CML

hallo cheryl ann
as i have told lynne we have heard from one of the drs on the board of thr trial
106 that novartis has decided to keep following the patients on the gleevec arm.
the interferon arm of this trial was closed after 1 year since almost all
patients on this arm switched to gleevec.
as far as i understood the decision to continue the trial is not limited in
time. when we joined the iris trial it was planned to continue for 5 years. i am
now midway through the 6 th year.
shalom
giora

Hi all just letting you know that Tim hasnt heard anything yet. He
phoned me today...fingers still crossed..and lots of prayers
so stay tuned
susie leech
Dx Nov 2002
Currently off Gleevec

Hi nancy and jane, not sure what they do other parts of the world
although ive heard many times that 400mg is the normal dose to start
on Gleevec and which maybe so...but when i started Gleevec in
Australia in Jan 03 there was no trial at that time with 400mg. Tim
started me on 600mg, he told me he didnt think that 400mg will hold
and your body will get use to it too soon...who knows they are always
changing their minds..I know Tim dosnt think much of anything below
600mg, In three years ive been diagnosed ive not heard of any trials
in asutralia with 400mg. Maybe there is and Tim just favours
600mg...who knows...I sometimes wished they started me on 400mg and
then maybe i mightve not had all this other stuff happend with gleevec.
Susie Leech
Dx Nov 2002
Currently off Gleevec

Hello All,
Just in case anyone would like help in covering the cost of their drugs,
below is an article that ran in the Wall Street Journal. In reading through
it there is a name of a charity that has been set up to offer assistance.
Through Charities, Drug Makers Help Patients and Help Themselves
By Donating Money, Firms Keep Patients Insured And Medicine Prices High
By GEETA ANAND Staff Reporter of THE WALL STREET JOURNALDecember 1, 2005;
Page A1
Nancy Oliva hadn't paid much attention to her insurance plan's requirement
that she pay half the cost of prescription drugs. Then the cashier at
ShopRite told her she owed $636 for seven pills. s. Oliva, 60 years old, was
diagnosed with a rare type of brain tumor earlier this year. She was
prescribed a new drug to be taken in combination with radiation. The retail
price of a one-week supply of the pill, called Temodar, is $1,272.
.
<http://online.wsj.com/article/SB113210858490898540.html?mod=article-outset-
box
<http://online.wsj.com/article/SB113202332063297223.html?mod=article-outset-
box
Ms. Oliva, who earns about $40,000 a year managing a clothing store in Long
Beach Island, N.J., pulled out her American Express card that day in
September and paid, unsure where she was going to find the money for the
next week's supply. Fortunately, the nurse at her doctor's office found help
for her from a charity, Patient Services Inc., which picked up her drug
co-payments -- $3,800 for a six-week course of treatment.
The twist: The money for her co-payments came from Schering-Plough Corp.,
the drug's maker.
To cope with rising medical costs, insurers are requiring patients to pay
higher premiums and co-payments for drugs. While poor uninsured patients can
often get expensive medicine free from drug companies, people with insurance
are increasingly finding it difficult to afford these drugs. In response,
drug companies are giving money to charities that are specifically set up to
help patients pay such costs.
Under this support system, drug-company money keeps patients insured -- and
keeps insurers paying for the high-priced medicine.
"It's a win-win situation," says Dana Kuhn, co-founder and president of
Patient Services, a Midlothian, Va., charity, which solicits money from drug
companies. "Patients are helped and companies are helped. They make a small
contribution to help the patient and get much more money back when the
insurer pays for the drug."
Drug companies also often take a tax deduction for their donation.
But critics contend the arrangements unfairly let drug companies protect the
prices of their most-expensive medicines. "I don't want to discount the
legitimate help they provide to people in need," says Scott Howell, an
internist who serves as vice president of pharmacy affairs at Highmark Inc.,
a Blue Cross and Blue Shield company in Pittsburgh. "But it's really a
clumsy way for manufacturers to game the system so they can continue their
high pricing."
The efforts, critics say, are a short-term fix that doesn't address the
underlying problem: the soaring cost of ultra-expensive drugs. They argue
that by paying patients' premiums or co-payments, drug companies are
shifting most of the price of these medicines to the patients' insurers, who
in turn spread the cost onto the other people they cover. "This is not a
sustainable level of spending," says Alan Garber, chairman of the Medicare
Coverage Advisory Committee and director of the Center for Health Policy at
Stanford University. "The idea of making drugs available to people who can't
afford it is very appealing, but the net effect is for the drug company to
appropriate most of the gain."
Drug companies say the high prices of new drugs allow them to recoup
development costs and invest in research, as well as provide return for
their shareholders. Donating to groups that make insurance payments helps
people get their medicine.
A Schering-Plough spokeswoman says the company contributes to Mr. Kuhn's
charity "as a resource for patients." She declined to say how much
Schering-Plough donates to such programs.
Patients are grateful for the help. "Whoever thought a week's worth of pills
could cost $1,200?" says Ms. Oliva, who is now taking another round of
Temodar. "But I'm so pleasantly surprised that someone is trying to help me
stay alive and it's the drug company of all people."
The need for financial-assistance programs is growing. The biotechnology
revolution has created hundreds of drugs for chronic, life-threatening
illnesses. But many are coming to market at high prices. In May, the U.S.
Food and Drug Administration approved a drug for a rare genetic disease,
called MPS-VI, made by California-based BioMarin Pharmaceutical Inc., which
costs an average of $300,000 a year. Other new drugs cost less, but are
still pricey, such as cancer drugs Avastin, at $50,000 a year, and Erbitux
at nearly $120,000 a year.
Unlike traditional medicines that are made by mixing chemicals, many newer
drugs are proteins grown in cells, which is a complex, expensive process.
Companies say costly manufacturing also leads to higher prices. On the other
hand, the gross profit margins on some of these drugs can exceed 90%.
While Patient Services developed the concept of soliciting drug-company
money to pay insurance premiums, the National Organization for Rare
Disorders, a Connecticut nonprofit, recently began performing the same kind
of middleman role. "Everybody knows what has to happen -- that these prices
have to come down," says Abbey Meyers, the group's president. For now, she
says, "we're trying to work with drug companies in a way that's acceptable
to them and that also helps patients. We're doing the best we can." A few
smaller charities have sprung up recently with similar plans.
Companies including Amgen Inc., Genentech Inc., Genzyme Corp., Teva
Pharmaceutical Industries Ltd., Baxter International Inc., Novartis AG and
ZLB Behring also donate to these programs.
Approaching Companies Mr. Kuhn, 52, who suffers from hemophilia, co-founded
Patient Services, also known as PSI, in 1989 while working as a counselor at
a Richmond, Va., hospital. He saw hemophiliacs struggling to pay rising
premiums to maintain insurance coverage for Factor VIII, the blood-clotting
protein they need to stay alive. The drug today costs about $100,000 a year.
Mr. Kuhn approached companies making the drug for a donation to help
patients pay premiums. "Our argument was, 'If you donate $50,000, we can
keep these people insured and provide revenue for you,' " he says.
Baxter and Armour Pharmaceutical Co., two of several companies that made the
drug, each contributed $50,000 the first year. The program has grown
steadily, now assisting people with 19 different chronic illnesses.
Last year, Patient Services raised $22 million, helping nearly 20,000
patients pay premiums and co-payments. About $17 million of that came from
13 drug companies. When he makes his pitch to companies, Mr. Kuhn says he
emphasizes that they can make money by donating. During a 2003 visit to
Genzyme, for instance, he brought along a chart showing how a donation would
affect a patient who needs the company's drug, Fabrazyme. Genzyme says the
drug typically costs between $175,000 and $200,000 a year. The chart showed
that if Genzyme donated $5,400 to cover the patient's premium for a year, it
would bring in about $185,000 by getting its drug paid for by the patient's
insurance. Genzyme signed up. "We wanted to do whatever we could to make
sure all patients who needed our treatment could get it," says a spokesman
for the company, based in Cambridge, Mass. He declined to say how much
Genzyme donates to Patient Services.
'Who Can Afford It?'
One of the first to get help was Jeremy Taylor, a 25-year-old auto mechanic
in Phoenix, who suffers from Fabry disease, a rare genetic disorder that can
cause kidney failure, heart attacks and death. It costs about $224,000 a
year for him to receive Genzyme's drug. His insurance pays for most of that,
but under the plan, he is required to pay about $27,000 annually, PSI says.
Mr. Taylor declined to be interviewed.
"It's a real miracle drug for us," says his father, Larry Taylor. "But who
can afford it?"
Patient Services says it provides $27,000, all donated by Genzyme, to keep
Mr. Taylor insured. Mr. Taylor's insurer pays the remaining $197,000 cost of
his treatment, according to PSI. Until Mr. Taylor's drug was covered by
insurance, Genzyme provided it to him for free, his father says.
Genzyme helps keep 167 patients with Fabry disease insured through its
charitable program, PSI says. Genzyme is the only donor for PSI's Fabry
program and it makes the only drug for the disease. The company donates less
than $2 million to the program, Mr. Kuhn says.
It isn't clear how much revenue Genzyme receives from the sale of the drug
to these patients. Assuming each patient receives the low-end estimate for a
year's dose, that could generate revenue of about $29 million.
"Of course we get revenue from patients who are insured," says a Genzyme
spokesman. But he declined to be specific on how much revenue the company
receives for patients it helps stay insured, saying that would incorrectly
imply the company makes donations "simply for financial gain." He says the
company makes donations "simply to insure access to care for patients."
Genzyme struck a similar arrangement with the National Gaucher Care
Foundation in 1993, soon after the company brought a drug to market to treat
Gaucher disease. Genzyme makes the most widely prescribed treatment for this
disease, which causes organs to swell and bones to deteriorate.
The foundation's patient-assistance budget this year is $1.6 million. The
biggest donor is Genzyme, according to Barbara Lichtenstein, program
director of the foundation. It helps about 200 patients with insurance
premiums and other medical expenses. Genzyme says its drug for this disease
costs an average of $200,000 per year.
Genzyme has a staff of 34 insurance specialists who try to keep patients who
take its drugs insured. If no insurance can be found, the company gives the
drug to patients free. Gaucher patients "are like gerbils on a wheel,"
continuously finding and losing insurance, Ms. Lichtenstein says. Some who
call her have hit their maximum lifetime caps of several million dollars on
insurance coverage and have to find new jobs to get additional health-care
coverage, she says.
Teva Neuroscience Inc. markets a multiple sclerosis drug that retails for
about $18,000 annually. "Market research told us early on we needed to do a
patient-support program" because some people wouldn't be able to afford
their co-payments, says Denise Lynch, director of customer management.
Teva donates to the National Organization for Rare Disorders to provide
co-payment assistance. Ms. Lynch says Teva didn't calculate the profit it
could receive when making its donation, "but from a common-sense
perspective, you can get there." She says Teva takes a tax deduction for its
donation.
Teva considered setting up a foundation on its own, she says, but concluded
it was "cleaner from a regulatory point of view to work through a third
party."
Some companies have been nervous about donating to his charity, Mr. Kuhn
says, fearing they might violate federal anti-kickback laws. These laws,
passed in the 1970s, forbid drug companies from giving financial assistance
to Medicare and other federally insured patients which could be an
inducement to choose one drug over another. The laws don't apply to people
who are privately insured.
To reassure drug companies it was legal to donate to his program, Mr. Kuhn
sought an opinion in 2000 from the Office of the Inspector General of the
U.S. Department of Health and Human Services.
In 2002, the Inspector General's office issued its opinion, saying it
wouldn't seek civil or criminal penalties from participants in Mr. Kuhn's
program. It said the program "interposes an independent charitable
organization between donors and patients in a manner that effectively
insulates" patients and doctors from making prescribing decisions based on
the donations. This is because PSI sets up programs not by individual drug,
but rather by disease -- so that all the companies making, say, multiple
sclerosis drugs, donate into a pool for patients with the disorder.
Applicants receive help based on financial need, regardless of what drug
they are prescribed, and even if the maker of a prescribed drug doesn't
contribute to the program.
For certain rare diseases, however, only one company makes a drug to treat
the condition.
After the favorable opinion, Mr. Kuhn says he found drug-company executives
eager to donate. "You could see the dollar signs shining in their eyes and
they would jump over the table and say, 'When can I start?' " he says. He
has raised $30 million so far this year and is assisting 25,000 patients.
Patient-assistance programs must walk a thin line. In 2002, the Inspector
General also issued a separate, unfavorable opinion on the subject. This was
to an unidentified drug company seeking to establish a nonprofit foundation
to cover co-payments only for patients on its drug.
"The proposed arrangement poses all the usual risks of fraud and abuse
associated with kickbacks," the opinion said. It said physicians would have
an incentive to prescribe the drug in question, which is infused in doctors'
offices, over another because they would be certain of being paid rather
than risk collecting the co-payment from the patient.
The opinion noted patient-assistance programs can be "very profitable to
manufacturers...Given that the marginal variable cost of a drug can be quite
low, the profit can be considerable, especially for an expensive drug for a
chronic condition."
A Working Balance
Third-party charities struggle to maintain a working balance with corporate
donors. Maria Hardin, vice president of patient services, at the National
Organization of Rare Disorders, says companies routinely press the group to
give out more patient information than it can legally provide. "There's a
lot of whining going on with them asking, 'What percentage of the fund is
taking care of our patients?' We can't provide that information," she says.
Mr. Kuhn's charity is growing so much that it plans to build a $1.7 million,
15,000-square-foot building. One reason he expects demand for assistance to
rise is that next year, Medicare will start a program to help the elderly
afford drugs. Currently, Medicare doesn't pay for most prescription drugs.
But the new Medicare program is structured so that some patients on
expensive drugs will still have to come up with thousands of dollars to pay
out-of-pocket costs.
Vivian Gushwa, 70, was prescribed the cancer drug Gleevec after her rare
gastrointestinal tumor recurred last year. Her husband, Ronald, went to Rite
Aid in Marion, Ohio, to pick up the medicine and came home crying. The
retail price of her prescription was $2,000 for two weeks' supply, which
would consume the couple's $2,000 a month in pension and Social Security
income, they say. "There's no way on God's green earth we can afford that,"
says Mr. Gushwa, 74, who worked most of his life at a local electric-power
company. He bought a two weeks' supply of the drug, using about half of
their $4,000 in savings. Novartis, the Swiss company that makes Gleevec,
provided free medicine for several months and then directed the couple to
apply to the federal government for coverage under a pilot Medicare program.
The Gushwas again suffered sticker shock. Their income of $2,000 a month put
them in a group required to pay $3,600 a year before being eligible for the
drug benefit. They also have to pay 5% of each prescription.
"Medication has to be paid for. We understand that," says Mrs. Gushwa. "But
how do people afford it? Do you just die?"
She says she overheard her husband weeping on the phone as he called around
seeking help. An official from Medicare referred him to PSI, which had just
started a program funded by Novartis. Mrs. Gushwa got help from the charity
and received the Novartis drug. "I'm just thankful to my doctors and God and
PSI," she says.
Paul Pochtar, executive director of oncology-managed marketing at Novartis,
says his company began donating to PSI last year. "It's a fairly new
phenomenon," he says.
Novartis donated several million dollars to PSI this year to help patients
make drug co-payments, a spokeswoman says. She says the donation was less
than $10 million, but wouldn't be more specific. This generates revenue for
the company. PSI says it helped 1,255 patients in two cancer programs for
which Novartis is the only donor -- with almost all of them receiving
Gleevec. The average wholesale price of the drug at the recommended dose is
about $37,000 a year. If the patients in the program receive the recommended
dose, that could generate tens of millions of dollars in revenue.
A Novartis spokeswoman wouldn't comment about the revenue generated. In a
statement, she said that the company's donation to PSI "helps insured
patients with co-pay obligations."
If these patients weren't insured, some might qualify for free drugs.
Novartis says it gave away $100 million of Gleevec in 2004. The company says
its patient-assistance programs have helped 12,000 people world-wide gain
access to Gleevec. Sales of the drug last year were $1.6 billion.
Long-term support from the charities is uncertain. Mr. Kuhn says patients
are guaranteed assistance for two years. After that, it is hoped that they
can be weaned off the program, by finding a different insurance plan or a
new job with better benefits. "We don't want to become a social-service
agency," he says.
A Letter to Ms. Samit
This is difficult for many. Carolyn Samit, 63, of Caldwell, N.J., suffers
from primary immune deficiency, an inability to produce enough antibodies to
fight off diseases. Because her care is expensive, her insurance premiums
are high. Last year, PSI paid her health-insurance premium of $53,000.
But Mr. Kuhn called her late last year, saying she needed to find some other
way of paying for insurance this year. He followed up with a letter, saying,
"This letter is being written to you, not to create panic, but to share the
truth with you about your assistance being in jeopardy." The letter, written
to all patients with immune disorders, said PSI couldn't guarantee help for
them because corporate donations for their particular drug program had
fallen.
Ms. Samit called Mr. Kuhn, crying and begging him not to drop her, saying
she had failed for years to find another insurer that would cover her care
for less. She takes Gamunex, an immune globulin or mix of antibodies
purified out of donor blood, sold by Talecris Biotherapeutics, for which she
says her insurer pays $47,000 annually. She also needs an antibiotic,
vancomycin, which costs about $46,000 because of her frequent use. Her
insurer, Celtic Insurance, of Chicago, didn't return calls.
The widow of an American Airlines executive, Ms. Samit lost coverage under
his plan after he died. She lives on his $22,000-a-year pension and says she
wiped out her savings and her daughter's trying to pay her rising premium
until PSI stepped in.
Mr. Kuhn says he told Ms. Samit he could continue to pay her premium only if
the charity received more money from companies that make her drug. So she
began calling around, asking drug makers to boost their donations.
Officials at Baxter and Talecris acknowledge receiving Ms. Samit's calls.
Both companies say they donated to PSI this year, but note that they don't
control decisions on which patients get helped by their donations. Mr. Kuhn
says the new money allowed him to pay Ms. Samit's premium and help other
patients for another year.
"I feel grateful every day for PSI and the companies that support them," Ms.
Samit says. "I was a middle-class person living a comfortable middle-class
life. It never occurred to me in a million years that I could lose insurance
and die."
Mr. Kuhn says it's important to focus on the fact that people are being
helped by drug companies' contributions to his charity. "Although they are
making money hand over fist, they are doing wonderful things for patients,"
he says.
Write to Geeta Anand at <mailto:geeta.anand@...
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<mailto:geeta.anand@...

Hello Lynn and Everyone,
In reviewing the information a bit closer it seems that in fact trial
106 may just well be closed. The information I have seen is that as of
their last update on their conditional approval status, which was dated
April 2003, they would have had to provide annual updates on trial 106
for three years. In January 2004, they would have provided reports for
2003, In January 2005, they would have reported 2004, and in January
2006, they would have reported for 2005 - three years.
If anyone else is getting kicked off the trial or needs assistance,
please let me know, maybe I can help put you in touch with the right
person at Novartis.
Cheers, Peace, Love and light,
Cheryl-Anne

Hey hey people let's all calm down. I think everybody here posts with
the best interests of managing this disease at heart. I am sorry if
my question caused this cos I understood where everyone was coming
from in their replies. In the end, we all have to make the decisions
that make sense to us and cannot hold people in this group responsible.
We are all facing a scary thing but we are so lucky that so much can
be done for us. All we need to do is keep informed and keep
connected. CML and ego don't seem to be able to live happily together!
On the subject of intimidating newbies...the most intimidating thing
is the use of acronyms - felt like I was swimming in an alphabet soup
for a while. I am slowly beginning to understand some of it and also
feeling more confident about asking the 'dumb' questions as I keep
onfinding that I am not the onlyone who gets consfused.
So...hang in there all of you....I need you!

Hi Jane,
No, people are not put on 800mg of Gleevec because their blood counts are
higher....the standard dose for chronic phase CML is 400mg but there are
places that are doing trials to see if starting on the higher dose will
give a quicker response to the drug. If you are accelerated, they will
usually start you on 600mg.
I know you don't live in the US, but most folks can get a copy of their
blood test results, which is what you should ask for (and keep your own
records). Everything is normal in the standard blood test is a start but it
really does not mean much in CML. Usually people on Gleevec have their
blood counts stabilized (or normal) within 3 to 6 weeks or so.....and this
is called a hematological response (some use the work remission but not
really appropriate). So, on the drug you now have a normal white blood
count (which would be elevated in untreated CML) and normal platelets
(which might also be high with CML).....but if this doctor doesn't even
want to share your blood counts with you, I would definitely shop for a new
hem/onc. And when you interview others, let them know from the start that
you want/intend to be a pro-active and involved patient. To my mind, a
doctor who doesn't want to share information, just wants to be in charge
and not have you involved in decisions....not appropriate with a chronic
illness.
Nancy C.

Hi Susie,
Which new drug was your dr. referring to? Is it Dasatinib?
My husband has been in a clinical study for Dasatinib after not responding to
Gleevec. I would like to correspond with others who have info on any other new
drugs and those also having to consider BMT. I am new to the group...looking on
info to give my husband who is not computer saavy.
Thanks...Judi
Susie <leechys@...
Hi all, well just a update for wishes to know. I saw Tim and yes he
suggested I have a BMT. He said given my age and my donor, now would
be a good time. He did phone about the new drug and said i need be
able to fill in three catagaries before i would even be looked at.
Well i have two of them.. He will make contact with my next
wednesday. If that fails, then he suggested interferon...i freaked
cause ive only heard bad news about that but he assured me there was
successful stories. But he said given my toxic level..he didnt think
I would handle that either. I asked about going on Gleevec with a
200 or 300mg dose..he isnt happy with that. So he told my hubby and
me to go home and think hard about doing transplant...He gave me
stastistics and then said if i survived then he could promise me 20
years ..but he said with all the new drugs that are coming although
sound good...they cant promise that..saying that though he knows i
have a sister who is 100% match...but that still dosnt ease my
mind..hehe...but ill sit and wait till next wednesday and hopefully
have more to tell you at chat..
fingers x..
Thanks guys for your support its been great..
and a big hug to zavie..hes my insperation...love him..thanks zavie..
still in adelaide having a few days break be speak to you all soon..
Susie Leech
Dx Nov 2002
Currently off Gleevec
SPONSORED LINKS
Individual medical Cml Leukemia Health professional Cancer
center

Hi all, well just a update for wishes to know. I saw Tim and yes he
suggested I have a BMT. He said given my age and my donor, now would
be a good time. He did phone about the new drug and said i need be
able to fill in three catagaries before i would even be looked at.
Well i have two of them.. He will make contact with my next
wednesday. If that fails, then he suggested interferon...i freaked
cause ive only heard bad news about that but he assured me there was
successful stories. But he said given my toxic level..he didnt think
I would handle that either. I asked about going on Gleevec with a
200 or 300mg dose..he isnt happy with that. So he told my hubby and
me to go home and think hard about doing transplant...He gave me
stastistics and then said if i survived then he could promise me 20
years ..but he said with all the new drugs that are coming although
sound good...they cant promise that..saying that though he knows i
have a sister who is 100% match...but that still dosnt ease my
mind..hehe...but ill sit and wait till next wednesday and hopefully
have more to tell you at chat..
fingers x..
Thanks guys for your support its been great..
and a big hug to zavie..hes my insperation...love him..thanks zavie..
still in adelaide having a few days break be speak to you all soon..
Susie Leech
Dx Nov 2002
Currently off Gleevec

In a message dated 2/16/2006 12:07:51 P.M. Eastern Standard Time,
cheryl.simoneau@... writes:
Lynn, if I were you, I would get in touch with Novartis in NJ, first
going through the medical information department, and aprise them of
your situation.
Anyone else who is facing the situation of being removed from
Cheryl, I went through their website and could not find any information to
contact them. The link that appears to be the one I want is down for repair or
something like that. It said it was being worked on. I don't know how to take
this further. - Lynne A.

Hello Folks,
You might want to know that part of the process that allowed
Novartis (and will be the same for BMS if I am not mistaken)
to "fast track" Gleevec through the approval process meant that they
needed to provide continuous data, post approval, to the FDA (and
other governments where applicable)on patients and outcomes for a
specified period. In the case of Novartis, from what I understand,
they needed to provide this data starting January 2004 which means
they should provide it for at least another year. Importantly,
Novartis is compelled to provide annual reports to the FDA
specifically on patients in trial 106. Failure to do so would
result in a warning or possibly a fine to be issued to Novartis.
Which none of us wold like to see.
Lynn, if I were you, I would get in touch with Novartis in NJ, first
going through the medical information department, and aprise them of
your situation.
Anyone else who is facing the situation of being removed from this
trial should contact Novartis immediately.
Hope this helps, and please let us know what the outcome is.
Best,
Cheryl-Anne

hi Jane
just to add another consideration re bmt versus gleevec, I have had cml since
1992, I had a bmt in 1993 and was in remission for 11 years, however in June
2004 i relapsed, my point being you can go through all the trauma of bmt and
still not have cure, I have been on gleevec now for 14 months and an in Zavie's
zero club, (699). If you choose the bmt road, maybe I can give you some helpful
hints, but do your research and be sure this is the best path for you, in 1993
there was no choice, I was 41 and had 4 children aged 8-17, it was a very
difficult time for them. Gleevec is such a successful drug for most people, I
take 400 mg and have very few side effects, transplant takes a looooong time to
recover from. Welcome to the group, and feel free to ask any questions, we are
all here to help
Judy Telford
Melbourne, Australia

In a message dated 2/15/2006 2:40:06 P.M. Eastern Standard Time,
giora1@... writes:
even said that novartis is flying patients or coming to their homes to do
the tests and follow up.
i suggest that you contact novartis usa, try to get to the person in charge
of clinical trieals their, and if not to barbara (i dont remember her last
name) who is a top public relation at novartis, and demend that they will keep
tracking you on the trial even if your centre does not want to do it.
i hope you will get what you deserve.
love
Well, thank you, Giora, that is good advice. I did not realize I could do
that. I will try it and see what comes of it. You must have several patients
so they are willing to continue with you as part of a larger group. I got the
impression Novartis was not interested in following me, as I was the only
patient in the area. I was told, "Gleevec is FDA approved, and so they don't
need your information." I was stunned, and did not react, and the person who
came in and delivered this statement got up and left, said she'd be in touch
with me later. I never met her before, nor did I have any warning this would
happen so suddenly.
Thanks for your kind comments and the information. As Always, gratefully
yours, Lynne A.

Hey Group:
After being given a contact 'asap' on 12/22 by my GYN doctors office, I've
been in one of my fogs. Spent Valentines Day in my bedroom doing nothing
constructive. The TV was on. . .watching me. I couldn't concentrate on a book
and I didn't do any of the rearranging of my closet or amoire drawers.
I finally had the procedure today and didn't have a biopsy, so Group. . .
"I AM FANTASTIC" again ! ! !
Take care and know that I have you all in my prayers.
"K"
"I AIN'T FINISHED YET"!!!

Just perusing the lists and I am sorry to see there is still some hurt
feelings amongst members. Hope the issues, whatever they are, get resolved
quickly and the list can move on again.
Anyway, just wanted to check in and let everyone know what is going on in my
world. I went into hospital yesterday and was told that now the 106 trial is
ending, I will be shoved off. It seems that even though there is an extension
of the trial ( I was not given this information from them, I found it out
from the group) it appears that I am the only CML patient on Trial 106 left at
UMass in Worcester, so they said due to the enormous amount of paperwork,
follow up, and their lack of staff, etc. it is not practical to keep me on any
longer. Now it is up to me to get my HMO to approve Gleevec and pay for it. It
is FDA approved so I don't think I'll have a hassle but one never knows with
these shaky HMO's.
So, after hearing that I was going off trial I was a bit upset, although I
knew one day this would happen. I just thought they'd keep me on the extension.
They tried to make it seem as though I should be happy for the freedom, but
I'm really not liking feeling that I'm in limbo.
That also comes from being told that once again, the oncologist I have been
seeing is leaving the hospital. This is Onc. #3 in one year's time! I get one
I like and he leaves, etc., etc. And, the doctor that I've been promised
from Hammersmith, the CML expert, is apparently not coming now. So I don't know
who my doctor is going to be, don't know where I'll be treated (don't know if
off-trial I'll be able to stay at this facility) and don't know if I'll get
the HMO to pay for Gleevec.
My counts were ok, a little concerned that they were on the high side (white
count was 8,400 from 5,500 last time) but I have been feeling a bit off
kilter for a while now so perhaps I'm fighting some flu or bug. I have been
having terrible bouts of nausea/vomiting every morning and have to live on
compazine practically all the time now. I do not know if it is a long lasting
stomach flu or something else, but it is getting to be of concern. The Gleevec
is
really doing a job on me this way for some reason. For the past 5 years the
only thing I've had to deal with is the bone pain and edema. Now this! It
started a few months ago, actually, and my doctor suggest that I now break up
the
dosing to 200 mgs. in a.m. and 200mgs. p.m.
OK, just wanted to check in and if there are any others (Giora?) on 106
could you let me know what's happening on your end? Thanks, Lynne A.

Jane
I was diagnosed in May 05. I am currently on Gleevec 600mg. I am
considered"young" as well at 33. I see a local oncologist here in Las Vegas
Nevada
and I fly to Portland Oregon to see Dr. Mauro and Dr. Druker, who is the one
who developed Gleevec.
They have explained it to me as Gleevec, being the "home run in Baseball"
it is putting people in a deeper, longer remission where before people with
CML only had BMT to turn to and that was if you are lucky enough to have a
match.
There are some pretty tough complications that go along with BMT. Neither of
my doctors are talking about BMT for me. We have had lengthy discussions
about them. They say with Gleevec and the second generation drugs coming, that
CML will be like treating diabetes or heart disease. It will be a chronic
disease and that is without BMT. The mortality rate with BMT is something I
have to take into consideration as I have 3 small children. Gleevec has given
us all an alternative and I suggest to you to take your individual situation
and research as much as you can regarding the meds available and the BMT so
that you with your doctor can make the best decision for you. EDUCATE
yourself so that you can assist in your medical treatment. Be an advocate for
yourself.
I wish you best wishes on your road with CML and I hope you find lots of
support from others on the CML sites.
Jennifer (33)
CML 5/13/05
Gleevec 600 mg

Hi Tracey,
I post on Jerry's BMS board.
The posts about doctors who are ignorant about CML has come up many times in
our discussions. Partly to blame is the relative small number of patients.
Some hematologists have never even seen a CML patient in their practice. We
have also discussed doctors who can be very cold and uncaring and not really
knowledgeable on how to approach patients with a potentially fatal disease.
They are out there. To their credit, most (but not all) do care to learn
about CML and do care about the treatment their new CML patients eventually
receive and will dedicate time and energy to better themselves. That
insensitivity seen in doctors is certainly not foreign on the boards as was
your experience. My humble suggestion, which I have given to patients who
are seemingly stuck to shall we say not brilliant doctors as well, is to
show patience and to educate them on the disease and/or to the reality of
the world. Make better use of your attention by dedicating yourself to those
board members who understand and live by a better manners code.
I caught your post because you talk about Jan's grandmother having such a
low ANC while she is adviced to continue to take a strong medicine dosage.
My wife, who is a CML patient, has been experiencing WBC and ANC count
crashing while under BMS therapy. She has been advised by our doctor and the
BMS team to stop taking the medication when she is crashing. If the crashing
persists on a 2nd attempt, her dosage has been reduced. We have gone thru
this cycle 3 times and are still fighting white blood and ANC stabilization.
In between she has also been taking, under medical advice, Neupogen shots to
simulate an infection and stimulate the bone marrow to raise white blood
cells. Despite the stops and starts and the chronic problem which we are
trying to find a solution for my wife has reached CCR, FISH negative and
prcu in a 1:10,000 cells sensitivity test.
I find it strage and very dangerous for Jan's grandma to keep taking a high
dosage of Gleevec while her ANC is below the safe level of 1, when potential
neutropenia problems can develop.
I would worry a ton if I were Jan and seek other medical advice as early as
yesterday.
Please pass this email by Jan because I don't have her address.
Sincerely: a care giver.
Mario
_____
From: Tracey [mailto:traceyincanada@...]
Sent: Tuesday, February 14, 2006 2:24 PM

Hi Jan,
First I want to say that I'm sorry you and your family have been
going through so much stress regarding your grandmother.
I also want to thank you very much for your post and your kind
words. You may (or may not) have noticed that I ended up taking
some slack for the original post that I sent out. It seems that
some people were terribly offended when I suggested that some
doctors may not know what they're doing when it comes to CML. Go
figure.
As far as your grandmother is concerned, you probably have read by
now that being on just 200mg of Gleevec (as she was), is considered
a sub-optimal dose and often leads to resistance. Also, I don't
know any doctor who would declare a patient to be in blast phase
without doing a bone marrow biopsy to confirm the number of blast
cells in the marrow.
I find it concerning that she is still on the 600mg dose with her
ANC only being 0.5. That is quite low (no doubt from the overdose
with Hydroxyurea). Many doctors would stop Gleevec treatment
altogether with such a low ANC (absolute neutrophil count). You can
find the Gleevec prescribing information in our files section (at
the end of the FAQ). It mentions how to handle crashing counts such
as when to stop Gleevec and when to restart depending on what the
ANC is.
The good news is that your Grandma is about to to see one of the
biggest CML experts in the world! And there are several options open
to her with the new trials so that's even more good news :)
I wish your Grandmother all the best in the world, as well as your
whole family. Please let us know what Dr. Druker says and how your
Grandma is doing.
Take care,
Tracey

Hello to my CML family,
I just wanted to express my feelings about what has transpired on
this site recently.
I think we all have the best intentions when we write to people on
this important site. We are either patients with CML or have loved
ones with it.
It is often confusing and frustrating to learn about a diagnosis. We
have such high hopes, and you almost have to completely immerse
yourself in this disease, just to understand it.
Some members have a great working knowledge of this disease, and they
are invaluable to this group. Others don't need to know all the in's
and outs of it, but just the simply the nuts and bolts, so to speak.
We are all here to gather information, sort through it, and try to
make sense of it all. Even the experts on CML disagree from time to
time. But, in the end, you have to take a step back, emotionally,
and realize that we all have only the best of intentions.
It's easy to get fired up, when you have a disease with no cure. Life
is difficult enough at times when you are well, but it's extra hard
when you are dealt with a chronic disease. All the while, we are
all still alive, moving along day to day, raising children, managing
households etc. and trying to carve out a meaningful life for
ourselves.
We, as a group, need to come together, and know that this is site is
used for learning, sharing our experience, happiness and
heartbreaks. We are all one family. A very rare family. One in
100,000 people get this. We come from all parts of world. I feel
privilged to be part of this group.
Sincerely,
Lynn (Snickersunny)
Dx'd 12/03
400 mg
PCRU

Hello, Everyone! I will be in Oregon to see Dr. Brian Druker on March
16th. If anyone is going to be out there at that time, let me know. I
wil arrive on March 15 and be staying through the 19, I think...unless
my hubby will let me go home on the 18th. I am having a Bone Marrow
Biopsy and Aspiration. I was not supposed to have another one BUT
since Dr. Druker lowered my dosage to 300mg (which he never does) he
feels obligated to give me a "pain in my butt!"
Being a most unusual case causes Dr. Druker to do unusual things! Maybe
he will have a change of heart but I do not think so!
YOU have ALL been a blessing to me, by the way! Thank you so much.
Hugs,
Susan Rosenthal
Miami, Florida
DX 1/08/03
Began Gleevec on 4/10/03 as first line treatment.
UNDETECTABLE Oct. 14, 2005, March 24, 2006 and October 13, 2006

Dear Susie,
From five years of experience on this list (or anyway on another one that
had many of these members) I can tell you that the sort of exchange you've
had is not that uncommon, it's a bit annoying, but it needn't be taken that
seriously. For whatever reason, several of our best members (I won't
mention names) come across as a little bit scrappy at times, though I'm
quite sure they don't mean to be. In my experience, often the best thing to
do when you are feeling that someone might be attacking you or arguing some
point a little too forcefully is to ignore it and not write back at all. Or
if you feel you need to write back, then do so offline (as I'm doing here,
with you) - which avoids other people jumping in to try to help, which often
seems to make things worse!
It's nice to have you on the list. Please stay with us, and roll with the
punches - which are really little love taps, I'm quite certain.
Yours,
Richard R

I have no intention to intimidate newbies (as I've been accused of
doing) but I just have to say how very disappointed I am in some
list members and the posts I've seen.
I posted earlier about how patients should get informed and realize
that some doctors don't know everything. I wanted to help patients
feel empowered and educated. In response, I was told how terrible
this was and that members should put their entire trust in their
doctor and not second guess anything he/she says.
Now I see a list member asking opinions after her doctor suggested
she should have a BMT and what happens? Some of these very same
list members who accused me of fear mongering, are telling her to do
her research and perhaps not listen to her doctor.
I'm absolutely disgusted at some of what has transpired over the
last few posts. I had nothing but the best of intentions when I
wanted members to feel empowered and in control of their lives. I
wanted them to know that they shouldn't be bullied by any doctors.
Judging from the responses I got, it's obvious that I offended
people in saying this which I find to be more than ridiculous.
I don't want the list to go through any more unnecessary turmoil
over this utter stupidity so I won't continue this discussion
further except to say this, Good luck to you all.
Tracey

Chat Reminder - Tuesday - 9:00 PM EST

I will start off by saying Thank you Susie for your reply. I really wanted
you to understand that I was simply concurring with Tracey regarding the
Doctor situation and I "think" she like me was referring to your regular
Oncologist not all of our CML experts, which by the way I forgot to mention
I have one of those too. But feel more comfortable keeping my Oncologist as
my primary. My expert is pretty much there as a back up in the event I
needed to join a new trial. Not that I am wanting to, but by experience I
know that I have a better chance of getting into a trial if necessary if I
am an active patient in a large Center that participates in the trials.
Chris,
You addressed your post to me only- at least it appears that way? Forgive me
if my perception is wrong but I saw only my name in the subject line.
Once again I am confused because you said " Please be more accepting to
difrent countries, people, cultures , ways, ilnesses,etc as not everyone in
the world is out there to attack, I looked at this as a help group but arent
finding it to be that way."
I have to be very honest with you ... I think I may have jumped into
something bad that was going on behind the scenes? Because I can't for the
life of me figure out where I said anything about ones culture or medical
system, countries etc.
And, I really don't have any clue about how other countries run there
medical care systems and what I do know is from what all the wonderful
people from the other countries post.
Some of things I read about other countries and their healthcare system
makes me very sad... and others leave me with a feeling of envy.
Personally, I thank God that we actually have a support group which includes
people from many other countries... this is invaluable as we can learn so
much from each other. I am also certain that the experts from different
countries work together to find a cure which is why many of us are still
alive and doing well.
As for America and our health care, there are days I "REALLY" think it sucks
When I think of all senior citizens and their medicare benefits...
To think that many of them have to choose between food and medicine?
Especially now with the new system they have in place that's suppose to be
better but instead it's even worse for the poor or for the very limited
income many of them live on. And yes "that's my opinion" and No I am not
attacking America. I love America. I just don't agree with all the politics
but I refuse to go there. And no, I am neither a democrat or a republican.
But then on many days like when I am getting treatment or picking up my
medications, I am so grateful that I can. Its then I think of those less
fortunate in our country and others.
I pay 180.00 US dollars per week for medical insurance which is very high
because I work for a very small company that does not get the same lower
price for benefits as the larger corporations do, but again, I am grateful
that I am alive and well enough to work so that I can have coverage.
Somehow I think this thread became very twisted and again it has to be all
one's perception...because of that I would like to apologize to you for
whatever made you feel like this is not a group where one can post what they
want and enjoy their freedom of opinions. But I ask that you too consider
that I am now feeling that I am being accused of being closed minded and
prejudice against other cultures, countries etc.
This feeling has me thinking I should feel regret for ever saying such
wonderful things about this group and the wonderful people who provide so
much support. And many of these people are from countries outside the US.
Crediting the group and the wonderful support we have on here was and is my
only intention...
However, I will not let this situation or any other be one that deters me
from staying here. If I chose to leave the group over something like this, I
know it would be my loss and the fact is people should and will continue to
share their opinions, as I will.
Chris' I think it's wonderful that you are trying to get support for your
friend. As a cancer patient I think many of us feel that we can help others
in their fight no matter what the battle is. I want you to know that this
group saved my life and I hope you find the same here for yourself and your
friend.
Susie' I saw the posts where individuals did come across as if they were
bashing your health care system and I wasn't sure why because your post did
not intend to bash ours in any way. At least I didn't take it that way. I
kind of saw it as if you were curious about how our system works - nut not
condemning it. And even if it were your intention, I think it would be
pretty immature for one to respond in the attack back mode.
I have never and will never attack anyone on this group or in any other
group. As a matter fact in over 5 years this is the only time I have ever
been part of something like this but I still don't know how it all happened
to end up this way? Usually when I see one of these threads going on I stay
out of it because I think it's senseless. But I now wonder how they all got
started? And I sure hope that they didn't start like this because it would
be very sad to know that people left this group or any other group we were
part of due to misperception.
With all this being said I hope that we are all done with this so we can
move on to better things like supporting one another. And please anyone who
feels the need to e-mail me directly for any further clarifications
regarding my posts and intentions, feel free.
Were all in this together and we can learn from each other.
Lisa
Message: 8
Date: Sat, 11 Feb 2006 19:30:00 +1100
From: "Chris Willis" <blueshar@...
Subject: Re: Re: putting blind faith in your doctor -Lisa
Date: Sat, 11 Feb 2006 15:52:51 +1100 (EST)
From: Chris willis <cawillis9@...
Subject: Re: [cml 2] Re: putting blind faith in your doctor -Lisa

HI Michelle,
I haven't posted in a while but had seen your email and responses. I just
wanted to share my experience with the group. I was diagnosed in 2003, just
went for my yearly checkup and found out I had CML. I live in the Cayman
Islands and did some research on Leukeima for the doctors here cannot treat it
or did not know what type of Leukeima I had. I myself found MD Anderson in
Houston Texas. My insurance here has been great and I have been very very lucky
in which the doctors there are superb and I haven't had a bad experience yet. I
have been on Gleevec, 800mg since...when first starting gleevec i had every
reaction to it, name it I had it...that is when i found this group. At the time
everyone was very helpful and kept me going through the bad days, Cheryl (who is
from Canada and has a friend who lives here in the Cayman Islands) and Zavie
especially. I made friends in which 2 (Linda and Jody) actually visited me here
on a cruise ship!!!! which was great for we don't have
any one here with CML!!! As far as the "bickering" I have seen it and just
chose to ignore it. Anywhere in the world you will have opinions and i believe
that is what this is "everyone's opinions". At the beginning of being diagnosed
I had so many questions and fears in which this group did answer. Your doctor
is there for you but at times you needed an answer immediately or just to find
out what everyone or someone is going through. We are all different in our
dealings and opinions with the disease and we are all effected differently by
the medications. Some have had bad experiences with doctors and ONC and some
good. In Cayman I jsut get my blood checked every 4-6 weeks by my family doctor
and go for my check ups to houston every 6 months now (use to go every 3 months
the first year), so i don't really depend on an ONC. Some have had terrible
experiences with their BMB and BMA others nothing, again it depends on where u
go!!!
Don't be scared, it does get beter as time goes on!!! Where do u get your
treatment at? Are they going to start you on Gleevec or any other trial.
This group has helped me through many times and still do when i need a
question asked if anyone has gone through something I have gone through!!!
CML isn't a death sentence anymore and I am sure with all the great trials and
medications coming out they will have a cure soon, and if not a cure it will be
very controllable!!!
Take care and please post again or join Zavie's chat (he is a riot you
know!!!!))
Warm wishes from the Cayman Islands
Penny
michelle_thompson68 <michelle_thompson68@...

Hi Jane and welcome to the club that nobody really wants to be a member
of.
Your side effects were just like mine when I started on Gleevec. It made
me very tired. I thought it would never end, but after about 9 months on
Gleevec, it simply stopped. I keep looking for side effects but can't
find any.
I started the Zero Club the day I started taking Gleevec (it was called
STI572 in the early days). That was in March 2001. Every time that
someone on the list reported that their count was 0/20 via BMB I
assigned them a number. That is how the Zero Club started. In September
2001 I became # 102 in my own club. My most recent entry is # 941 and I
hope to see you join real soon. It is a club of HOPE.
Please do your homework before opting for a BMT. Did you doctor mention
that up to 20% of the patients that undergo a BMT are dead within 12
months from complications of the BMT. Only 50% make it past 5 years.
Zavie
Zavie Miller (age 67)
67 Shoreham Avenue
Ottawa, Canada, dxd AUG/99
INF OCT/99 to FEB/00, CHF
No meds FEB/00 to JAN/01
Gleevec since MAR/27/01 (400 mg)
CCR SEP/01. #102 in Zero Club
PCRU 5/02 at RVH
2.8 log reduction Sep/05
3.0 log reduction Jan/06
e-mail: zmiller@...
Tel: 613-726-1117
Fax: 309-296-0807
Cell: 613-202-0204

Well thanks for the responses. Nice to feel welcome and also nice
to find others who are at a similar stage to me.
I have 2 questions (so far) ...what is the zero club?
And the next one is longer....
My onncologist and the haemotologist I saw both seem to feel that
because I am "so young" (47 is young?) I should be considering a
Bone Marrow Transplant within a year of diagnosis. My gut is
telling me that if, in a years time, the Gleevec is still doing its
job why should I go through the transplant? When I say this to them
they just shake their heads wisely and tell me they understand why I
should feel that way but Gleevec is not a cure and the BMT is the
only way to go.
Am I being naive to think this way? Especially if I continue to
tolerate the Gleevec well?
By the way, if you are wondering about the weird name..Regent and
Mahogany are my horses. Jane is my own name.

It takes another newbie to speak the words right out of my mouth ... I wonder
how many more people are going to make the comment about intimidation from this
group ... I am glad in some ways that I don't join in the live chats at present
because I couldn't stand it, the thought of putting some reasonable comment
forward to it thrown right back in my face.
I really hope that some of the 'oldies' to this group will realise what is
happening here and stop the bickering.

OK -have been lurking long enough. I have not felt able to post
before because I don't understand half of what you guys are talking
about. I was diagnosed in November 05, spent some weeks on Hydroxy
Urea and am on day 13 of Gleevec. I live in cape Town, South Africa.
I hope that the little spats I have seen are unusual because I group
ike this is so important. I must say, however, that it is quite
intimidating for a newly diagnosed person to join in. Perhaps we
need somebody to take on the job of inducting newbies?
Anyway...I have a question. I am on day 13 of Gleevec. I keep
hearing about all of you dealing with hectic side effects which are
so bad that you have to stop taking it etc. Other than feeling
really tired I have experienced nothing? Does that it mean it
hasn't kicked in yet? What should I expect and when should I expect
it?
I must admit to havingfelt really sore on Hydroxy urea but the
Gleevec seems not to have had any effect.
Any ideas?

Michelle-
Welcome to the group. You will find a wealth of information and support on
these sites. I know just getting diagnosed is a very scary and uncertain
time but trust me those feelings change into hope and faith in the new drugs.
Keep a positive attitude and outlook. You have a lot to be thankful for.
I was diagnosed just last May so I know more recently then some of the old
timers, yet good timers, how fresh those thoughts are, as I still struggle with
them recently. People on this site offer great support and advice. Take
what benefits you.
Maybe it would help you to share how you were diagnosed and what you are
currently doing medically. Lets us know what is going on with you and what you
and your doctors plan is. Stay involved!
Jennifer (33)
CML 5/13/05
Gleevec 600 mg

Hello Everyone,
During the weekend of January 28 and 29th we held two consecutive meetings,
one in Montreal and one in Toronto for CML patients, their families and
friends. Both meetings were very well attended. Below, I have provided a
synopsis of both meetings. Big thanks to both Novartis and Bristol Myers
Squibb for helping us defray the costs of these meetings. All funds secured
go to paying for costs directly related to the events. The Montreal meeting
was filmed by an expert film crew who volunteered their time for us and we
hope to put together a CD/DVD which we will make available to everyone. No
one involved in the planning/organizing of the meeting charged fees for
their services. We would also like to recognize the Marriott Eaton Centre
Hotel for offering us significant discounts allowing us to hold the event in
Toronto there.
A very special BIG THANK YOU to Annikim Comtois. She is a close friend of
my daughter who lives in Toronto and does event planning. She organized the
entire meeting for us in Toronto and stayed with us for the day, without
remuneration. She is a wonderfully talented young woman with a great deal
of enthusiasm for seeing the CML Society thrive. Thank you Annikim!
It has taken me a while to put these notes together as I have been working
for 21 straight days and away on business. Today being the first day I am
able to get around to posting this information.
Montreal:
Dr. Laneuville started off the meeting by providing a brief background on
CML, as we had quite a few new patients. Then he presented highlights from
ASH. He spoke about the results of the IRIS trial, as well as the
information from both the AMN 107 trials and the Dasatinib trials. I will
make a more extensive post on Dr. Laneuville's slides in another post. We
are always very grateful to have him with us. Dr. Laneuville is an
excellent source of information to us, and I am hoping we can post some of
his slides up on our site. Please check our website: www.cmlsociety.org for
more information
Suzan McNamara presented the IRIS information recalling that she was one of
the 454 patients enrolled in the study and:
.- IM study began in 1999 - 454 pts were enrolled
.- Late chronic phase CML - failed interferon therapy
.- At enrollment patients had an expected survival time of 2 yrs
The results to date show:
. - 5 yr follow up data showed that 80% of the patients are still alive and
showed no progression rate over time
. - Pts - achieved a major cytogenic remission at 3-12 months - 90% OS
.- Pts - could not achieve cytogenic remission - 71% OS
Suzan also presented about Quiescent cells and highlighted these points:
.- Quiescent cells are cells that are not dividing but still alive
.- Ph+ quiescent stem cells are insensitive to IM or Dasatinib
.- Our Ph+ (CML) quiescent cells are quite harmless until they awaken and
start dividing again
.- May hold a mutation or a mechanism to where they are insensitive
.- Stats have shown that if we do stop IM / Dasatinib relapse
.- Reason why we cannot stop IM or Dasatinib
.- Im and/or Dasatinib do not inhibit quiescent cells therefore they do not
eliminate our disease
Suzan's presentation also included some highlights from a study with Tessa
Holyoake on FTI - BMS 214662:
BMS-214662 Targets Quiescent Chronic Myeloid Leukaemia Stem Cells and
Enhances the Activity of Both Imatinib and Dasatinib
.- BMS-214662, a farnesyl transferase inhibitor or FTI
.- IM / Dasatinib synergized with BMS-214662
.- In vitro studies demonstrated that the combination had a greater effect
of killing the Ph+ quiescent stem cells <50%
.- Currently in Phase I clinical trials
I presented information on a study in Italy of 4 patients who went off of IM
therapy, 2 relapsed and 2 did not. The interesting thing was that the two
who did not relapse had prior therapy with IFN. This leads some
investigators to think that it is possible that IFN offers an immunological
response that may endure through IM therapy.
I also presented a re-cap of AMN 107 and Dasatinib.
Some of the salient points on AMN107:
.- In reviewing the material, I have learned that AMN107 requires a less
stringent topological fit to the ATP-binding pocket in the inactive
conformation of BCR ABL. Mutations in ABL, which change the shape of the
binding pocket, have less of an effect on AMN107 binding than on IM binding.
.- AMN107 has increased potency and selectivity for Abl in contrast to IM,
which is more selective in vitro for PDGFR, followed by KIT then by ABL.
.- AMN107 is about 25 fold more potent for ABL than IM.
.- AMN107 does not interact with other TK such as Src, FLT3, VEGFR, EGFR,
InsR, RET, MET, or IGFR.
.- AMN107 selectively induces apoptosis and inhibits proliferation of
primary leukemic cells and cells transfected with BCR ABL.
.- AMN107 inhibits proliferation and autophosphorylation of 32 of 33 BCR ABL
point mutants; the only exception is T315I
.- AMN107 is expected to offer an improved side-effect profile compared with
IM, which is most encouraging to many of us.
I'll post about Toronto's meeting in the next post.
Cheers,
Cheryl-Anne

Hello and welcome to the CML group
I just thought I would throw my hat in the ring on
Doctors and a few things..I do not post much but
read a lot.
It is sad that some of us live in places where the
doctors who have tons of experience in CML live.
So we have no choice but to go with what we have
and by putting trust in him/her , that is not to say
he/she is the best but is the best in the area we live
in.
In some cases our attitude and trust in our doctors
is
all we have or, in other cases, trust in what ever God
you believe in. In my case I mentioned to my doc
some of the suggestions that were bandied about here.
My doctor said that some of these new drugs are not
available here yet but up in Ont they are, he said
he would send me. I said no, I am content to stay
where I feel safe and secure. I have lived many years
with this CML and I have had it easy compared to
some of you. At this time I am off Gleevec until my
counts come up. I just had a platelet transfusion 4
units.
I go for blood test twice week and a standing order
for
whole blood if needed. I just had another BMB and
waiting for results. I never had a Hematologist until
last Christmas(2004) , nor did I want one then, but my
GP
insisted. So even if you do not believe in the Bible
I
suggest you go online Bible read a chapter that
is only in the Deuterocanonicals or Apocrypha, Chapter
38, read the whole thing the Chapter is Called
Sickness and Medicine.
Sorry for the long post, but I just hoped to quell the
anger
or hard feelings that have come up lately.
Be Safe all
SkipD
DX 28 years ago...still kicking.
It is only with the heart one see rightly,
what is essential is invisible to the eye, said the
fox
--- michelle_thompson68

Hey Group:
I haven't been online as I should have. . . trying to enjoy my gold life. Now
I have over 278 emails, not to add the CML groups emails which carry up to 25
posts each.
Newbies, bear with us. . . I remember joining the other group just as a
difference of opinions was arising and out of that. . . emerged this group. I
almost left the group, but now I am a member of both. You, too, must read the
posts and ignore the unnecessary as I did; don't leave the group. Though we are
different and opinionated, there's a wealth of information available to you from
both groups. I'm glad that I stayed. . . hope you will also.
Take care, I have all you guys in my prayers.
"K"
"I AIN'T FINISHED YET"!!!

Hi all when i put the site up for you to see i ended up clicking on it
to make sure it works and it comes up with the front homepage. When
you click on it go to the top left hand corner and youll see where it
says under 'QUICK LINKS' click on Information Booklets.
http://www.leukaemia.com/leukaemia-foundation/web/index.asp
Susie Leech
Dx Nov 2002

To all on the site--
Haven't we all had enough of the emails/comments/apologies over the last
week or so. I don't think anyone on here would intentionally hurt or say
something hurtful to another. We are all on here for the same respect and
support
as the next person. If we continue the attacks and emails as is, there is
going to be no one left on here and we will have lost everything that these
support groups are for. These areas are for support, comfort, advice and
opinions. We are not always going to agree with each other nor are we always
going
to agree with everyone else's doctor. No one has all the answers. That is
why we are all here isn't it? To share stories, voice questions, comments
and concerns. To offer advice and provide comfort to others when needed. I
know that is one of the reasons I started reading the site. Each person is
different, each story is individualized, no two people are the same. We must
remember to offer advice, comfort and listen. People come here to talk about
what they are going through, maybe looking for some advice to share with
someone else.
We come from different parts of the world with different technology,
different doctors, different healthcare. Maybe not one better then the other
but
what we have at this time to deal with our disease, at our location.
I know I need these web-sites to fall too on my bad days/weeks for comfort,
from others are going through it as well.
Maybe I just need to get this off my chest but I just didn't want to see
anyone turn away from this site, feeling hurt or that it was useless. I hope
to
continue getting the wealth of knowledge from the people who know first
hand. The CML society here!
Thanks for lending your ears. :)
Jennifer (33)
CML 5/13/05
Gleevec 600 mg
Las Vegas Nevada

Hi guys i just thought id put this site up. In australia we have a
thing called 'Luekaemia Foundation' Australia wide and this is the
booklet they give out.I went searching for a paticular Leukeamia for a
friend and rediscovered a old site...im just interested if other
people have seen them. When i was diagnosed they gave me a booklet on
CML just thought id pass it on...as you can view the booklet
online..its great for many other leukeamias if you know of other
people who sadly are suffering from this terrible disease.
When you look at the site you might have to refresh the page or do a
cut and paste.
http://www.leukaemia.com/leukaemia-foundation/web/index.asp?
m1=13&pg=62#cymle
Susie Leech
Dx Nov 2002

To cml2 post,
Im tired of tit for tat. Ive not outright attacked anyone, just added
to someone elses post/comment. And because I seemed to be agreeing
with someone, it meant that I was disagreeing with someone else but in
my eyes I just had a different outlook. Im sorry for any confusion or
offence.
Susie Leech
Dx Nov 2002

Hi Barb and others who knew Mendy,
She was my special CML birthday Sis (shared the same day, she much younger)
and also I was the first CMLer she met face to face on her way to
Portland/OHSU to start a drug trial.
Mendy was a brave and courageous CMLer who had wonderful philosophies about
life....she used to say "it is what it is"..........and "live in the
moment". She was a wonderful wife and mother of two young children and a
dedicated 7th grade teacher.
Her CML was never real stable, not even from the start.....and finally she
decided that a BMT was her best option, as advised by Dr. Druker and the
Stanford BMT team. She did not have an easy time following the
BMT.....actually spend much of her first 100 days in the hospital with
acute GVHD with many side effects of drugs she was on. She has her BMT in
Nov 2003 and did not make it home until March. Then in April she has a
flare-up of her GVHD of the gut. In June she was hit very hard.....with
CMV infection, a repeat of GVHD of the gut, liver and kidney problems,
diabetes, seizure and stroke.....this was all at about her 7th month
post-BMT. She was fighting hard for recovery and then in July she was
hospitalized with double pneumonia and put on a ventilator. Mendy passed on
to her 'new life' as guardian angel for her family on August 6th,
2004..........only 8th months post-BMT.
Through her special and loving husband Ken, she told us all that she had no
regrets.....that all her medical problems had brought her family closer and
she had lived in the moment. Her shortened life was well lived and one of
courage, wisdom, compassion and humor.
Mendy's friend,
Maui Nanc

Hi all.
I just popped in on Melinda (Mendy) Kerner's Caring Bridge site and was
delighted to see an update from Ken (Fester as he's better known to the
group). Some of you might remember brave Melinda went in for a BMT and
initially did well - but succumbed months later to a respiratory
illness (correct me someone if I am wrong on that). She was a
wonderful friend to all of us and CML advocate . . . and I will always
fondly remember her. She was always upbeat.
Here's the link if you want to see what 'Fester' has been up to!
http://www.caringbridge.org/ca/kerner/
Hope this finds everyone doing well!
Hugs,
Barb Heathcote

Hi Fred,
It seems like it's been light years since we've heard from you. I
just wanted to say that I'm sorry to hear about your prostate cancer
diagnosis and I hope you sail through the treatment. I've heard
wonderful sucess stories regarding prostate cancer and it sure sounds
like you're getting the best treatment possible in terms of doctors.
Good luck,
Tracey

I have read the posts and cannot see any problem or what you are
taking umbrage with. No one (including Tracey)attacked
anyone personally and differences of opinions are just that,
different opinions.
We are all dealing with a life ending disease, so the stakes for
being correct are the highest one can have in the human, non-
spiritual realm. There is no doubt in my mind that this group has
saved lives through the dissemination of information and personal
experiences with good and bad docs.
When your life is on the line, it is wise to get a second opinion and
question the experience of any doctor, especially if the disease is
obscure such as CML.
Here is a true example that may help.
When I was diagnosed with prostate cancer(far from an obscure form of
cancer), I talked to Dr Druker, my doctor. He conferenced with his
urology docs at OHSU and gave me THEIR opinion, not his, as he was
not as well versed in urology. Further, he referred me to a friend
and colleague of his, Dr Donald Trump, at Roswell Park Cancer Center
in Buffalo. Dr Trump is head of research in the Urology Department
and he brought in his head of Urology, Dr Mohler, who is also head of
surgery. All of these men are great men and they all wanted to work
together to arrive at the best solution for me. As it turns out,
the best for me is a robotic laproscopic radical prostetectomy, with
pieces of my prostate being used at both OHSU for research (by Dr
Druker)and Roswell by both Dr. Trump and the leukemia department.
The above long-winded exegesis is an attempt to show that doctors,
even research specialits, who are the best in the world, do not know
everything about all things and that great doctors seek other great
doctors for second opinions and help with problems all the time, as
they should.
Finally, I fired my first oncologist right on the spot, as she was a
complete boob, knowing nothing about Gleevec, knowing nothing of
sedation for BMBs (not feeling it necessary- of course, she never had
one- I asked!) and being a tranplant flag waver. My second doc,
Jonathan Wright, is the complete opposite. Knew about Gleevec and
went to bat for me with the insurance companies, as it was not
approved for first line treatment when I started it. Also had a BMB
done on himself in medical school to see what he would be putting his
patients through. Also is delighted that I see Dr. Druker and is
happy to get all of his input, as it makes him a better doctor. I
remember when Johns Hopkins was poo pooing Gleevec and insisting on
transplants as the only way to go. If a great institution like that
is slow on the uptake in a numereically small disease such as CML, it
logically follows that there are going to be doctors who are the same.
In closing, PT Barnum said it best: Caveat Emptor! Let the buyer
beware.
Fred

Hi Chris,
I have to admit that I'm totally confused as to what you are
referring to. Where did you read that people cannot voice their
opinions here or are attacking other countries? It seems to me that
if anyone is bothered by someone else's opinion, it's you. Why do
you feel that we don't have any more right to voice our opinions
than you do?
No one said that health care systems are the same every where in the
world and I don't see how this topic even came up. The topic that I
was talking about was about how CML is not a "run of the mill"
cancer and is treated very differently than most cancers. This is
why it's very important to have a doctor who is familiar with CML or
at least to have a base knowledge yourself to know what issues to
discuss with your doctor.
If you are confident in your doctor's ability then all the power to
you. This is what I was talking about. No where did I intend to
attack anyone's doctor or decision to stay with any particular
doctor but rather to inform people that not all doctors are created
equal when it comes to CML. If someone isn't fully confident in
their doctor, they shouldn't feel bad about finding a new one. I'm
baffled as to how you are finding this so offensive.
As I said in my first post, we've seen no shortage of people who
were treated very questionably over the years and these people were
from many different countries. Some of these people knew they
needed a new doctor but didn't know how to find one. Do you suggest
that we should encourage people to stay with their doctors no matter
if they are incompetent? I would like to see people empowered
enough to take control of their lives and their care, if you find
that offensive, I'm sorry.
Tracey

In and around Melbourne I guess there must be around 20 people with CML, now
that's a fair number for such a rare illness! My own GP who diagnosed me has a
couple of his own patients and my haemotologist sees one patient a year himself.
I'm not saying that these people are 'expert' by any means but I think they do
know what they are talking about.
I'm going to try and find out more because I don't think that this country is so
far off the beaten track as many people seem to believe.
SPONSORED LINKS
Individual medical Cml Leukemia
Health professional Cancer center

The Webcast is now on line. I especially enoyed the Panel Discussion and
the Q & A session.
Zavie

Date: Sat, 11 Feb 2006 15:52:51 +1100 (EST)
From: Chris willis <cawillis9@...
Subject: Re: [cml 2] Re: putting blind faith in your doctor -Lisa

Thank You Susie :-)
It is so good to read your comments, both this one and the other note you

Hello Lisa and thankyou for your reply,
Im sorry if you felt that i was attacking you personally in my post.
In no way was that my intention but i do believe you need to go back
to the original post and read what was written,this is a quote from
one of the post (CML is very rare and Gleevec is a state of the art
drug that works very differently than any other drug on the market.
The majority of hematologists/oncologists have maybe one or two CML
patients in their practice, if even that many. Do you think they
spend hours and hours researching this disease, travelling to
conferences and consulting with experts when less than 1% of their
clientel is affected? )(My Doctor Tim Hughes specilizes in all this
and goes international for many confernces and im sure he isnt the
only one) All in all the point i just wish to make is, yes we all
have lots of things that we can post and lots of advice we can give
but lets be open and be prepared for a reply. When one does reply it
dosnt mean we are wrong it just means we might not know all the
facts. Even though Ive had no other comment other than zavie and

GENZYME'S NEW DIAGNOSTIC MONITORS GLEEVEC RESISTANCE
Biotech firm Genzyme has launched a diagnostic test to monitor drug
resistance in chronic myeloid leukemia (CML) patients who are treated
with Novartis' cancer drug Gleevec.
Genzyme's new BCR-ABL Mutation Analysis test will help physicians
evaluate resistance to therapy and facilitate appropriate adjustments
to treatment, the firm said. Despite high response rates to Gleevec
(imatinib mesylate) roughly 4 to 5 percent of patients who were
initially treated successfully will develop resistance during therapy,
Genzyme added.
The molecular hallmark of CML is a mutation known as BCR-ABL. The
mutation is the specific target for Gleevec, and is found in 95
percent of patients with CML, the company said.
In relapse patients, the majority of secondary mutations in the ABL
portion of the gene correlate with treatment failure. Genzyme's new
test detects all secondary BCR-ABL mutations and therefore predicts
resistance to Gleevec.
This test provides with leukemia patients and their caregivers more
information about their disease and will give them the ability to
personalize their treatment, said Mara Aspinall, president of Genzyme
Genetics, the business unit of Genzyme focused on the research and
development of complex testing services.

Hello Susie,
If for any reason you perceived anything that I said in my post as too harsh
or close minded, I sincerely apologize because that was not my intention.
In fact I am very open minded... open minded enough to trust and believe in
this support group for many things including just needing someone to listen.
Zavie as you mentioned are one of those people who does have a lot of
knowledge and has provided a lot of support and I am almost positive that
the place he obtained all of this was from being on this support group and
being a cml'er himself.
I personally don't recall saying anything about the doctors attending
conferences all though I am glad to say that he does go to almost everyone
of them. And never misses the ASH.
I think that what Tracey and I were merely trying to say is that sometimes
Dr's don't know everything. You said so yourself:)
And I don't mean that in a bad way.
An example of what I mean is this:
This group which is made up of primarily people with CML and we chat about
different side affects etc. We notice the common thread and then share it
with our Doctors and then they are aware that a particular side affect is
common or not common and possibly even what to do about it providing someone
has shared how their doctor treated the symptom or how they as an individual
may have treated the symptom.
We were also trying to address the fact that people need to work as a team
with their doctors as oppose to just do whatever they say.
From personal experience I can tell you that in 2000 I met with a doctor who
was the head of the BMT unit in a major center.
Keep in mind a lot of Dr's were still very skeptical as my own oncologist
was about Gleevec (it was only in trial for about 2 years then)
Anyway, I had 4 consults and was almost done being prepped for a BMT but all
the while communicating with people who were in the trial and doing so very
good.
I took a recorder with me to every consult so that I could absorb more of
the things I needed to know or think of questions after that I would like to
have asked. Four 2 hour consults with a doctor who was head of a BMT unit
and who was pushing me very hard to go for BMT and at last I saved a simple
trick question for her... Do you know if I am 100% PH positive or not? I
knew the answer but she said she didn't know.
At that point I knew there was no way possible my life or my treatment would
be left in her hands. My darn file was right there in her hands.
She could have pretended to know the answer by looking at it!
After that I told my oncologist to forget about it and I would stay on
interferon and ARC until Gleevec was available. He didn't agree at that time
but when I asked him last year March 2004 if he would have made the same
choices that I did he replied with I can't tell you a matter fact answer
because it wasn't me it was you that was in the position and one never knows
how they will react or what they will do but I can tell you that hindsight
Knowing what I know now and seeing such good results with Gleevec I would
have hoped that I had made the same choice that you did.
He also never fails to tell me how grateful he is that I stay involved and
learn as much as I do here on this support group.
I use to be his only CML patient and since my dx in 2000 he now has 13!
He is no CML expert and I don't think one has to be... I just think a good
doctor needs to be open to change and not living in the old fashioned world
of I know everything and you will do what I say because I am right since I
am the doctor.
A few years ago for a doctor to work with an empowered patient was very
difficult, today it's a wonderful thing.
Also, I have never actually seen anyone telling someone what to do on this
list or pretending to be an Oncologist, but rather giving the best advice
they have to offer which is what most people are looking for when they share
their experiences and thoughts.
I have always seen people like Tracey, Zavie, Richard and Cheryl to name
just a few; advise one to see their doctor immediately whenever someone was
having a problem that required medical attention.
Again all that we read here is going to be about our own perception and we
all have the choice as you said to take it or leave it.
Also Susie I truly believe that anytime anyone takes the time to post to one
directly is because they genuinely care.
Hopefully you feel that too:)
Lisa
Lisa Martinez
From: "Zavie miller" <zmiller@...
Subject: RE: RE:putting blind faith in your doctor -Tracey/Lisa
Hi Susie,
Thank you for your kind words. I pray that you will make it into the
trial.
Zavie
Hi Tracey and Lisa..
I to believe in this group, Zavie has been a tower of strenght to me
through my trials with gleevec. But i do beg to differ in your
comment when saying about our doctors spending their time seeing cml
patients and going to comferences as well as how many cml patients
they have. I see Tim Hughes as many people know, he sees far more
than 1 or 2 patients and yes he does go to many conferences and
specialises in cml. Im sure that he isnt the only Oncolagist that
does this. I think we need to becauful in knocking other doctors as
they are the ones that go to the uni for many years and yes they can
be wrong and that is why we have this group so we can and share our
differences. As far as you saying tracey about being told to get
life in order...well thats the very first thing Tim told me yet you
all think him as a wonderful Oncologist. So some doctors may feel
that way and its not up to us to make judement on the way they treat
their patients we just have to be here for them when they want to
talk about it. I too get concerned how some people go on this
message board, you would think that they were the Oncologist. I
think we need to be careful in answering and giving advice sometimes
the way we answer comes across very harsh and with a closed mind..
My motto is if i place a question and i get a answer from zavie or
who ever i go with the flow and if it feels good i take it on if not
then i ditch it. And as much as I think zavie is great and has been
my strength and his heart is to be there and help many others ... he
knows that there has been some advice he has given me which ive not
agreed with, we just talk it through. I think its a free world and
we are all entitled to our say but its up to us as individuals how
we receive it.
Im not in this reply going against zavie (hes my mate) but there has
been many post from other people that replied to me that ive not
agreed and their answers come across as there way is the only way...
Susie Leech
Dx Nov 2002

Thanks Zavie, but what I am taking note of is this apparent
contradiction. Huh??
"Medscape: If a patient achieves a molecular response, is it safe to
discontinue therapy?
Dr. Goldman: <snip
will come back fairly rapidly in most cases. <snip
back and the quantity of disease in the body increases, the probability
of
disease progression (advanced phase or blastic transformation) will also
probably increase."
In other words, yeah, it's safe to stop taking it if you don't mind
dying? Many of you will recall my personal experience with stopping
treatment. I don't get Goldman's self-contradictory statements here.
Jennifer G.
www.upstairswindow.org

Hi everyone, just letting you know that I started Gleevec again last
thursday. Ive given it a week and all but one night ive vomited
everynight and ive been in such pain. Well last night was the finish
of it. I had two showers for pain then i ended up throwing up
constantly in shower second time. So ive made the decision to go off
Gleevec till i see Tim next Thursday. wish me luck..
Susie Leech
Dx Nov 2002

I don't know how far you are from Portland, Oregon but if it's
feasable for you to see Dr. Druker at OHSU, you can't get a bigger
expert than that. He developed Gleevec. Dr. Mauro (also at OHSU) is
another great option.
Take care,
Tracey

Take note of his recommendations for monitoring CML.
Zavie
Long-term Results for Imatinib-Treated Patients With CML: An Interview
With Professor John Goldman
Disclosures
Sally Church, PhD
Editor's Note:
Approximately 20,000 people suffer from chronic myeloid leukemia (CML)
in the United States, and approximately 4500 new cases are diagnosed
each year.[1] The International Randomized Interferon vs STI 571 (IRIS)
trial[2] initially randomized newly diagnosed patients in the chronic
phase of the disease to either the standard of care at the time,
interferon + ara-C, or vs imatinib. When treatment with imatinib showed
a clear survival advantage and received approval from the US Food and
Drug Administration (FDA), most of the patients on interferon chose to
switch to imatinib, and now, essentially, only the imatinib arm has been
followed long-term.
This year, the updated long-term survival data[3] in these patients were
eagerly awaited at the American Society of Hematology (ASH) annual
meeting. Medscape sat down with Professor John Goldman, Fogarty Scholar
at the National Institutes of Health, Bethesda, Maryland, who presented
the data, to discuss long-term follow-up in these patients. Dr. Goldman
emphasized the importance of regular monitoring, even in patients who
are well controlled on therapy.
Medscape: The updated IRIS data[3] are now available; can you tell us
how the patients are doing over the long term?
Dr. Goldman: The answer is that they are continuing to look very good.
About 550 patients with newly diagnosed chronic-phase CML were
randomized to receive imatinib as a single agent 400 mg/daily in the
year 2000. Four years later, which is the date of the most recent
analysis, the majority of those patients are alive, still in complete
chromosomal remission, and really doing very, very well.
The most fascinating data as of right now are from 125 of the patients
who had molecular monitoring and were found to have a considerable
degree of reduction of minimal residual disease by transcript numbers,
namely a 3.2 median log reduction of transcript numbers at 1 year. At 4
years -- that is, 3 years later -- those continuing imatinib have gone
on to 3.9 log reduction. That means that during the 3 years on imatinib
during which they continued in complete chromosomal remission, the level
of disease continued to fall (as measured by molecular technology known
as reverse transcriptase polymerase chain reaction [RT-PCR]). Because we
think the level of residual disease correlates with the probability of
disease progression -- in other words, the lower the level of residual
disease, the lower the probability of disease progression -- we believe
that these patients are going to have very substantial prolongation of
life compared with those who received previous therapies. This is very
good news for a subset of patients treated with imatinib. It does not,
however, apply to every single patient treated with imatinib -- this
result particularly applies to the 20% of patients we have been able to
analyze at 4 years, but it probably applies to more than that.
Medscape: If a patient achieves a molecular response, is it safe to
discontinue therapy?
Dr. Goldman: A major molecular response (MMR) is a 3-log reduction from
a standardized baseline, so having reached an MMR, would it be safe to
discontinue therapy? The answer is yes, it is safe -- but the disease
will come back fairly rapidly in most cases. In other words, the level
of residual disease will rise, and if you wait long enough, the patient
will develop leucocytosis and clinical features of chronic-phase CML.
The other point to keep in mind is that as the disease comes back and
the quantity of disease in the body increases, the probability of
disease progression (advanced phase or blastic transformation) will also
probably increase.
So, one has to say at the present time, the best advice must be to
continue imatinib forever. That is a little bit of an exaggeration, but
certainly imatinib treatment should be continued for a very long time.
We are nowhere near the situation where one would recommend stopping
treatment, no matter how well the patient is doing, as measured by
molecular criteria.
Medscape: What are the main reasons for regular monitoring in CML, and
how does that assist in evaluating how a therapy is performing?
Dr. Goldman: Why should you monitor patients on a regular basis, even if
they are responding well to a tyrosine kinase inhibitor? Well, the
answer is because a small proportion of patients either lose their
response to the particular tyrosine kinase inhibitor or show early signs
of progression. And I think in both cases, you should contemplate a
change of therapy. One of the most important considerations for change
of therapy is the availability of allogeneic stem cell transplant, if
there is a donor, or other alternatives such as chemotherapy,
immunotherapy, or even a clinical trial with other tyrosine kinase
inhibitors. So, ensuring that the patient who has responded well
continues to maintain a really good response is important, because if he
or she loses a really good response, one has to consider alternative and
fundamentally different forms of therapy.
In terms of what you should do, the first thing is to sit down and think
very hard: (a) has this person really lost response, or (b) could you
continue imatinib, for example, at a higher dose and gain some benefit?
If the answer is potentially yes, maybe you could continue imatinib. But
assuming that you have decided that imatinib is really not working at
the highest possible dose, what else can you do? Regarding alternative
tyrosine kinase inhibitors, there are a number currently undergoing
clinical trials[4-6] and there will certainly be others within the next
12 months.
In addition to allogeneic transplant, autologous transplant is another
option that certainly needs to be considered in appropriate patients.
Cytotoxic drugs such as cytosine arabinocide (Ara-C), daunorubicin,
homoharringtonine, arsenic compounds, and decitabine are all options,
especially in advanced disease. They are all worth considering, although
none is clearly established in this situation. There is also the
possibility of introducing an immunotherapeutic approach (with
interferon-alpha), which is very interesting indeed in terms of dealing
with minimal residual disease.
Medscape: How often would you recommend monitoring to optimize therapy,
and what options are available?
Dr. Goldman: The actual recommendations for monitoring disease are still
very much under discussion. My colleague, Michele Baccarani, from
Bologna in Italy, is preparing what were originally meant to be
guidelines, but I think we now call them recommendations, for
monitoring.
Quite simply, at the time of diagnosis, I think it is clear a patient
should have a full blood count, conventional examination of the bone
marrow, examination of the bone marrow for metaphase cytogenetics, and a
baseline real-time quantitative reverse transcriptase polymerase chain
reaction (RQ-PCR). I do think those are all really mandatory today, and
I recommend a bone marrow examination again at 3 months after starting
imatinib. I would also suggest that a patient has molecular monitoring
with RQ-PCR transcript numbers on peripheral blood at every clinic
visit. It really is my recommendation -- but if not that often, at no
less frequent intervals than every 3 months -- because as that patient
achieves complete chromosomal remission, the way to continue monitoring
is with RQ-PCR.
You can also use FISH (fluorescence in situ hybridization) for BCR-ABL
fusion gene at diagnosis, to exclude the possibility of
Philadelphia-negative, BCR-ABL-positive disease and to look for a 9Q+
deletion. You can certainly use FISH sequentially thereafter, as the
patient responds to therapy, but in my opinion it should not be the
criterion by which you judge the quality and the durability of response
to therapy. The standard should be RQ-PCR for BCR-ABL transcripts, which
is probably 2 or 3 orders of magnitude more sensitive than the b