Refining risk in historically high-risk pediatric B-cell acute lymphoblastic leukemia: response kinetics and outcomes
7 affiliations
- 1Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- 2Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
- 3Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan
- 4Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
- 5Department of Medical Technology, Kyorin University Faculty of Health Sciences, Mitaka, Japan
- 6Department of Hematology and Oncology, Saitama Prefectural Children’s Medical Center, Saitama, Japan
- 7Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Correspondence: Motohiro Kato, Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan;
Abstract
Outcomes in pediatric acute lymphoblastic leukemia (ALL) have improved substantially with contemporary risk-adapted therapy. However, the prognosis for historically high-risk subtypes, including KMT2A -rearranged ( KMT2A -r) and hypodiploid ALL, remains uncertain. We performed a post hoc analysis of 28 patients with KMT2A -r ALL and 27 with hypodiploid ALL enrolled in the nationwide Japan Children’s Cancer Group ALL-B12 trial to characterize early treatment response, measurable residual disease (MRD) kinetics, transplant exposure, and clinical outcomes. The 5-year event-free and overall survival were 85.7% and 89.3% for KMT2A -r ALL and 85.2% and 85.2% for hypodiploid ALL, respectively. Clinical behavior was heterogeneous within each subtype. In KMT2A :: AFF1 ALL, prednisolone poor response or persistent MRD was associated with a high risk of relapse despite hematopoietic stem cell transplantation (HSCT). Even among prednisolone good responders, patients with MRD ≥10 –3 at time point 1 remained at increased risk of relapse, whereas those with MRD ≥10 –4 but <10 –3 generally showed favorable outcomes. In contrast, non- AFF1 KMT2A -r patients demonstrated rapid MRD clearance and excellent survival. Among patients with hypodiploid ALL, those with low-diploid ALL showed excellent outcomes without HSCT. In other hypodiploid subgroups, some patients with favorable early response achieved long-term survival without transplantation. These findings suggest that historically high-risk ALL subtypes are clinically heterogeneous and that early response kinetics may help refine risk stratification and treatment intensification strategies, including indications for HSCT.
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BibTeX
@article{kubota2026refining,
title = {{Refining risk in historically high-risk pediatric B-cell acute lymphoblastic leukemia: response kinetics and outcomes}},
author = {Yasuo Kubota and Yasuhiro Okamoto and Toshihiko Imamura and Akiko Kada and Akiko M. Saito and Yuka Iijima-Yamashita and Masashi Sanada and Tomohiko Taki and Katsuyoshi Koh and Motohiro Kato},
journal = {Blood Neoplasia},
year = {2026},
month = sep,
doi = {10.1016/j.bneo.2026.100313},
url = {https://doi.org/10.1016/j.bneo.2026.100313},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Refining risk in historically high-risk pediatric B-cell acute lymphoblastic leukemia: response kinetics and outcomes
AU - Yasuo Kubota
AU - Yasuhiro Okamoto
AU - Toshihiko Imamura
AU - Akiko Kada
AU - Akiko M. Saito
AU - Yuka Iijima-Yamashita
AU - Masashi Sanada
AU - Tomohiko Taki
AU - Katsuyoshi Koh
AU - Motohiro Kato
PY - 2026
DA - 2026/09/19
JO - Blood Neoplasia
DO - 10.1016/j.bneo.2026.100313
UR - https://doi.org/10.1016/j.bneo.2026.100313
AB - Outcomes in pediatric acute lymphoblastic leukemia (ALL) have improved substantially with contemporary risk-adapted therapy. However, the prognosis for historically high-risk subtypes, including KMT2A -rearranged ( KMT2A -r) and hypodiploid ALL, remains uncertain. We performed a post hoc analysis of 28 patients with KMT2A -r ALL and 27 with hypodiploid ALL enrolled in the nationwide Japan Children’s Cancer Group ALL-B12 trial to characterize early treatment response, measurable residual disease (MRD) kinetics, transplant exposure, and clinical outcomes. The 5-year event-free and overall survival were 85.7% and 89.3% for KMT2A -r ALL and 85.2% and 85.2% for hypodiploid ALL, respectively. Clinical behavior was heterogeneous within each subtype. In KMT2A :: AFF1 ALL, prednisolone poor response or persistent MRD was associated with a high risk of relapse despite hematopoietic stem cell transplantation (HSCT). Even among prednisolone good responders, patients with MRD ≥10 –3 at time point 1 remained at increased risk of relapse, whereas those with MRD ≥10 –4 but <10 –3 generally showed favorable outcomes. In contrast, non- AFF1 KMT2A -r patients demonstrated rapid MRD clearance and excellent survival. Among patients with hypodiploid ALL, those with low-diploid ALL showed excellent outcomes without HSCT. In other hypodiploid subgroups, some patients with favorable early response achieved long-term survival without transplantation. These findings suggest that historically high-risk ALL subtypes are clinically heterogeneous and that early response kinetics may help refine risk stratification and treatment intensification strategies, including indications for HSCT.
SN - 2950-3280
ER -