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Chronic myeloid

Molecular Markers

in Chronic Myeloid Leukemia

Expert Opinion

Quick Facts

The sensitivity of a qPCR assay depends not only on the performance of the assay, but also on the quality of a given sample. As such, the term “complete molecular response” to denote undetectable BCR-ABL1 transcripts (a negative qPCR test) should be abandoned, as it may refer to very different levels of response, dependent on the quality of the sample. Laboratories can use their individual assays, but the BCR-ABL1 transcripts obtained in a given laboratory should be converted to the IS by applying a laboratory-specific conversion factor (CF).


Monitoring with qPCR (IS) every 3 months is recommended for all patients after initiating TKI therapy, including those who meet response milestones at 3, 6, and 12 months (≤10% BCR-ABL1 IS at 3 and 6 months, ≤1% BCR-ABL1 IS at 12 months, and ≤0.1% BCR-ABL1 IS at >12 months). After CCyR (≤1% BCR-ABL1 IS) has been achieved, molecular monitoring is recommended every 3 months for 2 years and every 3 to 6 months thereafter


NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) ...

Version 3.2020 — January 30, 2020

Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diag...


 Recommendation for management of CML

European leukemia net guidelines

When BCR-ABL1 kinase domain
mutation analysis is recommended?


• Chronic phase
Failure to reach response milestones
Any sign of loss of response (defined as hematologic or cytogenetic relapse)
1-log increase in BCR-ABL1 transcript levels and loss of MMR
• Disease progression to accelerated or blast phase


BCR-ABL1 mutations that should NOT be treated with bosutinib, dasatinib or nilotinib in the second-line setting?

Bosutinib : T315I, V299L, G250E or F317Lp

Dasatinib T315I/A, F317L/V/I/C or V299L

Nilotinib T315I, Y253H, E255K/V, or F359V/C/I or G250E

Ponatinib, Omacetaxine, allogeneic HCT ,or clinical trial : None



What are definitions for different kind of responses?

Molecular response:
• Early molecular response (EMR) - BCR-ABL1 (IS) ≤10% at 3 and 6 months
• Major molecular response (MMR) - BCR-ABL1 (IS) ≤0.1% or ≥3-log reduction in BCR-ABL1 mRNA from
the standardized baseline, if qPCR (IS) is not available
• Complete molecular response (CMR) is variably described, and is best defined by the assay’s level of
sensitivity (eg, MR4.5)
• Any sign of loss of response (defined as hematologic or cytogenetic relapse)
• 1-log increase in BCR-ABL1 transcript levels with loss of MMR should prompt bone marrow evaluation
for loss of CCyR but is not itself defined as relapse (eg, hematologic or cytogenetic relapse)



What are NCCN and ESMO recommendations for treatment discontinuation ?





When BCR- ABL is undetectable which factors define sensitivity and reliability of the test?



According to good laboratory practice and guidelines, what are minimum requirements for BCR-ABL test reports?