Re: Re: FISH and PCR tests

May 11, 2007

Thank you.

So I guess my question then is what defines complete cytogenic remission. Or,

whatever the final best stage of remission is.

Tracey <traceyincanada@...> wrote:

Hi Efrem,

A lot of doctors only do the PCR test once a person has reached CCR.

FISH tests are not that reliable and they are not very sensitive

either. A FISH test will only look at 200-500 cells whereas a PCR

test can look at up to a million cells (depending on the lab).

That's why you can be zero on a FISH test but not a PCR.

The analogy I like to use is this: if you took a swimming pool and

filled it up with ping pong balls. You put a trillion white ping

pong balls in it (which represent the good, healthy cells) and 10,000

blue ping pong balls (which represent the bad, leukemic cells) in

it. Then if you scooped out 500 balls, you could easily find all 500

to be white (good cells) but if you scooped out a million balls,

there's a much greater chance that you'll find a few blue ones in

there (bad cells).

The more cells they look at, the more chances they'll find one that

has the bcr/abl protein. In fact, just about everyone still has

bcr/abl positive cells, the question is if the lab is using a

sensitive enough PCR to detect them. Just because some people show

negative on a PCR, doesn't mean they don't have any leukemic cells in

them, it just means that the test wasn't sensitive enough to pick

them up.

Your goal in treatment is to reach a 3 log reduction from baseline

which is a thousand fold decrease in bcr/abl cells. Each lab has

what they consider to be their baseline so depending on the lab you

use, they'll either mark on your report how you compare with that

baseline or they'll give you the numbers and you'll have to figure it

out yourself.

I hope that helps,

Tracey

>

> I know that I have asked this question already but I lost my

responses.

>

> I have been on Gleevec for almost four months and reached

cytologic remission last month. My doctor drew some additional blood

this past week to now conduct a FISH test and do a PCR for the BCR-

ABL protein..

>

> Can someone please remind me the difference between the two tests

and why we do both.

>

> Also, my doctor told me that you can be FISH negative but still

have the BCR-ABL protein in your body. Can someone please elaborate

on that and explain how that is possible, and whatthat means as far

as remission.

>

> Thank You

>

> Efrem

>

May 11, 2007

That was a really good analogy!

--- Tracey <traceyincanada@...> wrote:

> Hi Efrem,

>

> A lot of doctors only do the PCR test once a person

> has reached CCR.

> FISH tests are not that reliable and they are not

> very sensitive

> either. A FISH test will only look at 200-500 cells

> whereas a PCR

> test can look at up to a million cells (depending on

> the lab).

> That's why you can be zero on a FISH test but not a

> PCR.

>

> The analogy I like to use is this: if you took a

> swimming pool and

> filled it up with ping pong balls. You put a

> trillion white ping

> pong balls in it (which represent the good, healthy

> cells) and 10,000

> blue ping pong balls (which represent the bad,

> leukemic cells) in

> it. Then if you scooped out 500 balls, you could

> easily find all 500

> to be white (good cells) but if you scooped out a

> million balls,

> there's a much greater chance that you'll find a few

> blue ones in

> there (bad cells).

>

> The more cells they look at, the more chances

> they'll find one that

> has the bcr/abl protein. In fact, just about

> everyone still has

> bcr/abl positive cells, the question is if the lab

> is using a

> sensitive enough PCR to detect them. Just because

> some people show

> negative on a PCR, doesn't mean they don't have any

> leukemic cells in

> them, it just means that the test wasn't sensitive

> enough to pick

> them up.

>

> Your goal in treatment is to reach a 3 log reduction

> from baseline

> which is a thousand fold decrease in bcr/abl cells.

> Each lab has

> what they consider to be their baseline so depending

> on the lab you

> use, they'll either mark on your report how you

> compare with that

> baseline or they'll give you the numbers and you'll

> have to figure it

> out yourself.

>

> I hope that helps,

> Tracey

>

> >

> > I know that I have asked this question already but

> I lost my

> responses.

> >

> > I have been on Gleevec for almost four months

> and reached

> cytologic remission last month. My doctor drew some

> additional blood

> this past week to now conduct a FISH test and do a

> PCR for the BCR-

> ABL protein..

> >

> > Can someone please remind me the difference

> between the two tests

> and why we do both.

> >

> > Also, my doctor told me that you can be FISH

> negative but still

> have the BCR-ABL protein in your body. Can someone

> please elaborate

> on that and explain how that is possible, and

> whatthat means as far

> as remission.

> >

> > Thank You

> >

> > Efrem

> >

> > [Non-text portions of this message have been

> removed]

> >

>

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May 11, 2007

CHR : Complete Hematologic Remission = blood counts normal

MCR : Major Cytogenetic Response = less than 33% of ph+ cells on the

cytogenetic test (looks at about 20 cells, depending on lab)

CCR : Complete Cytogenetic Remission = 0 ph+ cells on the cytogenetic test,

FISH can be zero or positive, in general less than 10%. 1 cell in 20 is 5%,

but as the sampling differs (not the same blood sample) the actual

cytogenetic and FISH results are in general different.

MMR : Major Molecular Response = 3 log reduction from baseline on the PCR

(quantitative PCR) test. This isn't very consistent from lab to lab, in

general something in the range 0.1% - 0.05% ph+ cells,depending on what

baseline value they choose. I think in theory you should use the value of

your first bmb at dx but I dunno if it is what all labs do. I started with

100% ph+, so I just use that.

CMR : Complete Molecular Remission = 0 on the PCR test. As Tracey said, it

doesn't mean there isn't any ph+ cells, it is just the sampling (number of

cells checked) is not large enough to have a good likelihood of finding one.

Great example with the pong balls in the pool.

Depending on the lab the results are expressed as a ratio (or in percentage.

The ratio 1/100 = 0.01 is 1%, 0.001 is 0.1%, etc. The information should be

given on the test result paper. The log for the MMR is in base ten, which

means that log(0.1)= -1, log(0.01)= -2, log (0.001)= -3. So if the baseline

is 100% ph+, and the PCR shows 0.001 = 0.1%, it is a 3 log reduction. If the

baseline is 50%, you need a 0.0005 = 0.05% PCR to have a 3 log reduction.

The drawback of the PCR test, much more sensitive than cytogenetics or FISH,

is that it looks only for 1 or 2 modifications of the genes at the BCR/ABL

area. Unlike the cytogenetic test it doesn't check for additional mutations.

Cheers,

Marcos.

On 5/11/07, fischer <efrem_fischer@...> wrote:

>

> Thank you.

> So I guess my question then is what defines complete cytogenic remission.

> Or, whatever the final best stage of remission is.

>

> Tracey <traceyincanada@... <traceyincanada%40>> wrote:

> Hi Efrem,

>

> A lot of doctors only do the PCR test once a person has reached CCR.

> FISH tests are not that reliable and they are not very sensitive

> either. A FISH test will only look at 200-500 cells whereas a PCR

> test can look at up to a million cells (depending on the lab).

> That's why you can be zero on a FISH test but not a PCR.

>

> The analogy I like to use is this: if you took a swimming pool and

> filled it up with ping pong balls. You put a trillion white ping

> pong balls in it (which represent the good, healthy cells) and 10,000

> blue ping pong balls (which represent the bad, leukemic cells) in

> it. Then if you scooped out 500 balls, you could easily find all 500

> to be white (good cells) but if you scooped out a million balls,

> there's a much greater chance that you'll find a few blue ones in

> there (bad cells).

>

> The more cells they look at, the more chances they'll find one that

> has the bcr/abl protein. In fact, just about everyone still has

> bcr/abl positive cells, the question is if the lab is using a

> sensitive enough PCR to detect them. Just because some people show

> negative on a PCR, doesn't mean they don't have any leukemic cells in

> them, it just means that the test wasn't sensitive enough to pick

> them up.

>

> Your goal in treatment is to reach a 3 log reduction from baseline

> which is a thousand fold decrease in bcr/abl cells. Each lab has

> what they consider to be their baseline so depending on the lab you

> use, they'll either mark on your report how you compare with that

> baseline or they'll give you the numbers and you'll have to figure it

> out yourself.

>

> I hope that helps,

> Tracey

>

> >

> > I know that I have asked this question already but I lost my

> responses.

> >

> > I have been on Gleevec for almost four months and reached

> cytologic remission last month. My doctor drew some additional blood

> this past week to now conduct a FISH test and do a PCR for the BCR-

> ABL protein..

> >

> > Can someone please remind me the difference between the two tests

> and why we do both.

> >

> > Also, my doctor told me that you can be FISH negative but still

> have the BCR-ABL protein in your body. Can someone please elaborate

> on that and explain how that is possible, and whatthat means as far

> as remission.

> >

> > Thank You

> >

> > Efrem

> >

May 11, 2007

Thanks for write up, printed it out so as I get to CHR I will know steps

Tn.

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May 11, 2007

Thank you all for the excellent explanations and examples.

Once you reach PCRU on the most sensitive PCR test on the planet, what then?

Well, you can go off Gleevec and see what happens. Some have tried this and

in almost all cases the CML has returned. I say almost every case because we

don't have any long term data. Also, no one has done a full scale clinical

trial to measure the percentage of patients that remain PCRU long term after

stopping Gleevec.

I recall when Giora was zero by the most sensitive PCRU test on the planet

(at that time) and he cycled off and on Gleevec on a monthly basis. The CML

was detected again after the second month off Gleevec.

In my own personal case, my PCR results are PCRU when done in a lab in

Ottawa and a 3.0 log reduction when done in a lab in Toronto.

So which one do you believe? The problem is that there is no standardization

of the PCR testing and you are the mercy of the lab running your test.

I just don't see any advantage to try and get to PCRU by raising the dose of

Gleevec once you have achieved a 3 log reduction.

Zavie

Zavie (age 68)

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

2.8 log reduction Sep/05

3.0 log reduction Jan/06

2.9 log reduction Feb/07

e-mail: zmiller@...

Tel: 613-726-1117

Fax: 309-296-0807

Cell: 613-202-0204

ID: zaviem

Re: [ ] Re: FISH and PCR tests