Leukaemia test finds candidates for treatment-free remission
A new breakthrough in chronic myeloid leukaemia (CML) testing can help identify patients who are strong candidates for lifelong treatment-free remission (TFR) — meaning they would be effectively cured of the disease.
CML causes the bone marrow to produce too many white blood cells, which can adversely affect normal blood cell production. In time, a shortage of blood cells can present as infection, anaemia or unexplained bleeding or bruising. People with CML might also experience discomfort beneath their ribs on the left-hand side of their body due to an enlarged spleen.
In the early 1990s, the disease had an average survival rate of less than five years — and while the development of tyrosine kinases inhibitors (TKIs) as a treatment dramatically increased survival rates, for many patients these caused debilitating side effects while losing efficacy over time. Ensuing research saw next-generation TKIs deliver longer-lasting impact and fewer side effects, but still patients faced lifelong management of the disease.
By 2006, researchers had shown it was possible for patients who had excellent responses to treatment to simply stop taking their medication and remain in remission. For them, TFR was effectively a cure — but there was no way to tell who would be successful and who would relapse. The new findings, published in the journal Blood, now challenge the assumption that response to TKI therapy is best assessed by measuring the presence of the leukaemia-defining BCR::ABL1 fusion gene in the blood of a CML patient.
“The assumption was that every blood cell that contained BCR::ABL1 was evidence of persistent disease that could lead to relapse,” said Dr Ilaria Pagani, from the South Australian Health and Medical Research Institute (SAHMRI).
“What we have now shown is that the chances of relapse depend greatly on which type of cell the disease is detected in — if it’s in what are known as myeloid cells, then the chances of TFR are sadly pretty low, but if it’s in lymphocytes, then that has limited impact on relapse likelihood.”
The result of the research is a blood test that can accurately determine the best course of treatment, giving TFR candidates greater confidence before ceasing treatment. According to Pagani, “This new lineage-specific BCR::ABL1 test can now be used to determine who can safely stop therapy, who should continue therapy for a longer period and who needs a different therapy before they could be considered for TFR.
“Sadly, not everyone will be a candidate for TFR with current approaches, but for those whose chance of relapse is high, we will now have greater information with which to design new therapeutic approaches that can lead to TFR even for these more challenging patients.
“Ultimately, our aim is to design a curative approach for all CML patients so that TFR becomes the mainstream pathway, rather than a pathway followed by a lucky minority.”
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