Dear Jeanie,

  Since PCRs are not standardized from lab to lab, we cannot compare
values like we do from the other tests unless we all do PCR at the same
lab.  Doctors recommend to watch the PCR trend so your next PCR value
is important.  Ideally, it should be going down.  I know we cannot
compare PCR values but just to give you an example, these are Roy's PCR
values to date:

0.8%
0.5%
0.4%
0.2%
0.1%
0.7%
0.4%

So, at our lab, his trend has been downwards except for the spike at
0.7%.  When that spike happened, our doctor immediately ordered a
retest and that gave 0.4%.  Be aware that minor fluctuations in the PCR
can happen and nothing to be alarmed.  Only when a PCR goes up by
10-fold say from 0.1% to 1%, doctors will order a retest and if same
results are shown, order a biopsy to see if there is any disease
progression in the marrow.

  It is important to stick to the same PCR lab and compare the PCR
trends in one lab since the technique has variables and CML experts
recommend to stick to one lab and compare trends there.

  There is a milestone the CML experts recommend to reach which is a
1000-fold reduction of PCR values from diagnosis.  Now, I know this is
your first PCR value and you may not have a diagnosis PCR value.  Roy
did not have one, either.  To circumvent, what PCR labs usually do is
have a baseline diagnosis PCR value from new patients testing at that
lab and you compare your value to the baseline at your PCR lab and see
if you have reached a 1000-fold reduction also called 3-log reduction
at your lab.  This may also be described as a major molecular response
or MMR.  From the IRIS trials, doctors have found that those who reach
this milestone have least risk of relapse from Gleevec.

  Here's what you can do:

1.  Monitor your PCR trends over time, if they are going down, it is
fine.  Our doctor does these tests every 3 months for Roy.  Monitor
like you would your disease reduction with a biopsy.  The PCR numbers
are a ratio of bad cells to good ones.

2.  Ask your doctor if you have reached MMR at your lab.  Some labs
will have a MMR or 3-log value and some do not.  If you have not, how
far away are you from this milestone and if your PCR values trend
downwards, you will reach this value with time.

Below, I have given you Dr. Deininger's excerpt on PCR from his talk at
ASH 2005.

  It took me awhile to learn about PCR testing, but since after CCR,
the disease will be monitored this way, it is better to know what to
look out for.

  Compare your 0.125% number to the next one.  Usually, in most labs
1-2% by PCR correlates to complete cytogenetic response so going by
that, your value looks fine.  You should see it going down in the next
test.

  What Dr. Deininger's excerpt is saying is that standardization of PCR
values worldwide is needed but in the meantime, look at the PCR trends
from the blood in one lab and compare to the lab MMR value to see how
you are doing.

Best Wishes,
Anjana
caregiver to Roy
d/x Jan 2002
Gleevec 400mg
CCR Sep 2002

http://www.asheducationbook.org/cgi/content/full/2005/1/174

Quantitative PCR.
qPCR has emerged as the method of choice for monitoring residual
disease in patients with CCR. Given that the majority of patients in
first chronic phase achieve CCR, qPCR is the only method that allows
disease monitoring in these patients and should be regarded as state of
the art for following patients with imatinib-induced CCR. In addition,
analysis of a subset of patients from the IRIS trial revealed a
significant correlation between the molecular response at 3 months and
CCR at 12 months.8 At 12 months patients with CCR can be classified
according to their molecular response into those with a reduction of
BCR-ABL transcripts by at least 3-log (MMR) and less than 3-log.24 With
42 months of follow-up, PFS for patients with CCR and  3-log reduction
was 98%, compared to 90% for patients with CCR but < 3-log reduction of
transcripts, and 75% for patients without CCR.3 Importantly, the log
reductions in this study were calculated with a pretherapeutic standard
derived from a group of untreated patients. This implies that qPCR
monitoring can be initiated at any time during imatinib therapy,
without the need for an individual pretherapeutic specimen. As there is
a very good correlation between BCR-ABL mRNA levels in the blood and
bone marrow,7 qPCR analysis can be performed on peripheral blood, which
is much more convenient for the patient. Current recommendations are to
perform qPCR on peripheral blood every 3 months. Standardization of
qPCR methodology is urgently required to allow for adequate monitoring
of patients outside of clinical trials and academic centers.

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