As a patient living with acute promyelocytic leukemia (APL), you may come across many new terms
related to your condition and treatment. Here, you will find definitions to terms you may encounter
during conversations with your healthcare team, or when doing your own research.
Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature white blood
cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute
nonlymphocytic leukemia.
Acute promyelocytic leukemia: APL. An aggressive (fast-growing) type of acute myeloid leukemia
(AML) in which there are too many immature blood-forming cells in the blood and bone marrow. It
is usually marked by an exchange of parts of chromosomes 15 and 17. Also called promyelocytic
leukemia.
Anemia: A condition in which the number of red blood cells is below normal.
Anthracycline: A type of antibiotic that comes from the fungus
Streptococcus peucetius.
Anthracyclines are used as treatments for cancer. Daunorubicin and idarubicin are two commonly
used anthracyclines.
Apoptosis: A type of cell death in which a series of molecular steps in a cell leads to its death.
This is the body's normal way of getting rid of unneeded or abnormal cells. The process of
apoptosis may be blocked in cancer cells. Also called programmed cell death.
Arsenic trioxide: A substance that induces programmed cell death (apoptosis) in certain
cancer cells. It belongs to the family of drugs called antineoplastics.
ATRA: All-trans retinoic acid. A form of vitamin A that is made by the body, and can also
be made in the laboratory. It is used to treat acute promyelocytic leukemia (APL), usually
together with other drugs. Also called tretinoin, retinoic acid, and vitamin A acid.
Biopsy (bone marrow): The removal of a sample of tissue from the bone marrow with a needle
for examination under a microscope.
Blasts: An immature blood cell.
Bone marrow aspiration: The removal of a small sample of bone marrow (usually from the hip)
through a needle for examination under a microscope.
Cell: The individual unit that makes up the tissues of the body. All living things are made
up of one or more cells.
Chemotherapy: Treatment with drugs that kill cancer cells.
Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs,
all human cells contain 46 chromosomes.
Clinical trial: A type of research study that tests how well new medical approaches work
in people. These studies test new methods of screening, prevention, diagnosis, or treatment of
a disease. Also called a clinical study.
Complete remission (CR): The disappearance of all signs of cancer in response to treatment.
This does not always mean the cancer has been cured. Also called a complete response.
Consolidation: A type of high-dose chemotherapy often given as the second phase (after
induction therapy) of a cancer treatment regimen for leukemia. Also called intensification therapy.
Cytochemistry: Placing cells from a blood or bone marrow sample on glass microscope slides
and exposing them to chemical stains (dyes) that react with only some types of leukemia cells
Cytogenetics: The study of chromosomes and chromosomal abnormalities.
Differentiation syndrome: A potential side effect of treatment with TRISENOX or ATRA.
Symptoms include fever, sudden weight gain, bone or joint pain, and fluid buildup around the
heart, lungs and chest leading to shortness of breath or difficulty breathing.
DNA: Deoxyribonucleic acid. The molecules inside cells that carry genetic information and
pass it from one generation to the next.
DNA mutations: Genetic defects.
Extramedullary spread: When leukemia cells spread outside the bone marrow.
Flow cytometry: A method of measuring the number of cells in a sample, the percentage of
live cells in a sample, and certain characteristics of cells, such as size, shape, and the
presence of tumor markers on the cell surface. The cells are stained with a light-sensitive dye,
placed in a fluid, and passed in a stream before a laser or other type of light. The measurements
are based on how the light-sensitive dye reacts to the light.
Gene: The functional and physical unit of heredity passed from parent to offspring. Genes
are pieces of DNA, and most genes contain the information for making a specific protein.
Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an
increased risk for developing a specific disease or disorder.
Immunocytochemistry: Cells from the bone marrow aspiration or biopsy sample are treated
with special antibodies that reach only to certain molecules. The sample is treated so that
certain types of cells change color. The color change can be seen only under a microscope. Like
flow cytometry, it is helpful in distinguishing different types of leukemia from one another.
Induction: Treatment designed to be used as a first step toward shrinking the cancer and
in evaluating response to drugs and other agents. Induction therapy is followed by additional
therapy to eliminate whatever cancer remains.
Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called
intravenous infusion.
Leukemia: Cancer that starts in blood-forming tissue such as the bone marrow, and causes
large numbers of blood cells to be produced and enter the bloodstream.
Leukocytosis: High white blood cell counts.
Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood
is reduced.
Maintenance: Treatment that is given to help a primary (original) treatment keep working.
Maintenance therapy is often given to help keep cancer in remission.
Myeloid: Having to do with or resembling the bone marrow. May also refer to certain types
of hematopoietic (blood-forming) cells found in the bone marrow. Sometimes used as a synonym for
myelogenous; for example, acute myeloid leukemia and acute myelogenous leukemia are the same disease.
Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell.
Partial remission (PR): A decrease in the extent of cancer in the body, in response to
treatment. Also called partial response.
Platelet: A type of blood cell that helps prevent bleeding by causing blood clots to form.
Also called a thrombocyte.
Pleural effusion: A buildup of fluid in the pleura, the membranes that line the outer lungs
and chest cavity, that may occur with ATRA therapy. Known as ATRA syndrome, or retinoic acid
syndrome.
Prognosis: The likely outcome or course of a disease; the chance of recovery or recurrence.
Promyelocytes: A type of immature white blood cell.
Protooncogenes: Genes that promote cell division.
QT interval prolongation: A potential side effect of treatment with TRISENOX. The time it
takes the heart to relax in between beats is longer than usual.
Red blood cell: RBC. A cell that carries oxygen to all parts of the body. Also called an
erythrocyte.
Refractory cancer: Cancer that does not respond to treatment. The cancer may be resistant
at the beginning of treatment or it may become resistant during treatment. Also called resistant
cancer.
Relapse: The return of signs and symptoms of cancer after a period of improvement.
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial
remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission,
all signs and symptoms of cancer have disappeared, although cancer still may be in the body.
RT-PCR: Reverse transcriptase-polymerase chain reaction. A genetic test that assesses for
the abnormalities that define acute promyelocytic leukemia (APL).
Stable disease: Cancer that is neither decreasing nor increasing in extent or severity.
Stem cells: A cell from which other types of cells develop. Blood cells develop from
blood-forming stem cells.
Stem cell transplantation: A method of replacing immature blood-forming cells that were
destroyed by cancer treatment. The stem cells are given to the person after treatment to help the
bone marrow recover and continue producing healthy blood cells.
Thrombocytopenia: A decrease in the number of platelets in the blood that may result in
easy bruising and excessive bleeding from wounds or bleeding in mucous membranes and other tissues.
Translocation: An exchange of DNA material between two chromosomes.
Tumor suppression genes: A type of gene (unit of heredity passed from parent to offspring)
that helps control cell growth. Blocking the action of tumor suppressor genes may lead to cancer.
White blood cell: WBC. Refers to a blood cell that does not contain hemoglobin. White blood
cells include lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. These cells
are made by bone marrow and help the body fight infection and other diseases.
Source: National Cancer Institute, www.cancer.gov. Accessed July 2009.
TRISENOX is indicated for induction of remission and consolidation in patients with APL who
are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose
APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
Serious adverse events, grade 3 or 4, were common. Those events attributable to TRISENOX in the Phase 2
study of 40 patients with refractory or relapsed APL included APL differentiation syndrome (n=3), hyperleukocytosis (n=3), QTc
interval prolongation (n=16), atrial dysrhythmias (n=2), hyperglycemia (n=2), and torsades de pointes (n=1).
In addition to QT interval prolongation, the most common drug-related side effects included leukocytosis, gastrointestinal events (nausea, vomiting, diarrhea, and abdominal pain), fatigue, swelling, hyperglycemia (an abnormal increased content of sugar in the blood), shortness of breath, cough, rash or itching, headache, and dizziness. Have your doctor review side effects with you.
In clinical trials, most patients taking TRISENOX experienced some drug-related toxicity, most commonly leukocytosis, gastrointestinal (nausea, vomiting, diarrhea, and abdominal pain), fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headache, and dizziness. These adverse effects have not been observed to be permanent or irreversible, nor do they usually require interruption of therapy.
It is important to call your doctor if you experience any treatment side effects.
WARNING
Experienced Physician and Institution:
TRISENOX® (arsenic trioxide) injection should be administered under the supervision
of a physician who is experienced in the management of patients with acute leukemia.
APL Differentiation Syndrome:
Some patients with APL treated with TRISENOX have experienced symptoms similar to a syndrome called
the retinoic-acid-acute promyelocytic leukemia (RA-APL) or APL differentiation syndrome, characterized
by fever, dyspnea, weight gain, pulmonary infiltrates and pleural or pericardial effusions, with or
without leukocytosis. This syndrome can be fatal. The management of the syndrome has not been fully
studied, but high-dose steroids have been used at the first suspicion of the APL differentiation
syndrome and appear to mitigate signs and symptoms. At the first signs that could suggest the syndrome
(unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory findings or radiographic
abnormalities), high-dose steroids (dexamethasone 10 mg intravenously BID) should be immediately
initiated, irrespective of the leukocyte count, and continued for at least 3 days or longer until
signs and symptoms have abated. The majority of patients do not require termination of TRISENOX therapy
during treatment of the APL differentiation syndrome.
ECG Abnormalities:
Arsenic trioxide can cause QT interval prolongation and complete atrioventricular block. QT prolongation can
lead to a torsade de pointes-type ventricular arrhythmia, which can be fatal. The risk of torsade de pointes
is related to the extent of QT prolongation, concomitant administration of QT prolonging drugs, a history of
torsade de pointes, pre-existing QT interval prolongation, congestive heart failure, administration of
potassium-wasting diuretics, or other conditions that result in hypokalemia or hypomagnesemia. One patient
(also receiving amphotericin B) had torsade de pointes during induction therapy for relapsed APL with arsenic
trioxide.
ECG and Electrolyte Monitoring Recommendations:
Prior to initiating therapy with TRISENOX, a 12-lead ECG should be performed and serum electrolytes (potassium,
calcium, and magnesium) and creatinine should be assessed; pre-existing electrolyte abnormalities should be
corrected and, if possible, drugs that are known to prolong the QT interval should be discontinued. For QTc
greater than 500 msec, corrective measures should be completed and the QTc reassessed with serial ECGs prior
to considering using TRISENOX. During therapy with TRISENOX, potassium concentrations should be kept above 4 mEq/L
and magnesium concentrations should be kept above 1.8 mg/dL. Patients who reach an absolute QT interval value > 500
msec should be reassessed and immediate action should be taken to correct concomitant risk factors, if any, while
the risk/benefit of continuing versus suspending TRISENOX therapy should be considered. If syncope, rapid or irregular
heartbeat develops, the patient should be hospitalized for monitoring, serum electrolytes should be assessed, TRISENOX
therapy should be temporarily discontinued until the QTc interval regresses to below 460 msec, electrolyte abnormalities
are corrected, and the syncope and irregular heartbeat cease. There are no data on the effect of TRISENOX on the QTc
interval during the infusion.