Introduction

Chronic Myeloid Leukemia (CML) has transformed from a life-threatening leukemia into a manageable chronic condition, thanks to targeted treatments. Today, many patients not only achieve long-term control of CML but may even reach treatment-free remission (TFR) – staying in remission after stopping therapy. Achieving this hopeful outcome hinges on one critical factor: accurate and early molecular monitoring. Rethix Molecular Diagnostic Lab’s BCR-ABL1 (IS) by Real-time PCR test is a state-of-the-art tool for tracking CML at the deepest levels. In this article, we explain the clinical importance of BCR-ABL1 testing, summarize recent research (including the 2025 DEMONSTRATE study), and highlight how Rethix’s cutting-edge diagnostics are empowering both patients and healthcare providers.

Understanding CML and the BCR-ABL1 Gene

CML is a blood cancer driven by a specific genetic change: the Philadelphia chromosome, which creates the BCR-ABL1 fusion gene. This gene produces an abnormal enzyme (tyrosine kinase) that causes uncontrolled white blood cell growth. Modern drugs known as tyrosine kinase inhibitors (TKIs) target this BCR-ABL1 enzyme, effectively suppressing the leukemia. Measuring the level of BCR-ABL1 in a patient’s blood is therefore like checking the “engine light” of CML – it shows how much disease is left. In fact, CML is essentially defined by the presence of BCR-ABL1. When patients respond to treatment, the amount of BCR-ABL1 drops dramatically. Doctors monitor this drop using molecular tests to see if patients are reaching certain milestones in response. Over time, many patients achieve a deep molecular response (DMR), meaning the BCR-ABL1 levels have become extremely low (for example, a 4-log reduction, called MR4.0, which is 0.01% on the International Scale). Achieving a deep response is wonderful news – it indicates the leukemia is under excellent control. But how do we detect such low levels reliably? This is where highly sensitive testing comes in.

Why Monitoring BCR-ABL1 Levels is Crucial

Monitoring CML isn’t just a routine formality; it’s a lifesaving practice. Regular BCR-ABL1 PCR testing allows doctors to track how well the treatment is working and adjust therapy if needed. In fact, measuring BCR-ABL1 over time is a “critically important part of treatment for people with CML,” according to the Leukemia & Lymphoma Society. If the BCR-ABL1 levels aren’t dropping as expected, doctors might change the TKI drug or dose to get a better response. Conversely, if levels hit major milestones (like ≤0.1% at 12 months, known as a major molecular response, MR3.0), it predicts a very low risk of disease progression and a high likelihood of eventually achieving a deep response (MR4.0). Each milestone is typically assessed on the International Scale (IS), a standardized scale for BCR-ABL1 results that allows comparisons across labs worldwide. Rethix’s test reports results on the IS, ensuring that your results align with global CML guidelines and benchmarks. In short, diligent monitoring of BCR-ABL1 levels helps your care team make timely decisions – whether that means intensifying treatment or, if you’re doing extremely well, preparing for a possible treatment break. Accurate monitoring is especially important when the disease level is very low; detecting tiny amounts of residual leukemia (called minimal residual disease, MRD) can be challenging, but it’s crucial for identifying patients who might achieve TFR.

Advances in Molecular Monitoring: From RT-qPCR to Digital PCR

For years, the gold standard for CML monitoring has been real-time quantitative PCR (RT-qPCR), which is the method Rethix’s BCR-ABL1 test uses. RT-qPCR is highly effective and sensitive, able to detect CML down to roughly a few cells in ten thousand. However, at extremely low disease levels (far below 0.01% BCR-ABL1), this method can approach its technical limits of precision. Enter digital PCR (dPCR) – a next-generation technique that takes sensitivity to an even higher level. Instead of amplifying DNA/RNA in one tube and measuring the overall signal, digital PCR splits the sample into thousands of micro-reactions (droplets or wells), so that individual BCR-ABL1 molecules can be counted directly. This approach can improve accuracy and detection when there are only trace amounts of leukemia left.

Just how much difference can a more sensitive test make? Recent findings from the DEMONSTRATE study (published in Annals of Hematology, 2025) offer an eye-opening answer. In this study, 79 CML patients in deep remission were monitored in parallel with traditional RT-qPCR and with digital PCR. The results showed that digital PCR was able to detect the achievement of deep molecular response earlier than RT-qPCR in a majority of patients. In 69 out of 79 patients (87%), dPCR either anticipated (caught it first) or at least coincided with the DMR that standard PCR eventually detected. In practical terms, this meant patients reached the “finish line” of deep remission faster on the dPCR readout. On average, among the patients where dPCR was ahead, the deep molecular response was detected months sooner by digital PCR than by conventional methods. (In over half of the participants, the median time to DMR was 10 months via dPCR versus 18 months via RT-qPCR – roughly an 8-month head start.) These findings are significant because they suggest some patients actually achieve a stable remission earlier than we would know with standard testing. The researchers noted that digital PCR could help with the early selection of patients who might be ready to attempt treatment discontinuation before one would normally consider it with regular PCR monitoring. In short, dPCR’s extra sensitivity provides a clearer picture of when CML truly hits an ultra-low level.

It’s worth noting that this greater sensitivity didn’t depend on the type of BCR-ABL1 transcript or the TKI drug used – digital PCR had an across-the-board ability to measure residual disease more finely. These advances don’t mean we abandon tried-and-true RT-qPCR (which remains the standard in guidelines), but they point to a future where labs like Rethix might incorporate digital PCR to further improve patient care. Rethix is closely following these developments. By validating emerging techniques and participating in quality networks, we ensure that if and when new technology offers real clinical benefit, we’ll be ready to bring it into practice.

The Road to Treatment-Free Remission (TFR) – Why Early Detection Matters

For many CML patients, an exciting question arises after years of successful therapy: “Could I stop taking my medication?” TFR, or treatment-free remission, is the possibility of discontinuing TKI therapy and staying in remission without it. This is a fairly new and hopeful goal in CML care – one that was unheard of before TKIs existed. Clinical trials over the past decade have shown that TFR is achievable for a significant subset of patients who meet certain criteria. The typical criteria to even consider a TKI stoppage are having a deep molecular response (such as MR4.0 or MR4.5, which is a 4 to 4.5 log reduction in BCR-ABL1) and maintaining that response for at least 2 years, along with a minimum number of years on therapy and other factors. In fact, expert panels and studies indicate that ≥2 years of sustained MR4.0 is associated with a high likelihood of successful TFR. Patients who don’t meet these deep response benchmarks are not advised to stop therapy because the risk of relapse is too high. Even among those who do meet the criteria, not everyone will maintain remission off drug – roughly 40%–60% of such patients can expect to remain in remission after stopping TKIs (the others will need to restart therapy if their BCR-ABL1 levels rise). This is why careful patient selection for TFR is so important. We want to identify those who have the best shot at staying in long-term remission without medication, and equally, to avoid stopping therapy in someone who is likely to relapse.

So how do we improve our ability to predict TFR success? This is where the quality of molecular monitoring makes a difference. The deeper and more confidently we can measure residual disease, the more informed our TFR decisions become. For example, the DEMONSTRATE study mentioned earlier found that a preliminary dPCR threshold of <0.468 BCR-ABL1 copies/µL in the blood was associated with a better probability of maintaining remission off treatment. In another recent study from a Dutch consortium, researchers identified an ultra-low BCR-ABL1 cutoff on the International Scale – 0.0023% IS – as a predictive marker for TFR success. Patients below this level before stopping had higher chances of staying in remission. These numbers might sound very technical, but for patients they translate to peace of mind: if your leukemia burden is that low, you and your doctor can be more confident about trying a therapy break. On the other hand, if any measurable disease above those thresholds is present, it suggests caution.

The bottom line is clear: early and accurate detection of deep molecular responses is directly linked to better TFR outcomes. If we can find out sooner that a patient has truly minimal residual disease, we might be able to safely pause treatment earlier, sparing them additional months of drug therapy and side effects. And if we can pinpoint the smallest traces of BCR-ABL1, we can more definitively say whether it’s safe to remain off therapy or if a recurrence is starting. This is why Rethix’s focus on high-sensitivity, high-quality BCR-ABL1 testing is so impactful for patient care.

Rethix’s Commitment to Cutting-Edge CML Care

As a world-class molecular diagnostics laboratory, Rethix is dedicated to delivering testing that meets the highest standards of accuracy, speed, and clinical relevance. Our BCR-ABL1 (IS) by Real-time PCR test for CML patients is performed with meticulous quality controls and alignment to international reference standards. Every result we report is on the International Scale, which means your doctor can directly compare it with global treatment guidelines and research findings. For example, if we report a BCR-ABL1 level of 0.01% IS, that corresponds to an MR4.0 – a key benchmark for deep remission and TFR consideration. By using the IS and participating in international quality networks (such as lab standardization efforts), Rethix ensures that our results are reliable and actionable.

Beyond our current services, Rethix continually looks ahead to emerging technologies. We’re excited by innovations like digital PCR, and while we provide the gold-standard RT-qPCR today, we are actively evaluating next-generation methods to further enhance sensitivity. Our team is involved in ongoing education and research review – for instance, staying up-to-date with studies like the 2025 Annals of Hematology publication on digital PCR in CML. When the evidence shows a clear benefit to patients and clinicians, you can trust that Rethix will be ready to incorporate those advancements. Our mission is to equip hematologists, oncologists, and patients with the best possible insights for decision-making. Whether it’s determining if a therapy is effective early on, or assessing if a patient might be ready to attempt treatment-free remission, Rethix stands by our partners every step of the way with accurate data.

Conclusion: CML treatment has come a long way – and with accurate monitoring, patients can dream big. By offering sensitive BCR-ABL1 testing and embracing scientific progress, Rethix Molecular Diagnostic Lab plays a key role in turning the possibility of TFR into a reality. When it comes to CML, we believe that knowledge is power – and our advanced molecular tests provide exactly that. With Rethix, you’re not just getting a lab result; you’re getting a compass guiding you toward a future of health and hope. 🩺🌟

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