The monitoring of the response to the treatment is a vital issue. With blood and marrow tests, the person’s level of response to treatment is evaluated. With these results, it is determined whether the KML is under control or not. If the disease is not well under control,

• Increase of dosage for a better response
• Stopping medication / decreasing the dosage due to side effects
• Trying a different medication or combinations for better control
• Trying a different medication or combinations to reduce side effects

may be considered.

There are general principles for evaluating the response to treatment after about a year of KML treatment. But it must be noted that each patient may react differently to treatment. Blood and marrow tests are used to evaluate the KML treatment response.

The patient’s response to treatment is compared to the tests before treatment. The patient’s blood and KML cells are periodically evaluated;

• After diagnosis, marrow test in the first year is done on the 6th and 12th months.
• Many doctors perform one or two matrrow tests in the following year.
• Once a good response is obtained, marrow tests may be repeated once every 12-18 months.

Your physician may use the terms haematological / cytogenetic / molecular responses.

Haematological response: A complete haematological response is evaluated with a blood cell count test (hemogram). In the test, the number of red and white blood cells and blood platelets is observed to be normal / close to normal.

Cytogenetic response: For a complete cytogenetic response, no cells with Ph chromosome and Bcr-Abl gene must be left. To evaluate this situation, FISH test is performed.

Molecular response: A partial molecular response means a decrease in the number of cells with Bcr-Abl cancer gene. A major molecular response means a 1000-time decrease in the number of cells with Bcr-Abl gene, compared to the number calculated at the beginning of the treatment. A complete molecular response means that there are no cells with Bcr-Abl cancer gene, detected by PCR. The remaining KML cells undetected by PCR are called “minimal residual disease”. The amount of cells with Bcr-Abl gene is detected by PCR. Since some PCR values (parameters?) may vay from lab to lab, it is essential that this test is performed at the same lab every time.

Tests For Monitoring Your Response To Treatment

Your physician may describe the goals of your treatment as follows.

1. Haematological response
2. Cytogenetic response
3. Molecular response

Regular tests are essential for evaluation of your response to treatment. Also, your physician will decide whether to adjust the dosage during treatment via test results. Blood or marrow samples may be taken for tests. The three main test types to monitor your response to medication are as follows.

1. Blood tests
2. Cytogenetic tests
3. Molecular tests

The results of these tests will help your physician evaluate your response to treatment and plan future treatments. The results also help in estimating how you will react to treatment in the long run.

Blood Tests

Blood tests may be called haematological tests by your physician or nurse. During the blood test, a blood sample is taken, usually from a vein on the arm, and placed in a special tube to be sent to a lab for analysis. In the simple blood test, which is called complete blood cell count or hemogram, blood cells of different types are counted using a specific machine. Then the results are compared to the expected numbers in the blood. Too high or too low numbers of certain blood cells points to different types of diseases.

In majority of the patients with Ph+ KML, the number of white blood cells in the first diagnosis is usually very high.

Haematological Response - Goals

1. Returning the number of white and red blood cells and platelets back to normal
2. Terminating the damaged white blood cells
3. Eliminating the symptoms of the disease

Cytogenetic Tests

Cytogenetic tests are performed to determine the number of cells with Philadelphia chromosome in the marrow. These tests are usually performed after your blood cell count returns to normal.

A marrow sample is necessary for cytogenetic tests. The sample usually taken from the hip bone with a special needle. Although it is a discomfortable process, it is vital to perform it regularly, since the only way to monitor the progress of the disease and the treatment is to view the chromosomes.

There are two main types of cytogenetic tests.

1. In one of the types, a microscope is used to examine the white blood cells on a small portion of the marrow sample. Usually at least 20 cells are checked for Philadelphia chromosome or other damaged chromosomes.
2. In the fluoresence in situ hybridization technique, FISH in short, defective Bcr-Abl gene is searched for in the blood or marrow sample. Keep in mind that the Bcr-Abl gene is a part of the Philadelphia chromosome. This test can detect one damaged cell among 200 to 500 normal cells. No detection of Philadelphia chromosome in any cells is called “complete cytogenetic response.”

Cytogenetic Response - Goals

• Complete cytogenetic response - Detection of no (% 0) Philadelphia chromosomes
• Partial cytogenetic response - % 1-34 of the cells in the sample (1-34 of every 100 cells) contains the Philadelphia chromosome.

Molecular Tests

The most accurate test for monitoring response to the Ph+ KML treatment is called the polymerase chain reaction (PCR). Blood or marrow sample is needed for PCR and this test can detect a single defective Bcr-Abl gene in about a million normal cells.

What is molecular response?

Since the number of cells with Bcr-Abl gene is greatly reduced to a certain extent after treatment, major molecular response is regarded as accomplished. Even if no Bcr-Abl gene is detected in the samples of the PCR test, cells with defective Philadelphia chromosome may still exist in the body. Therefore, even if your test results show great reponse to treatment, you still have to continue your medication as prescribed, unless your physician tells you otherwise.

How long should I continue medication?

You should keep in mind that even if no damaged or defective cells are detected in blood or marrow with the most accurate tests, such cells may still exist. Therefore, unless your physician tells you otherwise, it is vital that you continue your medication as prescribed, even if your test results show that you respond to treatment. Researches have shown that certain cells may be “sleepers” and do not replicate at that stage, yet are unresponsive to treatment. On the other hand, if you stop medication, these cells may replicate again, even if you have responded to treatment.