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Medication

Medication Summary

The goals of pharmacotherapy are to induce remission, prevent complications, and reduce morbidity in patients with acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA) should be prescribed on both an inpatient and outpatient basis. Patients should also be on prophylactic antifungal and antiviral medications during treatment, as these individuals have altered lymphocyte function due to both the underlying leukemia and cytotoxic therapy.

Class Summary

Antineoplastic agents inhibit cell growth and proliferation.

Arsenic trioxide (Trisenox)

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May cause DNA fragmentation and damage or degrade the fusion protein PML-RAR alpha. Used in APL patients who have the presence of the t(15;17) translocation or PML/RAR-alpha gene expression. It is indicated also for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy and in combination with tretinoin for treatment of adults with newly diagnosed low risk APL.

Idarubicin (Idamycin)

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

Tretinoin (Vesanoid)

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

Cytarabine (Cytosar-U)

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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.

Mitoxantrone (Novantrone)

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

Daunorubicin (Cerubidine)

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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.

Gemtuzumab (Mylotarg)

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Antibody-drug conjugate for newly diagnosed and relapsed or refractory CD33-positive acute myeloid leukemia. Gemtuzumab originally received accelerated approval in 2000; it was voluntarily withdrawn from the US market in 2010 after a confirmatory trial failed to show clinical benefit and reported an elevated rate of fatal toxicity, but was approved again in 2017 at a lower, fractionated dose. Gemtuzumab carries a black box warning for hepatotoxicity, including severe or fatal veno-occlusive disease.

Questions

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Media Gallery

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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Author

Sandy D Kotiah, MD Director of the Neuroendocrine Center, Hematology and Medical Oncology, Mercy Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, 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 Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H 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, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Additional Contributors

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

Clarence Sarkodee Adoo, MD, FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Acute Promyelocytic Leukemia Medication

Medication Summary

Antineoplastic Agents

Class Summary

Arsenic trioxide (Trisenox)

Arsenic trioxide (Trisenox)

Idarubicin (Idamycin)

Idarubicin (Idamycin)

Tretinoin (Vesanoid)

Tretinoin (Vesanoid)

Cytarabine (Cytosar-U)

Cytarabine (Cytosar-U)

Mitoxantrone (Novantrone)

Mitoxantrone (Novantrone)

Daunorubicin (Cerubidine)

Daunorubicin (Cerubidine)

Antineoplastics, Monoclonal Antibody

Gemtuzumab (Mylotarg)

Gemtuzumab (Mylotarg)

Acute Promyelocytic Leukemia Medication

Medication Summary

Antineoplastic Agents

Class Summary

Arsenic trioxide (Trisenox)

Arsenic trioxide (Trisenox)

Idarubicin (Idamycin)

Idarubicin (Idamycin)

Tretinoin (Vesanoid)

Tretinoin (Vesanoid)

Cytarabine (Cytosar-U)

Cytarabine (Cytosar-U)

Mitoxantrone (Novantrone)

Mitoxantrone (Novantrone)

Daunorubicin (Cerubidine)

Daunorubicin (Cerubidine)

Antineoplastics, Monoclonal Antibody

Gemtuzumab (Mylotarg)

Gemtuzumab (Mylotarg)

References

Tables

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