Enhanced Long-Term Survival and Acceptable Safety Profile of ATG/G-CSF-Based Haplo-HSCT

Overview

This study demonstrates that intensified conditioning with BU+MEL/TT significantly improves overall survival (OS) and leukemia-free survival (LFS) in pediatric non–DS–AMKL patients undergoing haplo-HSCT in first complete remission, without increasing early non-relapse mortality (NRM). Pre-transplant status is a critical factor influencing outcomes.

Background

Non–Down syndrome acute megakaryoblastic leukemia (non–DS–AMKL) is a rare and aggressive pediatric AML subtype with poor survival rates under standard treatment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended in first complete remission (CR1) to enhance survival, yet the optimal conditioning regimen remains uncertain. This study addresses the impact of intensified conditioning on transplant outcomes in this high-risk population.

Data Highlights

Key Findings

• Intensified conditioning with BU+MEL/TT improved 5-year OS (75.2% vs 50.0%, P = 0.045) and LFS (76.3% vs 50.0%, P = 0.039).
• Higher graft CD34+ and CD3+ cell doses were observed in the BU+MEL/TT group (P<0.001).
• No significant differences in engraftment, GVHD, or viral reactivations between groups.
• Pre-transplant NR/PR status was associated with significantly worse outcomes (OS: HR 5.53, P = 0.001).
• Intensified conditioning did not increase early NRM (6.67% vs 8.00%, P = 0.81).
• Complex cytogenetics were identified as independent adverse factors affecting OS and LFS.

Clinical Implications

The findings suggest that intensified conditioning regimens may be beneficial for improving survival outcomes in pediatric non–DS–AMKL patients undergoing haplo-HSCT. Clinicians should prioritize achieving remission before transplantation to mitigate the risks associated with pre-transplant NR/PR status.

Conclusion

Intensified conditioning with BU+MEL/TT offers a promising strategy to enhance survival in pediatric non–DS–AMKL without increasing early mortality risks, emphasizing the importance of pre-transplant remission status.

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