Impact of pre-transplant chemotherapy cycles on allogeneic hematopoietic cell transplant outcomes in pediatric acute myeloid leukemia in first complete remission.

BACKGROUND/AIMS: Optimal pre-transplant chemotherapy exposure for pediatric patients with high-risk acute myeloid leukemia (AML) in first complete remission (CR1) remains undefined. Many patients achieve measurable residual disease (MRD)-negative remission early, raising the question of whether additional chemotherapy prior to allogeneic hematopoietic cell transplantation (HCT) improves outcomes. We evaluated the impact of pre-HCT chemotherapy cycles on post-transplant outcomes. METHODS: We conducted a retrospective single-center cohort study of pediatric patients (age 0-18 years) with high-risk AML undergoing first myeloablative allogeneic HCT in MRD-negative CR1 between 2011 and 2023. Patients were stratified by receipt of 1-2 versus 3-4 pre-HCT chemotherapy cycles. Patients in the 3-4 cycle cohort who had achieved MRD-negative remission by the end of cycle 2 were assessed and compared to the 1-2 cycle cohort for rates of two-year relapse-free survival (RFS) and cumulative incidence of relapse. All patients in both cohorts were assessed for rates of two-year overall survival (OS) and one-year non-relapse mortality (NRM). RESULTS: Forty patients met inclusion criteria; 22 (55%) received 1-2 cycles and 18 (45%) received 3-4 cycles. Excluding patients who were not MRD-negative after 2 cycles, two-year RFS was 66% (95% CI 32-86) for 3-4 cycles vs 68% (45-83) for 1-2 cycles (Hazard Ratio [HR] 0.88 [95% CI 0.26-3.01], p=0.84). The cumulative incidence of relapse at two years was 34% (9-62) in the 3-4 cycle cohort and 14% (3-31) in the 1-2 cycle cohort (HR 2.39 [0.57-10.1], p=0.23). Two-year OS was 77% (49-91) for 3-4 cycles vs 67% (46-84) in the 1-2 cycle cohort (HR 0.63 [0.18-2.14], p=0.46). One-year NRM was 0% in the 3-4 cycle group and 18% (5-37) in the 1-2 cohort (HR NE, p=0.06). CONCLUSIONS: Among pediatric patients with high-risk AML undergoing allogeneic HCT in MRD-negative CR1 at a single center, 3-4 pre-transplant chemotherapy cycles were not associated with statistically significant differences in overall or relapse-free survival compared to 1-2 cycles, although the study was underpowered to exclude clinically meaningful differences. Consolidation with HCT after 1-2 cycles of chemotherapy, once MRD-negative remission is achieved, warrants prospective exploration of risk- and remission-guided treatment strategies.