Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A-Rearranged Acute Myeloid Leukemia

Autor: Romy E. van Weelderen, Kim Klein, Christine J. Harrison, Yilin Jiang, Jonas Abrahamsson, Nira Arad-Cohen, Emmanuelle Bart-Delabesse, Barbara Buldini, Barbara De Moerloose, Michael N. Dworzak, Sarah Elitzur, José M. Fernández Navarro, Robert B. Gerbing, Bianca F. Goemans, Hester A. de Groot-Kruseman, Erin Guest, Shau-Yin Ha, Henrik Hasle, Charikleia Kelaidi, Hélène Lapillonne, Guy Leverger, Franco Locatelli, Riccardo Masetti, Takako Miyamura, Ulrika Norén-Nyström, Sophia Polychronopoulou, Mareike Rasche, Jeffrey E. Rubnitz, Jan Stary, Anne Tierens, Daisuke Tomizawa, C. Michel Zwaan, Gertjan J.L. Kaspers
Přispěvatelé: Pediatrics, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 41(16), 2963-2974. American Society of Clinical Oncology
van Weelderen, R E, Klein, K, Harrison, C J, Jiang, Y, Abrahamsson, J, Arad-Cohen, N, Bart-Delabesse, E, Buldini, B, de Moerloose, B, Dworzak, M N, Elitzur, S, Fernández Navarro, J M, Gerbing, R B, Goemans, B F, de Groot-Kruseman, H A, Guest, E, Ha, S-Y, Hasle, H, Kelaidi, C, Lapillonne, H L, Leverger, G, Locatelli, F, Masetti, R, Miyamura, T, Norén-Nyström, U, Polychronopoulou, S, Rasche, M, Rubnitz, J E, Stary, J, Tierens, A, Tomizawa, D, Zwaan, C M & Kaspers, G J L 2023, ' Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A-Rearranged Acute Myeloid Leukemia : A Study by the International Berlin-Frankfurt-Münster Study Group ', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 41, no. 16, pp. 2963-2974 . https://doi.org/10.1200/JCO.22.02120
JOURNAL OF CLINICAL ONCOLOGY
ISSN: 0732-183X
1527-7755
Popis: PURPOSE A previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged ( KMT2A-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 KMT2A-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 (RESULTS The high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P < .0001), CIR (59.7% v 35.2%; P < .0001), and OS (49.2% v 70.5%; P < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P < .0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P < .0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P = .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]; P = .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 KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.
Databáze: OpenAIRE