The goals of CML monitoring:

•        Shows efficacy of the current therapy
•        Monitoring for treatment relapse or resistance
•        Analyzing mechanisms for treatment failure so that   
the best alternative therapy can be sought.

Different CML Tests:

1.        Conventional cytogenetics analysis (CA) using
chromosome G banding.  This test is still considered the
gold standard in CML monitoring by many CML doctors.  
CCR is defined from the CA of 20 evaluable metaphases.

2.        Fluorescent In-situ Hybridization(FISH) Studies

•        D-FISH (double-FISH) reduces the rates of false
positivity.
•        Interphase FISH does not require cells to be dividing
and thus can represent a wider population of cells.  
Interphase FISH is commonly used.
•        FISH studies are generally done from peripheral
blood and analyzes approximately 200 interphase cells and
is so more sensitive than CA.
•        There is also a narrower confidence level.  For a
patient having 50/200 positive CML cells or 25%Ph+, the
95% confidence interval is 19-32%.

3.        Quantitative polymerase chain reaction (PCR)

•        Quantitative real-time PCR is used to monitor
residual disease and results are reported as the BCR-ABL
to a reference gene (recommended genes include ABL,
BCR and GUSB).  Several technical aspects lack
standardization like sample source (blood or marrow) and
the effects of shipping and storage, the amount of sample
required, the techniques of RNA extraction and the
preferred reference gene.  Variations in all of these will
give rise to variation in comparative results between labs.
•        In the IRIS trials, the standardized baseline was
36% and a PCR 3-log reduction was therefore 0.036%.
•        Standardized baseline values have to be determined
by individual laboratories.  The baseline value can vary
from laboratory to laboratory and is not always included in
the report.
•        When negative results for PCR are reported, the
sensitivities of the assay are not always reported.

4.        Mutations Analysis

•        Some patients in chronic and advanced phases
develop mutations in the BCR-ABL kinase domain which
prevents the Gleevec from properly binding to the
oncoprotein.  There are techniques to detect these
mutations and the mutations are named according to at
which point they are found.  Mutational studies show that
advanced phase patients and late chronic phase patients
may have low levels of mutations before any therapy but
this has not been seen in early chronic phase patients.  1-
20% of patients may have mutations in chronic phase,
responding to Gleevec but they do not consistently persist
or proliferate and may not be associated with progression
of the disease.
•        Conversely, in clinically resistant disease, 30-50% of
patients can express BCR-ABL mutations.

The material in this webpage and links have been
paraphrased from 'Monitoring the Response and Course of
Chronic Myeloid Leukemia in the Modern Era of BCR-
ABL Tyrosine Kinase Inhibitors: Practical Advice on the
Use and Interpretation of Monitoring Methods' by
Hagop Kantarjian, M. D., Charles Schiffer, M.D., Dan
Jones, M.D., Jorge Cortes, M.D.1 published Nov 30, 2007
in Blood.
CML Monitoring Tests and Techniques
CML Monitoring and Tests
Milestones and Definitions of
Gleevec Failure and Suboptimal
Response

  • Diagnosis Warnings are High-risk
    by Sokal Score, having deletions in
    derivative chromosome 9 and
    additional chromosomal
    abnormalities in Ph+ cells.  These
    warnings may warrantee more
    stringent monitoring of the disease
    and response to therapy.
  • 3 months:  No hematologic
    response (normalization of blood
    counts) is deemed Gleevec failure
    at the dose given.
  • 6 months:  No cytogenetic
    response (Ph+ more than 95%) is
    deemed Gleevec failure at the dose
    given.  Less than Major cytogenetic
    response (less than 35%Ph+) is
    deemed a suboptimal response to
    the Gleevec dose given.
  • 12 months:  Less than Major
    Cytogenetic response is deemed
    Gleevec failure at the dose given.  
    Less than Complete Cytogenetic
    Response (CCR, 0%Ph+) is
    deemed a suboptimal response to
    Gleevec at the dose given.
  • 18 months:  Less than CCR is
    deemed Gleevec failure at the dose
    given.  Less than Major Molecular
    Response (MMR, a PCR 3-log
    reduction) is deemed a suboptimal
    response to Gleevec at the dose
    given.

From:  'Evolving Concepts In The
Management of CML.  
Recommendations from an expert panel
on behalf of the European
Leukaemianet' by Baccarani, M. et al.