Chronic Myelogenous Leukemia Medication

  • Author: Emmanuel C Besa, MD; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP   more...
 
Updated: Dec 14, 2011
 

Medication Summary

The medications used for patients with chronic-phase chronic myelogenous leukemia (CML) aim at delaying the onset of the accelerated or blastic phase. This has traditionally included a myelosuppressive agent to achieve hematologic remission, but more effective drugs—successively, interferon alfa then and targeted therapy with tyrosine kinase inhibitors such as imatinib mesylate, have gained greater importance. Chemotherapy may be used, particularly in preparation for bone marrow or hematopoietic stem cell transplantation.

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Antineoplastic Agents

Class Summary

To control the underlying hyperproliferation of the myeloid elements, a myelosuppressive agent is used to bring down WBC counts and, occasionally, elevated platelet counts. Spleen size correlates with WBC counts, and it shrinks as WBC counts approach the reference range. Also, intermediate and myeloblast cells disappear from the circulation.

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Hydroxyurea (Hydrea, Droxia)

 

Hydroxyurea is an inhibitor of deoxynucleotide synthesis. This agent is used to control high WBC counts during induction with imatinib; it is discontinued once control is established. Hydroxyurea is less leukemogenic than alkylating agents such as busulfan, melphalan (Alkeran), or chlorambucil. Myelosuppressive effects last a few days to a week and are easier to control than with alkylating agents; busulfan is associated with prolonged marrow suppression and can cause pulmonary fibrosis.

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Busulfan (Myleran, Busulfex)

 

Busulfan is a potent cytotoxic drug that, at recommended dosage, causes profound myelosuppression. As an alkylating agent, the mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

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Tyrosine Kinase Inhibitors

Class Summary

Tyrosine kinase inhibitors elicit strong inhibition of tyrosine kinase activity of the BCR/ABL abnormality in all phases of CML.

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Imatinib mesylate (Gleevec)

 

Imatinib is specifically designed to inhibit the tyrosine kinase activity of bcr-abl kinase in Ph1-positive leukemic CML cell lines. It is well absorbed after oral administration, with maximum concentrations achieved within 2-4 hours. Elimination is primarily in feces in the form of metabolites.

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Dasatinib (Sprycel)

 

Dasatinib is a multiple tyrosine kinase inhibitor. It inhibits growth of cell lines overexpressing BCR/ABL. It has been able to overcome imatinib resistance resulting from BCR/ABL kinase domain mutations.

Dasatinib was originally approved in 2006 by the US Food and Drug Administration (FDA) for the treatment of adult patients with chronic-phase CML resistant or intolerant to prior therapy that included imatinib. In October 2010, the FDA extended approval to include the treatment of newly diagnosed adult patients with Ph1-positive chronic-phase CML.[20]

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Nilotinib (Tasigna)

 

Nilotinib inhibits BCR/ABL kinase. It was originally approved in 2007 by the FDA for the treatment of adult patients with chronic-phase CML resistant or intolerant to prior therapy that included imatinib. In June 2010, the FDA extended approval to include the treatment of newly diagnosed adult patients with Ph1-positive chronic-phase CML.[21]

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Interferons

Class Summary

Alfa, beta, and gamma are the 3 types of interferons known to date. The alfa group has been found to inhibit propagation of Ph-positive hematopoietic clone, allowing return of normal cells in bone marrow.

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Peginterferon alfa 2a (Pegasys)

 

Alfa, beta, and gamma are the 3 types of interferons known to date. The alfa group has been found to inhibit propagation of Ph1-positive hematopoietic clones, allowing return of normal cells in bone marrow.

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Contributor Information and Disclosures
Author

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Coauthor(s)

Ulrich Josef Woermann, MD  Consulting Staff, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland

Disclosure: Nothing to disclose.

Chief Editor

Koyamangalath Krishnan, MD, FRCP, FACP  Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians

Disclosure: Nothing to disclose.

Additional Contributors

Bruce Buehler, MD Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Maurie Markman, MD Vice President for Medical Oncology Services, National Director for Medical Oncology, Cancer Treatment Centers of America

Maurie Markman, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Eli Lilly Honoraria Speaking and teaching; Genentech Consulting fee Consulting; Cellgene Consulting fee Consulting; Hana Pharmaceuticals Consulting fee Consulting; Boehringer Ingelheim Consulting fee Consulting; Ortho Biotech Consulting fee Consulting; Morphotech Consulting; Amgen Consulting fee Consulting

Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Clarence Sarkodee-Adoo, MD Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Disclosure: Takeda Millenium Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Blood film at 400X magnification demonstrates leukocytosis with the presence of precursor cells of the myeloid lineage. In addition, basophilia, eosinophilia, and thrombocytosis can be seen. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Blood film at 1000X magnification demonstrates the whole granulocytic lineage, including an eosinophil and a basophil. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Blood film at 1000X magnification shows a promyelocyte, an eosinophil, and 3 basophils. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Bone marrow film at 400X magnification demonstrates clear dominance of granulopoiesis. The number of eosinophils and megakaryocytes is increased. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
The Philadelphia chromosome, which is a diagnostic karyotypic abnormality for chronic myelogenous leukemia, is shown in this picture of the banded chromosomes 9 and 22. Shown is the result of the reciprocal translocation of 22q to the lower arm of 9 and 9q (c-abl to a specific breakpoint cluster region [bcr] of chromosome 22 indicated by the arrows). Courtesy of Peter C. Nowell, MD, Department of Pathology and Clinical Laboratory of the University of Pennsylvania School of Medicine.
Fluorescence in situ hybridization using unique-sequence, double-fusion DNA probes for bcr (22q11.2) in red and c-abl (9q34) gene regions in green. The abnormal bcr/abl fusion present in Philadelphia chromosome–positive cells is in yellow (right panel) compared with a control (left panel). Courtesy of Emmanuel C. Besa, MD.
 
 
 
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