Minimal Residual Disease or MRD is a common term used in CLL treatment and it can be tested from bone marrow and/or blood. It is often determined by an intricate blood test called flow cytometry. You can test up to 4 million events for more accuracy. It tests if cancer cells can be found during or post treatment. 10000, 100000 or 1 million cells can be tested. For 1 million you need another method of testing. It is a good source to test treatment success. As long as there are CLL cells in the blood there are also some in the marrow. So it does not always make sense to do a bone marrow biopsy. MRD has a different significance in each type of leukemia.

After reaching uMRD (the u stands for “undetectable”), which means in January 2018 I was without medication for 30 months. But then my doctor suspected that the Epstein Barr Virus caused some cancer cells to reoccur which might have hijacked my red blood cells too and my CLL disease returned. So I was advised to go on a twofold treatment Obinutuzumab and Venetoclax.

After Obinutuzumab was started I had to fight a bacterial infection Staphylococcus epidermidis which was treated with high dose antibiotics but I stayed on Obinutuzumab treatment anyway. Later Venetoclax was added and I achieved uMRD again in March 2021 after 6 months of treatment.

However this time they tested 100,000 cells and measured almost 4 million cells for more accuracy. 4 cells with the classical phenotype were found. So my doctors said I should stay on Venetoclax to get a deeper remission. I think this will not take long. But the question remains when you relapse you are supposed to take the drug for 2 years. The Murano study with another drug called Rituximab shows the trial results of this.

I wonder what benefit the Venetoclax would have after reaching a very deep remission. But there is the danger of developing multiple mutations in BCL2. So I am trying to evaluate my situation.

What effect does Venetoclax have on healthy blood cells if no cancer cells are detectable?

I stopped drugs in Jan 2018 because of uMRD but I also had kidney failure and a fatty liver stage 2. My organs are back to normal now. But this time it is a different situation. My iGs were low in 2018 and 2019 now igM is in normal range. My bcells are scarce only 0.12%..

I assume that the drug causes healthy cells to age faster. Will I get my b cell count up and what about erythrocytes despite taking the drug? My neutrophils weren’t impressed.

And there is another factor and this is cancer cell dormancy. These are malignant cells which sleep but can be reactivated. Does the drug work on them? I don’t think this is known.

What about the drug disrupting signaling between the microenvironment (viruses, bacteria, fungi and archae) and iGs? Does the drug make a difference? It may not and then is there a BTK to control the disease? But when no cancer cells are detectable? Too much BTK inhibitors can cause health issues, like joint pain, according this discussion with some top CLL specialists on Patient Power.

In order to keep the drug working it is best to stop in time and I think it is a good idea to monitor once you are off the drug too: bloodwork, iGs and MRD. For me MRD is a very reliable source especially when you relapse whatever the reason may be (f. e AIHA) Even small numbers can cause severe health issues. My cancer journey continues.

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edited by Lisa Wiest