External quality assessment for PML-RARα detection in acute promyelocytic leukemia: Findings and summary

Background: The confirmation of clinical diagnosis, molecular remission, and sequential minimal residual disease monitoring required PML-RARα detection in acute promyelocytic leukemia (APL). The current status of PML-RARα detection in various laboratories remains unknown.

Methods: In 2018, external quality assessment (EQA) for PML-RARα detection was carried out in China. Three EQA sample panels for PML-RARα isoform L/S/V were prepared by different mock leukocyte samples. The performances of PML-RARα detection, including admission screening, and qualitative and quantitative detection by real-time quantitative reverse transcription PCR (RT-qPCR), were assessed based on APL simulated clinical case.

Results: The mock leukocyte samples met the requirements of a clinically qualified sample for PML-RARα EQA panel. Among the laboratories, 13/50 (26.0%) were "competent," 21/50 (42%) classified as "acceptable," and 16/50 (32.0%) classified as "improvable." One (1/50, 2.0%) laboratory reported one screening mistake. Twenty-six (26/50, 52.0%) laboratories reported 29 false-positive and 19 false-negative results. Twenty-three (23/50, 46.0%) laboratories reported 42 quantitative incorrect results.

Conclusion: Significant differences were not found in PML-RARα detection performance among laboratories that used different extraction methods. The performances of qualitative and quantitative RT-qPCR detection were worse accurate for PML-RARα isoform V. Quantitative variation was higher for low-level samples. Further continuous external assessment and education are needed in the management of PML-RARα detection.