Introduction The SIL::TAL1 fusion gene, caused by a 1p32 deletion, is a common molecular alteration in T-cell acute lymphoblastic leukemia (T-ALL), with an incidence of 16–29%. It promotes leukemogenesis via aberrant activation of the TAL1 transcription factor. Although initial chemotherapy often induces complete remission (CR), long-term outcomes remain poor, with a median OS of 11–17 months and high relapse rates. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shown potential to improve prognosis in SIL::TAL1-positive T-ALL, but data remain limited. This study analyzed long-term outcomes following allo-HSCT in a cohort of SIL::TAL1-positive T-ALL patients.Methods We retrospectively analyzed 82 patients diagnosed with SIL::TAL1-positive T-ALL who underwent first allo-HSCT between June 2013 and September 2024 at two transplant centers. All patients were PCR-confirmed SIL::TAL1-positive by RT-qPCR. Primary endpoints included OS, DFS, cumulative incidence of relapse (CIR), and non-relapse mortality (NRM), with follow-up through April 1, 2025.Results Among the 82 patients, 57 (69.5%) were children (≤14 years), and 25 (30.5%) were adults; 74 (90.2%) were male. The median age was 11 years (range, 1–39), and the median WBC at diagnosis was 152.0×10⁹/L (range, 3.6–761.9). Gene mutations were detected in 69.5% of patients, most commonly NOTCH1 (24.3%), PTEN (23.1%), and FBXW7 (15.8%). At the time of transplant, 49 patients (59.8%) were in CR1, 32 (39.0%) in ≥CR2, and 1 (1.2%) in non-remission. MRD was negative in 91.5% and positive in 8.5%. CNS involvement was documented in 21.9% of patients. The majority (83.0%) underwent haploidentical HSCT with ATG/G-CSF-based conditioning, while 8.5% each received MSD-HSCT or MUD-HSCT. TBI-based conditioning was used in 91.5%, and BU-based in 8.5%. Median infused cell doses were: MNC 9.69×10⁸/kg, CD34⁺ 4.93×10⁶/kg, and CD3⁺ 1.75×10⁸/kg. Median neutrophil and platelet engraftment occurred on day 14 (range, 8–51) and day 13 (range, 5–47), respectively.With a median follow-up of 15.9 months (range, 0.7–139.1), patients in CR1 prior to transplant had significantly better survival outcomes than those in ≥CR2. The 2-year OS was 71.0% (95% CI, 57.7–84.3) in the CR1 group vs. 44.6% (95% CI, 29.4–59.9) in the ≥CR2 group (P=0.02). Similarly, 2-year DFS was 71.2% (95% CI, 57.9–84.4) vs. 44.9% (95% CI, 29.7–60.1) (P=0.02). The 2-year CIR was not significantly different between groups: 17.7% (95% CI, 9.4–33.2) in CR1 vs. 23.5% (95% CI, 13.7–40.5) in ≥CR2 (P=0.48). However, NRM was lower in the CR1 group: 13.4% (95% CI, 6.4–28.3) vs. 31.5% (95% CI, 20.0–49.5) (P=0.05), suggesting that achieving CR1 prior to transplant is critical for improving transplant outcomes.Patients with detectable SIL::TAL1 transcript at the time of transplant (n=10) had extremely poor outcomes compared to those who were negative (n=72). The 1-year OS and DFS in the positive group were both 0%, whereas the negative group had OS of 69.8% (95% CI, 58.9–80.6) and DFS of 70.0% (95% CI, 59.2–80.8) (P<0.001 for both). The 1-year CIR was significantly higher in the SIL::TAL1-positive group: 80.0% (95% CI, 56.9–100) vs. 13.3% in the negative group (P<0.001). The 1-year NRM was comparable between groups: 20.0% (95% CI, 5.8–69.1) vs. 21.6% (95% CI, 13.8–33.8) (P=0.89). These findings highlight the prognostic importance of achieving molecular negativity prior to transplant.When stratified by donor type, outcomes were similar between haploidentical HSCT (n=68) and MUD/MSD-HSCT (n=14). The 2-year OS was 60.3% (95% CI, 48.4–72.2) in the haplo group vs. 64.3% (95% CI, 39.2–89.4) in the MUD/MSD group (P=0.86). Similarly, 2-year DFS was 60.6% (95% CI, 48.7–72.4) vs. 64.3% (95% CI, 39.2–89.4) (P=0.95). CIR was also comparable (16.6% vs. 28.6%; P=0.22), as was NRM (24.5% vs. 7.1%; P=0.15), indicating that haplo-HSCT is a viable alternative to MUD/MSD in this setting.ConclusionAllo-HSCT provides favorable outcomes in SIL::TAL1-positive T-ALL, especially for patients in CR1 and with negative transcripts before transplant. SIL::TAL1 positivity at transplant predicts poor prognosis . Haplo-HSCT offers survival comparable to matched donors. Early transplant and molecular clearance are key to improved survival.

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2025
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