Impact of pre-transplant chemotherapy cycles on allogeneic hematopoietic cell transplant outcomes in pediatric acute myeloid leukemia in first complete remission.
In a retrospective single-center cohort of 40 pediatric patients with high-risk AML undergoing myeloablative allogeneic HCT in MRD-negative first remission, receiving 3–4 rather than 1–2 pre-transplant chemotherapy cycles was not associated with statistically significant differences in survival or relapse outcomes.
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In a retrospective single-center cohort of 40 pediatric patients with high-risk AML undergoing myeloablative allogeneic HCT in MRD-negative first remission, receiving 3–4 rather than 1–2 pre-transplant chemotherapy cycles was not associated with statistically significant differences in survival or relapse outcomes.
Research significance
The observed lack of significant outcome improvement with 3–4 cycles supports the hypothesis—not established by this underpowered observational study—that proceeding to HCT after 1–2 cycles once MRD-negative CR1 is achieved could avoid unnecessary chemotherapy exposure without compromising transplant outcomes.
Source abstract
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.