Great report, Cheryl and Mark. Thanks so much. Will you be going to Dr Sawyers presentation on Sunday? Sure wish I could be there, he is such a great doctor.
Have fun and keep up the good work. You are doing so much good for so many folks.
blessed be nancy w inyokern ca
cher111376 <[EMAIL PROTECTED]> wrote:
cher111376 <[EMAIL PROTECTED]> wrote:
Converting Cytogenetic Responses to Molecular Responses and Boosting
Suboptimal Responses: The Importance of Risk Stratification in CML �
Dr. Timothy Hughes, Australia
The overall take home message of this presentation was that patients
should be closely monitored with QPCR, and those patients not
achieving at least a 2 log reduction within six months of starting IM
therapy should be considered for mutation testing and/or dose
escalation.
Dr Hughes reviewed the following points:
� What have we learned from the IRIS molecular Study? � 400 mg
dose for newly diagnosed patients, evaluating molecular response for
the first 24 months in CCR patients.
o Patients with a major molecular response (MMR) (defined as 3
log reduction) by 12 months (40%) had a high probability of PFS
(Progression free survival)
o Very few patients had undetectable levels of BCR-ABL (3%)
which he defines as a 4 + log reduction.
o Of those people that had a greater than 3 log reduction there
was no progression at 36 months.
 Greater than 3 log reduction 100% were PFS
 Less than 3 log reduction were 93% PFS
 Thos that had no CCR in 12 mos. 81% were PFS
His Australasian study showed that BCR-ABL levels continued to
decrease over time, the bigger the log reduction the better and that
it goes without saying 4 log is better than 3. He presented a very
interesting chart which showed the absolute leukemic cell load versus
the QPCR response. This chart was interesting because it shows that
at CCR (Zero FISH = 2 log reduction) = 1,000,000,000 leukemic cells
are still estimated to be in your body. Even if you are PCRU, you
still may have 100,000 leukemic cells.
Patients who achieved a 3 log reduction went on to achieve a
further .7 log reduction between months 24 � 43.
Of interest to this list and particularly to Giora, he showed a case
of a patient who had a very good response to IM who became PCRU @ 6
months and stayed PCRU through 54 months and the question was, "Is
this person cured?" He doesn't want to risk taking the patient off
of IM to see, but he really wants to know is he cured, he thinks,
highly likely not. Editors note thanks to Giora, we have some
insight to this.
On the subject of mutations, as of today there are 40 known
mutations. A sobering thought. A few months ago there were only 33,
and 6 months ago it was only 16 or so.
Of the patients who will develop a resistance to IM, 20-30% do so
through some other mechanism than mutation. This spurred some
discussion on blood serum levels and resistance, Dr. Hughes said he
doesn't know and he hasn't seen research on this at this time.
In his study 7 of the 103 patients had evidence of resistance in the
first 12 months with the following outcomes:
2 went into blast phase
3 lost MCR or CCR
2 had rise in BCR ABL
Of those 7, 6 had mutations in the BCR-ABL kinase domain
Predictive power for mutations
He has a high confidence that a 2 fold (note this does not
mean a two log) increase represents a true rise rather than random
variance, and could be use as a predictor for mutation testing.
A two fold rise in QPCR provides a cost effective trigger for
mutation testing. Rather than testing everyone; the mutation testing
at this time would also give more time to decide treatment options.
Dr. Hughes suggested that there should be two criteria for mutation
testing:
2 fold rise as above
Turtles - < 1 log reduction at 6 months (mutation test should
be done every three months)
Cheers,
Your ASH reporters,
Cheryl-Anne & Mark Petersen
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