The lab tests performed to determine your diagnosis will be:
Cytochemistry, Cytogenetics, PCR, FISH, and Immunocytochemistry.
Cytochemistry
A combination of cytomorphological features and cytochemical staining reactions in the diagnoses of the different types of acute leukemia removes much of the subjective difficulty of diagnosis. The number of cytochemical stains used may be limited, and in our experience the PAS, combined NCE and ANE reactions, and either SB or Px staining will yield as much diagnostic information as needed in most cases. With regard to the prognostic implications, it would appear at the present time that the amount of ANE staining in the cytoplasm of blasts is inversely proportional to the chances of remission induction and length of survival in cases of acute leukemia. However, further studies must be carried out to verify this finding before using the information to compliment other prognostic variables, such as age of patient, previous therapy, cytokinetics,
etc.
Cytogenetics
Cells are harvested from two or more unstimulated cultures. Twenty metaphase spreads are fully analyzed and two karyotypes are prepared. If abnormalities are found, at least two karyotypes are prepared for each abnormal clone.
PCR
When a patient tests negative in the 20 cell cytogenetics test for the Ph chromosome as well as the 500 cell FISH
test for the BCR-ABL fusion gene, there is still residual CML disease left in the body, sometimes a million
leukemic cells or more. Polymerase chain reaction (PCR) test measures this low level disease by being able to
detect 1 leukemic cell in a million or more normal cells by amplifying one leukemic cell into many copies. The
PCR test is a molecular test and the results is the molecular response of a patient.
• Qualitative PCR gives a positive or negative value for the presence of disease.
• Quantitative PCR (Q-PCR) gives the level of disease positivity in numbers.
• Nested PCR can sometimes be more sensitive than the above as it uses double primers and repeats the
experiment so that errors are corrected.
Most doctors will recommend a quantitative PCR to measure residual disease. This can be recommended right
from diagnosis or after other tests show negative, it really depends on the doctor. However, it is the most
important tool, nowadays, to follow low disease load. You follow the disease by PCR numbers in the same way you
tracked the Ph chromosome when the disease load was high by other tests. Do remember, that absolute PCR
values cannot be compared to FISH and Cytogenetics values and also not between different PCR labs as it will be
different.
A PCR report looks like the one above. Quant BCR-ABL means a quantitative PCR was done to look for BCR-
ABL transcripts. In layman terms, it is looking for leukemic cells carrying the BCR-ABL signature. In the Q-
PCR experiment, a control is used and in most labs, that is ABL. A control correlates to the number of normal
cells. Therefore, when you see the result of 0.6%BCR-ABL/ABL, it means the percentage ratio of bad cells to
total cells.
• One PCR test, by itself, has little meaning. The PCR trend is important. Ideally, the PCR numbers should
be going down with time as the disease is controlled by therapy.
• There are two types of molecular response. A major molecular response (MMR) when the PCR value of a
patient has decreased 1000-fold or 3-log from diagnosis and complete molecular response (CMR) when the patient
tests negative for leukemia from the PCR tests.
• If there is a 10-fold or 1-log increase in PCR numbers, usually, doctors will first recommend a re-test and
many patients have reported a re-test showing the rise to be a fluke. If the re-test and subsequent tests show a
rising PCR trend, most doctors will recommend ABL point mutations testing to see if resistance to therapy is
being developed. These are special tests done only in a handful of laboratories around the world and it is usually
done from a blood draw.
• The goal of Gleevec therapy is to reach a 1000-fold or 3-log reduction from diagnosis PCR values as this
gives only a 0.5% risk of relapse per year. Many patients do not have diagnosis PCR values so a PCR lab has a
diagnosis PCR baseline from newly diagnosed patients and you can correlate your PCR value to that.
• A PCR test can be done from either the blood or marrow. However, recent medical studies have shown that
the two may not show absolute correlation so doctors recommend PCR testing from the blood only, to keep the
source constant and because recommendations are to do a PCR every 3 months and a bone marrow aspiration
every 3 months is considered invasive.
So, what are the questions to ask the doctor when you get a report as above?
• CML experts recommend a PCR sensitivity of 1 in 100,000 cells as the minimum so ask the doctor if the
PCR lab is able to detect 1 leukemic cell in 100,000 cells.
• If you do not have a diagnosis PCR value, ask the doctor what log reduction is 0.6% from the lab baseline.
If it is 3-log and below, you are in good molecular response.
• Watch the PCR trend over time and if you find that with your current dose of Gleevec, your PCR is not
going down any further after some time and you do not have a 3-log reduction, discuss with the doctor options of
raising Gleevec dose or his advice on what to do next.
For a schedule of recommended PCR monitoring, see the article below from ASH 2005 from Dr. Deininger of
OHSU.
http://www.asheducationbook.org/cgi/content/full/2005/1/174
FISH
It is a test can identify specific chromosomal and genetic abnormalities - leukemia, lymphomas, hematopoietic malignancies, some solid tumors.
Immunochemistry
Immunocytochemistry uses the same principle, employing antibodies to produce distinct color changes in the cell sample that allow the pathologist to identify the type of leukemia present.
TREATMENT OPTIONS
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type and stage of the cancer being treated.
Intrathecal chemotherapy may be used to treat adult ALL that has spread, or may spread, to the brain and spinal cord. When used to prevent cancer from spreading to the brain and spinal cord, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis. Intrathecal chemotherapy is given in addition to chemotherapy by mouth or vein.
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| Intrathecal chemotherapy. Anticancer drugs are injected into the intrathecal space, which is the space that holds the cerebrospinal fluid (CSF, shown in blue). There are two different ways to do this. One way, shown in the top part of the figure, is to inject the drugs into an Ommaya reservoir (a dome-shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain). The other way, shown in the bottom part of the figure, is to inject the drugs directly into the CSF in the lower part of the spinal column, after a small area on the lower back is numbed. |
See Drugs Approved for Acute Lymphoblastic Leukemia for more information.
Radiation therapy
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. External radiation therapy may be used to treat adult ALL that has spread, or may spread, to the brain and spinal cord. When used this way, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis.
Chemotherapy with stem cell transplant
Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.
See Drugs Approved for Acute Lymphoblastic Leukemia for more information.
Targeted therapy
Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.
Targeted therapy drugs called tyrosine kinase inhibitors are used to treat some types of adult ALL. These drugs block the enzyme, tyrosine kinase, that causes stem cells to develop into more white blood cells (blasts) than the body needs. Two of the drugs used are imatinib mesylate (Gleevec) and dasatinib.
See Drugs Approved for Acute Lymphoblastic Leukemia for more information.
New types of treatment are being tested in clinical trials.
This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.
Biologic therapy
Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.
Patients may want to think about taking part in a clinical trial.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the
http://www.cancer.gov/cancertopics/pdq/treatment/adultALL/Patient/page4
Options are: chemotherapy, radiation, or bone marrow transplant
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