Pediatric Acute Myelocytic Leukemia Medication
- Author: Mark E Weinblatt, MD; Chief Editor: Jennifer Reikes Willert, MD more...
The treatment of acute myeloid leukemia is directed toward 2 goals: destroying the leukemic cells and supporting the patient through long periods of pancytopenia. Chemotherapy meets the first goal, but many classes of other drugs must also be included in treatment. Such classes include broad-spectrum antibacterial, antiviral, and antifungal antibiotics; biologic-response modifiers; and other classes of supportive medications.
Although many chemotherapeutic agents are active, most current regimens include combinations of an anthracycline and cytosine arabinoside. Chemotherapeutic agents destroy myeloblasts in various mechanisms.
Cytarabine is a purine antimetabolite; it inhibits deoxyribonucleic acid (DNA) polymerase. The drug is used in the induction and intensification phases of treatment.
This is an anthracycline that binds to nucleic acids by intercalating between pairs of DNA, interfering with DNA synthesis. It is used in the induction phase of treatment.
Etoposide is a podophyllotoxin derivative. It is used in the induction and consolidation phases of treatment.
Mitoxantrone inhibits cell proliferation by intercalating DNA and inhibiting topoisomerase II. It is used in the consolidation phase of treatment.
Tretinoin, all-trans-retinoic acid
This is used in the induction and maintenance phases in patients with APL.
Arsenic trioxide may cause DNA fragmentation and damage or degrade fusion protein promyelocytic leukemia protein–retinoic acid receptor alpha (PML-RAR alpha).
This is used in the consolidation phase of therapy. It inhibits protein synthesis by hydrolyzing asparagines to aspartic acid and ammonia.
Gemtuzumab ozogamicin (Mylotarg)
Gemtuzumab ozogamicin is a monoclonal antibody against CD33 antigen, which is expressed on leukemic blasts in more than 80% of patients with acute myeloid leukemia and normal myeloid cells. The 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.
The drug is for administration to patients over age 60 years (CD33 positive) in first relapse who are not considered candidates for cytotoxic chemotherapy.
Gemtuzumab ozogamicin was withdrawn from United States market (June 21, 2010).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.
Antineoplastic-induced vomiting is stimulated by actions on the chemoreceptor trigger zone. This zone then stimulates the vomiting center in the brain. Increased activity of central neurotransmitters, dopamine in the chemoreceptor trigger zone or acetylcholine in the vomiting center, appears to be a major mediator in inducing vomiting. After antineoplastic agents are given, serotonin (5-HT) is released from enterochromaffin cells in the GI tract. With this release, and with the subsequent binding of 5-HT to 5-HT3 receptors, vagal neurons are stimulated and transmit signals to the vomiting center, resulting in nausea and vomiting.
Emesis is a notable problem in patients receiving high-dose chemotherapy. The resultant nutritional, metabolic, and fluid derangements can be unpleasant enough that patients may refuse further life-saving therapy. It is important to use these drugs prophylactically.
Ondansetron is a selective 5-HT3 receptor antagonist that blocks serotonin peripherally and centrally. It prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and whole-body radiotherapy.
At the chemoreceptor trigger zone, granisetron blocks serotonin centrally and peripherally on vagal nerve terminals.
Infections remain the biggest problem in acute myeloid leukemia. The use of prophylactic drugs can help to prevent several infections that are often life threatening.
Sulfa drugs can effectively prevent Pneumocystis (carinii) jiroveci pneumonia in this immunocompromised group of patients.
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