Signs and symptoms of APL
Acute promyelocytic leukemia (APL) can cause many different signs and symptoms.
Many patients will experience several generalized symptoms, such as weight loss,
unusual fatigue, fever, and loss of appetite, which are not specific to APL.
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The signs and symptoms specific to APL result from a shortage of normal blood cells
due to crowding out of normal blood cell-producing bone marrow by the leukemia cells.
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Common signs and symptoms of APL include:
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- Feeling tired or short of breath. This may be an effect of anemia, which
is a shortage of red blood cells.
- Pale complexion from anemia
- Slow healing of cuts or frequent minor infections. APL is usually associated
with a shortage of normal white blood cells (a condition called leukopenia) and,
in particular, too few mature granulocytes (neutropenia or granulocytopenia). This
results in a higher risk of infections. Although leukemia is often a cancer of white
blood cells and patients with leukemia may have very high white blood cell counts
(leukocytosis), the abnormal leukemia cells do not protect against infection.
- Mild fever or swollen glands
- Discomfort in bones or joints. Some patients with APL may have bone pain
or joint pain caused by the spread of leukemic cells to the surface of the bone
or into the joint from the marrow cavity. When leukemia cells spread outside the
bone marrow, the condition is called extramedullary spread.
- Bruising easily and bleeding. A hallmark of APL is a tendency to bleed. Because
of the increased risk of bleeding, there is reason for urgency in the treatment
of the disease. The disorder in clotting has historically been called disseminated
intravascular coagulopathy (DIC) but is now thought to be a more complicated consequence
of the leukemic cells. It can lead to excessive bruising, bleeding, frequent or
severe nosebleeds, bleeding from the gums, blood in the urine, and excessive bleeding
during menstruation or after needle sticks for blood draws. More serious bleeding
may also occur before the disease is under control.
>> Click here to find out if therapy with
TRISENOX® (arsenic trioxide) injection may be right for you.
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.
1. American Cancer Society. How Is Acute Myeloid Leukemia (AML) Diagnosed? Available
at:
http://www.cancer.org. Accessed July 21, 2009.