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Test to Predict TFR Success?

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Did anybody else read this article? I stumbled across it, but found it a little confusing. It says, "A leukemia test can help identify patients who are strong candidates for lifelong treatment free remission (TFR)—meaning they are effectively cured of the disease. Dr. Ilaria Pagani is first author on the research paper which was published today in the journal Blood. She says the breakthrough in chronic myeloid leukemia (CML) research is the cumulation of six years of investigation."

The article goes on to say: "Until now, the assumption was that every blood cell that contained BCR::ABL1 was evidence of persistent disease that could lead to relapse," Dr. Pagani said. "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."

I was curious if anyone's oncologist had mentioned this study and what exactly it might mean.

Thanks.

https://medicalxpress.com/news/2023-09-common-leukemia.amp

I went to the original paper published in "Blood" journal:
https://ashpublications.org/blood/article-abstract/142/25/2192/497613/Li...

The key observation is this statement: "The median BCR::ABL1 DNA level was higher in granulocytes and T cells, but not in other lineages, in patients who relapsed."

We know that cancer, in general, is a failure of our immune system to detect and destroy aberrant cells. T cells are the "natural killer" cells which have this primary role. When bcr:abl is present (according to the article linked above) in these cells, they tend not to perform as well in their function and may very well explain relapse.

This makes a lot of sense since CML is a hematopoietic stem cell disease and as the cells divide into myeloid and lymphoid cell lineages, having normal T-cells (lymphoid line) will give the patient a better chance at maintaining TFR.

CML cells are likely created all of the time by a chromosome 9 and chromosome 22 translocation given how these two chromosomes are packed in the nucleus (right at the break-point). This translocation likely happens naturally and the body takes care of it as it does with other DNA breaks. But a few thousand people per year develop disease resulting from this translocation because their immune system fails to stop it. After taking TKI's and achieving Remission, stopping therapy still requires the immune system to take over because this translocation is still going to happen. Having bcr-abl present in T-cells (according to the paper linked above) apparently limits the ability of these T cells to do their job. It is an interesting observation.

Scuba your explanation helps to understand the problem at hand. I actually read this article a few months back. I emailed Pagani’s team in Australia. I explained that I plan TFR in the future and could I participate in any study they plan to conduct. They are looking for funding right now and since I am in the US I may not be a good candidate for a study in Australia. In any event it’s important work and may help us know better how to attempt either TFR or drastic dose reduction.

Thank you Scuba, for taking the time to write this helpful explanatory reply.
You write from a position of knowledge, and you have the gift of being able to disentangle and simplify complex concepts.
All the best with your TFR
pigeon