Purpose Early T-cell precursor lymphoblastic leukemia (ETP-ALL) is an immunophenotypically defined subgroup of T-ALL associated with poor prognosis. However, emerging studies indicate that the prognosis of ETP-ALL is not inferior to that of non-ETP-ALL, underscoring the necessity to identify high-risk cases of ETP-ALL.

Patients and Methods We conducted a multicenter study involving 120 adult patients diagnosed with ETP-ALL who were treated with pediatric-inspired regimens. We collected survival outcomes, clinicobiological data, and genetic information, including next-generation sequencing (NGS), RNA-sequencing, and single-cell RNA sequencing for a comprehensive analysis.

Results Based on the absolute neutrophil count (ANC) at diagnosis, we observed that the population could be divided into an ANC_High group (61/120, 50.8%) and an ANC_Low group (59/120, 49.2%). The 5-year overall survival (OS) and event-free survival (EFS) were inferior in ANC_High group (OS: 40.6% vs 66.6%, P=0.0046; EFS: 36.9% vs 56.6%, P=0.029). NGS revealed that showed an increased prevalence of mutations in genes involved in epigenetic factors (SUZ12) and JAK signaling (JAK3, JAK1). RNA-sequencing profiling showed that the ETP and non-ETP groups formed distinct transcriptional clusters. The ETP-ALL blasts in the ANC_High group exhibit a stem cell-like transcriptional profile, indicative of a high differentiation potential. Furthermore, patients with high ANC count and positive end-induction minimal residual disease (MRD) had an extremely poor outcome, with 5-year EFS and OS rates of only 17.7% and 18.3%, respectively.

Conclusion Our results suggest that ANC is an independent prognostic indicator in ETP-ALL, proposing a novel and straightforward risk stratification.

Funding Hongsheng Zhou is supported by the National Natural Science Foundation of China (number 82170163 and 81970147). Li Xuan is supported by the National Key Research and Development Program (number 2022YFC2502600-5). Yang Xu is supported by the National Key Research and Development Program (number 2022YFC2502700).

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2025
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