Retrospective Comparison of Survival and Risk Stratification By Quantitative RT-PCR Monitoring in Newly Diagnosed Pediatric Acute Myeloid Leukemia with <i>RUNX1::RUNX1T1</i> Fusion Treated with AML-CAMS-2009 and AML-CAMS-2016

Objective: The study is intended to compare the clinical outcomes of pediatric patients with AML with RUNX1::RUNX1T1 fusion treated with the AML-CAMS-2009 and AML-CAMS-2016 regimens, as well as to explore early molecular thresholds with prognostic advice. Methods: The study retrospectively analyzed the clinical data of 146 pediatric patients newly diagnosed with AML with RUNX1::RUNX1T1 fusion who received treatment with AML-CAMS-2009 (n = 74) or AML-CAMS-2016 (n = 72) regimens in a single center. Patients on protocol 2009 were followed until December 31, 2020, with a median follow-up of 66 (1-135) months; patients on protocol 2016 were followed until November 30, 2022, with a median follow-up of 43.5 (1-82) months. Results: There was a trend toward improved overall survival with the 2016 regimen in comparison to the 2009 regimen (87.3±4.5% vs. 73.9±5.5%, P = 0.060). At remission following one course of induction chemotherapy, a ≥3 log reduction in RUNX1::RUNX1T1 transcripts in BM had a significant influence on RFS (93.3±6.4% vs. 63.4±8.9%, P = 0.013) and OS (100.0% vs. 69.3±8.6%, P = 0.013) in patients treated with regimen 2009. Compared to the 2009 regimen, the 2016 regimen improved the prognosis of patients with a ＜3 log reduction in RUNX1::RUNX1T1 transcripts, although the difference was not statistically significant (P = 0.162). Nevertheless, with the 2016 regimen, the worse survival of patients with a ＜ 3 log reduction in fusion gene by induction chemotherapy was not statistically significant (＜3 log vs. ≥3 log reduction: RFS 67.7±8.4% vs.91.3±5.9%, P=0.051; OS 83.8±7.4% vs. 100%, P=0.059). Fusion genes detected by quantitative real-time PCR of less than 0.4%, 0.2%, and 0.01% after induction chemotherapy, consolidation 1, and consolidation 2, respectively, significantly affected RFS in patients, both in 2009 and 2016 protocols (P＜0.050). Significant improvements in RFS and OS were seen in patients who achieved two or more detections of the above targeted quantification of fusion genes (P＜0.005). Conclusion: 1. The 2016 regimen did not result in a decrease in the overall prognosis, despite the fact that it reduced the intensity of therapy. 2. The extent of molecular remission following one course of induction chemotherapy has a substantial impact on the long-term prognosis. 3. Regardless of the regimen, integrating the response to the first three courses of chemotherapy provides prognostic significance.