from Jerry's site

[Guest guest]

I hope this is not illegal to copy from one site to another, I would hate to go

to jail!  But this is very interesting, and I'm not sure how many of you read

Jerry's site. Bobby

We (The CML

Society of Canada) are working to have September 22 declared CML day to

honor the work of Janet Rowley's discovery of the translocation between

chromosomes 9 and 22. One of our youngest patient advisers, Rav, came

up with this idea and we think he is just great for thinking about it.

To celebrate, the following is a short essay on the topic of " Is CML Curable? "

Is CML Curable?

We’ve been asked lately if CML is curable. Yes, CML is curable and here is

why we think this is so.

First, a Little History

Did

you know that the first case of CML was diagnosed in Scotland in 1845

and then a second case was reported a few weeks later in Berlin? In

1872, it was observed that leukemic stem cells come from the bone

marrow. However, it was in a lab in Philadelphia in 1962 that two

researchers working together, Lowell and Hungerford located the

Philadelphia Chromosome. This was a very significant event as it showed

that cancer, and CML in this case, could be traced to a problem in the

DNA. In 1972 Janet Rowley showed that there was a translocation, or

exchange of gene material, between chromosomes 9 and 22 associated with

leukemia, and specifically CML. Through the decades a variety of

treatments have been helping most patients extend their lives. But it

was a significant breakthrough by Levitzki who showed that

ABL inhibitors could be effectively used in inhibiting tyrosine kinases

and blocking cancer. Today we have three approved Tyrosine Kinase

Inhibitors and another one far advanced in clinical trials (M.

Deininger, ASH 2008, CML Educational Session). Most important thanks go

to Dr. B. Druker for his tenacity while working with Signal

Transductions Inhibitors, or STI 571, now known as Gleevec or Glivec,

that proved the concept of targeted therapies and greatly improved the

lives of CML patients. Dr. Druker’s worked rallied the entire CML

community of scientist, doctors and patients as never before.

Simply

put, tyrosine Kinase inhibitors block the function of ATP, which is

like an energy cell. Blocking the function of ATP in turn blocks the

function of the protein generated by BCR ABL, which slows proliferation

(which is what any cancer really is, over proliferation of cells that

go un-checked by the body’s immune system) of CML. This is a very

simple description of it; there are other more technical and much more

eloquently stated descriptions. Don’t hesitate to google and find the

one that helps you understand the best.

Before Tyrosine Kinase

Inhibitors there was Interferon. Interferon is a biological immune

modifier. Interferon on its own had a very difficult time to combat CML

and BCR ABL outsmarted and overwhelmed it. Consequently many patients

had to take incredibly high doses of Interferon to try to stop CML from

progressing to its more deadly accelerated phases. A high dose of

interferon induces an incredible amount of side effects that are very

difficult to deal with and greatly diminish a patient’s quality of

life. However, there was some good news; some patients, a small

percentage, close to 12% by some reports, could be successfully treated

with interferon and were able to stop taking the drug without

relapsing. Some of these patients have been tracked for more than 20

years without relapse. These results added to the data of the patients

who responded to an allogenic bone marrow transplant, suggest to us

that CML is curable.

We were all quite fortunate when Gleevecâ„¢,

the world’s first Tyrosine Kinase Inhibitor started in Phase I trials

and successfully went on to Phase II and expanded access programs. I am

not going to expound too much on the success of these drugs, the data

shows us that lives have been extended and with the newer drugs,

quality of life is improving as well. For those who have the misfortune

of developing resistance to one drug or another, we are lucky that

there are second-generation drugs such as Sprycelâ„¢ and Tasignaâ„¢ as well

as additional drugs in trials.

But what about the cure?

At

ASH 2008 there was an update on the study that was started by Dr.

Mahone in France and it is quite exciting. There were 15 patients in

France who decided to stop treatment with Gleevecâ„¢ for one reason or

another, so the opportunity was taken to observe what would happen to

them. 7 of the patients relapsed within 6 months, however, 8 of the

patients in this very small cohort pilot study, did not relapse. These

patients have been followed for more than 37 months. Interestingly it

was noted that these patients had been “pre-treated†with interferon.

Could it be that pretreatment with interferon confers some advantage?

That was the hypothesis, but the hypothesis would need further testing,

so they enrolled another 69 patients from 22 different centers in

France. The criterion was that they had to have been in a complete

molecular remission and PCR undetectable for two years consecutively,

before being allowed to stop Gleevecâ„¢. Of these 69 patients, 27

patients have relapsed; 13 were pretreated with IFN, and 14 were only

treated with Gleevecâ„¢.

The big news is that at 9 months follow

up 46% (or approximately 31) of these patients are still in remission,

of those 46% patients, 53% were pretreated with interferon and 39% are

“de novo†patients (have only been treated with Gleevec™). Earlier we

mentioned that on Interferon alone, some sources reported up to 12% of

patients could be taken off the drug. Added with this new information,

we can explore the hypothesis that the early results with interferon

alone could be greatly improved with the addition of a targeted therapy

like Gleevecâ„¢. The other good news is that most patients who relapsed

after stopping Gleevec™ quickly regained their molecular response: “Dr.

Mahon also emphasized that all of the patients who relapsed were

sensitive to Imatinib after it was restarted. Some of the relapsed

patients went back into remission very quickly, but for others, it is a

slower process. Although the follow-up in this particular study (69

patients, 22 centers) is short, patients in the pilot study have now

been followed for several years. “The results from both of these trials

confirm that complete molecular response can be sustained after

Imatinib is discontinued. This is particularly true for patients who

have been pretreated with interferon, said Dr. Mahonâ€.

It seems

possible that the combination of both Gleevecâ„¢ and other Tyrosine

Kinase Inhibitor’s for that matter, with something like Interferon can

improve the potential for patients to enjoy a relapse free and drug

free remission. Not sure if that is the exact same thing as a cure, but

we would like to see what it is like to not have to think about one

drug or another, wouldn’t you?

Earlier in this essay, it was

mentioned that CML could be traced to a problem in the DNA. This is

very good news, because now we know that our DNA doesn’t exactly “seal

our fate†as we once thought it did. There is new research about

epigenomes. The really basic take away about epigenes is that they can

be switched one way, and that means that they can be switched back too!

Read the really cool article about this here: Whew! Your DNA Isn't Your

Destiny

There are now more centers participating in allowing

patients to try to stop Gleevecâ„¢ and we think that this is very

exciting. Importantly, there is research going on in many areas that

helps us all to learn more about this disease. This is vitally

important to us as these drugs are very expensive and are creating a

significant socioeconomic hardship for CML patients and their families.

This was evident with the results of the international CML patients

survey presented at a satellite symposium at ASH in December 2008.

Visit the CML Society website for the video presentation.

Saying

CML isn’t curable would be ignoring the great successes we have had in

helping people with CML to enjoy improved survival rates. So stay

healthy, continue to learn along with us and importantly, stay informed.

Is CML Curable? We can certainly say we are counting on it!

Disclaimers:

Please note the clinical trial data presented here was from a

relatively small cohort of patients who were good responders to

therapy. While the results seem quite positive, do not attempt to stop

your therapy. If you have any questions about your current treatment,

please discuss them with your doctor.

a (Bobby) Doyle Brecksville, Ohio, USA DX 05/1995 02/2000 - Gleevec

Trial/OHSU 06/2002 - Gleevec/Trisenox Trial/OHSU 06/2003 - Gleevec/Zarnestra

Trial/OHSU 04/2004 - Sprycel Trial/MDACC, CCR in 10 months #840  -  

Zavie's Zero Club 09/2006 -  out of CCR 04/29/08 - XL228 trial/U of Michigan

01/09/ - PCR 5.69

02/13/09 - XL228 trial ended due to side effects

o4/13/09 - Ariad Trial U of Michigan

09/09/09 - PCR 0.017

04/13/09 - Ariad trial at U. of Michigan

09/09/09 - PCR 0.017

04/13/09 - Ariad trial, U. of Michigan

09/08/09 - PCR 0.017

[Guest guest]

Thanks for the info. I do not beleive that you have done anything wrong by

coping it from one website to another. You have given the proper credit to the

authors and persons where the info was located. This is required when

referencing material in term papers when in school and you are not attempting to

profit from its use.

H.

>

> I hope this is not illegal to copy from one site to another, I would hate to

go to jail!  But this is very interesting, and I'm not sure how many of you

read Jerry's site. Bobby

>

>

> We (The CML

> Society of Canada) are working to have September 22 declared CML day to

> honor the work of Janet Rowley's discovery of the translocation between

> chromosomes 9 and 22. One of our youngest patient advisers, Rav, came

> up with this idea and we think he is just great for thinking about it.

>

> To celebrate, the following is a short essay on the topic of " Is CML Curable? "

>

> Is CML Curable?

>

> We’ve been asked lately if CML is curable. Yes, CML is curable and here is

why we think this is so.

> First, a Little History

>

> Did

> you know that the first case of CML was diagnosed in Scotland in 1845

> and then a second case was reported a few weeks later in Berlin? In

> 1872, it was observed that leukemic stem cells come from the bone

> marrow. However, it was in a lab in Philadelphia in 1962 that two

> researchers working together, Lowell and Hungerford located the

> Philadelphia Chromosome. This was a very significant event as it showed

> that cancer, and CML in this case, could be traced to a problem in the

> DNA. In 1972 Janet Rowley showed that there was a translocation, or

> exchange of gene material, between chromosomes 9 and 22 associated with

> leukemia, and specifically CML. Through the decades a variety of

> treatments have been helping most patients extend their lives. But it

> was a significant breakthrough by Levitzki who showed that

> ABL inhibitors could be effectively used in inhibiting tyrosine kinases

> and blocking cancer. Today we have three approved Tyrosine Kinase

> Inhibitors and another one far advanced in clinical trials (M.

> Deininger, ASH 2008, CML Educational Session). Most important thanks go

> to Dr. B. Druker for his tenacity while working with Signal

> Transductions Inhibitors, or STI 571, now known as Gleevec or Glivec,

> that proved the concept of targeted therapies and greatly improved the

> lives of CML patients. Dr. Druker’s worked rallied the entire CML

> community of scientist, doctors and patients as never before.

>

> Simply

> put, tyrosine Kinase inhibitors block the function of ATP, which is

> like an energy cell. Blocking the function of ATP in turn blocks the

> function of the protein generated by BCR ABL, which slows proliferation

> (which is what any cancer really is, over proliferation of cells that

> go un-checked by the body’s immune system) of CML. This is a very

> simple description of it; there are other more technical and much more

> eloquently stated descriptions. Don’t hesitate to google and find the

> one that helps you understand the best.

>

> Before Tyrosine Kinase

> Inhibitors there was Interferon. Interferon is a biological immune

> modifier. Interferon on its own had a very difficult time to combat CML

> and BCR ABL outsmarted and overwhelmed it. Consequently many patients

> had to take incredibly high doses of Interferon to try to stop CML from

> progressing to its more deadly accelerated phases. A high dose of

> interferon induces an incredible amount of side effects that are very

> difficult to deal with and greatly diminish a patient’s quality of

> life. However, there was some good news; some patients, a small

> percentage, close to 12% by some reports, could be successfully treated

> with interferon and were able to stop taking the drug without

> relapsing. Some of these patients have been tracked for more than 20

> years without relapse. These results added to the data of the patients

> who responded to an allogenic bone marrow transplant, suggest to us

> that CML is curable.

>

> We were all quite fortunate when Gleevecâ„¢,

> the world’s first Tyrosine Kinase Inhibitor started in Phase I trials

> and successfully went on to Phase II and expanded access programs. I am

> not going to expound too much on the success of these drugs, the data

> shows us that lives have been extended and with the newer drugs,

> quality of life is improving as well. For those who have the misfortune

> of developing resistance to one drug or another, we are lucky that

> there are second-generation drugs such as Sprycelâ„¢ and Tasignaâ„¢ as well

> as additional drugs in trials.

>

>

> But what about the cure?

> At

> ASH 2008 there was an update on the study that was started by Dr.

> Mahone in France and it is quite exciting. There were 15 patients in

> France who decided to stop treatment with Gleevecâ„¢ for one reason or

> another, so the opportunity was taken to observe what would happen to

> them. 7 of the patients relapsed within 6 months, however, 8 of the

> patients in this very small cohort pilot study, did not relapse. These

> patients have been followed for more than 37 months. Interestingly it

> was noted that these patients had been “pre-treated†with interferon.

> Could it be that pretreatment with interferon confers some advantage?

> That was the hypothesis, but the hypothesis would need further testing,

> so they enrolled another 69 patients from 22 different centers in

> France. The criterion was that they had to have been in a complete

> molecular remission and PCR undetectable for two years consecutively,

> before being allowed to stop Gleevecâ„¢. Of these 69 patients, 27

> patients have relapsed; 13 were pretreated with IFN, and 14 were only

> treated with Gleevecâ„¢.

>

> The big news is that at 9 months follow

> up 46% (or approximately 31) of these patients are still in remission,

> of those 46% patients, 53% were pretreated with interferon and 39% are

> “de novo†patients (have only been treated with Gleevec™). Earlier we

> mentioned that on Interferon alone, some sources reported up to 12% of

> patients could be taken off the drug. Added with this new information,

> we can explore the hypothesis that the early results with interferon

> alone could be greatly improved with the addition of a targeted therapy

> like Gleevecâ„¢. The other good news is that most patients who relapsed

> after stopping Gleevec™ quickly regained their molecular response: “Dr.

> Mahon also emphasized that all of the patients who relapsed were

> sensitive to Imatinib after it was restarted. Some of the relapsed

> patients went back into remission very quickly, but for others, it is a

> slower process. Although the follow-up in this particular study (69

> patients, 22 centers) is short, patients in the pilot study have now

> been followed for several years. “The results from both of these trials

> confirm that complete molecular response can be sustained after

> Imatinib is discontinued. This is particularly true for patients who

> have been pretreated with interferon, said Dr. Mahonâ€.

>

> It seems

> possible that the combination of both Gleevecâ„¢ and other Tyrosine

> Kinase Inhibitor’s for that matter, with something like Interferon can

> improve the potential for patients to enjoy a relapse free and drug

> free remission. Not sure if that is the exact same thing as a cure, but

> we would like to see what it is like to not have to think about one

> drug or another, wouldn’t you?

>

> Earlier in this essay, it was

> mentioned that CML could be traced to a problem in the DNA. This is

> very good news, because now we know that our DNA doesn’t exactly “seal

> our fate†as we once thought it did. There is new research about

> epigenomes. The really basic take away about epigenes is that they can

> be switched one way, and that means that they can be switched back too!

> Read the really cool article about this here: Whew! Your DNA Isn't Your

> Destiny

> There are now more centers participating in allowing

> patients to try to stop Gleevecâ„¢ and we think that this is very

> exciting. Importantly, there is research going on in many areas that

> helps us all to learn more about this disease. This is vitally

> important to us as these drugs are very expensive and are creating a

> significant socioeconomic hardship for CML patients and their families.

> This was evident with the results of the international CML patients

> survey presented at a satellite symposium at ASH in December 2008.

> Visit the CML Society website for the video presentation.

> Saying

> CML isn’t curable would be ignoring the great successes we have had in

> helping people with CML to enjoy improved survival rates. So stay

> healthy, continue to learn along with us and importantly, stay informed.

> Is CML Curable? We can certainly say we are counting on it!

>

> Disclaimers:

> Please note the clinical trial data presented here was from a

> relatively small cohort of patients who were good responders to

> therapy. While the results seem quite positive, do not attempt to stop

> your therapy. If you have any questions about your current treatment,

> please discuss them with your doctor.

>

>

> a (Bobby) Doyle Brecksville, Ohio, USA DX 05/1995 02/2000 - Gleevec

Trial/OHSU 06/2002 - Gleevec/Trisenox Trial/OHSU 06/2003 - Gleevec/Zarnestra

Trial/OHSU 04/2004 - Sprycel Trial/MDACC, CCR in 10 months #840  -  

Zavie's Zero Club 09/2006 -  out of CCR 04/29/08 - XL228 trial/U of Michigan

> 01/09/ - PCR 5.69

> 02/13/09 - XL228 trial ended due to side effects

> o4/13/09 - Ariad Trial U of Michigan

> 09/09/09 - PCR 0.017

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

> 04/13/09 - Ariad trial at U. of Michigan

> 09/09/09 - PCR 0.017

>

>

>

> 04/13/09 - Ariad trial, U. of Michigan

> 09/08/09 - PCR 0.017

>

>

>

>

>