Leukemia

Monitoring Treatment in CML


Medically Reviewed On: December 22, 2010

Cytogenetic testing may be used throughout treatment to check for other possible chromosomal abnormalities that may develop over time.  But if treatment is successful, cytogenetic testing may prove insufficiently sensitive to check for progress in attacking the disease. The 20- or 30- cell sample is just not large enough.  In other words, if treatment is going well, and there seems to be a complete cytogenetic response, there still could be many cells present with the Philadelphia chromosome – below the threshold of detection with cytogenetic testing by microscope. Therefore effective treatment must be accompanied by increasingly sensitive monitoring.

FISH Testing
Doctors may turn to a fluorescent in-situ hybridization (FISH) test, which is a type of cytogenetic test performed on blood cells or marrow cells. That means that FISH can be done on a sample of either blood or bone marrow.  During a FISH test, several hundred cells are tagged with a chemical that can make certain genes visible under a special light.  With this test, lab technicians can detect the presence or absence of the BCR-ABL gene. FISH is often able to detect as few as one abnormal cell in 500.

PCR Testing
The most sensitive test for monitoring disease progress in CML treatment is the  polymerase chain reaction (PCR).  After taking a blood or bone marrow sample and performing a sophisticated technique called gene amplification, a lab technician can use PCR to look directly at the genetic makeup of blood cells. The test measures the quantity of the BCR-ABL gene. PCR testing is so sensitive that it can find one cell with the Philadelphia chromosome in a million healthy cells.  Many doctors say it is important to get a baseline PCR level at the start of CML drug therapy to measure response over time.

PCR test results can vary from laboratory to laboratory, and they can vary in sensitivity.  It is recommended that the same laboratory should be used for follow up PCR testing to provide more accurate and consistent evaluations of  response to drug therapy.  Doctors are now encouraging standardization so results from different labs can be used to track the same patient.

 Doctors are also encouraging the use of a type of PCR called “quantitative” PCR that returns results in terms of specific percentages of leukemic cells. Other tests, called “qualitative” PCR testing merely return “positive” or “negative” results with reference to a specified sensitivity. The problem with this approach is that changes over time are not measured.

A negative finding – often defined mathematically as a 3-log reduction, a 1,000 fold reduction from baseline, --  for the BCR-ABL gene by PCR test is a very good sign for patients.  However, he or she is likely to still have cells with the Philadelphia chromosome left in the body that are not detectable even by PCR.  Even with one cell left, CML can relapse.  It is for this reason that doctors will rarely declare that a person is cured of CML.

Disease Relapse
A small number of patients in the chronic phase of CML will relapse after being managed well for a period of time on imatinib.  That’s why regular monitoring should continue.  Doctors speak of a cytogenetic relapse if the percentage of cells with the Philadelphia chromosome starts going up after a period of decline according to cytogenetic tests.  Similarly, a hematological relapse occurs when your blood counts become abnormal after a period of good control.

Relapse after drug therapy can sometimes be treated with a higher dose of imatinib or with newer drug therapies. Sometimes a stem cell transplant may be considered.


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