BCR-ABL measurement by real-time quantitative PCR (RQ-PCR) has become an essential component for assessing treatment response for CML. A major molecular response (MMR) has prognostic significance and can be used to guide therapeutic decisions. However, the various methods are not standardized and the value representing MMR varies, which may lead to misinterpretation of molecular response. To align data, an international reporting scale (IS) was proposed where MMR is 0.10%. Conversion to the IS is achieved by applying laboratory (lab) specific conversion factors (CF). We aimed to
calculate CF for diverse RQ-PCR methods by reference of patient BCR-ABL values to those generated in a reference lab with an established CF;
validate the CF by subsequent patient sample exchange;
examine the concordance of BCR-ABL values after IS conversion;
determine if manufactured reference material is suitable for CF calculation. 34 labs from 13 countries (Australia/New Zealand 11, North/South America 9, Asia 8, Europe 6) sent 615 patient samples to the Adelaide reference lab to determine their specific CF.
The RQ-PCR methods varied by the control gene (ABL 17, BCR 12, GUSβ 4, G6PDH 2, β2M 1, GAPDH 1; 3 labs used 2 controls therefore 37 methods), instrument, probe technology and standards. The CF for each method was calculated from the bias of patient BCR-ABL values between the originating lab and the reference lab, providing the bias was consistent across the dynamic range (
Disclosure:Employment: KL is employed by Novartis. Consultancy: SB Novartis. Ownership Interests:; KL Novartis. Research Funding: SB, TH, GS, FP, MM, AH, NC, DWK, JR Novartis, Bristol Myers Squibb. Honoraria Information: SB, TH, AH, GS, DWK, JR, NC, JM - Novartis, Bristol Myers Squibb. Membership Information: TH, AH, GS, JM: Novartis, Bristol-Myers Squibb.