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?
• 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?