TY - JOUR
T1 - Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A-Rearranged Acute Myeloid Leukemia
T2 - A Study by the International Berlin-Frankfurt-Münster Study Group
AU - van Weelderen, Romy E.
AU - Klein, Kim
AU - Harrison, Christine J.
AU - Jiang, Yilin
AU - Abrahamsson, Jonas
AU - Arad-Cohen, Nira
AU - Bart-Delabesse, Emmanuelle
AU - Buldini, Barbara
AU - de Moerloose, Barbara
AU - Dworzak, Michael N.
AU - Elitzur, Sarah
AU - Fernández Navarro, José M.
AU - Gerbing, Robert B.
AU - Goemans, Bianca F.
AU - de Groot-Kruseman, Hester A.
AU - Guest, Erin
AU - Ha, Shau-Yin
AU - Hasle, Henrik
AU - Kelaidi, Charikleia
AU - Lapillonne, H. lène
AU - Leverger, Guy
AU - Locatelli, Franco
AU - Masetti, Riccardo
AU - Miyamura, Takako
AU - Norén-Nyström, Ulrika
AU - Polychronopoulou, Sophia
AU - Rasche, Mareike
AU - Rubnitz, Jeffrey E.
AU - Stary, Jan
AU - Tierens, Anne
AU - Tomizawa, Daisuke
AU - Zwaan, C. Michel
AU - Kaspers, Gertjan J. L.
N1 - Publisher Copyright: © American Society of Clinical Oncology.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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 (<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 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.
AB - 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 (<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 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.
UR - http://www.scopus.com/inward/record.url?scp=85160455151&partnerID=8YFLogxK
U2 - https://doi.org/10.1200/JCO.22.02120
DO - https://doi.org/10.1200/JCO.22.02120
M3 - Article
C2 - 36996387
SN - 0732-183X
VL - 41
SP - 2963
EP - 2974
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 16
ER -