Advanced Member
Posted 28 January 2016 - 12:37 PM
http://www.healio.co...tinue-dasatinib
Significance of this report is that discontinuation was attempted after 12 months of DMR status instead of the customary 24 months. The results were the same - essentially 50% of the patients remained in DMR (deep molecular response or PCRU) and 50% relapsed. Of the relapsed patients - none progressed, all regained DMR after re-start.
Diagnosed 11 May 2011 (100% FiSH, 155% PCR)
with b2a2 BCR-ABL fusion transcript coding for the 210kDa BCR-ABL protein
Sprycel: 20 mg per day - taken at lights out with Quercetin and/or Magnesium Taurate
6-8 grams Curcumin C3 complex.
2015 PCR: < 0.01% (M.D. Anderson scale)
2016 PCR: < 0.01% (M.D. Anderson scale)
March 2017 PCR: 0.01% (M.D. Anderson scale)
June 2017 PCR: "undetected"
September 2017 PCR: "undetected"
Advanced Member
Posted 28 January 2016 - 01:26 PM
Wow, interesting, Scuba. Should we all be getting our NK and T cell counts checked, I wonder? Do you know how those are tested?
Dx July 2009 on routine physical. WBC 94. Started Gleevec 400 mg Sept 2009. MMR at 2yrs. Side effects (malaise, depression/anxiety, fatigue, nausea, periorbital edema) never improved. Kidney issues developed because of Gleevec. Switched to Sprycel 70 mg in Aug 2011. Above side effects disappeared or improved. Have been MR3.5 - 4.5 ever since. Two untreated pleural effusions followed by one treated by stopping Sprycel Jan 2017. After 9 weeks, PCR showed loss of MMR; re-started Sprycel at 50 mg and in 3 months was back to <0.01% IS. Pleural effusion returned within a couple of months, same as before (moderate, left side only). Stopped Sprycel 50 mg for 12 weeks; pleural effusion resolved. At about a monthoff the drug, PCR was 0.03; at 11 weeks it was 2.06 - lost CCyR? Have returned to 50 mg Sprycel for 3 weeks, intending to reduce to 20 mg going forward.
Advanced Member
Posted 28 January 2016 - 02:50 PM
Guessing it will be mainly research hospitals that will be willing to try this. Still, it's good news.
DX 1/14; Sprycel 100 Mg, liver toxicity; Sprycel 80 Mg; down to 50 Mg for 5 months. Numbers going up. Back to 80 Mg 10/16 (with 50s slipped in to use up) BCR/ABL: .0047 12/15; .0302 4/16; .0528 8/16; .084 10/16; .045, 1/17 back up on 80 mg Sprycel; .006, 3/17; .016, 7/17; Shingles 8/17
Advanced Member
Posted 28 January 2016 - 03:04 PM
Select patients with CML may safely discontinue dasatinib http://goo.gl/4r2D6G
For the benefit of yourself and others please add your CML history into your Signature
02/2010 Gleevec 400mg
2011 Two weakly positives, PCRU, weakly positive
2012 PCRU, PCRU, PCRU, PCRU
2013 PCRU, PCRU, PCRU, weakly positive
2014 PCRU, PCRU, PCRU, PCRU (12/07 began dose reduction w/each continuing PCRU)
2015 300, 250, 200, 150
2016 100, 50/100, 100, 10/17 TFR
2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000
2018 01/16 TFR 0.0004 ... next quarterly PCR 04/17
At the earliest opportunity, and whenever possible, lower your TKI dosage; TKIs are toxic drugs and the less we take longterm the better off we are going to be ... this is especially true for older adults.
In hindsight I should have started my dosage reduction two years earlier; it might have helped minimize some of the longterm cumulative toxic effects of TKIs that I am beset with.
longterm side-effects Peripheral Artery Disease - legs (it's a bitch); continuing shoulder problems, right elbow inflammation. GFR and creatinine vastly improved after stopping Gleevec.
Cumulative Gleevec dosage estimated at 830 grams
Taking Gleevec 400mg an hour after my largest meal of the day helped eliminate the nausea that Gleevec is notorious for.
Trey's CML Blog - Stopping - The Odds - Stop Studies - Discussion Forum Cessation Study
Big PhRMA - Medicare Status - Social Security Status - Deficit/Debt
Advanced Member
Posted 28 January 2016 - 03:30 PM
NK and T cell interaction is a complex and very interesting subject. I have many references that I intend to post here in a sorted out fashion when I find the time.
In brief:
Our bodies require NK - and certain T-cells to activate in order to fight "foreign" and "domestic" disease. But our bodies also require NK and certain T-cells to de-activate (or down regulate) when the crisis has past. Otherwise If NK and certain T-cells stay active following disease inflammation and other bad things can happen.
When our immune system fails to "shut down" when told to - we develop an autoimmune disease. Rheumatoid arthritis is but one example. There are many others. Conversely, when our immune system fails to activate - we fall to disease and cancer. It is a delicate balance to keep our bodies ready for attack, but also under control after the attack is defeated.
All normal tissue cells of our bodies produce cytokines (proteins) that activate certain T-cells to keep the immune system in check. Think of it as a "stand down" order so that the paroling NK-cells and other kinds of T-cells don't attack healthy tissue. Unfortunately, cancer cells, which are not healthy tissue, know this trick and will put out these same cytokines to trick the body into "standing down". Fortunately, it takes a lot of cancer cells to get the upper hand on telling the body's defenses to stand down. When only a few cancer cells get started, they often self destruct (apoptosis) or they are attacked first before a foothold can get going. It is the T-cells that determine whether a tissue is attacked or allowed to grow. And it takes concentration of them for that to occur. Our tissues put out proteins "advising" these t-cells don't attack me. Cancer uses this mechanism to evade destruction often times.
The reason, I have come to understand and believe, that penetrating radiation can cause CML as well as other cancers is that high doses can generate many cancer cells all at once. And this sudden explosion in cancer cell population (leukemic stem cells come to mind) enable those very same cells to quash the bodies natural defense. Immune therapy is all about helping the body regain control and attacking bad cancer cells.
This is why I believe 50% of patients who try cessation after achieving rapid deep remission are successful in stopping therapy. Their TKI was able to reduce the CML population enough so that there is not enough cancer cells remaining (particularly the Leukemic stem cells) to produce enough T-cells to prevent attack. The body regains the upper hand and continues the process that the TKI's first achieved. The other 50%, for whatever reason, either require a much longer time or will never be able to fight CML without medical help.
This is all theory and conjecture, but based on what is emerging out of the scientific literature on the role of T-cells, NK cells and disease. It is an exciting area of research.
Diagnosed 11 May 2011 (100% FiSH, 155% PCR)
with b2a2 BCR-ABL fusion transcript coding for the 210kDa BCR-ABL protein
Sprycel: 20 mg per day - taken at lights out with Quercetin and/or Magnesium Taurate
6-8 grams Curcumin C3 complex.
2015 PCR: < 0.01% (M.D. Anderson scale)
2016 PCR: < 0.01% (M.D. Anderson scale)
March 2017 PCR: 0.01% (M.D. Anderson scale)
June 2017 PCR: "undetected"
September 2017 PCR: "undetected"
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