Hi Richard,

You bring up a very good point.  So far we've seen at least two 
presenters (Dr. Timothy Hughes and Dr. Hochhaus) touch on the 
correlation between leukemic load vs. response (CCR and QPCR 
specifically).  In both Dr. Hughes and Dr. Hochhaus presentations an 
upside down pyramid was used to graphically represent leukemic burden 
with horizontal lines overlayed on top of the pyramid used to denote 
the various responses (CCR, PCRU, etc.).  The impression that I got 
(and Cheryl and others feel free to chime in) was that the chart was 
simply an attempt to loosely describe the trend rather than to try 
and accurately describe the relationship.  In other words it was a 
very hand wavy chart that shows that the leukemic burden drops in 
some fashion as the response increases.  It wouldn't surprise me that 
the relationship is non-linear and maybe even exponential as you 
suggest.  

Of interest in this discussion is that the leukemic load for PCRU 
being displayed by Dr. Hughes and Dr. Hochhaus differed by a full 
log. This added to my feeling that the chart was very hand wavy.

I would like to know more about this relationship though, so if you e-
mail Dr. D., please let us know.  Similarly, if I hear more about 
this in the next few days in ASH,  I'll be sure to post it.  
Fundamentally it would be nice to know how many leukemic cells we 
have at PCRU. 

You also brought up an interesting point about the log reduction due 
to simply gaining a hematalogic response.  We tend to think along the 
lines of IM-only therapy when discussing log reductions but many 
patients are initially treated with Hydrea.  In my case for example, 
I had a full log reduction hematologically just due to hydrea alone. 
This implies that newly diagnosed patients should have their PCR test 
performed at initial diagnosis rather than at initial treatment for 
Gleevec.  This is something I hadn't thought of before and a possible 
reason why my initial PCR test was so low.  I'm going to have to look 
at the dates on my test results again.  Interesting food for thought!

Regards,
Mark

--- In [EMAIL PROTECTED], rrockef1 <[EMAIL PROTECTED]> wrote:
> I've heard this assertion before, but I don't believe it's not 
true. Let's
> stay you start out with a WBC of, say, 200,000, and that you 
are "100%"
> Philly positive by conventional cyto.  At that point it's estimated 
that you
> have 10E12 (I've more often heard 10E13, but never mind, the point 
I'm
> making will be the same) Phillies in your body.  If you respond 
well to IM
> and reduce your ANC to 2000, you're already lopped off two logs, 
down to
> 10E10; Let's say further that at diagnosis your ratio of Phillies 
to normal
> cells is 100/1 (obviously you're not really 100% Philly positive; 
it just
> looks it to the relatively insensitive conventional cyto test). 
When you
> reach CCR by conventional cyto, let's say that the ratio is now the
> opposite, 1 Philly to 100 normals.  If the ANC is still 2000, 
you've thus
> dropped another 2 logs, (4 logs total) to 10E8 Phillies, not the 
10E10
> that's asserted here. And if you reach CCR by FISH, you're more 
likely to
> have reduced your Phillies by 5 logs total.
> 
> Reaching CCR demonstrably decreases the qPCR by only a couple of 
logs, but
> there's an exponentialy, not a linear relationship between qPCR and 
leukemic
> load, as I've previously reported, and confirmed by the head of the
> laboratory at OHSU.
> 
> So is my reasoning right here, or am I missing something?  Any
> mathematicians out there who could help me out?  Or perhaps it's a
> physiological matter, having to do with the quantity of Phillies 
hanging out
> in the peripheral blood vs the bone marrow at various stages of 
remission.
> 
> Anyway, unless any of you has the answer, I think I'll email Dr. 
Druker
> about this once he gets back from ASH and see whether or not he 
agrees with
> Dr. H's assertion, and if so, how so.
> 
> Cheers,
> 
> Richard R






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