Rapid, reliable, comprehensive and sensitive detection of MDCC in AML by an optimized panel of 6 FISH probes

CPX-351 is approved for myelodysplasia related changes (MRC)-type AML which can be classified by MDS-defining cytogenetic changes (MDCC). According to WHO 2022 this entity is renamed AML-MR (myelodysplasia-related) and molecular features are considered too. In a prospective study we aimed to prove that a rapid identification of AML-MRC/MR cases with MDCC is practicable and reliable using a streamlined 6-probes FISH-panel. We assessed feasibility, success rate, sensitivity to detect cytogenetic aberrations, especially MDCC, turnaround times (TAT), and reliability of peripheral blood (pb) vs. bone marrow (bm) analysis in 131 patients with suspected AML. All 6 probes could be evaluated in 94.7%. In 45.8%, we identified cytogenetic abnormalities by FISH. In 19.1%, complex changes and distinct aberrations such as -5/5q- (20.6%), -7/7q- (19.1%), +11/+11q (12.2%), 12p- (10.7%) and ‑17/17p- (10.7%) and others were found. We also traced International Consensus Classification (ICC)-defined MDCC trisomy 8 (16.9%) and 20q- (4.4%) with additional probes. MDCC were detected in 34.4% (WHO 2022) and in 35.1% (ICC) of cases. Aberration rate with chromosome banding analysis (CBA) (n=115) was 48.7%. Statistical comparison of FISH vs. CBA demonstrated non-inferiority of FISH for the detection of chromosomal changes including MDCC as well as for the use of pb vs. bm. The mean TAT for the FISH panel analysis was 7 hours 48 minutes only. Our six-probes-FISH panel represents a reliable, rapid, cost-effective, and robust method for identifying MDCC in suspected AML, including when only pb samples are available. It can complement - or in time-critical cases potentially replace - CBA.