Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Mar 30. doi: 10.1200/JCO.22.02120 |
Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood -Rearranged Acute Myeloid Leukemia: A Study by the International Berlin-Frankfurt-Münster Study Group. |
van Weelderen RE1, Klein K2, Harrison CJ3, Jiang Y4, Abrahamsson J5, Arad-Cohen N6, Bart-Delabesse E7, Buldini B8, De Moerloose B9, Dworzak MN10, Elitzur S11, Fernández Navarro JM12, Gerbing RB13, Goemans BF14, de Groot-Kruseman HA15, Guest E16, Ha SY17, Hasle H18, Kelaidi C19, Lapillonne H20, Leverger G21, Locatelli F22, Masetti R23, Miyamura T24, Norén-Nyström U25, Polychronopoulou S26, Rasche M27, Rubnitz JE28, Stary J29, Tierens A30, Tomizawa D31, Zwaan CM32, Kaspers GJL33 |
Abstract PURPOSE: A previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood -rearranged (-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease. METHODS: A total of 1,130 children with -r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (≥0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS). RESULTS: The high-risk group had inferior EFS (30.3% high risk 54.0% non-high risk; < .0001), CIR (59.7% 35.2%; < .0001), and OS (49.2% 70.5%; < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity n = 43; 16.3% MRD positivity; < .0001) and OS (n = 413; 66.0% n = 43; 27.9%; < .0001), and showed a trend toward lower CIR (n = 392; 46.1% n = 26; 65.4%; = .016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; = .00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS. CONCLUSION: EOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood -r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis. |
Publikations ID: 36996387 Quelle: öffnen |