Re: I'm a newbie to this group and to CML

May 29, 2009

Dear

You have come to the right place. Welcome and we will all try to help.

I will let someone else more knowledgeable help with the terms and I will

learn too.

Hang in there you are going to be fine.

I just wanted to welcome you.

Sharon T

_____

From: [mailto: ] On Behalf Of

wendyphillips54

Sent: Friday, May 29, 2009 1:24 AM

Subject: [ ] I'm a newbie to this group and to CML

Hi, my name is and I learned about this group from Zavie. I was

diagnosed in February with CML. I am being treated with Gleevec but not

having any luck with it bringing my WBC down. My Dr increased my dosage from

400mg a day to 800mgs a day. I am not sure if it is helping yet or not.

Since I am new to CML, there are a lot of terms that I don't understand

yet...like log reduction and MMR and I think one was CHR. So if anyone would

like to educate me on the terms and what to look for, I would really

appreciate it. Is it normal to have leg cramps? I feel totally exhausted

most of the time. I am looking forward to hearing from some of y'all and

learning more about this disease....

May 29, 2009

Hi ,

You are in the right place for al the support and advice you will ever need I

was diagnosed with CML in Oct 2008 and during my research I came across this

info which helped me out a great deal.

I have cut and pasted this so this shouldhelp you understand all the bits that

confused us all in the beginning. Keep you chin up you will be ok different

people react in different ways.

Good reading and best wishes mark.....

There have been requests for information about the various tests done

on folks with CML, since it is often hard to understand the

terminology. This is designed as a general overview to provide a basic

layman's understanding of testing and CML. I will avoid the jargon and

keep this somewhat short, so this will not try to cover everything in

detail. For more details, Google the phrase and also ask your doctor/

Oncologist about tests for your specific situation.

There are tests to diagnose CML, evaluate response to therapy, assess

the levels of the remaining disease, and to check for specific

problems. These include Complete Blood Count (CBC), Bone Marrow Biopsy

(BMB), Bone Marrow Aspiration (BMA), Cytogenetics Testing,

Fluorescence In Situ Hybridization (FISH) testing, Polymerase Chain

Reaction (PCR) testing, and other specialized tests.

When a person is suspected of having CML, testing is done to confirm

the diagnosis. A Complete Blood Count (CBC) test will usually show a

very high white blood cell (WBC) count, and may also show high

platelets (PLT) and other abnormalities. But this does not confirm

that a person has CML. The confirmation of CML is usually done by

Cytogenetics Testing on cells taken during a Bone Marrow Biopsy

process. During a BMB, a core sample is taken from the hip bone, and

marrow cells are collected that cling to that bone sample. While the

hole is open in the hip bone, fluid from the hip marrow is also taken

out by a syringe, and this second part is called a Bone Marrow

Aspiration. The BMA aspirate or fluid is extracted through the hole

created during the BMB. Cytogenetics Testing (looking at the genetic

structure of the cells) is then done on the core sample and aspirate

fluid. The marrow cells are viewed by a lab technician and/or doctor

under a microscope, where the chromosomes are treated with a dye and

observed, and the Philadelphia Chromosome (Ph+ chromosome), which is

the marker of CML, can be seen and a diagnosis made. The core sample

(bone and marrow) is also checked for other abnormalities. So

Cytogenetics Testing is done using the BMB core sample and aspirate

viewed under a microscope. Cytogenetics Testing is also used to check

for other chromosome mutations and abnormalities, so a BMB might be

done again at six months post-diagnosis, and then every 12-18 months

after that, or sooner if other tests show a suspected problem such as

loss of response to drug therapy. When therapy reduces the levels of

CML disease to where the Cytogenetics Testing can no longer detect any

Ph+ chromosome cells among the approx 20 that are counted, that person

has achieved a Complete Cytogenetic Response (CCR).

After diagnosis, it is important to continually monitor response to

therapy with regular Complete Blood Count tests. When these CBC tests

show that the blood counts have returned to normal levels, and

especially the WBC and platelet counts, the person has achieved a

Complete Hematological Response (CHR). After that, the CBCs should

still be continued, but the frequency is often reduced. If the CBC

counts show a loss of CHR, a BMB is generally ordered to assess the

situation in the marrow. However, CBCs for folks with CML often are

not completely normal ranges due to the supressing effects of drug

therapy.

The BMA fluid taken after a BMB core sample procedure can also be used

to perform a FISH or PCR test. Or circulating (peripheral) blood can

also be used nowadays with nearly equal confidence levels to perform a

FISH or PCR. Both FISH and PCR show the levels of CML disease, and are

used to monitor progress, or detect setbacks or loss of response to

therapy. A FISH test checks approximately 200 - 500 cells, and counts

the number of cells that have the Ph+ chromosome (technically it looks

for the BCR-ABL gene in the cells). This is done by a machine which

uses a dye process, isolates approx 200 - 500 cells, and counts the

leukemic cells. The result is given as a percentage of leukemic cells

to good cells, so the person can say that X% of their cells are

leukemic. The limitation of FISH is that it can only count a small

sample of cells, so if the level of disease is only a few percent, the

FISH report will likely be zero (a zero FISH is also CCR, same as a

zero Cytogenetics Test). So FISH is generally not used once the level

of leukemia drops below approximately 5%. At that point PCR testing is

used to monitor CML patients in this Minimal Residual Disease (MRD)

status, since it is far more sensitive. A trend among Oncologists is

to start doing PCRs early instead of FISH, since PCRs are more

sensitive and can be used to track log reductions in disease levels,

and FISH cannot track log reductions.

There are two types of PCR tests. One is called a Qualitative PCR,

which is a simple " yes/no " test that says it either detected BCR-ABL

(leukemic cells) or did not detect them, but no number - this is

generally only useful to help diagnose CML since it helps distinguish

between CML and a type of Ph+ ALL leukemia. The other type of PCR, the

Quantitative PCR, counts the number of BCR-ABL (Ph+ chromosome cells)

and reports it, so this is the type of PCR that is useful to track

treatment progress, especially in Minimal Residual Disease (MRD)

status. Some Oncologists will do a baseline Quantitative PCR at or

near diagnosis to establish a baseline from which to evaluate progress

toward a 3 log reduction in disease levels. Since a baseline PCR is

not always done, it makes the 3 log reduction goal difficult to track,

since many do not know where they started at diagnosis. Because drugs

like Gleevec and Sprycel can rapidly reduce the levels of leukemic

cells, if the first PCR is not done before starting drug therapy, the

baseline for calculating a 3 log reduction will not be very

accurate.

PCR tests a sample of blood or marrow fluid, and can detect

approximately 1 leukemic cell out of 1 million cells in the sample. As

such, it is the most sensitive testing available at this time. PCR

testing can be done with relatively equivalent results from either

blood or BMA fluid. During a PCR test, the BCR-ABL in leukemic cells

is counted and the result of the test is given as a percentage ratio

of BCR-ABL (leukemic cells) to another gene in the cells (called a

control gene). So PCR results are not a ratio of leukemic cells to

good cells as we might think, which technically means that a PCR

result is not actually a total percentage of leukemic cells in the

body. This is one reason why PCR results from one person to another,

and one lab to another, are not equivalent, due to lack of

standardization among labs regarding equipment and which control genes

are used (there are several different control genes used for CML

PCRs). That is a reason for sticking with the same lab, so the results

will be directly comparable for each PCR done, and trends can be

watched. It is important when switching labs that the first PCR from

the new lab be used to set a new baseline, and not be directly

compared to the previous PCR from the other lab.

PCR results are very useful for showing trends, whether progress or

retrogression. The hope for PCR results is to see progress toward a 3

logarithmic (3 log) reduction from the level of disease that existed

at the time of diagnosis. This 3 log reduction is called a Major

Molecular Response (MMR). The main issue is that many folks with CML

do not have a baseline quantitative PCR done at diagnosis before

starting drug therapy, and many labs do not have a scale that equates

to CCR, MMR, etc., so determining the 3 log reduction is not always

easy. If someone has a baseline PCR value, the 3 log goal can be

calculated by taking the baseline PCR number and moving the decimal

point 3 places to the left. For example, if the PCR at diagnosis was

35.0%, moving the decimal point one place to the left is 3.50% (1

log), two decimal places is .35% (2 log), and three decimal places is .

035%, which is a 3 log reduction. So 3 log/MMR for that person at that

lab would be .035%. If someone does not have a baseline PCR, using a

PCR value that was done weeks or months after starting drug therapy

should not become a cause for concern that a 3 log reduction from that

first PCR was not achieved, since it is not a valid comparison. In

that case, one would need to assume some level of reduction occurred

before that first PCR, possibly even a significant drop.

If a 3 log reduction is achieved, the next goal becomes maintaining

the 3 log reduction or even continued reduction toward PCR

undetectable (PCRU), where the PCR is not sensitive enough to detect

any leukemic cells in the sample. This PCRU is called Complete

Molecular Response (CMR), which is the deepest level of response

currently measurable. In PCRU status, the leukemic cells are most

likely still there, although fewer than 1 in a million. There is no

test to determine if a person with CML is actually cured (usually

associated with a stem cell/marrow transplant). The current indicator

is 5 years without therapy coupled with continuous PCRU.

There are other tests that are used for monitoring CML patients, such

as a Liver Function Test to make sure the liver is not adversely

affected by CML drugs; a Basic Metabolic Profile which checks both

mineral levels and kidney function; heart function tests (a disputed

issue among researchers); CAT Scans or physical checks for enlarged

spleen, checks for enlarged lymph nodes; and complete or partial

physical exams. There are also other lab tests to check for specific

problems when suspected.

>

> Hi, my name is and I learned about this group from Zavie. I was

diagnosed in February with CML. I am being treated with Gleevec but not having

any luck with it bringing my WBC down. My Dr increased my dosage from 400mg a

day to 800mgs a day. I am not sure if it is helping yet or not. Since I am new

to CML, there are a lot of terms that I don't understand yet...like log

reduction and MMR and I think one was CHR. So if anyone would like to educate me

on the terms and what to look for, I would really appreciate it. Is it normal to

have leg cramps? I feel totally exhausted most of the time. I am looking forward

to hearing from some of y'all and learning more about this disease....

>

May 30, 2009

Hi Sharon and thanks so much for welcoming me into the group. I can tell from

reading everyone else's post that there is a lot more to this disease than I

thought. I am looking forward to learning more about it.....

From: Sharon Teichera <onthewtr@...>

Subject: RE: [ ] I'm a newbie to this group and to CML

Date: Friday, May 29, 2009, 1:44 PM