Jeff,
I understand that various CML clinicians are seeing more serious long term side effects with
2G TKIs- particularly the cardiac effects cited in the articles you have provided links for. I do agree that it might be a worry - but with little option for those who are either resistant to or intolerant of imatinib, this is a risk that one has to take a view on. Of course dasatinib is available (which carries other risks) through application to the Cancer Drug Fund, as is bosutinib through clinical trial or compassionate use so there are alternative therapies.
No drug/therapy is without side effects, and will be a problem for those with pre-existing medical problems such as diabetes or heart disease.
I suppose the message must be that 'disease' is a complex issue and often with multiple contributory factors. In fact current research has identified that statins often used to reduce cholesterol levels, might not be the answer.
Of course we as individuals need to keep ourselves informed about the risks associated with any therapy we might be required to take. Personally I needed to decide on whether it was worth me taking the risk of SCT as opposed to taking the risk not to have one. Given that for me at the time there was no alternative I chose to take the risk that I might suffer serious long term effects from the chemotherapy drugs used in the 'induction' process. Luckily I have not suffered any ongoing effects- at least up to now.
I am sure you will have been talking with your doctor about the serious effects you are suffering from nilotinib. I am not sure if dasatinib is an appropriate TKI for you, or if your doctor would prescribe bosutinib (currently in NICE appraisal). However, I do know of another patient who has tried several TKIs and suffered serious cardiovascular effects requiring surgery etc. from nilotinib, but since changing his treatment to bosutinib (at quite a low dose) he has responded very well clinically speaking. The bonus is his quality of life has improved significantly with a reduction in all kinds of side effects.
Sandy
I have just read an interesting article about Vit D levels which I have copied here....
Friday, June 21, 2013. The annual conference of the European Society of Human Genetics was the site of a presentation on June 11 by Dr Karani S. Vimaleswaran of the finding of a causative role for vitamin D in the development of hypertension. "We knew from earlier observational studies that low 25(OH)D concentrations were likely to be associated with increases in blood pressure and hypertension, but correlation is not causality", remarked Dr Vimaleswaran, of University College London.
Dr. Vimaleswaran reported the findings of the D-CarDia collaboration that included over 35 studies involving up to 108,173 participants which associated higher serum 25-hydroxyvitamin D levels with lower blood pressure. To validate causation, a team of researchers examined the association of four vitamin D-related genetic variants known as single nucleotide polymorphisms (SNPs) with 25-hyroxyvitamin D levels and with hypertension.
An association with serum 25-hydroxyvitamin D levels was confirmed for all SNPs. The researchers uncovered an association between one SNP (CYP2R1) and diastolic blood pressure and hypertension. Following further analysis, they concluded that reduced vitamin D levels have a modest causal association with hypertension, with a 0.24 mmHg decrease in diastolic blood pressure and a 7% decrease in the risk of hypertension associated with each 10% increase in serum 25-hydroxyvitamin D. "Even with the likely presence of unobserved confounding factors, the approach we followed, known as Mendelian randomization, allows us to draw conclusions about causality because the genetic influence on disease is not affected by confounding," Dr Vimaleswaran stated. "To put it in simple terms, by using this approach we can determine the cause and effect and be pretty sure that we've come to the right conclusion on the subject."
"Our study strongly suggests that some cases of cardiovascular disease could be prevented through vitamin D supplements or food fortification," he noted. "Our new data provide further support for the important non-skeletal effects of vitamin D. We now intend to continue this work by examining the causal relationship between vitamin D status and other cardiovascular disease-related outcomes such as lipid-related phenotypes, for example, cholesterol, inflammatory markers such as C-reactive protein, and type 2 diabetes and markers of glucose metabolism. We believe that we still have a lot to find out about the effect of vitamin D deficiency on health, and we now know that we have the tools to do so."