Re: Queries on CML prognosis

December 14, 2009

>

> I have queries regarding prognosis of CML patients:

>

> 1. What are the signs and symptoms of a patient developing mutation

(especially T315I)? Is it something that happens gradually?

>

> 2. What are the possible causes? Who are likely to develop mutations?

>

> 3. If a patient has been responding well to Glivec(i.e. PCRU or MMR), what are

the chances of becoming resistant to it or developing mutation? Would you be

aware of any instance where a patient has been responding well with Glivec and

suddenly became resistant?

_________________________

Hi ,

Some people think that a mutation like T315I is actually present at diagnosis in

a small % of the person's cells. When a drug like Gleevec kills off the 'normal'

cml cells, then mainly those with the mutation are left, and they do not respond

to Gleevec. This person would initially have a good response to the drug (pcr or

some other test indicating response) and then it would look like they relapsed

and the numbers would start going back up (either a % or a pcr number) because

most of their cml cells would have the mutation and not respond to the drug. So,

this could happen even if the person were CCR or MMR, but it would usually

happen relatively soon, like in the first year or so from diagnosis.

Other people may develop the mutation and just like the original Ph+ cell, the

mutation can be random. It is also felt that if someone is one too low a dose

(non-therapeutic) of some drug, that could lead to a mutation, in which the cml

cell adapts and becomes resistant. This might also happen if someone takes

breaks from drugs.

The longer period of time that your cml has been stable or improving, the less

likely you are to develop any resistance...esp. if you have a good response to

your drug.

The primary sign that you might have a mutation is that your response is

relapsing and your test scores are not as good over a series of 3 tests. If your

% or pcr is going up over 3 tests, then they need to determine why.

Hope this helps, but, yes, in the first year or so, someone could go from a good

response to a relapse for the reason explained above.

C.

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