I am not sure you will find that current guidelines will differ that much year on year. So guidelines from 2007 will be pretty much the standard in 2009.
I have taken a look at the European Leukaemia Network current guidelines and copied the information relevant to the questions asked in previous posts.
Hope this is helpful,
Sandy
Assessment In Ph+ CML
Evidence obtained in clinical trials and post-approval setting with targeted therapy has prompted experts to formulate consensus recommendations for response assessment and treatment of patients with Ph+ CML.
The European LeukemiaNet recommendations propose a schedule of response expectations at various time points of targeted therapy.
CML Treatment Goals Objectives:
Stabilise blood counts
Haematological response
Cytogenetic Response
Molecular response
Haematological Response:
Normalise WBC counts
Eliminate immature myeloid cells
Eradicate signs and symptoms of disease
Maintain response for >4 weeks
Cytogenetic Response:
Complete cytogenetic response — elimination of the Ph chromosome
Partial cytogenetic response — 1% to 35% Ph+ cells
Major cytogenetic response = complete cytogenetic response + partial cytogenetic response
Molecular Response:
Standarization studies are ongoing and definitions of molecular response currently vary.
*Complete molecular response — no detectable bcr-abl
transcripts by RT-PCR
*Major molecular response — ?3-log reduction in the level of
bcr-abl transcripts or
bcr-abl/abl ratio ?0.05%
*Molecular Analysis at Diagnosis
Assessment of Bcr-Abl transcript, by RQ-PCR at diagnosis is necessary to confirm Ph+CML and establish the type of Bcr-Abl fusion present.
In rare, complex karyotypic rearrangements, fluorescence in situ hybridization (FISH) must be performed to detect the presence of gene deletions or variant translocations, whose precise prognostic significance still needs to be established.
Molecular Monitoring During Therapy:
European LeukemiaNet experts recommend continued molecular monitoring during targeted therapy.
Patients with Ph+ CML should have molecular response assessment performed at regular 3-month intervals.
A steady decline in Bcr-Abl transcripts indicates an ideal response to therapy.
The IRIS trial demonstrated that molecular responses generally continue to improve with time on targeted therapy.
A substantial portion of patients without CCyR or MMR at 12 months, and some after 18 months, eventually achieved these levels of molecular response during continued therapy.
In a recent study, a number of patients without CCyR at 1 year could reach the same levels of molecular response as those patients with CCyR at 12 months after 3 or 4 years.
***Together these results indicate that the time at which patients may achieve molecular responses varies and some patients require a year or more to achieve MMR.
Ph+ CML patients who achieve CCyR and MMR have the best prognosis compared with patients who achieve only CCyR without MMR or no CCyR.
A 5-fold to 10-fold (0.5 or 1 log) increase in Bcr-Abl transcript levels is currently proposed as the threshold for molecular relapse or resistance.
This avoids the potential for raising concern over potentially clinically irrelevant fluctuations in Bcr-Abl transcript levels.
Such fluctuations, however, indicate that the measurement reliability of the RQ-PCR assay should be optimized.
A rise in Bcr-Abl transcript levels can be used to trigger analysis for resistant Bcr-Abl mutations.
At present, direct gene sequencing for mutation detection is a commonly used approach.
Finally, it must be considered that a meaningful rise in Bcr-Abl transcripts could also be due to inadequate drug levels caused by pharmacokinetic factors or lack of adherence to therapy.
You can find a link to these guidelines and others on the
CMLallianceNet website - go to Links on main menu
Sandy
