Neens,
I have read some things on the internet about mutations and relapse. I am not sure how much of what I have read might be accurate - or that I understand it completely. I understand that mutations are the main reasons that newer drug treatments have been developed. Sprycel and Nilotinib are both much more effective against mutant types of CML than Gleevec.
The Philadelphia mutation is the basic chromosome mutation that is common in CML patients. Presence of this mutation (referred to as Ph+) is the basic confirmation of leukemia as a diagnosis. Ph+ happens when there is an incorrect copy made by swapping a piece of chromosome 9 for a piece of chromosome 22. This is sometimes called the bcr-abl gene. "Abl" is a gene named after the discoverer whose name was Abelson. Bcr refers to the "breakpoint cluster region" where the gene most often comes apart.
The gene mutations are not necessarily identical for each patient. Last I read there were more than 40 slightly different mutations identified. Gleevec is effective against the most common mutations, about half of the total. Sprycel and Nilotinib are effective against nearly all of the identified mutations. None of these is effective against one particular mutation labeled T315I. T315I is a relatively rare mutation - more typical of advanced stages of the disease.
Beating T315I is the next big step in treating CML. Lots of things have been found to kill it in the lab, but few (if any) are ready for human testing, yet. Still, with that much attention focused on it, perhaps beating T315I is not too far into the future.
Wow. Sprycel worked too well - that is amazing. I read once that penicillin was so effective against bubonic plague that it had to be given in small, sub-critical doses at first to avoid having so many of the killed plague cells accumulate that the patient's kidneys shut down. I'm a little surprised that your mother-in-law's treatment program swapped medication rather than decreasing the dose. On the other hand, perhaps changing to a different medication will help prevent proliferation of a wider variety of mutations - relieve the side effects.
Nilotinib was actually my first (and only) treatment protocol. I was given Hydrea for a few days before starting on Nilotinib. The hydrea was needed to kill off the excess (and malformed) white blood cells. I never took Gleevec, and was considered for a test protocol for Sprycel, but I did not match the eligibility requirements. I was eligible for the Nilotinib test, so I enrolled in that.
I am always asked about any side effects in my follow up visits. I can't actually report anything that I am sure is a side effect. My hair is turning grey and brittle, my skin is dry and sometimes flakey. However, those are also primary effects of being 53 years old, so who is to say if it is the disease, the drug, or just my age? I am regularly tested for the worst side effect - extended QT interval. This is a heart rhythm problem that some class of drugs (called CYP3A4 inhibitors) display that can cause the heart to get "out of synch" with itself. Nothing like that has ever shown on my EKGs, so far.
If you want to know more about the disease, treatments, tests, etc. I suggest contacting the Leukemia & Lymphoma Society or check out their web site. They have a lot of information and do a great job explaining it in terms easier to understand than articles that are often intended for doctors or researchers. The hospital your mother-in-law is being treated at probably can put you in touch with information resources, too.
Try not to worry. It sounds like your mother-in-law is in good hands: yours, her doctor's and God's.
Doug
