University School of Medicine

Disclosures

Disclosure: John F. DiPersio, MD, PhD, has nothing to disclose.

Brian J Druker, MD

JELD-WEN Chair of Leukemia Research, Professor of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University (OHSU), Director of the OHSU Cancer Institute Leukemia Center; Joint academic appointments: Department of Cell and Developmental Biology and the Department of Biochemistry and Molecular Biology

Disclosures

Disclosure: Brian J. Druker, MD, is a consultant for Novartis Pharmaceuticals Corporation.

Sergio Giralt, MD

Associate Professor of Medicine, Associate Internist, Blood and Marrow Transplantation Department, University of Texas M.D. Anderson Cancer Center, Houston, TX; Medical Director and Clinic Chief, Blood and Marrow Center, M.D. Anderson Cancer Center, Houston, TX

Disclosures

Disclosure: Sergio Giralt, MD, receives research support from Schering and Berlex. He is a consultant and receives honorarium from Schering.

François Guilhot, MD

Professor of Clinical Hematology, University Hospital of Poitiers, France; Head of the Bone Marrow Transplant Unit, Head of the Department of Oncology, Hematology and Cell Therapy

Disclosures

Disclosure: Frangois Guilhot, MD, has nothing to disclose.

Rüdiger Hehlmann, MD

Professor of Medicine, University of Heidelberg; Chief of the III. Med. Klinik, University Heidelberg, Mannheim, Germany.

Disclosures

Disclosure: Rüdiger Hehlmann, MD, has nothing to disclose.

Hagop M Kantarjian, MD

Professor of Medicine and Internist, Chairman, Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX

Disclosures

Disclosure: Hagop M. Kantarjian, MD, receives research support from Schering, Roche, Novartis, ILEX, Sugen, and others.

Richard A Larson, MD

Professor of Medicine, Section of Hematology/Oncology, Pritzker School of Medicine, University of Chicago, Chicago, IL

Disclosures

Disclosure: Richard A. Larson, MD, receives research support, honorarium, and is a consultant for Novartis.

Stephen D Nimer, MD

Head of the Division, Hematologic Oncology, Chief of the Hematology Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Professor of Medicine, Cornell University Medical College

Disclosures

Disclosure: Stephen D. Nimer, MD, is on the speakers' bureau for Novartis.

Charles A Schiffer, MD

Professor of Medicine/Oncology, Wayne State University School of Medicine, Detroit, Michigan; Director Leukemia/Lymphoma Group, Karmanos Cancer Insitute, Detroit, Michigan

Disclosures

Disclosure: Charles A. Schiffer, MD, receives research support, is a consultant, and serves on the speakers' bureau for Novartis.

Rainer F Storb, MD

Professor of Medicine, Division of Oncology, University of Washington School of Medicine, Seattle, WA; Program Head of Transplantation Biology, Fred Hutchinson Cancer Research Center, Seattle, WA.

Disclosures

Disclosure: Rainer F. Storb, MD, has nothing to disclose.

Accreditation Statements

For Physicians

This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the sponsorship of the Wayne State University School of Medicine. The Wayne State University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education provide continuing medical education for physicians.

The Wayne State University School of Medicine designates this education activity for a maximum of 3 hours in category 1 towards the AMA Physician's Recognition Award. Each physician should claim only those hours that he/she actually spent in the educational activity.

Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

Follow these steps to earn CME/CE credit:

Read the target audience, learning objectives, and author disclosures.
Study the educational content online or printed out.
Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. Medscape encourages you to complete the Activity Evaluation to provide feedback for future programming.

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The credit that you receive is based on your user profile.

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Introduction , Presented by Stephen D. Nimer, MD

Overview of Chronic Myelogenous Leukemia

Dr. Nimer: I'd like to start with a very brief introduction. We have a very esteemed group of speakers and I'd like to give them plenty of opportunity to present their views on the management of chronic myelogenous leukemia (CML).

Controversies in the Management of CML
Instant Poll

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Slide 1.

Introduction

CML is one of the myeloproliferative diseases, and these diseases are characterized by an intact differentiation potential and an intact proliferative potential.
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Slide 2.

Myeloproliferative Diseases

CML, unlike these other diseases, is characterized by a unique cytogenetic abnormality, namely the Philadelphia chromosome, and this chromosome, which is the very small chromosomederived from chromosome 22, was identified 41 years ago by Nowell and Hungerford.
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Slide 3.

Description of the Philadelphia Chromosome - Ph¹

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Slide 4.

The Philadelphia Chromosome: t(9;22): BCR-ABL

We now know that this Philadelphia chromosome fuses the bcr-abl gene with the Ableson tyrosine kinase, and the fusion protein has a constitutively activated tyrosine kinase activity. There are different cytogenetic and clinical phases of CML. In the chronic phase, the disease is characterized by the presence of the Philadelphia chromosome, and as the disease advances, it is quite common for there to be additional cytogenetic abnormalities and additional Philadelphia chromosomes or others that are listed.

The identification of specific genetic lesions with the Philadelphia chromosome offers the opportunity for some targeted therapy.
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Slide 5.

Cytogenetic Phases of CML

Treatment Options for Chronic Myelogenous Leukemia

Drug X is an oral agent; it has almost no side effects. It's nearly 100% active in the chronic phase, it starts working within days, and it targets the key enzyme in gene expression. The drug is hydroxyurea. Hydroxyurea actually targets ribonucleotide reductase, which is a key enzyme in gene expression. However, what we're talking about when we talk about targeted therapy is the ability to target a lesion that is in the leukemia cell or the cancer cell and not in the normal cells in the body.
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Slide 6.

Drug X

This shows the Phase II results for STI571, also referred to imatinib mesylate (Gleevec) for chronic phase CML, and what has been remarkable has been the high rate of complete hematologic responses and major cytogenetic responses.
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Slide 7.

Imatinib Mesylate for Chronic Phase CML

There have been a number of milestones in the treatment of CML. In the 1860s, arsenic trioxide was used to treat CML. This was followed later by radiotherapy and busulfan, and in the year 2001, STI571 became available to target the bcr-abl kinase. We've had some other kinds of negative milestones; in 1912, a benzene therapy was used to control CML and, fortunately, we don't do that any more.
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Slide 8.

Milestones in the Treatment of CML

The treatment options are listed here. We know that allogeneic stem cell transplantation has the ability to cure this disease. The other treatments can control it. The data with STI571 is early. The real question will be: which approach provides the best chance for long-term survival?
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Slide 9.

Treatment Options for Chronic Phase CML

Page 1 of 6

Is Imatinib Mesylate or SCT the Therapy of Choice for De Novo CML Patients?

Faculty and Disclosures

Author(s)

John F DiPersio, MD, PhD

Brian J Druker, MD

Sergio Giralt, MD

François Guilhot, MD

Rüdiger Hehlmann, MD

Hagop M Kantarjian, MD

Richard A Larson, MD

Stephen D Nimer, MD

Charles A Schiffer, MD

Rainer F Storb, MD

CME

Controversies in the Management of CML

Target Audience and Goal Statement

Author(s)

John F DiPersio, MD, PhD

Brian J Druker, MD

Sergio Giralt, MD

François Guilhot, MD

Rüdiger Hehlmann, MD

Hagop M Kantarjian, MD

Richard A Larson, MD

Stephen D Nimer, MD

Charles A Schiffer, MD

Rainer F Storb, MD

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Controversies in the Management of CML

Introduction , Presented by Stephen D. Nimer, MD

Overview of Chronic Myelogenous Leukemia

Slide 1.

Slide 2.

Slide 3.

Slide 4.

Slide 5.

Treatment Options for Chronic Myelogenous Leukemia

Slide 6.

Slide 7.

Slide 8.

Slide 9.