What causes the BCR-ABL PCR result to rise in patients with chronic myelogenous leukemia (CML)?

Updated: May 23, 2021
  • Author: Emmanuel C Besa, MD; Chief Editor: Sara J Grethlein, MD, FACP  more...
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The BCR-ABL PCR result may rise in a patient for a number of reasons. One possibility is decreased compliance, especially in the context of an expensive drug and a patient who has had a good molecular response (a situation where the temptation to enjoy a “drug holiday” is strong). Second, variability in the test itself may result in some increase or decrease, especially when the tumor burden is very low. In most laboratories, however, a 5- to 10-fold change in the PCR result is probably “real.”

However, it is possible that BCR-ABL levels may vary naturally over time in patients on TKI therapy. CML is known to have cyclic oscillations, with peaks and troughs occurring at even 1- to 2-month intervals, and this has not been studied in cases with residual disease. Several lines of evidence suggest that a truly rising BCR-ABL deserves concern. First, several studies have shown that a rising BCR-ABL is associated with a greater increase of the acquisition of an Abl point mutation and resistance. [68]  In addition, loss of MMR is associated with an increased risk of relapse and lower disease-free survival. [69]  

Nonetheless, not all patients with a rise in BCR-ABL, or a detectable mutation, inevitably relapse. A reasonable first action is to repeat the test (eg, in a month). If the result is still increased (or is increasing), then mutation testing should be undertaken. The next response depends on how high the BCR-ABL level has risen. A rise from the lowest levels of detection (0.0001%) to a value even 50 times higher would still be well with the range of a MMR. However, a patient who begins at the MMR and rises above that level is certainly heading toward cytogenetic relapse, and here a bone marrow aspirate looking for cytogenetic recurrence would be warranted.  

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