Page 263 - Haematologica Vol. 110 - January 2025

LETTER TO THE EDITOR
not significantly different (Online Supplementary Figure S2D, E). No significant interaction between KIT exon 17 mutations and GO treatment was observed either in EFS (P=0.159) or OS (P= 0.966).
This study provided a new insight into the combined in- fluence of KIT exon 17 mutations and flow-MRD levels on prognosis in pediatric AML with RUNX1::RUNX1T1. Patients with positive MRD had a dismal prognosis, regardless of the presence or absence of KIT exon 17 mutations. Further, even when limited to the MRD-negative group, patients with KIT exon 17 mutations had a significantly worse prognosis compared to those without the mutations. In multivariable analysis, regardless of whether MRD levels were included as a covariate, KIT exon 17 mutations were associated with a significantly inferior prognosis. These results highlight that the prognostic impact of KIT exon 17 mutations should be prioritized even under MRD-guided therapy and patients with KIT exon 17 mutations require treatment intensification irrespective of MRD levels.
In contrast, no significant association of KIT exon 17 mu- tations on prognosis in pediatric AML with RUNX1::RUNX1T1 was revealed by public data from the TARGET dataset. This discrepancy between the two cohorts may be attributed to GO treatment. Therapeutic benefits of GO treatment in pediatric core binding factor AML with KIT exon 17 muta- tions were revealed in a previous study.15 Further, studies reporting a poor prognosis of patients with KIT mutations have adopted treatment regimens without GO.3,9-11 These observations indicated that GO treatment may improve the prognosis of AML with RUNX1::RUNX1T1 and KIT mu- tations. Adding GO to the treatment of patients with KIT mutations might demonstrate a significant influence on the prognosis of pediatric patients in Japan, considering the higher prevalence of KIT exon 17 mutations in children with RUNX1::RUNX1T1-positive AML than patients in the TARGET cohort and in other countries or regions.4,9,10
In conclusion, pediatric AML with RUNX1::RUNX1T1 and KIT exon 17 mutations demonstrated a poor long-term prognosis even among patients with negative MRD, thereby requir- ing treatment intensification for these patients regardless of MRD levels. The comparison between the AML-12 and TARGET cohorts indicated GO as a potential candidate for future therapeutic development, although a prospective study is warranted to confirm this finding.
Authors
Shota Kato,1* Shin-Ichi Tsujimoto,2* Jun Matsubayashi,3 Shotaro Iwamoto,4 Hidefumi Hiramatsu,5 Yusuke Okuno,6 Tatsuya Kamitori,5 Kentaro Ohki,7 Takao Deguchi,8 Nobutaka Kiyokawa,7 Motohiro Kato,1 Junko Takita,5 Shiro Tanaka,9 Souichi Adachi,10 Daisuke Tomizawa11 and Norio Shiba2
1Department of Pediatrics, Graduate School of Medicine, the
University of Tokyo, Tokyo; 2Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama; 3Center for Clinical Research and Advanced Medicine, Shiga University of Medical Science, Otsu; 4Department of Pediatrics, Graduate School of Medicine Mie University, Tsu; 5Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto; 6Department of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya; 7Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo; 8Division of Cancer Immunodiagnostics, Children’s Cancer Center, National Center for Child Health and Development, Tokyo; 9Department of Clinical Biostatistics, Graduate School of Medicine, Kyoto University, Kyoto; 10Human Health Science, Graduate School of Medicine Kyoto University, Kyoto and 11Division of Leukemia and Lymphoma, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan
*SK and S-IT contributed equally as first authors.
Correspondence:
N. SHIBA - nshiba@yokohama-cu.ac.jp
https://doi.org/10.3324/haematol.2024.286243
Received: July 8, 2024. Accepted: August 28, 2024. Early view: September 5, 2024.
©2025 Ferrata Storti Foundation Published under a CC BY-NC license
Disclosures
No conflicts of interest to disclose.
Contributions
SK, S-IT, JM, ST, DT, and NS designed the study. S-IT, ST, SA, DT, and NS acquired financial support. SK, S-IT, SI, HH, TK, MK, JT, SA, DT and NS collected materials and data. All authors analyzed and interpreted data. SK, S-IT, JM, ST, and NS wrote the manuscript. SI, HH, YO, TK, KO, TD, NK, MK, JT, SA, and DT critically edited the manuscript; and all authors approved the final version of the manuscript and are accountable for all aspects of the work.
Acknowledgments
The authors thank the patients and their parents/guardians who participated in the AML-12 trial and the clinicians at the participating institutions.
Funding
This study was supported by a Grant-in-Aid for Scientific Research (KAKEN, grant number JP19K08350 [to NS] and JP21K15870 and JP24K11004 [to ST]) and Exploratory Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development (AMED, grant number
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