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A parallel-risk framework accurately predicts hematopoietic stem cell transplantation outcomes and identifies benefiting patients in pediatric AML

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A parallel-risk framework accurately predicts hematopoietic stem cell transplantation outcomes and identifies benefiting patients in pediatric AML

Feng Yance
Shen Yali
Huang Ke
Li Qian
Tao Yu
Liu Rongqiu
Zhan Liping
Yang Hua
Xun Yang
Xu Yichao
Tang Wenli
Xiong Binjun
Shi Hui
Cheng Liting
Wei Li
You Hua
Genes & Diseases第13卷, 第5期纸质出版 2026-09-01在线发表 2025-12-23
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Pediatric acute myeloid leukemia (pAML) has a poorer prognosis than acute lymphoblastic leukemia, and hematopoietic stem cell transplantation (HSCT) offers curative potential in high-risk or relapsed cases. Current models cannot accurately determine which individual patients will truly benefit from HSCT, leading to overtreatment or undertreatment. We developed HSCT-64, the first parallel transcriptomic risk framework for pediatric AML, conceptually analogous to a causal G-formula approach. It comprises two treatment-specific models, aHSCT-64 for allo-HSCT recipients and nHSCT-64 for non-HSCT patients, derived from a shared 64-gene signature identified from diagnostic RNA-sequencing data, enabling individualized survival prediction under both treatment scenarios at diagnosis. Trained on 1647 cases from four COG/TARGET cohorts and validated in 233 independent patients, HSCT-64 achieved a C-index of 0.791 and AUC of 0.794 for allo-HSCT overall survival, outperforming existing clinical, cytogenetic, and leukemia stem cell-based models. Comparing risk ranks between two models identified an HSCT-benefiting subgroup patients with a predicted risk rank reduction from HSCT who experienced a 5.88-fold mortality reduction post-transplant (Hazard Ratio, HR = 0.17, P = 0.0066), while no survival gain was seen in the nonbenefiting subgroup (HR = 0.94, P = 0.899). HSCT-64 enables precise, diagnosis-time identification of pAML patients most likely to benefit from transplantation, marking a shift from high-risk-based recommendations toward individualized, transcriptome-driven decision-making.

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Hematopoietic stem cell transplantationParallel-risk frameworkPediatric acute myeloid leukemiaPrognosisTranscriptome