I found this article today and it holds some very exciting avenues for research into a CML.
http://www.hindawi.com/journals/sci/2013/724360/
It's maybe a little heavy going for some tastes, but gives a thorough overview of the routes to targeting CML stem cells - with more research this is the (potential) path to a cure.
Chris
Thanks Chris,
this is a really good overview of where we've been, where we are and were we are (should be)going. The high cost of drugs is a really hot discussion point at the moment and especially so in the UK! I will put the link on the home page.....after I've read it ;o)
Hope you're MRD is low?
Sandy
Hi Chris,
I have managed a quick read of this excellent article and noticed a particularly interesting chapter see below. I know Tessa Holyoake and the team at Glasgow have been working on leukaemic stems cells for some years now- particularly in their apparent quiescent or sleeping format- but regarding autophagy and its protection of CML stem/progenitor cells, the CHOICES study is currently in phase ll.....see clinical trials page for the link. Interesting times as always.
Sandy
7.5. Autophagy
"The initiation of autophagy serves as a protection mechanism for CML stem cells against TKI-mediated apoptosis. The combination of imatinib and Chloroquine (CQ), an inhibitor of autophagy, eliminates CML stem cells in long-term culture assays [70, 71]. Inhibition of autophagy can also restore CML stem cells sensitivity to TKI.
Currently CHOICES (CHlOroquine and Imatinib Combination to Eliminate Stem cells), the first clinical trial to use autophagy inhibition in CML treatment, is in its phase II [68]."
Hi just wanted to add that I'm on the choices trial and seems to be going well. I am actually on the hydroxychiroquine 800mg and hoping when I finish my last cycle and final bone marrow results will be clearer. I am awaiting my most recent pcr but only had 2 positive cells on last test 3 months ago (0.009%). It's a very exciting time and I'm delighted to be involved in this study.
Hi Sandy,
i'm good, just bouncing along round the 3 - 3.5 log area. I seem to have a sustained plateau on Tasigna; I'm not particularly worried about it though. I reckon Sprycel might improve my response but Tasigna is doing well and i have a tolerable side effects profile with a reasonable QoL, so if it's not broken...
Best Wishes
Chris
Hi Lyndsey,
Thanks for your update, it is obvious that you are doing very well as your last PCR result shows. Can you let us know how you have got on with the new therapy? ... has the HCQ caused you any problems, extra side effects etc.
Best wishes,
Sandy
ChOICES
A Randomised phase II trial of Imatinib (IM) versus hydroxycholorquine (HCQ) and IM for patients with Chronic Myloid Leukaemia (CML) in Major Cytogenetic Response (MCyR) with residual disease detectable by quantitative polymerase chain reaction (Q-PCR).
UK Multi centre: currently recruiting in Scotland, England and N.Ireland:
Chief Investigator: Prof Tessa Holyoake
Research Summary
This is a randomised phase 2 trial with a safety run-in, designed to study the safety and efficacy of HCQ in combination with Imatinib. CML CP patients who are in MCyR after >1 and <3 years of Imatinib treatment and tolerating Imatinib well will be randomised between Imatinib alone and Imatinib and HCQ 800mg/day. Imatinib will be given at the patient’s current stable dose. Treatment will be given continuously. Treatment with IM + HCQ will be continued for 12 cycles to further study tolerance and to study the efficacy of the combination to reduce or eliminate BCR/ABL+ cells. 33 patients will be randomised to each treatment to a total of 66 patients, recruited in 3 centres. Time required for accrual of all patients is anticipated to be 24 months. Time on study IM + HCQ treatment for each patient is 12 months. Follow-up assessments for each patient continue to 24 months. All patients will continue on their daily dose of Imatinib treatment that they were receiving prior to entry in the trial.
http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=8492
I have tolerated it very well. Initially after 3 weeks on drug I got constant diarrhoea the drug was stopped until settled. Sample etc taken to rule out infection then drug restarted at same dosage. I was offered a reduced dosage but wanted to get back on to the drugs. Started again at 800mgs and prescribed loperamide when required again after 3 weeks diarrhoea kicked in again but just took loperamide for couple of days and all settled. Now every 4-6 weeks I get a bout of diarrhoea for a day or 2 but its not bad and dont bother with the loperamide. So other than the diarrhoea I have had no other side effects at all.
Thanks sandy
I am on the HCQ 800mg along side the imatinib 400mg. Next bone marrow oct. Prof Holyoake is very good at explaining things and you can see her passion when she speaks. She is hopeful I go undectectable within next 6 months. I feel very lucky to be on this trial and also to get on the HCQ arm. I will update as soon as I know more although could be a while. They have worked out a formula to compare both arms to see if this would be my normal response without the HCQ or not.
