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Curing CML with imatinib—a dream come true?


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#1 CallMeLucky

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Posted 07 March 2011 - 12:09 PM

Hematology: Curing CML with imatinib—a dream  come true?

Michael Deininger

Abstract

Imatinib was discontinued in patients with chronic myeloid  leukemia (CML) who gained a complete molecular response (CMR). Of those patients  with at least 12 months follow-up, 61% experienced recurrence, all of whom  responded to rechallenge. The remaining patients maintained CMR, suggesting that  imatinib may 'cure' a small proportion of patients with CML.

Can imatinib cure chronic myeloid  leukemia (CML)? No other question in the field of CML has been debated with the  same fervor since it was recognized that some patients with a complete molecular  response (CMR, defined as consistently negative tests for BCR-ABL transcripts in the blood), maintain this response after  discontinuation of therapy.1 As almost all of the patients in this original report had  previously been treated with interferon-? (IFN-?) it remained unclear whether or not this response could be  accomplished with imatinib alone.1

Mahon and colleagues now report the first  results of the Stop Imatinib (STIM) trial, which enrolled 100 patients who  discontinued imatinib after achieving and maintaining CMR for 2 years or more,  including 49 patients who had never received IFN-?.2 Of the 69 patients with at  least 12 months of follow-up (median 24 months), 42 (61%) experienced a  re-emergence of BCR-ABL transcripts; the remaining patients  maintained their CMR. Factors independently associated with recurrence were  female sex, shorter duration of imatinib therapy and high Sokal risk disease at  diagnosis, whereas previous exposure to IFN-? was not  relevant. All but one of the recurrences occurred within 7 months of stopping  imatinib, and all patients with recurrent disease responded to imatinib  rechallenge. This finding suggests that stopping imatinib may be safe if done  with close monitoring, and that the term 'recurrence' should be used to  distinguish this situation from 'relapse', which implies progression despite  continued therapy. As it is possible to determine relatively early those  patients whose disease is destined to recur, one might be able to decrease the  frequency of monitoring once a patient has maintained CMR for a yet to be  determined length of follow-up.

Are patients with sustained CMR off  imatinib truly cured of CML? At this point, the answer is a qualified 'maybe'.  First we have to be sure that what we are seeing is indeed a genuine plateau and  not a slow but inexorable attrition. A study reported in 2010 using a  patient-specific DNA-based assay found residual leukemia in seven out of eight  patients who maintained CMR after imatinib discontinuation;3 it is quite possible that these seven  patients will eventually proceed to negativity but it is also possible that the  apparent inability to eradicate all residual BCR-ABL-positive cells is a sign that a patient's disease will  eventually recur. The second consideration is more conceptual: how do we define  'cure'? A first thought would be to equate cure with the complete absence of  BCR-ABL. This definition is radical but impractical, as it  cannot be tested experimentally. Moreover, we know that highly sensitive assays  can detect BCR-ABL transcripts even in healthy  volunteers.4 Thus, another  concept of cure is needed that takes account of the ability to safely  discontinue treatment but not the certainty of having annihilated all CML cells.  In this frame of thinking, cure would be defined as a likelihood of developing  clinical CML that is no different from the general population. The fact that  occasional relapses have occurred almost two decades after allogeneic stem-cell  transplant suggests that considerable observation time will be needed before  making this call.5 The  major concern is that stopping imatinib in the absence of clonal extinction  might lead to renewed exposure of CML stem cells to BCR-ABL  kinase activity, promoting genomic instability and, ultimately, disease  progression.6

The STIM study found no association  between sustained CMR and previous exposure to IFN-?.  These data are somewhat at odds with the French STI571 Prospective Randomized  Interferon Trial (SPIRIT) that reported increased CMR rates in patients  receiving a combination of imatinib plus pegylated IFN-?  compared with imatinib alone.7 It remains possible that simultaneous administration of  imatinib and IFN-? is required rather than sequential  administration. At some point this hypothesis may be tested by controlled  discontinuation of therapy in a subset of the SPIRIT study.

Perhaps the most fascinating observation  in the STIM study is the apparent dichotomy of outcomes: early recurrence versus  no recurrence. What tentative conclusions can we draw from this phenomenon about  the disease biology in the two groups? The behavior of the first cohort (those  with early recurrence) is consistent with the current concept of residual  disease in imatinib-treated CML. Leukemic progenitor cells, unlike stem cells,  are sensitive to imatinib suggesting that the reconstitution of leukemic  hematopoiesis at the expense of normal hematopoiesis may start immediately after  imatinib treatment is stopped. The kinetics of recurrence in the STIM study—an  increase in leukemia load of approximately one log per month—suggests that  residual leukemia 'smolders' at a level that is 10-107 times lower  than the detection limit of the PCR assay (Figure 1).  Importantly, a high Sokal risk is a reliable predictor of recurrence. This  situation is strikingly different from patients with CMR who continue therapy  and have a very low risk of relapse irrespective of their risk at  presentation.8 Thus, some  cases of CML must have biological properties that are controlled only by  continued therapy, irrespective of CMR. The second distinct feature of patients  with a rapid recurrence is a shorter duration of imatinib therapy. At first  glance, this finding seems to suggest a higher level of residual leukemia,  consistent with the slow but steady reduction of BCR-ABL  transcripts in imatinib responders treated on the International Randomized study  of Interferon and STI571 (IRIS) trial.9 However, in this case one would expect to see recurrences  continue with time, rather than the dichotomy observed in the STIM study. To  reconcile prediction and observation we postulate the existence of a threshold  with a minimum residual number of leukemic cells required to reconstitute  leukemic hematopoiesis (in analogy to minimum viable population sizes in animal  species10). Once  suppressed below this threshold, the BCR-ABL-positive clone  may lose its reconstitution potential; certain immunological mechanisms may  control it or it may finally become extinct by chance (Figure 1).


Figure 1 | Hypothetical model of chronic myeloid leukemia  persistence and recurrence versus extinction. Whether the  leukemic clone can be erradicated may depend on inherent feature of the disease  or on the duration of therapy or both.

Mahon and colleagues estimate that 10% of  patients with CML may be eligible for a trial of imatinib discontinuation.2 Thus, with a 40% rate of  sustained CMR, 4% of CML patients may be 'curable' with imatinib. The big  question is whether the more potent BCR-ABL inhibitors  nilotinib and dasatinib will increase this rate by a significant margin. At  least two scenarios are possible. Firstly, a more potent inhibitor will drive  disease burden below the 'threshold of no return' in a larger proportion of  patients. The observation that a longer duration of imatinib therapy predicts a  higher likelihood of maintaining CMR after stopping could support this scenario.  Secondly, the capacity of the CML clone to undergo complete involution may  represent an infrequent biological feature—extremely low risk—that is determined  a priori, and not modified by BCR-ABL  kinase inhibitors. In this case, the rates of non-recurrence would remain at a  comparable level with more-potent tyrosine kinase inhibitors. Whatever the case,  the most meaningful end point of any future interventional study in CML, as  Mahon and colleagues propose, will be the ability to discontinue therapy after  inducing CMR.


«...4% of CML patients may be 'curable' with  imatinib»

What are the practical implications for patients with CML in 2011?  First and foremost: caution. At this point the STIM data are preliminary and  follow-up is too short for changes in clinical practice. As with any  experimental treatment, patients who wish to stop imatinib should enroll in a  controlled trial. If this approach is not feasible and a patient insists on  being taken off therapy, then intense monitoring with high-quality reverse  transcription PCR (RT-PCR) is mandatory. Inclusion in the STIM study required at  least five negative RT-PCR tests over a 2-year period using highly sensitive  assays, and similarly stringent criteria must be applied in every other setting.  The biggest concern is that the results of the STIM trial are misinterpreted as  a carte blanche to stop therapy in unsuitable patients and with insufficient  monitoring. The good news, however, is that CMR achieved with imatinib  monotherapy may in some patients continue indefinitely after stopping therapy.  If this finding really holds true we might start talking about a cure.

Practice point

The stop imatinib (STIM) study suggests that CML patients who  consistently tested negative for BCR-ABL by reverse  transcription PCR for at least 2 years may safely stop imatinib, provided they  are subjected to intense monitoring to detect disease recurrence. Given the  limited experience with the approach and the short follow-up of the study this  should be done only in the setting of a clinical trial.

Top of page

Acknowledgments

I am grateful to John Goldman, Imperial College London, for his  comments on the manuscript.

Competing interests statement

The author declares competing  interests.

Top of page

References

  1. Rousselot, P. et al. Imatinib mesylate  discontinuation in patients with chronic myelogenous leukemia in complete  molecular remission for more than 2 years. Blood  109, 58-60 (2007).

  2. Mahon, F. X. et al. Discontinuation of  imatinib in patients with chronic myeloid leukaemia who have maintained complete  molecular remission for at least 2 years: the prospective, multicentre Stop  Imatinib (STIM) trial. Lancet Oncol. 11, 1029-1035 (2010).

  3. Ross, D. M. et al. Patients with chronic  myeloid leukemia who maintain a complete molecular response after stopping  imatinib treatment have evidence of persistent leukemia by DNA PCR. Leukemia 24, 1719-1724 (2010).

  4. Bose, S., Deininger, M., Gora-Tybor, J., Goldman, J. M. &  Melo, J. V. The presence of BCR-ABL fusion genes in leukocytes  of normal individuals: implications for the assessment of minimal residual  disease. Blood 92,  3362-3367 (1998).

  5. Goldman, J. M. et al. Relapse and late  mortality in 5-year survivors of myeloablative allogeneic hematopoietic cell  transplantation for chronic myeloid leukemia in first chronic phase.  J. Clin. Oncol. 28, 1888-1895  (2010).

  6. Koptyra, M. et al. BCR/ABL kinase  induces self-mutagenesis via reactive oxygen species to encode imatinib  resistance. Blood 108,  319-327 (2006).

  7. Guilhot, F. et al. Significant higher  rates of undetectable molecular residual disease and molecular responses with  pegylated form of interferon a2a in combination with imatinib (IM) for the  treatment of newly diagnosed chronic phase (CP) chronic myeloid leukaemia (CML)  patients (pts): confirmatory results at 18 months of part 1 of the Spirit phase  III randomized trial of the French CML Group (FI LMC) [abstract]. Blood 114, a340 (2009).

  8. Druker, B. J. et al. Five-year follow-up  of patients receiving imatinib for chronic myeloid leukemia. N. Engl. J. Med. 355, 2408-2417 (2006).

  9. Hughes, T. P. et al. Long-term  prognostic significance of early molecular response to imatinib in newly  diagnosed chronic myeloid leukemia: an analysis from the International  Randomized Study of Interferon and STI571 (IRIS). Blood 116, 3758-3765 (2010).

  10. Traill, L. W., Bradshaw, C. J. & Brook, B. W. Minimum viable population size: A meta-analysis of 30 years of  published estimates. Biological Conservation 139, 159-166 (2007).

Author affiliations

M. Deininger
Division of Hematology  and Hematologic Malignancies, University of Utah, Huntsman Cancer Institute,  2000 Circle of Hope, Room 4280, Salt Lake City, UT 84112-5550, USA.
michael.deininger@hci.utah.edu

Published online 1 February 2011


Date  -  Lab  -  Scale  -  Drug  -  Dosage MG  - PCR
2010/Jul -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 1.2%
2010/Oct -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.25%
2010/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.367%
2011/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.0081%
2011/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2011/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.00084%
2011/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.004%
2012/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Dec -  MSKCC  -  Non-IS  -  Sprycel  - 100 - 0%
2013/Jan -  Quest  -  IS  -  Sprycel  -  50-60-70  - 0%
2013/Mar -  Quest  -  IS  -  Sprycel  -  60-70  - 0%
2013/Apr -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.036%
2013/May -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.046%
2013/Jun -  Genoptix  -  IS  -  Sprycel  - 50 - 0.0239%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0192%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0034%
2013/Oct -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0054%
2014/Jan -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0093%
2014/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.013%
2014/Apr -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0048%
2014/Jul -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2014/Nov -  Genoptix  -  IS  -  Sprycel  - 100 - 0.047%
2014/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0228%
2016/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Dec - Genoptix  -  IS  -  Sprycel  -  100 - 0%
 

 


#2 cousineg

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Posted 07 March 2011 - 08:09 PM

Thank you for this article!   I love it!  

Other links:        Discontinuation of imatinib may be possible in chronic myelogenous leukemia
                         March 3, 2011, Cancer Journal for Clinicians

                         Cure possible for CML?

                         The STIM trial



#3 VickiW

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Posted 07 March 2011 - 10:01 PM

WONDERFUL HOPE FOR MANY.  BUMMER FOR THOSE OF US WHOM LOST EFFICY ON GLEEVEC AND HAD TO SWITCH, BUT, JUST MAYBE, THE 2ND GENERATION DRUGS MAY ALSO SUCCEED!  I CAN DREAM (HOPE) CAN'T I?


Dxd 2007

started on Gleevec switched to Sprycel 100mg in 2009

PCRU since 2011

20mg Sprycel every other day since Dec. 2014

Began TFR 4-18-16


#4 valiantchong

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Posted 08 March 2011 - 01:26 AM

Wonderfull news... however should we take this positively....

I have a question why Interferon alfa can induce 12% of cure, in record there were about 12% with Interferon could stop Interferon treatment without CML relapse, eventhough with MRD. In Imatinib only 4% could stop ? Why the 'cure' % is smaller than Interferon ? Some patient has more than 10 years off Interferon without relapse, is Imatinib a better 'cure' rate ?

Since Interferon had been more than 20 years of history we are still unable to stop...I was wondering how far is the horizon of 'cure' in TKI ?

I wish we could Stop TKI in less than 5 years... Wish this will come true....



#5 CallMeLucky

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Posted 08 March 2011 - 03:31 PM

I think we need to keep in perspective why most CML patients are on TKI and not interferon.  If interferon worked that well, more people would be on it.  I don't know that much about it, but what I have heard and read is that most people do not tolerate it well.  I'm not talking about TKI types of stomach aches, I'm talking about so sick you can't do anything.  There were some who could tolerate it, but most patients, it wasn't a pleasant experience.  My wife has a friend who's father has CML.  He had it before TKI drugs and was on Interferon.  After some time on treatment he spoke with his daughter and told her he was stopping treatment, he said he couldn't continue to live feeling that horrible and that he would rather die.  Fortunately, this was happening around the time of the first Gleevec trial and he got into the trial.  He is doing well today and for the most part you would have no idea he has CML.

Newer approaches to combining low dose Interferon with TKI in combination are being explored and perhaps that will show some promissing results.  High dose interferon is brutal, perhaps at a low dose there can be something that is beneficial.  Time will tell.  In the mean time, I'm glad to have my TKI life preserver.


Date  -  Lab  -  Scale  -  Drug  -  Dosage MG  - PCR
2010/Jul -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 1.2%
2010/Oct -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.25%
2010/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.367%
2011/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.0081%
2011/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2011/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.00084%
2011/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.004%
2012/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Dec -  MSKCC  -  Non-IS  -  Sprycel  - 100 - 0%
2013/Jan -  Quest  -  IS  -  Sprycel  -  50-60-70  - 0%
2013/Mar -  Quest  -  IS  -  Sprycel  -  60-70  - 0%
2013/Apr -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.036%
2013/May -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.046%
2013/Jun -  Genoptix  -  IS  -  Sprycel  - 50 - 0.0239%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0192%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0034%
2013/Oct -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0054%
2014/Jan -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0093%
2014/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.013%
2014/Apr -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0048%
2014/Jul -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2014/Nov -  Genoptix  -  IS  -  Sprycel  - 100 - 0.047%
2014/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0228%
2016/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Dec - Genoptix  -  IS  -  Sprycel  -  100 - 0%
 

 


#6 fychien@yahoo.com

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Posted 08 March 2011 - 10:01 PM

Great information. I asked my son's doctor of any protocol for CML treatement. She told me that Texas Oncology has one protocol to stopping taking medicine after two years of undetected lukemia cells. Now, I understand it means PCRu from this article.



#7 valiantchong

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Posted 08 March 2011 - 11:37 PM

Great reply, I hope, there will be more and more hospital will practice this protocol to collect more data. As then we will have enough data to move forward and one day soon most of us will stop taking TKI.



#8 rct

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Posted 09 March 2011 - 07:55 AM

We did that.  Mrs at PCRu for more than two years, was back in numbers and moving to the left after only about 4 weeeks of no Gleevec.  It is quite possibly a dream yes, but a dream for probably very very few of the already very few people with CML.  Some better dreams would be more realistic side effect management and mitigation. Being realistic about the actual effect on the marrow and cell production that these drugs have. Maybe a more realistic approach to the idea that none of this stuff is even a bet for everyone much less a sure bet for anyone.

I think of each and every one of you each and every day and I hope it is going as well for you as it possibly can.

rct



#9 valiantchong

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Posted 09 March 2011 - 10:04 AM

Hi, Understand what you mean by bet, however even in HSCT there is a risk of only 60% recovery for 2 years for patients > 40 years old. The accumulated success I believe is even less than this. So what is the current best bet ?

I do hope with future vaccines and IL1RAP will give us more hope towards a cure.,,,  



#10 CallMeLucky

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Posted 09 March 2011 - 12:00 PM

"So what is the current best bet ?"

Physically - find TKI that works and stay on it

Mentally - figure out how to accept being on drug for rest of life.

At least that is what I am trying to do...


Date  -  Lab  -  Scale  -  Drug  -  Dosage MG  - PCR
2010/Jul -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 1.2%
2010/Oct -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.25%
2010/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.367%
2011/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.0081%
2011/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2011/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.00084%
2011/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.004%
2012/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Dec -  MSKCC  -  Non-IS  -  Sprycel  - 100 - 0%
2013/Jan -  Quest  -  IS  -  Sprycel  -  50-60-70  - 0%
2013/Mar -  Quest  -  IS  -  Sprycel  -  60-70  - 0%
2013/Apr -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.036%
2013/May -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.046%
2013/Jun -  Genoptix  -  IS  -  Sprycel  - 50 - 0.0239%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0192%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0034%
2013/Oct -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0054%
2014/Jan -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0093%
2014/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.013%
2014/Apr -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0048%
2014/Jul -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2014/Nov -  Genoptix  -  IS  -  Sprycel  - 100 - 0.047%
2014/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0228%
2016/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Dec - Genoptix  -  IS  -  Sprycel  -  100 - 0%
 

 


#11 helenet

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Posted 09 March 2011 - 01:26 PM

Trey-- you are being very quiet! Nothing to say here?



#12 Trey

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Posted 09 March 2011 - 10:38 PM

Being very quiet -- did not want to wake them.....shhhhhhhhh



#13 Guest_billronm_*

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Posted 10 March 2011 - 01:42 AM

Dear rct,

That was a very nice comment, It,s nice to know there are people out there who truly try to understand cml.

                                                                                                           Billie



#14 rct

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Posted 10 March 2011 - 08:07 AM

Well Billie Murawski, I think that time spent on things that just aren't happening in my current lifetime is time wasted that could be used to first and foremost help my Mrs of more than 30 years as she is slowly but surely dragging ever downward after coming up on 5 years of Gleevec and we are pretty sure at least 5 years before that of un, mis, and otherwise erronesously not diagonosed CML.

After that, I think it is a waste and a disservice to all of you peoples doing all of the very different things you have to to get through each day.

People can't even get dang disability without a congressional inquiry and we're(the imperial we, not anyone specifically here) talking about cures that will never happen?  It's ridiculous and I'm pretty sure that 5 years along the road lots of others will be feeling the same way.

Sorry if I offended anyone.  I hope a good day for everyone, every day.

rct



#15 valiantchong

valiantchong

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Posted 10 March 2011 - 09:08 AM

HI RCT,

Understand what in your mind, you are being realistic of current medical knowledge on CML. Your are right on current medical prognosis, since the so call 'cure' trial only apply 4% of the sample CML population. This is actually nothing new, since on previous Interferon alfa history of 20 years ago, which has a 'cure' of a very small group of patients able to achieve PCRU, off drugs.

If one is being realistic and base on estimation of the medication record, Interferon alfa to Imatinib takes 20 years, so it may take another 20 years to find a new paradigm shift than current TKIs which is not effective on the LSC...Then again this 'cure' may apply to higher % and not for everyone... I think you did not offend anyone, but just being realistic....



#16 PhilB

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Posted 10 March 2011 - 09:19 AM

Lucky talked about trying to " accept being on drug for rest of life".  Look on the bright side, Gleevec has already lowered my cholesterol and now there's even a study suggesting it might, just possibly, help prevent Alzheimers.  Who knows what other unexpected bonuses we may have in store that we'd lose if they went and found a cure!

Phil



#17 valiantchong

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Posted 12 March 2011 - 11:07 PM

Hi Phil,

That is a very optimistic view, to get bonus out of the medication, everyday. Hope that is true, however I am feeling that the side effect could affect other organ....liver, heart or kidney due to the quality of blood affected by the medication... what comes around go around....I could  not help thinking of the sickness.. I really hope one day when the 'cure' come and we can forget about it and live our worried free life again....When will that be... ?






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