Acute Promyelocytic Leukemia Medication

  • Author: Sandy D Kotiah, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Aug 2, 2011
 

Medication Summary

The goals of pharmacotherapy are to induce remission, prevent complications, and reduce morbidity in patients with acute promyelocytic leukemia (APL).

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Antineoplastic Agents

Class Summary

Antineoplastic agents inhibit cell growth and proliferation.

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Arsenic trioxide (Trisenox)

 

May cause DNA fragmentation and damage or degrade the fusion protein PML-RAR alpha. Use only in patients whose disease has relapsed or is refractory to retinoid or anthracycline chemotherapy.

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Idarubicin (Idamycin)

 

Used for induction or consolidation therapy. Topoisomerase-II inhibitor. Inhibits cell proliferation by inhibiting DNA and RNA polymerase.

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Tretinoin (Vesanoid)

 

Induces maturation of acute promyelocytic leukemia cells in cultures. Used in both induction and maintenance phases for patients with acute promyelocytic leukemia.

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Gemtuzumab ozogamicin (Mylotarg)

 

Withdrawn from United States market (June 21, 2010). A confirmatory, postapproval clinical trial was begun in 2004. The trial was designed to determine whether adding gemtuzumab to standard chemotherapy demonstrated an improvement in clinical benefit (survival time) to patients with AML. The trial was stopped early when no improvement in clinical benefit was observed and after a greater number of deaths occurred in the group of patients who received gemtuzumab compared with those receiving chemotherapy alone. At initial approval in 2000, gemtuzumab was associated with a serious liver condition called veno-occlusive disease, which can be fatal. This rate has increased in the postmarket setting.

Monoclonal antibody against CD33 antigen, which is expressed on leukemic blasts in >80% of patients with acute myeloid leukemia and normal myeloid cells. Antibody-antigen complex is then internalized and the calicheamicin derivative is released inside the myeloid cell where it binds to DNA, resulting in double-strand breaks and cell death. Nonhematopoietic and pluripotent cells are not affected.

For administration to patients >60 years (CD33 positive) in first relapse who are not considered candidates for cytotoxic chemotherapy.

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Cytarabine (Cytosar-U)

 

Converted intracellularly to active compound cytarabine-5'-triphosphate, which inhibits DNA polymerase. Cell cycle S phase specific. Blocks the progression from G1 to S phase and in turn kills cells that undergo DNA synthesis in S phase of cell proliferation cycle.

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Mitoxantrone (Novantrone)

 

Used for induction or consolidation therapy. Inhibits cell proliferation by intercalating DNA and inhibiting topoisomerase II.

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Daunorubicin (Cerubidine)

 

Anthracycline antibiotic. Binds to nucleic acids by intercalation between base pairs of DNA, interfering with DNA synthesis. Causes inhibition of DNA topoisomerase II. Half-life is 14-20 h (23-40 h for active metabolite). Used in the induction phase of treatment.

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Contributor Information and Disclosures
Author

Sandy D Kotiah, MD  Fellow in Hematology Oncology, Thomas Jefferson University Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

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.

Specialty Editor Board

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

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

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

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.

Acknowledgments

I would like to acknowledge Dr. Emmanuel Besa for allowing me the opportunity to write this article.

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Bone marrow aspirate hybridized with the RARA dual color break-apart probe set (Abbott-Vysis). The cell to the left shows a normal cell with 2 fusion signals, as the 5'RARA probe (orange) and the 3'RARA probe (green) are not separated. The cell on the right shows split signals for one RARA gene, indicating a chromosomal rearrangement disrupting the RARA gene. Image courtesy of Dr. Tina Edmonston from the Department of Pathology at Thomas Jefferson University Hospital.
Bone marrow aspirate hybridized with PML/RARA dual color translocation probe set (Abbott-Vysis). The cell to the right shows a normal cell with 2 separate PML (orange) and RARA (green) signals each. The cell to the left shows an abnormal cell characterized by a single fusion signal juxtaposing the PML and RARA signals, suggestive of a translocation of the 2 genes. Images courtesy of Dr. Tina Edmonston from the Department of Pathology at Thomas Jefferson University Hospital.
Hypogranular subtype of acute promyelocytic leukemia. Image courtesy of Dr. William Kocher.
Regularly hypergranular subtype of acute promyelocytic leukemia. Image courtesy of Dr. William Kocher.
 
 
 
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