Reporting BCR-ABL1 Quantitative Measurements

Transcription

1 Reporting BCR-ABL1 Quantitative Measurements Based on recommendations from literature and experts in the field, reports should contain at minimum: Information on specimen tested and pre-analytical parameters Information on test, including key analytical performance parameters Information on acceptance criteria Raw results and IS percent ratio Information necessary to understand how the test is performed and how to interpret the data Clear explanation of terminology All historical data (when available) to further help data interpretation

2 Report Example, Page 1 of 2 Endogenous control gene used Results validity criteria Limit of detection for quantitative result (LLOQ) Value of IS conversion factor Raw results Percent ratio on the IS Graphical representation of historical data showing MMR cutoff (0.1% on the IS) Method used for standardization

3 Report Example, Page 2 of 2 Tabular representation of historical data including IS % ratios, CF values and other information not captured in the graphic Description of test and results interpretation Explanation of terms used in report

4 Other Considerations Samples with no BCR-ABL1 signal should Not be reported if endogenous control (EC) copy number < cutoff value Be reported as BCR-ABL1 not detected if EC copy number > cutoff value (not as negative for BCR-ABL1 ) Samples with BCR-ABL1 above limit of detection (LOD) but below limit of quantification (LOQ) should be reported as positive but below LOQ or positive but below linear range For samples with BCR-ABL1 above LOQ, interpretation relative to clinically validated landmarks (e.g. MMR or MR 3.0 ) can only be done for percent ratios on the IS Deep molecular responses characteristic of second generation TKIs can only be interpreted for percent ratios on the IS and in the context of ABL1 copy number: MR 4.0 = either detectable disease <0.01% on the IS or undetectable BCR-ABL1 in cdna with >10,000 ABL1 copies MR 4.5 = either detectable disease <0.0032% on the IS or undetectable BCR-ABL1 in cdna with >32,000 ABL1 copies

5 References Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, et al. Chronic myeloid leukemia: An update of concepts and management recommendations of european leukemianet. J Clin Oncol 2009;27: Branford S, Cross NC, Hochhaus A, Radich J, Saglio G, Kaeda J, et al. Rationale for the recommendations for harmonizing current methodology for detecting bcr-abl transcripts in patients with chronic myeloid leukaemia. Leukemia 2006;20: Branford S, Fletcher L, Cross NC, Muller MC, Hochhaus A, Kim DW, et al. Desirable performance characteristics for bcr-abl measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials. Blood 2008;112: Cross NC, White HE, Muller MC, Saglio G, Hochhaus A. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 2003;349: Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, et al. Monitoring cml patients responding to treatment with tyrosine kinase inhibitors: Review and recommendations for harmonizing current methodology for detecting bcr-abl transcripts and kinase domain mutations and for expressing results. Blood 2006;108: Kantarjian HM, Baccarani M, Jabbour E, Saglio G, Cortes JE. Second-generation tyrosine kinase inhibitors: The future of frontline cml therapy. Clin Cancer Res 2011;17: Muller MC, Cross NC, Erben P, Schenk T, Hanfstein B, Ernst T, et al. Harmonization of molecular monitoring of cml therapy in europe. Leukemia 2009;23: White HE, Matejtschuk P, Rigsby P, Gabert J, Lin F, Lynn Wang Y, et al. Establishment of the first world health organization international genetic reference panel for quantitation of bcr-abl mrna. Blood 2010;116:e111-7.