On my 12 month visit to my consultant two weeks ago, he said that my bone marrow aspirate results showed I am still in MMR, hooray, just waiting for result from Hammersmith to confirm levels. PCR test should come back soon too. This all seems good. But then he says they found that I have Philadelphia Negative Abnormal Cytogenetic Clones in my cells. I have a limited understanding but he said three of my chromosomes are now negative abnormal clones, what this means they don't know. How it will affect me they don't know. They want to do another bone marrow biopsy on the 10th July to see what they are doing. It did put me in a bit of a low. So much they don't know about our drugs. I am not sure if I am more scared of my Cml coming back or what damage Nilotonib is going to do to me long term. I don't want to sound ungrateful, I know this ride is full of ups and downs and mine so far have always come back up after a down were others have not been so lucky. However I am scared. There I said it. I have been so positive but now I am scared. So I'll let you know, what happens, what I find out, what my PCR score is when I get it.
Hope you are all well
Emma x
Please excuse any mistakes I am doing this at the school gate on my phone!
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Philadelphia Negative Abnormal Cytogenetic Clone
Dear Emma,
I understand why you are worried and 'scared' by the abnormal clones in Ph neg. cells. This phenomena has been documented over a long period since imatinb therapy was introduced and it is quite a rare event. the thinking over time is/was that it might be that these abnormal Ph neg cells were there all along but in very small numbers and more or less invisible because of the dominant Ph positive cell population. As imatinib (and other TKIs) effectively reduce the Ph+ population it becomes apparent in some rarer cases that there are also abnormalities in non CML (Ph neg) cells.
Those most frequently identified are Trisomy 8 and monosomy 7 but in CML it is still not clear what the significance or prognosis of these abnormalities might be for individual patients. There is ongoing research and study and from what I have read the consensus is-(including also from recent research by the team at Hammersmith) that patients identified with abnormalities in the Ph neg cells should be closely monitored by both PCR and cytogenetics- but that it is not at all clear if these clones are significant over the longer term. Particularly for those who have a major CyR or as in your case an major molecular response to TKI therapy.
Just to put this in some perspective, a friend and fellow CML patient has been treated with all 3 TKis over the last 8 years, she has no identifiable mutations but does have Trisomy 8. She has never got below 6% Ph+ over those years... in fact her PCRs and bone marrow results have always shown Ph+ at 6-8% with the presence of trisomy 8 in her Ph neg cells. She has remained doggedly consistent in her therapy and has been treated with nilotinib for around the last 3 years.
I have just heard from her that she has at last (after 8 years) achieved complete cytogenetic remission - and still has trysomy 8. So her case shows that this particular clone is probably not significant in CML. I know that other patients have seen this particular clone disappear over time.
In MDS (myelodysplastic syndrome) rather than CML, these kinds of abnormal clones are significant... you would need to know which clones HH have identified and consider their feedback with your doctor.
So.... sorry for the long winded post.... when your doctor says that they are not sure of the significance of Ph neg abnormalities in CML patients, he telling you the truth. You will need to be monitored particularly closely, but given that you have an MMR this is very reassuring and I am sure he/HH would agree. Try not be overly scared- although I know that is easy to say. I have no doubt you are in good hands.
Best..Sandy
"... the clinical significance of chromosomal evolution
in the Philadelphia (Ph)-negative clone during therapy is not fully
understood. We evaluated 94 CML patients in the chronic phase of CML
during treatment of the disease. Six of them had Ph-negative chromosome
abnormalities during treatment. Four patients with a single abnormality
and a good molecular response showed no obvious complications from
the chromosomal changes,...."
Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate.
O'Dwyer ME, Gatter KM, Loriaux M, Druker BJ, Olson SB, Magenis RE, Lawce H, Mauro MJ, Maziarz RT, Braziel RM.
Source: Division of Hematology and Ocology, Department of Medicine, Oregon Health & Science University, Portland 97201, USA.