Objective To explore the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of high-risk acute T-lymphoblastic leukemia (T-ALL) in children, compare the efficacy differences of different treatment regimens, and explore the influence of pretreatment regimens on allo-HSCT in T-ALL patients. To compare the effects of two conditioning regimens, one containing cladribine (Cla) and the other without (fludarabine, Flu), in umbilical cord blood transplantation (UCBT), as well as the differences between this and the peripheral blood hematopoietic stem cell transplantation (PBSCT) based on total body irradiation (TBI). Methods A retrospective analysis was conducted on the clinical data of children with high-risk T-ALL who underwent allo-HSCT from February 2017 to March 2023. The Kaplan-Meier method was used to analyze the 3-year overall survival (OS) rate, leukemia-free survival (LFS) rate, cumulative incidence of chronic graft-versus-host disease (cGVHD), cumulative incidence of relapse (CIR), and cumulative transplant-related mortality (TRM) of the children. The Log-rank test was used to analyze the factors influencing the prognosis of high-risk T-ALL children. The differences in pre-treatment related toxic reactions, post-transplant infections, and 3-year OS rates among different pre-treatment regimens (UCBT-Cla group, UCBT-Flu group, and PBSCT-TBI group) were compared. Results Among the 23 children with high-risk T-ALL, 19 were boys (82.6%) and 4 were girls (17.4%), with a median age of 9.5 (1.9-14) years, and the median time from diagnosis to transplantation was 7.5 (6-29) months. Among the 23 high-risk T-ALL children, neutrophil engraftment was successfully achieved in all cases. The median time to engraftment was 18 (12 - 38) days for UCBT patients and 12 (11 - 15) days for PBSCT patients. The median time to platelet engraftment was 36 (27-61) days in UCBT recipients, with one case failing to achieve platelet engraftment; all PBSCT recipients achieved platelet engraftment, with a median time of 13 (9-25) days. Five children (21.7%) experienced grade ≥3 conditioning-related toxicities (primarily manifested as gastrointestinal reactions, oral mucositis, and infections), 14 had grade 1-2 toxicities, and 4 had no toxicities. No deaths occurred within 100 days post-transplantation among the 23 children. The incidence of grade Ⅲ-Ⅳ aGVHD was 26.1% (6/23). The 3-year cumulative incidence of cGVHD was (27.15 ± 13.33) %. Eighteen children (78.3%) experienced infections of varying severity and locations after transplantation, primarily pneumonia (10 cases), BK polyomavirus-associated hemorrhagic cystitis (7 cases), and invasive fungal infections (6 cases). The median post-transplant follow-up time was 34 (5-92) months. LFS was observed in 18 children, and 5 children died. The 3-year OS and LFS rate were both (77.5 ± 8.9) %. The 3-year CIR and TRM were (13.04 ± 7.19) % and (9.21 ± 6.4)%, respectively. The neutrophil and platelet engraftment times in the PBSCT-TBI group were significantly shorter than those in the UCBT-Cla and UCBT-Flu groups (P<0.05). No statistically significant differences were observed among the UCBT-Cla, UCBT-Flu, and PBSCT-TBI groups in terms of conditioning-related toxicities, incidence of aGVHD and cGVHD, post-transplant infections, or 3-year OS rate (P>0.05). The log-rank test revealed that central nervous system (CNS) involvement at initial diagnosis may be a high-risk factor affecting the overall survival (OS) of children with high-risk T-ALL (P<0.05). Age≥10 years, CNS involvement at initial diagnosis, pre-transplant disease status in second complete remission (CR2), and meeting the criteria for refractory leukemia may be high-risk factors for post-transplant relapse in high-risk T-ALL (P<0.05). Conclusions Allo-HSCT can effectively improve long-term survival in children with high-risk T-ALL and is associated with low TRM. CNS involvement at initial diagnosis is an important marker of poor prognosis. The cla-containing conditioning regimen in UCBT demonstrates potential for reducing relapse rates and improving survival outcomes. The Cla-containing conditioning regimen demonstrates potential in UCBT to reduce relapse rates and improve survival. The UCBT-Cla regimen may be a promising alternative option worthy of further investigation.