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PubMed This is a summary of 12 peer-reviewed journal articles Updated
Hematology

What Do BCR-ABL1 Fluctuations Mean During CML Treatment?

At a Glance

A small change in BCR-ABL1 during CML treatment does not automatically mean the TKI has stopped working. Doctors compare results over time, preferably from the same laboratory, and check response milestones, medication adherence, interactions, and significant upward trends.

In this answer

2 sections

01

Why Do BCR-ABL1 Levels Fluctuate?

02

How Doctors Assess a Loss of Response

If your BCR-ABL1 number went up slightly on your last blood test, it is natural to feel anxious and worry that your chronic myeloid leukemia (CML) treatment has stopped working. However, a single small increase does not automatically mean your medication has failed [1][2]. Minor fluctuations in BCR-ABL1 levels are common and often do not require an immediate change in your treatment plan [3].

Before making any major decisions, your care team will consider your entire treatment history, including how long you have been on treatment and whether the change crosses a significant clinical milestone [4][5].

What You Should Do Now

  • Keep taking your medication: Do not stop, skip, or change the dose of your tyrosine kinase inhibitor (TKI) without speaking to your doctor.
  • Contact your hematologist: Let them know about your concern and ask them to help you interpret the specific numbers.
  • List your medications: Write down any new prescription drugs, over-the-counter medicines, or herbal supplements you have started recently so you can discuss them with your care team.

Why Do BCR-ABL1 Levels Fluctuate?

When you take a targeted therapy (called a tyrosine kinase inhibitor, or TKI) for CML, your doctor monitors your response using a highly sensitive blood test called a quantitative PCR (or RT-qPCR) [5][6]. This test does not directly count leukemia cells. Instead, it measures the amount of BCR-ABL1 genetic material (RNA transcripts) in your blood compared to a normal control gene, usually reporting the result as a percentage on the International Scale (IS) [7].

Because the test is so sensitive, minor variations are expected for a few reasons:

  • Testing Sensitivity and Lab Differences: Different laboratories use slightly different testing equipment and methods [7]. Even when tests are standardized on the International Scale, slight differences in how the test is run or the test’s detection limits can cause your numbers to bounce up or down slightly [8][9].
  • Biological Variability: The amount of genetic material in your blood can naturally fluctuate from day to day, especially when the levels are already very low.

Because of these factors, it is highly recommended to have your PCR tests done at the same laboratory every time to ensure the results are as comparable as possible.

How Doctors Assess a Loss of Response

Hematologists look for a true “loss of response”—which means your numbers have crossed specific, established thresholds or continue to rise significantly. For example, a Major Molecular Response (MMR) is generally defined as a BCR-ABL1 level of 0.1% or lower on the International Scale. If your number was previously below 0.1% and rises above it, your doctor will evaluate this more closely than a minor fluctuation that stays below the 0.1% mark.

If a test shows a concerning increase, your doctor will perform a therapeutic reassessment [4]. This may involve:

  • Repeat Testing: Your doctor will determine the best timeline for another PCR test to see if the upward trend continues. A concerning rise may prompt an earlier test rather than waiting for your next routine appointment.
  • Reviewing Medication Adherence and Interactions: Missing doses can reduce the effectiveness of your treatment. Additionally, some TKIs can interact with other medicines (like certain acid-reducing drugs) or supplements (like St. John’s wort), which can affect how well your TKI works. Always review everything you take with your pharmacist or hematologist.
  • Checking Other Lab Results: Your doctor will check your complete blood count (CBC) to assess your overall blood health, though a normal CBC does not rule out a molecular change.

Mutation Testing

If you experience a significant loss of response or a clinically important rise, your doctor may order a BCR-ABL1 mutation test [10][11]. This test checks if the leukemia cells have developed a genetic change that makes them resistant to your current TKI [12]. Finding a mutation is just one possible reason for a rising number. If a mutation is found, your care team will use that information—along with your medical history and potential side effects—to decide if switching to a different TKI is the best path forward.

Common questions in this guide

Does a small rise in BCR-ABL1 mean my CML treatment has failed?
Not necessarily. A single small increase can result from normal biological variation or differences between tests, and your hematologist will look at the overall trend, your treatment history, and whether you crossed an important response milestone.
Why can my BCR-ABL1 result change from one test to the next?
The PCR test is very sensitive, so small changes may reflect day-to-day biological variation, the amount of genetic material in the blood sample, or differences in laboratory methods. Using the same laboratory and testing method whenever possible makes results easier to compare.
What does a BCR-ABL1 result above 0.1% mean?
A BCR-ABL1 level of 0.1% or lower on the International Scale generally represents a Major Molecular Response, or MMR. If a result rises from below 0.1% to above it, your doctor will evaluate it more closely, but one result alone does not determine whether treatment has failed.
What should I do if my BCR-ABL1 number goes up?
Keep taking your TKI exactly as prescribed and do not stop or change the dose on your own. Contact your hematologist, share the exact results, and mention missed doses, new medicines, over-the-counter products, or herbal supplements.
Can missed doses or other medicines affect BCR-ABL1 levels?
Yes. Missed TKI doses and interactions with some medicines, including certain acid-reducing drugs, or supplements such as St. John’s wort can reduce how well treatment works. Review everything you take with your hematologist or pharmacist before making changes.
When would my doctor order BCR-ABL1 mutation testing?
Mutation testing may be considered after a significant loss of response or a clinically important rise in BCR-ABL1. It looks for genetic changes that can make leukemia cells resistant to the current TKI, and the result is considered with your treatment history and possible side effects when deciding next steps.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What were my previous and current BCR-ABL1 percentage values on the International Scale?
  2. 2.Am I still in a Major Molecular Response (MMR) or another response category?
  3. 3.Were my last few PCR tests processed at the same laboratory using the same assay?
  4. 4.Does this increase mean I have lost a molecular milestone, or is it within the normal range of fluctuation?
  5. 5.What result or trend would lead to an earlier repeat test, mutation analysis, or a treatment review?

Questions For You

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Related questions

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References

References (12)
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    Chronic Myeloid Leukemia Monitoring after Imatinib Failure: Still More Questions than Answers.

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    Acta haematologica 2015; (134(4)):246-7 doi:10.1159/000433413.

    PMID: 26159353
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    Practical Laboratory Tools for Monitoring of BCR-ABL1 Transcripts and Tyrosine Kinase (TK) Domain Mutations in Chronic Myeloid Leukemia Patients Undergoing TK Inhibitor Therapy: A Single-Center Experience in Thailand.

    Limsuwanachot N, Kongruang A, Rerkamnuaychoke B, et al.

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    Monitoring of Minimal Residual Disease (MRD) in Chronic Myeloid Leukemia: Recent Advances.

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    Cancer management and research 2020; (12()):3175-3189 doi:10.2147/CMAR.S232752.

    PMID: 32440215
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    How I Evaluate and Treat Resistance and Relapse in CML.

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    Blood 2025; doi:10.1182/blood.2024026511.

    PMID: 40373278
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    Declaration of Bcr-Abl1 independence.

    Zhao H, Deininger MW

    Leukemia 2020; (34(11)):2827-2836 doi:10.1038/s41375-020-01037-9.

    PMID: 32908250
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    Molecular monitoring in chronic myeloid leukemia-how low can you go?

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    One Target, Different Results: The Clinical Impact of Diagnostic Kit Choice in BCR::ABL1 Testing for Chronic Myeloid Leukemia.

    Suver Stević M, Periša V, Vujičić K, et al.

    Diagnostics (Basel, Switzerland) 2026; (16(14)) doi:10.3390/diagnostics16142216.

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    Analytical Validation of a Highly Sensitive, Multiplexed Chronic Myeloid Leukemia Monitoring System Targeting BCR-ABL1 RNA.

    Brown JT, Beldorth IJ, Laosinchai-Wolf W, et al.

    The Journal of molecular diagnostics : JMD 2019; (21(4)):718-733 doi:10.1016/j.jmoldx.2019.03.002.

    PMID: 31026597
  9. 9

    Characterization of a novel variant BCR-ABL1 fusion transcript in a patient with chronic myeloid leukemia: Implications for molecular monitoring.

    Crampe M, Haslam K, Kelly J, et al.

    Hematology/oncology and stem cell therapy 2017; (10(2)):85-88 doi:10.1016/j.hemonc.2016.02.002.

    PMID: 27013275
  10. 10

    BCR::ABL1 kinase domain mutations and their predictive value for treatment outcomes in patients with chronic myeloid leukemia treated with first-line imatinib in a low-income setting: Experience from Côte d'Ivoire.

    Koffi KG, Bognini SA, Silué DA, et al.

    Leukemia research reports 2025; (24()):100544 doi:10.1016/j.lrr.2025.100544.

    PMID: 41467077
  11. 11

    Optimal Time Points for BCR-ABL1 Tyrosine Kinase Domain Mutation Analysis on the Basis of European LeukemiaNet Recommendations in Chronic Myeloid Leukemia.

    Yoo HL, Kim SH, Choi SY, et al.

    Clinical lymphoma, myeloma & leukemia 2019; (19(7)):406-412.e1 doi:10.1016/j.clml.2019.02.003.

    PMID: 30928650
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    Beyond BCR::ABL1-The Role of Genomic Analyses in the Management of CML.

    Branford S, Fernandes A, Shahrin N, et al.

    Journal of the National Comprehensive Cancer Network : JNCCN 2024; (22(1)).

    PMID: 38394774

This page explains BCR-ABL1 test fluctuations during CML treatment for informational purposes only and does not constitute medical advice. Discuss your results and medication with your hematologist before making changes.

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