Improved Survival outcomes with allo-HSCT in NUP214::ABL1-Positive Acute leukemia: A pooled analysis and single-center experience

Abstract Introduction The NUP214::ABL1 fusion gene, resulting from the fusion of nucleoporin NUP214 and the tyrosine kinase ABL1, harbors kinase activity similar to that of BCR::ABL1 and acts as an oncogenic driver in acute leukemia (AL). This fusion is exceedingly rare in clinical practice and is predominantly observed in acute lymphoblastic leukemia (ALL), often with aggressive clinical behavior. Although tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib show activity, relapse and drug resistance are common. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered a potentially curative option, but clinical data remain limited. Aims To investigate the clinical characteristics of NUP214::ABL1-positive AL and compare outcomes between chemotherapy and allo-HSCT, we analyzed cases from our center alongside those reported in the literature. Methods This study included pts diagnosed with NUP214::ABL1-positive ALL by polymerase chain reaction (PCR) screening and confirmed by quantitative reverse transcription PCR (RT-qPCR) at Hebei Yanda Lu Daopei Hospital and Beijing Lu Daopei Hospital between January 2020 and January 2024. Additionally, a systematic literature searching PubMed, Web of Science, and CNKI from 2000 to 2024, yielding 12 eligible studies with 25 cases for pooled analysis. Pts were grouped according to treatment modality (chemotherapy vs. allo-HSCT). Results Among 4,512 newly diagnosed AL pts at our center, 7 (0.16%) harbored the NUP214::ABL1 fusion, including 2 cases of T-ALL and 5 of B-ALL (2 males, 5 females), with a median age of 29 years (range, 11–61). Hyperleukocytosis was observed in 5/7 (71.4%) pts, with a median WBC count of 365.8×10⁹/L and median bone marrow blast percentage of 87.3% (range, 31.3–94.9%). One pt achieved CR after VDLP chemotherapy and relapsed 27 months later, dying shortly thereafter. The remaining 6 pts underwent allo-HSCT in CR. Five received CAR-T therapy prior to transplant: two were treated with naturally selected CD7- targeted CAR-T (NS7CAR) (1×10⁶/kg and 2×10⁶/kg, respectively), two with CD19 CAR-T (5×10⁵/kg and 1×10⁶/kg), and one with CD19/CD22 CAR-T (3×10⁵/kg). All (100%) achieved MRD-negative CR by day 28 post-infusion and proceeded to first allo-HSCT after a median of 2 months. Donor types included HID (n=4) and MSD (n=1). One additional patient underwent allo-HSCT in CR following chemotherapy alone. Notably, after a median follow-up of 37.5 months (range, 17–75), all six pts remained alive and relapse-free, with 3-year OS and LFS of 100%. Combined with 25 cases from published reports, a total of 32 pts were analyzed. Both the chemotherapy and allo-HSCT groups included 16 pts, with similar gender distributions. T-ALL predominated in the chemotherapy group (13/16, 81.3%), while B-ALL was more frequently observed in the allo-HSCT group (8/16, 50%) and median age was higher (21 vs. 14 years). Four pts in each group received TKI therapy. With a median follow-up of 14 months (range, 0.5–194), the 1-year OS showed a favorable trend in the allo-HSCT group compared with the chemotherapy group (83.3%, 95% CI: 62.3–100 vs. 65.0%, 95% CI: 39.7–90.3), although the difference was not statistically significant (p > 0.05). In contrast, the 1-year LFS was significantly higher in the allo-HSCT group (91.7%, 95% CI: 76.0–100 vs. 65.0%, 95% CI: 39.7–90.3; p < 0.05), and the 1-year cumulative incidence of relapse was significantly lower (8.3%, 95% CI: 1.3–54.4 vs. 43.1%, 95% CI: 23.2–80.1; p < 0.05). Conclusion NUP214::ABL1 -positive AL is rare and often presents with high disease burden and frequent hyperleukocytosis. In this study, pts in our center who received allo-HSCT in CR, particularly with CAR-T bridging, showed excellent long-term outcomes. In the combined analysis, allo-HSCT was associated with significantly improved LFS and lower RI, supporting its potential benefit in this high-risk subset. But further validation in larger, prospective studies is warranted.