Testing procedures for APL
If signs and symptoms suggest that you have leukemia, your doctor will examine your
blood cells with a test called a
complete blood count. If the
results are abnormal, the doctor or nurse may talk to you about a
bone
marrow biopsy.
Genetic testing can help track disease status, predict relapse, and improve outcomes.
For acute promyelocytic leukemia (APL) patients, one test for diagnosing APL
specifically,
and tracking disease progress, is reverse transcriptase-polymerase chain reaction
testing, or
RT-PCR testing. The RT-PCR test may be used to
determine disease status and adjust therapy if necessary. Studies have shown that
a positive test may predict relapse, whereas repeatedly negative results are associated
with long-term survival in the majority of patients.
1 These studies report
that patients who show a positive RT-PCR test may be given chemotherapy earlier,
which may help to improve outcome versus delaying treatment until further evidence
of a relapse is present.
1,2
>> Click here to learn more about RT-PCR testing.
To learn more about the tests involved in diagnosing and treating acute myeloid
leukemia (AML) and its subtypes, such as APL, click on the links below:
Blood cell counts and blood cell examination
Changes in the numbers of different blood cell types and how the cells look under
a microscope can suggest leukemia. People with APL have too many immature blood
cells, known as promyelocytes, which cannot carry out their normal functions and
which block the production of normal mature cells. Even though presence of these
immature cells may suggest leukemia, usually the disease cannot be diagnosed without
getting a sample of bone marrow cells.
3
Bone marrow aspiration and biopsy
In bone marrow aspiration, a syringe is used to remove a small amount of liquid
bone marrow (about 1 teaspoon). The bone marrow sample is generally taken from the
pelvic (hip) bone. Sometimes the needle going into the bone is painful, but it only
lasts a short time. The removal of the bone marrow is often painful or at least
uncomfortable for a brief time.
3
The aspiration may be followed by a bone marrow biopsy in the same area. The doctor
may use the same or a larger needle to collect a second sample called a core biopsy.
This contains a small solid piece of bone and marrow. You may feel some pressure
as the doctor removes the marrow specimen. After the biopsy needle is pulled out,
this solid sample is pushed out of the needle with a wire so that it can be examined
under a microscope.
3
RT-PCR testing
RT-PCR testing analyzes the genetic abnormalities that define APL specifically.
In general, chromosome changes give us one clue to prognosis for cancer patients.
APL is usually marked by an exchange of genes between chromosomes 15 and 17. This
exchange is called a translocation. This translocation is written in a shorthand
form as t(15;17), meaning a part of chromosome 15 is now located on chromosome 17,
and vice versa.
4-7 When the genes trade places, a mutant gene is formed
and it is this mutant gene that prevents leukemia cells from aging in a healthy
way and causes leukemia cells to increase in number.
4-8
The presence of this mutant gene produced by the exchange of genes between chromosomes
15 and 17 is detected with the RT-PCR test.
1 The test is performed to
diagnose APL and is performed between rounds of therapy to assess a patient’s disease
status.
>> Click here to learn more about the underlying
causes of APL, including chromosome translocation.
Other tests
Your doctor may perform a variety of lab tests, including microscopic examinations
that analyze any samples taken (i.e., blood, bone marrow) under a microscope. Many
specialized tests may be done to determine the exact type of leukemia. Genetic testing
involves looking at a cell's chromosomes under a microscope to detect abnormalities.
3
Talk to your doctor about what tests and procedures may be involved in your treatment.
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. Lowenberg B, Griffin JD, Tallman MS. Acute myeloid leukemia and acute promyelocytic
leukemia.
Hematology Am Soc Hematol Educ Program. 2003;82-101.
2. Lo Coco F, Diverio D, Avvisati G, et al. Therapy of molecular relapse in acute
promyelocytic leukemia.
Blood. 1999;94:2225-2229.
3. American Cancer Society. How Is Acute Myeloid Leukemia (AML) Diagnosed? Available
at:
http://www.cancer.org. Accessed July 21, 2009.
4. Grignani F, Fagioli M, Alcalay M, et al. Acute promyelocytic leukemia: from genetics
to treatment.
Blood. 1994;83:10-25.
5. Douer D, Tallman MS. Arsenic trioxide: new clinical experience with an old medication
in hematologic malignancies.
J Clin Oncol. 2005;23:2396-2410.
6. Miller WH Jr, Schipper HM, Lee JS, et al. Mechanisms of action of arsenic trioxide.
Cancer Res. 2002;62:3893-3903.
7. Davison K, Mann KK, Miller WH Jr. Arsenic trioxide: mechanisms of action.
Semin
Hematol. 2002;39(2 Suppl 1):3-7.
8. Melnick A, Licht JD. Deconstructing a disease: RAR alpha, its fusion partners,
and their roles in the pathogenesis of acute promyelocytic leukemia.
Blood.
1999;93:3167-3215.