Frontiers in oncology · 2026
Superior long-term survival with acceptable safety of ATG/G-CSF-based haplo-HSCT with intensified BU+MEL/TT conditioning in CR Pediatric Non-DS-AMKL.
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Pan Fei, Long Jing, Cao Xing-Yu, Lu Yue, Zhang Jian-Ping, Zhao Yan-Li, Xiong Min, Pan Fang-Min, Yue Guan-Lan, Gao Kang, Wei Zhi-Jie
Аннотация
BACKGROUND: Non-Down syndrome acute megakaryoblastic leukemia (non-DS-AMKL) is a rare but high-risk subtype of pediatric AML with dismal outcomes. Allo-HSCT in first complete remission (CR1) is recommended as the preferred strategy for improving survival, yet the benefit of BU/CY intensification with melphalan (MEL) or thiotepa (TT) remains unclear.
METHODS: We retrospectively analyzed 70 pediatric non-DS-AMKL patients undergoing ATG/G-CSF-based haplo-HSCT between March 2010 and February 2024, comparing standard BU/CY (n=25) with intensified BU+MEL/TT (n=45). Endpoints included OS, LFS, RI, NRM, and TRM. Survival was estimated by Kaplan-Meier and compared with the log-rank test, while cumulative incidences were analyzed using Gray's test. Cox proportional hazards and Fine-Gray competing-risk regression models were applied for univariate and multivariate analyses, as appropriate.
RESULTS: Baseline clinical characteristics were comparable between groups, whereas graft CD34+ (median, 10.40×106/kg vs 5.85×106/kg) and CD3+ (median, 4.54×108/kg vs 1.89×108/kg) cell doses were significantly higher in the BU+MEL/TT group (both P<0.001). Median follow-up was 25 months (range, 13-91.2). Day-100 TRM was similar between groups (6.67% vs 8.00%, P = 0.81), with no significant differences in engraftment, GVHD, viral reactivations. No VOD/SOS or TMA events were observed. Among patients transplanted in CR, the BU+MEL/TT group demonstrated superior 5-year OS (75.2% vs 50.0%, P = 0.045) and LFS (76.3% vs 50.0%, P = 0.039), with numerically lower RI and NRM. In contrast, patients transplanted in NR/PR had poor outcomes in both groups, with 1-year OS and LFS of approximately 20%. In multivariable Cox analyses, intensified conditioning (BU+MEL/TT vs BU) improved OS (HR 0.20, P = 0.047) and LFS (HR 0.29, P = 0.034). Complex cytogenetics (OS: HR 2.38, P = 0.016; LFS: HR 2.58, P = 0.011) and pre-transplant NR/PR status (OS: HR 5.53, P = 0.001; LFS: HR 3.55, P = 0.004) were independent adverse factors. In competing-risk models, conditioning was not associated with RI or NRM, whereas NR/PR status significantly increased relapse (HR 3.39, P = 0.019) and NRM (HR 3.73, P = 0.007).
CONCLUSIONS: In pediatric non-DS-AMKL, intensified conditioning (BU+MEL/TT) independently improved OS and LFS in patients transplanted in CR without increasing early NRM. Pre-transplant NR/PR status was the strongest adverse factor, markedly increasing RI and NRM, underscoring the importance of achieving remission before transplantation.
METHODS: We retrospectively analyzed 70 pediatric non-DS-AMKL patients undergoing ATG/G-CSF-based haplo-HSCT between March 2010 and February 2024, comparing standard BU/CY (n=25) with intensified BU+MEL/TT (n=45). Endpoints included OS, LFS, RI, NRM, and TRM. Survival was estimated by Kaplan-Meier and compared with the log-rank test, while cumulative incidences were analyzed using Gray's test. Cox proportional hazards and Fine-Gray competing-risk regression models were applied for univariate and multivariate analyses, as appropriate.
RESULTS: Baseline clinical characteristics were comparable between groups, whereas graft CD34+ (median, 10.40×106/kg vs 5.85×106/kg) and CD3+ (median, 4.54×108/kg vs 1.89×108/kg) cell doses were significantly higher in the BU+MEL/TT group (both P<0.001). Median follow-up was 25 months (range, 13-91.2). Day-100 TRM was similar between groups (6.67% vs 8.00%, P = 0.81), with no significant differences in engraftment, GVHD, viral reactivations. No VOD/SOS or TMA events were observed. Among patients transplanted in CR, the BU+MEL/TT group demonstrated superior 5-year OS (75.2% vs 50.0%, P = 0.045) and LFS (76.3% vs 50.0%, P = 0.039), with numerically lower RI and NRM. In contrast, patients transplanted in NR/PR had poor outcomes in both groups, with 1-year OS and LFS of approximately 20%. In multivariable Cox analyses, intensified conditioning (BU+MEL/TT vs BU) improved OS (HR 0.20, P = 0.047) and LFS (HR 0.29, P = 0.034). Complex cytogenetics (OS: HR 2.38, P = 0.016; LFS: HR 2.58, P = 0.011) and pre-transplant NR/PR status (OS: HR 5.53, P = 0.001; LFS: HR 3.55, P = 0.004) were independent adverse factors. In competing-risk models, conditioning was not associated with RI or NRM, whereas NR/PR status significantly increased relapse (HR 3.39, P = 0.019) and NRM (HR 3.73, P = 0.007).
CONCLUSIONS: In pediatric non-DS-AMKL, intensified conditioning (BU+MEL/TT) independently improved OS and LFS in patients transplanted in CR without increasing early NRM. Pre-transplant NR/PR status was the strongest adverse factor, markedly increasing RI and NRM, underscoring the importance of achieving remission before transplantation.